The Handbook of Clinical Neuropsychology

Neuropsychology: past, present, and future
University Press Scholarship Online
Oxford Scholarship Online
The Handbook of Clinical Neuropsychology

Jennifer Gurd, Udo Kischka, and John Marshall
Print publication date: 2010

Print ISBN-13: 9780199234110
Published to Oxford Scholarship Online: September 2010
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Neuropsychology: past, present, and

future
John C. Marshall
Jennifer M. Gurd
DOI:10.1093/acprof:oso/9780199234110.003.01
Abstract and Keywords

This chapter discusses the past, present, and future of
neuropsychology. The first golden age of neuropsychology, as
practised by behavioural neurologists and neuropsychiatrists
from 1861 to 1914, was associated with significant advances
in the fractionation of the aphasias (Bastian, Broca, Wernicke),
the agnosias (Lissauer), the apraxias (Liepmann), and the
alexias (Déjerine), along with the relevant autopsy-confirmed
anatomoclinical correlations. By the end of the 1950s,
psychologists had a secure role in all aspects of the
assessment and rehabilitation of patients with cognitive
disorders. Predicting the future and extrapolating current
trends are enterprises that have somewhat different risks
attached. However, what can confidently be predicted is that
clinical neuropsychologists will not be short of work in the
foreseeable future.
Keywords: clinical neuropsychology, cognitive disorders, neuropsychological

approaches, aphasias, agnosias, apraxias, alexias
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1 Past
Just how far back one might wish to trace the prehistory of
neuropsychology is a moot point. Evidence of trepanning of
living ‘patients’ in the Mesolithic period (Lillie 1998) suggests,
although it does not prove, that early modern man had some
idea of the importance of that cold grey mass within the skull.
But we must wait for the Egyptians before hard evidence
becomes available. Egyptian surgeons certainly knew that
brain and behaviour are related: The Edwin Smith surgical
papyrus, which dates from 1700 BCE, describes language
disorder consequent on brain damage after head injury. And
over a millennium later the Hippocratic corpus (circa 425
BCE) states unambiguously that all mental functions have their
seat in the brain:
It ought to be generally known that the source of our

pleasure, merriment, laughter, and amusement, as of our
grief, pain, anxiety, and tears, is none other than the
brain. It is specially the organ which enables us to think,
see, and hear, and to distinguish the ugly and the
beautiful, the bad and the good, pleasant and
unpleasant… It is the brain too which is the seat of
madness and delirium, of the fears and frights which
assail us, often by night, but sometimes even by day; it is
there where lies the cause of insomnia and sleep-
walking, of thoughts that will not come, forgotten duties,
and eccentricities.
Aristotle (384–322 BCE), who believed that the brain merely

cools the blood, had clearly not been keeping up with the
literature.
Nonetheless, it was another two millennia before relatively

reliable associations were discovered between the locus of
brain damage (established at autopsy) and the nature of the
mental impairment (aphasia, agnosia, apraxia, amnesia, etc.)
that in life had resulted therefrom. The ground had been
prepared by the Viennese physician Franz Joseph Gall (1758–
1828) who conjectured that the brain consists of many ‘mental
organs’, each dedicated to a particular cognitive, conative, or
affective function. Many of the organs in Gall’s classificatory
scheme proved to be valid psychobiological modules that
could, to a first approximation, be independently impaired by
brain damage. The Gallist organs of form, size, weight, colour,
arithmetic calculation, locality (topographic learning and
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memory), eventuality (memory for facts), time, music, and

language are still of intense interest to neuropsychologists. In
one instance, that of language, Gall even managed to get the
(frontal) localization correct.
(p.4) Inspired by Gall’s achievements, the first golden age of

neuropsychology, as practised by behavioural neurologists and
neuropsychiatrists from 1861 to 1914, was associated with
significant advances in the fractionation of the aphasias
(Bastian, Broca, Wernicke), the agnosias (Lissauer), the
apraxias (Liepmann), and the alexias (Déjerine), along with the
relevant autopsy-confirmed anatomoclinical correlations.
Jackson (who first suggested that the right hemisphere was
‘leading for spatial cognition’) and Balint began to elucidate a
wide range of spatial disorders, and Bianchi explored the role
of the frontal lobes in reasoning and planning. The study of
neurodegenerative diseases that could lead to different types
of dementia was also inaugurated by Alzheimer, Korsakoff, and
Pick. It is of interest that the early aphasiologists made serious
attempts to retrain language skills, often deploying many of
the same pedagogical techniques that were currently used to
teach children. In Paris, Paul Broca himself attempted to
remediate language and reading problems, but noted that the
time a busy clinician could devote to speech and language
therapy was ridiculously brief. Although employing traditional
teaching methods, Broca nonetheless thought it probable that
‘the adult and the child will follow different procedures to
attain the same end’ (Howard and Hatfield 1987). He also
conjectured that recovery from aphasia involved training the
right hemisphere homologue of (what became known as)
Broca’s area to take over the functions of the damaged frontal
language region in the left hemisphere.
For the most part, classical neuropsychology was based upon

patients who had suffered cerebrovascular accidents (and
patients with progressive or degenerative conditions,
including neurosyphilis). But the period from 1914 to 1956
saw two world wars and the Korean war (and their medical
aftermaths). In contrast to previous patients who had typically
been elderly and sick, neurologists were now also dealing with
the behavioural sequelae of focal lesions caused by high-
velocity projectile injury to the brains of young, previously
healthy men (and, more rarely, women). Many of the seminal
contributions of Gordon Holmes to the understanding of visual
and visuospatial deficits were made while he was on active
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service as a consultant neurologist in France during World

War I. Likewise, the neurologist Pierre Marie spent the war
studying ‘les aphasies de guerre’ after gun-shot and shrapnel
injuries. Such wounds are often self-sterilizing consequent
upon the heat generated by the transit of the missile: As a
result there were often fewer medical complications than
might initially have been anticipated. Accordingly, the
necessity of cognitive rehabilitation became far more pressing
as patients who recovered medically from their injuries could
often look forward to another 30, 40, or even 50 years of life.
This period also saw the development of more formal testing
procedures (to ensure the comparability of observations made
on different patients). The desirability of using standardized
tests and test-batteries (with appropriate norms) for the
assessment of language, memory, praxis, and visuospatial skill
was reinforced by the earlier success of Alfred Binet in
devising intelligence tests for Parisian children (cf.
Weisenburg and McBride 1935). When, in Cologne,
Poppelreuter (1917/1990) was studying impairments of visual
attention in brain-injured soldiers, he noted that ‘only a result
that lies below the normal range should be judged to be
definitely pathological’. Poppelreuter’s (1917/1990)
monograph, Disturbances of lower and higher visual capacities
caused by occipital damage, (p.5) is subtitled ‘with special
reference to the psychopathological, pedagogical, industrial,
and social implications’, which reflects the concerns of the
time. Poppelreuter, a neurologist who had also trained in
psychology (with Carl Stumpf in Berlin), was well placed to
address these concerns. Rehabilitation was also stressed in
the Berlin clinic of Hermann Gutzmann where psychologists
and speech therapists treated both organic and functional
disorders of language, speech, and voice in the casualties of
trench warfare on the Western Front.
Classical neuropsychology had also taken an interest in

affective disorders as well as cognitive impairments. The
Hippocratic corpus incorporated a humoural theory of the
emotions with different temperaments being associated with a
preponderance of black bile, phlegm, blood, or yellow bile.
Much later, Otto Loewi discovered (in 1924) that synaptic
transmission from the vagus nerve to the heart muscle was
chemically controlled: The first of many neurotransmitter
substances (acetylcholine) had been found. A long and
tortuous journey then led to the conjecture that too much or
Page 4 of 16
too little of various neurotransmitters was implicated in many

neurological and psychiatric conditions (cf. Parkinson’s
disease, schizophrenia, and bipolar disorder).
The further integration of psychology (and psychologists) into

medical teams concerned with acquired cognitive and affective
disorders can be illustrated from the career of Kurt Goldstein
(1878–1965). Shortly after the outbreak of World War I,
Goldstein was appointed medical director of the Frankfurt
Hospital and Research Institute for the study of brain-injured
soldiers. The institute rapidly developed into a major clinical
centre for the diagnosis, treatment, and rehabilitation of
military casualties suffering from neurological and psychiatric
impairments. Goldstein insisted on treating ‘the whole person’
and, to that end, involved psychologists in all the work of the
Institute: Adhémar Gelb, with whom Goldstein investigated
reasoning after brain damage, and Egon Weigl, whose main
interest was in the aphasias, were two of the more notable of
Goldstein’s psychologist collaborators. By one of those fierce
ironies of European history, when Goldstein (1942) wrote
Aftereffects of brain injuries in war, their evaluation and
treatment, the United States had entered World War II and
Goldstein was working in New York, an exile since 1933 from
the Third Reich. But in America too, Goldstein stressed the
crucial contributions that psychologists made to the
assessment of cognitive impairments: He worked with Martin
Scheerer on devising tests of abstract and concrete behaviour,
and with Marianne Simmel on acquired disorders of reading.
The latter work was an important precursor of current interest
in the nature of paralexic errors. Goldstein’s concept of
‘biological intelligence’ as a function of the frontal lobes has
similarly been echoed in more recent work on ‘fluid’
intelligence (Duncan et al. 1995).
2 Present
By the end of the 1950s, psychologists had a secure role in all
aspects of the assessment and rehabilitation of patients with
cognitive disorders. Alexander Romanovitch Luria in Moscow,
Oliver Zangwill in Edinburgh and then Cambridge, and Hans-
Lukas Teuber in New York and Boston stand out among those
who pioneered modern testing methods (p.6) and laid the
foundations of modern neuropsychology. Furthermore,
physicians such as Norman Geschwind in Boston, Henri
Page 5 of 16
Hécaen in Paris, and Ennio De Renzi in Milan, sometimes in

collaboration with psychologists, were instrumental in
vitalizing post-war behavioural neurology.
Building upon the achievements of these seminal figures, the

chapters that follow present an extensive and detailed
overview of current knowledge relevant to clinical
neuropsychology and best practice therein. This section can
accordingly be fairly brief. Nonetheless, it may be useful to
highlight some of the innovations that took place between
Scoville and Milner’s 1957 paper on the memory impairments
of the patient H.M. and the consolidation and widespread
adoption of functional neuroimaging to study both the healthy
and the damaged brain in 2001. We also note some
continuities with previous work, e.g. the involvement of
psychologists in the study of traumatic brain injury (TBI). But
nowadays—in the Western world at least—such injuries result
more frequently from the impact of large projectiles (motor
vehicles) than from small ones (bullets and shrapnel).
Clinical neuropsychology is now a recognized profession with

most practitioners working with patients in hospitals and
rehabilitation centres, or in private practice. By contrast,
experimental neuropsychologists, typically university-based,
have often worked with healthy participants in the laboratory,
devising and testing theories of normal relationships between
the brain and mental life. The distinction, however, has
become increasingly blurred as experimental psychologists
began seeing patients for research purposes and clinical
neuropsychologists began to take a more lively interest in the
theoretical foundations of their practice. This erosion of
professional boundaries accelerated when the widespread
revival of cognitive psychology in the 1960s gave renewed
impetus to all manner of questions that had previously seemed
of dubious propriety. The death of behaviourism, the birth of
transformational grammar, and the inspiration of information
theory and computer science renewed interest in the ‘mind’ as
programmed software that ‘ran’ on the computer hardware (or
more accurately, wetware) of the brain. Experimental
psychologists were encouraged to propose and test models of
cognitive competence and performance that allowed as many
‘mental computations’ as the tasks required and the empirical
data would support.
Page 6 of 16
Cognitive neuropsychology also underwent a renaissance in

the 1960s and 1970s, driven by many of the same factors that
had revitalized experimental psychology. The revival of
commissurotomy (in the hands of Joe Bogen) for the relief of
otherwise intractable epilepsy also drove an intense interest in
the cerebral lateralization of cognitive functions (Sperry et al.
1969). The overall aim of the discipline was seen as effecting
the integration of clinical neuropsychology (the principled
description of disorders consequent, for the most part, upon
demonstrable brain pathology) and normal cognitive
psychology (the construction and empirical validation of
general models of complex mental functions). The distinctive
character of cognitive neuropsychology lies in the explicit
endeavour to interpret disorders of cognition in relation to
formal information-processing models of normal (brain/mind)
systems.
(p.7) Seen in this light, the study of pathologies of cognition

serves a threefold purpose.
◆ Neuropathological fractionations of cognition impose

strong constraints upon theories of the normal system. The
striking dissociations of impaired and preserved
performance seen after brain damage indicate which overt
behavioural abilities must not be analysed together as
manifestations of a single underlying function.
◆ The interpretation of pathological performance by

reference to normal theory allows the investigator to move
beyond the mere description of overt symptomatology to
accounts of the underlying processes that are impaired.
◆ In any complex system, identical overt failures and errors

can arise from malfunction of different underlying
components. Such ambiguities must be resolved by linking
the patterns of impaired and preserved performance to
specified (and justified) information-processing
components.
The relevance of this framework to the practical concerns of

clinical neuropsychologists is clear. The obtaining of
standardized scores on standardized tests may be a necessary
step in examining the patient, but is not a sufficient one. One
needs to know why this particular patient shows this
particular pattern of vitiated and intact skills. One needs to
understand the underlying impairments, not just to describe
Page 7 of 16
the overt signs and symptoms of cognitive breakdown. Initially,

observations made within this framework were systematized
by ‘box-and-arrow’ diagrams that would have seemed entirely
familiar to late nineteenth-century behavioural neurologists
(compare, for example, Lichtheim 1885 and Marshall and
Newcombe 1973). More recently, such models have been
implemented in a computationally more rigorous form
(Coltheart et al. 1993; Plaut and Shallice 1993).
Progress was first made in the description and interpretation

of reading disorders (Marshall and Newcombe 1966) and
verbal short-term memory (Warrington and Shallice 1969). But
the approach characteristic of cognitive neuropsychology
progressively colonized all the traditional domains of
behavioural neurology: disorders of language (Caplan and
Hildebrandt 1988); object- and face-recognition (Farah 1990;
Young 1992); calculation (Butterworth 1999); spatial cognition
(Robertson and Marshall 1993); praxis (Rothi et al. 1997);
episodic memory (Schacter 1996); and planning and executive
control (Rabbitt 1997). Eventually, it even became possible to
admit to an interest in the neurobiology of consciousness,
although the most striking results to date seem to concern
what the mind/brain can achieve without conscious awareness
(Weiskrantz 1997).
Early work that mapped the performance of individual patients

on to (normal) models of the impaired domain quickly showed
that the habitual symptom complexes of behavioural neurology
(Broca’s aphasia, dyslexia with dysgraphia, retrograde
amnesia, associative agnosia, ideational apraxia, etc.)
fractioned into a wide variety of clinically distinct (and
theoretically meaningful) forms. Furthermore, in some
domains, knowledge of lesion locus (the traditional correlate
of behavioural syndromes) was judged to be irrelevant to the
description of pathology-induced cognitive breakdown. The
contribution of psychologists to the work of neurosurgical
teams concerned with the relief of epilepsy by cortical ablation
constitutes the most notable exception to this latter
generalization (p.8) (Scoville and Milner 1957), although it
was the horrendous memory impairment of one patient, H.M.,
that first showed the importance of this work. The success of
‘radical’ cognitive neuropsychology soon became apparent
from the insights it gave into the structure of impaired mental
Page 8 of 16
functions, and the way in which it drove justified changes to

models of normal cognition.
Current work has to a large extent preserved a keen distrust

of syndromes (except as clinical shorthand), and single-case
studies continue to play a supreme role in theoretical
innovation and in the evidential support and disconfirmation of
cognitive models. In this respect, contemporary studies greatly
resemble those of the first golden age (Marshall and
Newcombe 1984). Nevertheless, the importance of group
studies is now recognized when, for example, effect sizes are
small or when correlational analysis of patterns of impaired
and preserved performance is demanded (Gurd 2000;
Newcombe and Marshall 1988). In some instances, large
samples become interesting in their own right. For example, in
a major follow-up of World War II veterans, Newcombe (1969)
showed that, although selective impairments were frequent
after missile injury to the brain, ‘no generalized intellectual
deterioration was detected in these men as a group’. Interest
in neuroanatomical and neurophysiological localization has
also grown, driven in the first place by the widespread
availability of computerized tomography (CT) and magnetic
resonance imaging (MRI) and, more recently, by advances in
functional brain imaging using such techniques as positron
emission tomography (PET), functional MRI, and
magnetoencephalography (MEG) (Frackowiak et al. 1997;
Cabeza and Kingstone 2001).
With respect to rehabilitation, the 1970s and 80s saw the

revival of efforts to produce rational therapies and (even more
importantly) rational evaluations of efficacy. An important
randomized UK trial of speech therapy for aphasia gave
somewhat mixed results: David et al. (1982) found that
patients seen by professional speech therapists and by
untrained volunteers seemed to recover at much the same rate
and that patients who started treatment late made as much
progress as those who started earlier. Such results suggested
that therapies might be more effective if explicitly tailored to
the strengths and weaknesses of the individual patient as
assessed by a detailed neuropsychological examination.
This single-case approach to therapy for cognitive

impairments drew heavily upon arguments that had previously
been advanced as to why the description and interpretation of
neuropsychological symptoms should be based upon the
Page 9 of 16
performance of individual patients and case-series. The

polytypic syndromes characteristic of behavioural neurology
may not be an appropriate knowledge-base on which to plan
therapy. What is required in the first place are longitudinal
single-subject experimental designs that can evaluate the
efficacy of treatment in the individual. Potentially effective
treatments can then be tested on larger samples in a case-by-
case fashion. A number of such protocols are now available,
including reversal and withdrawal designs, multiple baseline
designs, and crossover treatment designs (cf. Willmes and
Deloche 1997). Preliminary results from the new theoretically
motivated therapies can be found in Riddoch and Humphreys
(1994) and Berndt and Mitchum (1995).
(p.9) It is not yet clear whether long-term, generalized gains

actually accrue from such behavioural retraining of cognitive
deficit or attempted substitution of alternative strategies that
bypass the deficit (Shallice 2000). Knowing what is wrong does
not automatically lead to knowing what should be done to
ameliorate the problem.
Page 10 of 16
3 Future
Predicting the future and extrapolating current trends are
enterprises that have somewhat different risks attached. It is
the latter that we will essay here. What can confidently be
predicted, however, is that clinical neuropsychologists will not
be short of work in the foreseeable future (cf. Denes and
Pizzamiglio 1999).
Populations (in the developed world at least) are growing ever

more elderly and hence suffering more and more from
neurodegenerative diseases that have a potentially disastrous
impact on cognitive functions and quality of life. When better
cognition-enhancing drugs (and transplants) become available,
it will be necessary to measure their true efficacy, to
distinguish any pharmacological amelioration of performance
from placebo effects, and to check for unforeseen side-effects.
In younger populations, autoimmune deficiency syndrome
(AIDS)-related cognitive impairments are analogous to those
associated with neurosyphilis in the nineteenth century, with
drug-resistant strains of human immunodeficiency virus (HIV)
becoming more and more common. As with the diseases of
ageing, significant work will be required to assess the efficacy
of new drugs upon cognitive decline in AIDS. The impact of the
Human Genome Project will no doubt increase substantially as
more knowledge becomes available about neurological and
psychiatric conditions whose onset is multiply determined by
genetic and epigenetic susceptibility, developmental
conditions, and environmental stressors.
The paradigms characteristic of cognitive neuropsychology

will undoubtedly make further inroads into our understanding
of psychiatric and other ‘functional’ disorders (Frith 1992). In
this context, we note with alarm the high proportion of
seemingly ‘neurological’ conditions for which no organic
disorder can be found that would explain the patient’s
hemiparesis, somatosensory loss, visual field constriction, etc.
(Halligan et al. 2001). We are already seeing a significant
revival of interest in the neurobiology of the emotions (LeDoux
1992) and greater concern with how mood and affect interact
with problem-solving and decision-making (Damasio 1999).
The study of grossly disturbed reasoning and delusion
formation should also yield major advances in the relatively
near future. It is perhaps in the domain of psychiatric and
affective disorders that functional neuroimaging techniques
and analysis procedures will have one of their most important
Page 11 of 16
clinical applications. Advances in the calculation of functional

or effective connectivity between brain regions will help
imaging techniques to address more directly the functional
architecture of cognition, praxis, and affect and their
disorders. Nonetheless, we must stress that there is no
substitute for the controlled observation of the patient’s
behavioural strengths and weaknesses. Brain imaging is not
an alternative to neuropsychological practice and, in some
instances, the neuropsychological examination may even be a
better guide to the anatomical localization of deficit.
(p.10) We can also look forward to further insights into the

social brain in its natural habitat (Brothers 1997; Cacioppo et
al. 2002). Too often in the past, clinicians have regarded the
individual patient and his or her test scores as the primary
‘object’ of neuropsychological practice. Without in any way
wishing to deny the importance of the individual, we
emphasize that the ‘subject’ of our discipline is the person in
his or her social and environmental setting. At the moment, it
could be embarrassing to inquire too deeply into the ecological
validity of many of our neuropsychological measures and
rehabilitation programmes. In too many instances we only pay
lip service to the distinctions between impairment
(abnormality of function), disability (the effects of impairment
on ability), and handicap (the effects of disability in interaction
with the patient’s physical and social environment). A future in
which we paid more attention to how our patients (or are we
now only allowed to say ‘clients’?) functioned in the kitchen,
the department store, the office, the bingo club, and the
dinner party would be ‘a consummation devoutly to be
wished’ (but cf. Foundas et al. 1995).
Acknowledgements
We are grateful to Graham Beaumont for allowing us to use
suggestions from his unpublished manuscript on the history of
clinical neuropsychology.
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a neuropsychological exploration. Oxford University Press,
Oxford.
Willmes, K. and Deloche, G. (eds.) (1997). Methodological

issues in neuropsychological assessment and rehabilitation.
Psychology Press, Hove, East Sussex.
Young, A.W. (1992). Face recognition impairments. Phil.

Trans. R. Soc. Lond. B 335, 47–54.
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Page 16 of 16
Basic concepts and principles of neuropsychological assessment


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Basic concepts and principles of

neuropsychological assessment
Jonathan J. Evans
DOI:10.1093/acprof:oso/9780199234110.003.02

This chapter begins with a discussion of the objectives of
neuropsychological assessment. It then discusses the
behavioural neurology and neuropsychology approaches to
assessment, assessment prerequisites, contra-indicators to
assessment validity, the assessment process, cerebral
organization and laterality, and specific cognitive skills
examined during neuropsychological assessment.
Keywords: neuropsychological testing, neuropsychology, cerebral organization,

cognitive skills
1 Assessment objectives
Neuropsychological assessment is concerned with identifying
the cognitive, emotional, and behavioural consequences of
brain dysfunction. This type of assessment is used to address a
number of different questions.
1.1 Is there evidence of organic brain dysfunction?

Despite considerable technological advances, it is not always
possible to diagnose brain dysfunction purely on the basis of
evidence from brain imaging, neurophysiological assessment,
Page 1 of 20
or other physical tests. In some cases, cognitive impairment is

the only indicator of a pathological process. The most common
situation of this sort involves identifying whether someone
who complains of a memory problem is suffering from an
organic brain disease such as dementia of the Alzheimer’s type
or a mood disorder such as depression. A question that occurs
frequently in medico-legal cases is whether someone who has
experienced a mild head injury or whiplash has suffered a
brain injury sufficient to affect cognitive processing.
1.2 What is the nature and extent of cognitive impairment?

In some cases, the existence of brain dysfunction is not in
dispute, but the nature and extent of any cognitive impairment
needs to be clarified through more detailed
neuropsychological assessment. Neuropsychological
assessment is used to identify both cognitive impairment and
areas of relative cognitive strength. Some neurological
disorders present with specific patterns of neuropsychological
impairment and therefore neuropsychological assessment may
also contribute to differential diagnosis. One of the duties of
the Neuropsychologist is to enable the patient to understand,
or make sense of, his or her cognitive strengths and deficits.
1.3 What are the practical consequences of cognitive impairment?

A comprehensive neuropsychological assessment should
address the practical or functional consequences of cognitive
impairment for the individual in terms of limitations on the
ability to participate in activities of daily living, work,
education, leisure, and (p.16) social relationships. In some
circumstances the main question for the assessment is simply
whether or not a person is suffering with some form of brain
dysfunction, but it is always useful to consider what practical
impact particular cognitive, emotional, or behavioural
problems might have on the individual’s life. For this purpose
the use of questionnaires such as symptom checklists or rating
scales relating to the performance of everyday tasks are often
useful. When possible, it is helpful to observe the patient in
practical situations. Although this inevitably produces only
qualitative information, if used in combination with
standardized test data it is likely to produce more accurate
predictions about the practical consequences of brain injury.
Neuropsychological assessment is used in forming an opinion
Page 2 of 20
regarding a person’s capacity to manage his or her affairs,

particularly financial affairs, or consent to treatment.
1.4 How are an individual’s mood and behaviour affected by brain

dysfunction?
Although the central focus of neuropsychological assessment
is cognition, the neuropsychologist should also examine the
impact of brain dysfunction on mood, personality, and
behaviour. There are two major reasons why an assessment of
mood is essential.
◆ The presence of a mood disorder, caused directly or

indirectly by brain injury, is an important area of
psychological assessment in its own right.
◆ A mood disorder may have a significant impact on

performance on cognitive tests and therefore must be taken
into account when interpreting test results.
1.5 Does cognitive performance change over time?
A further use for neuropsychological assessment is in
measuring change over time. This might involve charting the
process of decline in cognitive functioning associated with
progressive disorders such as Alzheimer’s disease, monitoring
recovery from head injury or stroke, or measuring fluctuations
in cognitive performance in conditions such as epilepsy. One
problem with the use of neuropsychological tests for
monitoring change is that many tests are vulnerable to
practice effects. A practice effect occurs when the patient who
is tested for a second, third, or fourth time on the same test
improves simply because of increased familiarity with the test
materials and test demands, rather than as a result of any real
change in the underlying cognitive skill. This is particularly
the case if tests are repeated within a matter of a few weeks,
but practice effects may last a lot longer. One solution is to use
parallel versions of tests on each occasion, though the number
of neuropsychological tests with multiple parallel tests
remains very small.
Page 3 of 20
1.6 What are the implications of the pattern of cognitive strengths

and weaknesses for the rehabilitation process?
Information about cognitive strengths and weaknesses is used
in planning rehabilitation interventions. The presence of
severe impairments in some areas of cognition will have
implications for the types of intervention that are possible (e.g.
external aid or self-initiated mental strategy) or the way in
which patients learn new information or skills. (p.17)
Information about areas of retained cognitive strength can
help to plan how to compensate for deficits. The most
straightforward example of this occurs when an individual has
intact visual memory and impaired verbal memory, or vice
versa. Rehabilitation efforts may then involve helping the
individual to develop compensatory strategies using the intact
system. Performance on cognitive tests, however, is not the
best way of measuring the impact of rehabilitation, at least not
in the post-acute stages. Rehabilitation at this stage is
primarily concerned with helping individuals to cope with or
compensate for cognitive deficits and improve practical
performance in everyday life. In other words, the aim is
usually to reduce the activity limitations imposed by the
impairment, rather than reducing the impairment. Using a
measure of impairment is therefore unlikely to reflect
functional gains made in rehabilitation.
1.7 How might cognitive function be affected by neurosurgery?

One specialist role for neuropsychological assessment is in
examining the potential impact on cognitive functioning of
surgery carried out, (e.g. for the relief of epilepsy). The Wada
assessment involves temporarily shutting down each cerebral
hemisphere by an injection of sodium amobarbital. The effect
on cognitive processes, particularly language and memory, can
then be assessed and the information used to inform clinical
decision-making about the appropriateness of a surgical
intervention.
1.8 How is cognitive function affected by medication?

Many medicines affect cognitive performance.
Neuropsychological assessment may be used to monitor the
effect of starting a particular medication. Medications, such as
those used in the management of epilepsy, Parkinson’s disease
or psychosis may affect cognition negatively, or sometimes
positively, and neuropsychological assessment may therefore
Page 4 of 20
contribute to clinical decision making in relation to

prescribing or managing cognitive side effects.
2 Approaches to assessment—behavioural neurology and

neuropsychology
In the behavioural neurology approach, observable signs or
symptoms are used as indices of brain pathology. However,
whilst some patterns of behaviour are clearly absent in the
person with no neurological condition and only occur in the
context of brain lesions, many forms of cognitive impairment
do not fit this dichotomy. For most cognitive skills, there is a
continuum of performance in the non-neurological population.
Nevertheless, the skilled observer can determine a large
amount of information from relatively short interactions with
the patient. By spending time talking with or observing the
patient, it is possible to identify deficits in a number of
cognitive domains. Short bedside tests can also be useful in
highlighting the presence of some disorders. However,
qualitative observation is usually not sufficient to judge the
severity of impairment and may not detect certain forms of
more subtle cognitive dysfunction at all.
Page 5 of 20
(p.18) 2.1 The standardized test

The main tool of the neuropsychological assessment is the
standardized, or psychometric test. Psychometric tests are
tasks that have been designed to assess specified cognitive
functions and are administered in a standardized fashion
defined in a test manual. Such tests have been given to a
normative sample group in order that the performance of the
patient can be compared with that of a representative
reference or ‘normal control group’, (i.e. individuals who have
not suffered any form of neurological condition). The typical
scores of the normal control group are used to produce
‘norms’. The statistical properties and issues of validation of
such tests are considered in Chapter 3. Suffice it to say here
that a test is considered to have ‘good norms’ if the reference
group is representative of the general population in terms of
all factors likely to influence test performance (e.g. age, level
of education, gender). Sometimes, if a particular factor is
likely to have a large influence on test performance, separate
sets of norms are provided for each category of that factor
(e.g. different age bands). With norms available, the
performance of the patient can be compared with the average
performance of individuals of a similar age, taking into
account how much variability there is in ‘normal’ performance.
Test scores are expressed in terms of a ‘standard score’ or a
percentile. A standard score is a measure of the distance of
the patient’s score from the average of the reference group,
taking into account the amount of variability in the scores of
the reference group. A percentile is the percentage of the
reference group who score the same as, or less than, the
patient.
Standardized tests are the most effective tools for quantifying

impairments. However, whenever possible, it is also useful to
use information from observation of the patient carrying out
practical or functional tasks. Some areas of cognitive function
are relatively poorly assessed by standardized tests. For
example, many of the formal, structured, and time-limited
standardized tests may be insensitive to problems of initiation,
problem-solving, and sustained attention associated with
executive functioning. Although more sensitive, ecologically
valid standardized tests are emerging, the qualitative
information gained from a task such as planning and
preparing an unfamiliar meal can help formulate the patient’s
impairments. Furthermore, given that one task of the
Page 6 of 20
neuropsychologist is to identify the practical or functional

consequences of brain injury, supporting evidence from
functional situations makes this process a lot easier, and more
valid.
3 Assessment prerequisites
Before proceeding with a neuropsychological assessment
involving the administration of standardized tests, a number of
prerequisites must be checked.
3.1 Concentration
The patient must be able to concentrate for at least the time
needed to administer any one test. Most full
neuropsychological assessments take several hours to
complete, although testing is usually carried out over several
shorter sessions. However long the assessment session, it is
always necessary for the examiner to be attentive to how well
the patient is able to concentrate on task instructions and on
carrying out the test. An injury-related (p.19) impairment in
attention might make the patient distractible and unable to
sustain attention to the task in hand. Pain, particularly
headaches, will impair concentration. Preoccupation with
worrying thoughts associated with anxiety or depression can
be distracting. Fatigue is also a common problem after brain
injury and cognitively demanding tests may cause the patient
to fatigue rapidly. Poor sleep may mean that the patient is
fatigued even before an assessment has begun. Therefore,
when testing is likely to proceed over a long time period, it is
necessary to ensure that adequate breaks are taken.
3.2 Comprehension
The patient must also be able to comprehend the task
instructions for any test given. This does not mean that some
tests cannot be given to a person with verbal comprehension
difficulties since, of course, the administration of language
tests is one means of identifying the presence of receptive
dysphasia. Nevertheless, if a test is given to a patient who
cannot understand what he or she is required to do, then the
results of that test will be invalid. These issues highlight the
fact that there are no pure tests of any one cognitive function.
For example, verbal memory tests are dependent upon
adequate language skills so that, if a memory test involves
remembering a short story and the patient does not
understand the content of the story, the test results will reflect
the patient’s language deficits rather than testing memory
Page 7 of 20
functioning. Similarly, visual memory tests are dependent

upon adequate perceptual skills so there is little point testing
a person’s memory for a complex design by asking the patient
to draw the design from memory if the person cannot
adequately copy the design.
3.3 Motivation and effort

A further issue is the motivation of the patient to engage in the
assessment process. Brain injury can cause motivational
problems directly when the centres in the brain responsible
for drive and initiation of activity are damaged. In more
extreme forms of this disorder the patient may experience an
inability to initiate action unless prompted at every stage. In
less extreme forms, the patient may simply not apply him or
herself to the task in the same way that it is reasonable to
assume that most normative subjects would have done. Once
again, therefore, this would result in test results reflecting
lack of effort more than the cognitive skill under scrutiny.
Alternatively, motivation problems may be a result of a mood

disorder. The patient who is depressed may not feel able to
make an effort during testing and the results of the patient’s
performance may overestimate the level of impairment. Whilst
this issue can affect performance on almost any cognitive test,
certain tests are more vulnerable to the effects of motivational
problems. For example, tests of memory such as story recall
may be more sensitive to motivation problems than tests that
use recognition of information as the means of assessing
whether information is remembered.
3.3.1 Motivation by hopes of secondary gain

Sometimes a patient is motivated by secondary gain to
perform more poorly than determined by the level of
impairment that actually exists. This is most likely to occur in
the (p.20) context of medicolegal assessments when the level
of a patient’s compensation award is dependent upon the
severity of the impairment or forensic settings when
judgement of a person’s mental capacity is involved. In such
situations the person may be compliant with the assessment
process, but may attempt to ‘fake bad’. This might be in the
context of the patient actually having no cognitive deficit at all
or, more probably, in the context where the patient is
attempting to exaggerate the severity of a genuine
impairment. While examples of frank malingering are quite
Page 8 of 20
rare, it is necessary to consider the possibility that insufficient

effort has been applied in any assessment, particularly in any
medicolegal assessment (cf. Halligan, Bass & Oakley 2003).
This issue can be addressed in several ways. First, the

examiner needs to be attentive to the situation where the
severity of the complaints of the patient appears to be
inconsistent with the severity of the injury. However, it is not
possible to rely on this type of comparison alone since the
relationship between injury severity indicators, such as length
of coma or posttraumatic amnesia, and cognitive or functional
impairments is not straightforward. For this reason, it is
important to use tests that have been specifically designed to
identify the patient who is not applying a normal level of
effort. Most tests of this sort rely on the assumption that such
patients will have a limited knowledge of the typical
consequences of brain injury on cognitive functioning or have
a poor knowledge of test procedures. As a result of this test
naivety the patient may produce a performance that is
significantly worse than that of most genuinely impaired
patients. In some cases, performance on tests is inconsistent
with level of functioning in daily life (i.e. patient is severely
impaired on tests, but everyday functioning is not affected).
For further discussion of the assessment of feigned or non-
credible performance, (cf. Boone 2007).
4 Contra-indicators to assessment validity

Even when the assessment prerequisites have been checked,
several other factors can significantly affect a patient’s
performance on neuropsychological tests. Groth-Marnat
(2000, p. 95) lists 18 factors that could render the results of
neuropsychological tests invalid.
◆ Physical problems may affect performance. In addition to

pain, which will affect concentration, sensory or motor
disturbances are likely to affect performance speed.
◆ Intoxication with alcohol or recreational drugs may

impair cognition, as will some prescription medications (cf.
Powell, 2004).
◆ Current or pre-existing psychiatric disorder or learning

disability will affect results.
Page 9 of 20
◆ Congenital or pre-existing neurological conditions

including prior brain injury, insult, or epilepsy are also
relevant factors.
◆ People for whom the language in which they are tested is

not their first language may be disadvantaged.
◆ Some tests are considered to be culturally biased, which

will compromise the results of someone whose cultural
background is different.
◆ A patient may appear motivated to comply with testing,

but assessment reveals sub-optimal effort which may
invalidate results from tests administered.
(p.21) ◆ The performance of patients may vary from one

testing session to another for a variety of reasons and
therefore the neuropsychologist must be cautious in
interpreting the results from just one session.
It is critical therefore that the neuropsychologist assesses for

the presence of any of these factors and considers carefully
their potential impact on each individual assessment.
5 The assessment process

5.1 Review of information provided by the referrer
The assessment process begins with a review of the
information provided by the referrer. Sometimes a great deal
of information is available, including a detailed clinical history,
brain imaging data, and results of neurological evaluation. At
other times, the only information may be that the patient is
complaining of a particular problem (e.g. difficulty in
remembering names or appointments), or that the patient has
experienced a particular incident (e.g. a mild head injury).
5.2 Interviewing the patient and his/her relative or carer

Upon arrival the patient should be helped to feel at ease.
Neuropsychological assessment is often a lengthy process,
which can be upsetting for people who may be faced with
difficulties of which they are only partially aware. Thus, the
need to maintain their cooperation is vital. An initial interview
is used to establish the patient’s perspective on the problems,
the history, and the impact of the problems on daily living. In
addition to the patient, it is usually necessary to interview a
relative or carer who knows the patient well. Whilst it is
important to obtain the patient’s view of the problems,
difficulties with insight or memory may mean that this
Page 10 of 20
personal account may be inaccurate or limited in scope. Many

clinicians will use a semi-structured interview format for this
clinical interview. Symptom checklists are also useful in
prompting patients and relatives to report problems that may
otherwise be forgotten or unstated. It is helpful to interview
the patient’s relative without the patient being present, so that
the relative has the opportunity to express concerns that
would otherwise not be discussed through embarrassment or
protecting the feelings of the patient.
5.3 Administration of standardized tests
Page 11 of 20
5.3.1 The use of cognitive screening tests

There are many different tests designed to provide a brief
screening assessment of cognitive function. Cullen et al. (2007)
reviewed 39 such tools, noting that they are typically used for
one of three main purposes; (1) brief assessment in the
doctor’s office; (2) large scale community screening; (3)
domain specific screening to guide further assessment. The
Mini-Mental State Examination (MMSE; Folstein et al., 1975)
is the most ubiquitous in clinical practice, though tools which
assess a broader range of cognitive domains than the MMSE,
such as the Addenbrookes Cognitive Examination – Revised
(ACE-R; Mioshi et al. 2006), (p.22) are now being used more
widely. For whatever purpose they are used, interpretation of
results from cognitive screening tests should be cautious.
Some patients present with a clear history of
neuropsychological difficulties and are impaired on the
screening test, while others perform well on the screening test
and have few or no everyday problems. In these situations
interpretation is straightforward, though even when there is
clear evidence of dysfunction, more detailed assessment may
be useful to clarify areas of specific deficit and retained
abilities. Some patients will present with everyday difficulties,
but perform well on a screening test, whilst others may be
impaired on a screening test, but present with everyday
neuropsychological problems. In these two situations, further
evidence must be collected via more detailed
neuropsychological and, where possible, neuropsychological
assessment.
There is no universally agreed set of tests used for

neuropsychological assessment. Some clinical
neuropsychologists routinely use a screening test at the start
of the assessment process as a means of formulating initial
hypotheses about areas of cognitive strength and impairment
(before proceeding to a more detailed examination). Other
neuropsychologists prefer to routinely administer a fixed
battery of tests to systematically address all cognitive domains
in reasonable detail - in this situation, the screening test would
be of little or no use. These two approaches to assessment
have been characterized as the ‘hypothesis-testing’ approach
and the ‘big battery’ approach (see Miller 1992; Lezak et al.
2004; Groth-Marnat 2000).
Page 12 of 20
5.3.2 The ‘big battery’ versus the individualized hypothesis-testing

approach
The big battery approach uses, as the name implies, a battery
of tasks that is designed to assess most types of cognitive skill
on the premise that, if a deficit is present, the battery will
detect it. The main disadvantage of this approach is that it can
be too time-consuming and may not assess some types of
cognitive skill in sufficient detail to fully formulate the
impairment.
By contrast, the individualized, hypothesis-testing approach is

based on the particular question posed in the assessment.
Information available prior to and during the assessment
about the patient’s strengths and weaknesses is used to select
tests to assess in detail particular areas of deficit. For
example, the main question in some assessments is whether or
not brain damage is present. In this case the clinician will try
to select those tests that are most sensitive to any form of
brain injury. However, these tests are often not the best ones
for making predictions concerning the ‘real-life’ impact of
cognitive impairment. If predicting everyday problems and
guiding rehabilitation are the main issues, then other tests
may be selected. The main disadvantage of the hypothesis-
testing approach is that the clinician is vulnerable to failing to
assess a particular cognitive skill because a deficit is not
readily apparent.
In practice, most clinicians probably use a combination of

these approaches, by selecting a broad set of tasks designed to
screen most areas of cognitive skill (or using a specifically
designed screening test), and incorporating other tests as
needed on the basis of test performance, the complaints of the
patient or others, or the particular assessment question.
(p.23) 5.3.3 The importance of good normative data

A further issue for test selection is the importance of using
well standardized tests that therefore have good normative
data. Although the importance of accompanying information
concerning performance in everyday life has been emphasized,
the standardized test provides objective evidence of the nature
and extent of cognitive impairment. Certain groups are not
well represented in most normative samples for cognitive tests
(e.g. people with low pre-morbid intellectual ability or very old
Page 13 of 20
people). In such cases the neuropsychologist must be cautious

in test interpretation.
6 Cerebral organization and laterality

The brain is not cognitively symmetrical. While some cognitive
processes are represented in both cerebral hemispheres,
others are more localized to one or other hemisphere or to
particular areas within a hemisphere. This is consistent with
the currently prevailing view that many cognitive functions are
modular in nature and that different cognitive modules rely on
different brain regions.
The asymmetry of cerebral organization is most strikingly

illustrated with language skills, which for most people are
localized to the left hemisphere. It is also illustrated by the
phenomenon of handedness, whereby one hand is ‘dominant’
in terms of being used for tasks requiring higher levels of fine
motor skill. Handedness is typically assessed through
questions about which hand or foot is used for various tasks or
by asking the patient to perform or mime tasks such as writing
or throwing and kicking a ball.
The majority of right-handed people (95%) have language

skills in the left hemisphere, but the picture is more complex
for left-handers, with most (around 80%) also having language
on the left, some on the right, and some with language
represented bilaterally. The identification of the speech
dominant hemisphere is most critical when surgical
procedures are planned, but for these purposes laboratory
assessments such as the Wada technique are used.
With the advent of more sophisticated imaging techniques, the

usefulness of assessing handedness, in combination with
cognitive test performance, for the purposes of lesion location
has diminished. Although there are reported group differences
in cognitive strengths between left- and right-handers, such
differences are at best modest and are unlikely to be helpful
when accounting for patterns of performance on an
individualized basis. The assessment of cerebral dominance
can, however, help with the interpretation of patterns of
neuropsychological test results. The assessment of
handedness becomes most relevant when an unexpected
pattern of performance on cognitive tests is shown (e.g. when
Page 14 of 20
a patient with a right hemisphere lesion demonstrates

significant language disorder).
7 Specific cognitive skills examined during the

neuropsychological assessment
The following sections describe in brief the cognitive skills
that are the subject of neuropsychological assessment. More
detailed accounts of the assessment process in each (p.24)
cognitive domain are provided in the following chapters. Some
of these areas are not assessed in detail unless there are
indications of possible problems, though the clinician should
be attentive to difficulties that require more detailed
examination. The section begins with a discussion of the
importance of assessing pre-morbid functioning.
7.1 Premorbid functioning

In the neurologically normal population there is a wide range
of ability in almost all forms of cognitive skill. Brain injury can
lead to performance on a cognitive test that is worse than that
of almost any person who has not suffered a brain injury.
However, it is also possible for a person who pre-morbidly
functioned at a high level of ability to suffer an impairment,
while his or her test score remains within a normal range.
While the score is not abnormal in relation to the general
population, it is abnormal for that individual. When evaluating
a patient’s scores on any cognitive test, it is therefore
necessary to consider what the patient’s expected score would
have been before the brain injury.
Most people will not have had any form of cognitive

assessment pre-morbidly and therefore pre-injury performance
has to be estimated. The three most common ways of doing
this are to use:
◆ general demographic information (age, years of

education, social class);
◆ the individual’s best performance on any of the cognitive

tests presented;
◆ a test that is usually resistant to the general effects of

brain injury.
The most commonly used tests for estimating pre-morbid

ability are those that examine performance reading words with
atypical grapheme to phoneme relationships. Such tests
include the Wechsler Test of Adult Reading (WTAR; Wechsler
Page 15 of 20
2001) and the National Adult Reading Test, 2nd edition

(Nelson and Willison 1994). These tests have been shown to
correlate highly with performance on measures of general
intelligence such as the Wechsler Adult Intelligence Scale
(Wechsler 1999) in a normative sample and so can be used to
estimate pre-morbid intellectual level, except where there is
evidence of a pre- or post-morbid dyslexia. An alternative test
of this sort is the Spot the Word subtest, from the Speed and
Capacity of Language Processing Test (Baddeley et al. 1992).
Spot the Word is a lexical decision task in which pairs of words
are presented, only one of which is real, with the task being to
identify the real word.
7.2 Current intellectual functioning

Most clinicians will administer a test, or battery of tests,
designed to capture an individual’s general level of intellectual
functioning. The Wechsler Adult Intelligence Scale (WAIS; now
in its third edition) is the most widely used tool for this
purpose. The main aims of using such a battery are to provide
a means of identifying whether an individual is likely to have
suffered deterioration in cognitive performance in relation to
estimates of pre-morbid functioning and to highlight particular
areas of deficit that may need further investigation.
It is worth noting that neither the WAIS nor its subsequent

incarnations were designed as neuropsychological assessment
tools and poor performance on any one subtest cannot (p.25)
be used to diagnose a deficit in a particular cognitive domain.
A formulation of a patient’s impairments must be developed by
careful analysis of the pattern of performance over a range of
tests. While the WAIS can be used to determine an intelligence
quotient (IQ) score (which is compared with estimates of pre-
morbid IQ in the identification of brain dysfunction), in the
neuropsychological context one must be cautious in expressing
performance on a range of tests in terms of an IQ score. This
is because a cognitive deficit in just one domain may lead to an
extremely poor performance on a small number of subtests,
while performance on other tests remains entirely normal. The
averaging process used to calculate the IQ score could
therefore mask a severe impairment in just one domain.
Crawford (2004) makes a cogent argument that the primary
level of analysis of WAIS III performance should be at the level
of the Indexes (Verbal Comprehension, Perceptual
Page 16 of 20
Organisation, Working Memory, Processing Speed) as these

are empirically derived and have superior reliability.
7.3 Memory
A range of different types of memory function must be
assessed. (cf. Chapters 9 and 10.)
7.4 Attention and concentration

The terms attention and concentration are used
interchangeably to refer to the ability to focus upon a
particular stimulus and to maintain that stimulus in mind,
sometimes over an extended period of time. (cf. Chapters 5
and 6.)
7.5 Speech, language, and communication skills

Although speech, language, and communication skills are
often the domain of the speech therapist/pathologist, in the
clinical setting it is necessary for the neuropsychologist to
have a good knowledge of the nature of aphasic (language)
disorders and dysarthia (impaired articulation), since these
problems will impact on performance on other tests and be
relevant to considerations of the functional impact of cognitive
impairments. (cf.Chapters 13,14, 15 and 16.)
7.6 Visuospatial perception and constructional skills

Brain injury may cause visual field disorders, problems with
visual acuity, spatial contrast sensitivity, visual (light and dark)
adaptation, colour perception, figure–ground separation, or
movement perception. Some of these problems can be
addressed in opthalmological or neurological examinations
and, if such problems are suspected to be present, then
appropriate referral should be made. Other visual perception
deficits such as agnosia, prosopagnosia, and unilateral neglect
are examined within the neuropsychological assessment.
(cf.Chapters 7 and 11.)
7.7 Executive functioning

Executive functioning refers to the ability to plan and problem-
solve, self-monitor, and regulate behaviour (see Chapters 19
and 20).
(p.26) 7.8 Mood, personality, and behaviour

Direct consequences of brain injury may arise when the
regions of the brain responsible for emotional processing or
emotional control have been damaged. Indirect consequences
Page 17 of 20
arise from the stress of adjusting to losses of cognitive or

physical functioning, role, or relationships.
Emotional lability is a common consequence of brain injury.

Irritability and anger control are major problems for many
patients. Although diagnostically controversial, some people
with brain injury suffer from posttraumatic stress syndrome.
While they do not usually remember the accident or injury, a
small number of individuals suffer flashbacks to isolated
memory fragments (islands of memory) of the event or
perhaps waking in hospital, which for some is itself traumatic.
Attributions made by relatives concerning changes in

personality are often related to changes in levels of inhibitory
control and initiative. Those people who are disinhibited, more
impulsive, and emotionally labile, or those who are unable to
initiate activity in the same way, are those who are most
commonly described as having changed in personality.
8 Conclusion
There are no pure tests of any single cognitive skill. The
formulation of a patient’s pattern of cognitive strengths and
weaknesses is a complex task involving the assimilation of
information from a wide range of different sources including
the detailed history of the client’s presenting problems and
pre-morbid functioning, results from standardized tests and
functional observation, and an assessment of the mood and
motivation of the patient. Many problems experienced after
brain injury or illness are very obvious from a short
conversation with the patient. Some problems may be revealed
by brief cognitive screening tools, but others are much more
subtle, albeit no less disabling, and require more detailed
assessment.
Baddeley, A.D. Emslie, H. and Nimmo-Smith, I. (1992).

The Speed and Capacity of Language Processing Test.
Pearson, Oxford.
Boone, K.B. (2007). Assessment of Feigned Cognitive

Impairment. Guilford Press, New York.
Page 18 of 20
Crawford, J. (2004). Psychometric foundations of

neuropsychological assessment. In Clinical neuropsychology: a
practical guide to assessment and management for clinicians
(eds. L.H. Goldstein and J.E. McNeil), pp. 99–119. Wiley,
Chichester, West Sussex.
Cullen, B., O’Neill, B., Evans, J.J., Coen, R.F. and Lawlor,
B.A. (2007). A review of screening tests for cognitive
impairment. Journal of Neurology, Neurosurgery and
Psychiatry , 78, 790–799.
Folstein, M.F., Folstein, S.E. and McHugh, P.R. (1975).

“Mini-Mental State”. A practical method for grading the
cognitive state of patients for the clinician. Journal of
Psychiatric Research, 12, 189–198.
Groth-Marnat, G. (2000). Neuropsychological assessment in

clinical practice. John Wiley and Sons Inc, New York.
Halligan, P.W., Bass, C. and Oakley, D. (2003). Malingering

and Illness Deception. Oxford University Press, Oxford.
Lezak, M.D., Howieson, D.B and Loring, D.W. (2004).

Neuropsychological Assessment, 4th edn. Oxford University
Press, Oxford.
(p.27) Miller, E. (1992). Some basic principles of

neuropsychological assessment. In A handbook of
neuropsychological assessment (ed. J.R. Crawford, D.M.
Parker, and W.W. McKinlay), pp. 10–11. Lawrence Erlbaum
Mioshi, E., Dawson, K., Mitchell, J., Arnold, R. and

Hodges, J. (2006). The Addenbrookes Cognitive Examination
Revised (ACE-R): a brief cognitive test battery for dementia
screening. International Journal of Geriatric Psychiatry , 21,
1078–1089.
Nelson, H. and Willison, J. (1994). National Adult Reading

Test, 2nd edn. NFER, Windsor.
Powell, J. (2004). The effect of medication and other

substances on cognitive functioning. In Clinical
neuropsychology: a practical guide to assessment and
Page 19 of 20
management for clinicians (eds. L.H. Goldstein and J.E.

McNeil), pp. 99–119. Wiley, Chichester, West Sussex.
Wechsler, D. (1999). Wechsler Adult Intelligence Scale-Third

Edition. Harcourt, San Antonio, TX
Wechsler, D (2001). Wechsler Test of Adult Reading.

Harcourt, San Antonio, TX.
Page 20 of 20
The methodological and statistical foundations of neuropsychological assessment


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The methodological and statistical

foundations of neuropsychological
assessment
Klaus Willmes
DOI:10.1093/acprof:oso/9780199234110.003.03

This chapter begins with a discussion of psychometric aspects
of neuropsychological tests. It then discusses the classical test
theory model, criterion-referenced testing, probabilistic test
models, individual case classification, psychometric single-
case analysis, and comparison of a single case to a small
control or normative sample.
Keywords: neuropsychological testing, case analysis, neuropsychology,

classical test theory model, probalistic test models
1 Basic psychometric considerations

Neuropsychological tests are not different from psychological
tests in general, as far as psychometric aspects are concerned.
Psychometrics is a specific domain of measurement in
psychology concerned with the assignment of numerals to one
(or several) property/ies of objects or events according to fixed
rules. Measurement proper (or a scaling process) occurs when
a quantitative value is assigned to the sample of behaviour
Page 1 of 34
collected with a test from which test users draw inferences

about the amount or extent of the theoretical construct (trait)
that is taken to be characteristic of a person.
◆ Unlike physical attributes, psychological attributes of a

person cannot be measured directly.
◆ Psychological attributes are constructs or hypothetical

concepts the existence of which can never be confirmed in
an absolute way nor is there universal acceptance how to
measure any construct.
◆ The degree or extent to which some psychological

construct is characteristic of a person can only be inferred
from limited samples of that person’s behaviour.
◆ Before any measurement of a construct can be made, one

has to establish an operational definition (i.e. a rule of
correspondence between the theoretical construct and
observable behaviours that may be considered indicators of
the construct).
◆ Any measurement obtained is always subject to error.
◆ The units of measurement on the measurement scales are

not well-defined per se.
◆ The measurements on one construct must also have

demonstrated relationships to other constructs within a
theoretical system.
In psychology, a test is a standard procedure for obtaining a

sample of behaviour from some specific domain. One can
furthermore make a distinction between:
◆ (aptitude, achievement, proficiency) tests, with which one

can obtain a behavioural sample of a person’s optimal
performance,
◆ questionnaires or inventories collecting a person’s typical

performance,
(p.29) ◆ sampling typical performance with a standard

schedule and list of behaviours in a naturalistic setting (e.g.
observation checklists).
2 The classical test theory model

Test theory is concerned with methods for estimating the
extent to which the specifics of assessment of psychological
Page 2 of 34
functions influence the measurements in a given situation and

with methods for minimising these problems.
2.1 Basic properties

Most neuropsychological tests - as the majority of
psychological tests in general - are constructed along the
rational of the classical test theory model or classical true
score model (Gulliksen 1987, Lord and Novick 1968) with a
subject’s observed score assumed to be additively composed of
a true performance level and a random error.
2.2 Reliability
Basic properties and principles of the classical test

theory model
◆ The observed score random variable Xij (denoting the

hypothetical distribution of potential scores) for subject
i in test j is composed additively of the subject’s true
score Tij for test j and the error random variable Eij:
◆ The true score can be interpreted as the average of

observed scores obtained over an infinite number of
repeated test administrations (i.e. the expected value)
with the same test.
◆ The test score of a different examinee represents

another random variable with a potentially different
true score.
◆ The expected value of the error variable Eij is zero.
◆ In a population of examinees the expected error is

zero, as well as the correlation between true score and
error score.
In order to obtain information about how closely related

observed score and true scores are for some examinee in a
given test (dropping the index j for the moment) one has to
make use of the reliability coefficient ρ. The higher the
reliability, the better the observed score represents the true
score. The reliability coefficient is defined as the ratio of true
Page 3 of 34
score variance σ 2(T) to observed score variance σ 2(X) in the

population of examinees:
(p.30) The reliability coefficient ρ is the square of the

reliability index ρ XT which denotes the correlation between
true and observed scores. The above expression does not have
practical value because true scores are not directly
observable. Different approaches to actually assessing
reliability are parallel test-, split half-, and retest reliability, as
well as measures of consistency.
Different approaches to determining reliability
Parallel test reliability

This is the correlation between parallel tests. In classical
true score theory two tests A and A’ are defined as parallel
when
— each examinee has the same true score on both forms

of the test
— the error variances for the two forms are identical.
(Due to these properties, parallel tests also have identical

observed score means and variances. The more general
assumption of essential τ-equivalence, i.e. the true scores
may only differ by a fixed constant across all subjects, is
also sufficient.)
— With the additional assumption of uncorrelated error

variables for the two separate tests the reliability
coefficient is identical to the correlation between both
observed variables X, X’:
Retest-reliability:
This is a measure of the correlation between two
administrations of the same test; may only be interpreted
as a reliability coefficient, if the assumptions of parallel
tests are satisfied. In particular, the identity (except for an
inter-individually constant term in essentially τ-equivalent
measures) of true scores across the two measurement
occasions for each person may be problematic; it calls for
Page 4 of 34
the absolute stability of inter-individual differences (with

respect to the theoretical (true score) variable of interest.
Split-half reliability:
This measure of the correlation of the item totals of a test
split into two halves may only be interpreted as a reliability
coefficient, if the assumptions of parallel (more general:
essentially τ-equivalent) tests are satisfied for both test
halves. Since there are only half of the items in each part,
reliability will be underestimated. The reliability ρ* of the
full-length test is:
There are many ways to split a test (e.g. odd vs. even
items; first vs. second half, etc.).
The last formula represents a special case of the general

Spearman-Brown (prophecy) formula for modifying the
number of items in a test by a factor K (K = 2 in the split-
half case); the reliability coefficient ρ* for the modified
length test is:
Standardized item alpha reliability coefficient

This measures the average correlation ave(ρ) between all
K(K - 1)/2 pairs of parallel items scaled to a test of length
K:
Cronbach alpha coefficient of consistency

This is a lower bound to standardized item alpha ρ* for
non-parallel items:
where σ2 l is the variance of the l-th item and σ2 X the

variance of the total score. In case of parallel (more
generally: essentially τ-equivalent) items, the right-hand
side in the last formula is identical to ρXX’ with X denoting
the total score (or arithmetic mean) of the K items.
In the case of dichotomous items, Cronbach alpha equals

Kuder-Richardson Formula-20 (KR-20). For more details,
see Crocker and Algina (1986) and Suen (1990).
Reliability of difference score
Page 5 of 34
Let D = X - Y; assuming uncorrelated errors among X and Y,
In case of parallel measures, ρDD’ = 0.
Example (with identical variances): ρXX’ = 0.90, ρYY’ = 0.95

and ρXY = 0.70 gives ρDD’ = 0.75 only; but a low correlation
ρXY = 0.30 would yield a higher ρDD’ = 0.89.
(p.31) The reliability of a difference score may be of

particular interest when diagnostic decisions have to be based
on the difference D = X – Y between two measures. Often, the
reliability of the difference score is less than the one of both
original measures. Rather, reliable difference scores will result
when one chooses measures that are both highly reliable, but
are not highly correlated. In case of correlated error variables
or a correlation between X and X –Y, the reliability of the
difference score may be higher than for either of the two
measures.
The techniques for assessing reliability described so far cannot

capture all relevant aspects of reliability estimation. Most
restrictive is the assumption of just one non-differentiated (p.
32) error component (resp. one undifferentiated source of
unreliability) in the classical true score model.
Generalizability theory, as a generalisation of reliability theory,

allows for the introduction of several sources of unreliability
(cf. Crocker and Algina 1986, Chapter 8).
2.3 Standard error of measurement and standard error of estimate

One important diagnostic question is how measurement errors
have an influence on the interpretation of an individual
person’s scores. The exact size of error in a given score cannot
be determined, but classical test theory allows for computing
the expected variation of an individual subject’s observed
score around the true score, the standard error of
measurement, i.e. the square root σE of the error variance. If
one additionally assumes that the error variable E follows a
normal distribution, a person’s true score lies within the
confidence limits of X - σE and X + σE with a probability of
about 68%. The standard error of measurement will not be
identical for all examinees and σE expresses the average of all
examinees’ individual standard errors; thus the standard error
Page 6 of 34
of measurement provides an interval for the average

examinee. Furthermore, the confidence interval has the same
width irrespective of the value of X, i.e. the uncertainty about
the exact value of the true score is assumed to be the same for
poor, medium and good performance.
Another relevant error, the standard error of estimate, is

defined as the discrepancy between an examinee’s observed
score on one test and the predicted score on a parallel form of
that test.
Standard error of measurement and standard error

of estimate
◆ The standard error of measurement is related to

observed score variance and reliability coefficient:
Often, the 95%-confidence interval for the true score

around the observed score X is reported for a test and it is
computed as:
Example: with σX = 10 and ρXX’ = 0.91, the standard error

is
◆ The standard error of estimate is:
The standard error of measurement is less than the

standard error of estimate except for the case of perfect or
zero reliability; in the example σXX’ = 4.15.
(p.33) 2.4 Normative data, standardization

An examinee’s raw score usually cannot lead to useful
interpretations or inferences. For example, with 40 items in a
visual discrimination test (composed of 50 items) answered
correctly, a statement about visual discrimination ability
depends on the difficulty of the test and/or the performance of
other similar examinees.
◆ The use of norms, i.e. an external reference, helps to

enhance interpretability of scores.
Page 7 of 34
◆ A normative score provides information about an

examinee’s performance in comparison to the (total) score
distribution of some reference group or norm sample
representing a well-defined population. It is required to
describe the normative sample with respect to demographic
characteristics (gender, age, educational background). In
neuropsychology, characteristics of the pathological
condition will be of interest as well: etiology, size and site of
brain lesion, time post onset, (clinical) syndrome
assignment, etc. One also has to decide on the normative
sample size, since it determines how adequately the
normative sample represents the reference population.
◆ The percentile rank (PR) is one common type of normative

score, denoting the percentage of examinees in the norm
sample scoring below or identical to a given raw score.
Although the PR is easy to interpret, one has to consider
that the PR scale is a non-linear transformation of the raw
score scale with the same gain in raw scores possibly
indicating a varying gain in PR scores at different locations
on the raw score scale.
◆ A normalized z-scale is often constructed in the case of a

non-normal raw score distribution by identifying a certain
PR with the corresponding quantile of the standard normal
distribution. In case of more marked deviations from a
normal raw score distribution this procedure will introduce
substantial distortion often at the lower and/or upper end of
the raw score scale.
◆ Linear z-scores are derived from raw scores in the case of

their distribution being normal and they are further
transformed into standard norms with means and standard
deviations that lend themselves to an easy interpretation.
In the case of dependence of test performance on age or

education (school grade), separate norms for different age or
education sub-populations or grade and age equivalents are
determined. Another approach is to determine the (linear)
regression of age on the raw score for the whole
standardization sample and compute a correction score.
Page 8 of 34
Norms
◆ The percentile rank of a raw score x is defined as:
where cum fx is the cumulative frequency for all scores less

than the score of interest, fx is the frequency of the score of
interest, and N is the normative sample size. Usually, the
PR is rounded to the nearest integer number.
◆ Normalized z-scale (mean zero, standard deviation

one): a certain PR is identified with the corresponding
quantile of the standard normal distribution, i.e. with
that z-score below which PR percent of a normally
distributed trait are to be found.
◆ Linear z-score and standard norms: linear

transformation of raw score x in normative sample:
For better interpretability, linear transformation L + Kz

into a standard norm with mean L and standard deviation
K:
T = 50 + 10z(T-score) W = 10 + 3z (Wechsler scaled

score)
Z = 100 + 10z(Standard score) C = 5 + 2z (Centile

score)
IQ = 100 + 15z (Deviation IQ)
(p.34) 2.5 Validity
Page 9 of 34
◆ Validity is the potential of the true score to reflect what a

test intends to assess; in most cases this is an unobservable
trait or psychological construct. Validity has always been
regarded as the most fundamental and important property
of psychometric instruments. The validity of a test is the
extent to which it measures what it purports to measure.
Generally, the chosen measure and its related true score
only quantify some relevant aspect of a construct; it can
never be fully captured by one or a few measures. A
measure cannot simply be classified as being valid or
invalid in an absolute fashion, rather validity is a relative
property always to be considered with respect to some
intended purpose. Validity is an overall evaluative
judgement, founded on empirical evidence and theoretical
rationales, of the adequacy and appropriateness of
inferences and actions based on test scores (Messick in
Wainer and Braun 1988, p. 33).
◆ Validation describes the process by which a test developer

collects evidence to support the types of inferences that
may be drawn from test scores.
Changes in emphasis and orientation towards validity have

taken place in the history of psychometrics with an emphasis
on the concept of construct validity in more recent times. Key
validity issues are the interpretability, relevance, and utility
test of scores.
Three main aspects of validity are generally discerned:
◆ Construct validity refers to a mutual verification of a

measurement instrument and the theory of the construct it
is intended to measure by way of testable hypotheses.
There are several approaches to construct validation. Most
of them are related to analyzing the pattern and size of
correlations implied by consequences from the theoretical
conceptions or the differentiation between groups in terms
of theoretically implied expected differences (see Crocker
and Algina 1986, pp. 232–4).
(p.35)
◆ Criterion-related (or criterion) validity refers to relating
one measure of a construct to another measure of the same
construct or some ‘gold standard’, if available. The criterion
can take several forms:
Page 10 of 34
— Concurrent validity is looked for in the case of

another measure of accepted validity;
— Predictive validity captures the relation of a

measure with some aspect of the expected future, a
major aspect of screening and prognostic measures.
◆ Content validity – often employed with achievement tests

- refers to how well one can draw inferences from an
examinee’s test score to a larger item domain similar to
those belonging to the actual test instrument. Content
validation is often based on expert ratings about how well
the generation of items from some performance domain has
been specified and how well the actual items reflect that
domain. Several indices have been proposed to
quantitatively summarize expert decisions about item
adequacy (cf. Crocker and Algina 1986, pp. 221–2).
3 Criterion-referenced measurement
Validity coefficient
Validity coefficient: the correlation between the true score

TX of a test variable X and the true score TY of a second
variable Y (e.g. a criterion variable):
This equation is also called the correction for attenuation.

It also follows that
indicating that only reliable measures can present with a

high validity coefficient.
In cognitive neuropsychological single-case studies with

specifically tailored assessment procedures for some cognitive
functions, another type of testing approach, criterion-
referenced testing, is employed at least implicitly. A criterion-
referenced test ascertains a person’s status with respect to a
well-defined behavioural domain (Berk 1980). The principle
concern is to obtain rigorous and precise domain
specifications to maximize the validity and interpretability of a
person’s domain score (e.g. test of simple arithmetic: visually
presented addition tasks ‘a + b = ?’ requiring a written
Page 11 of 34
number as the answer; explicitly state the range of numbers to

be employed, whether carrying is required, etc.). In tests
constructed according to the classical test theory model, less
rigorous specifications are the rule and item selection is
dominated by empirical aspects, e.g. item difficulty and item
discriminability (i.e. its correlation with the total score).
3.1 Basic concepts

◆ Content validity is taken to be the major criterion for item
generation and item selection. A test is called content valid
if it (completely) contains or represents a universe (domain)
of items.
(p.36)
◆ A domain is defined either by exhaustive enumeration of
its elements or, more often, by stating its properties via
generation rules that an item from that particular domain
has to fulfil.
◆ A representative item sample from that domain

constitutes an actual test.
◆ A domain is usually stratified (structured) according to

one or more aspects in a hierarchical or completely crossed
fashion with representative item samples drawn from each
stratum (subdomain) or combination of strata.
As a test author one has to decide which of these parameters

one wants to vary systematically and which parameters one is
willing to ignore or control for by allocating items with these
properties at random to the strata or strata combinations.
Representativeness can often be obtained by drawing a
random sample of prespecified size from the subset.
◆ Content valid parallel tests can be generated by drawing

distinct representative samples from the domain of interest.
◆ For a specified domain, the degree of competence

(achievement, proficiency, ability) for a subject i can be
defined as the probability pi of correctly answering items
from that domain. Empirically, the level of competence is
estimated from a representative sample of items from that
domain. The properties of the ability estimate are
dependent on the particular test model used (e.g. the
binomial model; see below).
Page 12 of 34
◆ Persons can also be characterised according to their

mastery/non-mastery with respect to a domain. Mastery can
operationally be defined as holding if the competence level
pi is no less than some (lower-bound) criterion probability
pc, often fixed at some high value of pc = 0.90 resp. 0.95 or
even 0.99.
Mastery and criterion-referenced testing thus relate a person’s

test performance to an absolute level of competence, not to a
relative distribution of scores across some reference
population, as in the classical true score model.
3.2 The binomial test model

◆ The binomial distribution gives the probability for the
number x of critical events in n independent replications (0
≤ x ≤ n) of the same chance experiment with a constant
probability p for the critical event to happen (e.g. critical
event ‘head up’ in each of n tosses of a regular coin).
◆ The binomial model is invoked implicitly when the

competence level is estimated from dichotomously scored
items using the relative frequency of items solved correctly
as its estimate. But even for very homogeneous domains it
is unrealistic to assume identical item difficulties.
◆ The ‘sampling model’ version of the binomial model is

more adequate. With a new random sample of items drawn
from a domain to assess a new subject, the total score
correct follows a binomial distribution across subjects even
for items with varying difficulty. With PC-based item
generation facilities there is no principled limitation to (p.
37) proceeding this way. The assumption of (local)
stochastical independence among items (independent
replications of the same chance experiment) cannot be
tested in a single subject. Nevertheless, care can be taken
not to choose a sequence of items that provokes practice,
fatigue, or learning/transfer effects.
◆ The most simple mastery decision is based on the exact

(1 - α)-confidence interval around the observed relative
frequency of items scored correct: if the upper confidence
limit > pc, then the individual competence level pi is
compatible with mastery. More complicated decision rules
also taking into account the error of falsely declaring non-
mastery have been proposed as well.
Page 13 of 34
(Example: n = 80 items, x = 72 correct for person i;

competence level estimate = 72/80 = 0.9; exact 95%-
confidence interval (0.8124, 0.9558), computed using StatXact
(Mehta and Patel 1999) or using software available for free via
the internet; decision of mastery, since pc = .95 is covered by
the confidence interval.)
3.3 Operational definition of performance dissociation

◆ The concept of mastery can be employed to empirically
demonstrate the intactness of some processing components
and/or routes in a cognitive neuropsychological model.
◆ The criterion referenced measurement approach, utilizing

the binomial model in combination with exact statistical
tests for dichotomous scores (Fisher’s exact test for 2×2
tables, exact version of the McNemar test), can be
employed to give an operational definition and a procedure
for detecting (double) dissociation of performance in
individual patients, also distinguishing classical, strong, and
trend dissociations as proposed by Shallice (1988, Chapter
10):
◆ Classical dissociation: performance in some task A well

below the normal range and much inferior to task B within
the normal range (possibly close to the pre-morbid level).
— For tasks with almost no variability in normal

subjects, adopt a very high level of mastery (pc =
0.99) for competence level pB in task B; for tasks with
more variability in competence among healthy
controls, pc to be equated with some low quantile in
the score distribution of normal subjects (Table 3.1).
— Much lower competence level pA for task A, e.g.

compatible with chance level for multiple-choice
items, definitely significantly lower than task B (e.g.
using Fisher’s exact test).
— Moreover, a large effect size (difference h between

arcsin-transformed pB and pA) to be actually
observed to warrant adequate statistical power (e.g.
1 - β = 0.95; Cohen 1988).
◆ Strong dissociation: performance in some task A well

below the normal range and much inferior to task B also
below the normal range.
Page 14 of 34
— Standards for effect size the same as for a

classical dissociation.
(p.38)
Page 15 of 34
Table 3.1 Operational definition of different

levels of dissociation using two tasks A (impaired
performance) and B (better preserved
performance) with dichotomous items
(employing the exact Fisher test)
Dissociation
Classical Strong Trend

(robust)
Requirement For the better preserved competence pB in

task B (pB = pc)
1. Normal pc = 0.99 pc = 0.80 pc definitely

performance (definitely below
at ceiling below normal normal
performance) performance
2. Normal pc related to pc below pc definitely

performance e.g. 25%- normal below
with quantile of performance, normal
variability normal if known, or performance
performance, fixed
if known, or arbitrarily
fixed
arbitrarily
Requirement For the poorer competence pA < pB in task

A; determination of number of items such
that effect size h can be attained with test
power 1 - β for type-I error α = 0.05 one-
tailed
Planned effect large: h = 0.8 large: h = 0.8 medium: h =

size* 0.5
Planned test 1 - β = 0.95 1 - β = 0.95 1 - β = 0.80 –

power 0.95
Empirical large large medium

effect size
(*) h = 2arcsin√pB – 2arcsin√pA; standards for high and
medium proposed by Cohen (1988)
◆ Trend dissociation: degree of competence for both tasks

well below mastery levels.
Page 16 of 34
— Number of items large enough for good statistical

power in comparison of competence levels
— Effect size less than for the other types of

dissociations (e.g. medium).
◆ Double dissociation: two complementary dissociations in

two different patients; for exclusion of resource artefacts
falsely indicating a double dissociation, reject 4 null
hypotheses such that: (i) within pt. 1: competence task B >
task A, (ii) within pt 2: task A > task B as well as (iii) for task
A: pt. 2 > pt. 1, (iv) for task B: pt. 1 > pt 2. A worked-out
example can be found in Deloche and Willmes (2000).
3.4 Reliability
Reliability of a criterion-referenced test comprises two
aspects: reliability of domain score estimation and reliability
(consistency) of mastery classification, which is of more
interest when a test is primarily used for mastery
classification(s) (cf. Crocker and Algina 1986, pp. 197-212).
4 Probabilistic test models
Page 17 of 34
4.1 Basic considerations

There are three attitudes towards the construction of
measurement instruments (Rost 1988):
◆ The test score of a measurement instrument is chosen to

be the sum total of the item scores and granted interval
scale properties per fiat taken to be justified empirically if
(p.39) it provides a powerful predictor for some relevant
criterion measure (‘validity pragmatism’).
◆ The use of total scores is justified via deriving

standardised or normative scores for some reference
population (‘norm pragmatism’).
◆ Every assignment of numbers to persons requires a

formal model stating testable assumptions and properties
for that assignment (‘model priority’).
Almost all tests and scales in neuropsychological assessment

are lacking a firm measurement basis (cf. Wade 1992, Chapter
2); e.g. for the Barthel-Index (cf. Wade 1992) the differential
weighting of items and use of different numbers of scale points
per item has not been justified psychometrically, nor has it
been shown that the total score expresses a position on a uni-
dimensional (latent psychological) continuum. On the other
hand, e.g. the Glasgow Coma Scale has been shown to lack
uni-dimensionality (Koziol and Hacke, 1990). Since the
ground-breaking publication of the probabilistic test theory
model (latent trait model) for dichotomous item scores by
Rasch (1960, 1980) and its several extensions to polytomous
items (general term: item response theory (IRT); cf. Wright and
Masters 1982; Rost and Langeheine 1997) there is no
principled excuse for skipping the stage of analysing the
measurement properties, in particular the uni-dimensionality,
of a new test or scale. Otherwise, assigning a total score over
items to some patient may provide invalid information about
the level of ability/competence/typical behaviour. Willmes
(1997) has shown the partial credit model, a very general
model for polytomously scored items (Masters 1982), to hold
within each of the different item groups making up the Subtest
Written Language of the Aachen Aphasia Test (AAT) with a (m
=) 4-point graded item scoring.
4.2 The dichotomous Rasch model
Page 18 of 34
In item response theory a mathematical model equation

specifies how examinees at different ability levels respond to
an item. The item characteristic curve (ICC) reveals how the
probability P(+) of responding correctly to an item depends on
the latent uni-dimensional trait θ that is assumed to underlie
performance in the dichotomous items constituting a test.
◆ For the Rasch model one has the following (logistic) ICC
(see Figure 3.1):
The ability βn of a person n and the difficulty σi of an item i are

measured on the same unidimensional (interval) scale θ. The
item difficulty is the point on the latent dimension where
P(+,θ) = 0.5.
◆ In a uni-dimensional test, statistical dependence among

items can be accounted for by a single latent trait: For a
specified θ, characterising a homogeneous subpopulation of
examinees with that extent or amount of the latent trait,
items are statistically independent (local stochastical
independence property).
(p.40)
◆ If the
above
model
holds,
estimation
of βn only
requires
the number
of items
scored
correctly Fig. 3.1 Logistic item characteristic
curve (ICC) for the Rasch model with
dichotomous item scores; item difficulty
σi is the point on the latent dimension for
θ with P(+,θ) = 0.5.
irrespective of the actual pattern of items solved correctly.

Likewise, estimation of item difficulty σi requires only the
number of examinees with a correct solution for item i.
Page 19 of 34
◆ In the case of model adequacy, item difficulty can be

estimated in a specifically objective way, i.e. the item
difficulty estimate (resp. person ability estimate) is
independent of the distribution of person ability estimates
(resp. distribution of item difficulty estimates) in the
sample.
(For details on estimation procedures and a discussion of the

concept of specific objectivity, cf. Wright and Masters (1982).)
A practical restriction to the use of the Rasch model is the

rather substantial number of subjects (usually n > 100) to be
examined for sufficiently precise parameter estimation and
testing of model adequacy. For a demonstration of the
unidimensionality and application of the Rasch model to the
Token Test see Willmes (1981). An informative homepage with
references to IRT publications and software is http://
www.winsteps.com/.
5 Individual case classification

Classification procedures allocate a single subject to a certain
pre-specified group. The most common questions in clinical
neuropsychological diagnostic examinations:
◆ How is a patient doing in relation to a normative sample

of healthy subjects (assignment of deficit yes/no); possibly
after adjustment for age and/or educational level?
◆ To which group does a patient belong among a set of

explicitly stated populations?
Soundness of classification is important in clinical work when

providing a nosological label or a statement about the
normality/deficit status. Preferably, the assignment to a
population is qualified with a probability statement. It is often
also reasonable to include a ‘non-classifiable’ alternative.
(p.41) 5.1 Normality judgement

Normality can be approached from the perspective of:
◆ mastery, with the level of performance judged in relation

to some task inherent standard,
◆ statistical normality, with performance judged in relation

to a (large) group of similar subjects:
Page 20 of 34
— Separate norms for different combinations of

demographic variables are rare, a viable way is to
work with one fixed norm but adjust an original raw
score xi of patient i by means of a (multiple linear
regression) model equation specifying the influence
of demographic variables:
— The adjusted score is then related to the norm

data from the healthy reference population.
There are several ways to reach a decision about (statistical)

normality:
◆ Tolerance limits, i.e. limits within which a given

percentage (e.g. 95%) of the population is expected to be
observed, together with control of the inferential risk
involved because only a limited standardisation sample
from the population is considered:
— Outer tolerance limit: If the subject’s score falls

outside the limits, a decision with a controlled risk
about non-normality can be made. In
neuropsychology, often a uni-directional tolerance
limit is required; non-normality is only related to the
region of poor performance.
— Inner tolerance limit: If the subject’s score falls

inside the limits, the decision is ‘normal’.
◆ For scores in the gap between both limits no control of

the inferential risk is possible.
— Parametric tolerance limits require the true

distribution of original scores to be known or to be
estimable from a big sample. After correction for the
influence of demographic variables, scale properties
of adjusted scores degenerate for scales with fixed
upper and lower scores.
Page 21 of 34
— Nonparametric (one-sided) tolerance limits specify

that above the value of the r-th ranked observation in
the standardisation sample there is at least a pre-
specified proportion of the population with an error
risk specified apriori (cf. Capitani and Laiacona
2000); e.g. the 10th ranked score for a sample of n =
321 equals the one-sided outer tolerance limit for the
lowest 5% of the population with a risk of 5% that a
larger proportion of normal subjects performs below
the limit. This way of specifying tolerance limits also
works with the ranks of adjusted scores.
There are also ways to set bi- or multivariate (non-)parametric

tolerance limits.
◆ Operationally declaring a PR or standard norm score to

constitute the (one-sided) cut-off between normality and
non-normality; e.g. PR = 1, 5 or 10 or norm scores 2, 2.5, or
3 standard deviations below the mean norm score. In
cognitive neuropsychology, (p.42) frequently a cut-off has
even been determined deliberately from a small normative
sample simply taking the mean minus 2, 2.5 or 3 standard
deviations as a cut-off.
◆ Inferential statistical decision about significantly worse

performance in comparison to a (small) healthy control
sample (approach advocated by Crawford and coworkers,
see below).
5.2 Classification based on discriminant analysis
Discriminant analysis (DA) methods use an allocation rule,
determined with previous samples from explicitly specified
populations that optimises the classification of examinees to
either one of a set of populations, preferably with a probability
statement. It is desirable to also have a ‘non-classifiable’
statement when the allocation probability for any of the
populations considered falls below some operationally set cut-
off value. The allocation rule may be based on parametric
(linear or quadratic) discriminant functions assuming the data
to be (multivariate) normal in the different populations or on
nonparametric techniques, which estimate the true
distributions from the sample data and use a general Bayes
theorem for the computation of the allocation probabilities (cf.
Willmes 1985).
5.3 Deficit measurement
Page 22 of 34
The notion of deficit presupposes some ideal, normal or

premorbid level of performance against which the actual
functioning of a patient may be compared.
◆ Both normative standards and individual comparison

standards are used.
◆ Direct methods of individual comparison standards

presuppose premorbid test scores, school grades or other
data to be available; but they are often non-existent or very
difficult to obtain.
◆ Indirect methods aim at estimating the original ability

level based on historical and observational data; this
provides only shaky evidence in most cases.
◆ Consequently, different approaches to estimating the

missing information from the test scores actually obtained
have been used: e.g. premorbid intellectual ability level
estimated from a vocabulary score or reading performance,
but they all have substantial problems as discussed in Lezak
(1995, pp. 102–5).
◆ Inferential statistical decision about significantly deviant

performance in comparison to a (small) healthy control
sample without explixit reference to premorbid level
(approach advocated by Crawford and coworkers, see
below).
6 Psychometric single-case analysis

A comprehensive inferential statistical approach was
suggested by Huber (1973) for:
◆ comparison of performances within an individual

subject’s profile of standardised test scores;
◆ comparison of two individual performance profiles, e.g.

before and after some intervention (see Willmes 1985, for
an application; a free PC-program CASE123 for
psychometric single-case analysis is available from
[email protected]).
(p.43) 6.1 Basic concepts
6.1.1 Roots
Zubin’s postulates (1950) for the statistical treatment of
intraindividual observations are as follows.
Page 23 of 34
◆ Each individual, in particular if not from the healthy

population, has to be treated as an independent ‘universe’,
not to be classified prematurely into one patient group.
◆ Each subject is characterised by a given level and degree

of variability of performance.
◆ Internal or external causes (spontaneous recovery,

disease progression or therapeutic intervention) may affect
either level or scatter of performance or both.
6.1.2 Principle idea

Treat diagnostic hypotheses about a person’s identity of true
scores (true performance levels) in two (sub) tests like other
statistical hypotheses e.g. about the identity of parameters of
distributions (e.g. t-test: identity of means from two normal
distributions).
6.1.3 Connection to classical test theory model

The observed score Xij of subject i in test j is considered a one-
element random sample from the distribution of potentially
observable scores; it is assumed to be additively composed of
the person’s true score Tij (individual true performance level)
and error Eij (about that true level). An individual diagnostic
examination cannot provide information concerning variability,
and repetitive testing is not feasible as well.
6.1.4 Fundamental homogeneity assumption

Identity of the test specific error variance is assumed to hold
across all subjects of the reference population for which
normative data and reliability information have been obtained;
in this case, the test specific error variance is identical to the
square of the standard error of measurement, i.e.
, for the particular test j with σ2(Xj) the raw score variance in
the reference population and ρjj a reliability coefficient
(internal consistency, split-half or parallel test reliability) for
test j. Both are regularly available in a test manual. Normative
data must be available for the general normal (healthy)
population and/or for some (well defined) patient
population(s).
6.1.5 Concept of τ-standardisation

For a comparison of performance across subtests, only
standard scores can be employed, since different subtests will
usually show differences in difficulty. Diagnostic hypotheses
are concerned with the identity of true scores, e.g. Tij = Tih.
Page 24 of 34
But identity of true raw scores only implies identity of true

standardised scores if the reliability of both tests is identical
(see Huber 1973). In the case of differences between subtest
reliabilities, an additional transformation, the so called τ-
standardisation, has to be carried out on the standardised
score (x denoting observed score standardisation), which
provides the best estimate of true standardised
performance:
(p.44) The higher a test’s reliability the smaller is the

difference between both types of standardised scores. In the
case of identical reliabilities, ordinary x-standardised scores,
as described above, will suffice and the same (average)
reliability estimate ρ from the subtests involved is considered.
6.1.6 Choice of error probabilities

When deciding on diagnostic null hypotheses about true
standardised scores by means of inferential statistical
procedures, type-I and type-II errors occur just as with any
statistical test. In the case of diagnostic hypotheses,
commitment of type-II errors, i.e. overlooking some difference
in true performance levels, may have more detrimental
consequences for a patient than committing type-I errors, i.e.
falsely declaring an observed difference in standardised scores
to be indicative of a true difference in performance. Therefore,
a more liberal default type-I error level of α = 10% is
recommended as default.
6.1.7 Practical requirements

Good reliability estimates for all (sub)tests in the profile (>
0.85 approximately) and normative data from a large
standardisation sample (n > 400–500).
There are two aspects when testing for differences in

performance:
◆ Reliability aspect: Is a performance difference unlikely

due to errors of measurement alone?
◆ Aspect of diagnostic validity: In the case of a reliable

difference, what is the probability of observing a still larger
difference in the reference population?
Page 25 of 34
If that probability is < 20%, this difference in performance is

taken to be diagnostically valid, i.e. potentially indicative of
some relevant piece of diagnostic information (e.g.
dissociation, see below).
6.2 Individual profile analysis

When analysing a performance profile of m subtests, level,
scatter, and shape can be discerned:
◆ Profile level: weighted mean of τ-standardised subtest

scores with higher reliability implying more weight.
◆ Profile scatter: overall differences among m subtest

performances are assessed via the sum of reliability-
weighted squared differences between subtest scores and
profile level. In the case of significant profile scatter (value
> 90%-quantile of -distribution), the profile is declared
real, i.e. representing true performance level differences.
◆ Profile shape: to be analysed in more detail for a real

profile under the reliability aspect.
— Without a specific (neuro-) psychological

hypothesis concerning relations of subtest
performances, all M = m(m - 1)/2 pairwise
comparisons of subtests (j, h) are carried out with
individual type-I error adjustment such that overall,
the type-I error <10% (Holm 1979).
(p.45)
— A linear contrast of two non-overlapping groups of
subtests, I with m1 (≥ 1) and II with m2 (≥ 1) (m1 +
m2 ≤ m) may be diagnostically more interesting (e.g.
comparing verbal and non-verbal subtests in an
intelligence test battery or expressive and receptive
subtests in some aphasia test). Technically, the
profile level resp. for subgroups I and II is
computed and the linear contrast
determined.
— Profile shape may additionally be analysed under

the diagnostic validity aspect.
6.3 Intra-individual profile comparison
Psychometric single-case analysis also offers a way of
comparing two profiles of the same subject or patient
examined twice in the course of some neurological condition,
Page 26 of 34
possibly before and after some phase of therapy or training, or

perhaps in a follow-up examination some time after an
intervention, in order to find out whether performance has
improved, stabilised or deteriorated again. Three steps of
analysis may be discerned:
6.3.1 Global profile comparison

— Profile identity: identity of two profiles for the same test-
battery – both in level and shape – are assessed via the sum
of reliability weighted squared subtest differences between
examinations 1 and 2. In the case of significant deviation
from identity (value > 90%-quantile of χ2 m-distribution),
one proceeds to profile comparisons of level and shape.
— Identity of profile levels: the difference of both profile

levels is tested for deviation from zero. Depending on the
diagnostic hypothesis, this test is one-sided (improvement
after therapy or due to expected spontaneous recovery
resp. deterioration after some progressive disorder) or two-
sided (e.g. stability at follow-up).
— Identity of profile shapes: for a pure comparison of

profile shapes, the sum of level-difference adjusted squared
subtest differences between examinations 1 and 2 is
assessed. In the case of a significant shape difference
(value > 90%-quantile of χ2 m-1-distribution), additional
comparisons serve to study these differences in profile
scatter in more detail.
6.3.2 Specific comparisons for profile shape differences

— Without a specific (neuro-)psychological hypothesis, a
change of the relation in performance between a pair (j, h)
of subtests from examination 1 to examination 2 is carried
out for all M = m(m - 1)/2 pairs of subtests, applying Holm’s
adjustment for multiple testing.
— If a specific change in the performance pattern can be

expected as a consequence of some intervention or disease
progress, the same linear contrast may be compared
between both examinations 1 and 2, i.e. is tested
for a deviation from zero.
6.3.3 Comparison of all profile components

A more conventional comparison between two profiles - in the
case of no identity - that does not involve relations between
Page 27 of 34
profile components simply asks whether true subtest

performance has changed between two examinations. Again,
these comparisons may be one- or two-sided, and adjustment
for multiple testing, applying Holm’s procedure, is required.
(p.46) 6.4 Specific applications in neuropsychology

◆ Performance dissociation: In order to back-up a selective
sparing/impairment of some cognitive function one can
examine whether true performance in that specific subtest s
is reliably and diagnostically validly above/below all or a
subset of all other subtests. One computes all m - 1 (or a
smaller subset) pairwise differences , which all must
be reliable (one-tailed) using Holm’s procedure and have
diagnostic validity probabilities < 20%/(m - 1).
◆ Specific therapy effects: test for a predicted change of

some specific (set of) linear contrast(s) after an intervention
period by carrying out one (or several) specific profile
comparisons: e.g. this approach has been chosen to
substantiate the assumed presence of primary progressive
aphasia (Poeck and Luzzatti 1988): Besides language
impairments revealed in an aphasia test it was shown that a
linear contrast comparing language bound subtests of an
intelligence test battery with non-language bound ones was
reliable and diagnostically valid at initial clinical testing.
But in the course of disease progression the strong
discrepancy between both subtest groups became
significantly smaller at an overall lower performance level.
◆ Definition of responders: The profile comparison methods

may be used to generate operational criteria for identifying
responders to some specific intervention, a more promising
approach than only looking for significant group
differences.
7 Comparison of a single case to a small control or

normative sample
There is a comprehensive inferential statistical approach
available, suggested by Crawford and co-workers (see http://
www.abdn.ac.uk/∼psy086/dept/SingleCaseMethodology.htm,
also providing access to free software) for the intermediate
case of comparison between an individual patient’s
performance and a small or modestly sized control sample,
mostly consisting of healthy subjects more or less well
matched for relevant demographic and other properties (sex,
Page 28 of 34
age, education, etc.). One encounters two basic problems

when relating a patient’s performance to that of a matched
control sample:
◆ detection of a performance deficit for a single patient
◆ detection of a significant difference in performance for a

single patient possibly for the demonstration of a
dissociation of function.
7.1 Performance deficit
The performance score x* of an individual patient on some
performance measure X is related to the arithmetic mean and
the standard deviation sX in the control sample via a
“modified” t-test with df = n - 1 proposed by Crawford and
Howell (1998) for the single case context:
(p.47)
◆ This test allows one to examine the research hypothesis
at a prespecified type-I error level α that a patient does not
belong to the population of control subjects via probing the
null hypothesis that the patient’s performance score is
indeed an observation from the control population
(mirroring the reliability aspect of the psychometric single-
case approach).
◆ There is also a method using the exact p-value of the

modified t-test (Crawford and Garthwaite 2002) for
computing confidence limits on the probability of obtaining
a still more deviant score than the patient’s performance x*
in the control population (mirroring the diagnostic validity
aspect).
(Example: Let the score of the patient be x* = 50 in an 80-item

task with arithmetic mean 70 and standard deviation 10 in a
control group consisting of n = 20 matched subjects. Program
SINGLIMS.EXE provides t(19) = -1.952 with a one-tailed p =
0.033 indicating a significantly decreased performance, with
the 95%-confidence interval for the estimated percentage =
3.29% of the control population falling below the patient’s
score comprising 0.29%–11.07%. Since the upper limit of the
confidence interval is small, i.e. below 20%, this performance
difference may be considered a performance deficit.)
7.2 Difference in performance
Page 29 of 34
Different tasks in single-case studies often comprise different

numbers of items and/or show differences in difficulty, most
probably resulting in different arithmetic means and standard
deviations for two tasks A and B, to be meaningfully compared
with reference to some processing model.
◆ For a reasonable comparison of both tasks it is mandatory

to use standardized scores only.
◆ The test statistic tD with df = n - 1 as proposed by

Crawford, Howell and Garthwaite (1998) is composed of the
individual patient’s performance difference in terms of
standardized scores z X and z Y for both observed score
variables X und Y - using the means and standard deviations
for X and Y in the control sample of size n - divided by the
standard error of that difference, which contains the
correlation rXY among both measures in the control sample:
◆ Only if the standard deviations and the correlation of both

measures were treated as parameters – not reasonable for
small control samples - the test statistic tD would have a t-
distribution. Garthwaite and Crawford (2004) have
proposed a revised standardised difference test (program
RSDT.EXE) with a more complicated looking test statistic
that does not contain parameters and may well be
approximated by a t-distribution with df = n - 1.
(Example: Let the scores of the patient be x* = 20 resp. y* =

50 in a 60-item task A resp. 70-item task B with arithmetic
mean 50 (resp. 55) and standard deviation 10 (resp. 5) in a
control group of n = 20 matched subjects with correlation rXY
= 0.70 among both tasks (p.48) in the control sample. The
individual standardized scores are zX = - 3 resp. zY = -1.
Program RSDT.EXE provides t(19) = 2.394 with a two-tailed p
= 0.027 indicating a significant performance difference, with
an estimated percentage = 1.357% in the control population
for a more extreme difference between the poorer
performance on task A as compared to task B.)
◆ The test for individual differences between tasks A and B

can be combined with the test for a performance deficit in
task A with respect to task B to allow for an operational
definition of a classical performance dissociation. Let the
performance on task A be assumed to be the impaired one.
Page 30 of 34
For a classical dissociation one has to show that the

following set of criteria is fulfilled:
— a significant difference in performance between

tasks A and B
— a deficit for task A and no deficit for task B.
(Example: Using the data from the example before, program

DISSOCS.EXE provides the same results as before for the
comparison aspect as well as the following for the deficit
aspect: for task A t(19) = -2.928 with a one-sided p = 0.004
(95%-confidence interval from 0.003% to 2.559%) there is a
performance deficit but not for task B with t(19) = - 0.976 and
one-sided p = 0.19.)
A complementary definition of a classical dissociation for

another patient can be given by just exchanging the labels
task A and B, thus also providing an operational definition for a
classical double dissociation if the criteria for both
complementary single dissociations are fulfilled. It has been
demonstrated via simulations that the operational criteria
have a very small probability of falsely identifying a subject
from the control sample as showing a classical dissociation
and that the criteria are quite robust in cases of skewed score
distributions in the control sample. Likewise, there is only a
small probability of misclassifying a patient with equivalent
deficits in both tasks as presenting with a classical
dissociation. The power to detect a classical dissociation is
quite low in most cognitive neuropsychological single-case
research since the single patient is compared to a rather small
control sample which usually also shows considerable
interindividual differences in performance (except for easy
tasks which lead to ceiling effects). Power gets higher for pairs
of tasks with sizeable correlations in the control population
and with increasing sample size.
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Capitani, E. and Laiacona, M. (2000). Classification and

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Boller, J. Grafman, and G. Rizzolatti), pp. 53–76. Elsevier,
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Cohen J. (1988). Statistical power analysis for the behavioral

sciences (2nd ed.). Lawrence Erlbaum Associates, Hillsdale, NJ.
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abnormality of test scores and test score differences.
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Lord, F. M. and Novick, M. R. (1968). Statistical theories of

mental tests scores. Addison-Wesley, Reading, MA.
Masters, G. N. (1982). A Rasch model for partial credit

scoring. Psychometrika , 47, 149–174.
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User manual. CYTEL Software Corporation, Cambridge, MA.
Poeck, K. and Luzzatti, C. (1988). Slowly progressive

aphasia in three patients. The problem of accompanying
neurological deficit. Brain , 111, 151–168.
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Shallice, T. (1988). From neuropsychology to mental

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to the Subtest Written Language of the Aachen Aphasia Test
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Page 34 of 34
Principles of cognitive rehabilitation


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001

Nicole D. Anderson
Gordon Winocur
Heather Palmer
DOI:10.1093/acprof:oso/9780199234110.003.04

Cognitive rehabilitation can be defined as an intervention in
which patients and their families work with health
professionals to restore or compensate for cognitive deficits,
thereby improving the patients' everyday functioning. This
chapter discusses issues in cognitive rehabilitation,
approaches to cognitive rehabilitation, and new directions in
rehabilitation.
Keywords: cognitive rehabilitation, cognitive skills, brain injury, new directions
1 Overview
Cognitive rehabilitation can be defined as an intervention in
which patients and their families work with health
professionals to restore or compensate for cognitive deficits,
thereby improving the patients’ everyday functioning. Three
features of this working definition are important.
◆ Cognitive rehabilitation is a team effort. The patient’s

awareness of his/her deficit and his/her motivation to
Page 1 of 50
improve, the family’s involvement and support, and the

therapists’ expertise are all crucial elements for a
successful outcome.
◆ An important theoretical distinction in cognitive

rehabilitation is whether the aim is to restore function to its
original level, or to compensate for lost functioning. This
distinction will be discussed in greater detail later in this
section.
◆ The ultimate goal of cognitive rehabilitation is to facilitate

meaningful and measurable improvements in patients’
everyday functioning, be it functional, academic, vocational,
social, or recreational. Later in this chapter we discuss the
need to build these aspects of everyday functioning into
rehabilitation practice.
Dixon and Bäckman (1999) argue that the need for

rehabilitation (‘compensation’ in their terms) arises when
there is a mismatch between a person’s actual performance
levels on the one hand, and environmental demands on the
other. Various causes of such a mismatch exist. Some of these
are developmental (e.g., autism, learning disabilities,
schizophrenia), some are acquired (e.g., traumatic brain injury,
stroke, neurodegenerative diseases such as Alzheimer’s), and
some occur as part of the normal aging process. This review
focuses on cognitive rehabilitation for adults. See Ylvisaker et
al. (2005) for a recent review of cognitive rehabilitation for
children.
The International Classification of Functioning, Disability, and

Health (World Health Organization, 2001) describes three
levels of functioning: body functions structures, activities, and
participation. In the context of cognitive neuropsychology:
◆ Impairment refers to damaged brain structures (e.g.,

frontal lobe damage) or neuropsychological functions (e.g.,
executive dysfunction);
◆ Activity limitations refer to changes in an individual’s

ability to carry out day-to-day behaviours (e.g., preparing a
meal);
(p.51)
Page 2 of 50
◆ Participation restrictions refer to changes in an

individual’s involvement in various life arenas (e.g., work or
social engagements).
An individual’s impairments and the presence of personality or

psychological factors (e.g., depression) can result in activity
limitations and/or participation restrictions. In addition, the
environment or social setting can contribute to participation
restrictions (e.g., barriers to vocational training).
Cognitive programs that emphasize retraining of abilities aim

to improve functioning of a damaged structure or underlying
process, while those that focus on compensatory mechanisms
aim to minimize activity limitations. Cognitive rehabilitation
may also focus on participation restrictions insofar as their
root is psychological or the effect of an environment that does
not facilitate effective functioning (e.g. a cluttered workspace).
Generally, however, participation is best addressed in practical
ways in multidisciplinary settings that include social workers
and/or occupational therapists.
The distinction between treating impairments or activity

limitations is important on two counts. Treatments of the
underlying neuropsychological impairments are often artificial
and therefore must demonstrate transfer to ‘real life’
situations to be justifiable. Treatments of activity limitations,
on the other hand effectively bypass this step because they
focus on the functional consequences of impairments in a
reality-based context. The second important difference
between impairment- and activity-oriented treatments pertains
to assumptions about the underlying brain mechanisms
involved in recovery.
Cognitive retraining approaches assume that treatment helps

to speed spontaneous neural recovery or promote neural
plasticity and/or regeneration. That is, a restorative process is
assumed. By contrast, compensatory approaches assume that
treatment helps to induce neural substitution or functional
reorganization, whereby undamaged brain regions assume the
function of damaged regions. Later in this chapter we will
discuss the use of neuroimaging tools to help explicate the
neural mechanisms of functional improvement.
Page 3 of 50
Wilson (2002) argues that while cognitive rehabilitation has

grown from disparate models of cognitive and neural
functioning, what is truly needed is a comprehensive model
that encompasses neural, cognitive, behavioural, emotional
and psychosocial components in order to best identify
problems, target treatments, explain mechanisms of recovery,
and evaluate outcome. Holistic and multidimensional
approaches to cognitive rehabilitation discussed later in this
chapter are best geared to meet this goal.
2 Issues in cognitive rehabilitation

2.1 Factors affecting rehabilitation outcome
A number of factors affect rehabilitative outcome including
neurological symptoms, neuropsychological status,
psychosocial status, background history and supports (see Box
4.1).
(p.52) 2.1.1 Neurological symptoms

The location, size, and type of lesion are critical determinants
of cognitive consequences and the likelihood of recovery. The
natural history of TBI recovery depends on whether the head
injury is diffuse or focal, with recovery from diffuse injury
following a more stereotypic course (coma, post-traumatic
amnesia [PTA], post-acute recovery), and recovery from focal
injury being more dependent on the lesion location and size
(Katz and Mills 1999). Coma severity (typically measured by
the Glasgow Coma Scale), coma duration, and (p.53) PTA
duration have been identified as significant predictors of
functional outcome from diffuse TBI (c.f. Sherer et al. 2007, for
a detailed analysis of these indicators). Secondary effects of
trauma such as edema, increased intracranial pressure, and
hematomas can add variability to recovery prognosis (c.f. Katz
and Mills 1999, for a more complete discussion of primary and
secondary effects). Moreover, progressive atrophy in both gray
and white matter can occur up to a year post-injury, perhaps
contributing to neuropsychological and functional difficulties
(Bramlett and Dietrich 2007; Sidaros et al. 2009).
Box 4.1 Factors affecting rehabilitative outcome
Neurological Symptoms
◆ Location, Type, and Extent of Lesion
Page 4 of 50
◆ Secondary Effects (e.g., edema, increased intracranial

pressure, hematoma)
◆ Coma Severity and Duration
◆ Post-Traumatic Amnesia Duration
Neuropsychological Functioning
◆ Attention
◆ Memory
◆ Language Functioning
◆ Visual-Spatial Skills
◆ Motor Skills
◆ Problem-Solving/Mental Flexibility
◆ Information Processing Speed
Psychosocial Factors
◆ Awareness of Deficit
◆ Motivation
◆ Coping Style
◆ Anxiety and Depression
Background History and Supports

◆ Age
◆ Personality
◆ Premorbid Level of Functioning
◆ Social Supports
◆ Financial Supports
2.1.2 Neuropsychological status

A comprehensive neuropsychological evaluation (see Box 4.1
above) is recommended, to determine which skills have been
compromised and need to be rehabilitated versus those skills
which survived and can be recruited to compensate for lost
functioning. Deficits in executive functioning and sustained
attention pose particular challenges for the patient’s ability to
engage in effortful, extended cognitive rehabilitation, and to
reintegrate into social and vocational activities. Nevertheless,
it must be noted that most standard neuropsychological tests
assess cognitive impairments rather than disabilities. Hence,
Page 5 of 50
they are modest predictors of functional outcome, although

some measures (e.g., general cognitive screens and executive
control measures) appear to correlate with more complex
functional activities (e.g., medical decision making) (Royall et
al. 2007). The last couple of decades saw attempts to create
more ecologically valid neuropsychological tests. These
include the Rivermead Behavioural Memory Test (Wilson et al.
1985), the Test of Everyday Attention (Robertson et al. 1994),
and the Behavioural Assessment of the Dysexecutive
Syndrome (Wilson et al. 1996). In addition, Wilson (1995)
stresses the importance of direct assessment of everyday
problems via interviews, questionnaires, observation, and the
patient and family’s recording of the difficulties encountered.
2.1.3 Psychosocial factors

It is widely known that psychosocial status and lifestyle affect
cognitive function in vulnerable populations and hence these
factors need to be addressed in treatment programs (e.g.,
Winocur, Moscovitch, and Freedman, 1987; Mateer, Sira and
O’Connell 2005). Prigatano (2005) has conducted considerable
research into the relationship between patients’ awareness of
their functional disabilities and their ability to benefit from
rehabilitation. Poor awareness can lead to passive or resistant
behaviour in therapeutic settings. Different approaches have
been taken to help improve awareness and/or motivation.
These include
◆ patient and family education about common sequelae of

brain injury (Anderson 1996);
◆ records of patients’ behaviour (through logs or videotape)

to provide the patient with a more objective view of their
behaviour (Mateer 1999);
◆ psychotherapy to help patients cope with their disabilities

(Ben-Yishay and Diller 1993; Mateer and Sira 2006).
Psychological problems, including anxiety, depression, social

withdrawal, loneliness and changes in personality are
commonly associated with brain injury (Morton and (p.54)
Wehman 1995; Prigatano et al. 1998). Poor psychosocial
adjustment (e.g., Dawson et al. 1999; Fields et al. 1998) and
avoidant coping (Krpan et al. 2007) are related to poorer
cognitive functioning in areas such as attention, memory and
information processing speed. In addition locus of control, self-
efficacy and optimism appear to influence rehabilitative
Page 6 of 50
outcome (Dawson and Winocur, 2008). These and related

findings have led to widespread agreement that problems with
awareness, motivation, emotion, and personality need to be
addressed as part of any comprehensive cognitive
rehabilitation program (e.g., Mateer et al. 2005; Prigatano
2005; Williams et al. 1999; Wilson 1995).
2.1.4 Background history and supports

Although the patients’ background characteristics and social
supports play an important role in rehabilitative outcome, they
are rarely, with the exception of patients’ age (younger
individuals have a more positive recovery after brain injury),
integrated into rehabilitation therapies or outcome evaluations
in an objective way. Studies demonstrating the importance of
premorbid patient characteristics have found that patients
with poor outcome following mild TBI were likely to have had
past neurological and psychiatric problems as well as other
life stressors (Ponsford et al. 2000; Wagner et al. 2002).
Similarly, a number of studies have documented reductions in
patients’ social support networks following TBI (Morton and
Wehman 1995); reductions which may negatively affect
recovery outcome (Lezak 1995). To address these needs, Ruff
and Camenzuli (1991) recommend a multi-axial classification
system to help identify factors that may influence
rehabilitative outcome. This classification system includes
premorbid and current emotional, psychological, psychosocial,
and vocational status; factors that should be considered prior
to establishing outcome goals and expectations.
2.2 Issues in rehabilitation design and outcome assessment

How rehabilitation is designed and outcomes assessed, are
complicated issues and the reader is referred to several
excellent reviews on the subject (e.g., Cicerone 2008; Sohlberg
and Raskin 1996). Here, we limit our discussion to three
primary issues.
Page 7 of 50
2.2.1 Individual versus group approaches

Group sessions have the benefit of being more economical, as
well as affording greater development of interpersonal
adaptation and acceptance of impairments (Caetano and
Christensen 1997; Wilson 1995). However, controlled trials
examining the efficacy of group versus individual therapy are
lacking (Wilson and Moffat 1992). Given that patients vary
widely in their neurological, cognitive, and emotional status, a
strong case can be made for tailoring programs to meet
individual needs (Sohlberg and Raskin 1996; Wilson 1995),
although individual programs suffer the disadvantages of
being costly and inefficient, and depriving patients of valuable
group support. Moreover, the evidence regarding outcome is
mixed. One recommended solution is to offer a combination of
individual and group rehabilitation (e.g., Cicerone et al. 2000;
Prigatano 1997; Wilson 1997).
(p.55) The efficacy of individual or group therapy approaches

can be assessed with either single-subject or group designs.
Single-subject designs need not be limited to a sample size of
one, as the design can be applied repeatedly to multiple
patients to establish generalization across subjects. Some
investigators prefer single-subject designs, given the sizeable
variability among patients in neurological, psychosocial, and
cognitive terms (e.g., Sohlberg and Mateer 1989a), however
group designs typically entail more uniform therapy practices
across individuals. Once again, a combined individual/group
approach that examines both group and individual effects may
be advisable.
Page 8 of 50
2.2.2 Control groups

The inclusion of appropriate control groups is essential in
order to demonstrate the efficacy of rehabilitation. Only the
treatment should differ between the control and treatment
groups, and patients who desire treatment should be randomly
assigned to treatment or control groups in order to avoid
selection biases related to factors such as motivation,
education, and age. Park and Ingles’s (2001) meta-analysis of
attention retraining studies revealed that, on average, pre- to
post-treatment gains were significant only in studies that did
not include a control group, thus indicating that the bulk of
the gains reflected practice effects. Moreover, control groups
tend to fare better in randomized controlled trials than in
observational studies (Sacks, Chalmers, and Smith 1982),
thereby inflating treatment effects in the latter group. While
this difference has been interpreted in terms of participant
selection effects, in the case of a waitlist control design, there
may also be negative consequences to having an anticipated
treatment delayed (c.f. Winocur et al. 2007a). One way to
minimize this undesired effect is to provide the control group
either with standard care or some alternate activity equal in
therapist and interpersonal interaction to the treatment, so
that the general effects of being in a therapeutic milieu are
equated.
Page 9 of 50
2.2.3 Generalization
The need to show generalization to other similar tasks and to
everyday functioning is perhaps the most important issue in
cognitive rehabilitation research. With few exceptions (c.f.,
Hall and Cope 1995), most studies have not even attempted to
show generalization to everyday functional or psychosocial
aspects of life, despite the fact that this is the ultimate goal of
cognitive rehabilitation. Instead, most studies have examined
whether training generalizes to similar but untrained cognitive
tasks, and have found transfer only when the training and
target tasks require very similar underlying processes
(Cicerone et al. 2000; Park and Ingles, 2001).
There are several approaches to the issue of generalization

(Stokes and Baer 1977). Historically, investigators have been
content to assume somewhat optimistically, that their
treatments will generalize in a meaningful way. Far preferable
(to this ‘train and hope’ approach) is to build generalization
into training from the outset; that is a ‘train to generalize’
approach. Sohlberg and Raskin (1996) recommend that
therapists use everyday stimuli in training and conduct
training in a variety of settings in order to (p.56) facilitate
generalization. Ruff and Camenzuli (1991) and High et al.
(1995) recommend seeking generalization, not only to similar
activities in everyday life, but also to psychosocial
improvements.
3 Approaches to cognitive rehabilitation

There are three traditional approaches to cognitive
rehabilitation:
◆ cognitive retraining;
◆ compensatory approaches;
◆ holistic approaches.
Recently, we have witnessed the emergence of a

multidimensional approach which in a sense borrows from
each of these, and attempts to organize their essential
features into integrated, formalized programs. In addition, it is
necessary to consider the pharmacological approach, for its
inherent value, and because of the potential benefits from
combining drug and behavioural therapies. Regardless of
orientation, the goal of each approach is to rehabilitate
Page 10 of 50
cognitive functioning over and above that which might occur

naturally with the passage of time, or through generalized
practice. Each approach is reviewed in turn.
3.1 Cognitive retraining
Page 11 of 50
Retraining programs usually involve repeated practice of

specific cognitive exercises designed to strengthen basic skills
(e.g., attention, encoding) that are essential for more complex
cognitive function. This approach is continuing to develop and
one promising adaptation is a scaffolding approach whereby
training begins with basic processes and progresses to more
complex skills. The approach is clearly reflected in Sohlberg
and Mateer’s (1989a) ‘process oriented’ model in which
component processes presumed to mediate particular
cognitive skills are trained in a hierarchical order, such that
progressively more complex processes are trained as learning
occurs. Within each level of training, skills are repetitively
practiced under the assumption that repeated practice in a
structured setting is a necessary component for strengthening
and re-automatizing cognitive skills (Mateer 1999).
A specific example of the process-oriented model is Sohlberg

and Mateer’s Attention Process Training, which includes
training in various aspects of attention including sustained,
selective, alternating, and divided attention (1989a; 2001;
Park et al. 1999; and c.f., Gray and Robertson 1989, and Sturm
et al. 1997, for similar approaches). The efficacy of attention
training has been demonstrated in a number of studies
showing improvements on independent, untrained tasks that
were presumed to tap the same functions (c.f. Mateer 1999,
for a review). Subsequent developments of this model
(Sohlberg et al. 1993) added methods to enhance patients’
monitoring of their attention performance in order to improve
self-control over other cognitive weaknesses.
While direct retraining has historically been ineffective when

targeted at memory functioning (Sohlberg and Mateer 2001),
one memory retraining paradigm developed for (p.57) older
adults holds considerable promise. Based on evidence that
aging disrupts conscious effortful memory for prior events in
their spatial-temporal context (recollection) but leaves intact
automatic memory for prior events devoid of contextual
information (familiarity), Jennings and Jacoby (2003) devised a
recollection training paradigm. Participants studied a list of
words, and then performed a yes-no recognition test on a new
list, consisting of the studied as well as new, unstudied words.
Each of the new words was presented twice during the
recognition test. Participants were instructed to respond “yes”
only to studied words. Repeated new words elicited a feeling
of familiarity; a familiarity which needed to be offset by
Page 12 of 50
recollection of the words’ original context (i.e., as a new,

unstudied word) (Jennings and Jacoby 1997). Training began
with just a couple of words intervening before the new word
was repeated (the “lag”). This progressed over 28 sessions (15
min per session), held over seven days of training, until the lag
was gradually increased (as participants met criterion
performance). By the end of training, the older participants
were responding correctly at an average lag of 28 words,
suggesting vast improvement in the ability to recollect
information. Moreover, Jennings and her colleagues (Jennings
et al. 2005) later showed that the recollection training benefits
did transfer to other tasks requiring recollection (e.g. as n-
back and self-ordered pointing). As indicated by positive
results from an initial study of 10 individuals with acquired
brain injury (Lillie and Mateer 2006), this type of memory
training technique seems to benefit any individual with
recollection impairments (although clearly, further evidence is
required).
3.2 Compensatory approaches

Compensatory approaches are based on the principle that
individuals can offset reduced cognitive abilities by utilizing
different ways of performing a task. Internal strategies can
help individuals to make the necessary effort required to solve
a problem. Such techniques place considerable demands on
the individual’s ability to use them appropriately. However, as
West (1995) points out, one added benefit of such effort is the
increased attention to task. With external strategies, the goal
is to identify environmental objects which can assume some of
the demands normally placed on cognitive processing. The
following are some examples of compensatory techniques
thought to be of value in cognitive rehabilitation.
Page 13 of 50
3.2.1 Internal strategies

To varying degrees, normal adults depend on well-established
internal strategies to support learning and memory.
Cognitively impaired patients are less able to do this, but are
able to benefit from direct training. Numerous strategies
involving verbal and visual aids, organization of information
and executive skills training are available. Their usefulness
depends partly on the type of information to be remembered.
One example of an internal strategy that makes use of visual

aids comes from the work of Yesavage and his colleagues
(1983, 1990). They successfully trained older adults to use a
face-name strategy in which one identifies a salient facial
feature (e.g., a ruddy nose), creates a concrete image
transformation of a person’s name (e.g., a rose for ‘Rosie’), (p.
58) and then forms an interactive visual image of the facial
feature and the name transformation (e.g., a rose in place of
her nose). While this kind of approach has been used
successfully for individuals with mild memory problems (c.f.,
Troyer et al. 2006), it has generally been less successful for
patients with moderate to severe memory impairments (e.g.,
Gade 1994; but c.f., Kaschel et al. 2002). The familiar method-
of-loci, in which a visual image is associated with each of a
series of locations or items on a list, is another example of the
use of interactive imagery, due to its difficulty however, it is
seldom practical for use with brain injured individuals
(Richardson 1995).
Improved memory performance has also been reported

following spaced retrieval training. Sohlberg and Mateer have
successfully applied spaced retrieval techniques to train
prospective memory – the ability to remember to do things in
the future (1989a; Sohlberg et al. 1992a, 1992b). In this
technique, individuals are trained to recall information at
progressively longer intervals. The principle is that this
experience facilitates the spontaneous use of efficient retrieval
strategies.
Internal strategies that make use of verbal mediators such as

forming semantically meaningful associates or easily
connected rhymes of material to be remembered, are
considered useful in learning people’s names, or short words
lists and sequences (e.g., ‘Thirty days hath September…’). For
longer lists or more complex material, creating a story can be
a useful aid. The idea here is to devise personalized
Page 14 of 50
associations to each of the items that can be represented in

meaningful and integrated ways, and easily accessed at
retrieval. Other learning techniques encourage the
organization of new information (i.e., into units of a
manageable size or by taxonomic categories). Identifying as
many contextual features as possible can also be useful for
purposes of registering or encoding new information, and
providing effective retrieval cues during recall.
There has been considerable debate concerning the value of

training brain-damaged people to use internal strategies, and
the extent to which, in the absence of other forms of training,
they generalize from the training environment (Prigatano et al.
1998; Wilson and Kapur 2008). Wilson (1995) emphasizes that
relatives, therapists, and teachers can use these strategies to
help facilitate memory-impaired individuals’ learning. At the
same time, there is evidence that severely brain-damaged
patients with limited potential for recovery, can benefit (to
some degree) from intensive internal-strategy training
(Thoene and Glisky 1995).
Techniques designed to rehabilitate executive skills have been

used effectively with patients who have relatively small brain
lesions and moderate cognitive impairment. One technique is
to help patients regulate their behavior through self-
instruction, wherein one talks his/her way through an activity
in order to maintain appropriate attention (Cicerone and Wood
1987; Cicerone and Giacino 1992; Ownsworth and McFarland
1999; Meichenbaum 1977). This technique helps individuals to
gain control over thought processes needed to plan and
regulate behaviours appropriately.
Robertson’s (1996) ‘Goal Management Training’ program was

also designed to reduce executive impairments related to
frontal lobe damage. This is a manual-based protocol for
helping patients organize their behaviour and execute tasks in
a goal-directed manner. (p.59) Patients are taught that
successful task completion requires the implementation of
several related strategies:
◆ evaluating the current situation and generating

appropriate goals;
◆ selecting goals;
Page 15 of 50
◆ parsing overall goals into sub-goals;
◆ learning and retaining the goals and sub-goals;
◆ evaluating outcome against the goals.
Goal Management Training is an intensive program that

places considerable demands on patients’ residual skills.
Nevertheless, there is some evidence that it can be effective.
Levine et al. (2000) demonstrated the utility of this method in
a real-life setting. They described a single-case study of a
woman recovering from meningo-encephalitis. Despite normal
performance on standard neuropsychological tests of memory
and executive functioning, she performed poorly on the more
naturalistic tests of everyday attention and memory (described
earlier in this section). One of her chief complaints was
difficulty managing meal preparations. After Goal
Management Training, there was a significant reduction in her
number of cooking errors. For example, she was more likely to
assemble the necessary ingredients, and better able to follow
the sequence of a recipe, keep to the task, and get back on
track when sidetracked. The primary advantage of this
strategy is its applicability to everyday activities that require
self-regulated, organized behaviour (c.f., Von Cramon et al.
1991).
3.2.2 External strategies

External strategies make use of objects in the environment to
compensate for cognitive deficits. A simple approach is to
design environments with built-in cues that reduce
disorientation and help navigation. For example, lines painted
on floors or ceilings can help guide in-patients to the cafeteria.
Labels on cabinets, maps in buildings, and doors painted
different colours are other examples of orientation cues.
Effective treatments for executive dysfunction have included:
◆ using checklists to facilitate appropriate task sequencing

in vocational settings;
◆ providing concurrent verbal feedback to reinforce and

shape behaviour (Burke et al. 1991);
◆ cueing to improve self-initiation (Sohlberg et al. 1988);
◆ introducing response cost methods to decrease

disinhibited behavior (Alderman et al. 1995).
Page 16 of 50
In the memory domain, external aids include common

reminders such as lists, calendars, and alarm clocks, and a
‘memory place’ in which important objects such as glasses,
keys, and wallets are kept (West 1995).
Harris (1978) argued that external aids should meet three

criteria.
◆ They should be active, rather than passive. Passive cues

like calendars require one to initiate a checking behaviour,
and initiating action is problematic for (p.60) brain-injured
individuals. Active cues, such as those that employ alarms,
draw attention to the cue.
◆ They should be timely. That is, the cue should draw

attention at the appropriate time when an action must be
performed.
◆ They should be specific. A string around a finger may

remind someone that they need to do something, but it does
not specify which activity should be performed.
A very practical external memory aid is a memory book.

Memory books often contain sections for personal information
(e.g., name, address, phone number), a calendar, daily
schedule, and ‘things to do’ list. Additional sections are added
as needed (e.g., medication lists). Sohlberg and Mateer
(1989b) described a rehabilitation approach to memory book
training that involves three stages:
◆ Acquisition. In this phase, patients are taught the name,

purpose, and proper use of each section of the memory
book.
◆ Application. In this phase, patients practice the use of

each section by following the therapist’s role-playing
instructions.
◆ Adaptation. In this phase, the use of the book is

transferred to naturalistic settings.
Sohlberg and Mateer present a case study illustrating the

success of this method (c.f. Burke et al. 1994).
Newer technology has provided increasingly portable and

powerful memory aids. Wilson et al. (2001) describe the
efficacy of an easy-to-use pager system that cues memory-
impaired individuals when particular actions must be
Page 17 of 50
performed. Devices such as a Palm Pilot® or BlackBerry® offer

even more flexibility, and their efficacy in memory
rehabilitation has received some attention (Dry et al. 2006;
Gentry 2008; Kim et al. 1999). Technology can have
drawbacks, however. Many of these devices are expensive, and
the risk of losing them must be considered. In addition, as
electronic aids become more flexible, there are greater
opportunities for confusion and interference during learning.
Investigators and therapists are advised to restrict training to
the essential functions afforded by the devises and to use
training methods that prevent errors during learning.
Examples of such methods are described in the next section.
3.2.3 Domain-specific techniques

Domain-specific approaches capitalize on preserved cognitive
domains, or systems, to train functions that are normally
mediated by other, impaired systems. For example, amnesics
are severely impaired on tests of explicit memory (e.g., free
recall), but perform normally on tests of implicit memory in
which no reference is made to a previous event but where past
experience nevertheless influences current behaviour (e.g.,
Schacter and Graf 1986). Specifically, amnesics would not be
able to recall many words from a previously presented list.
However, if provided with the first few letters of each word
and asked to complete these ‘word stems’ with the first word
that came to mind, amnesics would be as likely as healthy
individuals to provide words that had been presented earlier.
That is, their implicit memory for the previous event is intact,
despite the fact that their explicit memory for past events is
severely impaired.
(p.61) Two approaches are based on these principles.
◆ In the method of vanishing cues (Glisky et al. 1994),

memory-impaired people are provided with enough cues to
allow successful performance, and as learning occurs, cues
are gradually withdrawn. This method has been
successfully employed to teach amnesics new computer
skills (Glisky et al. 1986a, 1986b, 1994), but a meta-analysis
found that when averaged across studies, the benefits of
vanishing cues are small and non-significant (Kessels and
de Haan 2003).
Page 18 of 50
◆ A similar approach is the errorless learning procedure.

Baddeley and Wilson (1994) observed that once a memory-
impaired patient makes an error, he or she is more likely to
repeat that error. They reasoned that the preserved implicit
memory system is poorly equipped to resolve the
interference. A number of investigators have demonstrated
that errorless learning is more effective than standard
conditions in which errors are allowed (c.f. Clare and Jones
2008).
3.3 Holistic approaches
In contrast to retraining and compensatory approaches,
holistic approaches are more broadly concerned with the
overall human condition. As such, they address cognitive,
social, emotional, and functional issues that result from brain
impairment. Holistic programs aim for practical benefits by
emphasizing self-awareness with the aim of creating more
insight into the changes that have taken place following brain
injury. These include:
◆ self-regulatory skills in coping with social and cognitive

demands;
◆ feelings of well-being that relate to confidence and self-

esteem;
◆ communication skills considered essential to successful

social interactions.
The holistic approaches are predicated on several key

assumptions:
◆ Cognitive therapies must not be isolated from other

therapies (physical, psychological) that are essential to
functional rehabilitation;
◆ Cognitive interventions must proceed in sequential

fashion from lower levels to more complex functions;
◆ The disorganized and sometimes chaotic nature of

thought processes in brain-damaged people necessitate an
orderly and structured therapeutic program;
◆ because the problems of brain-injured people are highly

personalized, treatment must be as individualized as
possible (c.f., Ben-Yishay 1996).
Page 19 of 50
Holistic programs involve both group and individual therapy,

often extend for years, and are demanding in terms of
resources and commitment on the part of the patient.
Individuals participate in intensive remedial intervention that
includes simple drills and retraining exercises, as well as
learning compensatory techniques. An important objective is
that patients gain an appreciation of their strengths and
weaknesses, and the practical limitations imposed by their
brain damage. The expectation is that they will then be better
equipped to restructure their lives in realistic ways.
(p.62) Two prominent holistic programs are those developed

by Ben-Yishay (1978), a pioneer in the field, and Prigatano
(1986). Ben-Yishay’s approach is characterized by the creation
of a ‘therapeutic community’ in which the patients, members
of the therapeutic team, family and significant others, work
together to promote the rehabilitative process. Prigatano
follows a similar approach but attaches great importance to
the psychosocial consequences of neuropsychological
disturbances. Prigatano’s program focuses on residual
function and is guided by the philosophy that optimal use of
these functions can be achieved if the patient has
psychologically adjusted to the injury-induced changes and is
coping effectively. While there is continuing need to evaluate
the holistic approach, evidence from several studies points to
significant benefits to TBI patients in terms of
neuropsychological test performance, vocational status, and
emotional functioning (Cicerone et al. 2008; Prigatano et al.
1998; Salazar et al. 2000).
3.4 Multidimensional approaches
Page 20 of 50
The recognition that cognitive impairment is a multi-faceted

problem, as reflected in the holistic approach, is also apparent
in the emergence of multidimensional rehabilitation programs
that take into account combinations of biological, social, and
psychological factors that impact on cognitive expression in
individuals with brain dysfunction. In addition to their broad
approaches, these programs share a number of important
features. For example, they are evidence-based in that they
attempt to integrate accepted clinical practice with
empirically-derived theory of cognitive processes and
cognitive impairment. Each has been evaluated by a rigorous
randomized control trial that includes short- and long-term
outcome assessment under carefully controlled conditions. In
contrast to traditional individualized programs, which can
extend for years and are resource-intensive, these programs
are delivered in small-groups over relatively brief time
periods.
Interestingly, the major multidimensional cognitive

rehabilitation programs were developed initially for normal
older adults and tested successfully in this population.
However, the considerable overlap in the cognitive profiles of
cognitively impaired populations suggests that in principle,
brain-damaged individuals with mild to moderate cognitive
loss could also benefit from such programs. Two different
treatment approaches are as follows.
3.4.1 Specific-process training strategy

The specific-process approach is guided by the rationale that
improvement in designated functional domains is best
achieved by cognitive retraining that selectively targets those
domains. Programs that follow this approach have been
influenced heavily by studies that demonstrated relationships
between improvements in specific cognitive abilities and
improvements in performance in various everyday activities
(Jobe et al. 2001). The first such approach to be reported in
detail is the SIMA project (Oswald et al. 1996), in which 390
older adults living in the community were assigned to one of
three following training conditions:
◆ memory: general competence, which focused on coping

with everyday problems;
Page 21 of 50
◆ psychomotor: to improve visuo-motor coordination and

response time;
◆ memory + psychomotor: general competence +

psychomotor.
(p.63) After a nine-month training program, there was

evidence that participants benefited in the specific areas in
which they were trained, although there was little
generalization to other areas. Memory training appeared to
have the strongest effect and, when it was combined with
psychomotor training, resulted in some protection against
cognitive decline.
In 1998, the Advanced Cognitive Training for Independent and

Vital Elderly (ACTIVE) program was launched as a multi-
centre trial in which 2802 independent-living older adults
received a six-week training program directed at memory
skills, reasoning abilities, or speed of information-processing
(Jobe et al. 2001; Ball et al. 2002). Outcome measures included
basic cognitive functions in the training domains, everyday
tasks (e.g., financial management, driving skills), health-
related activities (e.g., quality of life, mobility, health services
utilization), and instrumental activities of daily living.
The trial was conducted over a three year period with

outcomes assessed immediately (< 10 days), 12 months, and
24 months after training. Relative to baseline, each
intervention resulted in improved performance in its targeted
domain. As in the SIMA study, there was no evidence of
generalization to non-trained cognitive abilities or to
performance of everyday tasks. Participants in the speed of
processing and reasoning groups, but not the memory groups,
exhibited improvement on quality of life measures that were
still manifest five years post-training (Wolinsky et al. 2006).
Finally, a sub-group of 193 memory-impaired individuals
representing all three training conditions was identified and
compared to the remaining unimpaired participants. The
memory-impaired participants showed typical gains after
receiving reasoning or speed of processing training but,
interestingly, not following memory training. This unexpected
pattern which may have reflected the heterogeneity of the
impaired population, underscores the need for caution in
Page 22 of 50
applying training programs designed for a particular

population to other populations.
Page 23 of 50
3.4.2 Comprehensive training strategy

A team of scientists and clinicians at the Rotman Research
Institute in Toronto took a different approach to developing a
multidimensional cognitive rehabilitation program (Stuss et al.
2007; Winocur et al. 2007 a, b; Craik et al. 2007; Levine et al.
2007). Their program is guided by a general model of strategic
processing which assumes that cognitive tasks, whether they
involve straight-forward aspects of learning and memory or
complex problem solving, require strategic thought directed at
achieving a particular goal. Cognitively-impaired individuals
are limited in their ability to apply strategies spontaneously
and, unlike normal young adults, fail to adjust to the fact that
conscious effort is now required. An essential premise is that,
with direction and insights gained from the program,
participants’ use of effective strategies would increase and
their overall cognitive performance would improve.
The protocol divides into three, four-week modules:
◆ memory skills training; in which various, mainly internal,

memory strategies of the kinds described in section 3.2.1
are taught and applied to everyday life situations
(p.64)
◆ practical task training; an adaptation of Levine et al.’s
(2000) Goal Management Training program, which focuses
on strategies for performing everyday cognitive tasks;
◆ psychosocial training in which the aim is to enhance

psychological well-being and confidence in participants’
ability to follow a strategic approach in problem solving.
The trial was conducted on 49 community-dwelling, normal

older adults, following a multiple baseline, cross-over design
that allowed for between- and within-group comparisons to
evaluate training effects. Memory, practical task planning, and
psychosocial status were evaluated before training,
immediately and six months after the completion of training.
Notwithstanding the small sample size, significant gains were
achieved in all three domains. Notably, there were
improvements in performing simulated real-life tasks which
reflected generalization of improved cognitive skills to
everyday situations. Training-related benefits were maintained
over the long-term. On some measures, there was progressive
improvement over the six-month follow-up period, suggesting
Page 24 of 50
that participants were continuing to practice and benefit from

techniques acquired during rehabilitation training.
The results of the Rotman trial add to those of the ACTIVE and
SIMA trials and reinforce the value of the multi-dimensional
approach. At the same time, they raise important questions.
Future research will determine whether focusing on specific
processes or following a more comprehensive strategy will be
more efficacious, or whether circumstances (e.g., type of
patient, availability of resources) will dictate treatment
selection. Also to be resolved is the suitability of the respective
protocols for different clinical populations. The ACTIVE trial
indicated that caution must be exercised in attempting such
applications. The Rotman protocol has been revised for
individuals with diagnosed cognitive impairment and trials
involving brain-damaged populations are underway. Related to
this, the programs were designed for individuals with age-
related cognitive decline or relatively mild impairment. It
remains to be seen whether the programs can be adapted to
patients with more severe cognitive impairment and co-
existing mental health problems.
Finally, an important question relates to how well such

programs work in combination with pharmacological
therapies. As indicated below, the use of cognitive-enhancing
drugs (eg., anti-cholinesterase, methylphenidate) to treat
cognitive impairment is increasing, and there is some evidence
of added benefits in patients with Mild Cognitive Impairment
when such treatment is combined with cognitive training.
Systematic study, including appropriate control groups, is
needed to determine whether there are benefits to combining
drug therapy with multidimensional cognitive rehabilitation
over and above those to be gained from each form of
treatment on its own.
Page 25 of 50
3.5 Pharmacological Approach

Drug therapy in the treatment of cognitive impairment
derives, of course from the medical model. The origins of this
approach are in the cholinergic hypothesis (Bartus 1982),
which relates memory loss (i.e. of the type seen in old age,
Mild Cognitive Impairment, and the early stages of
Alzheimer’s disease), to a depletion of acetylcholine levels in
basal forebrain and hippocampal brain regions. As a result,
several drugs, notably donepezil (Aricept), rivastigmine
(Excelon), galantamine (Reminyl), were developed to increase
(p.65) cholinergic function by increasing the supply of a key
enzyme – choline acetyltransferase. The drugs, which are
widely used, are well tolerated. Several studies, including
some randomized control trials, have shown that they can help
stabilize and improve cognitive function in individuals
experiencing mild to moderate memory loss (Farlow et al. 2000;
Mohs et al. 2001; Gauthier et al. 2002; Raskind et al. 2004).
Some studies suggest that cholinergic drugs may be effective
in treating memory impairment following TBI (Cardenas et al.
1994; Walker et al. 2004).
In terms of relative effectiveness, the Cochrane Dementia and

Cognitive Impairment Group recently published separate
meta-analyses of double-blind randomized control trials of
donepezil (Birks and Harvey, 2006), galantamine (Loy and
Schneider 2007), and rivastigmine (Birks et al. 2000). Each
was associated with significant cognitive improvement relative
to placebo treatment, and there seemed to be little difference
in over-all efficacy (see also Hogan et al. 2004). The few
studies that attempted to compare directly the effects of the
different cholinergic drugs (e.g., Hogan et al. 2004; Wilcock et
al. 2003; Wilkinson et al. 2002), have not yielded definitive
conclusions.
Not all studies have reported positive effects of cholinergic

treatment. In a recent review, Lanctôt et al. (2003) identified
several factors that may affect outcome. These include APOε4
status, post-treatment autonomic responses, disease status,
neuropsychiatric profile, and several biological markers,
including CSF metabolites, and the metabolic status of the
amyloid precursor protein. This suggests that only a subset of
memory-impaired individuals can benefit from cholinergic
Page 26 of 50
treatment, which underscores the need to characterize those

individuals.
Other cognitive-enhancing drugs whose effects are mediated

by different pharmacological pathways are becoming
available. Memantine, an NMDA receptor antagonist, has been
approved recently in the USA and Canada. There is evidence
that memantine may be effective in relatively advanced stages
of Alzheimer’s disease (Reisberg 2003), and a study by Tariot
(2004) suggests that its effectiveness may increase when
combined with donepezil. Finally, methylphenidate, a CNS
stimulant that acts on dopaminergic and serotinergic systems
is being used increasingly to treat cognitive impairment in
various clinical populations, including ADHD (Szobot et al.
2003), TBI (Kaelin et al. 1996), brain tumour (Meyers et al.
1998), and stroke (Goldstein 2003).
The overall consensus is that cholinergic drugs and other

approved drugs do offer cognitive benefits to at least some
individuals with Alzheimer’s disease and possibly other
cognitively impaired people as well. The gains are often
modest and there are conflicting findings but the results to
date can be viewed as promising. Further investigation of the
cognitive enhancing properties of pharmacological agents is
clearly warranted.
4 New directions in rehabilitation

4.1 Range of service
Cognitive rehabilitation as a field has primarily developed with
the needs of individuals with acquired brain injuries in mind.
Increasingly however, patients with cognitive impairments due
to much broader array of etiologies are also requesting
rehabilitation (see box 4.2 below). (p.66)
One area of particular focus is the cognitive effects associated

with cancer and cancer treatment. Cognitive disruption
following cancer diagnosis and treatment is becoming
universally accepted by patients, health care professionals and
researchers. In one study, as many as 75% of breast cancer
patients experienced cognitive changes as a result of cancer
and cancer treatment (Weineke and Dienst, 1995). This
research is limited by methodological challenges and the lack
of standardization of neuropsychological tests (Vardy et al.
Page 27 of 50
2007). The following neurocognitive changes are most

common:
◆ verbal and visual memory;
◆ attention/concentration;
◆ language;
◆ motor skills;
◆ mental slowing;
◆ difficulties multi-tasking;
◆ ability to organize.
Box 4.2 Etiologies of focus in adult cognitive

rehabilitation
◆ Traumatic Brain Injury
◆ Stroke and White Matter Disease
◆ Aphasia and other language disorders
◆ Healthy Aging
◆ Healthy Working Adults
◆ Dementia and Mild Cognitive Impairment
◆ Multiple Sclerosis
◆ Epilepsy
◆ Attention Deficit Hyperactivity Disorder
◆ Schizophrenia and Schizotypy
◆ Mood Disorders
◆ Pain
◆ Addiction
◆ Cancer and cancer treatment (p.78)
(p.78)
This cluster has lead some to suggest that frontal-subcortical

networks are particularly vulnerable to cancer treatment
effects (Wefel et al. 2004).
Page 28 of 50
The mechanisms for cognitive change following cancer

diagnosis and treatment are largely unknown. One obvious
culprit is the direct effects of radiation or chemotherapy. (p.
67) Cranial irradiation can cause cognitive deficits, even
dementia (Taphoorn and Klein, 2004), and patients receiving
high dose chemotherapy are at greater risk for cognitive
disruption following treatment than patients receiving low
dose chemotherapy (Schagen et al. 2006; Stewart et al. 2008;
Van Dam et al. 1998). However, not only do many cancer
patients experience cognitive loss in the absence of any
radiation or chemotherapy treatment, research has found pre-
treatment neuropsychological impairments in Stage 1–3 breast
cancer patients relative to Stage 0 patients and healthy
controls (Ahles et al. 2007). This would suggest that either the
cancer itself, or psychosocial effects such as anxiety,
depression and post traumatic stress disorder (Hermelink et al.
2007), and a host of other factors (e.g., impact of surgery and
anesthesia; comorbid illnesses) may play a role. Fortunately,
long term post-treatment cognitive changes seem to persist in
only a subset (17%–34%) of cancer survivors treated with
chemotherapy (Ahles and Saykin, 2007).
Considerable effort has been placed on rehabilitation for these

changes, with rehabilitation in pediatric and adolescent cancer
patients leading the way (c.f. Butler and Mulhern, 2005). As an
example from the adult population, Ferguson et al. (2007)
administered Memory and Attention Adaptation Training
(MAAT) to 29 women (averaging 8 years post-chemotherapy
for stage 1 and 2 breast cancer). MAAT consisted of a
workbook and four individual monthly visits. The 30–50 minute
individual monthly visits involved a review of the patients
current knowledge of cancer-associated memory problems,
identification of ‘at risk’ situations where memory failures
arise, and learning and practicing both internal and external
compensatory strategies specific to the kinds of mistakes they
were prone to make. Application of the strategies in their
home environments via homework assignments provided
additional opportunities to rehearse and consolidate the
information learned. Telephone contacts between the monthly
visits served as reminders and additional support for applying
the strategies. Participants were assessed on:
◆ quality of life;
Page 29 of 50
◆ depression;
◆ anxiety;
◆ self reported cognitive complaints;
◆ measures of attention/concentration;
◆ spatial memory;
◆ verbal memory;
◆ language;
◆ executive function.
Assessment occurred at four points during the study; baseline,

immediately following the program, 2 months and 6 months
following the program. Significant improvement over baseline
was observed at each assessment on measures of verbal
memory and processing speed complimented by a significant
reduction in self-reported daily cognitive complaints. This
group now has a large scale study currently underway with
expectations of promising results.
(p.68) Although the research into cognitive changes

associated with cancer is in its infancy, great strides have been
made in a short time. Given the improvement in mortality
rates associated with cancer (specifically breast cancer), the
need for efficacious cognitive rehabilitation programs is
becoming increasingly vital.
Page 30 of 50
4.2 Use of neuroimaging tools

A large number of studies have used neuroimaging tools to
explore the neural correlates of cognitive difficulties
associated with TBI, stroke, aging, and dementia, but only
more recently have these tools been applied to studying the
neural correlates of performance gains associated with
rehabilitation. In the previous edition of this book, we
reviewed Robertson and Murre’s (1999) framework
integrating rehabilitation and neural recovery. In short, they
argued that recovery depends on a number of factors
including the extent to which an underlying neural network is
disrupted, the extent to which the neural network is
distributed versus localized, and the type of stimulation
affecting recovery (bottom-up versus top-down). Research on
practice-related plasticity in healthy individuals provides some
support for the notion that neural change (or recovery)
depends on these factors (c.f. Kelly et al. 2006). Practice of
simpler cognitive tasks (e.g., sensorimotor tasks) generally
increases task-related activation, usually involving more
extensive areas of activation (e.g., broader activation of
primary motor cortex) after practice of a finger-to-thumb
opposition sequence (Karni et al. 1995). By contrast, practice
of complex cognitive tasks (e.g., working memory) generally
decreases task-related activation, most notably in prefrontal
and parietal regions, suggesting a decreased reliance on top-
down control processes (Erickson et al. 2007).
The same principles may not apply in the case of training

effects on brain activations in brain injured individuals. Sturm
et al. (2004) explored brain activation during an attention task
before and after alertness training in individuals who had
suffered a right-hemisphere stroke. Training was associated
with increased activation in right frontal and parietal regions
activated at baseline by a healthy control group. Meinzer et al.
(2008) found similar perilesional increases in activation
following language training after stroke. Kim et al. (2009)
reported reduced activation of middle and inferior prefrontal
cortex and increased activation of the anterior cingulate after
attention training following TBI. All three studies suggest that
training effects were mediated more by restoration
(“normalized” activation patterns) than by compensation
(recruitment of additional brain areas). However, the pattern
of results is likely to depend on a complex interplay among
factors such as etiology, particular aspects of training (e.g.,
Page 31 of 50
duration and frequency), and time-since-injury. Compensation

may be more likely in the case of slowly developing etiologies
such as aging (c.f. Cabeza 2002). In patients with acute
injuries, compensation may precede restoration, as Saur et al.
(2006) found for language recovery following stroke. Although
the use of neuroimaging tools is too new to draw conclusions
about the neural mechanisms of recovery and rehabilitation,
we expect significant progress in this regard in the coming
years.
(p.69) 4.3 Incorporation of adjuvant interventions

The results from recent studies have identified two factors
that have fairly profound effects on cognitive and neural
functioning that have yet to be incorporated into cognitive
rehabilitation: physical fitness and diet. Studies in non-human
animals have identified that physical exercise promotes neural
angiogenesis, neurogenesis, and up-regulation of
neuroprotective molecules (e.g., brain-derived neurotrophic
factor) (c.f. Kramer et al., 2008). When sedentary older adults
are engaged in aerobic training (particularly if combined with
strength and flexibility training), cognitive improvements are
noted especially in executive abilities (Colcombe and Kramer
2003). Aerobic training during an attentional control task
yields increased activation in prefrontal and parietal regions
(Colcombe et al. 2004), as well as in grey matter volumetric
increases in prefrontal and superior temporal regions (c.f.
Kramer et al., 2008). In terms of diet, both proper intake of
particular micronutrients (e.g., vitamins, antioxidants, folate)
and low intake of particular macronutrients (saturated fats and
cholesterol) are associated with better cognitive functioning;
this due possibly to the role of these nutrients in
neurovascular health (Greenwood 2003). These benefits of
physical exercise and diet intervention may enhance the
efficacy of cognitive rehabilitation programs. Preliminary
support for this idea comes from a study by Small et al. (2006),
which combined exercise, diet, stress reduction, and
mnemonics interventions in a group of middle aged adults, and
found improvements in verbal fluency and activation of
prefrontal regions. Future studies will help to identify the
particular combinations that best facilitate recovery or
improvement of functioning and the combinations best tailored
to different client groups.
5 Conclusion
Page 32 of 50
Despite the relatively new development of cognitive

rehabilitation as a clinical discipline, the studies reviewed
above provide grounds for optimism. The refinement of
standard approaches offer more reasons to be optimistic but
perhaps the most encouraging development is the growing
willingness to combine the best of the various approaches. The
result is the emergence of holistic and multidimensional
approaches which have been associated with positive
outcomes. Equally encouraging is the broad consensus that
cognitive rehabilitation programs must be evidence-based and
derive from solid empirical and theoretical bases (Cicerone et
al. 2005).
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Assessment of attention


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Joke Spikman
Ed van Zomeren
DOI:10.1093/acprof:oso/9780199234110.003.05

Clinicians are interested in different aspects of attention
depending on the type of brain damage involved and the
practical questions to be addressed. For instance, the
assessment of transient cognitive impairments may be critical
in epileptic patients, whereas in stroke patients hemi-neglect
will be most relevant. In head-injured patients, the clinician
might want to study speed of information-processing. This
chapter discusses ways of assessing attention, assessing the
speed of information processing, assessment of focused and
divided attention, testing attention on the strategic level,
hemi-inattention, and cognitive rehabilitation of attention.
Keywords: attention, neuropsychological assessment, cognitive rehabilitation,

brain damage
1 Introduction
Attention is a broad concept that has been defined in various
ways. In everyday daily language it is often used to mean
concentration, which refers to selective looking or listening;
effortful processes. Thus, attention has two broad dimensions:
selectivity and intensity. These dimensions are readily visible
Page 1 of 25
in the spotlight metaphor: attention can be directed like a

spotlight to illuminate a certain object, while the intensity of
the light may vary. Attention can be seen as a quality of
information-processing; perception, processing, storage,
retrieval and use of information are optimal when the system
is directed properly and when the required level of intensity is
present. Thus, attention can be defined as the state of a
processing system that is optimally tuned in terms of
selectivity and intensity. The concept of attention is closely
related to speed of information processing. As the capacity of
the information processing system is too limited to process all
available information, selection of relevant information is
essential.
It is important to note that despite this definition, attention is

not a unitary concept. Our definition already distinguishes two
dimensions. When attentional behaviour is described, several
additional task-related terms appear (for example, when
investigators speak of divided attention or sustained
attention). In fact, different taxonomies of attention have been
proposed, some of them psychological (Mirsky et al. 1991; van
Zomeren and Brouwer 1994), and others based on
neuroanatomy (Mesulam 1985; Posner and Petersen 1990).
The existence of these different approaches inspires two
caveats.
◆ General statements about ‘the attention’ of a patient

should be avoided. The situation (or the task) to a large
extent determine which aspects of attention will be
essential and whether deficits will become apparent. A
patient’s attention may be adequate for a social chat, but
inadequate for driving a car through dense traffic in rush
hour. Thus, statements about the attention of a patient
should always be qualified in terms of the specific task and
situation.
◆ The assessment of attention should never be limited to

performance on a single task. For example, recording of
simple reaction time can tell us something about the basic
speed of processing in a particular patient, but tells us little
or nothing about his or her ability to react flexibly on a dual
task, or to sustain attention over half an hour.
Page 2 of 25
In practice, the clinician will be interested in certain aspects

of attention, depending on the type of brain damage involved
and the practical questions to be addressed. In the (p.82)
assessment of epileptic patients transient cognitive
impairments may be critical, whereas in stroke patients hemi-
neglect will be most relevant. In head-injured patients the
clinician might want to study speed of information-processing.
Practical questions may include fitness to drive (in which
divided attention is important), in educational situations (in
which sustained attention to a task in a noisy environment is
essential). Hence, the selection of attention tests should be
made relevant to the patient’s neurological diagnosis, and
daily life (including occupational risks).
2 Ways of assessing attention

As a mental construct, attention can only be measured
indirectly, since, in Section 1, attention can be defined as a
quality in the subject’s perception, processing, storing,
retrieval and use of information. This implies that attention
has to be measured through other behaviours (e.g., by
studying the efficiency of visual search or the speed of visuo-
motor responses). In this sense one could say, ‘There are no
tests of attention.’ The ideal paradigm for studying the
attentional component of a particular activity consists of a task
with two conditions (and a variation that taps a certain aspect
of attention). For example, focused attention can be tested by
presenting the same task twice i.e. with and without
distraction by irrelevant stimuli. The best known paradigm in
this regard is the Stroop Colour Word Test, where speed of
colour naming is measured twice; the second time under
distraction by word meaning. Hence the efficiency of a certain
aspect of attention is expressed as a difference between two
time scores. Unfortunately, difference scores raise a number of
metric and reliability problems, among them decreased
reliability. Solutions to such problems differ in their clinical
usefulness, but the use of ratio scores seems more fruitful
than covariance analyses (Spikman et al. 1996; Zoccolotti and
Caracciolo 2002).
A second problem is that most available clinical tests tap more

than one aspect of attention. A time score obtained in a visual
search task may reflect both the speed of processing of visual
Page 3 of 25
information, and higher-order aspects of attention such as

strategy and flexibility.
A third problem concerns the fact that there is a gap between

attention tests and everyday life situations that tap the same
attentional aspects. Ideally, assessment of attention should
have ecological validity, that is, predictive value for the
patient’s daily life functioning. This does not necessarily imply
that attention tests should look like daily life tasks. Rather,
they should require the same cognitive abilities as daily life
situations do.
2.1 Observation and rating

The oldest approach to the assessment of attention as a
psychological construct is clinical observation. Observation
has obvious advantages: it does not require any equipment,
and it hardly requires extra time, since it is integrated into the
natural contact between clinician and patient. During bedside
conversation or an apparent social chat on the way to the
neuropsychology department, the psychologist may observe
whether the patient is (p.83) alert and attending to the
environment and the investigator, or whether there are signs
of hemi-neglect or drifting attention (Stuss and Benson 1986).
During formal assessment one may note whether patients are
distracted by noises from outside, and whether they are
attending adequately to tasks that in themselves, are not
considered attention tests.
Observation can be standardized by the use of rating scales.

The Neurobehavioral Rating Scale, devised by Levin et al.
(1987), contains a few items aimed at attention. The scale has
satisfactory inter-judge reliability and validity. A questionnaire
that can be filled out by patients and their relatives is the
Cognitive Failures Questionnaire (Broadbent et al. 1982). A
Rating Scale of Attentional Behaviour (RSAB) was developed
by Ponsford and Kinsella (1991). This instrument uses 5-point
scales to record the frequency of attentional problems in
patients. Its validity and usefulness were demonstrated in a
rehabilitation institute where professionals (speech therapists
and ergotherapists) rated aspects of attention in head-injured
patients. The RSAB has a high inter-rater reliability (0.91).
2.2 Categorization of attention tests
Page 4 of 25
Any review of attention tests is confronted with an

organizational challenge. Although division into focused
attention, divided attention, and sustained attention may
appear useful, it is actually an unsatisfactory approach. As
mentioned above, several taxonomies of attention have been
proposed and the choice of a particular one for the
organization of assessment methods is always arbitrary. Also,
there is evidence from statistical studies that shows that
concepts that seem quite useful for the description of
behaviour (such as divided attention or sustained attention),
are not necessarily supported by the evidence from factor
analyses of large series of subjects tested on attention tests.
Spikman et al. (2001) studied the construct validity of well
known attentional concepts, listing several statistical studies
that showed little agreement on useful factors. It appeared
that each investigation produced new factors and hence new
constructs. Still, two main factors were noted to appear, albeit
under various names, in most of the statistical studies:
◆ speed or processing capacity;
◆ control or working memory.
Thus, a distinction on an empirical statistical basis is available.

In our own experience, this is quite helpful for the analysis of
attention problems in head-injured subjects (Spikman et al.
2001). However, it also seems useful for the practical
categorization of attention tests. The two concepts of speed
and control are not completely independent: control processes
occur at a certain speed and these processes may slow down
in cases of brain damage. Moreover, changes in processing
speed may affect control: when speed of processing increases
or decreases, this will bring changes in the amount and nature
of control required.
The relative weights of speed and control can vary from task
to task. This is partly due to task characteristics or task
demands. Some tasks are experienced as easy and proceeding
almost ‘on their own’ once they have been started. For
example, finger tapping performance is an easy, repetitive
motor task requiring very little control—the only control
required is to monitor one’s tapping speed. On the other hand,
writing a letter of (p.84) application requires intensive
control, although speed is rarely essential. Generally speaking,
control requirements are maximal in unstructured tasks that
cannot be tackled using routine responses. Control invariably
Page 5 of 25
implies working memory activity, in which rules for the

performance of the task need to be kept activated. A second
task characteristic is the time pressure involved.
Another source of variation is subject characteristics, in

particular, learning effects. In general, the amount of control
required decreases as a function of task learning. In fact,
many well-trained tasks require so little control that we
consider them to be automatized and not requiring much
effort. Learning to drive is a good example of a task consisting
of many subtasks which require control and a great deal of
effort (in the first lessons), but which becomes highly
automatized in the experienced driver. A second important
characteristic is speed/accuracy trade-off.
Thus, the distinction between speed and control is related to

the distinction between time pressure and structure. This
allows us to look at attention tests on three levels: the
operational level, the tactical level and the strategic level.
2.2.1 Operational level

At this level speed is the main factor, while control is minimal.
Time pressure is high as patients are either instructed to work
as quickly as possible, or are presented with stimuli at a high
rate. On the other hand, the task presented to the subject is
highly structured, signals and responses are simple and
unambiguous, and through instruction the subject knows
exactly what to do. Attention can be tested at a basic level,
here with time being the essential dependent variable. At this
level, the subject can do little other than ‘pay attention and try
to be quick’. Performance on these basic tasks may be called
stimulus-driven (see Table 5.1). Because the task stimuli direct
subjects on what to do the working memory load is minimized.
2.2.2 Tactical level

At this level, both time pressure and structure are
intermediate. Tasks are more complicated and being fast is no
longer sufficient for optimal performance. A certain amount of
control is required, because the stimuli are often ambiguous,
but the operation to be performed on them is specified in the
instructions. For example, subjects are instructed to ignore
distracting stimuli, or to divide their attention while reacting
to two kinds of symbols. At this level, subjects have to find a
personal speed/accuracy trade-off (i.e. a balance between
Page 6 of 25
working speed and error rate). Performance on this level can

be considered
Table 5.1 Characteristics of the three levels of

attention tests
Level Time pressure Structure of task
Operational High Highly structured, stimulus-

driven
Tactical Intermediate Partially structured, memory-

driven
Strategic Low Unstructured, strategy-driven
(p.85) memory-driven, since instructions and rules for

performance must be kept activated in working memory.
2.2.3 Strategic level
At this level, time pressure is minimal but subjects have to find
their own approach for an optimal performance of the task.
Hence, instructions do not dictate completely what should be
done and, in this sense, these tests of attention offer less
structure than tests that are aimed at the operational and
tactical levels. Basically, the subject has to apply his or her
own strategy (i.e. performance is strategy-driven).
3 The operational level: speed of information-processing

At this level time scores are essential although errors do not
assume any importance. An example would be the recording of
simple reaction times in response to either visual or auditory
stimuli. Neurological patients may be slow on this task, but the
signals are clear and the responses are so simple that errors
are extremely rare and thus not useful as assessment. What
one tries to assess at this level is the basic speed of
information-processing.
3.1 Assessing mental slowness

Reaction time recordings (as they feature in many
computerized test batteries), are an excellent method of
assessing basic mental speed. However, it is important that
the task permits total reaction time to be split into decision
and movement components, in order to disentangle the
confounding effects of peripheral slowness on central
slowness. The test forms S1-S5 of the Reaction Test in the
Vienna Test System allow for this possibility (Schufried, 2006).
Reliabilities (Cronbach’s Alpha) for these tests vary between .
Page 7 of 25
83, and .98 for the reaction times, and between .84 and .95 for
the motor times. Apart from reaction times, the clinician may
use the basic conditions of well known clinical tools such as
Trailmaking A, and word reading and colour naming of the
Stroop Colour Word Test. Test–retest reliability is satisfactory
for both tests, ranging from 0.70 to 0.90 for Trailmaking A,
and from 0.83 to 0.91 for reading and colour naming in the
Stroop test (Spreen and Strauss 1991). Also, the subtest Digit
Symbol from the Wechsler Adult Intelligence Scale (WAIS)-R
can be used for the assessment of mental speed.
As noted in Section 1, no attention test ever taps one aspect of

attention only. This will be clear from the tests mentioned
above: many of them require some visuo-motor skill. A second
important point is that the assessment of speed of processing
requires finely graded norms. In particular, age is an
important factor. Generally speaking, processing speed
decreases with increasing age. For some tasks, gender is also
important. For example, men react slightly faster than women
to simple signals. Thus, the clinician should take age and sex
into account when testing attention in the basic sense of speed
of processing.
Theoretically, the question of domain-specific slowness can be

raised. In the clinical literature, mental slowness is usually
discussed as a global phenomenon that manifests itself in all
task domains and all sensory modalities. In practice, this
simplification (p.86) seems justified. In case of diffuse injury
to the brain or of (more or less) diffuse degenerative processes
such as Alzheimer’s disease, the slowness indeed manifests
itself in all aspects of behaviour. Even in the case of focal
damage such as that caused by stroke or neoplasm, a general
mental slowness is often noted and confirmed on subsequent
testing. However, it is conceivable that a focal lesion may
disrupt or slow down specific processes only, (e.g. the
manipulation of verbal information in the case of left
hemisphere damage in right-handed subjects).
4 The tactical level: focused and divided attention
Page 8 of 25
In tests at this level, subjects are still expected to work as

quickly as possible, but more control is required in order to
prevent errors. A good example would be Trailmaking B. While
in Trailmaking A the instruction is rather straightforward—to
connect numbered circles by a pencil line—in Trailmaking B a
certain load is placed on working memory in which two
sequences have to be kept active, i.e. the alphabet and the
numbers from 1 to 13. As the correct response depends on
keeping track in both sequences and using them alternately,
there is ample opportunity for making errors. As far as visuo-
motor behaviour is required, Trailmaking B is roughly
comparable to Trailmaking A. Hence, the fact that healthy
subjects need more than twice the time required for A when
doing B reflects the far greater amount of control involved in
the latter condition of the test.
On the tactical level, the distinction between tests of focused

and divided attention is useful.
◆ The concept of focused attention can be applied whenever

the subject has to respond selectively, i.e. when irrelevant
stimuli are present;
◆ The concept of divided attention refers to task situations

in which there are more subtasks that have to be performed
simultaneously or that require more than one type of
response.
In the 1990s, two batteries of attention tests were presented

that assess attention mainly at the tactical level. Both of them
can be seen as attempts to approach assessment with a firm
theoretical basis and well-defined concepts and both of them
originated in Europe. Zimmerman and Fimm (1993) devised
the Test for Attentional Performance (TAP), a computerized
battery with unusual psychometric qualities. While each
subtest was based on the relevant theoretical literature, the
authors have made an effort to make the tasks feasible in a
clinical setting, in terms of ease of administration,
standardization of instructions, and solid normative data.
Among its subtests are tests of Divided Attention, a Go/No go
task and Visual Scanning. The psychometric characteristics of
the TAP are discussed extensively by Zimmermann and Fimm
(2002).
Page 9 of 25
A second useful battery of attention tests was presented in

1994 by Robertson et al. The Test of Everyday Attention (TEA)
is marked by its attempt to demonstrate ecological validity.
Like the TAP, the TEA attempts to assess attention from a
sound theoretical background, but its outward appearance is
quite different. While the TAP is computerized, the TEA
requires minimal instrumentation as its visual tasks are paper-
and-pencil while the acoustic tasks require a tape recorder for
presentation. Ecological validity is (p.87) created by
choosing tasks that closely resemble daily life situations. The
validity of the TEA has been studied in cerebrovascular
accident (CVA) and head-injured patients and can be judged as
satisfactory. The reliability of all subtests is good, with the
exception of Telephone Search while Counting.
4.1 Assessing focused attention

When irrelevant stimuli can act as distractors, subjects have to
focus on the relevant ones. Visual search tasks are attention
tests that require some selectivity, as all stimuli are irrelevant
except the ones designated as targets. In Trailmaking A, all
numbered circles are to be regarded as ‘noise’ except the
number that the subject is searching for. An important
distinction should be made between structured and
unstructured fields of search. Visual search tasks with a
structured field are easier, i.e. require less control, than tests
with an unstructured field. For example, some letter
cancellation tasks present letters in horizontal lines, and the
d-2 test (Brickenkamp 1981) also presents its stimuli in
convenient lines. In contrast, some visual search tasks present
quasirandom fields, thus forcing the subjects to scan the field
according to their own insight. Trailmaking is a good example,
but tests for the detection of hemi-neglect also make use of
unstructured fields (e.g., the Bells test, Gauthier et al. 1989).
The Test of Everyday Attention (Robertson et al. 1994) contains
two visual search tasks assessing focused attention with
ecological validity and satisfactory reliability—Map Search and
Telephone Search. In the first of these subtests, the subject is
required to search for gas stations or restaurants on a real
map; in the second the subject has to find certain items in a
telephone directory.
Many visual search tasks allow the clinician to consider the

speed/accuracy trade-off in patients, by studying number of
Page 10 of 25
errors in relation to speed. For example, in our own laboratory

we found that severely head-injured patients were working
slowly but accurately on the Bourdon dot configuration test
(van Zomeren and Brouwer 1994).
In most visual search tasks, all distractors are present

simultaneously. A classic test of focused attention, the
Continuous Performance Test, presents distractors
successively in time, while the subject is on the look-out for
the target letter A. This test also has a condition requiring
slightly more control by working memory—in the XA condition,
the letter A is a target only when it is preceded by an X.
The S3 and S4 test forms in the Reaction Test of the Vienna

Test System (Schuhfried, 2006) can also be considered to be
tasks measuring focused attention because the subject must
only react to a specific stimulus combination and inhibit
responses to irrelevant stimulus configurations.
Distractors differ greatly in their distracting power. In the case

of visual search, it is usually quite easy to search for a target
while processing all other stimuli very superficially only. A
good example of a strong distractor is found in the classic
Stroop paradigm, where stimuli have two features: a colour
and a word meaning that conflicts with the colour. As reading
is highly automatized, the instruction to focus on the colours
of the words creates a strong response interference that is
measured in a slowing of performance, compared to (p.88)
that in simple colour naming. For this interference subtask of
the Stroop, reliability coefficients of 0.89 and 0.91 have been
reported (Spreen and Strauss 1991).
4.2 Assessing divided attention

The classic paradigm to test divided attention is a dual task, in
which a subject is instructed to perform two or more tasks
simultaneously. In some tests this involves mainly switching
between two or more response tracks or modalities, thus
requiring flexibility, in others this involves the combination of
several activities under time pressure in order to produce the
correct response. The complexity of such tasks may vary
greatly, depending on the amount of control required in each
subtask. Park et al. (1999) demonstrated that divided attention
is impaired in head-injured subjects when the tasks require
controlled processing, but not when the tasks can be carried
out relatively automatically. Unfortunately, the dual-task
Page 11 of 25
paradigm has hardly been used in clinical assessment. The

Test of Everyday Attention (TEA, Robertson et al. 1994)
contains the subtest Telephone Search while Counting, in
which subjects have to find items in a telephone directory
while at the same time counting the number of tones in a tape-
recorded series. Unfortunately, reliability of the dual-task
decrement effect was not high; satisfactory in two groups of
non-brain-damaged subjects (0.59 and 0.61) but somewhat
lower in a group of patients with cerebrovascular accidents
(0.40).
A typical example of a task requiring switching between two

response modes is the Trailmaking B, in which the subject has
to keep track both of the numbers as well as the letters while
alternating between them. Correction for the confounding
effect of visuomotor slowness is allowed by using the B:A ratio;
several authors (Mitrushina, 2005) found a ratio score greater
than 3 reflecting deficient performance on part B indicating a
problem with alternating switches.
The Determination Test (DT) of the Vienna Test System

(Schuhfried, 2006) requires the division of attention between
different stimulus modalities, namely visual and acoustic, as
well as between different response possibilities, namely
pressing a hand button or a foot pedal. It was found that the
test discriminated between groups of neurological and
psychiatric patients and a group of healthy controls.
A well known instrument is the Paced Auditory Serial Addition

Task (PASAT; Gronwall and Sampson 1974). This presents
series of 61 digits to the subject, with the instruction to add
the last digit to the preceding one, giving the answer aloud.
This task can be seen as a divided attention task, as subjects
are dividing their processing capacity over several activities:
listening, adding, answering, and keeping track in their
working memory. However, the smaller the inter-stimulus
interval (ISI), the more these subtasks will overlap in time and
consequently, the more the ability to divide attention is
required. Several studies have demonstrated the validity of
PASAT (i.e. sensitivity to the effects of head injury, and factor
analytic evidence of loading on an attention/concentration
factor). Gronwall and Sampson claimed that performance on
PASAT was not related to arithmetic ability (or general
intelligence), but this claim has been challenged. As Zoccolotti
and Caracciolo (2002) put it: ‘The overall picture seems to
Page 12 of 25
reveal a mild to moderate link (p.89) between general

intellectual abilities and performance on the PASAT. Clinicians
should consider this finding and further research might allow
for a possible adjustment of normative data based on the
general intelligence g factor.’
5 The strategic level: supervisory control

Testing attention on the strategic level meets with a paradox:
strategy can be deployed only in an unstructured situation, but
a test requires standardization and hence structure. As a
result of this paradox, it is hard to find paradigms that truly
assess the higher aspects of attention, i.e. supervisory
attentional control. Still, there are a few instruments that can
be recommended.
5.1 Assessing supervisory control

The oldest of these is the Wisconsin Card Sorting Test (Lezak
1995). In this task, the subject has to change his or her
response set on the basis of feedback by the experimenter.
That is, while sorting cards according to a principle originally
chosen by the subject (e.g. colour of symbols on the cards),
from a certain point in the process the experimenter no longer
confirms the sortings, now indicating that the subject is
sorting cards on the wrong pile. Thus, the subject has to find a
new principle (e.g. number of symbols on the cards). This
shifting can be seen as requiring higher order flexibility, which
links it to attention on the strategic level. There exists an
extensive literature on the validity of the WCST and its revised
versions. While originally it was believed that the WCST was
especially sensitive to frontal brain damage, this view has
been criticized with good arguments.
Shallice (1988) devised the Tower of London test. This test,

derived from an oriental puzzle game, is closely connected to
the theoretical model of the Supervisory Attentional System as
proposed by the same author. Three coloured beads (red, blue,
and yellow) have to be arranged on three sticks of increasing
length, in order to reach a certain pattern in a prescribed
number of moves. There are restrictions in the handling of the
beads, e.g. one may handle only one of them at a given time,
and they may not be put down on the table. The solving of
each puzzle item requires some thinking ahead and practically
always a certain bead has to be placed temporarily on a stick
that is not its final destination. Thus, subjects have to plan
their moves and to suppress impulsive ‘solutions’, and in this
Page 13 of 25
regard it might tap supervisory attentional control.

Unfortunately, normative data are lacking and both validity
and reliability are unknown.
Thirdly, located within a battery called the Behavioural

Assessment of the Dysexecutive Syndrome (BADS; Wilson et
al. 1996), there is an interesting task called the Six Elements
Test. In this task, subjects are given 10 minutes to perform six
tasks. They are expected to use this limited time wisely and to
respect certain shifting rules. For example, the six tasks fall in
three categories but the subject is not allowed to shift from
task A to B within the same category. The Six Elements Test is
largely unstructured, as it does not tell the subject how to
divide the available time over the different tasks. Hence, it
offers good opportunity to observe the subject’s strategy. In
particular, the test has a strong ecological appeal as it enables
us to judge whether the subject is paying attention to passing
time—there is a little clock on the desk counting down the
minutes and seconds.
(p.90) Finally, the BADS also contains the Zoo Test, in which
subjects have to visit a number of sites in a certain order,
while respecting certain rules. Finding the correct route
requires planning and overview in a fairly complex situation,
and thus the task taps aspects of supervisory control.
Page 14 of 25
5.2 Testing the strategic level in daily life

Still, these four tests are far removed from essential
attentional strategies in daily life. What one would like to test
is the subject’s ability to attend to highly relevant but
unpredictable cues in an unstructured situation. For example,
attention for nonverbal cues in the social domain is essential
for the maintaining of smooth relationships, both in private life
and in professional situations. However, it is hardly possible to
devise standardized situations that deserve the name of ‘test’
and that will yield objective and quantified information on
these higher aspects of attention. Spikman et al. (2000)
attempted to assess executive functioning in head-injured
patients in a chronic stage (2–5 years after injury) by
observing them when they were trying to find their way
through the University Hospital in Groningen. It was recorded
how these subjects used available information (signs) and
searched for additional information by addressing passers-by
and hospital staff. Spikman et al. found that their head-injured
subjects, were less efficient in the search for and use of
information, and needed more cues to carry on with the task.
Within this group, patients with frontal lesions (detected by
neuroimaging) had poorer performance. With respect to the
Executive Route Finding Task (Boyd and Sautter 1993) which
assesses ‘attention for sources of additional information’, it
may be viewed as a test of attention on the strategic level.
Recently, Spikman and colleagues developed a new,

ecologically valid test, called the Executive Secretariat Task
(EST), measuring higher order control in a daily life situation.
In this three-hour task, a job assessment procedure is
simulated. The subject is left alone in a room with a box in
which a series of simple secretarial assignments, which have
to be organized and executed, some with a deadline. No cues
are provided about how to carry out the assignments, but
necessary materials and information are all available, and at
fixed times, the ‘manager’, sitting in the room next door, can
be asked questions. During the assessment, the subject is
interrupted with an urgent new assignment. It was found that
this test was sensitive to executive dysfunctioning in TBI as
well as stroke patients (Spikman et al. 2007).
6 Sustained attention and sustained control
Page 15 of 25
The term ‘sustained attention’ refers to assessment on a

longer timescale than usual, covering intervals from 10 to 30
minutes. A distinction should be made between high event-rate
tasks and low event-rate tasks. In the former subjects are kept
quite busy, in the latter they are exposed to a boring situation
and their main task is to maintain an adequate level of
alertness in order to detect rare and subtle stimuli. The former
type of task is called a continuous performance test; the latter
type a vigilance test.
(p.91) Unfortunately, in clinical practice it is often concluded

that ‘sustained attention is poor’ when a patient is performing
below standard, for whatever reason, on a lengthy test. In
most cases, this will be unjustified. Even when patients are
reacting slowly on a continuous reaction time (RT) task or
missing many signals in a vigilance task, it may well be that
they are sustaining their ‘poor’ attention quite well.
Conclusions about sustained attention should be based on
time-on-task effects (TOTs). These are changes in performance
over time, and sustained attention may be considered
insufficient when a patient shows an abnormal TOT, i.e.
abnormally increasing response times or an abnormal increase
of missed signals or errors. To detect such deterioration, the
duration of the test should be divided in blocks (e.g. of 5
minutes each).
The demands of a sustained attention test depend on whether

the task is self-paced or experimenter-paced. In other words,
who determines the time pressure? If one uses a prolonged
visual search task such as the Bourdon dot configuration test
(lasting 12 to 15 minutes) subjects choose their own speed of
working. Many well known tests, however, are experimenter-
paced (e.g. the Continuous Performance Test). The essential
difference, of course, is that time pressure cannot be
influenced by the subjects in experimenter-paced tasks.
Another important feature of sustained attention tests is the

amount of control required. In our experience, brain-damaged
subjects can usually deal with prolonged tasks if these are self-
paced and require little control (see Fig. 5.1). On the other
hand, head-injured patients very frequently complain of
increased mental fatigue, indicating that they cannot
concentrate long on daily-life tasks that require some mental
effort. This suggests that
Page 16 of 25
(p.92)
prolonged
control is the
key feature in
the question of
sustained
attention in
subjects with
brain lesions.
6.1 Tests
assessing
sustained
attention
Fig. 5.1 A case of low speed but
The classical
adequate control. Performance of chronic
test for the
stage head-injured patients (HI), and
assessment of
matched controls (MC) on a visual search
sustained
task (Bourdon) lasting 15 minutes. In this
attention is
self-paced task, subjects have to search
the
for groups of four dots, in lines that
Continuous
contain 25 groups of three, four, and five
Performance
dots. Patients need about 3 seconds more
Test (Rosvold
per line than control subjects, but at this
et al. 1956) in
working speed their accuracy is normal;
which
their response curves are strikingly
subjects have
similar and no special time-on-task
to react to the
effects are visible in the head-injured
target letter A
group.
in a long
random series
of letters. The
TAP battery (Zimmermann and Fimm 1993, 2002) contains a
useful Vigilance Test in an auditory and a visual format, with
adequate norms. The Test of Everyday Attention (Robertson et
al. 1994) contains subtests that can be conceived as tests for
sustained attention. The first of these is Lottery, in which
subjects have to listen for their ‘winning number’ that ends in
‘55’. They are presented with a 10-minute tape recorded list of
numbers such as BC 143 and LD 967, and their task is to write
down the two letters preceding all 10 target numbers. The
other subtest is Elevator Counting, which has an unusually
short timescale, and which operationalises the concept in a
highly specific way via counting strings of audio taped tones.
The tasks have an interesting link with neuroanatomy (i.e. the
right frontal lobe). Both subtests have a satisfactory validity
and reliability.
Page 17 of 25
The TAP contains sustained-attention related paradigms such

as Alertness and Vigilance. In the subtest Alertness, the
difference between reaction times with and without warning
signal is calculated. The subtest Vigilance presents a classic
vigilance task (i.e. a quite boring situation in which the subject
is required to watch a monotonously moving line for 15 or 30
minutes, and to push a button whenever an irregularity in this
movement occurs).
Robertson and Manly (1997) devised a paradigm that is not

yet available as a formal test, but might turn out to be quite
useful—the Sustained Attention for Response Test or SART.
This offers a high-event-rate situation, in which subjects have
to react continuously to a random series of digits (0 to 9)
appearing on a screen. Only the digit 3 is a non-target, i.e. a
response to any 3 should be suppressed. As the digits come at
a high rate, approximately one per second, the responding
quickly gets automatised, with the result that subjects are
lured into reacting to the non-target 3 (‘Oops!’). Robertson
and Manly demonstrated that their paradigm has some validity
in the study of head-injured subjects: these patients do not
sustain their control as well as healthy subjects.
7 Hemi-inattention
Hemi-neglect or hemi-inattention differs from other
impairments of attention by its basic nature: it is a disturbance
in a preconscious aspect, i.e. our normally symmetrical
orientation with respect to the outside world. This biological
prerequisite is realized by a cortico–limbic–reticular loop and
thus it can be disturbed by lesions at different anatomical
levels (Mesulam 1985). Hemi-inattention, or neglect of one-
half of the outer world, can manifest itself in all sensory
domains and also in the motor domain. Clinically most
important, however, is visual-spatial hemi-inattention. This is
seen most frequently after lesions in the right hemisphere, in
which case patients fail to attend to the left side of space and/
or their body and this failure cannot be explained by primary
sensory or motor deficits.
(p.93) 7.1 Assessing hemi-inattention

The first method of assessment is observation. A patient may
bump into furniture on the left side or against the left
doorpost. During testing, it can happen that the patient
Page 18 of 25
overlooks the first words or coloured stimuli in the Stroop

Colour Words Test.
7.1.1 Line bisecting and drawing

For formal testing of neglect a large array of tests is available
(Lezak 1995). A classic method of assessment of neglect is line
bisecting, in which subjects have to mark the centre point of a
horizontal line by placing an X on it (Marshall and Halligan
1990). Patients with left-sided neglect tend to deviate to the
right pole of the lines, as they are not aware of the left half of
these lines. Another paper-and-pencil approach of neglect is
drawing: patients will often leave their drawings of a clock,
star, or flower incomplete on the left side (Halligan and
Marshall 1997). For obvious reasons, objects that are more or
less symmetrical are most suitable for the judgment of hemi-
inattention.
7.1.2 Visual search tasks

Next, neglect can be assessed with visual search tasks with
either structured or unstructured fields. Structured fields
consist of lines of stimuli as in some Letter Cancellation Tests,
while unstructured fields present quasi-random arrays of
stimuli such as the Star Cancellation Test or the Bells Test. In
the latter, target stimuli are in fact grouped into seven
columns and a ratio for neglect can be calculated based on
numbers of omissions in 3 columns on the left versus 3 on the
right side (Vanier et al. 1990).
7.1.3 Reading tests

Visual neglect can also be assessed with reading tests, in
which words on the far left are neglected by the subject. A
special case is the Indented Paragraph Reading Test (Caplan
1987) in which the first word of each line is indented from 0 to
25 spaces. This lay-out precludes the possibility that the
neglecting subject could form a compensatory ‘spatial set’, as
each refixation from the end of one line to the beginning of the
next requires a separate act of controlled scanning.
7.1.4 Tests measuring lateral bias and extinction

The Grey Scales task (Mattingley et al. 1994) was designed to
assess the early automatic orienting of attention towards the
ipsilesional side of space. The Grey scale is a semi-continuous
horizontal scale of different grey shades varying between
black and white. The subject is presented with sheets of paper
with two vertically aligned rectangular grey scales of equal
Page 19 of 25
length, whereby the pairs are the mirror reverse of each other.
The subject is asked to judge which of the two appears overall
darker; the upper or the lower scale. Test performance can be
qualified in terms of a rightward or leftward bias. Tant et al.
(2002) found that this test was specifically sensitive in
detecting hemi-neglect.
The Test of Attentional Performance (Zimmermann and Fimm

2001) contains a subtest in which 3-digits numbers are
presented that are distributed randomly over the screen of a
personal computer. Among these, there are target numbers
that seem to flicker, as their (p.94) value is changing at a
high rate. Subjects have to react to these apparently moving
targets. As neglect patients attend predominantly to the non-
target stimuli in the ipsilesional visual field, they miss the
critical stimuli on the left half of the screen due to extinction.
7.1.5 The Behavioural Inattention Test

For those who want to study neglect extensively, Wilson et al.
(1987) developed an attractive battery called the Behavioural
Inattention Test. This test is composed partly of traditional
hemi-neglect tests such as letter cancellation and line
bisection, but it also contains tasks with a clear ecological
validity, such as telephone dialing, coin sorting, and map
navigation. For the set of conventional subtests, reliability is
satisfactory (r = 0.75) while for the behavioural set it is
excellent (test–retest r = 0.97).
8 Cognitive rehabilitation of attention

A more detailed review of the cognitive rehabilitation of
attention is provided in Chapter 6. However, a few remarks
can be made. First, the clinical neuropsychologist can advise
his patients on how to cope with their attentional limitations
(i.e. coach them in the ‘management of slowness’, Spikman
2001). This boils down to supplying general guidelines that will
be useful in various daily life tasks and situations. In Section
2.2 it was argued that the attentional demands of a given task
situation are determined by two task characteristics: time
pressure and structure. Thus, several guidelines can be
formulated to reduce time pressure and improve the structure
of tasks.
◆ Avoid or reduce time pressure.
◆ Create structure.
Page 20 of 25
◆ Keep subtasks separate when possible.
◆ Avoid interruptions.
◆ Determine priorities in advance.
This approach has been formalized and validated by Fasotti et

al. (2000) who devised a training called Time Pressure
Management (TPM). This compensatory strategy training TPM
teaches patients how to deal with their slowness. It consists of
a general self-instruction (‘Let me give myself enough time to
do the task’) followed by four specific steps in the form of
questions the patient has to ask himself. These steps are as
follows.
1 Anticipate time pressure by analysing stages in the

task where two or more things have to be done at the
same time.
2 Make a plan for things that can be done before the
actual task begins.
3 Make an emergency plan to deal as quickly and
effectively as possible with overwhelming time
pressure.
4 Make regular use of the anticipatory plan and the
emergency plan.
Fasotti et al. demonstrated that head-injured patients could

learn this strategy and apply it to a new task, which consisted
of reproducing the relevant information of a videotaped short
story.
(p.95) As described in Section 2.2, performance on a task is

also determined by subject characteristics, in particular
learning and experience. The history of attention training has
shown that ‘attention in general’ cannot be trained by
stimulation or repetition. Time and again, it was found that
training effects do not, or do not sufficiently, generalize to
attention-demanding tasks in daily life. In contrast, task-
specific training can be effective: it is possible to teach
subjects to attend to relevant aspects within a given daily life
task, even when this effect does not generalize. Hence, for the
cognitive rehabilitation of attention, two options seem to exist:
strategy training or task-specific training (cf. Fasotti and
Spikman 2002).
Page 21 of 25
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Page 25 of 25
The rehabilitation of attention


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001

Tom Manly
Jessica Fish
Ian H. Robertson
DOI:10.1093/acprof:oso/9780199234110.003.006

This chapter examines various attempts to enhance the
natural recovery of attentional processes, or to better manage
the consequences of impairment, following brain injury
acquired in adulthood. The results reviewed give grounds for
cautious optimism. However, rehabilitation is about working
with patients to achieve functional goals in everyday life. If the
promising findings showing changes on neuropsychological
tests are to usefully filter through to clinical care, the extent to
which these translate into meaningful functional
improvements must be evaluated.
Keywords: attentional processes, cognitive rehabilitation, neuropsychological

assessment, brain injury
1 Overview
In recent years there have been considerable developments in
how we understand attention. Of most relevance to the clinical
field is the view that attention is not a single entity but rather
a fractionated set of brain processes that are vulnerable to
selective damage. With a clearer idea of what we are looking
Page 1 of 40
at, the role of attention in influencing clinical outcome is

becoming increasingly apparent - both as a function in its own
right and as essential adjunct to the useful expression of other
abilities.
As we will discuss, attention and other ‘central’ functions

cannot be observed directly. The scientific inferential
techniques of neuropsychology and clinical neuropsychology
are essential in determining how these processes operate (and
break down) and in developing specific assessments. The
contribution of a particular impairment to difficulties faced by
patients in daily life is not always clear. In the rehabilitation of
attention, as with any deficit, a broader psychological
perspective that takes into account co-existing impairment,
pre-morbid factors and the psychosocial context of a patient is
vital. Pharmacological interventions for attentional disorders,
at least for adults with neurological damage, are at a relatively
early stage (cf. Warden et al., 2006). Although very useful
developments may take place in this respect, the role of the
neuropsychologist in careful assessment and targeted
rehabilitation is likely to remain crucial in fostering positive
outcomes.
Here we examine various attempts to enhance the natural

recovery of attentional processes, or to better manage the
consequences of impairment, following brain injury acquired
in adulthood. The results we review give grounds for cautious
optimism. However, rehabilitation is about working with
patients to achieve functional goals in everyday life. If the
promising findings showing changes on neuropsychological
tests are to usefully filter through to clinical care, the extent to
which these translate into meaningful functional
improvements must be evaluated.
Page 2 of 40
2 Contemporary views of attention

Improvements in quantification often trigger theoretical
advances. In the case of attention, such quantification is
inherently difficult. We cannot measure what happens when
people attend in the abstract, so we must give them an activity
to perform (read a passage, press a button, name colours and
so forth). Variations in all the other abilities necessary for this
task may well be just as influential as our ‘hidden’ attention
system in (p.98) determining performance. One way around
this problem, and one that has probably underpinned much of
the resurgence in scientific interest in attention over the past
few decades, is to infer ‘its’ presence from the systematic
variation in performance under different attentional
conditions. A simple and highly influential example of this
approach can be found in visual cueing paradigms. Here
participants are asked to keep their gaze fixated at the centre
of a screen and to press a button as soon as they see a target
appear. Whilst for the most part they will have no idea where
this will be (and therefore should ideally monitor the whole
screen), on a few trials they receive a helpful cue as to the
most probable location. Such cues, when accurate, result in
significant reductions in reaction times and, when inaccurate,
in significant increases. As all other aspects of the task remain
constant, these differences can be attributed to the
participants prioritising signals from one location - in other
words - the movement of spatial attention (Posner, 1980). A
similar approach focusing on decrement and enhancement
underpins many other areas such as the effect of distraction,
the effect of time, and the consequences of attempting to
perform two tasks simultaneously.
Such methods have led to much clearer accounts of the

capacities and limitations of normal human attention and,
when combined with the study of brain damaged patients,
neuroimaging and neurophysiological techniques, to the
neural basis of these abilities. Reviewing the area in 1990,
Posner and Petersen proposed three key principles of
attentional function;
Page 3 of 40
"First… the attention system of the brain is anatomically

separate from the data processing systems that perform
operations on specific inputs even when attention is
oriented elsewhere. In this sense, the attention system is
like other sensory and motor systems. It interacts with
other parts of the brain but maintains its own identity.
Second, attention is carried out by a network of
anatomical areas. It is neither the property of a single
centre, nor a general function of the brain operating as a
whole… Third, the areas involved in attention carry out
different functions and these specific computations can
be specified in cognitive terms." (p.26)
They proposed that these different functions included; as

discussed, the capacity to prioritise signals from one spatial
location (spatial attention); to prioritise some forms of
information and to suppress others on the basis of a functional
goal or a stored representation of a target (selective or
focused attention); and to self-maintain an alert, ready to
respond state (arousal/sustained attention). This and similar
taxonomies (e.g. Van Zomeren et al., 1984; Mirsky et al., 1991;
Cohen & Kaplan, 1993) are of course provisional and
vulnerable to further fractionation. The most important clinical
implication is that deficits can arise that are exclusively or
predominantly attentional in nature and that quite distinct
forms of impairment profile (with quite different functional
implications) can arise depending on the location and extent of
damage. This should influence how we perform assessment
and how we go about rehabilitation.
3 A note on terminology
There is a great deal of conceptual overlap between the fields
of attention, executive function and aspects of working
memory - and whether one or other is used is often more to
(p.99) do with terminological or theoretical preference than
any imagined hard division. For example, the executive
functions of the brain can be seen as resulting from a
‘Supervisory Attentional System’ (Norman & Shallice, 1980) or
attention viewed as the product of a Central Executive
(Baddeley, 1993). Certainly for rehabilitation it is often of
greater use to specify more clearly what a patient actually has
difficulty with (e.g. finds it difficult to follow conversations in
noisy environments, fails to follow or adjust plans) than to
Page 4 of 40
subsume such problems beneath any of these higher order

theoretical categories.
4 Attention and outcome

As attention in one form or another pervades almost all
aspects of our cognitive life, we would expect far-reaching
consequences of serious impairment. As the assessment of
attention becomes more widespread, evidence supporting this
contention is increasingly apparent. For example
improvements in attention, as indexed by simple reaction time,
are one of the earliest predictors of emergence from
posttraumatic amnesia following traumatic brain injury,
consistent with a general role in ‘bootstrapping’ the rest of the
cognitive system (Wilson et al., 1999). Further down the line,
persistent problems in attention are associated with poor
social and occupational outcome (Brooks & McKinlay, 1987;
McPherson et al., 1997; Woischneck et al., 1997).
In learning to cope with the consequences of brain damage,

patients need to be aware of when they are experiencing
difficulties, to focus on rehabilitation techniques and, often, to
learn new strategies to get around problems. In each stage
impairments in attention are likely to undermine progress. In
addition to these functional properties there is now evidence
that the neural correlates of ‘paying attention’ may play a
more direct role in the recovery and organisation of damaged
circuits. Attention has been observed to modulate or ‘gate’
activity in primary sensory areas of the brain (Desimone &
Duncan, 1995). This has been reported in vision (Moran &
Desimone, 1985), audition (Woldorff et al., 1993), and in
somatosensory perception (Drevets et al., 1995). The role of
such inputs in influencing synaptic connectivity is suggested
by both animal (Recanzone et al., 1993) and now human
studies. Pascual-Leone and colleagues, for example, found that
areas of the motor cortex associated with a particular action
were enlarged following purely mental practice of this skill
(Pascual-Leone et al., 1995).
Such factors may account for why the ability to attend and
maintain a focus of attention may form a good predictor of
recovery in other capacities. To take one example, Robertson
and colleagues found that sustained attention function
assessed at two months post-stroke formed a significant
predictor of motor function and ability to perform activities of
Page 5 of 40
everyday living two years later (Robertson et al., 1997b; cf.

Ben-Yishay et al., 1968).
One very important reason for us to target attention deficits,

therefore, is that in addition to any direct effects, their
presence may undermine recovery in of other capacities and
prevent the useful expression of abilities that may be relatively
intact.
(p.100) 5 A note on rehabilitation

Clinical neuropsychology largely developed from (or in a
parallel with) the academic discipline of cognitive
neuropsychology. However, the two fields should have very
different priorities. In order to constrain models, cognitive
psychology requires more and more focused assessments
capable of isolating one or other specific capacity. For clinical
neuropsychology an important aim is to predict difficulties in
everyday life, for which such specific assessments may, at
times, be rather ill-suited (cf. Wilson, 1999; Burgess et al.,
1998). The same difficulty can pervade what is viewed as
rehabilitation. For many cognitive psychologists, rehabilitation
is most interesting if it helps to constrain a model of the
function in question, e.g. that a particular rehabilitative
gambit might improve working memory as indexed by digit
span performance. In contrast, patients - and therefore
clinicians - should be most interested in what improves
outcome at the level of functional goals. Having a long digit
span might be nice for all sorts of reasons but it doesn’t (in
itself) get you to the shops.
In this chapter we therefore adopt a broad definition of

rehabilitation that encompasses interventions at a number of
levels; the restitution or enhancement of basic function,
training in compensatory strategies and the use of
environmental aids. While our focus is on research that allows
conclusions about specific interventions, it almost goes
without saying that for individual patients a combination of
approaches directed at achieving his or her particular goals is
desirable.
6 Unilateral neglect
Unilateral neglect (or hemi-spatial neglect) is one of the most
striking and extensively studied forms of attentional
impairment. Perhaps not coincidentally, it is also the area
where rehabilitation is most advanced. Unilateral neglect
Page 6 of 40
refers to a difficulty in detecting, acting on or even thinking

about information from one side of space. Patients may fail to
notice food on the left side of their plate, fail to dress or wash
the left side of their body, have difficulty in imagining the left
side of familiar objects and, in some cases, even deny
ownership of their own left limbs. Although classically
associated with lesions to the right posterior parietal cortex
(Heilman & Watson, 1977; Vallar & Perani, 1986), neglect has
been observed following damage to a variety of brain
structures including the right prefrontal cortex and subcortical
areas (Damasio et al., 1980; Mesulam, 1981; Samuelsson, et al.,
1997; Karnath et al., 2001).
6.1 The natural recovery of neglect

An attentional neglect of contralesional space is less prevalent
and markedly less persistent following damage to the left,
compared with the right hemisphere (Bowen McKenna & Tallis
1999). Estimates regarding number of people with right
hemisphere stroke who show neglect in the acute stage vary
considerably depending on the sensitivity of the tests applied
and when the measurement is taken. In one study 84% of
patients were missing information on the left 3 days after their
stroke (Stone et al., 1993), while other estimates are closer to
50% (Bowen, et al., 1999; Farne et al., 2004; Buxbaum et al.,
2004). (p.101) This variability also pervades estimates of
persistence. While some patients certainly undergo quite rapid
spontaneous recovery, a review of relevant studies reported
that, on average, 42% of right hemisphere patients will
continue to show neglect at 3–6 months post-stroke (Bowen et
al., 1999).
An example of unilateral neglect
Page 7 of 40
Joan suffered a right hemisphere stroke in July of 1999

that left her with quite extensive damage to the right
parietal and temporal cortices. After an initial period in
which she was very confused, staff at the hospital noted
her tendency to keep her trunk, head and eyes oriented to
the right. Often she would fail to notice people
approaching her from the left (unless they were able to
attract her attention by raising their voices) and would be
unable to locate objects such as her teacup if it was to the
left of her bed-table. Although her language and memory
appeared relatively unaffected by the stroke she had great
difficulty in making any sense of what she read. Sometimes
she appeared very confused, for example, claiming after
she had been moved to a different bed, that she was no
longer in the same hospital. Although she was capable of
making some movements with her left arm, hand or leg she
largely ignored them. When asked by the psychologist to
imitate an action with her left hand, she simply performed
it with her right. Joan required help with washing and
dressing and in navigating her wheelchair around the
ward.
Four months after her stroke, Joan’s persistent problems

with left space were having serious implications for her
rehabilitation sessions. The physiotherapists found it very
difficult to get her to focus on left-sided movements and
the occupational therapists found that many activities that
she would have been able to perform without thinking,
such as making a sandwich, were now an almost
insurmountable ordeal. Unless there was to be a
considerable change in these symptoms, the chances of
Joan being able to return to an independent lifestyle were
slim.
An important question in thinking about rehabilitation is

whether the spontaneous improvements in neglect take place
primarily because of recovery of the underlying systems (e.g.
through a reduction in diaschitic effects) or through the
operation of compensatory mechanisms. Goodale, Milner,
Jakobson, and Carey (1990) studied a group of nine right
hemisphere patients twenty-one weeks after they had
experienced a stroke. None of the patients now showed
clinically significant signs of neglect and were able to reach
Page 8 of 40
for visual targets with the same accuracy as a control group.

However, when the reach trajectories were analysed,
significant deviations into right space were observed -
deviations that were only corrected just before the hand
reached the target. In addition, when patients were asked to
estimate and reach towards the mid-point between two
targets, significant rightward deviations were again apparent.
Taken together with the results of Mattingley et al. (1994), this
suggests that underlying distortions in the representation of
space may persist in some or many cases but be masked in
most day-to-day activity.
(p.102) There is some evidence to suggest that these

compensatory processes make demands on limited capacity
resources. Robertson and Frasca (1992), for example, worked
with patients who had apparently recovered from many
aspects of neglect. When performing a simple reaction time
task to left- and right-sided stimuli, no clear spatial bias was
apparent. When however, they were asked to simultaneously
perform another attentionally demanding task, reaction times
to left sided targets were disproportionately compromised.
Bartolomeo (2000) recently found that dual task interference
with a spatial task was relatively greater for ‘recovered’
neglect patients than for patients still showing clinical
evidence of the disorder (who, by inference, were not yet
using a compensatory strategy). In a later section we will
return to limitations in non-spatial attentional capacity as a
marker of persistent neglect.
Spontaneous reductions in neglect therefore occur for the

majority of patients without the need for specific intervention -
and compensation for a persistent spatial bias appears to be
one mechanism underpinning these changes. Many patients
who do not show spontaneous improvement are, however, able
to become temporarily more aware of left sided information if
cued to do so (e.g. Riddoch & Humphreys, 1983; Mattingley et
al., 1993). The investigation of whether chronic patients can
be trained to make compensatory ocular scans has therefore
been central to rehabilitation in this area.
Page 9 of 40
6.1.1 Scanning training

Early attempts at encouraging leftward ocular scans, such as
asking patients to find the left side of a line of text before
trying to read it, tended to show significant improvements on
the trained materials, but little generalisation to other
activities (Lawson, 1962; Seron et al., 1989; Wagenaar et al.,
1992; Robertson, 1990). At times the specificity could be
striking, in one case not even transferring between two
different editions of the same book (Lawson, 1962). Although
such failure to generalise does not preclude a useful
rehabilitation effect, needing to train in each and every
important context that a patient encounters would have clear
resource implications.
It is possible that one barrier to generalised improvements in

these studies lay not in the methods used per se, but in the
diversity and duration of training. Pizzamiglio et al., (1992)
provided scanning training to thirteen patients between three
and thirty-four months post-stroke. The training, which took
place over 40 sessions, included a wide variety of scanning
tasks with cues (such as warning tones, flashing lights to the
left of the display) being systematically faded as performance
improved. Significant improvements were observed on the
trained tasks and, most importantly, on untrained measures
and life-like structured activities. Subsequent evaluation using
a full randomised-controlled design verified the efficacy of
these techniques (Antonucci et al., 1995).
6.1.2 Forcing attention to the left: Non-volitional leftward

scanning methods
Neglect is known to operate within different spatial
frameworks. Patients may, for example, neglect the left side of
objects within an array despite the represented (right) side of
those objects being to the left of the array as a whole (object-
centred neglect; Driver and Halligan, 1991), or show
dissociation between the degree of spatial bias between near
(p.103) (within arms reach) and far space (Halligan and
Marshall, 1991). There is also strong evidence of a distortion
within egocentric co-ordinates and, in particular, a
displacement of subjective body-midline to the right (Karnath,
1994).
We discussed how the spontaneous compensatory strategies

adopted by apparently recovered neglect patients appear to
use limited capacity resources - which for some patients are a
Page 10 of 40
rather scarce commodity. A number of interventions are

known, however, to induce distortions in the perception of
(egocentric) space with healthy individuals regardless of their
intentions. These include optokinetic stimulation, caloric
vestibular stimulation, neck muscle vibration and prism lens
adaptation. In each case, the basis of the effect is to use
idiosyncrasies of the sensory system to induce an illusion that
you are in a different location or are moving in a different
direction to what is actually the case. By these means, the
compensatory responses of the brain in the opposite direction
have the potential for rehabilitation or training gains. In
optokinetic stimulation, for example, patients are asked to
perform a task against a moving background (e.g. dots on a
computer monitor moving in a coherent direction) which gives
the illusion that one is moving in the other direction, like the
illusion that one’s own train is moving when a nearby train,
filling the view from the window, is moving in the opposite
direction (Pizzamiglio et al., 1990). The patients’ responses
take into account this ‘movement’ and can therefore be biased
in the opposite direction. Similarly, caloric vestibular
stimulation (CVS) and neck muscle vibration induce the
illusion of that you are rotating in a certain direction by
imposing a temperature gradient between the left and right
vestibular system (in practice irrigating the contralesional ear
with cold water and/or the ipsilesional ear with warm water
(Cappa et al., 1987; Rubens, 1983) or by vibration of the
posterior neck muscle on the contralesional side (Karnath et
al., 1993) respectively.
Such interventions have been theoretically useful in

calibrating the spatial biases of neglect, but the generally
short-lived effects and requirement for less-than-portable
apparatus have led to pessimism about their role in
rehabilitation. Early optimism that optokinetic stimulation may
enhance scanning training, for example, was not supported by
clinical trial data. (Pizzamiglio et al., 2004). However, it is
possible that they may serve an important role as part of a
more general training programme, particularly where patients
have difficulty in exerting even temporary corrective control
over neglect (Antonucci et al., 1995). Beis et al. (1999), for
example, used patches to occlude the right-visual field as a
means of forcing increased awareness of left space. Three
months after training the technique was associated with
Page 11 of 40
significantly improved eye-movements and performance of

everyday activities (compared with patching of the entire left
eye and a no treatment control).
While the full implications of these techniques for

rehabilitation, and in particular the improvement of functional
activity, have yet to be explored, we turn to another
intervention based on a displacement illusion that has been
the subject of intense activity over recent years: adaptation to
rightward deviating prism lenses.
6.1.3 Prism adaptation (PA) training

Prism lenses worn as spectacles induce an optical deviation,
making an object that is straight ahead appear to be, say, to
the right. When first wearing such glasses, if asked to (p.104)
reach for the straight-ahead object, individuals will tend to
miss (the misdirection reflecting the rightward distortion). The
error is clearly visible and is generally corrected within a few
attempts. After multiple reaching trials, the brain’s automatic
adaptation to this distortion is apparent when the glasses are
removed and errors occur for a short time in the opposite
direction. Rossetti et al. (1998) investigated the effect of
asking patients with left neglect to make repeated reaches to
left and right arms-length targets over 5 minutes, while
wearing rightward deviating prism glasses. Once the glasses
were removed, the patients showed significantly reduced
rightward bias on spatial tasks. What was surprising was that
these benefits persisted for at least 2 hours. In the largest
clinical study to have examined PA training, benefits persisted
for at least 6 weeks after cessation of training (Frassinetti et
al., 2002). Prism training, it appeared, could be used to re-
calibrate neglect patients’ sense of space. Benefits for some,
but not all patients, have subsequently been reported on a
variety of spatial measures and in various modalities (e.g.
Farne et al., 2002; Jacquin-Courtois et al., 2008; McIntosh et
al., 2002; Rode et al., 2001; Rode et al., 1998). A recent review
claimed, while conceding that further controlled studies were
required, that PA was the treatment of choice for neglect
(Luaute et al., 2009). It is easy to see why, if effective, it is an
attractive therapy. The equipment required is relatively cheap
and is only required for training rather than as a prosthesis,
meaning that in principle at least, one set of goggles could be
Page 12 of 40
used by many patients. Similarly, the training can be

performed by anyone who can follow the basic instructions.
In terms of the mechanisms of PA training, it has been

suggested that the beneficial effects stem from adaptive re-
calibration of one’s spatial representation caused by the
disruptive experience of the PA procedure. Relatively few
functional imaging studies have so far addressed this question,
although Clower et al. (1996) found, in neurologically healthy
volunteers, that posterior parietal cortex (PPC) is specifically
involved in this re-calibration process. In a more recent PET
study, Lauate et al. (2006b) scanned 5 neglect patients
performing a line bisection judgement task, both before and
after completing one session of PA training. They looked
specifically for brain areas where rCBF changes pre- and post-
training covaried with the observed behavioural change
exerted by PA. Increases were observed in three clusters – the
left globus pallidus and left thalamus; the dentate nucleus of
the right cerebellum and lobule V of the right cerebellar
hemisphere; and BA 19 in the left occipital lobe, and BA37 in
left fusiform gyrus. Decreased rCBF was seen in two clusters,
the first in the left medial temporal lobe and the second in the
right posterior parietal lobe (precuneus, BA37). The authors
proposed that PA prompted short-term sensorimotor plasticity
through recruitment of intact brain regions involved in normal
visuospatial attention (cerebellum, dentate nucleus, thalamus,
globus pallidus, parts of the ventral stream). Based on
observations of patients with PPC and cerebellar lesions,
Pisella et al. (2006) suggested that the cerebellum is
principally involved in the realignment component of PA (and
leads to persistent and generalised benefits), whereas
posterior parietal cortex is involved in a more strategic
component of PA. Their proposed mechanism of PA benefits in
neglect patients is that error-signals produced by the PA
procedure are processed in left occipital cortex, eliciting
spatial realignment processes in the right cerebellum, which
(p.105) subsequently modulate projections to frontal,
temporal and posterior parietal cortices in the undamaged
hemisphere.
As the popularity of PA based therapy has grown, however, a

number of studies have now failed to identify any beneficial
effects (e.g. Morris et al., 2004; Rousseaux, Bernati, Saj &
Kozlowski, 2006). A recent placebo-controlled RCT of PA for
neglect (Nys et al., 2008) demonstrated that neglect patients
Page 13 of 40
in the acute phase (2–23 days post-stroke) receiving PA

training for four consecutive days improved on 2/4 measures
of spatial performance (line bisection and letter cancellation,
but not line cancellation or scene copying) compared with
patients undergoing an identical training procedure with
placebo glasses. However, there was no detectable difference
between prism and placebo-training groups on either
conventional or ecological tests at one-month follow-up. Such
appropriate controls for the general effects of therapy are
important and suggest that when and for whom PA benefits
occur remains an important research area. As we will discuss
further, an interesting question given the association between
persistent neglect and a range of non-spatial capacity
limitations is whether an intervention that operates exclusively
on the spatial aspects of the disorder will provide the hoped
for general improvements in outcome.
6.1.4 Limb-activation
Influential views of spatial attention suggest that it is
intimately linked with the preparation for action (e.g.
Rizzolatti & Camarda, 1987; Allport, 1992). It is certainly the
case that changes in the motor context (e.g. the difference
between reaching to point and reaching to pick up) can exert a
significant influence on the degree of spatial bias shown by
neglect patients (Robertson et al.,1995a). Halligan and
Marshall (1989) reported that when a patient used his left
hand to perform a spatial task he showed significantly less
neglect of left space than when he used his right. Robertson
and colleagues systematically examined these effects. In
particular they controlled for the inevitable out of sight whilst
performing a spatial task that required only a verbal (naming)
response (Robertson & North, 1992; Robertson & North, 1993;
Robertson & North, 1994; Robertson et al., 1994).
The results of this series of studies are summarised in Figure

6.1 overleaf. They show that the most significant reductions in
left-sided omissions are associated with the left hand moving
within left space (defined relative to the patient’s midline).
Movement of the right hand within left space, or of the left
hand within right space produced much less dramatic effects,
and simultaneous movements of both hands abolished any
benefits of left limb movement.
Page 14 of 40
The important question is whether this striking experimental

effect can be extended into improving everyday function. Two
recent studies suggest that this is the case. Robertson and
colleagues developed a portable ‘neglect alert device’ to
prompt patients to continue to make left hand movements (a
buzzer sounded if the button was not pressed regularly).
Significant improvements in a number of everyday spatial
activities (including combing the hair and navigating around a
hospital route) coincided with the onset of training (Robertson
et al., 1998a). Wilson et al. (2000) worked with a 62 year old
man whose very severe left neglect (including of his own body)
was seriously affecting his ability to take care of himself. To
create an ecological measure his morning washing (p.106)
Fig. 6.1 Summary of the results from the

limb activation studies of Robertson and
colleagues.Unseen movement of the left
hand to the left side of the body is
associated with a reliable reduction in
spatial attention bias. Movement of the
left hand on the right, or of the right
hand on the left produces less striking
Page 15 of 40
(p.107) effects (units are the number of target

routine was omissions made by the patients).
divided into
distinct steps
(washing both arms, washing both legs and so on). The measure of
his independence was the number of prompts he required to
complete each stage (prompts were given if activity stopped for 20
seconds). As shown in Figure 6.2, after a 10 day baseline the
introduction of limb activation training was associated with a
significant increase in his independence. Importantly, as was the
case for some patients in Robertson et al.’s study, these gains were
well maintained even when formal training had stopped. It seems
possible, therefore, that in some cases the initial encouragement to
use the left hand enhances awareness of left space, which in turn
leads to greater spontaneous use of the left hand. By this means, a
positive feedback loop could be established that maintains and
enhances the effect.
Page 16 of 40
6.1.5 Sustained attention training

From reading textbooks in neuropsychology, one might
imagine that the only difficulty experienced by patients with
unilateral neglect is their curious lack of awareness of left
space. This is rarely the case. Clinically, one very noticeable
feature of such patients is the immense difficulty they can
have remaining engaged in any task, regardless of its spatial
content. This impression is supported by research showing
that patients with neglect have particularly poor sustained
attention, even when compared to other patients with right
hemisphere lesions (Robertson et al., 1997a; Samuelsson et al.,
1988).
(p.108) As
with leftward
cueing and
use of the left
hand,
experimental
evidence that
the associated
deficits of
neglect and
poorly
maintained
alertness Fig. 6.2 Improvement in independence in
were a morning self-care programme with the
functionally introduction of limb activation training.
connected
may inform a
different approach to rehabilitation. Such evidence emerged
from a study in which patients were occasionally alerted by a
loud tone as they performed a spatial task. Although the tone
had no predictive value for whether a target would appear on
the left or right, when presented it completely abolished (and
is some cases even reversed) the neglect (Robertson et al.,
1998b).
Robertson et al. (1995b) examined whether longer term

training in self-maintaining an alert, ‘ready to respond’ state
could reduce neglect. In the training patients were asked to
perform various non-spatial and rather tedious activities.
Every so often (with the patient’s prior consent) the therapist
would bang the table top - both to cause an involuntary
alerting effect and to cue the patients to say to themselves
Page 17 of 40
“WAKE UP!” or “ATTEND”. In line with a procedure first

described by Meichenbaum & Goodman (1971; cf.
Meichenbaum & Cameron, 1973) the external cueing was
progressively faded. In a multiple baseline x patient design (a
method of controlling for spontaneous improvements), one
week of daily training produced significant reductions in
neglect on non-trained measures (Robertson et al., 1995b). A
similar type of self-alerting training, using biofeedback, has
recently been found to improve sustained attention in adults
with Attention Deficit Hyperactivity Disorder (O’Connell et al.,
2008) suggesting that wider application of such techniques is
warranted.
Following a related rationale, Thimm et al. (2006) studied the

behavioural effects of a 3-week computerised alertness-
training program in a group of 7 neglect patients, along with
fMRI correlates of such effects. Though benefits consistent
with a beneficial effect of training were found on behavioural
measures of spatial bias, and these were accompanied by
increased fMRI activation in networks associated with spatial
attention, the behavioural benefits disappeared once training
had ceased (although the increased fMRI activations
remained). Further work in this area is clearly needed to
determine whether maintenance of such short-term benefits
can be promoted.
At least four very different approaches have therefore

produced significant rehabilitative results with unilateral
neglect. Unilateral neglect is a highly fractionated set of
symptoms that can arise from damage to a variety of brain
areas. More research is needed in clarifying the applicability
of these methods to different manifestations of spatial bias -
and indeed whether the effects may be additive in some cases.
A recent Cochrane review (Bowen & Lincoln, 2007) concluded
that there was some evidence that interventions for neglect
could improve performance on tests of spatial ability (i.e. at
the impairment level), but that there was no available
evidence of an effect on measures of disability (i.e. that the
benefits translated to improvements in functionality). The
authors pointed out that these rather negative findings were
the result of paucity of randomized control trial (RCT)
evidence and an over-emphasis on changes in test scores
rather than functional disability. While there are positive
indications from studies employing non-RCT methods, in order
for definitive statements to be made regarding efficacy, studies
Page 18 of 40
that are adequately randomized, with blind assessment, and

include measures of functional handicap need to be
conducted.
(p.109) 7 Non-spatial attention
Page 19 of 40
7.1 A behavioural, goal based approach
An example of non-spatial attention
Brian was a well-educated man in his mid 40’s. In 1995 he

suffered a serious head injury in a road accident that left
him in coma for 3 days. In many ways his recovery was
remarkable. Over two years his performance on tests of
reasoning and memory returned to above average levels.
Unfortunately, it was only when Brian returned to work
that his remaining deficits became apparent. His job
required a great deal of flexibility. In order to achieve goals
and meet deadlines he would need to keep track of a
changing situation, re-prioritise, and switch between one
activity and another. It was precisely this level of
organisation that Brian now found so difficult. He was now
highly distractible and would leave jobs unfinished or fail
to notice crucial details that he had omitted. At home he
found it difficult to complete simple jobs without needing
constant reminders and was described by his wife as often
drifting into a world of his own. Despite retaining many of
his premorbid abilities, Brian was now very frustrated by
his inability to harness these effectively in order to achieve
goals.
Our discussion of unilateral neglect has focused on

interventions designed to improve underlying ability, as this
can represent a more general solution to the functional
problems experienced by the patient. When the underlying
problems are less clearly understood, as is the currently the
case for many forms of non-spatial attention, it can be more
appropriate to tackle a specific activity. Wilson and Robertson
(1992), for example, adopted a behavioural approach in
working with a man whose severe head injury had left him
with problems in ‘keeping his mind’ on what he was reading.
Initially the man was asked to monitor how many times his
attention slipped when he was reading. In training he was
initially encouraged to read for only very brief periods. If these
were completed without slip the duration of the subsequent
session was increased by ten percent. Following 160 sessions
over 40 days, the goal of reliably reading for 5 minutes
without a slip was attained. Most importantly, the number of
Page 20 of 40
slips reported when reading material relevant to his job had

also significantly reduced, even though this had not been
directly trained.
This systematic, shaping approach does not tell us a great deal

about the underlying nature of the difficulties experienced by
the patient. There was also little evidence that the training
produced any improvements in other activities in this case
(although this can be very hard to measure). It does show,
however, that appropriate reinforcement and learning can
modulate the consequences of poor attention and offers a
technique that could be easily applied to many situations.
7.2 Improving attention through general training

We have seen how, in the case of scanning training for spatial
neglect, the duration of rehabilitation may be crucial
(Pizzamilio et al., 1992). The revolution in computer (p.110)
technology and price over the last three decades has made
long periods of systematic and reflexive training increasingly
possible. For researchers, the use of computers to ‘deliver’
therapy also means that exposure to treatment can be highly
standardised - improving the interpretation of particular
factors that can promote performance change.
In a study by Gray et al. (1992), thirty-one patients with

reported attention difficulties were randomly allocated to one
of two conditions. One consisted of approximately 15 hours of
computerised training including; a) a reaction time task with
feedback on speed; b) a task requiring the identification two
identical digit strings from a briefly presented array of 4; c) a
digit-symbol translation task; and d) a colour-word Stroop
task. The other was 15 hours of recreational computing.
Immediately following the 3–9 week training, the experimental
group showed significant improvements on two non-trained
tasks relative to the controls (the WAIS-R Picture Completion
subtest, requiring visual search and reasoning, and the Paced
Auditory Serial Addition Task (PASAT), widely considered as
primarily a measure of processing speed (Gronwall &
Sampson, 1974). At six months follow-up, the benefits on these
measures had been maintained and, in addition, further
untrained measures were showing training benefit (backward
digit span, mental arithmetic, and WAIS-R Block Design).
Page 21 of 40
As the groups were well matched on task performance prior to

training, the results suggested both that the training had
produced generalised improvements and that a ‘sleeper effect’
led to continued improvement beyond the training period.
While little evidence exists on this, it is possible to speculate
that such effects emerge both through consolidation of the
learning and from the increased exposure to attentionally
demanding situations consequent upon initial improvements.
The results are persuasive in suggesting a specific effect that,

thanks to the well matched control group, cannot be
interpreted in terms of generalised recovery. The
generalisation to functional activities of everyday life was not,
however, examined in this study.
Page 22 of 40
7.3 Training specific attention functions

We have discussed how attention has been viewed as a
fractionated set of processes. In a strong form of this
argument, training one form of attention may have minimal
consequences for another. Sturm et al. (1997) examined this by
randomly allocating 38 stroke patients to different training
programmes. The programmes, now published as part of the
“AIXTENT” training package, were made up of separate
modules targeting a particular form of attention. They used
this idea to evaluate a programme in which all participants
received training but in which the modules were completed in
different orders.If attentional functions were relatively
encapsulated, they argued, observed improvements should
broadly follow the order of training.
Each of the exercises was in the form of a computer game that

became more challenging as performance improved.
Alertness, for example, was trained using a motorbike
simulation while selective attention required the patients to
‘shoot’ one but not another form of target. Improvements were
evaluated on an untrained computerised measure
(Zimmermann et al., 1993). After approximately 56 hours of
training the hypothesis was (p.111) substantially supported.
The detection rate for targets in the untrained test battery
vigilance task was significantly improved only after vigilance
training and not following training in selective or divided
attention. Similarly, reaction times in the selective attention
test were improved following selective, but not sustained
attention training. As might be expected, some crossover
effects were also observed. Performance on the divided
attention task, for example, was significantly enhanced
following training in selective, as well as divided, forms of
attention. Note that this training procedure was the same as
that used in the previously discussed study examining
alertness training for neglect (Thimm et al., 2006).
Comparable results were obtained in a further study of effects
of the AIXTENT training in people with multiple sclerosis
(Plohmann et al., 1998). Further studies, with appropriate
controls, are clearly warranted.
Sohlberg et al. (2000) conducted a randomised control

crossover trial to evaluate the efficacy of another form of
attention training, referred to as Attention Process Training
(APT). Participants received 24 hours of APT over 10 weeks,
with the sessions involving completion of non-computerised
Page 23 of 40
tasks taxing different aspects of attention (e.g. detecting

target sounds within distractor noise, listening to a sentence
and alphabetising the component words). The control
condition involved a total of 10 hours of brain injury education
and supportive listening, over 10 weeks. Across the whole
group, benefits specific to APT were seen in two tests of
“executive attention” (the Paced Serial Addition Task PASAT
(Gronwall & Sampson, 1974), and the Sternberg (1966)
memory for locations test). In a subset of participants with
poor vigilance performance, APT-specific improvements were
also seen on the Stroop (1935) and Trail Making Tasks (Reitan
& Wolfson, 1985). There were also benefits of APT on self-
reported attention and memory functioning.
A recent development has been the working memory (WM)

training studies of Klingberg and colleagues. Olesen et al.
(2004) reported that subjects who engaged in around 40
minutes of repeated practise on three working memory tasks
over 5 weeks showed faster and more accurate responses on
WM tasks in comparison with untrained participants. Crucially,
there was some evidence of generalised benefits to untrained
tasks including the Stroop task and the Raven’s Matrices fluid
intelligence measure. These changes were accompanied by
increased fMRI activation during WM performance in the right
middle frontal gyrus, right inferior parietal cortex and bilateral
intraparietal sulcus. Based on this work, a training program,
RoboMemo© (Cognitive Medical Systems AB, Stockholm), has
been developed, and its effects have been evaluated in two
recent randomised controlled trials. The program involves
various WM tasks, some visuo-spatial WM (effectively
computerised versions of the corsi-block task), and three
verbal tasks (remembering phonemes, letters or digits). In all
tasks, the difficulty level is titrated to match individual WM
span. The first study, an RCT with blind assessment and a
stringent placebo-control, involved 56 children with ADHD
(Klingberg et al., 2005). Participants were randomly assigned
to either experimental or control arms of the trial, with
children in the former group being subjected to either 40
minutes of RoboMemo training for 25 days, and those in the
latter group, an equivalent period of training on the same
software, but without automatic titration of task difficulty (e.g.
just repeating 2–3 (p.112) item span tasks). Benefits specific
to the experimental training were seen in a variety of
untrained tests of WM, as well as on the Stroop task and
Page 24 of 40
Raven’s matrices, and were maintained at 3-month follow-up.

Parent-ratings of ADHD symptoms also improved with
training, and were also maintained at follow-up.
Westerberg et al. (2007) reported similar findings in a small

(n=18) RCT involving adults in the chronic (>1 year) phase
post-stroke. Here, the experimental training was the same as
that described in Klingberg et al. (2005), but training effects
were determined by comparison with a no-training (passive)
control group – an obvious limitation of the study. Performance
on two untrained tests of WM, the PASAT and the Ruff (1992)
2 and 7 test (assessing sustained and selective attention) all
improved disproportionately in the training group.
Futhermore, self-reported lapses in attention and memory as
indexed by the Cognitive Failures Questionnaire also
decreased with training.
Taken together, there is certainly promising evidence that

repeated (and ideally progressive) training in attentional and
WM tasks, if carried out over a sufficient period of time, can
produce generalised changes in function as assessed on
untrained tasks and, crucially, in people’s reports of everyday
difficulties.
Page 25 of 40
7.4 Environmental support for attention

Within specialist clinical settings it is possible to organise the
environment in a way that minimises demands on patients’
deficient attentional and executive skills (e.g. reducing
distraction, having a very set schedule, keeping a written
record of an agreed plan, systematic reinforcement of goal-
directed behaviour). Such techniques can be useful in helping
very severely impaired patients to control inappropriate
behaviour and to focus on other important rehabilitation goals
(cf. Alderman & Ward, 1991; Alderman & Burgess, 1994;
Alderman, 1996) - but are clearly inappropriate for many
patients with less severe problems. Recently we have been
examining whether it is possible to introduce ‘portable’
environmental support for attention that is compatible with
(and hopefully enhances) independence. This type of approach
is neatly demonstrated in a case study by Evans et al. (1998).
They describe a patient who had suffered bilateral damage to
the frontal lobes following a subarachnoid haemorrhage.
Although on many standard IQ and memory tests her function
was relatively well preserved, in everyday life she had great
difficulty in achieving goals and was highly dependent on the
support of others. In particular (as has been described in a
number of frontal patients) she appeared to get overly caught
up in whatever activity she was currently performing to the
severe detriment her other essential activities. The patient
was given an electronic pager that had originally been
designed for memory-impaired patients, which remotely sent
messages to cue an important activity (The ‘Neuropage’
system; Hersch & Treadgold, 1994; Wilson et al., 1997, 2001).
In this case, its introduction significantly improved her
capacity to begin goal directed activity, often without her
needing to see the content of the message. It appeared that
this environmental intrusion was acting to refocus her
attention on her goals - and once this had occurred, her other
intact capacities allowed her to achieve them.
To investigate these effects at a group level we (Manly et al.,

2002) developed a modification of the ‘Six Elements
Test’ (Shallice & Burgess, 1991) in which patients were asked
(p.113) to perform a number of tasks associated with
running a hotel (calculating bills, ordering conference labels
alphabetically, proof-reading a tourism leaflet and so on). As
with the Six Elements, the key feature was that the total time
available for the test (15 minutes) was far less than the time
Page 26 of 40
required to fully complete each component task. In order to

comply with the goal of trying some of each activity in the test,
patients would therefore need to plan at the outset to switch
tasks with a certain regularity and to keep this goal actively in
mind throughout the test. As with the patient reported by
Evans et al. the key error made by the traumatically brain
injured patients we worked with was to become so engrossed
in one activity that this goal was neglected.
The patients were administered two versions of the task in

random order one week apart. During one session we told the
patients that they would periodically hear a rather salient
bleeping noise - and that this was a reminder to them to think
about what they were doing in the task. In this group, not only
did the presence of the tone significantly improve their
performance, it had now become indistinguishable from that of
healthy control participants. This result was useful in ruling
out a number of other causes of poor performance in the test
such as failure to understand the task or remember what the
plan was. Most importantly it suggests that, even if attention
could not be directly improved, its functional consequences on
complex activities can be minimised. We recently
demonstrated a similar beneficial effect on the everyday
prospective memory performance of a group of patients with
acquired executive impairments by sending randomly timed
text messages to participants’ mobile phones (Fish et al.,
2007). As mobile phone and palm-top technology is
increasingly available, and more frequently used by patients
with brain injury, such interventions may become all the more
important.
8 Summary
The scientific study of functions that are specifically
attentional are at an early stage, but have begun to inform
improved assessment and rehabilitation for neurological
patients. Perhaps the most important development lies in
seeing attention not as a single entity but as a set of processes
that are vulnerable to separate damage and which can have
very different consequences. As assessment has improved, the
negative impact that poor attention has on recovery and
outcome is increasingly clear - evidence that makes
interventions designed to enhance natural recovery in these
systems a particularly pressing clinical goal.
Page 27 of 40
We have reviewed different approaches to working with

attentional deficits; attempting to improve underlying
function, targeting particular behavioural/functional goals, and
using external aids to maximise residual function. Work with
unilateral neglect is by far the most advanced. Four separate
interventions, training patients to make compensatory left-
ward scans, encouraging use of the left hand and arm, prism
adaptation therapy, and teaching self-alerting techniques have
all produced generalised improvements - other techniques
exploiting new experimental effects may well follow. Although
often more loosely defined, work with non-spatial attentional
functions has also produced positive results. It has been
demonstrated that systematic practice and reinforcement can
shape attentive behaviour - perhaps to a much greater degree
than has proved possible in the rehabilitation of memory
(Wilson, 1999). Carefully evaluated computer training (p.114)
packages have produced clear improvements in attentional
function, and there are now hints that these changes indeed
translate to improvements in everyday function.
A key feature in a number of the studies we have considered

seems to lie in the duration of training. Whether the processes
necessary to enhance basic function are learning new
strategies, using different neural pathways to achieve the
same ends, or plastic re-organisation within damaged areas,
effects should not be expected within a few sessions.
For researchers, clinicians, and most particularly, patients,

careful evaluation of interventions is essential. Showing
changes in well controlled experimental designs and using
targeted neuropsychological measures is essential in
understanding the specific relationship between what we do
and any improvements, but this is not, in itself, rehabilitation.
Many of our operational definitions of attention have been
imported from cognitive psychology and the relationships
between these entities and everyday difficulties can sometimes
be obscure. While it defies belief to argue that we have
cognitive capacities that are only tapped by
neuropsychological tasks and untouched in daily life, a great
deal more work is needed in examining the impact of
particular deficits and the functional consequences of any
improvements that we might help bring about.
Page 28 of 40
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damaged patients. Tubingen: G Narr-Verlagg.
Page 40 of 40
Assessment of perceptual disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001

L.D. Kartsounis
DOI:10.1093/acprof:oso/9780199234110.003.07

This chapter reviews the principles of assessment of
perceptual disorders, auditory recognition deficits, tactile
recognition deficits, and visual object recognition deficits. The
implicit assumption is that visual object recognition skills have
a hierarchical and parallel organization. In ordinary clinical
practice however, object recognition disorders are ‘random’.
The question arises as to where a clinician should start when
assessing a patient with object and/or face recognition
problems. The first consideration is to obtain information on
potential sensory problems, visuospatial neglect, aphasia, etc.
that may at least partly account for perceptual/agnosic
deficits. As a general rule, clinicians should be alert to the
complaints and errors patients make during other tasks
involving picture interpretation. If the patient fails these tests,
there is no need for tests of visual agnosias either of the
aperceptive or associative type — any agnosia diagnosed in
this context would be ‘pseudoagnosia’.
Keywords: perceptual disorder, visual object recognition, auditory recognition

deficit, tactile recognition deficit
1 Sensation and perception
Page 1 of 27
For many centuries philosophers have been asking questions

about the validity of human experiences in that things are not
always what they seem. More strikingly, perhaps, we have
experiences in the absence of actual physical stimulation, e.g.
hypnagogic hallucinations are not uncommon within the
normal population (Collerton et al. 2005). In addressing these
matters, a distinction should be made between sensation and
perception. The senses capture information from the
environment in various forms of physical energy (stimulus).
They accomplish this via specially dedicated receptors of a
single cell or a group of cells. The receptors convert this
energy into appropriate neural signals (sensory transduction).
Subsequent elaborations and interpretations of the neural
signals in different parts of the brain (broadly referred to as
perceptual processes) enable one to become aware of external
stimulation. It is often forgotten that we do not solely derive
our experience of the outside world from our senses.
1.1 Principles of assessment of perceptual disorders

The neural events taking place between sensory stimulation
and interpretation are normally experienced as ‘automatic’.
This ‘automaticity’ may be lost with brain damage/disease
(injury, stroke, tumour, anoxia, degenerative disorder). The
affected patient is then unable to analyse environmental
stimuli meaningfully. Neurologists, neuropsychologists, and
other professionals are asked to identify the deficit(s)
responsible for the breakdown—a task often akin to a
detective’s work.
For the assessment of perceptual impairments the examiner

needs to be acquainted with the chain of events between
sensory stimulation and awareness of stimuli. It requires
sound understanding of both the nature of stimuli as sounds,
sights or smells and the abilities of humans to discriminate
disparate types of neural signals. Different techniques have
been developed for the assessment of perceptual skills as they
relate to physical stimuli (psychophysics). Some testing
procedures have been refined into standardized formal tests.
However, from time to time, procedures may need to be
invented ‘on the spot’. Clearly, these procedures are not in
keeping with mental test theory and lack normative data. The
implicit assumption in these cases is that there is
Page 2 of 27
discontinuity between normal and abnormal performance that

can readily and universally be understood.
(p.121) When perceptual skills are assessed, a range of

constitutional, cultural, and other factors ought to be taken
into account, including the following.
◆ Individuals may vary in their ability to distinguish

different stimulus signals due to primary sensory deficits.
Some people have defects in the eyes that prevent them
from experiencing the full range of colours. Others have
defects in their ears or tongues and are unable to
experience aspects of sounds (e.g. pitch) and taste (e.g.
bitter).
◆ With advancing age, senses become less sensitive and

perceptual experiences become ‘bland’.
◆ The state of the perceiver may influence the perception of

a stimulus. The experience of the warmth of water in a
basin does not depend on the temperature in the water
alone but on the perceiver’s own state at the time. If his or
her hand had previously been in hot water, the water of the
basin would feel cold and vice versa (John Locke).
◆ Cognitive processes (memories, expectations, etc) and

emotional states (anxiety, mood disorders, etc) may
influence perceptions.
◆ A patient may be unable to comply with the demands of

tests due to deficits in skills different to those being
examined, (e.g. severe language problems), would hinder a
patient responding appropriately to tests of tactile
sensitivity.
In clinical practice the assessments of perceptual skills are

undertaken by different professionals. Neurological
examinations include the assessment of sensory organs (eye,
ear, nose), perception of pain, touch, etc. in different parts of
the body. From a neuropsychological point of view the best
known types of perceptual deficits are:
◆ auditory;
◆ tactile;
◆ visual.
Page 3 of 27
A common term, ‘agnosia’, may be applied to all of them,

implying inability to know or interpret sensory experiences.
2 Auditory recognition deficits

This is a group of disorders consisting of impairments in the
ability to recognize verbal and nonverbal sounds. They may
arise as a result of damage or dysfunction in different parts of
the auditory system through which sounds are being
processed. The auditory system includes the outer ear, the
middle ear and the inner ear where neural impulses are
generated (sensory transduction) and are transmitted to the
brain via the auditory nerve. The auditory nerve branches into
several pathways projecting to the brain stem and to other
parts of the brain and then they reconvene at the auditory
cortex. Each pathway processes different aspects of auditory
information. Auditory perceptual deficits may be due to
conduction loss or neural damage. The former relates to a
disorder in the outer ear or in the middle ear due to wax,
infection or otosclerosis, (i.e. immobilization of the small bones
in the middle ear). Conduction loss may partially be remedied
by hearing aids, mainly amplifying the sounds of speech. At
central processing the range of sound (p.122) frequencies
over which cells respond become narrow. A cortically deaf
patient may present with a range of auditory perceptual
deficits, including abnormal pure tone, sound localization, and
temporal auditory analysis.
The term ‘auditory sound agnosia’ refers to a loss of the ability

to recognize common sounds (e.g. bell ringing, dog barking,
and train, that is not due to cortical deafness). When asked to
identify these sounds the patient makes mistakes, e.g. a
telephone ring may be interpreted as a sound of a railroad
crossing. Auditory agnosia is often associated with bilateral
lesions in the region of the superior temporal lobe (Griffiths,
2002). More generally, auditory agnosia occurs in the context
of bilateral temporo-parietal pathology or bilateral subcortical
pathology (Taniwaki et al. 2000).
2.1 Word deafness (verbal auditory agnosia)

There are more neurons dedicated to analyzing frequencies
involved in speech (200–8000 hz) than other types of sounds.
The term ‘pure word deafness’ refers to the impairment in
analysing/understanding spoken words in the context of
preserved recognition of nonverbal sounds and relative
preservation of spontaneous speech, reading, and writing.
Page 4 of 27
Unlike patients with primary comprehension problems

(transcortical sensory aphasia), those with pure word deafness
deficits are impaired on word repetition tasks. Word deafness
is associated with bilateral pathology of the primary auditory
cortex or of the underlying deep white matter (Tanaka et al.
1991). The critical lesions are thought to disconnect
Wernicke’s areas from auditory input. This is in keeping with
observations indicating that the patients are neither deaf nor
aphasic.
Despite the adjective ‘pure’, clinical experience suggests that

word deafness may be associated with impairment in temporal
resolution of auditory stimuli or abnormal click-fusion
thresholds, although the predominant deficit involves spoken
word stimuli. It is critical that the clinician establishes the
integrity of primary auditory perceptual skills before a
diagnosis of word deafness is made. As a first step, ask the
patient to discriminate softly spoken words or finger snaps.
For proper delineation of a patient’s auditory sensory/
perceptual skills, however, an audiological assessment is
required. This includes measures of pure tone audiometry and
speech detection thresholds. Provided significant auditory
sensory deficits and aphasia are excluded, the assessment for
word deafness may proceed by asking the patient to
discriminate whether spoken pairs of words and nonwords are
the same or different (house/house versus house/mouse, pef/
bef) (e.g. Kay et al. 1992). These tests require special care.
◆ Prevent lip reading.
◆ Make sure the patient is able to ‘hold’ in mind and

compare two items.
◆ Stimulus pairs may differ according to the examiner’s

voice and accent (use a native speaker with clear
articulation).
◆ It may be difficult to convey to the patient the

requirements of the test and you will need to use pictorial
material to demonstrate the nature of the task.
Page 5 of 27
(p.123) 2.2 Auditory amusia

This refers to a loss of the ability to recognize familiar music
(well-known melodies or a particular voice). Both hemispheres
contribute to music appreciation and the anatomical correlates
of amusia are multiple, underpinning the multifactorial nature
of music (Stewart et al. 2006). Given also the wide range of
individual differences in innate ability and musical education/
exposure, the assessment of auditory amusia is very difficult.
Melody perception, however, may be assessed by various
subtests of the Seashore Test of Musical Talent.
3 Tactile recognition deficits

The tactile system is the largest sensory system in the body. A
multitude of different kinds of receptors give rise to sensations
of touch, texture, mechanical consistency, heat / cold and pain.
The skin in the human hand, in particular, contains thousands
of “mechanoreceptors” (receptors sensitive to mechanical
pressure) that, together with a complex set of muscles, explore
the surface of an object. The perceptual processes that
underpin tactile object recognition are not well understood
and may be differentially affected by different classes of object
properties (Bohlhalter et al. 2002). Generally, impairments in
tactile object recognition skills should be diagnosed in the
absence of significant somatosensory impairment, neglect,
aphasia, or dementia.
The somatosensory cortex receives touch information from the

thalamus and this is further processed and elaborated in other
parts of the cortex. Each hemisphere receives information
from the contralateral side of the body. Related to the sense of
touch is the information about the positions of our limbs,
known as proprioception (kinaesthesis). The receptors of
proprioception are in the muscles, tendons and joints. Tactile
information is closely associated with proprioception and they
both contribute to the representation of an object.
Tactile agnosia as a selective disorder has been the subject of

dispute in the past, not least due to lack of precise quantitative
measures. In clinical practice a useful guide to the assessment
of disorders of touch is by Caselli (1997). According to this
scheme, somaesthetic functions may be divided into basic,
intermediate, and complex types
Page 6 of 27
◆ Basic somaesthetic impairments include light touch,

position sense, vibration, two-point discrimination, pain
perception, and temperature (usually assessed by
neurologists).
◆ Intermediate somaesthetic impairments include texture

discrimination and simple form discrimination that is part
of astereognosis (usually assessed by neurologists,
sometimes by neuropsychologists).
◆ Complex somaesthetic impairments are disorders of pure

forms of tactile agnosia, with preserved basic and
intermediate functions. Tactile agnosia is usually associated
with damage to parietal operculum.
(p.124) As implied above, somaesthetic deficits are unilateral

and the examiner may use a patient’s good hand as control.
Tactile agnosia may initially be assessed by light touch,
position sense, etc. Patients are asked to discriminate texture
and basic form by touch (e.g. between different kinds of edges,
flat and curved surfaces). If they pass these tests (reflecting
basic and intermediate skills), ask them to name objects by
touch. Each object (e.g. a cassette tape) is placed randomly in
either hand. Tests of tactual memory may be added, e.g.
‘Which is smoother an almond or a walnut’, to ensure that the
deficit is specific to the tactile modality (cf. Reed et al. 1996).
If patients are aphasic they will have difficulty in naming
objects placed in either hand. When they have a specific
difficulty in naming objects palpated with only one hand,
tactile agnosia may be inferred.
4 Visual object recognition deficits

About 40 percent or more of the human brain is thought to be
involved in vision (Werner et al. 2007). In keeping with this,
visual object recognition deficits are more common (than those
in other sensory modalities) to clinical neuropsychological
practice. They are also much better understood and hence, in
this review, they are presented in greater detail.
The optic nerve is formed by the axons of the retinal ganglion

cells. At the optic chiasm, fibers from the inner half of each
retina cross over and enter the contralateral hemisphere. Each
eye, therefore, projects visual information to each hemisphere.
Each visual pathway travels backwards to the Lateral
Geniculate Body (LGB) that may be considered as a
subdivision of the thalamus. The LGB transmits information to
Page 7 of 27
the visual cortex and this final part of the optic pathway is
known as “optic radiation” (or “geniculo-calcarine tract”).
The optic radiation is commonly compromised by vascular
disorders or brain tumours, giving rise to a variety of visual
object recognition deficits. It is noted that lesions that
interrupt the visual pathways may also cause different visual
field defects, depending on the lesion site, of which the clinical
neuropsychologist needs to be aware during patient
assessment.
4.1 Historical background

The first descriptions of visual object recognition disorders
can be traced to the nineteenth century. In 1890 Lissauer
made a distinction between deficits in the ability to
consciously perceive stimuli, versus inability to ascribe
meaning to what is perceived. He referred to them as
aperceptive and associative ‘mindblindness’, respectively.
Similarly, in 1891 Freud made a distinction between deficits of
sensation and disorders of ‘gnosis’ (knowledge)—hence the
term ‘agnosia’ (without knowledge). This terminology has
largely survived but there is no general agreement as to what
the term ‘perceptual’ (as in aperceptive mindblindness)
denotes. For some cognitive neuropsychologists it
encapsulates a wide range of deficits ranging from early visual
processing to high-level object recognition impairments (e.g.
Farah 1990, Humphreys, and Riddoch 1987). For others
(including the present author) the term refers to more
circumscribed deficits that arise after satisfactory early visual
processing is accomplished and before meaning is ascribed
(p.125) to stimuli (see McCarthy and Warrington 1990). This
is not just a theoretical point—the distinction between early
visual (cortical) deficits and aperceptive deficits corresponds
to different anatomical correlates and is therefore of
diagnostic significance (Table 7.1). There is a wider ongoing
debate regarding the classification of impairments in visual
cognition. Unlike cognitive psychologists, visual physiologists
and anatomists appear reluctant to accept notions of high-
level visual ‘agnosic’ deficits. Instead, they consider them to
signify impairments in integrating sensory information or
accessing long-term memory. Moreover, it has recently been
suggested that the thin retina tissue in the eye is capable of
parsing visual information into a dozen discrete components.
That is, it is thought that a significant amount of
preprocessing occurs inside the eye, which subsequently
Page 8 of 27
sends a series of partial representations (“movies”) to the

brain for interpretation (Werblin and Roska, 2007). For the
diagnosis of patients, however, we can continue to rely on the
clinically validated neuropsychological model of object
recognition deficits, as outlined in this chapter and
represented in Table 7.1.
4.2 Caveats
The assessment of deficits in object recognition needs to be
flexible and adaptable to the individual patient. A patient’s
performance may be impaired as a result of deficits in other
cognitive domains.
◆ A test involving drawing for example, may primarily be

failed due to motor deficits (sensory/motor weaknesses,
dyspraxia), or planning (executive) problems.
◆ Visual object recognition tests may be failed due to

sensory deficits, visuospatial neglect, severely restricted
visual fields, or impairments in eye movements. The latter
include disorders involving subcortical/brainstem structures
and frontal eye fields (e.g. Luria 1976).
◆ Tests dependent on verbal responses may not be

appropriate for dysphasic patients.
Table 7.1 Object recognition deficits

Early visual Visual agnosias
processing
Aperceptive Associative
Acuity Inability to Inability to

Eye fixation (visual access structure/ access meaning
disorientation) spatial of
Movement properties of visual stimuli
(akinetopsia) visual stimuli
Shape
discrimination
Figure/ground
discrimination
Colour
(achromatopsia)
Texture
Page 9 of 27

processing
Anatomical
correlates
Posterior brain Right post- Inferior left

(occipital lobes) Rolandic post-Rolandic
hemisphere
No hemispheric hemisphere
asymmetry
(p.126) When multiple deficits are present, one needs to

validate observations with additional testing (this requires
considerable expertise, and at times, inventiveness by the
examiner).
It should always be remembered that visual object recognition

impairments may be due to a variety of deficits, although the
outcome is the same. They range from early visual (cortical)
processing disorders to high-level deficits relating to the
structure and identity of objects (visual agnosias).
4.3 Early visual processing disorders

Early visual processing skills are organized in a modular form.
They involve specialized areas of the posterior part of the
brain that code different properties, including colour, size,
basic shape, and movement. Given their segregation, these
skills may be selectively impaired with brain damage/disease
in the occipital lobes (partial cortical blindness). There is no
asymmetry between the two hemispheres at this level of visual
processing. Early visual processing deficits are generally
assessed with tests measuring physical differences between
two or more stimuli.
4.3.1 Acuity
Occipital lobe damage may affect visual acuity similarly to
disorders of the eye or optic nerve. There may be effects on
the ability to detect the presence or absence of light, different
changes in contrast sensitivity, and a target varying in size. A
significant impairment in one of these aspects of acuity results
in deficits in object recognition by sight. Acuity can be
Page 10 of 27
assessed by Snellen charts and other similar ophthalmological

instruments.
When assessing visual acuity the ability of the patient to cope

with the demands of commonly used acuity charts needs to be
considered. Patients with lesions in the posterior areas of the
brain may perform poorly for reasons other than poor acuity.
They may find it difficult to fixate on or scan visual targets due
to visual disorientation (below), visuospatial neglect, or
simultanagnosia (inability to perceive more than one stimulus
at a time). The acuity of these patients may be assessed with a
test comprising simple shapes (square, circle, triangle)
decreasing in size. Each target stimulus is presented
individually and the clinician obtains good visual acuity
measures (James et al. 2001).
4.3.2 Visual disorientation

This term refers to a difficulty in visually localising the
position or distance of objects in space. As a result, the patient
may bump into things and does not show the normal blink
response when the hand of the examiner is moved rapidly
towards his/her face. Related to this deficit is optic ataxia , a
visuo-motor disorder, in which the patient has a specific
difficulty in reaching (by hand) visual targets under visual
guidance (Perenin and Vighetto, 1988). Both these types of
early visual processing deficits are associated with lesions in
the occipito-parietal boundaries (McCarthy and Warrington,
1990, Karnath and Perenin, 2005). In clinical work, the term
“Balint’s syndrome” in association with posterior cortical
lesions is also encountered. This term lacks specificity in that
it is thought to give rise to the aforementioned and additional
deficits, including problems of (p.127) inattention/neglect
and a difficulty in processing objects that are seen sequentially
at the same location (Malcolm and Barton, 2007).
To assess visual disorientation, ask the patient to count or

point to random arrays of dots (e.g. Counting Dots test, Visual
Object and Space Perception (VOSP) battery; Warrington and
James 1991), or to pick up small items (e.g. paper clips) from a
desk. You may also ask the patient to reach with the index
finger towards a visual target in different parts of space, or to
judge which of two differently coloured tokens or small objects
placed on a desk is nearer/further from him/her. Patients with
visual disorientation are impaired in all these tasks. Those
Page 11 of 27
with optic ataxia are only impaired on tasks involving reaching

targets by hand under visual guidance.
4.3.3 Movement
The ability to locate points in space (Section 4.3.1) dissociates
from the ability to detect movement of stimuli in space. A
selective impairment in the perception of movement
(akinetopsia) is very rare and associated with lateral
occipitotemporal lesions. The perception of motion is thought
to be retinotopically organized (confined to one visual field
contralateral to the lesion).
Zihl et al. (1991) described a female patient who was able to

locate targets in space but was unable to detect their
movements. Visual scenes appeared to her as a series of static
snapshots. She was unable to perceive traffic or to use motion
as a cue when attempting to pour liquid.
For the assessment of akinetopsia, record what a patient

reports when observing moving objects in space, e.g. vehicles.
The patient may report a car in positions A and B but not
between these two points. Milder forms of this disorder need
to be studied with special equipment in ophthalmological
departments.
4.3.4 Size
Some patients may be able to recognize small but not ‘large’
visual stimuli, e.g. letters of the alphabet (Kartsounis and
Warrington 1991). This disorder may be independent of any
sensory problems, including restrictions in visual fields.
Assessment of size perception:
◆ Ask the patient to judge whether lines of the same or

different lengths are the same or not. Present pairs of lines
in random order, one pair at a time. To control for possible
visual field defects or inattention, the lines may be printed
horizontally, vertically, and in other directions.
(p.128)
Page 12 of 27
◆ Ask the
patient to
judge
whether
pairs of
simple
geometric
shapes
(e.g.
circles) are
of the same
size or not
(Fig. 7.1).
Randomly
present the
same and
different
pairs of
shapes.
4.3.5 Shape/
form
Patients may
become
impaired in
form
perception
due to Fig. 7.2 Efron shapes matched for total
bilateral surface.
occipital
lesions. These
Fig. 7.1 Circles for a size discrimination
patients may
test.
have good
visual acuity
and be able to
perceive colours, match surface textures, and locate obstacles
in space.
Efron (1968) described a patient who was unable to recognize

objects and his impairment was attributed to this fundamental
deficit. Efron devised a shape discrimination test comprising
stimuli of squares and oblongs matched for total surface area
and contrast (simplified form of the test in Fig. 7.2). Each test
Page 13 of 27
stimulus is presented individually and the patient is asked to

indicate whether it is a square or an oblong.
Research has indicated that certain visual skills may support

action but not conscious discrimination of stimuli. A patient
described by Milner and colleagues performed at chance level
in discriminating a square from an oblong pattern of equal
area, up to a ratio of 1:2. Despite her lack of awareness of
shapes, she was able to reach and pick up solid rectangular
blocks of different widths without difficulty. Her grip was
perfectly precalibrated (aperture between her index finger and
thumb) during midreach for a skilled grasp. These
observations are consistent with the notion that there are two
visual systems, one serving action (dorsal stream) and the
other serving visual discrimination and cognition (ventral
stream) (Milner 1997). (For implications of these notions on
conscious experience, see Goodale and Milner, 2004.)
4.3.6 Figure—ground discrimination

Early visual processing skill involves figure—ground
discrimination. This enables the viewer to analyse the defining
outlines of a stimulus and its background separately.
Impairments of this skill are associated with occipital lesions
and may dissociate from form perception deficits (Kartsounis
and Warrington, 1991; Davidoff and Warrington 1993). A test
for the assessment of figure—ground discrimination deficits is
included in the VOSP (Warrington and James 1991) (Fig.
7.3(a)).
Several other tasks can be used for the assessment of this

disorder. Ask the patient to identify line drawings of simple
geometric shapes, e.g. a square, circle or triangle, each (p.
129)
Page 14 of 27
printed Fig. 7.3 Examples of figure ground

separately on a
discrimination tests. (a) Adapted from
card. If the
VOSP. (b) Overlapping geometric shapes.
patient
performs this
(c) Kanizsa type figures.
task
satisfactorily,
then proceed with overlapping drawings comprising geometric
shapes. Patients with figure—ground discrimination impairment
may fail to report whole shapes or report parts of them (Fig. 7.3(b)).
They may similarly be impaired in perceiving subjective contours
(Fig. 7.3(c)).
4.3.7 Colour
Achromatopsia refers to impairment in colour perception. A
patient may be unable to see colour at all or perceive colours
as lacking in intensity. Impairments in colour perception are
associated with occipitotemporal lesions. They may be
confined to one visual field contralateral to a lesion
(retinotopic).
Assessment of colour perception:
◆ Exclude congenital abnormalities.
◆ Ask the patient to name, match colour patches, or

arrange them in a series according to brightness or
saturation.
— The Holmgren Wool Test consists of pieces of wool

that the patient is asked to sort according to their
hues.
— The Farnsworth–Munsell 100-Hue and

Dichotomous Test for Color Vision (Farnsworth 1943)
is a more demanding task requiring the patient to
arrange in the appropriate sequence coloured small
counters (matched for saturation and brightness)
according to hue.
— The Ishihara plates can also be used for testing

colour vision but they may not be sensitive to milder
cases of achromatopsia. (p.130)
Page 15 of 27
Unlike patients
with retinal
coloured
blindness,
achromatopsic
patients are
impaired in all
sectors of the
spectrum, Fig. 7.4 (a) Perspective influences
although perceived size. (b) Texture gradient.
discrimination
of shades of
grey may be preserved.
◆ For some patients who are unable to cope with tasks
involving a large number of items (above), a new test has
been devised. It comprises arrays of a few colour patches of
the same hue varying in brightness, including one colour
patch of ‘medium’ brightness but of different hue. The
patient is asked to indicate which patch is the odd one out
(James et al. 2001).
Patients with left posterior lesions may have normal colour

vision but are impaired in naming/comprehending colour
names. Others may present with a loss of colour knowledge
(colour agnosia). These patients find it difficult to accurately
colour with crayons black and white drawings of objects, fruit,
animals (e.g. a frog may be painted blue). These tests require
special care—a deficit in object recognition (Section 4.4) may
confound results.
4.3.8 Texture
Psychology textbooks refer to different examples of illusory
phenomena whereby perspective (impression of depth)
influences perceived size (Fig. 7.4(a)). However, surfaces that
recede in depth (Fig. 7.4(b)) and have a visible texture, e.g. the
grain in wood, may have additional effects. Texture gradients
may provide precise information about the distances of
surfaces and the sizes of stimuli on these surfaces. Abrupt
changes in texture gradient may signal the presence of edges
and corners, and strongly influence the perception of stimuli
(Gibson 1950). It is likely that texture perception is selectively
preserved or impaired in the same way as other early visual
processing skills.
Assessment of texture perception:
Page 16 of 27
◆ Ask the patient to describe stimuli with different texture

gradients. Impairment is identified when the patient is
unable to perceive the effects of texture (analogous deficit
to the inability to perceive illusory phenomena).
4.4 Higher visual recognition disorders
These deficits refer to visual agnosias for objects or faces
(prosopagnosia). The diagnosis of these disorders presupposes
well preserved primary sensory and early visual processing
systems (Section 4.3). Higher visual recognition problems are
due to a failure in attainment (p.131) of a coherent
structured percept (structural perception) or in assignment of
meaning to an object or face (semantic processing).
4.4.1 Structural perception of objects

In life, objects are encountered in unlimited variations.
Normally, we are able to recognize them both in prototypical,
and in a range of unconventional views and lighting
conditions. This ability relates to object constancy, which may
become impaired with right post-Rolandic lesions.
Patients with this disorder (aperceptive agnosia) are unable to

process the necessary information for the attainment of
coherent spatial properties of objects. It is thought that there
is stored representation of objects (object-centred
representation) with information about volume and structure
of familiar objects. When this information cannot be accessed,
the patient cannot identify degraded (or rotated) versions of
familiar objects. In non-optimal conditions this results in
misidentification of objects.
For the assessment of deficits in structural perception (‘visual

perceptual deficits’ proper) a variety of test materials can be
used, examples of which can be seen in Fig. 7.5. Many
perceptual tasks are dependent on the ability of the patient to
communicate verbally. The Object Decision test (one of the
tests in VOSP) does not require verbal responses and can be
used for the assessment of aphasic patients (the patient is
simply required to point to target stimuli). Other tests may
also be used without requiring the patient to respond
Page 17 of 27
(p.132)
verbally—ask
the patient to
match
incomplete
stimuli, with
their complete
versions, e.g.
incomplete
letters, with
alternative
‘solid’ letters.
4.4.2 Semantic
processing of
objects
Patients with
a disorder in
Fig. 7.5 Examples of perceptual tests. (a)
semantic
Incomplete letter. (b) Silhouette of object.
processing
(c) Conventional view; unconventional
(associative
view of object.
visual
agnosia)
perform satisfactorily on early visual processing and
perceptual tests (Sections 4.3 and 4.4.1). They are able to copy
objects and pictures of stimuli but fail to say what they are.
Their problem is not a naming deficit. This reflects their
inability to provide accurate information about the uses of
objects, colour, and size and where they can be found. These
patients cannot indicate whether two visually distinct
examples of the ‘same’ object, e.g. two types of glass, have
identical function. However, they may be able to identify
objects by touch. Associative visual agnosia does not
necessarily affect all types of visual stimuli, e.g. face
recognition may be spared. Studies in the past suggested that
semantic processing deficits are associated with bilateral
posterior brain lesions. More recently, single-case studies of
agnosic patients with unilateral left posterior (inferotemporal)
lesions have superseded the earlier reports (e.g. McCarthy
and Warrington 1986). That unilateral left posterior lesions are
sufficient to give rise to associative visual agnosia is also
indicated from group studies—patients with right posterior
hemisphere lesions are impaired on perceptual tasks; patients
with left posterior lesions are impaired on matching tasks.
Assessment of associative visual agnosia:
Page 18 of 27
◆ Present patients with pictures or models of animals, tools,

or other objects and ask them to name them, ask them
about their properties and where they can be found. A
naming test that includes different categories of stimuli can
be used for this purpose (McKenna 1997).
Beware. Patients may be unable to identify objects by name

due to optic aphasia. Both visual and verbal semantic
knowledge may be preserved but a disconnection between
these two cognitive domains prevents the patient from naming
an object. Patients with optic aphasia are able to demonstrate
the use of objects by other (nonverbal) means.
◆ Present patients with pictures of a wide range of objects

(e.g. kitchen items, tools, sport equipment, animals, means
of transport) and ask them to sort them according to use or
the category to which they belong.
◆ Real and unreal objects (comprising configurations of

features of objects that may or may not be encountered in
the real world) can also be used (Riddoch and Humphreys
1993; Fig. 7.6). Ask patients to say whether these items
exist in the real world or not.
◆ Ask patients to choose which one of two pictures relates

to a target picture (Fig. 7.7). A test using this technique is
the Pyramids and Palms Trees Test (Howard and Patterson
1992). The distractors in this task are chosen to be similar
to the items matched so that the patient finds it difficult to
choose simply on the basis of visual similarity.
4.4.3 Structural perception of faces

Impairments in recognition of familiar faces are collectively
referred to as prosopagnosia. These are thought to be distinct
deficits in visual recognition. The core deficit lies in a (p.133)
Page 19 of 27
selective,
faulty
perceptual
analysis of
faces (other
types of visual
stimuli may be
perceived
normally). This
disorder is
associated with
lesions in the
posterior
regions of the Fig. 7.6 Examples of unreal objects and
right animals.
hemisphere.
Assessment of
deficits in the structural perception of faces:
◆ Patients may be assessed on tasks involving photographs

of three or more faces differing in sex or age (‘who is the
oldest?’), with faces photographed from different
viewpoints or with same/different expressions (‘is it the
same or a different person?’). Patients affected by
structural deficits find it difficult to tackle these tasks or
are very slow in their responses, tending to use a feature-
by-feature analysis.
◆ More formally, structural disorders in face recognition

can be assessed with the Benton Facial Recognition Test
(Benton et al. 1978). Patients are required to find a target
face amongst six alternative faces shown in different
viewpoints and different lighting conditions.
4.4.4 Semantic processing of faces

Patients with this type of prosopagnosia are capable of passing
structural perceptual tests (Section 4.4.3) but are unable to
recognize familiar faces. They may be able to recognize them
by other features, including their voices, hairstyles, and
clothing. Semantic deficits in face recognition can be assessed
using photographs of family members, friends, and well known
public figures. (p.134)
Page 20 of 27
A test for
assessing face
recognition
ability has
been devised
by Young and
colleagues
(Ellis et al.
1989). It
consists of two
sets of public
figures, one
comprising 20
very well
known people
(e.g. Margaret
Thatcher, John
Wayne) and Fig. 7.7 Example of Pyramids and Palm
another Trees Test.
comprising 20
‘low-
familiarity’ faces (e.g. Marlene Dietrich and Max Bygraves). A
further set of 20 comprises unfamiliar faces. The test requires that
each face is first rated for familiarity on a 7-point scale (‘totally
unfamiliar’–‘highly familiar’). The subject is then asked to provide
the known person’s profession and name. This is a sensitive test,
yielding quantitative measures at different levels of familiarity,
leading to complete recognition of a face. It is limited by the fact
that ‘familiar’ faces need to be updated. Another potential critical
variable that may confound results is the individual patient’s media
exposure (or lack thereof) (e.g. Kapur et al. 1999).
Prosopagnosic patients may show covert recognition skills for
faces. Although unable to identify faces verbally, they may
show differential electrodermal responses to familiar and
unfamiliar faces involving correct and incorrect face–name
pairings. They may also show different reaction times and
memory performance towards familiar versus unfamiliar faces.
However, these techniques are not readily accessible to the
clinical neuropsychologist (and are usually used as research
tools).
(p.135) 4.4.5 False recognition of faces

A complementary deficit to prosopagnosia may be observed in
patients with right frontal lesions, that is, ‘recognition’ for
unfamiliar faces. This type of deficit is considered to be due to
Page 21 of 27
an impairment in strategic memory retrieval and monitoring,

typical of patients with frontal lesions.
4.4.6 Recognition of emotional expressions

The ability to recognize emotional expressions may dissociate
from the ability to identify faces. Patients with right
hemisphere damage are more likely to be impaired than those
with left hemisphere damage. They may become impaired in
recognizing the emotion of fear (following amygdalectomy)
and disgust (presymptomatic patients with Huntington’s
disease). For the assessment of these disorders clinicians may
use a test by Young et al. (2002) or devise their own stimuli
depicting unambiguous emotions. For a greater variety of
emotional expressions see e.g. Ekman et al. (1972).
5 Conclusion
The implicit assumption in the above review is that visual
object recognition skills have a hierarchical and parallel
organization (Table 7.1). In ordinary clinical practice however,
object recognition disorders are ‘random’. The question arises
as to where a clinician should start when assessing a patient
with object and/or face recognition problems.
The first consideration is to obtain information on potential

sensory problems, visuospatial neglect, aphasia, etc. that may
at least partly account for perceptual/agnosic deficits. As a
general rule, clinicians should be alert to the complaints and
errors patients make during other tasks involving picture
interpretation. They may ‘misname’ (misperceive) common
objects or give ‘don’t know’ answers when asked to name
them. Questions about the properties/uses of these stimuli
may elicit further information about the underlying
impairments—e.g. whether these reflect language or visual
recognition deficits. Patients’ answers may also suggest the
level of the visual recognition deficit.
◆ If they refer to very limited, basic features of an object

when shown a picture (e.g. ‘there is a line here and another
one there…’), it may be assumed that the disorder reflects
an early visual processing deficit. Formal tests of early
visual processing should then be the starting point (e.g.
point localization to exclude visual disorientation, form
perception, figure/ground discrimination).
Page 22 of 27
◆ If patients are able to indicate the basic structural form of

a stimulus but fail to identify it correctly, their deficits are
more likely to be of a higher order. In these cases the
assessment should start with tests of aperceptive agnosia
(object decision, incomplete letters tasks, and other
degraded stimuli).
◆ When perceptual skills are found to be well preserved,

proceed with tests of associative agnosia (questions about
properties of objects, matching tasks, etc.) (Table 7.2).
Clearly, when a patient is known to be grossly impaired in

analysing a wide range of real stimuli, including objects, faces,
etc., testing should begin with early visual processing tasks.
(p.136)
Table 7.2 Tests of object recognition deficits

processing
◆ Acuity Snellen Incomplete Questions re

charts, Queen Letters, Object names, colour,
Square* Decision, size
Silhouettes location,
(VOSP) functions of
objects (pictures/
models)
◆ Visual Stimuli shown Sorting of

disorientation from stimuli (pictures/
Point Localization, unconventional models)
Dot Counting Size: views (BORB) according to
see Fig. 7.1 category
◆ Shape: see Fig. Copying tasks Matching objects

7.2 that are visually
dissimilar but
have the same
function
◆ Figure/ground The Pyramids

VOSP and Palm Trees
Test
◆ Colour
Holmgren Wool Test,
Page 23 of 27

processing
Farnsworth–Munsell 100-Hue Test, Queen Square*,
Ishihara
◆ Texture: see Fig. 7.4(b)

*Queen Square Cortical Vision Screening Test.
if the patient fails these tests, there is no need for tests of visual
agnosias either of the aperceptive or associative type—any agnosia
diagnosed in this context would be ‘pseudo-agnosia’ (Warrington
1985).
The assessment methods outlined above are adequate for the
identification of the main types of impairments in object
recognition. Occasionally, and for a more precise definition of
a deficit, the clinician may need to devise a series of new tests.
In doing so, both the precise nature of a deficit may be
delineated and refinement in our knowledge of object
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Page 27 of 27
Recovery and treatment of sensory perceptual disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Recovery and treatment of sensory

perceptual disorders
C. Groh-Bordin
G. Kerkhoff
DOI:10.1093/acprof:oso/9780199234110.003.08

This chapter discusses recovery from and treatment
techniques for sensory perceptual disorders in the visual,
somatosensory, and auditory modalities. There is growing
evidence for the efficacy of cognitive rehabilitation in general,
and visuoperceptual training in particular, for patients with
brain damage. Systematic treatments of somatosensory
dysfunctions are just developing, despite their frequency and
relevance to the patient. Nevertheless, the techniques
discussed provide promising approaches towards significant
improvements to patients' disturbances.
Keywords: visual disorders, somatosensory disorders, auditory disorders,

cognitive rehabilitation, brain damage
Page 1 of 33
1 Basic principles of perceptual (re)-learning

In an early survey of studies about learning in the three main
modalities, Gibson (1953) showed that nearly any sensory or
motor ability can be improved considerably by training in
healthy subjects. More recently, the neural changes within the
sensory cortices have been described as the neural substrate
of such perceptual learning processes (cf. Gilbert et al. 2001;
Fahle 2005). This cortical plasticity can be assumed to be a
prerequisite for sensory-perceptual relearning after brain
damage. However, the capacity for full recovery through
training is often limited by several factors, (e. g. aetiology, age,
and size of lesion), as well as the affected modality and the
preserved sensory ability. In any case, perceptual
rehabilitation accounts for some basic principles which are
briefly illustrated below.
Principles of treatment in sensory perceptual

neurorehabilitation
◆ Restitution. Direct, repetitive training of the

impaired function is expected to promote improvements
that are important in themselves, but also relevant for
other related abilities (e.g. training of basic
somatosensory abilities not only improves these
abilities, but also has positive effects on motor
performance since somatosensory perception is
important for motor control; see Section 3.2). The
efficacy of restitutive treatments is more limited in
“lower” cortical areas (e.g. primary sensory cortex) than
in “higher cortical areas” (parietal lobe; Buonomano
and Merzenich 1998).
◆ Compensation. Utilization of a spared function to

compensate for a deficit; e.g. in patients with
homonymous scotomata the treatment of visual
scanning and reading effectively reduces everyday
problems associated with the field cut (bumping into
obstacles or persons, slow reading) but has little effect
on the field defect itself. Compensation techniques are
widely used in sensory perceptual rehabilitation
because restitution of elementary sensory deficits is
Page 2 of 33
often strictly limited due to the relatively fixed brain

topography of primary sensory cortical representations
(primary visual, auditory, or somatosensory cortices).
◆ Substitution. Use of technical/prosthetic devices to

compensate for a deficit (e.g. use of special light-
absorbing glasses in patients with blinding, to reduce
the amount of light). Also, environmental changes
designed to adapt the patient’s environment optimally
to those deficits that cannot be cured by restitution or
compensation treatments (e.g. modifying the house of a
patient to improve his spatial orientation and reduce
falls).
◆ Combination of Principles. In sensory perceptual

neurorehabilitation it is often necessary and fruitful to
combine any of the principles listed above to maximize
the outcome for the patient.
(p.140) In the following sections of this chapter, information

on recovery from and treatment techniques for sensory
perceptual disorders in the visual, somatosensory, and
auditory modalities will be provided.
2 Visual disorders
Visual-perceptual disorders occur after brain damage in about
30% of patients with cerebrovascular disorders and some 50%
of patients with traumatic brain injury (TBI). Consequently,
routine screening of the various types of visual deficits is
necessary for rehabilitation planning. Non-neglecting patients
can easily be assessed using the following questionnaire (and
respond correctly in 95% of the cases) (see Table 8.1).
2.1 Visual acuity

Primary and secondary causes of impaired static visual acuity
have to be distinguished before initiating treatment.
◆ Primary causes: Bilateral postchiasmatic lesions (Frisén

1980) may cause between partial and total loss of visual
acuity in both eyes which cannot be corrected by glasses.
This is often associated with bilateral visual field defects
(Kerkhoff 1999).
Page 3 of 33
◆ Secondary causes: Disturbed visual exploration, fixation

difficulties due to Balint’s syndrome, impaired contrast
sensitivity, eccentric fixation due to cerebral hypoxia, or
nystagmus. Impairments in acuity for moving targets
(dynamic acuity) are caused by deficient smooth pursuit eye
movements (Haarmeier and Thier 1999).
2.1.1 Recovery
Recovery is frequent in patients with secondary, but rare in
those with primary causes of disturbed visual acuity. As
impaired acuity affects all subsequent visual activities as well
as neuropsychological testing, treatment of the secondary
causes should be started immediately.
2.1.2 Treatment
The following short interventions can be given (cf. Kerkhoff
2000)
◆ Bilateral postchiasmatic lesion: Use magnification

software (for PCs), or screen reading machines for
permanent enlargement of printed text, pictures, and
letters.
(p.141)
Table 8.1 Schema for the anamnesis of visual

disorders after acquired brain lesions. Insert the
questions in the table into the following phrase:
“Have you experienced… since your brain
lesion?” (Based on Kerkhoff et al. 1990)
Question Purpose of Question,

Underlying Disorder
1. … any changes in - Awareness of deficits?

vision …? Information about case history
2. … diplopia …? - Type of gaze palsy? If

transiently/permanently? transient: fusional disorder?
3. … reading problems - Hemianopic alexia?

…? Differential diagnosis of
… syllables/words neglect dyslexia, aphasic
missing, change of line, alexia, or pure alexia
reduced reading span …?
Page 4 of 33

Underlying Disorder
4. … problems in - Depth perception? Optic

estimating depth on a ataxia?
staircase …?
… reaching with your
unimpaired hand for a
cup, hand, door handle
…?
5. … bumping into - Visual exploration deficits in

obstacles …? homonymous visual field
… failure to notice disorders?
persons …? at which
side?
6. … blinding after - Foveal photopic adaptation?

exposure to bright light
…?
7. … dark vision …? - Foveal scotopic adaptation?

… that you need more
light for reading … ?
8. … blurred vision …? - Contrast sensitivity? Acuity?

transiently/permanently? Fusion?
9. … that colours look - Colour hue discrimination?

darker, paler, less Impaired contrast sensitivity?
saturated …?
10. … that faces look - Face discrimination/

darker, paler, unfamiliar recognition disorders?
…?
11. … problems in - Object discrimination/

recognizing objects …? recognition disorders?
12. … problems in finding - Topographic orientation

your way in familiar/ deficits?
unfamiliar environments
…?
13. … visual - Simple or complex visual

hallucinations (stars, hallucinations, illusions?
dots, lines, fog, faces, Awareness about illusory
objects …) or illusions character?
Page 5 of 33

Underlying Disorder
(distorted objects, faces
…) …?
◆ Visual exploration deficit: Improve visual search by

providing the patient with a systematic (horizontal or
vertical) saccadic search strategy. Acuity will improve when
visual search is more systematic, quicker and when
omissions are reduced (see Section 2.5.2).
◆ Nystagmus: Calm nystagmus with orthoptic (prisms) or

pharmacological means (Straube and Kennard 1996).
◆ Spasmodic fixation (Balint’s syndrome): Test acuity with

single letter charts; acuity for single letters should be
normal. Furthermore, improving simultaneous perception
by repetitive treatment enlarges the useful field of view
(Perez et al. 1996) and improves activities of daily living.
◆ Dynamic visual acuity: Treat smooth pursuit eye

movements in the horizontal domain (left, right) for
different velocities. The recognition of moving objects is
important for vocational tasks (Gur and Ron 1992) and
mobility in the environment. It improves in parallel with the
increase of smooth pursuit gain.
(p.142) 2.2 Spatial contrast sensitivity (CS), foveal photopic and
scotopic adaptation, visual discomfort
Spatial CS denotes the ability to discriminate between striped
patterns (gratings) of differing luminance (contrast) and stripe
width (spatial frequency). It is often impaired in posterior
brain lesions (80%, Bulens et al. 1989).
◆ Foveal photopic adaptation means the continuous

adapting to a brighter illumination;
◆ scotopic adaptation means the adaptation to a darker

illumination than the present one.
Both processes are dissociable and impaired in some 20% of

patients with posterior cerebral artery infarctions or cerebral
hypoxia (Zihl and Kerkhoff 1990).
2.2.1 Recovery
◆ Contrast Sensitivity: Rapid recovery in the majority of
patients; permanent deficits in about 20%.
Page 6 of 33
◆ Adaptation: No recovery (even after years) present in the

patients tested so far (Zihl and Kerkhoff 1990).
2.2.2 Treatment
◆ Impaired CS: CS can be trained effectively in normal
subjects but this has never been tried in brain damaged
patients. In those 20% with permanent deficits the use of
additional, indirect lighting is helpful because it improves
contrast.
◆ Isolated loss of photopic adaptation or combined disorder:
— Avoid direct lighting, use dimmer to adjust light

individually;
— Avoid flickering neon lights;
— Use sun glasses outside buildings;
— Avoid continuously adapting sun glasses (Varilux)

because they are too expensive and too slow in
readapting inside a building.
— Car driving at night (“blinding”) is not advisable.
◆ Isolated loss of scotopic adaptation: Increase indirect

lighting by additional light bulbs, use dimmer to adjust
lighting individually.
2.3 Stereopsis and convergent fusion
Local and global stereopsis are reduced in patients with
occipital, parietal or temporal brain lesions and impair manual
activities in near space (reaching and grasping, technical
work, depth perception), which is relevant for vocational
rehabilitation. Convergent fusion is a prerequisite of
stereopsis and refers to the fusion of the left and right eye’s
image to one combined (fused) picture of the world. Fusion is
impaired in some 20% of patients with posterior vascular
lesions and about 1/3 of TBI patients (Kerkhoff 2000). Patients
with impaired fusion have severe reading problems after some
10 minutes. They rapidly develop diplopia and are impaired in
all near-work activities.
(p.143) 2.3.1 Recovery

The percentage of patients showing recovery is unknown in
stereopsis. In TBI patients with fusional disorders 3/4 have
persistent disorders for years after their injury (Hart 1969).
2.3.2 Treatment
Page 7 of 33
Fusion and stereopsis can be trained together using simple

orthoptic or binocular devices (Kerkhoff and Stögerer 1994)
within the following treatment plan:
◆ Anamnesis: Asthenopic disorders (eye pressure, fatigue in

reading or PC-work), blurred vision, problems in near-work
activities?
◆ Therapy: Improvement of fusion and stereopsis by

repetitive display of dichoptic images with increasing
disparity angle; 8-20 sessions advisable.
◆ Outcome: Favourable in 80% of patients; improvements in

reading duration, stereopsis and fusional range; relief from
asthenopia; better functioning in vocational life.
◆ Exclusion criteria: Premorbid deficits in binocular

integration; permanent diplopia with angle >15°.
2.4 Visual discomfort
Looking at homogeneous, regular patterns like lines, written
text, flagstones or stripes of a certain spatial frequency (3-4
cycles per degree visual angle, Wilkins 1986) elicit unpleasant
sensations (termed “visual discomfort”), blurred vision and
headaches in some healthy subjects, but much more so in
patients with cerebral visual disorders. Visual discomfort in
brain lesioned patients may reduce sustained visual activities
considerably and lead to asthenopic symptoms.
2.4.1 Recovery
Unknown.
2.4.2 Treatment
In reading, visual discomfort can be eliminated by using a
simple mask that covers all lines except the one that is
currently read.
2.5 Homonymous visual field disorders (VFDs)

VFDs are present in 20–30% of all neurological patients in
neurorehabilitation centers. Visual field sparing is 5° or less in
70% of them (Zihl and von Cramon 1986). VFD patients may
present with three types of associated deficits: visual
exploration deficits, reading disorders and visuospatial
deficits.
◆ Visual exploration deficit: Time-consuming, inefficient

visual search due to loss of overview and unsystematic
Page 8 of 33
search strategies; numerous, small-amplitude staircase-

saccades in blind hemifield; omissions of targets in blind
field
(Zihl 1995a, Pambakian et al. 2000, 2004).
(p.144)
◆ Hemianopic reading disorder: Slow reading with few
errors in VFDs with field sparing < 5°, also present in
paracentral scotomas and quadrantanopia; reading of short,
single words is normal (no aphasia or alexia; Zihl 1995b,
Leff et al. 2000).
◆ Visuospatial deficits: Subjective midline (in line bisection)

is shifted towards the blind field (horizontally in left/right
VFDs, vertically in altitudinal VFDs) in 90% of patients
(Kerkhoff 1993, Barton and Black 1998); this shift is also
evident in daily life (walking through doorways, sitting in
front of a table).
2.5.1 Recovery
Field recovery is present in the first 2–3 months post-lesion in
up to 40% of the patients with a stable aetiology (Zhang et al.
2006). After 6 months postlesion, spontaneous recovery is
extremely unlikely (Zihl and von Cramon 1986, Zhang et al.
2006).
2.5.2 Treatment
Since field recovery is very limited, restorative field training is
appropriate only in a very small group of patients (detailed
below). For the majority of VFD patients (95%) compensatory
visual field treatment of the associated disorders in reading
and visual scanning is advocated (see Table 8.2).
Recently, Bologninie et al. (2006) have suggested cross-modal

(visual-auditory) training for the improvement of reading and
scanning in hemianopia. Here, visual and auditory targets are
presented time-locked in different locations of the visual field,
and the patient has to saccade to them. This is an effective
additional training.
Ineffective or disadvantageous therapies:
◆ Prisms are in most cases useless for the treatment of

VFDs because patients become confused. However, in
Page 9 of 33
selected cases small prisms fitted to a spectacle have been

found useful.
◆ Compensatory head shifts towards the scotoma (either

spontaneously adopted by the patient or instructed by staff)
are of no use in the rehabiltation of VFDs, because they lead
to visual exploration deficits in the ipsilesional visual field,
stays of the neck muscles, and delay treatment progress in
visual scanning training (Kerkhoff et al 1992).
◆ Training of ‘blindsight’ in VFDs is probably not a useful

therapy (Zihl and Kennard 1996) because it does not lead to
improved functioning in daily life.
In the last decade, restorative visual field training has been

revived after publication of advantageous results following
new training procedures (Kasten et al. 1998). However,
numerous replication studies have not found significant visual
field enlargements (Nelles et al. 2001, Pambakian et al. 2004,
Reinhard et al. 2005). Table 8.3 summarizes the main findings
of the discussion. The results clearly suggest that
compensatory visual field training is advisable for 95% of
patients with visual field defects, whereas restorative field
training is only promising when lesions are incomplete and a
high degree of visual capacities (light, motion, form, or colour
perception) are preserved in specific regions of the scotoma
(Kerkhoff 2000). (p.145)
2.6 Visual hallucinations
Table 8.2 Summary of compensatory (hemianopic

reading and visual exploration training) and
restorative (visual field training) approaches in
patients with postchiasmatic scotoma
Compensatory visual field training: hemianopic reading

training
1. Anamnesis: change of line, types of errors

(omissions, substitutions, problems with long words
or numbers), maximum reading duration,
asthenopic disorders
Page 10 of 33
Compensatory visual field training: hemianopic reading

training
2. Type of Treatment: improvement of oculomotor
reading strategies to substitute the lost parafoveal
visual field; tachistoscopic reading of single words,
moving window technique, floating words, search
for words in a text, scanning reading technique,
training of numbers with embedded zeros; variation
of physical and linguistic parameters: word length
and frequency, position on screen (left, centre,
right), number of words, presentation time,
complexity of text, variation of instructions
3. Transfer: reading of newspapers, books, own
manuscripts; text editing on a PC, increase of
maximal reading duration
4. Outcome and follow-up: increase in reading
speed; 500% reduction in reading errors; partial
field recovery (mean 5 °) in 1/3 of patients
Compensatory visual field training: visual exploration

training
1. Anamnesis: limited overview, bumping into

persons and obstacles, defective orientation in
visual space, e.g. crowded situations, traffic
2. Type of Treatment: increase amplitude and
velocity of saccadic eye movements towards
scotoma: variation of size, reduction of saccadic
reaction time; discourage head movements or
compensatory head shifts; teach systematic,
spatially organized (horizontal or vertical) visual
search strategy on wide-field displays; start search
in blind field; use visual displays requiring serial
and parallel search; possibly combination with
other stimulation devices (optokinetic stimulation);
alternative account: audiovisual (crossmodal)
training (see text for details)
3. Transfer: treat orientation in clinic, own urban
district, new environments, management of visual
ADLs: find objects on table or in room, find
therapist’s room, find objects in supermarket, cross
street, use public traffic, find way home
Page 11 of 33
Compensatory visual field training: visual exploration

training
4. Outcome and follow-up: reduction of omissions
and search time; partial field recovery (mean: 5–7
°) in 34% of patients
Restorative visual field training
1. Anamnesis: residual visual capacities (often

movement of a stimulus) in regions of scotoma;
search for amblyopic transition zones (with partially
preserved function) which are most likely
candidates for field recovery; however, such
transition zones are present only in some 10–20%
of patients.
2. Type of Treatment: improvement of saccadic
localization at field border or in amblyopic
transition zone; recognition of colour, form,
orientation, or luminance of the target
3. Transfer: improvement in reading und subjective
awareness of visual problems
4. Outcome and follow-up: mean field increase:
5–10°; stability at follow-up; 70% of patients have a
field recovery < 5°
Simple, formed, visual hallucinations (light dots, bars, lines,

stars, fog, coloured sensations, etc.; Lance 1976) are
frequently reported by patients (only when questioned
systematically!) with posterior vascular lesions, and occur
most frequently following occipital lesions. More complex
visual hallucinations and illusions are rare and most often
associated with temporal lobe lesions (Kölmel 1984, 1985). (p.
146)
2.6.1 Recovery
Table 8.3 A comparison of compensatory versus

restorative visual field training
Page 12 of 33
Compensatory Restorative visual

visual field training field training
(reading, saccadic
scanning training)
Objective visual +, 0–5° in a +, 2–5° in

field subgroup of computer-based
enlargement patients, no field campimetry,
after treatment? improvement in the no field
majority of patients enlargement
(0.0°) in fundus-
controlled visual
field tests
Objective +++, 20–50% +, 8%

improvements in improvement in improvement in
reading and reading (speed and reading (speed)
visual scanning? errors)
Subjective +++, great +, small

improvements in improvements in improvements
visual activities 90% of patients
of daily living? treated
Number of ++, 25–50 hours +++, 100–150

required (for reading and hours
treatment scanning training)
sessions?
Vocational +++, return to job ?

improvements in >90 % of treated
after therapy? hemianopic
patients
Costs? ++ (max 1000 Euro +++, 5000 Euro

for software) for software
Legend: + (small), ++ (medium), +++ (high), ? (not known)
Recovery is rapid and complete in 95% of patients, so that at 6

weeks postlesion the occurrence is quite rare (Kölmel 1984,
1985).
2.6.2 Treatment
As hallucinations and illusions are irritating but mostly
transient phenomena, therefore information to and
reassurance of the patient are important.
Page 13 of 33
◆ Inform your patient: Visual hallucinations are quite

normal but transient phenomenon after a vascular brain
lesion.
◆ Calm your patient: Most patients experiencing simple

hallucinations know that they perceive erroneous visual
stimuli not present in the outer visual world. Tell the patient
that he/she is not going mad. If necessary, demonstrate to
the patient that hallucinations can be provoked in any
person by pressing the eye-ball (pressure phosphenes) or
when suddenly rising from a supine position (blood-
pressure-related).
◆ Complex vs. simple hallucinations: Complex visual scenes

have a higher reality character than simple hallucinations,
and are therefore more frightening for the patient. These
patients are very reluctant to talk about their experience
because they fear being misdiagnosed as a psychiatric case.
Note, that psychiatric patients more frequently experience
auditory versus visual hallucinations, while the opposite
holds true for patients with organic visual hallucinations
following posterior brain lesions. Furthermore, brain
damaged patients very rarely report “hearing voices”.
◆ Persistent visual hallucinations: Check whether there is

an epileptic focus (EEG), the possibility of a new infarction
developing, or a psychiatric disease.
(p.147) 2.7 Colour perception
Colour and form perception can be impaired within a scotoma
after postchiasmatic VFD, or within central vision after
postchiasmatic lesions of various aetiologies (Meadows 1974;
Zeki 1990). The deficit in central vision may range from a
subtle deficit in hue discrimination (often with unilateral
occipitotemporal lesions) to a nearly total achromatopsia after
bilateral lesions.
2.7.1 Recovery
Recovery of colour and form vision within a scotoma are often
observed in patients with partial field recovery (Zihl and von
Cramon 1985). As a rule, the progression of visual recovery (if
there is one!) in VFDs is as follows:
Light detection → light localization → brightness discrimination

→ form discrimination → colour perception.
Page 14 of 33
Hence, colour vision is the last to recover. In those patients

with colour vision deficits in central vision, no recovery has
been reported over six years in one study (Pearlman et al.
1979).
2.7.2 Treatment
◆ Defective colour vision in visual field regions: In patients
with residual colour perception in a scotoma and
incomplete lesions, improvement of colour discrimination
can be trained by displaying coloured targets at the field
border and having the patient saccade to them and
discriminate the colour (as described in Table 8.2, visual
field training).
◆ Defective colour perception in central vision: Forced

discrimination of differently coloured forms is partially
effective in cerebral anoxia, however with limited transfer
to non-trained colours (Merrill and Kewman 1986). Often,
the patients can learn to base their colour judgments on
other cues such as the brightness or saturation despite
permanently impaired hue discrimination.
2.8 Visual form recognition
Recognition deficits for simple visual forms (rectangle, square,
triangle, etc.) without a semantic dimension (such as real
objects) is only observed in patients with extensive bilateral or
diffuse-disseminated, posterior brain lesions. When present,
the patients are unable to discriminate simple geometric forms
equated for total luminance (Milner et al. 1991). The rareness
of the disorder is due to the fact that it occurs most often after
extensive anoxic brain damage.
2.8.1 Recovery
Recovery is often incomplete or even absent, possibly due to
the bilateral or diffuse-disseminated lesions in cerebral anoxia
or carbon monoxide poisoning. The case reported by Sparr et
al. (1991) showed the disorder to be stable for more than 40
years. Recovery may be more likely in patients with
cerebrovascular aetiologies and/or unilateral lesions.
(p.148) 2.8.2 Treatment

Visual form recognition can be improved by repetitive
discrimination training for simple geometric forms equated for
total luminance. Verbal or computerized feedback is essential,
as are progressive increase in the similarity of the stimuli to
be discriminated. As a result, visual form discrimination of
Page 15 of 33
simple geometric forms but also of line drawings and partially

of photographs displaying real objects is improved, along with
increased visual acuity and contrast sensitivity. Treatment can
be accomplished either with self-constructed paper-made
stimuli, or with computerized devices which give detailed
quantitative feedback and allow variations of colours, sizes
and forms (c. f. Kerkhoff and Marquardt 1998).
2.9 Visual object and face perception

The inability to recognize visual objects (visual agnosia) and
faces (prosopagnosia) are rare conditions, occurring probably
in less than 1% of all neurological patients (Zihl and Kennard
1996). Both types of agnosia occur most frequently after
bilateral occipitotemporal lesions (Farah 1990). In object
agnosia, a more perceptual (apperceptive agnosia) and a more
conceptual (associative agnosia) subform are usually
distinguished. The former indicates a deficit in perceptual
object discrimination; the latter implies a loss of semantic
knowledge related to visually presented objects (Farah 1990).
2.9.1 Recovery
Detailed case reports about recovery are rare. Partial recovery
in the recognition of real life objects has been occasionally
noted, while recognition of photographs of objects or faces
rarely improves. Recovery is particularly unlikely in anoxic
brain damage, probably due to the widespread diffuse lesions
and the additional cognitive impairment impeding the
acquisition of compensatory strategies (Sparr et al. 1991).
Partial recovery is more likely in traumatic or vascular lesions
and in those few cases with unilateral right sided lesions
showing face agnosia (Farah 1990).
2.9.2 Treatment
Controlled treatment studies are rare. Zihl and Kennard
(1996) noted improvement of object and face discrimination on
photographs and in real life in three patients following an
intensive (120 hours) treatment procedure focusing on the
specific search for key features of objects or faces.
Furthermore, the use of context information (knowledge about
objects and faces and the relevant social situation) is advisable
and helpful for these patients.
2.10 Visual motion perception
Page 16 of 33
Relative impairments of visual motion perception may occur

after focal lesions of the motion centre in the occipito-parieto-
temporal cortex, but permanent deficits are probably rare, and
even in these patients only relative (frequency of relative
deficits: 13%, Schenk and Zihl 1997). However, many brain
damaged patients subjectively report problems in estimating
the velocity and position-changes of moving vehicles in traffic
(as a pedestrian, or in a car). This may result either from
impaired motion perception (linearly or in depth), disturbed
visuospatial perception, or a combination of both.
(p.149) 2.10.1 Recovery

Little is known about recovery. In those rare patients with
bilateral lesions, no recovery has been reported (Zihl et al.
1991), while those with unilateral lesions may show recovery.
Even the motion-blind patient reported by Zihl et al. (1991)
readapted to moving stimuli in daily life by certain
compensatory techniques, despite her permanent motion
deficit under laboratory conditions.
2.10.2 Treatment
Due to the rarity of severe impairments in visual motion
processing and the probable multiplicity of cortical and
subcortical areas involved in visual motion perception,
treatment approaches have not been developed. However, the
treatment of an associated ability, that is, smooth pursuit eye
movements when tracking a moving target, is useful for
improving visual scanning on PC-screens and visual
orientation in daily life (Gur and Ron 1992). Treatment can be
accomplished by use of a large PCscreen, where the subject
follows a moving target in different directions with a stabilized
head. Target velocity should be adapted so that pursuit eye
movements can be performed with relatively few catch-up
saccades. In addition, a training of situations in daily life
where motion is important (crossing a street, using a moving
staircase), can improve orientation and reduce the likelihood
of accidents due to reduced motion perception. Secondary
cues may help to code visual motion of vehicles (i.e. by
position or size changes), despite a stable impairment in
motion processing under laboratory conditions.
3 Somatosensory disorders
Somatosensory deficits are present in the majority of
hemiplegic patients and hence in about 30–40% of all stroke
patients with unilateral lesions. Hermsdörfer et al. (1994)
Page 17 of 33
found in a large sample of 272 brain damaged patients, 29.8%

had somatosensory disorders, and 37.9% subjectively reported
somatosensory hallucinations, metamorphognosia,
hypersensitivity, or pain. Of those patients impaired on
somatosensory testing, the frequencies of differential deficits
were:
◆ Impaired passive movement discrimination of fingers

(82.7%), wrist (70.4%), elbow (51.8%), shoulder (48.2%)
◆ Impaired localisation of finger parts (55.5%)
◆ Impaired two-point discrimination of the index finger

(53.1%)
◆ Impaired astereognosis (37.1%)
◆ Impaired detection of light finger touches (32.1%)

3.1 Recovery
Few systematic patient studies of recovery exist. Primate
studies indicate substantial recovery of somatosensory
dysfunctions spontaneously and after controlled treatment
(Jenkins et al. 1990).
(p.150) 3.2 Treatment

The few controlled treatment studies for patients with tactile
deficits indicate that these can be trained efficiently (Goldman
1966; Zane and Goldman 1966; Yekutiel and Guttman 1993;
Carey and Matyas 2005). The following types of treatment are
useful and have been evaluated quantitatively:
◆ Retraining of different somatosensory functions: Most

somatosensory abilities can be trained (location of touch,
sense of elbow position, two-point-discrimination,
stereognosis) using the following therapeutic principles
(Yekutiel and Guttman 1993):
a) Improve awareness of sensory dysfunction by
allocating attention to it;
b) Start treatment with sensory tasks the patient

can do in order to improve motivation and reduce
frustration;
c) Use or develop tasks that are interesting and

relevant for the patient, which involve selective
Page 18 of 33
attention because this improves sensory

functioning;
d) Also use vision and the good hand during

training to teach tactics and useful strategies of
perception;
e) Frequent rests are necessary.
One key feature of this approach is the implementation of

systematic sensory training in relevant functional tasks.
Examples of such tasks are: identification of line orientations;
discrimination of shape, size, weight, or temperature of
objects placed in patient’s contralesional hand; identification
of forms drawn with a pencil on the patient’s hand/arm from a
visually presented multiple-choice display (detailed in Yekutiel
and Guttman 1993).
◆ Tactile extinction training: The objective is to improve the

patient’s attention to double simultaneous stimulation
(DSS) of the hand’s surface. For this purpose, either light
touches of different fingers or positions on the hand or any
other body region can be used. Patients are required to
direct their attention to the touch on the impaired hand,
which should be hidden from direct vision. The
improvements obtained with this simple procedure are
impressive, reducing tactile extinction of contralesional
stimuli considerably (Goldman 1966; Zane and Goldman
1966). A critical therapeutic element is the focussing of
attention towards the contralesional tactile stimulus and
the relearning of the’twoness’ of the DSS task.
◆ Improvement of tactile functions by peripheral magnetic

stimulation (RPMS): With this novel method the dorsal palm
of the contralesional hand is stimulated magnetically (non-
painfully). After a single (20 minute) stimulation session we
found a 27% reduction in tactile extinction for different
surfaces delivered to both hands, while a matched control
group did not show any improvement (Heldmann et al.
2000). Probably, multiple stimulation sessions lead to stable
and greater improvements. Subjectively, the patients report
that they feel more in their contralesional arm; this could
be especially helpful in patients with tactile neglect and
unawareness of their contralesional hand/arm.
(p.151)
Page 19 of 33
◆ Optokinetic stimulation (OKS): OKS moving to the

contralesional hemispace in patients with tactile neglect
(Vallar et al. 1997) improves the subjective awareness of
different angular arm positions (contra- and ipsilesional
arm) and reduces tactile extinction (Nico 1999) transiently.
Repetitive OKS over several sessions should improve tactile
and kinaesthetic functions permanently.
◆ Treatment combinations: Although speculative, the

combination of several treatments might be most effective
and could improve the patient’s self-awareness for the
contralesional body side. Furthermore, the use of visual
imagery might be helpful for patients with astereognosis
since this process is helpful in tactile object recognition and
mediated by the intact visual cortices (Deibert et al. 1999).
4 Auditory disorders
Significant alterations to a variety of auditory-perceptual
functions have been reported following lesions below as well
as beyond the medial geniculate bodies (auditory radiation).
For the most part, the deficits can be categorized into audio-
spatial disorders and auditory feature discrimination deficits,
suggestive of modular processing in audition (Rauschecker
1998).
4.1 Audiospatial disorders

Among these, the following deficits have been reported, and
will be summarized here together with the few findings about
recovery and treatment.
4.1.1 Deviation of the subjective straight ahead or midline

position
Patients with spatial neglect, often following right parietal
lesions, show a significant shift of their subjective auditory
midline in the horizontal plane in front and back space. This
shift may be to the ipsilesional side in front and back space
(Vallar et al. 1995), or ipsilesionally in front space and
contralesionally in back space (Kerkhoff et al. 2006). Patients
without neglect, but with homonymous hemianopia show the
opposite, contralesional deviation (i. e. towards the scotoma;
Kerkhoff et al. 1999).
◆ Recovery: During recovery from multimodal neglect the

ipsilesional auditory midline shift often regresses. Likewise,
during improvement of compensatory visual exploration
Page 20 of 33
functions in patients with homonymous visual field

disorders (see 2.5.2), a reduction of the contralesional
auditory midline shift is also observed.
◆ Treatment: Optokinetic stimulation (OKS) towards the

neglected hemispace normalizes the auditory midline shift
transiently and permanently after repetitive treatment
(Kerkhoff et al. 2001).
4.1.2 General spatial uncertainty of auditory localization

Patients with visual neglect after right parietal lesions (Pavani
et al. 2001) often have a general deficit in auditory localization
(but not necessarily in detection) in their contralesional
hemispace (horizontally and vertically). Patients undergoing
cerebral (p.152) hemispherectomy initially also show large
localization errors in their contra-operated hemispace.
◆ Recovery: Zatorre et al. (1995) reported substantial

recovery of auditory localisation in the contralesional
hemispace in patients with unilateral hemispherectomy.
Obviously, long-term experience can lead to a substantial
reorganisation of the brain processes responsible for spatial
hearing. Clinical experience in neglect patients indicates
that localization accuracy improves as general attentional
capacities improve (see Chapters 5, 6, 23).
◆ Treatment: No systematic studies are available. As in

visuospatial neglect, sustained attention training may
reduce the general uncertainty of neglect patients in
auditory localization.
4.1.3 Auditory extinction of contralesional stimuli

This occurs after lesions of the auditory pathways in the
temporal lobes (De Renzi et al. 1984) of either hemisphere, or
in small lacunar lesions (Arboix et al. 1996).
◆ Recovery: Rapid recovery is found after frontal lobe

lesions while persisting auditory extinction occurs following
lesions of the auditory pathways (De Renzi et al. 1984).
◆ Treatment: No systematic studies are available.
4.1.4 Auditory motion processing

The right parietal cortex is involved in horizontal auditory
motion perception (Griffiths et al.1998), and consequently
right parietal cortex lesions impair auditory motion
discrimination (Griffiths et al. 1996).
Page 21 of 33
◆ Recovery: Unknown.
◆ Treatment: Unknown.
4.2 Deficits in auditory feature discrimination
The following deficits have been reported and will be
summarized together with the few findings on recovery and
treatment.
4.2.1 Cortical deafness

Cortical deafness is an extremely rare condition resulting
either from brain-stem lesions, subcortical lesions disrupting
the auditory pathways, or from bilateral temporal lobe lesions
destroying the primary auditory cortex bilaterally (cf. Polster
and Rose 1998). It comprises, as in cerebral blindness, the
total or near-total inability to hear any sounds despite
preserved afferent pathways to the primary auditory cortices.
Recovery: Some degree of recovery has been noted (Mendez

and Geehan 1988). Usually, cortical deafness evolves into
auditory agnosia, followed by selective auditory agnosia for
certain tasks, pure word deafness, and/or amusia, and finally a
residual disorder of temporal processing.
◆ Treatment: No treatments have been published due to the

rareness of permanent deficits.
(p.153) 4.2.2 Auditory agnosia

Auditory agnosia is the inability to recognise auditorily
presented sounds independent of any deficit of processing
spoken language. This may include the inability to recognise
environmental (i.e. different vehicles) and human sounds
(coughing, baby cries), although perception and perceptual
discrimination of these sounds is unimpaired, and peripheral
hearing is normal as well. Generally, the disorder is thought to
be analogous to the two types of visual object agnosia found
after bilateral occipitotemporal lesions (apperceptive and
associative agnosia, see 2.9). As in vision, a differentiation into
a more perceptual deficit, probably most often found after
right-hemispheric (temporal lobe) lesions, and a more
associative-semantic deficit, most often seen in left-
hemispheric lesions is made (Polster and Rose 1998).
Page 22 of 33
◆ Recovery: Engelien et al. (1995) observed recovery in a

case of auditory agnosia which was paralleled by
activations (assessed with PET) in a large bilateral frontal,
middle temporal, and inferior parietal network. Further,
they noted activation of peri-infarct cortices which may
enable recovery from auditory agnosia. In a case with “deaf-
hearing” after bilateral auditory cortex lesions, directing
selective attention to sound recognition improved auditory
functions considerably and was paralleled by bilateral PET-
activations in the lateral prefrontal, middle temporal, and
cerebellar cortices (Engelien et al. 2000). In summary,
selective attention may play a key role in adapting to
auditory disorders. Surviving perilesional cortex, as well as
more widespread cortical networks in both hemispheres
may be critical for behavioural recovery.
◆ Treatment: Fechtelpeter et al. (1990) described a

treatment for environmental sound recognition in a patient
with auditory agnosia due to bilateral temporal lesions. The
four-week treatment included the following elements and
may be paradigmatic for similar cases:
— Sound imitation: The patient had to imitate or

actually perform a typical sound of an object (e.g.
telephone) and was then later confronted with the
tape-recorded sound of this object and asked to
decide whether they were the same;
— Semantic association: The patient had to associate

a sound to a specific object out of a sample of ten
visually presented objects;
— Auditory analysis: The therapist taught the patient

acoustic features of specific sounds (a starting car
first makes a deep sound, and then interrupted
sounds according to the different gears).
All treatment techniques effectively reduced the auditory

deficits with a significant transfer to daily life in this case.
These or similar, individually adapted techniques may be used
to treat patients with auditory agnosia or more subtle
perceptual deficits.
4.2.3 Pure word deafness

This is defined as the inability to process spoken words despite
normal hearing thresholds and normal processing of auditory,
non-language stimuli.
Page 23 of 33
(p.154)
◆ Recovery: As mentioned above, pure word deafness often
evolves into a more subtle auditory-perceptual disorder
(Mendez and Geehan, 1988).
◆ Treatment: Unknown.
4.2.4 Nonverbal auditory perception and recognition disorders

Among these the following types of deficits have been
described:
◆ Phonagnosia: Impaired recognition of familiar voices due

to right hemispheric lesions (reviewed in Polster and Rose
1998).
◆ Voice discrimination disorders: Impaired perceptual

discrimination of different voices (unfamiliar) after right
temporal lesions (cf. Polster and Rose 1998).
◆ Impaired perception of emotional prosody: This occurs

preferentially in right-hemispheric lesions and denotes the
inability to understand affectively intoned speech (Ross
1981).
◆ Impaired perception of pitch direction: This occurs after

right temporal lesions (Johnsrude et al. 2000).
◆ Altered music perception: This is mostly impaired after

right or bilateral temporal lesions (cf. Polster and Rose
1998).
◆ Nonrecognition of environmental sounds: This occurs in

right temporal lesions (cf. Polster and Rose 1998).
◆ Temporal processing disorders: These have been

described in unilateral lesions of either hemisphere, but the
left hemisphere is most critical for short acoustic
transients.
◆ Hypersensitivity to sounds: This occurs in TBI patients

(Waddell 1984) and is often coupled with hypersensitivity to
light (blinding, see 2.2.2). The problem is important in work
rehabilitation (avoid noisy workplaces!).
◆ Recovery and treatment: No systematic studies are

available.
5 Conclusion
Page 24 of 33
There is now growing evidence for the efficacy of cognitive

rehabilitation in general (Cicerone et al. 2005), and
visuoperceptual training in particular (Jutai et al. 2003), for
patients with brain damage. Systematic treatments of
somatosensory dysfunctions are just developing, despite their
frequency and relevance to the patient. Nevertheless, the
above mentioned techniques provide promising approaches
towards significant improvements to the patients’
disturbances (for further review, see Nowak and Hermsdörfer
2008). The consequences of auditory-perceptual deficits in
daily life are increasingly well understood. Often it is assumed
that most of these deficits can be compensated for easily, since
either preserved auditory abilities may be used for
compensation, or multiple cues are available in daily life.
However, this view may be wrong, as many patients do not
spontaneously report, and therefore fail to be aware of, their
auditory deficits. Hence, the consequences for nonverbal
communication are likely to be underestimated (as for
example in neglect patients who seldom complain about their
auditory deficits).
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Barton, J. J. S., and Black, S. (1998). Line bisection in

hemianopia. Journal of Neurology Neurosurgery and
Bellmann, A., Meuli, R., and Clarke, S. (2001). Two types

of auditory neglect. Brain, 124, 676–687.
Bisiach, E., Cornacchia, R., Sterzi, R., and Vallar, G.

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Bolognini, N., Rasi, F., Coccia, M., and Ladavas, E. (2005).

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Page 33 of 33
Neuropsychological assessment of memory disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Neuropsychological assessment of
memory disorders
Veronica Bradley
Narinder Kapur
DOI:10.1093/acprof:oso/9780199234110.003.009

Memory difficulties are often the first and the most prominent
sign of insidious or acute cerebral dysfunction, and may also
represent the most common, or most notable, disability that
remains after initial recovery from brain pathology. Most
neuropsychological assessments will include tests of memory,
and the clinician will select tests that will enable him/her to
answer questions that differ according to the context of the
referral. This chapter discusses the theoretical background
and terminology of memory, the assessment of memory,
questionnaires and rating scales, and memory tests.
Keywords: memory assessment, neuropsychological testing, memory

dysfunction, cerebral dysfunction, tests of memory
Page 1 of 46
1 Introduction
Memory difficulties are often the first and the most prominent
sign of insidious or acute cerebral dysfunction, and may also
represent the most common, or most notable, disability that
remains after initial recovery from brain pathology. This is
because of the wide range of brain regions that are usually
involved in performing a memory task, even one that appears
quite simple in its demands; at least one component of
memory processing - encoding, storage or utilisation
(retrieval, recognition, etc.) is likely to be affected. It follows
that most neuropsychological assessments will include tests of
memory, and the clinician will select tests that will enable him/
her to answer questions that differ according to the context of
the referral. When the main purpose of the assessment is
diagnostic, consideration of the pattern of performance on
memory tests and the severity of the memory deficit relative to
deficits in other areas of cognitive functioning will enable an
opinion to be given about the most likely cause of the
impairment. For example, memory loss is the hallmark of the
majority of presentations of Alzheimer’s disease. In the early
and middle stages of the illness the memory impairment will
be marked in relation to other cognitive deficits, while in the
cortico-subcortical dementias (which may accompany, for
example, Parkinson’s disease, Huntington’s disease, and
progressive supranuclear palsy) memory impairment may be
more subtle and accompanied by characteristic executive
deficits and slowing of response. Other questions that should
be addressed in the diagnostic assessment are the following:
◆ To what extent can the patient continue with his/her

normal activities?
◆ What coping strategies can be recommended on the basis

of the strengths and weaknesses identified in the
assessment?
The information obtained from the assessment may inform the

decision to treat. For example, in normal pressure
hydrocephalus, the extent to which cognitive impairment
affects quality of life will be taken into account when the
neurosurgeon discusses with the patient the benefits and risks
of insertion of a shunt. Additionally, the presence of a co-
occurring disorder will affect the risk-benefit ratio. A certain
amount of information on prognosis can be given on the basis
of a single assessment, but repeated assessment will provide
Page 2 of 46
additional information. Repeat assessment is essential when

the requirement is to monitor the recovery or decline of
memory function which occurs naturally or following medical/
surgical intervention.
(p.160) When the assessment is carried out for the purposes

of rehabilitation the assessment results will help to identify
areas of weakness that may be targeted in the rehabilitation
programme, as well as preserved abilities that may help the
patient to compensate for deficits. More generally, information
about the patient’s capacity to learn will always be helpful in
determining the most fruitful approach to rehabilitation. For
example, if there is relative preservation of learning, repeated
instruction or repeated presentation of material may pay off. If
there is little capacity to benefit from repeated presentation of
material then external cues may need to be provided.
The effects of memory disorders on everyday life vary with the

severity and nature of the disorder, from mild deficits that can
be effectively managed with the help of memory aids (such as
a diary or a notebook) to severe difficulties that render
independent living impossible. It should, however, be borne in
mind that even mild impairments can be quite disruptive for
people whose jobs or personal circumstances require highly
efficient memory processing. Kapur and Moakes (1995)
describe the devastating effects of post-encephalitic amnesia
on a young woman’s everyday life. She regained some degree
of quality of life, but a return to her job as a teacher was not
possible. Household chores could be completed, but only by
following a strict routine. Even the preparation of a shopping
list was a problem because, as the authors point out, knowing
that a particular item is needed requires memory. Different
types of memory impairment can give rise to more
circumscribed (and more easily managed) difficulties, such as
inability to do mental arithmetic resulting from working
memory deficit (Campbell and Conway 1995).
2 Memory: theoretical background and terminology
Page 3 of 46
There is now a considerable body of research indicating that

human memory is a multi-component system. Theories about
different components of the system abound. For clinical
purposes, a model developed from studies of dysfunctional
memory resulting from neurological illness or insult is
appropriate. Such a model also underpins a good deal of
experimental work, including investigations of neurologically
unimpaired subjects. Some components of the memory system,
such as perceptual representation memory, which briefly
records a visual or auditory image of a stimulus (termed iconic
and echoic memory, respectively), have been investigated
quite extensively in experimental studies, but are not readily
testable in the clinical setting and will not be discussed here.
In recent years, experimental studies using techniques such a
positron emission tomography (PET) scanning and functional
magnetic resonance imaging (fMRI) have enhanced our
understanding of brain activity during both clinical and
experimental tests. These developments have not yet
fundamentally changed approaches to the assessment of
memory disorders in the clinic, though they may do so in the
future (Bigler 2001).
2.1 Terminology (Fig. 9.1)

2.1.1 Short- and long-term memory
A pervasive distinction in clinical and experimental studies of
human memory is that between short- and long-term memory,
though aspects of this distinction have been (p.161)
Fig. 9.1 Memory systems & associated

components.
Page 4 of 46
called into question (Ranganath and Blumenfeld, 2005). Short-term

memory has typically been used to refer to a system that stores a
limited amount of information for a short period of time.
Neuropsychologists should be aware that the medical profession,
and indeed the general public, may have a rather different
understanding of the term ‘short-term memory’. They use it to refer
to everyday episodic memory settings, covering events over a few
hours, days or weeks, often using it as synonymous with the term
‘recent memory’. They contrast this with memory for events that
have occurred many years before, which in clinical settings is
termed long-term memory or ‘remote memory’. Most clinical and
cognitive psychologists use the term ‘short-term memory’ or, more
commonly, working memory, to refer to a set of processes for
holding and manipulating in temporary store, over a period of
seconds, information that has just been acquired.
2.1.2 Implicit versus explicit memory
Two further broad distinctions, based on testing methodology,
have been made in memory research. One distinguishes
implicit from explicit memory. The terms do not describe
memory systems as such, and are generally used to refer to
varying states of awareness of the individual with respect to
stored memories.
◆ Implicit memory is memory that is expressed through

behavioural or physiological changes, where the individual
has absent or limited conscious awareness of the
information that has been stored. It usually includes tasks
such as priming, conditioning, and skill learning. An
important set of observations that gave rise to the concept
of implicit memory indicates that amnesic patients who
present with profound explicit memory impairment may be
able to implicitly retain new information, or learn new
skills. An example is the ability to learn to perform a pursuit
rotor task where a moving target is tracked by a probe.
Implicit memory has been extensively investigated
experimentally. It is not routinely assessed in the clinical
setting, partly because of the absence of standardised tests,
but spared or impaired functioning may be detectable in the
pattern of performance on certain tests, such as enhanced
naming of pictures on repeat testing. Standardised tests of
implicit memory have been considered but are not currently
available (see Section 5.3).
Page 5 of 46
◆ The term explicit memory usually refers to memory that is

consciously accessed, and covers most standard memory
tasks.
(p.162) 2.1.3 Semantic and episodic memory

A further broad-ranging distinction is between semantic and
episodic memory.
◆ The term semantic memory refers to an organized body of

knowledge about words and concepts, and culturally and
educationally acquired facts. It includes general knowledge,
and covers a wide range of materials and modalities –
familiar faces, language, and knowledge of the world.
◆ The term episodic memory generally refers to the

encoding, storage, and utilization of memory for personally
experienced events that can be related to specific spatial
and temporal contexts.
2.1.4 Recent and remote memory

As indicated earlier, clinicians, particularly those working in
medical settings, often distinguish between recent and remote
memory.
◆ Recent memories are those stored within the last few

hours, days or weeks, or even months.
◆ Remote memories date from childhood and early

adulthood.
There is no clear cut-off point between the two, but the

distinction is an important one in clinical neuropsychology, in
that many patients with early-stage dementia will describe
problems with recent memory in the context of preserved
remote memory.
2.1.5 Anterograde and retrograde memory loss

Particularly relevant in clinical settings is the distinction
between anterograde andretrograde memory loss.
◆ Anterograde amnesia is characterized by difficulty in

acquiring new material and remembering events from the
point at which neurological illness or traumatic injury to the
brain occurred. Memory for events prior to the illness or
injury may be unaffected, even when the anterograde
amnesia is severe.
Page 6 of 46
◆ The term retrograde amnesia is used when memory for

events preceding the onset of brain damage is affected. The
retrograde amnesia may cover a relatively short period (e.g.
a few minutes or hours preceding a head injury) or can
extend over decades. Conditions in which extensive
retrograde memory loss can occur include Korsakoff
syndrome, herpes simplex encephalitis, and late-stage
dementia of the Alzheimer type.
2.1.6 Prospective memory

Prospective memory requires interaction between episodic
memory and executive functions to enable an individual to
remember to do something at a particular time in the future,
or in relation to the occurrence of a particular event or activity
in the future.
2.1.7 Material specificity

Another important concept is that of material specificity.
Memory for nonverbal and verbal material may be
differentially affected by neurological illness or injury. In
general, verbal information is dealt with by the left cerebral
hemisphere, and nonverbal information by (p.163) the right,
although it has been generally accepted that encoding and
retrieval processes are not lateralised in this way. This position
regarding encoding and retrieval processes has, however,
been challenged, with a suggestion that encoding/retrieval
differences may be as hemisphere-specific as other memory
processes (Kennepohl et al. 2007).
2.1.8 Recall and recognition

Different techniques for the assessment of memory are
available and some patients may be shown to be more or less
impaired according to the type of test used. There is an
important distinction to be made between recall and
recognition.
◆ Recall is uncued retrieval and involves an active search

process.
◆ In tests based on a recognition paradigm there is thought

to be a familiarity and a recall component, since the
individual selects from a number of stimuli that include the
target (forced-choice) or states whether or not the stimulus
presented is familiar (free-choice). Although tests
developed for clinical use do not generally measure the
extent to which explicit recollective processes are
Page 7 of 46
operating, relevant information can be obtained

experimentally through the use of remember-know
paradigms and through confidence judgements.
Recognition is almost always easier than recall, for the

neurologically unimpaired as well as the neurologically
impaired, and test norms reflect this. In some cases, e.g.
certain cortico-subcortical or frontal presentations,
recognition memory may be spared relative to recall, with
discrepancies evident on standardized tests. Such differences
in performance can be important diagnostic indicators.
Learning can occur after a single presentation, but the term is

usually used in clinical neuropsychology to refer to tests in
which there is repeated presentation and recall of material.
Recall or recognition is typically tested after a period of

roughly 30 minutes (occasionally less) when a delayed trial is
included. There are situations in which it would be helpful to
assess long-term anterograde forgetting. In particular, some
patients with a variety of temporal lobe epilepsy – transient
epileptic amnesia (Butler et al. 2007) - sometimes report
‘fading’ memory of an event, such as a holiday or social
occasion, which a relative or friend has said that they initially
remembered quite well. Unfortunately, we do not have well-
established norms for retrieval trials over weeks or months.
Existing test materials may be used in this way, but
interpretation will need to be carried out in the context of
experimental studies (e.g. Blake et al. 2000) or locally-derived
norms.
3 Assessment of memory: the clinical interview

In some types of referral, especially those with a diagnostic
component and where the patient may have limited insight
and/or memory for his difficulties, the presence of a relative/
close friend/carer will be valuable. Two main sets of
information should be sought:
◆ the memory symptoms which the patient or informant

offers spontaneously;
◆ an indication of the patient’s memory functioning gained

from general questioning about recent autobiographical
and public events, or recent factual knowledge such as
names of grandchildren, personalities in the news, etc.
Page 8 of 46
(p.164) Once an account of symptoms has been given,

specific probes may be made for symptoms such as the
following:
◆ forgetting a telephone message;
◆ a high frequency of repetitive behaviour (repetitive

questioning or repeating information in conversation) that
cannot be explained by anxiety;
◆ losing track of conversation;
◆ forgetting to keep appointments;
◆ forgetting what has been read, or events in TV films/ soap

operas;
◆ inability to navigate in familiar places.
The patient may be asked questions relating to his/her medical

history (when she/he last saw the doctor, medication
prescribed, and, if an inpatient, when she/he was admitted and
what investigations have been carried out). Word-finding
difficulties that could come under the rubric of semantic
memory should also be probed. In the case of public events, it
may be worth sampling both memory for famous personalities
and memory for discrete events. This can be done by asking
about a famous personality who has recently died and
indirectly probing whether the patient knows that the
personality is dead and how she/he died. In the case of a news
event, it may be useful to start with a cue word to see if the
patient can provide a news event relating to that word, and
then probe for more specific information. Very accurate or
very inaccurate responses to questions such as these may give
a rough guide as to the direction in which more detailed
memory assessment should proceed, although in some cases
the responses may be equivocal, e.g. if there is patchy
knowledge of recent news events in a patient who has little
interest in the news and limited exposure to the news media.
To obtain maximal information, this part of the clinical
interview and its interpretation should be tailored to the
individual patient.
The context in which the memory impairment is occurring is

always relevant, and particularly so when assessment is
carried out for diagnostic purposes. Marked variability in
cognitive symptoms (eg. present in work but not in domestic
settings), may point to psychological factors being important.
Page 9 of 46
Note whether the patient presents as alert or lethargic and

whether there is evidence of affective disorder or test anxiety.
Is the patient willing to persevere with difficult tasks or does
she/he respond with frequent ‘Don’t know’ or ‘Can’t
remember’ responses? The following questions should elicit
useful diagnostic information:
◆ How severe is the memory impairment? To what extent

has it necessitated a change in the patient’s daily routine
and ability to take part in activities that were once
performed with ease?
◆ Has it affected ability to work or to engage in pastimes?
◆ Was the onset of the memory impairment sudden or

gradual?
◆ Is the memory impairment consistently present or does it

occur only on certain occasions?
◆ Is the memory impairment constant or are there

fluctuations in severity?
(p.165)
◆ Has it been remarked upon by other members of the
family?
(The clinician may wish to obtain details in a separate
interview.)
◆ Has it progressed over time?
◆ Is the memory impairment occurring in isolation, or is the

patient aware of impairment of other cognitive functions?
(Note that many impairments such as dyspraxia or
dyscalculia may be experienced by the patient as memory
problems –‘I can’t remember how to write letters of the
alphabet’; I can’t remember how to add up.’)
◆ Are there accompanying physical or mental symptoms

(e.g. headache, movement disorder, hallucinations)?
◆ Does sleep disturbance result in tiredness and poor

concentration the following day?
◆ What is the patient’s alcohol consumption? Does she/he

take prescribed drugs or use recreational drugs? Has she/
he been exposed to toxic chemicals?
Page 10 of 46
Following assessment, the issue of consistency, both in terms

of performance on different tests and the extent to which test
performance is compatible with reported disruption to daily
life, should be considered.
4 Questionnaires and rating scales

With a thorough clinical interview there is seldom a need to
use formal questionnaires or rating scales. However, there
may be occasions on which these may prove useful. For
example, when assessment is carried out in a forensic and/or
medico-legal setting, a normed questionnaire or rating scale
may be considered more objective than interview data alone.
◆ The Neurobehavioral Functioning Inventory, devised by

Kreutzer et al. (1999), includes a number of items relating
to memory and has the advantage of there being two
versions of the form, one for the patient and one for the
family to complete. Responses to the items that make up
the various scales, which include a Memory /Attention
Scale, are summed and can be converted into standardized
scores. The standardization sample is composed of pairs of
patients and informants, the patients having sustained
traumatic brain injury.
◆ The Cognitive Symptoms Checklists, developed by O’Hara

et al. (1993), include a Memory Checklist, with questions
divided according to different potential areas of difficulty,
such as ‘safety’, ‘money management’, and ‘time’. The
completed checklist forms the basis for an in-depth clinical
interview and has been designed with the setting of
rehabilitation goals in mind.
◆ The Cognitive Behaviour Rating Scales (Williams 1987)

are designed for completion by a relative or carer, and
include a Memory Disorder Scale. This scale may be helpful
in evaluating the cognitive sequelae of dementia.
◆ The AD8 Scale (Galvin et al. 2006, 2007a, 2007b)

comprises a series of eight questions, which ask about
problems in judgment, lack of interest in hobbies,
repetitious speech, difficulties learning how to use a
gadget, forgetting the month or year, difficulty handling
complex financial matters, failure to keep appointments and
daily frequency of (p.166) memory/thinking difficulties.
Galvin et al. (2007b) have suggested that in some
Page 11 of 46
situations, e.g. when given to an informant and combined

with delayed word-list recall, this scale may be sensitive to
subtle changes in the early stages of Alzheimer’s disease.
In some cases, memory assessment procedures may have to be

improvised. For example, in monitoring the effects of memory
aids on everyday memory functioning, the clinician may wish
to have a carer keep a daily diary of specific everyday memory
lapses recorded before and after the therapeutic intervention.
5 Memory tests
5.1 Test selection
Issues of validity and reliability apply to the selection of all
neuropsychological tests and will not be discussed here. The
issue of ecological validity is also widely applicable, but can be
particularly relevant to memory assessment, as everyday
situations in which memory comes into play can be very hard
to simulate. The question of ecological validity is especially
important when critical decisions, e.g. about the patient’s
capacity to return to work or to live independently, are under
consideration. A good understanding of the demands that will
be made on the patient in a given setting and an awareness of
the way in which the clinic differs from real-life settings are
important. For example, during assessment the patient will be
in a one-to-one situation that is deliberately kept as free from
distraction as possible. This should give rise to optimal
performance on formal tests but may be very different from a
real-life situation in which there is extraneous noise and other
competing demands on attention. Memory may need to be
assessed sequentially to monitor recovery or rate of
progression in degenerative illness. In this case, the existence
of parallel forms of tests is invaluable. Finally, the severity of
memory impairment may vary from mild forgetfulness to
profound amnesia. Care must be taken to avoid floor and
ceiling effects, which can occur if tests that are, respectively,
too difficult or too easy for the patient are used.
Reference is made to specific tests in the sections that follow.

The intention is not to supply an exhaustive list of tests
suitable for assessing different aspects of memory, but to give
examples. Where possible, examples are selected from tests or
test batteries that are widely used and are likely to be readily
available. In many cases, alternatives exist (for example the
Memory Module of the Neuropsychological Assessment
Battery, the Kaplan Baycrest Neurocognitive Assessment and
Page 12 of 46
the Hopkins Verbal Learning Test – Revised) that will do the

job just as well. For details of such tests the reader is referred
to test suppliers’ websites (in particular the Professional
Assessment Resources site –www.parinc.com and the Harcourt
Assessment sites –www.harcourtassessment.com and
www.harcourt-uk.com) as well as to books which review
available tests such as Lezak et al. (2004) and Strauss et al.
(2006).
5.2 Working memory/short-term memory

This is usually measured by span tasks. The Wechsler Adult
Intelligence Scale-III (WAIS-III; Wechsler 1998a) and the
Wechsler Memory Scale-III (WMS-III; Wechsler 1998b) contain
verbal digit span tasks. The WAIS-III also contains a letter-
number sequencing (p.167) which is slightly more
demanding than the ‘digits backward’ section of the digit span
task. With regard to visuospatial span, the WMS-III contains a
visual span task similar to the Corsi Block-Tapping Test,
described by Milner (1971). Fourth UK versions of both tests
are due for publication early in 2010.
Since the early 1970s, dual task paradigms have been used
widely in experimental settings. Only a few tasks requiring
dual tasking are available clinically. These are discussed in
Chapter 5, of this volume.
5.3 Implicit memory

As noted earlier, this aspect of memory has traditionally been
tested in the context of experimental studies rather than in
clinical settings. Barbara Wilson and colleagues have taken
steps towards the development of a formal test of implicit
memory containing fractionated pictures and a stem
completion task; the test (which was to have been
standardised alongside the RBMT-III) is not currently under
active development but may be published at a future date.
5.4 Semantic memory

◆ General knowledge is readily assessable using the
‘Information’subtest of the WAIS-III. It is advisable to have
details of the patient’s educational history when
interpreting test results as this test is education-related.
◆ Knowledge of word meanings can be assessed using the

‘Vocabulary’ and ‘Similarities’ subtests of the WAIS-III.
Page 13 of 46
◆ Verbal semantic breakdown can show up on tests of

confrontation object naming, such as the Graded Naming
Test (McKenna and Warrington 1983, now available from
Cambridge Cognition, address provided in Section 5.7; see
Warrington 1997 for up-dated norms and Bird and Cipolotti
2007 for confirmation of its reliability and sensitivity in
clinical populations) or the Boston Naming Test (Kaplan et
al. 2001). These picture naming tests are sensitive to
anomia (difficulty in naming), which can have a number of
underlying causes. One cause is disturbance of
comprehension – if a patient no longer has a store of
semantic information about a visually presented object, she/
he will be unlikely to be able to name it.
All of the above require a spoken response, which, in some

cases, may render them inappropriate for use with aphasic
patients.
◆ The Pyramids and Palm Trees Test (Howard and Patterson

1992), while not designed to assess semantic memory per
se, is a useful test of a patient’s ability to access detailed
semantic representations from words and pictures. It is a
matching test that does not require a spoken response. The
authors provide normative data from control groups, and a
cut-off score. Although the test has been used extensively
with clinical populations, norms from these populations are
not included in the manual, since it is the pattern of
performance, rather than the subject’s absolute score, that
is felt to be important in understanding semantic
impairment.
(p.168) Throughout the last decade, there has been

particular interest in the syndrome termed semantic dementia,
a condition in which progressive impairment of semantic
memory occurs in the absence of more widespread impairment
of cognitive function; for example there is usually relative
sparing of everyday episodic memory. Investigation of the
deficits shown by patients with this disorder has enhanced our
understanding of the semantic system (Hodges et al. 1992;
Garrard and Hodges 2000). The tests described so far are
(inter alia) routinely used in the neuropsychological diagnosis
of semantic dementia, whether for clinical or research
purposes. Two additional tests are described below:
Page 14 of 46
◆ The Speed and Capacity of Language Processing (SCOLP)

Test (Baddeley et al. 1992) is designed to provide a holistic
measure of the efficiency of language comprehension. It
includes the ‘Speed of Comprehension Test’, which is based
on Collins and Quillian’s (1969) ‘Silly Sentences’. Simple
statements about the world must be judged to be true or
false.
◆ The Autobiographical Memory Interview (AMI) (Kopelman

et al. 1990), as its title suggests, takes the form of a
structured interview. It encompasses two components. The
first is what the authors call ‘personal semantic’. It assesses
the patients’ recall of facts about their earlier life. These
facts, such as the pre-school address and the names of
primary and secondary schools attended, are likely to have
been acquired without conscious recollection of their
acquisition – hence the inclusion of this part of the
instrument in this section. The second component, relating
to memory for personally experienced events, is discussed
in Section 5.4.1.
5.5 Episodic memory
By far the greatest number of memory tests routinely used in
the practice of clinical neuropsychology are tests of episodic
memory. The majority are tests of recent memory. They
require the patient to memorize information and retrieve it
immediately after presentation or within half an hour or so. It
is more difficult formally to test remote memory in the clinical
setting but an instrument has been devised and will be
discussed before looking at the range of tests of recent
memory that are available. The examples of tests of recent
episodic memory reflect the number and range available. Tests
mentioned in Sections 5.5.2 and 5.5.3 are summarized in Table
9.1.
5.5.1 Remote episodic memory

The second component of the AMI (see Section 5.3) assesses
the patients’ recall of specific events in childhood and early
adulthood, as well as memory for more recent personal events.
A potential problem for a test of this type is the absence of any
way of checking the accuracy of the patient’s recall. Even if a
relative or carer is present, she/he may not recall or be aware
of certain incidents and events that have occurred in the
patient’s life. As part of their validation procedure the authors
checked the accuracy of recall with relatives of patients in
Page 15 of 46
their validation sample. Although they concluded that the

tendency was for patients’ responses to be accurate on about
90% of occasions, the normative (p.169)
Page 16 of 46
Table 9.1 Tests of episodic memory
Test* Measur Age No. of Ceiling Suitable Response Ecologi

e Range parallel Effects for use required cal
(years) forms possible in validity
severe a
deficit feature
Recogni Recall Learnin Delayed recall Prospec Spoken Comple

tion g tive x motor
memory
Short Long†
AMIPB + + 18–75 2 +
Design
Learnin
g
AMIPB + + 18–75 2 +
Figure
Recall
AMIPB + + 18–75 2 +
List
Learnin
g
AMIPB + + 18–75 2 +
Story
Recall
Page 17 of 46
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severe a
deficit feature

tion g tive x motor
memory
Short Long†
BMIPB + + 16–89 4 +
Design
Learnin
g
BMIPB + + 16–89 4 +
Figure
Recall
BMIPB + + 16–89 4 +
List
Learnin
g
BMIPB + + 16–89 4 +
Story
Recall
Page 18 of 46

severe a
deficit feature

tion g tive x motor
memory
Short Long†
Californ + + + + 16–89 2 +
ia
Verbal
Learnin
g Test
Camden + 18–85 + +
Face
Recogni
tion
Camden + 18–85 + + +
Paired
Associat
e
Learnin
g
Page 19 of 46

severe a
deficit feature

tion g tive x motor
memory
Short Long†
Camden + 18–85 + +
Pictoria
l
Recogni
tion
Camden + 18–85 + +
Topogra
phical
Recogni
tion
Camden + 18–85 + +
Word
Recogni
tion
Page 20 of 46

severe a
deficit feature

tion g tive x motor
memory
Short Long†
Doors + + + 5–97z + +
and
People
Verbal
Recall
Doors + 5–97z +
and
People
Verbal
Recogni
tion
Doors + + + 5–97z + +
and
People
Visual
Recall
Page 21 of 46

severe a
deficit feature

tion g tive x motor
memory
Short Long†
Doors + 5–97z +
and
People
Visual
Recogni
tion
Rey + + 13–97‡ 3§ +
Auditor ,§
y Verbal
Learnin
g Test
Rey– +x + + 6–89‡ ,§ 2§ +
Osterrei
th
Comple
x
Page 22 of 46

severe a
deficit feature

tion g tive x motor
memory
Short Long†
Figure
RBMT + 16–96y 4 + + +¶ +
Appoint
ment
RBMT-E + 16–76y 2 +¶ +
Appoint
ment
RBMT- + 16–96y 2 + +¶ +
III
Appoint
ment
RBMT + 16–96y 4 + + +¶ +
Belongi
ng
Page 23 of 46

severe a
deficit feature

tion g tive x motor
memory
Short Long†
RBMT-E + 16–76 y 2 +¶ +
Belongi
ng
RBMT- + 16–96 y 2 + +¶ +
III
Belongi
ng
RBMT + + 16–96 y 4 + + +
Faces
RBMT-E + + 16–76 y 2 +
Faces
RBMT- 16–96 y 2 + +
III
Faces
Page 24 of 46

severe a
deficit feature

tion g tive x motor
memory
Short Long†
RBMT + + 16–96 y 4 + + +
Messag
e
RBMT-E + + 16–76 y 2 +
Messag
e
RBMT- 16–96 y 2 + +
III
Messag
e
RBMT + 16–96 y 4 + + + +
Name
RBMT-E + 16–76 y 2 + +
Name
Page 25 of 46

severe a
deficit feature

tion g tive x motor
memory
Short Long†
RBMT- 16–96 y 2 + + +
III
Names
RBMT + 16–96 y 4 + + +
Pictures
RBMT-E + 16–76 y 2 +
Pictures
RBMT- 16–96 y 2 + +
III
Pictures
RBMT + + 16–96 y 4 + + +
Route
RBMT-E + + 16–76 y 2 +
Route
Page 26 of 46

severe a
deficit feature

tion g tive x motor
memory
Short Long†
RBMT- 16–96 y 2 + +
III
Route
RBMT + + 16–96 y 4 + + + +
Story
RBMT-E + + 16–76 y 2 + +
Story
RBMT- 16–96 y 2 + + +
III Story
Warring + 18–70
ton
RMT
Faces
Warring + 18–70 +
ton
Page 27 of 46

severe a
deficit feature

tion g tive x motor
memory
Short Long†
RMT
Words
WMS- + +
III**
Face
Recogni
tion
WMS- + + 16–89 +
III**
Family
Pictures
WMS- + + + + 16–89 +
III**
List
Learnin
g
Page 28 of 46

severe a
deficit feature

tion g tive x motor
memory
Short Long†
WMS- + + +II + 16–89 +

III**
Logical
Memory
WMS- + + + 16–89 +
III**
Paired
Associat
e
Learnin
g
WMS- + + + 16–89 +
III**
Visual
Reprod
uction
Page 29 of 46
* AMIPB, Adult Memory and Information Processing Battery; BMIPB, BIRT Memory and Information Processing Battery; RBMT,
Rivermead Behavioural Memory Test (-E, extended version; -III, current revision); WMS, Wechsler Memory Scale.
(†) In most cases this is a 30-minute delay; the BMIPB delay is 40-minutes
(‡) When normative studies are combined; individual studies have narrower ranges.
(§) Readily available. Additional parallel forms and normative studies are in existence.
(¶) Only a minimal spoken response required; could be used with aphasic patients.
(II) One passage is presented twice and a learning slope calculation can be made.
(x) In the Meyers and Meyers (1995) version only.
(y) Excluding modified children’s versions.
(z) The new manual gives adult and child norms.
(**) The WMS-IV UK is due for publication early in 2010
Page 30 of 46
(p.170) (p.171) (p.172) (p.173) (p.174) sample was

relatively small and, in clinical settings, a degree of caution should
be exercised in interpreting patients’ responses. Responses that
are not obviously confabulatory (confabulatory responses may be
bizarre and illogical or may not be consistent with other
information which the patient has given) are scored as correct and,
in theory, therefore, the instrument can be used with patients who
are not accompanied by a relative or carer. However, the question
of reliability of answers needs to be kept in mind, as well as the
possibility that some autobiographical memories may be intact but
are not tapped by the particular episodic memory items in the test.
5.5.2 Batteries and sets of tests assessing recent episodic memory
It is almost always necessary to administer a range of memory
tests in order to obtain meaningful information about the
status of a patient’s memory functioning. When the purpose of
assessment is to obtain a diagnostic profile, different tests are
included to establish whether impairment is generalized or
whether there are discrete areas of impairment, occurring in
the context of preserved function in other areas.
A number of batteries that sample a range of abilities using

different techniques are available. When there is a need to
compare performance on different tests (e.g. those using
nonverbal and verbal stimuli, it is worth selecting tests from
the same set or battery where possible, since they will have
been normed on the same population).
The Wechsler Memory Scales
The Wechsler Memory Scales (WMS) are probably the best-

known and most widely used batteries. They have expanded in
scope since the original scale was published in 1945. Revisions
in 1987 and 1998 brought the tests up to date. The fourth UK
version is due for publication early in 2010. The WMS-III
(Wechsler 1998b) is described here. It contains six primary
subtests, used in calculating ‘Index Scores’ that are directly
comparable with WAIS-III IQs.
◆ Two of these, a verbal digit span task and a visual span

task, are tests of working memory and have been discussed
in Section 5.2.
◆ The Logical Memory test comprises two short stories that

are read to the patient. Free recall is required immediately
after presentation and after a half-hour delay. It is also
possible to examine recognition memory for the story.
Page 31 of 46
◆ The other primary test of verbal memory is a paired

associate learning task, in which the patient is required to
learn novel word associations over a number of trials and to
respond with the second word of a pair when presented
with the first.
◆ On the nonverbal side, a series of 24 photographs of faces

is presented. Memory for these faces is tested through
recognition immediately and after a thirty minute delay –
the patient is asked to pick out the target photographs from
a set that includes distractors.
◆ In the Family Pictures subtest, a family photograph and a

series of scenes are presented. The patient is asked to
recall who is in each scene, what they are doing, and where
in the picture they are. This new addition to the battery was
designed as a nonverbal analogue to the Logical Memory
test, but it is not clear that it is entirely (p.175) a test of
nonverbal memory as a certain amount of verbal encoding
could improve performance.
All of these tests require immediate and delayed recall.

Although a half-hour delay is not particularly significant in
terms of models of memory – both immediate and delayed
trials test recent episodic memory – the inclusion of delayed
recall trials is clinically significant. Performance in conditions
such as Alzheimer’s disease, in which material is lost over a
delay, contrasts with performance in (e.g. the subcortical
dementias or in anxiety states), in which there may be
problems at the encoding stage, while material that is
successfully encoded may be retained reasonably well over a
delay.
Optional subtests in the WMS-III include
◆ a verbal learning task, in which the patient is asked to

recall the contents of a 12-word list presented on four
consecutive trials plus delayed recall and recognition trials;
◆ a nonverbal memory task, in which the patient is required

to draw from memory a series of five designs, with delayed
recall and recognition memory also assessed.
The battery is psychometrically quite complex, and a number

of composite scores can be calculated in addition to the Index
Scores. Administration of the entire battery to neurologically
impaired patients is usually too demanding, but one advantage
Page 32 of 46
that this latest revision has over earlier versions is that norms
for individual tests are available, so that the clinician can
select appropriate tests from the battery when time
constraints or lack of stamina on the patient’s part preclude
administration of the entire battery.
One disadvantage that the current revision does have is the

absence of a parallel form, which was available for the first
WMS. This means that interpretation of the results of repeated
presentation within six months (or longer in some cases in
which memory is reasonably well-preserved) is complicated by
the possibility of practice effects.
The Rivermead Behavioural Memory Test (RBMT)
The RBMT (Wilson et al. 1985) was devised specifically to meet

the objection that many memory tests used in the clinical
setting are adapted from laboratory-based tests and lack
ecological validity. The test has been revised twice and an
extended form produced (RBMT-E; Wilson et al. 1999). The
most recent version (RBMT-III; Wilson et al. 2008) supersedes
previous versions. It uses more up-to-date material, is
designed to assess a wider range of abilities and provides
revised normative data.
In addition to story recall, recall of names, and picture and

face recognition tests, the RBMT-III also contains a number of
subtests that are rather different from those contained in most
other batteries, and that are felt to be closer to the everyday
situations in which a patient might experience memory
difficulties. One example is a subtest in which the patient is
required to remember and follow a short route within the
testing room. A number of tests of prospective memory are
included (these are discussed in Section 5.6) and a test of the
ability to learn a new skill has been added.
The original RBMT had four parallel versions to allow for

repeated assessments; the RBMT-E and RBMT-III have two.
The RBMT (its first revision), and the RBMT-E yield two
scores; a screening score based on a pass/fail grading of each
item, and a more detailed (p.176) profile score. The scoring
system for the RBMT-III is still under development. There is a
children’s version (RBMT-C; Wilson et al. 1991) which provides
norms for children aged 5 years to 10 years 11 months.
Page 33 of 46
The BIRT Memory and Information Processing Battery

(BMIPB).
The BMIPB (Coughlan et al. 2007; available from Dr M. Oddy,

Kerwin Court, Five Oaks Rd, Slindon, Horsham, West Sussex
RH13 0TP) has been developed under the auspices of the
Brain Injury Rehabilitation Trust. It is modelled on the AMIPB
(Adult Memory and Information Processing Battery: Coughlan
and Hollows, 1985) but includes new features and is based on
more extensive and up-to-date normative data. The battery
uses entirely new material but the memory tests (story recall,
word-list learning, figure recall and design learning) are
similar to those in the AMIPB. There are some changes to the
way in which tests are administered (for example, the interval
between delayed and immediate recall of the story and figure
has been extended from thirty to forty minutes) and there are
useful additions in the form of recognition trials for the
learning tasks.
The design learning test is felt to be a particularly good

measure of nonverbal memory since it is very difficult to
encode any part of the design verbally. Both learning tests, as
previously, include a delayed recall trial following interference
before administration of the newly-developed recognition
trials. Norms are provided for each individual test. There is no
overall memory quotient or composite score but this is in no
way a disadvantage in clinical neuropsychological settings,
where the focus is on relative strengths and weaknesses. The
BMIPB has the advantage of four parallel forms and the test
authors have given considerable thought to the issue of
practice effects; the manual contains an extremely useful
section on the subject and an accompanying CD enables the
user to obtain, as a supplement to the percentile tables in the
manual, continuous regression-based norms for each
individual tested.
The Doors and People Battery.
The Doors and People Battery (Baddeley et al. 1994) was

designed principally to provide an improved measure of
nonverbal episodic memory that would be acceptable to a wide
range of subjects. It includes verbal recall and recognition
tasks as well as nonverbal recall and recognition tests. Tests
are relatively short and the battery is easy to administer.
Norms are available for individual tests and an overall score.
Page 34 of 46
Scaled scores are also provided for nonverbal - verbal

discrepancies and recall – recognition discrepancies.
There is now a children’s version (Doors and People for

Children; Baddeley et al. 2006). Changes to the adult test are
minimal and the authors state that the adult test in its current
form can be used with the child norms. The new manual
provides both adult and child norms.
The Recognition Memory Test (RMT).
This battery (Warrington 1984) contains only two subtests. The

verbal test uses visually presented words and the nonverbal
test uses faces. Both are forced-choice recognition memory
tests. A discrepancy score can be calculated to assist the
evaluation of differences between scores on the tests. Each
test contains 50 items and, although they are easy to
administer and usually quite pleasant from the patient’s point
of view, they are less suitable than some of the shorter tests
for (p.177) patients who have severe impairments of memory
or problems with maintaining attention. However, there is the
possibility of ceiling effects when the verbal test is used with
very mildly impaired patients. As stimuli are visually
presented, with a recognition testing format, it is an
appropriate measure of memory for patients with certain types
of language impairment. One disadvantage is the test’s rather
large intra-subject variability which makes it unsuitable for
monitoring gradual change in degenerative or recovering
conditions (Bird and Cipolotti 2007); another is the fact that
the faces stimuli in the nonverbal test are somewhat dated.
The Camden Memory Tests.
This set (Warrington 1996) contains five tests – two verbal and
three nonverbal – that are intended to be presented
individually and not as a battery. They are all presented
visually. Four are forced-choice recognition tests and do not
require a spoken response. The fifth is a paired-associate
learning test that requires a single-word spoken response.
These tests are shorter than the subtests of the Recognition
Memory Test and include word and face recognition memory
tests with similar formats. The least demanding is the
‘Pictorial Recognition Memory Test’ in which stimuli are
photographs of London scenes. Selection of the target is made
from unrelated distractors. This test is subject to ceiling
effects when used with patients with mild or even moderate
Page 35 of 46
problems, but it is extremely useful for patients who have

severe memory impairments or limited stamina in the early
days following neurological insult. In relation to the latter
group, all of the tests are easy to administer at the bedside. It
may also be helpful in detecting memory loss due to reduced
effort or motivational factors.
5.5.3 Individual tests assessing recent episodic memory

The Rey Auditory Verbal Learning Test (RAVLT).
The RAVLT (Rey 1964) requires recall of an auditorily

presented 15-word list over five learning trials. Delayed recall
tests, following an interference trial, and a recognition test are
provided. A number of parallel forms have been developed
since the initial publication of the test. A selection of these can
be found in Lezak (2004). Normative data are provided by
Strauss et al. (2006). Schmidt (2003) has collected norms,
validity studies and different administration and scoring
procedures in a handbook.
The Rey-Osterreith Complex Figure.
This test of visual recall was devised by Rey in 1941 and

standardized by Osterreith in 1944 (papers translated by
Corwin and Bylsma 1993). Taylor (1979) contributed a parallel
form and scoring criteria. Until 1995 the test was not available
from a commercial source. Information detailed enough to
permit the clinician to design his/her own stimuli and score
sheets are provided by Lezak (2004) and Strauss et al. (2006).
A version is now commercially available (Meyers and Meyers
1995). Knight and Kaplan (2004) discuss clinical and research
applications of the test (however this book is currently
unavailable from the publishers).
The California Verbal Learning Test (CVLT).
The CVLT (Delis et al. 2001) is another word-list learning task,

which differs from the RAVLT and AMIPB list learning tasks in
that stimuli are semantically related. In each list, items have
been selected from a limited number of semantic categories
and there are cued recall trials that ask for items (p.178)
within a given category. In the first edition of the test (Delis et
al. 1987), items that could make up shopping lists were used,
with the aim of increasing the test’s ecological validity. This
aspect of the test has been abandoned in the 2001 edition, in
Page 36 of 46
order to improve ease of understanding. Short- and long-delay

recall is required and there is a long-delay recognition trial.
Norms are provided for a range of measures, such as

vulnerability to interference and learning strategy. Computer-
assisted scoring is an option. A children’s version is available
(Delis et al. 1994). The first edition of the test did not have a
parallel form, but one was developed and published by Delis et
al. (1991). The second edition has one parallel form, and this
edition also includes a short form that roughly halves
administration time.
Page 37 of 46
5.6 Prospective memory

A number of items tapping prospective memory are included
in the RBMT and RBMT-III (Wilson et al. 1985; Wilson et al.
2008, see Section 5.5.2). In the RBMT-III the patient must
remember to:
◆ pick up and deliver a message.
◆ ask two questions relating to the near future when an

alarm sounds.
◆ request the return of two belongings with information

about their locations at a predetermined point.
The time-span over which the patient is required to remember

varies for different items. It ranges from a few seconds for the
immediate trial of memory for a route that includes
remembering to pick up and deliver a message after a 25-
minute time delay for remembering to ask questions when a
timer rings; the request for the return of belongings must be
made at the end of the session.
A welcome addition to prospective memory testing is the

CAMPROMPT (Wilson et al. 2005). It includes six prospective
memory tasks, three cued by time and three by events, to be
carried out within a 25-minute period. The authors have
devised tasks that are analogous to everyday tasks and
patients are permitted to use their own strategies (such as
making written notes) as memory aids. (An interesting finding
in the standardisation studies is the importance of written
notes; the test scores of patients who made full notes did not
differ significantly from those of controls who made full notes,
while patients who made no or partial notes differed
significantly from controls.) A parallel form is provided. A note
of caution in relation to this test is that dissociations between
perceived/reported prospective memory dysfunction and
objectively-measured prospective memory impairment have
been described in experimental studies (e.g. Woods et al.
2007) although studies in which this dissociation has been
reported have not used the CAMPROMPT. The CAMPROMPT
manual reports correlations with some RBMT scores and other
cognitive measures (but the issue of correlation with perceived
prospective memory status or with recorded everyday
prospective memory lapses is not addressed).
(p.179) 5.7 Computerized assessment
Page 38 of 46
Computerized batteries that include tests of memory are

available, but these tests have not been included as examples
because, in spite of considerable interest in their development
and use over the past 3 decades, none have yet come into
general use in clinical settings. As mentioned previously,
computer-assisted scoring is available for the CVLT, but this
simply facilitates response recording and data analysis, and
does not change the nature of the test in any way.
It is probable that administration of memory tests will be

computer-assisted rather than fully computerized for the
foreseeable future. An extremely sophisticated system would
be required to capture qualitative data, give encouragement
and reassurance, and deal with unexpected hitches in order to
replace the clinician. Nevertheless, this may well be a growth
area in the coming decade.
At present, the most readily available battery is probably the

CANTAB Battery (available from Cambridge Cognition,
Tunbridge Court, Tunbridge Lane, Bottisham, Cambridge
CB25 9TU; cf. Robbins and Sahakian 1994), which has been
developed and researched over many years. It has been
designed primarily with applications for therapeutic trials in
mind, but has been reported to be useful in some diagnostic
settings – some clinical norms are now available. It includes
tests of visuospatial and working memory. Like most
computerized tests, it can be an expensive option.
5.8 Symptom validity in memory assessment

There are a number of ways in which the neuropsychologist
may detect consciously or unconsciously poor motivation or
lack of effort. Certain tests can be helpful in checking the
validity of a memory complaint. A common indicator of a
motivatio-nal problem is inconsistency between the patient’s
day-to-day functioning and performance on memory tests. The
latter may show profound impairment, yet the patient is able
to answer questions about certain recent events, or to cope
independently at home.
Tests, such as Rey’s Memorization of 15 Items (Rey 1964; cf.

Lezak 2004), which are presented as demanding but are, in
fact, quite easy for the patient who is not severely impaired,
are likely to be failed by patients who are motivated to fail
rather than to succeed. The forward digit span may be
unexpectedly short and performance on forced-choice
Page 39 of 46
recognition tests, such as the RMT or Camden tests described

above, can be revealing in that such a patient may score well
below chance (cf. Halligan et al. 2003). Tests specifically
designed to detect lack of effort are available. One of the most
frequently used is the Test of Memory Malingering (Tombaugh
1996).
It is important to be aware that the assessment of motivation

is complex, and no one test score in isolation can provide an
answer to the question of whether or not the patient is
adequately motivated. Test scores should be interpreted in the
context of other information such as clinical history, symptom
profile, radiological findings and so on.
(p.180) 5.9 Normative data for older adults

A helpful development over the last few years is the extension
upwards of norms when new tests are developed or existing
tests revised. WMS III norms are now provided for adults up to
89 years. Camden norms go up to 85 years, and the Doors and
People standardization sample includes individuals up to 97
years. Testing the older adult is, in this respect, much easier
than it was a decade ago when norms were often not available
for the over-75s. Mayo’s Older Americans Norms (Ivnik et al.
1992) have now been largely superseded by revisions of the
WAIS and WMS. However, norms up to age 97 for the Rey
AVLT may still be of value. Lezak (2004), Spreen and Strauss
(1998), and Strauss et al. (2006) give additional test norms
that are updated with each revision of their books.
If appropriate age norms for a test are not provided in the test
manual or in one of these volumes, it is worth checking
journals for normative studies. The Clinical Neuropsychologist
and the Journal of Clinical and Experimental Neuropsychology
(both published by Swets and Zeitlinger) are good sources for
such material.
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Page 46 of 46
The natural recovery and treatment of learning and memory disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The natural recovery and treatment

of learning and memory disorders
Barbara A. Wilson
DOI:10.1093/acprof:oso/9780199234110.003.010

This chapter focuses on people who have memory problems
resulting from a neurological condition such as traumatic head
injury, stroke, encephalitis, and hypoxic brain damage. Topics
discussed include the meaning of recovery, factors affecting
recovery, mechanisms of recovery, how much recovery takes
place, improving natural recovery, and whether treatment is
effective in helping people with memory and learning
difficulties.
Keywords: learning disorders, memory problems, recovery, mechanisms of

recovery
Page 1 of 29
1 People with memory and learning disorders

This chapter focuses on people who have memory problems
resulting from a neurological condition such as traumatic head
injury, stroke, encephalitis, and hypoxic brain damage. It is not
concerned with those who have developmental learning
difficulties. Because learning is, to a large extent, dependent
on memory, people with memory problems have difficulty
learning new information. People with progressive
neurological conditions such as Alzheimer’s disease and
multiple sclerosis also experience memory and learning
difficulties and, although it is possible to reduce the everyday
problems faced by these people (e.g., Clare and Woods 2001,
Clare 2007), they will not be discussed here because they are
not expected to recover or improve their functioning.
The typical person with memory and learning difficulties will

have:
◆ a normal or nearly normal immediate memory when this

is measured by forward digit span;
◆ difficulty learning and retaining most new information;
◆ a period of retrograde amnesia, i.e. a memory gap for a

period preceding the insult.
Some will have normal functioning of other cognitive abilities

and are said to have a pure amnesic syndrome. The majority
will have additional cognitive deficits such as poor attention,
word-finding difficulties, impaired problem-solving, and
slowed information-processing.
Page 2 of 29
2 What do we mean by recovery?

Recovery can be understood in several different ways. Finger
and Almli (1988) see recovery as a complete regaining of the
identical functions that were lost or impaired after brain
injury. Few people with memory and learning disorders
achieve recovery in this sense. Jennett and Bond (1975) regard
recovery as resumption of normal life even though there may
be minor neurological and psychological deficits. This is
sometimes achievable for those with organic memory
problems. Marshall (1985) defines recovery as the diminution
of impairments in behavioural or physiological functions over
time. Probably most people who sustain memory and learning
deficits following non-progressive brain (p.185) injury will
show some diminution of their impairments over the first few
days, weeks, or months. Kolb (1995) suggests that recovery
typically involves partial recovery of function together with
substitution of function. Wilson (1998, p. 281) defined
recovery operationally as ‘complete or partial resolution of
deficits incurred as a result of an insult to the brain’.
The most common cause of brain damage (and memory

impairment) in people under the age of 25 years is traumatic
head injury. People incurring such injury usually undergo
some, and often considerable, recovery. This is likely to be
fairly rapid in the early weeks and months post injury, followed
by a slower recovery that can continue for many years. A
similar pattern may be seen following other kinds of non-
progressive injury such as hypoxia, encephalitis, and
cerebrovascular accident. In these latter cases, however, the
recovery process may last months rather than years.
3 Factors affecting recovery

A number of factors influence the extent of recovery, some of
which we can do nothing about once the damage has occurred.
These include the age of the person at the time of insult, the
severity of damage, the location of damage, the status of
undamaged areas of the brain, and the premorbid cognitive
status of the brain. Other factors such as motivation, emotions,
and the quality of rehabilitation available can be manipulated.
3.1 Age
Age, often thought to be an important factor, is less clear-cut
than many believe. Despite evidence to the contrary, there is a
widespread belief that children recover from an injury to the
brain better than adults. (Johnson et al 2003). This is known as
Page 3 of 29
the ‘Kennard principle’ after Kennard (1940) who showed that

young primates with lesions in the motor and premotor cortex
exhibited sparing and partial recovery of motor function. Even
Kennard, however, recognized that such sparing did not
always occur and that some problems became worse over
time. Several studies have shown that younger children fare
worse than older children (Forsyth et al. 2001, Konczak et al.
2005, Anderson et al. 2000, 2006 and Hessen et al. 2007).
These findings suggest that younger children, particularly
those below the age of two years, fare worse in the long term
than older children. Those studies suggesting the opposite
(Montour-Proulx et al. 2004) or suggest no difference (Mosch
et al. 2005) are looking at children with focal rather than
diffuse lesions.
Age, then, is just one factor in the recovery process that has to
be considered alongside other perhaps more important
factors, e.g.:
◆ whether the lesion is focal or diffuse (Levin 2003);
◆ the severity of the insult; (Catroppa and Anderson 2007);
◆ the time since acquisition of the function under

consideration (e.g. someone who has just learned to read at
the time of the insult is more likely to show reading deficits
than someone who learned to read many years before).
(p.186) 3.2 Cognitive reserve
The concept of ‘cognitive reserve’ refers to the fact that
people with more education and high intelligence may show
less impairment than those with poor education and low
intelligence. Stern (2007) suggests that individuals with high
intelligence may process tasks in a more efficient way.
Consequently, in cases of Alzheimer’s disease, task impairment
manifests itself later in the disease in people with such
cognitive reserve. He also says that most clinicians are aware
of the fact that any insult of the same severity can produce
profound damage in one patient and minimal damage in
another. This may explain differences in recovery following
non-progressive brain injury for, as Symonds (1937, p. 1092)
said in an often quoted remark, ‘It is not only the kind of head
injury that matters but the kind of head.’
Page 4 of 29
Stern (2007) argues that there is no direct relationship

between the degree of damage and the clinical manifestation
of that damage. He believes that there are two separate
models of cognitive reserve namely a passive model dependent
on brain size or neuronal count and an active model whereby
the brain uses its cognitive processing strategies or
compensatory techniques to deal with the damage.
Bigler (2007) believes that the passive model of cognitive

reserve helps to explain not only the initial recovery from TBI
but also recovery across the lifespan. Furthermore, the model
allows us to understand why there is an increased risk of
dementia in survivors of TBI. Schutz (2007) gives support to
the active model of cognitive reserve in the description of nine
highly successful survivors of severe TBI. These were far more
successful than their peers in cognitive, academic and social
achievements because they implemented procedures to
minimize the impact of their deficits.
3.3 Gender
As long ago as 1987, it was suggested that female animals may
be protected against the effects of brain injury at certain
stages of their cycle due to the effects of oestrogen and
progesterone (Attella et al. 1987). This was confirmed by Roof
and Hall 2000). Potentially important for rehabilitation (Stein
2007), progesterone has been given to survivors of TBI with
some suggestion that this leads to a better outcome (Wright et
al. 2007). In addition, studies have looked at the long term
outcome for females and males following TBI. There are
conflicting reports with Ratcliff et al. (2007) suggesting that
females do better, with Farace and Alves (2000) and Ponsford
et al (2008) finding that the outcome for women was worse.
The latter study controlled for Glasgow Coma Scale score, age
and cause of injury. They found that females had a lower rate
of survival and a lower rate of good outcome at 6 months post
injury. The authors thought this reflected the lower rate of
initial survival. They found no evidence that women did better
and some evidence that they did worse.
4 Mechanisms of recovery
Insults to the brain cause rapid cell death and a disruption of
functional circuits in the affected regions (Wieloch and
Nikolich 2006). The effects of brain injury can remain (p.187)
active for days or weeks after the primary insult (Bramlett
and Dietrich 2007), with progressive atrophy of both gray and
Page 5 of 29
white matter structures continuing up to a year post-insult.

This could explain some of the long-term consequences
observed in patients with TBI. Recovery from TBI is variable
and far from uniform (Millis et al 2001). In some individuals
recovery can continue for years (ibid).
The process of recovery is not well understood and probably

involves different biological processes (Taupin 2006).
Properties of plasticity of the central nervous system (CNS),
such as the reorganization of the pre-existing network and
axonal sprouting have all been implicated in recovery (ibid).
Changes seen in the first few minutes (e.g. after a mild head
injury) presumably reflect the resolution of temporary
dysfunction without accompanying structural damage. This is
akin to what Robertson and Murre (1999) refer to when they
say that plastic reorganization may occur because of a rapidly
occurring alteration in synaptic activity taking place over
seconds or minutes. Recovery after several days is more likely
to be due to resolution of temporary structural abnormalities
such as oedema or vascular disruption (Jennett 1990), or to
the depression of metabolic enzyme activity (Whyte 1990).
Recovery after months or years is even less well understood.

Stein and Hoffman (2003) suggest several ways in which this
might be achieved including regeneration, diaschisis, and
plasticity.
Page 6 of 29
4.1 Regeneration
Following brain damage, neurons initially begin to regrow, but
this regrowth ceases as fibrotic scarring occurs preventing
reconnection of severed neuronal pathways. Consequently,
functional recovery from such injuries is poor (Logan et al.
2007). Voss et al. (2006), however, suggested that axonal
regrowth may take place many years after severe brain injury
leading, in at least one patient, to functional speech after he
had been in a minimally conscious state for 19 years. For
regeneration to take place, it is necessary for new cells and
axons to survive, and integrate into existing neural networks
(Johansson 2007). One way this may be achieved is through
cell implantation. Ma et al. 2007 found that when injected
directly into the brain, the cerebrospinal fluid or bloodstream,
bone marrow stromal cells can promote recovery from TBI.
The authors warn that although this is a promising treatment,
there are still problems to be resolved. Indeed, Parr et al.
(2007) say that the transplantation of bone marrow cells is
unlikely to be a major factor in recovery from TBI and that
other factors such as neuroprotection and enriched
environments are likely to play a greater role. Taupin (2006)
claims that after TBI and stroke new neuronal cells are
generated at the sites of injury where they replace some of the
degenerated nerve cells. And this represents an attempt by the
CNS to regenerate itself.
There is now plenty of evidence that some regeneration of

brain cells occurs after brain damage and the view held for
many years that cerebral plasticity is severely restricted in the
adult human brain is no longer credible. Taupin (2006) says
there is a striking amount of neurological recovery in the
months and years following brain (p.188) damage despite
often permanent structural damage. What is less clear
however, is the extent to which regeneration can lead to
functional gains in coping with real-life problems.
Page 7 of 29
4.2 Diaschisis
Diaschisis is a term coined by von Monakow (1914, translated
by Pribram, 1969). It assumes that damage to a specific area
of the brain can result in neural shock or disruption elsewhere
in the brain. The secondary neural shock can be adjacent to
the site of the primary insult or much further away (Miller
1984). In either case, the shock follows a particular neural
route. Similar to this, although not identical, is Luria’s (1963)
theory of inhibition. In inhibition, however, the shock is more
diffuse and affects the brain as a whole. Robertson and Murre
(1999, p. 547) interpret diaschisis as ‘a weakening of synaptic
connections between the damaged and undamaged sites,
contingent on the reduced level of activity in the lesioned
area’. Because cells in the two areas are no longer firing
together, synaptic connectivity between them is weakened and
this results in the depression of functioning in the undamaged
but partly disconnected remote site. Reggia (2004) used a
computational model to explain diaschisis. He suggests that it
can be accounted for by a single model of hemispheric
interactions.
4.3 Plasticity
While regeneration refers to the regrowth or repair of
damaged areas of the brain, plasticity implies anatomical
reorganization based on the idea that undamaged areas of the
brain can take on the functions subserved by a damaged area.
“Cerebral plasticity is the dynamic potential of the brain to
reorganize itself during ontogeny, learning, or following
damage” (Duffau 2006, p. 885). Until recently, this idea was
discredited as an explanation for recovery in adults, although
views are now changing. Bütefisch (2004) says that the human
adult brain retains the ability to reorganize itself throughout
life. Cecatto and Chadi (2007) suggest that behavioral
experience and neuronal stimulation play a part in modifying
the functional organization of remaining cortical tissue and
leading to clinical improvements.
Robertson (2002) suggests that recovery is rapid for deficits

that are subserved by multiple circuits such as unilateral
neglect and slowest for deficits that are subserved by a more
limited number of circuits such as hemianopia because fewer
alternative pathways are available to take over the functioning
of the damaged pathways. This could be the reason why
Page 8 of 29
language functions appear to show better recovery over time

than memory functions (Kolb 1995). Robertson and Murre
(1999), in a thought-provoking paper, suggest that plastic
reorganization may occur because of:
◆ a rapidly occurring alteration in synaptic activity taking

place over seconds or minutes;
◆ structural changes taking place over days and weeks.
The authors focus in particular on people who are likely to

show recovery provided they have assistance and
rehabilitation.
(p.189) According to Robertson and Murre:
◆ there are some individuals who show autonomous

recovery;
◆ others show very little recovery, even over a period of

years;
◆ still others show reasonably good recovery provided they

receive rehabilitation.
They refer to this as a triage of spontaneous recovery, assisted

recovery, and no recovery. Robertson and Murre argue that
the spontaneous recovery group do not need rehabilitation as
they will get better anyway. They suggest that the strategy of
choice for people in the no-recovery group is to teach
compensatory approaches. Consequently, they focus on the
assisted recovery group to address issues concerning brain
plasticity. They also believe that the severity of the lesion maps
on to this triage, with:
◆ mild lesions resulting in spontaneous recovery;
◆ moderate lesions benefiting from assisted recovery;
◆ severe lesions necessitating the compensatory approach.
Although heuristically useful, this idea may be too simplistic.

For example, people with mild lesions in the frontal lobes
could be more disadvantaged in terms of recovery than people
with severe lesions in the left anterior temporal lobe. The
former group might have attention, planning, and organization
problems precluding them from gaining the maximum benefit
from the rehabilitation on offer, whereas the latter group, with
Page 9 of 29
language problems, could show considerable plasticity by

transferring some of the language functions to the right
hemisphere.
Nevertheless, Robertson and Murre (1999) make some

interesting arguments and present a model of self-repair in
neural networks based on a connectionist model of recovery of
function. Plaut (1996) also uses a connectionist model to
predict recovery. He argues that the degree of relearning and
generalization varies considerably depending on the lesion
location, and this in turn has implications for the nature and
variability of recovery. A more recent connectionist model
looking at recovery of reading following brain damage is
provided by Welbourne and Lambon-Ralph (2005). They
believe that plasticity as reflected by changes in the pattern of
connectivity is as important in recovery as is the pre-morbid
structure of the reading system.
5 How much recovery takes place?

Kapur and Graham (2002) provide a review of recovery of long
term episodic memory functioning and consider both single
case and group studies. They look at the shrinkage of
retrograde amnesia in individual patients with traumatic injury
(which can be seen as one of the characteristics of post
traumatic amnesia) and also look at patients with transient
global amnesia. These conditions are temporary so we would
expect some, perhaps substantial recovery to take place
depending on the length of the PTA (Wilson et al. 1999).
Indeed, this is confirmed in the group studies reported by
Kapur and Graham. They conclude however, that recovery of
memory function “remains a relatively uncharted map in the
geography of cognitive neuroscience” (p. 245). Therefore we
only have very tentative answers when we ask questions about
recovery.
(p.190) Another recent review of recovery is that by Kertesz

and Gold (2003). Although this review is particularly
concerned with recovery from aphasia, the authors briefly
consider recovery of memory and also consider recovery from
different diagnoses likely to give rise to memory problems
such as traumatic brain injury and encephalitis. Like Kapur
and Graham (2002), they look at shrinkage of retrograde
amnesia and at recovery from Post Traumatic Amnesia,
pointing out that prognosis of long term memory impairment
Page 10 of 29
is correlated with the length of PTA. They have little to say on

recovery of memory functioning in people no longer in PTA but
with more stable memory deficits.
A few studies have looked at the natural history of ‘recovery’

of memory functioning over a period of years. Vargha-Khadem
et al. (1997) for example, report on three children who
sustained early bilateral hippocampal damage. These children
were followed for several years and showed reasonable levels
of language and general knowledge despite remaining
severely amnesic. Thus they were able to learn information
despite their impoverished memories. Broman et al. (1997)
also describe a child who became amnesic following a cardiac
arrest when he was 8 years old. He sustained bilateral
hippocampal lesions and was followed for 19 years. At that
time he was still severely amnesic showing no recovery. The
most famous amnesic patient in the world is probably H.M.,
reported initially by Scoville and Milner (1957), who appears
to have shown no recovery since his original operation to
relieve epilepsy. Wilson et al. (2008) also describe a man with
a dense amnesia following herpes simplex encephalitis at the
age of 45 years. The follow-up covered a 20-year period with
no change in his memory functioning.
It is possible that memory shows less natural recovery over

time than other functions such as language (Kolb 1995; Wilson
1998) and this is true for children and adults. Hughes et al.
2002 followed a child said to have made a dramatic recovery
following near drowning. The child was submerged for 66
minutes and one report published 6 years post insult said she
had ‘recovered completely’. Neuropsychological assessment,
at 12 years post insult when the girl was 14 years old however,
found a global memory impairment.
Another factor appearing to influence recovery is the condition

that caused the memory problem. People with head injuries
often do better than people with other diagnoses. Newcombe
(1996) for example, reported on a cohort of World War II
veterans who survived missile wounds to the brain. This group
has been followed since 1963 and is thus one of the most
important follow-up studies of people with brain injury.
Newcombe found a striking preservation of ability in the group
as a whole, despite the fact that some members had selective
impairments as a result of lesions in specific locations. In
people with closed head injury (i.e. not from penetrating
Page 11 of 29
wounds), some have found that age and coma duration predict
recovery (Zwaagstra et al. 1996), despite contradictory
findings on age mentioned earlier. Fleming et al. (1997), like
others, found that psychosocial problems are more persistent
than physical problems one-year post-brain injury. People with
encephalitis who remain with memory difficulties several
months post insult appear to show less recovery over time.
McGrath et al. (1997) found that 70% of encephalitis survivors
showed memory impairment. The single-case studies of Wilson
et al. (1995) and Funnell and de Mornay Davies (1996) found
little change over time. A study looking at (p.191) long-term
outcome of 18 patients with hypoxic brain damage (Wilson
1996) found that, several years post insult, 11 had memory
problems, usually together with other cognitive problems, and
four were too severely intellectually impaired to be assessed
on adult neuropsychological tests. Although recovery from
stroke has been studied (e.g. Robertson et al. 1997), most
studies focus on recovery of motor functions or attention.
Robertson et al. found that ability to sustain attention was
associated with better functional recovery.
6 Can we improve on natural recovery?

Although until recently it was believed that brain cells do not
regenerate, Conover and Notti (2008) state that stem cells of
the adult human brain support regeneration in the
hippocampus through neuronal replacement. We have already
seen that there is controversy as to how much, if any,
functional recovery may take place through the replacement of
stem cells, but it is certainly one area for further research that
could enhance recovery of memory (Zeitlow et al. 2008).
Animal studies have shown that it is possible to regenerate
cells in the dentate gyrus through the provision of specific
learning tasks (Griesbach et al. 2004) or through enriched
environments (Dhanushkodi and Shetty, 2008; Döbrössy and
Dunnett 2004). Thus it might be possible to enhance natural
recovery through enriched environments and focused
rehabilitation strategies. Furthermore, such programmes
might indeed lead to neurogenesis in the human brain (see
McMillan et al. 1999 and Ogden 2000 for further discussion).
We now have the technology, through imaging procedures, to
see whether it is possible to improve memory functioning
(rather than relying primarily on compensatory approaches)
and to see whether any observed behavioural change results
in structural changes to the brain (Levin 2006). Grady and
Page 12 of 29
Kapur (1999) suggest that imaging studies may enable us to

measure specific changes occurring in the brain during
recovery and therefore allow us to determine whether
recovery is the result of:
◆ reorganization within an existing framework; or
◆ recruitment of new areas into the network; or
◆ plasticity in regions surrounding the damaged area.
A few studies using imagery techniques to look at recovery

from brain injury have appeared. One of the first papers in this
area reported changes in regional cerebral blood flow (rCBF)
after cognitive rehabilitation for people who had sustained
encephalopathy following exposure to toxins (Lindgren et al.
1997). Later the same year, positron emission tomography
(PET) was used to identify the neural correlates of stimulation
procedures employed in the rehabilitation of people with
dysphasia (Carlomagno et al. 1997). Laatsch et al. (1997, 1999)
used single-photon emission computerized tomography
(SPECT) to evaluate rCBF during recovery from brain injury.
The authors suggested that specific changes in rCBF appeared
to be related to
◆ the location of the injury;
◆ strategies used in cognitive rehabilitation.
(p.192) Continued improvements in the three patients in the

1997 study were documented in rCBF, functional abilities, and
cognitive skills up to 45 months post insult. A further study by
Laatsch et al. (2004) showed that improvements following
Cognitive Rehabilitation could be detected by fMRI.
In 1998, Pizzamiglio et al. used functional imaging to monitor

the effects of rehabilitation for unilateral neglect. The brain
regions most active after recovery were almost identical to the
areas active in control participants engaged in the same tasks.
This would appear to support the view that some rehabilitation
methods repair the lesioned network and do not simply work
through compensation or behavioural change.
A recent paper by Baxter et al. (2007) described a patient with

non-paraneoplastic limbic encephalitis who had severe
anterograde amnesia with subsequent recovery. They used
fMRI to show increased hippocampal activation before and
Page 13 of 29
after recovery. Does this happen after memory rehabilitation?

We do not yet know the answer to this question, but there is a
growing interest in determining:
◆ whether attempts to restore memory functioning and

attempts to help people compensate result in structural
changes to the brain;
◆ whether any changes seen are different depending on the

approach employed.
In reality, of course, the two approaches are not mutually

exclusive and a combination of the two may prove to be the
most practically useful.
7 Is treatment effective in helping people with memory

and learning difficulties?
Perhaps the people who have done the major investigations
into the efficacy of cognitive rehabilitation are Cicerone and
his colleagues (Cicerone et al. 2000 and 2005). They looked at
several cognitive domains including attention difficulties,
visuo-spatial deficits, apraxia, language and communication
problems, memory deficits, executive functioning, problem
solving and awareness. On the issue of retraining versus
compensation they found that retraining was effective for
some cognitive functions for example, language whereas
compensations were necessary for others such as memory
deficits. Their overall conclusion was “There is now a
substantial body of evidence demonstrating that patients with
TBI or stroke benefit from cognitive rehabilitation” (Cicerone
et al. 2005 p. 1689). These authors also state that “Future
research should move beyond the simple question of whether
cognitive rehabilitation is effective, and examine the therapy
factors and patient characteristics that optimize the clinical
outcomes of cognitive rehabilitation” (p. 1681). Halligan and
Wade (2005) provide a summary of much of the work on the
effectiveness of rehabilitation for cognitive deficits.
There would appear to be four major approaches to cognitive

rehabilitation:
◆ cognitive retraining through stimulation or exercises;
◆ strategies derived from cognitive-neuropsychological

theoretical models;
Page 14 of 29
◆ techniques combining methodologies and theories from a

number of different fields (particularly behavioural
psychology, neuropsychology, and cognitive psychology);
(p.193)
◆ holistic approaches that address social and emotional
problems alongside the cognitive ones.
The nature of these approaches together with their strengths

and weaknesses are addressed in further detail by Wilson
(1997 a, b).
7.1 Compensatory approaches

There is increasing evidence to suggest that rehabilitation can
improve cognitive functioning (Cicerone et al. 2005). In the
field of memory disorders a good review is provided by
Sohlberg et al. (2007). The method of choice for reducing
everyday problems (rather than improving memory
functioning) is probably to teach compensatory approaches.
Several publications show that people with memory
impairments can function independently if they are able to use
strategies to get round their difficulties. Wilson et al. (1997)
describe J.C., a young man who became densely amnesic
following a ruptured aneurysm on the left posterior cerebral
artery. Over a 10-year period, J.C. developed a sophisticated
system of memory aids enabling him to live alone, hold down a
job, and be totally independent despite the fact that he
remains severely amnesic. The paper describes the natural
history of the development of J.C.’s compensatory system,
which began by his writing on scraps of paper a few weeks
after his stroke and over time developing his highly successful
system.
Another encouraging study describes the rehabilitation of a

young woman who became amnesic following status
epilepticus (Kime et al. 1996). This woman was taught to use a
personal organizer (datebook), refer to it regularly, and
monitor a number of daily events. Over a period of several
weeks, she was able to learn the different sections of a
datebook and use this to manage her life. After leaving the
rehabilitation centre, she worked in a voluntary capacity (still
using her system) and eventually was taken on as a paid
employee.
Page 15 of 29
Even with those people who are unable to return to work,

memory compensations can assist independent living. One
instrument that has been helpful to a number of memory-
impaired people is NeuroPage®, an alphanumeric pager
attached to a belt that sends out daily reminders. In a pilot
study (Wilson et al. 1997), 100% of 15 people with memory
and/or planning problems showed a statistically significant
improvement in achieving everyday target behaviours (e.g.
taking medication, feeding the dog, collecting children from
school) with the pager than they had achieved during a
baseline period. Further work with the pager showed how
effective this could be for individuals (Evans et al. 1998;
Wilson et al. 1999). Findings have since been replicated with a
larger study of 143 people (Wilson et al. 2001) and diagnostic
subgroups have also been reported including TBI (Wilson et al.
2005), encephalitis (Emslie et al. 2007), stroke (Fish et al.,
2008) and children (Wilson et al.). An interesting new
development for helping people with prospective memory
difficulties is reported by Fish et al. 2007.
7.2 ‘Errorless’ learning

In addition to compensations in the form of external memory
aids, techniques for improving learning in memory-impaired
people are a major part of rehabilitation. It has been
demonstrated that people with amnesia learn better if they are
prevented from (p.194) making mistakes during the learning
process (Baddeley and Wilson 1994). Most of us benefit from
trial-and-error learning if we can remember our previous
mistakes. People with amnesia, of course, cannot do this
because once a mistake has been made, it may be
strengthened or reinforced or be indistinguishable from the
correct response. Consequently, it is better to prevent the
incorrect response being made in the first place. Following the
original Baddeley and Wilson (1994) paper, several studies
have been carried out applying the ‘errorless learning’
principle to teaching real-life tasks (Wilson et al. 1994; Clare
2003; Campbell et al. 2007). In a meta-analysis of Errorless
Learning Kessels and De Haan (2003) found a large effect size
of EL. Akhtar et al. (2006) showed the method was also useful
for people with mild cognitive impairment. Page et al. (2006)
suggest that the benefits of errorless learning are dependent
on the implicit memory system which is normal or nearly
normal in most amnesic patients. Although a number of
questions, both clinical and theoretical, remain to be answered
Page 16 of 29
about ‘errorless learning’, the principle would appear to be

better than trial-and-error learning for teaching people with
memory difficulties useful information to help them cope in
everyday life.
7.3 A holistic approach

Finally, holistic programmes for helping people with memory
problems would address emotional problems such as anxiety
and depression together with any cognitive deficits. Such
programmes feature both group and individual therapy
embedded in a goal-planning approach to reduce emotional
and cognitive problems. The goals would be negotiated
between clients/patients, family members, and staff. Long-
term goals are those that should be achieved by the time of
discharge from the rehabilitation programme and short-term
goals are the steps taken to reach the long-term goals. Thus,
long-term aims might be to:
◆ ‘develop a system for scheduling appointments’;
◆ learn how to use a computer program for managing one’s

finances;
◆ learn the location of the nearest bank;
◆ reduce anxiety about meeting new people.
Short-term objectives for ‘developing a system for scheduling

appointments’ might include:
◆ the occupational therapist accompanying the client to

purchase an electronic organizer;
◆ the psychologist using an errorless learning procedure to

teach the client how to enter an appointment;
◆ the client learning how to check a message when the

alarm sounds;
◆ in the memory group the client will practise using the

machine to schedule appointments and respond
appropriately.
Each long-term aim would require a different set of short-term

objectives.Examples of this approach with individual clients
can be found in Wilson et al. (2002). The important aspects of
the approach are:
Page 17 of 29
◆ addressing both emotional and cognitive difficulties;
(p.195)
◆ involving the client/patient and the family in the decision-
making process;
◆ setting goals which are of practical everyday value as well

as being realistic and achievable;
◆ monitoring and recording progress, as well as reasons for

failure in achieving certain goals.
Cicerone et al. (2004) say: “Intensive, holistic, cognitive

rehabilitation is an effective form of rehabilitation particularly
for persons with TBI who have previously been unable to
resume community functioning” (p. 943).
8 Summary and conclusions

People with memory problems typically show some resolution
of deficits acquired as a result of an insult to the brain.
Following traumatic brain injury the recovery process can
continue for a number of years. In other conditions, such as
encephalitis or hypoxic brain damage, the recovery process
may not continue for such a long period. Age may have some
bearing on the amount of recovery attainable, but other
factors, such as whether the lesion is focal or diffuse, and the
amount of time since the skill was originally learned will also
play a part.
The mechanisms of recovery are not well understood but

several processes may be involved including regeneration of
brain cells, diaschisis, and plasticity or reorganization of brain
functions. Memory functions certainly show some recovery in
the early days and weeks following an insult to the brain and,
once again, the amount of recovery may depend on the cause
of the brain damage (e.g. traumatic brain injury or
encephalitis). It is not clear to what extent brain areas
involved in memory can regenerate and whether such
regeneration can be influenced by enriched environments,
rehabilitation programmes, or other specific training
strategies. Imaging techniques may enable us to answer some
of these questions.
Rehabilitation can certainly reduce some of the everyday

problems faced by people with memory deficits. Helping them
to compensate for their poor memory skills is, at present, one
of the most fruitful methods. Technology, including a new
Page 18 of 29
paging system, has significantly enhanced the ability to carry

out everyday tasks in a recent randomized control cross-over
design with 143 brain-injured people. Errorless learning
techniques (i.e. avoiding trial-and-error learning) have proved
beneficial in helping people to learn more efficiently. Holistic
programmes addressing both emotional and cognitive
problems are recommended in the rehabilitation of people
with memory and learning difficulties, particularly when
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Assessment and treatment of disorders of visuospatial, imaginal, and constructional
processes


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Assessment and treatment of

disorders of visuospatial, imaginal,
and constructional processes
Lilianne Manning
DOI:10.1093/acprof:oso/9780199234110.003.11

This chapter discusses deficits that reflect a disturbance of the
processing of sensory information. Specifically, it discusses the
assessment and treatment of defects in visuospatial processes,
imaginal processes, and constructional processes.
Keywords: sensory information processing, visuospatial process, imaginal

process, constructional process
1 Introduction
The usual screening neuropsychological batteries have
practically ignored the assessment of visuospatial, imaginal,
and constructional deficits. The general tendencies underlying
current approaches consist of:
◆ an early assessment of these functions;
◆ the introduction of everyday life parameters, particularly,

in rehabilitation.
Page 1 of 21
processes
The first tendency can be achieved by adding simple measures

in order to increase the sensitivity of routine tests and guide
the clinician to detect, from the very beginning of the
assessment, one or more nonverbal disorders of the type
covered in this chapter. An example is the enhancement of the
sensitivity of the Mini Mental Status Examination by adding a
clock drawing.
The second current tendency, studying the relationships

between a given disorder and some measures of activity in
daily living, implies the construction of highly targeted
programmes based on both the patient’s description
(whenever possible) of his/her most disabling symptom(s) and
a comprehensive assessment of deficits and preserved
cognitive functions. It is worthwhile noting that everyday
function can improve with the appropriate treatment without
there being any improvement in cognitive test scores. The
current ‘ecological’ concern also consists of using assessment
and rehabilitation based on virtual environment technology
when working with the real environment is impossible or
unsuitable (e.g. for elderly patients) and when the aim of the
programme cannot be achieved by using traditional
neuropsychological methods. It basically consists of dynamic
three-dimensional stimulus environments, in which a wide
range of nonverbal deficits can be recorded, particularly
concerning visual, topographical, and constructional
processes.
(p.203) 2 Defects in visuospatial processes

Visuospatial processing ability can be defined as the capacity
to localize objects in relation to each other in space and to
know the location of single objects with respect to oneself. The
major clinically different forms of visuospatial disorders are:
◆ visual disorientation;
◆ defective complex visuospatial processing;
◆ unilateral visual neglect;
◆ Balint’s syndrome.
Balint’s syndrome is triggered predominantly by attentional

defects as is visual neglect—however, the latter can also be of
an intentional and representational nature. Balint’s syndrome
and visual neglect are both dealt with elsewhere in this
volume (see Chapter 8). Several other less frequently observed
Page 2 of 21
processes
visuospatial deficits, such as impaired performance on mazes,

have not been included in this section. The two forms of
visuospatial disorders covered here are visual disorientation
and defective complex visual processing.
2.1 Visual disorientation

2.1.1 Clinical presentation
Patients are unable to localize single objects, and act as if they
were blind.
◆ They have marked difficulty in directing voluntary eye

movements towards an object. Patients asked to look at the
examiner’s face look at many different points and are
unable to ‘stop’ voluntarily at the face in front of them.
◆ They also have problems in reaching for or pointing to an

object. They will almost invariably position the hand at the
wrong distance in one or more of the three spatial
dimensions. This deficit, observed despite the object
actually being seen, is called optic ataxia. Note that patients
with optic ataxia have no difficulty in localizing their own
body parts. If the patient succeeds (often with help) in
picking up food with a fork, he/she will bring it with no
hesitation whatever to his/her mouth.
◆ Attentional processes are also impaired (see Chapters 5

and 6).
2.1.2 Brain damage localization

The brain damage is usually observed in the dorsal,
occipitoparietal projections, i.e. the ‘where’ pathway. Lesions
are generally bilateral, though there are some reports of visual
location deficit in the hemi-field contralateral to the lesion.
Visual disorientation, after either bilateral or unilateral
lesions, is rare and its most severe form is found in patients
with Balint’s syndrome.
2.1.3 Diagnosis
The diagnosis of visual disorientation, i.e. impaired single-
object localization, applies to the patient who, besides normal
visual acuity, is able to localize external sounds (e.g. correctly
pointing to the source of a voice while blindfolded) and tactile
stimulation on (p.204) his/her own body. This is necessary to
rule out motor deficits and demonstrate accurate body
sensations and normal use of body parts.
2.1.4 Assessment
Page 3 of 21
processes
A neuropsychological examination should only be conducted in

patients who have successfully completed an ophthalmological
examination.
◆ Ask the patient to look at an object and to point at an

object or a dot on a sheet of paper to test simple
localization.
◆ Assess depth discrimination by asking him/her to estimate

distance of objects in the natural environment and by
showing the patient two objects either on the same
horizontal plane or on different planes, one of the objects
being clearly closer to him/her. Can the patient say whether
or not they are at the same distance? Carry out the same
task moving the patient’s finger from one object to the
other. This tactile test should be normal.
◆ To test size discrimination place different sized real

objects at the same distance from the patient. Can he/she
say which is larger? The number of trials and the
comparative size of the objects presented will depend on
the initial results.
◆ Optic ataxia needs two conditions of testing:
— First, ask the patient to reach out and grasp an

object that he/she is looking at.
— Second, repeat the manoeuvre but with a screen

(a file or similar) placed between the patient’s head
and his/her arm to prevent him/her from seeing the
hand movement.
Optic ataxic patients succeed in the second condition only.
◆ Test the patient’s spatial scan and single-point localization

using a dot-counting task. Norms exist for different groups
of brain-damaged patients and normal controls (Warrington
and James 1991).
Page 4 of 21
processes
2.1.5 Recovery and rehabilitation

Spontaneous recovery has been observed after unilateral right
hemisphere damage. ‘Improvement’ of visuospatial difficulties
has been observed after non-specific training programmes on
visual material reflecting a general increase in the level of
attention and awareness. Rehabilitation programmes in
patients presenting impaired visual fixation, difficulty in
scanning dot arrays, and inability to reach objects on visual
guidance have been carried out. New rehabilitation
programmes can be developed to improve on existing
programmes provided that the rationale behind the
intervention, the articulation of stages, and the time required
to obtain results are all compatible with the case at hand. See,
for example, Zihl (2000, pp. 107–32). His rationale was to
improve localization of objects by fixating and reaching. He
designed a progressively complex training scheme, the last
stage being reading treatment demanding a very high level of
visual control of eye movement. The whole programme took
nearly 100 sessions. The results are encouraging. The patient
improved her vision in everyday life, and improved fixation
and localization helped her to achieve better identification of
objects.
Case report
Patient H.B., a 63-year-old woman, obtained a Verbal IQ of

100 (Wechsler Adult Intelligence Scale (WAIS-R). She was
able to name objects from a description but unable to carry
out the Performance IQ. This combination of preliminary
results both oriented the interview and indicated a test of
visual process. She showed poor visual acuity but relatively
well preserved ability to perceive shapes. Colour and face
perception were preserved. Preliminary visual orientation
was tested by asking her to point to a finger and to 1 cm
diameter coloured dots presented one by one in different
positions on a sheet of white paper. Her performance was
markedly impaired. It was observed that she retained the
ability to localize points on her body and the source of the
examiner’s voice with eyes closed. These few results
suggested that both diffuse neurodegenerative processes
and shape disorders could be ruled out and pointed to a
Page 5 of 21
processes
differential diagnosis of visual disorientation. It was

decided to carry out several of the tests described above
(see Section 2.1.4).
(p.205) 2.2 Complex visuospatial processing

Disorders in complex visuospatial processing are subdivided
into two types:
◆ topographical disorientation;
◆ spatial analysis deficits.
2.2.1 Topographical disorientation

Clinical presentation
This deficit considerably hinders patients’ everyday life.

Characteristically, they have difficulty in finding their way
from one location to another, despite intact basic visual
processes. Moreover, they may present preserved topo-
graphical visual recognition and memory—they are able to
recognize places while getting lost on familiar and/or simple
routes or have difficulty in finding objects at home. The
opposite pattern of performance, i.e. loss of topographical
recognition and preserved spatial knowledge, results in an
inability to recognize buildings and places while managing
accurate accounts of journeys.
Brain localization
Predominantly right parietal damage.
Diagnosis
Diagnosis is based on interviews with the patient and a

relative or carer about the extent and characteristics of
topographical disorientation.
◆ Does the patient get lost in familiar surroundings?
◆ Is he/she unable to learn new simple routes?
◆ Was his/her way-finding good before the illness?
Take into account the fact that this disorder can be either a
feature of dementia or a selective impairment with other
functions well preserved (see ‘Recovery and rehabilitation’ in
this section).
(p.206) Assessment
Page 6 of 21
processes
Ask patient questions such as:
◆ How did you get here?
◆ Can you tell me how to get from X to Y? (X and Y being

two places familiar to the patient).
◆ How do you go from this room to your ward?
◆ Can you describe your home/flat/room?
Maps or plans are often used for the patient to locate well
known places in his/her country or city. It can also be useful to
present a large square on a sheet of paper, to represent the
patient’s bedroom, and ask him/her to locate furniture, doors,
and windows.
Recovery and rehabilitation
◆ Patients having difficulty in locating items in their

familiar places benefit from written lists, e.g. of contents of
cupboards.
◆ Patients getting lost on familiar routes can be helped by

photographs of prominent environmental cues to be used as
landmarks.
◆ Written instructions are also useful for some patients.
◆ To increase meaningful associations concerning well

delimited locations of daily journeys between several
places, teach the patient simple mnemonics combining
names of streets and their location.
◆ A further real-life orientated treatment consists of

walking with the patient in familiar surroundings, briefly or
for a few minutes (depending on the patient’s degree of
deficit), then asking him/her to go back to the starting
point. The length of time and the number of changes of
direction are gradually increased. Finally, the patient can be
asked to draw the route.
Rehabilitation programmes are more frequently constructed

(and reported) when topo-graphical disorientation is isolated
rather than embedded in a diffuse clinical picture. However, it
is important to bear in mind that the isolated presentation can
be the result of combined effects of several impairments such
as space perception and nonverbal memory. Treatment can
focus on one of these. When deciding on the type of treatment
Page 7 of 21
processes
it is helpful to have the patient’s description of the most

disabling symptom in his or her everyday life.
2.2.2 Spatial analysis deficits

◆ Clinical presentation. These deficits are often only
revealed through testing. Patients suffering from spatial
analysis deficits have difficulty in position discrimination
and/or line orientation discrimination. Detection of
discrimination impairments requires fairly elaborate tasks
(see ‘Assessment’ in this section).
◆ Brain localization. Predominantly right parietal damage.
◆ Diagnosis of spatial analysis deficits is based on

quantitative results in a series of specially constructed
tests.
(p.207) Assessment
The following tests assessing the patient’s capacity to perceive

the relative position of objects in two-dimensional space have
been standardized (Warrington and James 1991).
◆ Position Discrimination consists of sets of two adjacent

horizontal squares, one with a dot printed in the centre and
one with a dot slightly off-centre. Ask the patient to point to
the dot that is in the centre (cut-off, 17/20). Carry out the
next task even if the patient’s performance is normal.
◆ Number Location consists of sets of two non-adjacent

squares placed one above the other. The bottom square
contains one single dot corresponding to one of the
randomly placed nine numbers of the top square. Ask the
patient to say or point to the number that matches the
position of the dot (cut-off, 7/10).
◆ Cube Analysis. The patient has to interpret three-

dimensional space in two-dimensional representations (see
Fig. 11.1). Ask the patient to count the number of solid
bricks (cut-off, 6/10).
◆ Discrimination of line orientation is tested with a graded

difficulty task consisting of two figures, one above the
other, showing a ‘sun ray’ of lines of different orientation:
the top figure shows two ‘rays’, the bottom figure shows 11
‘rays’ covering 180°. Ask the patient to match the two lines
of the top figure to those that have the same slant in the
‘sun ray’ bottom figure. The task is fairly sensitive and
Page 8 of 21
processes
provides norms for groups of brain-damaged patients and

normal controls (Benton et al. 1983, pp. 56–62). (See Table
11.1 for a synopsis.)
Recovery and rehabilitation
Measurement of specific visuospatial abilities at time of

admission may help the rehabilitation prognosis.
(p.208)
Fig. 11.1 Example of stimuli from a

spatial analysis test, the Cube Analysis
task (Warrington and James 1991).
(Reproduced with permission of the
publisher Pearson Assessment. (2009)
Copyright © 1991. All rights reserved. No
part of this publication may be
reproduced or transmitted in any form or
by any means electronic or mechanical,
Page 9 of 21
processes
including photocopy, recording or any

information or retrieval system, without
permission in writing from the publisher.)
Table 11.1 Visuospatial processes: synopsis of

deficits and tests
Visuospatial Complex visual

disorientation processing
Topographical Spatial analysis

deficits deficits
Simple item ‘How did you get Position

localization here?’ Discrimination
Depth ‘Go from X to Y’ Number

discrimination Location
Size discrimination ‘Show me … on this Cube Analysis

map’
Reaching out tests ‘Draw your flat/ Line Orientation

room’ Test
◆ Treatment could be attempted using the tactile versions

of the cube analysis subtest or the line orientation test, with
patients presenting deficits on spatial analysis in the visual
modality only.
◆ A treatment using the tactile and the visual modalities

consists of fitting different shapes into the correct holes in
a board, as quickly as possible.
◆ Computer-generated virtual environments that can be

explored in real time could be used to treat acquired
visuospatial deficits.
◆ Finally, patients with some musical abilities could benefit

from a rehabilitation programme combining increasing
levels of difficulty, figures of cubes (of the type presented in
Fig. 11.1), and musical isomers. It has been suggested that
the latter facilitate visuospatial relations since the same
holistic processes appear to be at work both in the
perception of musical contour and in mental manipulations
of two-dimensional figures.
3 Deficits in imaginal processes
Page 10 of 21
processes
Case report
Patient C.S., a 73-year-old woman, obtained a verbal IQ of

99 and a performance IQ of 87 (WAIS-R). Naming on
description was very good. Verbal recognition memory was
adequate (it was orally presented). She was unable to
recognize unusual views of common objects but recognized
20/20 when the canonical view was presented. This result
led to her being asked to perform several visuoperceptual
tasks (not commented on here) and visuospatial tasks.
Concerning the latter, she failed the Position
Discrimination test (8/20), and the Cube Analysis task
(2/10). These preliminary results suggested that there was
a deterioration affecting, in particular, perceptual and
visuospatial skills, with verbal abilities remaining relatively
intact. A further assessment session was decided with a
view to obtaining a complete cognitive profile.
There are two forms of imaginal deficits: deficits in visual

imagery and in spatial imagery. Visual or spatial imagery can
be selectively impaired.
(p.209) 3.1 Visual imagery

Visual imagery is defined as the conscious reproduction of
previously experienced events and objects, their shape, colour,
size, and any other visual attributes that we know.
◆ Clinical presentation. Patients may not realize that the

brain lesion has induced a loss of imaginal visual attributes.
On the contrary, they may be surprised not to be able to
perform some tests. Loss of visual imagery may be observed
together with visual agnosia or in the context of preserved
visual recognition. Patients frequently also have right
homonymous hemianopsia. Right hemiplegia and/or
language disturbances (particularly shortly after a stroke)
can also be present.
◆ Brain damage localization. Left posterior lesions.
◆ Diagnosis. Loss of visual imagery can be diagnosed only if

the capacity to copy models and describe their visual
characteristics is preserved (see Manning 2000).
Page 11 of 21
processes
3.1.1 Assessment
◆ Ask the patient to draw from memory and then to copy
from canonical models, objects such as a cube, a flower, etc.
This very simple and informative task can be carried out
even at bedside.
◆ Ask the patient questions rich in visual attributes (e.g.

‘what’s the name of the bird with a hooked beak, large, flat
face, round head, large eyes, and soft plumage?’) and
questions concerning functions only (e.g. ‘the bird that
stays awake all night long, flies, and hoots?’). Results are
fairly straightforward: patients with no aphasic symptoms
and impaired visual imagery fail selectively the ‘visual’
questions.
◆ Present the patient with coloured line drawings of

canonical views of animals. Ask the patient to indicate
whether the tail of the animal is long or short relative to its
body in each of the following three conditions:
— the perceptual control condition, in which the

patient has to respond while looking at the depicted
animal; if failed, the test should be discontinued;
— the test situation proper, in which the tail of the

animal is masked;
— the auditory condition, where only the name of the

animal is given.
This test allows comparisons to be drawn between the

patient’s ability to conjure up mental images from incomplete
visual items and from auditory input. Patients with genuine
loss of visual imagery will fail the test on the last two
conditions.
◆ To test visual imagery of colours, administer the following

tests:
— Control condition. Present the patient with 10

different coloured patches. Ask him/her to point to
the same coloured patch as indicated by the
examiner on a set of identical coloured patches
distributed differently. If the patient fails this task,
discontinue the colour examination.
Page 12 of 21
processes
— Present the patient with 10 or more uncoloured

canonical line drawings and a good set of crayons.
Ask him/her to fill in the line drawings with the
appropriate colour.
(p.210)
— Auditory condition. Ask the patient the colour of
different fruits (cherry, banana, tangerine), animals
(tiger, elephant, parrot), and personal objects (his/
her toothbrush, front door, car).

A treatment using nonvisual information consists of a series of
familiar (e.g. spoon, key, watch) and less familiar objects (e.g.
stapler, funnel, pair of goggles) to be tactilely explored by the
patient. Objects’ surfaces, or part of them, are covered with
fabrics of different textures, which are associated with
colours. Instruct the patient to describe the shape, imagine the
colour (from the texture), imagine the object on a table, in a
bag, near the window, etc.
The issue of imaginal rehabilitation is crucial for patients with

artistic activity. Copying sufficiently elaborated models may
allow the patient to re-acquire at least some of his/her
technical and artistic skills. Models to be copied, which should
be very well known to the patient, could be presented with
progressively fewer parts as training of visual imagery
progresses.
3.2 Spatial imagery

Spatial imagery is the ability to conjure up images of the
location and structure of objects in three dimensions. The
capacity to manipulate images is crucial to mental spatial
transformations.
◆ Clinical presentation. It is not unusual for patients with

spatial imagery deficits to say that they have more difficulty
in ‘working things out’ than they used to before the brain
accident.
◆ Brain damage localization. Left posterior lesions.
◆ Diagnosis. Deficits in spatial imagery are diagnosed if the

patient fails tests of mental transformations, regardless of
his/her ability or inability to conjure up visual images.
3.2.1 Assessment
Page 13 of 21
processes
◆ Present the patient with a sheet of paper containing

capital letters in random order, half of them upside-down.
Ask the patient to indicate which letters are the right way
up. This is probably the easiest task and it is useful to start
with it in order to reduce anxiety in patients who feel ill at
ease when asked to perform spatial tasks.
◆ Ask the patient to imagine a capital letter and to count

the corners. This task is sensitive enough to indicate if
extended testing on spatial imagery is necessary.
◆ Give orally a series of letters, with (Q, G, etc.) or without

(L, E, etc.) curves. Ask the patient to imagine them in the
upper-case form and to indicate whether or not they have
curves.
◆ Present a series of drawings of a man holding a black disc

sometimes in his right and sometimes in his left hand. The
figure should be shown upright or upside-down and from
the front or from behind. Ask the patient to indicate in
which hand the ‘manikin’ is holding the black disc. This
rotation task is particularly useful in cases of association
(p.211) of visual and spatial imagery, since the task elicits
mental transformation but not generation of mental images.

A tactile training device utilizing a board with rotated, made
fast letters can be used to treat spatial imagery.
4 Deficits in constructional processes

Constructional processes involve the ability to produce
properly organized ‘constructions’ such as drawings and
building tasks, i.e. to assemble patterns of simple
arrangements made up of blocks, tokens, or sticks. They
involve the ability of normal visual and motor systems to
execute visuomotor tasks.
Clinicians use the term ‘constructional apraxia’ for

convenience rather than as a term with a precise meaning.
Different factors may provoke constructional difficulties.
However, the symptoms are sufficiently distinctive to be
defined independently of other classical apraxias and
visuoperceptive deficits (see Andrewes 2001, pp. 35–81).
4.1 Clinical presentation
Page 14 of 21
processes
The patient is unable to grasp the way in which the component

elements relate to the final model to be (re)-produced, and
then to fit the components together in the correct spatial
organization.
4.2 Brain localization

Either right or left parietal lesions. Incidence is higher after a
right injury (right: left ratio of 3 : 1) and the deficit is more
severe in right and bilaterally injured patients. Independently
of the side, the predominantly posterior localization of lesions
is confirmed by significant correlations between the damaged
neural substrate of Brodmann’s area 18 and constructional
ability.
◆ Left lesions result in oversimplification of the model

within the context of a relatively preserved spatial relation.
The cause is failure in the organization of actions necessary
for constructing tasks.
◆ Right lesion patients produce overelaborate, often

irrelevant fragments showing spatial disorganization. The
cause is failure in the organization of space.
4.3 Diagnosis
The patient’s inability to perform drawing and construction
tasks occurs in the context of the following preserved
functions:
◆ visual form perception;
◆ spatial localization;
◆ ideomotor praxis.
(p.212) Although ‘pure’ constructional apraxic patients are

rarely encountered in everyday practice, at least a relative
preservation of the above functions must be demonstrated
before this can be diagnosed.
Note that relatively complex tasks make demands on sustained

attention and therefore could be performed defectively
without any clinical significance for constructional processes
(e.g. the Complex Rey Figure Test). Should this be the case,
base diagnosis on easier tasks (e.g. copy of a cube). Likewise,
aphasic patients should have demonstrated their
understanding of the verbal instructions before a
constructional disability is diagnosed.
Page 15 of 21
processes
4.4 Assessment
◆ Ask the patient to carry out a spontaneous drawing. Note
that it can be difficult to score drawings produced on verbal
command (right lesion patients may produce marked lateral
neglect drawings; left lesion patients may be unable to
perform—see Section 4.2.).
◆ If this is the case, ask him/her to draw a bicycle (see

Lezak 1995, pp. 74–81) and to comment on as many details
as possible about the way in which the different parts relate
to each other. (For example, a right parietal patient
produced an elaborate defective bicycle with the pedals
close to the saddle. Asked how she made it work, she told
me, ‘you have to bend your knees up’. Her verbal response
was tailored to the defective relation of a component part to
the whole, which she was unable to correct.)
◆ Ask the patient to copy a line drawing, an abstract design

such as the Rey Complex Figure. Scoring procedures for
this and some other copying tasks (e.g. the copying section
of the Benton Visual Retention Test; Benton 1962) are
reliable and norms exist for different groups of brain-
damaged patients and normal individuals (but see Section
4.2). Time of completion can be important for the
qualitative analysis.
◆ To assess greater demands on the spatial component of

perception than those made by the drawing tests, present
block construction tests. They test three-dimensional
construction processes, which call upon a particular set of
functions since they elicit deficits not shown on two-
dimensional tests. The Benton Constructional Test, which
has detailed norms, is frequently used together with two
simple tasks from the Stanford–Binet battery, the Tower and
the Bridge. The latter two tasks are useful for severely
impaired patients.
◆ The Block Design test (WAIS subtest or similar) is one of

the most frequently used clinical tools. The patient is
normally instructed to reproduce the models within a time
limit since this is an IQ subtest for which norms are reliable
and can be found in many different countries. However,
when the task is used to assess constructional processes, no
time limit should be imposed.
Page 16 of 21
processes
◆ Constructing stick patterns and copying from stick

patterns are both rapid and less demanding tasks, but
norms are not readily available. Qualitatively, despite their
simplicity, they have proved sensitive to constructional
impairment.
(p.213) The common and characteristic factor among these

constructional tasks is that they all need to be carried out in
extrapersonal space. On this basis, it is useful to bear in mind
that right- and left-damaged patients fail constructional tests
for different reasons: an inability to correctly organize the
parts of an object and an inability to analyse those parts,
respectively.
Note that visuoconstructional processes need to be assessed

by at least two different tests, mainly due to only moderate
intertest correlation coefficients and differing test sensitivity.
Analysis of this latter point showed that clinicians relying on
the WAIS Block Design alone could easily underestimate a
high percentage of constructional apraxia patients whose
impaired performance is apparent on the more sensitive Rey
Complex Figure Test. A final point concerns constructional
processes in neurodegenerative diseases. In demented
patients of the Alzheimer type, impairments in constructional
tests requiring access to semantic and lexical knowledge (e.g.
drawing or constructing something meaningful) are present in
the early phase of the disease, while impairments in
constructional tests that do not require that access (e.g.
copying the Rey Complex Figure) become evident in later
phases. Digressions from this general pattern of deficits may
prompt the clinician to envisage the administration of
extended constructional batteries aiming at clarifying an early
involvement of the posterior associative cortex in the onset of
Alzheimer dementia in a given patient. In patients suffering
from Parkinson’s disease, performance on constructional
tasks, particularly copying a cube, is associated with mobility
in daily life and social cognition.
4.5 Recovery and rehabilitation

Spontaneous recovery has been observed in two-thirds of
patients. The size of the lesion is not related to the rate of
recovery from constructional disability. There is a difference in
average recovery depending on the side of brain injury.
Patients in the left-hemisphere group show better recovery a
few months postonset than the right-hemisphere group.
Page 17 of 21
processes
Rehabilitation programme reports are virtually non-existent in

the literature. Compared to language or memory deficits, the
inability to reproduce a line drawing or build a tower seems
insignificant. ‘Pure’ cases are extremely rare and, whenever
an intervention is reported, it is in the context of either motor
or visuoperceptive impairments. Patients may never complain
of being unable to reproduce patterns since this ability mostly
involves non-ecological tasks.
Some empirical suggestions to be taken into account in a

tailor-made rehabilitation programme follow.
◆ Analyse the patient’s constructional errors concerning the

whole, the parts, and the ‘boundedness’. Observe the
effects of time constraints. Some tasks (e.g. Block Design)
are usually timed. It may be useful to obtain a score for
standard time limit completion and a separate score for
performance with no time constraints. However marginally
patients may benefit from the extra time allowed them in
terms of improved performance, comparisons of
productions with and without a time limit might be helpful
in determining whether different types of difficulty appear
in each situation.
(p.214)
Table 11.2 ‘What to test and when’: suggestions

for everyday clinics for patients whose medical
files and referral requests do not specify the
symptoms (see text for more information)
Patient’s characteristics Suggested disorder

to be tested
Defective pointing to and copying Visual disorientation

tasks; preserved shape recognition
Defective way and objects finding; Topographical

preserved memory disorientation
Defective or weak score on any Visuospatial analysis

subtest of the VOSP in routine disorder
examination
Defective drawings from memory; Loss of visual

preserved copies from models imagery
Page 18 of 21
processes
Patient’s characteristics Suggested disorder

to be tested
Explicit complaint or loss of visual Loss of spatial

imagery imagery
Defective score on the Block Design Constructional

task on routine assessment apraxia
◆ Concerning daily life treatment, it is useful to bear in

mind that
— there is a correlation between the WAIS-R Block

Design subtest (see above) and meal preparation
skills;
— some patients suffering from constructional

apraxia may have difficulty in dressing (not the full-
blown dressing apraxia picture), because a portion of
the inability to dress is perceptual, not motor in
origin. Constructional praxis treatment may produce
some gains in the ability to dress.
Finally, computer-aided training programmes are available.

The ‘Visuoconstructive Abilities KONS’ (Visuoconstructive
Abilities Kons 1997) is intended for patients with mild or
moderate constructional apraxia whose memory is preserved.
The programme consists of 18 levels of difficulty. The authors
state that the adaptive nature of the programme allows a great
deal of variation in training. This has the advantage of
ensuring maximum adjustment per patient, whose
improvement is recorded. However, the programme makes no
provision for quantitative data for groups of patients.
Table 11.3 Examples of treatments reported to

have had positive effects on the patient’s
everyday life (see text for more information)
Disorder Treatment Everyday life
Visual Fixating and Improved ‘vision’ in

disorientation reaching objects familiar
surroundings
Topographical Written lists and Find objects at

disorientation instructions home
Page 19 of 21
processes
Disorder Treatment Everyday life
Mnemonics to Find familiar

create routes
associations
Back to the Find familiar

starting point task routes
Loss of visual Copy and Helps artistic

imagery complete well- production
in artists known
pictures
Constructional Training in Meal preparation

apraxia constructional
tasks
Ability to dress
(p.215) 5 Conclusion
◆ The deficits referred to in this chapter reflect a
disturbance of the processing of sensory information, the
sense organs usually remaining intact.
◆ Deciding ‘What to test and when’ considers both impaired

and preserved functions, as shown in Table 11.2.
◆ To ensure that the patient receives appropriate treatment

these syndromes must be diagnosed as early as possible.
Table 11.3 lists the treatments that have been shown to
have beneficial effects on everyday life.
Andrewes, D. (2001). Neuropsychology from theory to

practice. Psychology Press Ltd, Hove, East Sussex.
Benton, A. (1962). The visual retention test as a

constructional praxis test. Confina Neurologica 22, 141–55.
Benton, A., Hamsher, K., Varney, N., and Spreen, O.

(1983). Contributions to neuropsychological assessment.
Lezak, M. (1995). Neuropsychological assessment, 3rd edn.

Page 20 of 21
processes
Manning, L. (2000). Loss of visual imagery and defective

recognition of parts of wholes in optic aphasia. Neurocase 6,
111–28.
Visuoconstructive Abilities KONS. (1997). REHA COM.

Schuhfried, Moedling.
Warrington, E. and James, M. (1991). The Visual Object and

Space Perception Battery. Thames Valley Test Company, Bury
St Edmunds.
Zihl, J. (2000). Rehabilitation of visual disorders after brain

injury. Psychology Press, Hove, East Sussex.
Page 21 of 21
Assessing disorders of awareness and representation of body parts


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Assessing disorders of awareness

and representation of body parts
Carlo Semenza
DOI:10.1093/acprof:oso/9780199234110.003.12

This chapter begins with a discussion of the various
pathological conditions involved in disorders of awareness and
representation of body parts. It then discusses autotopagnosia,
personal neglect and related disorders, alien hand syndrome,
altered muscular proprioception, phantom limb and related
phenomena, and body-specific cognitive biases in eating
disorders.
Keywords: autotopagnosia, alien hand syndrome, altered muscular

proprioception, phantom limb, eating disorders
1 Introduction
Disorders of awareness and representation of body parts
traditionally encompass a number of very heterogeneous
pathological conditions, whose link with one another share a
common intuition that something about the representation of
body has been damaged. This chapter acknowledges this
tradition in the absence of a better way to cover the whole
Page 1 of 32
topic in a clinical handbook. Some provisos, however, must

precede the description of single pathological entities.
For some time, the common factor grouping together these

different behavioural pathologies was their effect on the so-
called ‘body schema’. This largely underspecified concept has
enjoyed an immense, undeserved, and potentially damaging
popularity. First, the concept has always been very vague.
Second, a large variety of symptoms have been attributed to a
‘disturbance of body schema’ and then used to prove the
validity of the concept. The circularity of this line of reasoning
was first pointed out by Poeck and Orgass (1971), but it took
several years for neuropsychologists to become aware of this
problem and avoid the concept. Serious theorizing about
disorders of bodily awareness and representation must thus be
regarded, with the exception of a few studies, to be the result
of a relatively recent enterprise that has taken place, over the
past 3 decades. This whole matter is dealt with, in detail, in
several recent reviews (e.g. Denes 1989; Semenza 2001).
Quite apart from poor theorizing, the field has also suffered
from inappropriate procedures and a failure to demonstrate
body specificity for the effects emerging from clinical
investigations. These all have seriously hampered traditional
assessment and the theoretical conclusions derived from such
methods. A good example is the request to draw one’s own
body as a method to test a subject’s knowledge and sensory
experience of their ‘body schema’. Typically, such a procedure,
suggested by authorities such as Schilder (1935), ignored the
fact that drawing abilities were spared in all cases.
2 Overview: the variety of pathologies (representation and

awareness)
One reason for the neglect of theory in the field is that the
most significant pathological conditions (Table 12.1) are, in
general, rare and often difficult to spot, especially since most
patients do not spontaneously complain about them.
(p.217)
Table 12.1 Disorders of body representation and

awareness
Autotopagnosia
Somatosensory hallucinations and illusions
Page 2 of 32
Hemisomatagnosia (personal neglect) and related

disorders
Allochiria
Somatoparaphrenia
Extinction of contralesional stimuli to bilateral stimulation
Distal extinction on unilateral double stimulation
Altered muscular proprioception

Proprioceptive deafferentation
Deafferentation after parietal lesions
Alien hand syndrome (including Anarchic Hand)
Phantom limb and related disorders
Body-specific cognitive biases in eating disorders
◆ The clearest example of body-specific representation

disorder is autotopoagnosia, a rare condition where the
patient cannot locate body parts on verbal command. The
neuropsychological instruments used to detect such a
disorder are paradigmatic and were developed from
principled criteria. Consequently, they will be mentioned
first.
◆ Hemisomatoagnosia or personal neglect and related

disorders such as allochiria and extinction of contralesional
stimuli to bilateral tactile stimulation are traditionally
ascribed to malfunctioning of body awareness. Distal
extinction on uni-lateral double stimulation is another
interesting condition with a different clinical meaning. This
group of quite commonly observed disturbances have been
extensively investigated and clinicians can therefore profit
from a large repertory of clinical tools.
◆ The alien hand syndrome, though sometimes overlapping

conceptually with hemisomatoagnosia, is an uncommon
cluster of symptoms wherein involuntary limb movements
are coupled with a sense of estrangement from or of
personification of the limb.
◆ Somatosensory hallucinations and illusions mainly consist

of the experience of a larger, a smaller, or even a duplicated
body. Some patients also report being ‘unable to recognize
their body boundaries’ or their posture. There is no
established assessment for these disorders, most reports
being anecdotal. They will, therefore, not be discussed
Page 3 of 32
here, except for the more common ones, i.e. those

associated with personal neglect that concern the
contralesional side of the body.
◆ The consequences of altered muscular proprioception,

proprioceptive deafferentation, and deafferentation after
parietal lesion will also be described here, although well
reported cases are extremely rare.
◆ Consciousness of missing body parts, i.e. phantom limb

and related phenomena, constitutes a less traditional
domain for neuropsychological investigation, since no (p.
218) direct damage to the brain is involved (despite
considerable reorganization of the cortical representation
of missing body parts). A detailed assessment of these
conditions, rather frequent in amputees, depends on careful
observational and experimental studies.
◆ Finally, body-specific cognitive biases in eating disorders

will be considered. The reason for including this is not that
these problems are treated as ‘body schema’ or ‘body
image’ disorders. However, it has been recently shown that
such biases (basically consisting of misjudgements of size
and weight) can be body-specific. These observations were
derived from, among other things, neuropsychological data.
Theoretically motivated rehabilitation of all the above

disorders has rarely been attempted, except in the case of
personal neglect, and often only in severe cases, where the
condition dramatically interfered with everyday life.
3 Autotopagnosia
Page 4 of 32
Autotopagnosia is the inability to locate body parts in response

to command. The nature of this disturbance is not well
understood in terms of the mental representations and
cognitive processes involved.
The main preoccupation for researchers has been to make

sure that the observed phenomenon is related to experience of
the body. This deficit has to be the primary deficit, i.e. it
should not result from other cognitive disorders. In its
assessment, as in any case of agnosia, other sources of error
should be ruled out. It is therefore important to make sure
that aphasia, attentional deficits (e.g. neglect), visual or tactile
agnosia, apraxia, or reaching disturbances, as well as more
peripheral motor and sensory disorders, cannot explain the
observed inability. Other more subtle and less well known
deficits must equally be ruled out, such as the inability to
isolate parts from a whole—a rare disorder that, in the past,
was thought to be the basis of what seemed, in all other
respects, to be true cases of autotopagnosia (De Renzi and
Scotti 1970)
The term ‘autotopagnosia’ itself is not without problems. As

Gerstman (1942) observed, and as the prefix ‘auto’ implies,
‘autotopagnosia should, in principle, refer to a difficulty in
indicating one’s own body parts and not the body parts of
other persons, of mannequins or drawings of a body’.
Gerstman proposed the term ‘somatotopagnosia’ to include
difficulties with the body parts of others. Indeed, no reported
case has been shown where the difficulty only concerns one’s
own body parts and not also those of other people. Thus, in a
strict sense, pure autotopagnosia has never been described.
The arguably more correct term ‘somatotopagnosia’, however,
was never fully adopted, and ‘autotopagnosia’ remains the
currently used name for the disorder.
A detailed theoretical treatment of autotopagnosia and the

operational tasks used to reveal such a disturbance has never
been attempted. Available empirical evidence, however,
suggests that specific transcoding mechanisms support the
localization of body parts. Various input (verbal, visual, tactile)
and output (motor, verbal) modalities are involved, with or
without the mediation of a body-specific representation in (p.
219) semantic memory. Both spatial and functional
components have been identified as constituents of this
Page 5 of 32
representation (see later in this section), although it is still

unclear as to what proportion these contribute and which
tasks tap which component.
Assessment of the few known cases of autotopagnosia (Table

12.2) has been performed using four specific tasks (Semenza
and Goodglass 1985; Semenza 2001; Semenza and Delazer,
2003) and several control tasks.
3.1 Pointing tasks

The request to point to body parts is the task that originally
uncovered autotopagnosia as a clinical entity, when the subject
showed an inability to carry it out. This task should be
assessed in at least two conditions: a verbal and a nonverbal
one. Failure in the verbal condition only may be attributed to
aphasia (though not necessarily in an uninteresting way: if
found to be specific for the names of body parts, for instance,
a comprehension disorder would be a relatively rare category-
specific aphasia).
Several transcoding subtests, varying in stimulus and

response, are also required in order to:
◆ ascertain whether the symptom concerns parts of one’s

own and also those of other’s bodies (though so far the two
deficits have never been found to dissociate);
◆ be reasonably sure that the problem is not one of

isolating one part within the whole (see later for further
testing).
Table 12.2 Transcoding tasks used in the

assessment of autotopagnosia
Stimulus Example Response
Pointing tasks
Verbal ‘Show me the ear’ Pointing to self

command Pointing to other
person
Pointing to drawing
(full size)
Pointing to drawing
(single parts)
Page 6 of 32
Stimulus Example Response
Nonverbal Examiner touches Pointing to self

command self Pointing to other
Examiner touches person
the patient Pointing to drawing
(who must keep (full size)
the eyes closed) Pointing to drawing
Examiner shows a (cut-out single
picture of isolated parts)
parts
Verification ‘Am I touching the Yes/no (verbal or

tasks ear?’ nonverbal
indication)
Construction From pieces of

tasks puppets, etc.
Description
tasks
Structural ‘Is the nose above

description or below the
mouth?’
‘Is the wrist next
to the forearm?’
Functional ‘What is the nose

description for?’
‘Is the nose for
smelling?’
(p.220) Of particular importance are tests in which the

patient is touched while keeping his/her eyes closed and then
requested to point to the stimulated part on someone else’s
body. The observed difficulty in this task allowed Semenza and
Goodglass (1985) to conclude that authentic, body-specific,
autotopagnosic errors could be detected after left-
hemisphere brain damage.
Classification of the patient’s errors is important and is indeed

necessary to understand the nature of the mental
representation whose disturbance is thought to result in the
problem. Semenza and Goodglass (1985) divided
autotopagnosic errors into three types of categories.
Page 7 of 32
◆ Contiguity (spatial) errors, same limb as stimulus or face–

head response for a face–head stimulus; this group includes
errors that reflect misreaching.
◆ Conceptual errors. Different types of errors are included

under this label: joint for joint, eye–ear–nose substitutions
and contiguity errors where alternative response choices
are presented as cut-out parts in a multiple choice display.
This last type of error is not classified as spatial because it
cannot possibly result from a spatially vague indication. It is
indeed likely to derive from a disorder in the conceptual
representation or in its output.
◆ Random errors include all the remaining.
A prevalence of conceptual or contiguity errors may indicate

the type of autotopagnosia. It has been recently recognized
that, in some of the reported cases (e.g. I.S. in Semenza 1988),
a conceptual component is crucial to the defect, while in other
cases (e.g. patients V.M. and D.A. in Denes et al. 2000) the
spatial component appears to be overwhelming.
A sufficient number of body parts must appear in pointing

tests (Semenza and Goodglass used 18), including parts of the
head, of the limbs, and of the trunk. For special purposes, the
investigator may want to include less prominent parts like
wrists, nails, etc. No dissociation concerning these parts has,
however, been described.
3.2 Verification tasks

Published cases of autotopagnosia have reported patients who
perform this task flawlessly. Thus autotopagnosia does not
affect recognition for body parts but rather affects transcoding
tasks that include pointing to body parts as an output.
Page 8 of 32
3.3 Construction tasks

These tasks require the subject to build up a two- or three-
dimensional body (or just a head; Ogden 1985) from separate
pieces. Typically, autotopagnosics cannot perform these tasks
and tend to miss correct positions. Ogden’s patient, for
instance, put the ears where the eyes should go and vice versa
or put the mouth at the top of the head.
Patients are invariably unhappy with their performance and

appear puzzled on completion. They cannot, however, tell what
exactly is wrong with their construction. While this behaviour
underlines the importance of the spatial component, it also
suggests (p.221) that a functional component must be
disturbed as well. Since simple recognition of single body
parts (as shown in verification tasks) is unaffected, it appears
that knowledge of their exact function, which would allow the
patient, for instance, to spot a hand/foot confusion, is less than
intact.
3.4 Description tasks

These tests are meant to tap knowledge of body parts as
stored in the semantic system. Such tests require at least two
different kinds of description: that of structural attributes and
that of functional attributes. Either questions requiring a
categorical response (yes/no) or more open questions
involving different degrees of difficulty have been used.
Questions implying structural descriptions include:
◆ Is the wrist next to the forearm?
◆ Is the mouth above or below the nose?
◆ Where is the elbow?
Examples of questions implying functional descriptions

include:
◆ Is the mouth for eating?
◆ What is the mouth for?
Unfortunately, no published study of autotopagnosia has

pursued a thorough investigation using these or similar tasks.
Patients seem to be more disturbed on structural items than
on functional ones. An isolated deficit for ‘description’ tasks
has never been reported.
3.5 Control tasks
Page 9 of 32
Body specificity should be the only defining feature of

autotopagnosia. It is thus necessary to collect evidence of the
patient’s ability to locate parts of other complex objects. If the
patient fails also in this task, he/she cannot be considered a
‘genuine’ autotopoagnosic. If the deficit cannot be attributed
to more general problems, such as reaching inabilities, visual
agnosia, etc., it must be attributed to the ‘inability to locate
parts within a whole’, cases of which were described by De
Renzi and Scotti (1970) and by De Renzi and Faglioni (1963)
and never reported since.
A good control task was used in Semenza’s (1988) study. The

patient was asked to locate on verbal command parts of a bike,
a shoe, and a pair of glasses. In a nonverbal condition, the
same parts on the object were first pointed to by the examiner
—the patient had then to point to the equivalent part on a
different object of the same kind, but with a different shape.
For instance the examiner pointed to the heel of a heavy boot
and the patient had to point to the heel of a high-heeled
elegant lady’s shoe. Patient I.S. was flawless in both the verbal
and the nonverbal condition.
Control tasks should also be devised for construction and

description tasks. In the case of ‘construction’ tasks, a
dissociation is unlikely to be found because constructional
apraxia is likely to be a concurrent deficit. The diagnosis of
autotopagnosia thus rests mainly on pointing tasks. Selective
deficits or a selective sparing within semantic (p.222)
memory of bodily knowledge (functional and/or structural)
have never been properly investigated.
4 Personal neglect and related disorders (see Chapter 6)

Unilateral spatial neglect and a number of less frequent but
often associated disorders are a relatively common
consequence of right hemisphere lesions (and, in particular,
stroke). In addition to extrapersonal space and peripersonal
space, unilateral neglect may affect one-half of the patient’s
body. This condition is called personal neglect or
hemisomatagnosia. According to Bisiach and Vallar (2000),
this phenomenon is less frequent than extrasomatic neglect.
Somatic and extrasomatic neglect are usually found in
association, but double dissociations have been observed.
While, however, severe extrasomatic neglect may be found in
many patients where somatic neglect is absent, severe somatic
Page 10 of 32
neglect unaccompanied by neglect of extrasomatic space is

very infrequent (Bisiach et al. 1986; Bisiach and Vallar 2000).
Selective personal neglect mostly occurs after right-sided

lesions. However, neglect of the right personal space may also
be a consequence, in the early phases of the disease (Peru and
Pinna 1997), of a left-sided lesion. Indeed, it often occurs in
the form of paroxysmal symptomatology, most frequently in
the course of epilepsy or migrane (De Renzi 1982). For further
details concerning localization, including symptoms raising
after left-sided lesions, the reader is referred to Bisiach and
Vallar’s (2000) review.
In the absence of relevant primary motor deficits, unilateral

neglect may affect motor functions of contralateral limbs. In
this condition automatic movements may, however, be
relatively preserved.
4.1 Related disorders

4.1.1 Allochiria
Allochiria is a disorder, often associated with unilateral visual
neglect, wherein tactile stimuli delivered to the contralesional
side of somatic (or extrasomatic) space are referred to the
symmetrical location on the ipsilateral side. Less frequently,
analogous phenomena may be observed in the auditory or in
the visual modality (but see Halligan et al. 1995).
Page 11 of 32
4.1.2 Anton–Babinski’s syndrome

A frequently associated disorder is anosognosia for deficits
contralateral to the lesion, known as Anton–Babinski’s
syndrome. While Anton (1899) first noted this condition,
Babinski (1914) recognized it as resulting from a focal cortical
lesion. This disorder may or may not be accompanied by a
generalized anosognosia for illness. This condition has been
observed to double dissociate from somatosensory and motor
neglect (Bisiach et al. 1986; Stone et al. 1993).
Patients who are anosognosic for deficits contralateral to their

lesion may show all degrees of severity, from minimization to
obstinate denial of illness or of possession of the affected limb,
even in the face of demonstrations by the examiners.
Furthermore, (p.223) delusions and confabulation
concerning the affected side may appear (somatoparaphrenias;
Gerstman 1942), a typical instance of which is the attribution
of a plegic limb to the examiner or to other people (Bottini et
al. 2002). Other pathological attitudes include showing
indifference (anosodiaphoria; Babinski 1914), an expression of
dislike for the affected side (misoplegia), and personification,
where affected limbs are spoken about in third person (he,
she, etc.). These delusions may even include the belief that
another person lies permanently on the affected side (Zingerle
1913; Nightingale 1982). This ‘person’ may elicit intense
emotion and even erotic sensations. Concrete examples of
delusions described in the literature are reported in Table
12.3.
4.1.3 Extinction of contralesional stimuli on bilateral stimulation

(or double simultaneous stimulation)
This may be found in patients who can otherwise detect single
contralesional stimuli (Oppenheim 1911; Bender et al. 1948;
Head and Holmes 1911; Denny Brown et al. 1952). This
phenomenon has been reported to occur in the tactile,
auditory, visual, and olfactory modalities. While it equally
affects all modalities, double dissociations have been reported
(De Renzi et al. 1984; Vallar et al. 1994) among modalities and
with personal and extrapersonal neglect.
Table 12.3 Examples of somatoparaphrenic

delusions reported in the literature
Page 12 of 32
◆ ‘[The left side of my body] belongs to a woman lying

beside me’ (Zingerle 1913)
◆ ‘My old left hand began to shrink and a new hand has
emerged, becoming fleshier and more voluminous’ ‘I have
a nest of hands in my bed’ (Ehrenwald 1930)
◆ ‘[This arm] is not mine: I found it in the bathroom, when

I fell. It’s not mine because it’s too heavy; it should be
yours. I can move and do everything; when I feel it too
heavy, I put it on my stomach. It doesn’t hurt me, it’s
kind.’ (Rode et al. 1992)
◆ ‘They took two fingers and joined them back together.

The left hand, it’s cut down the centre, but it still functions
quite well. It’s a nice hand.’
‘It’s difficult … to live with a foot that isn’t yours …. I came
to the conclusion that it was a cow’s foot …. But .I adopted
it.’
My mother has a suitcase and there are at least three
pairs of fingers in there, and they are all functional … we
brought them through the customs. The customs men
were all shocked when they saw these fingers in a box. It
wasn’t conducive to good relations.’
I could never tell why the doctors were so interested in
amputating my arms, or my fingers … or my legs.’ ‘I wake
up with this arm lying in my bed with me … but I
remember the hairs and this nick here, and I realize it’s
my arm. It was a bit strange and disconnected. It had
come loose from its bindings and was covered in blood.
Not a nice thing. Sometimes it goes away … It goes back
to my mother’s suitcase where it belongs ….’
The same patient four years later:

‘A few years ago it was somebody else’s leg, not mine. To
start with, I didn’t think that my left arm and leg were my
own. I thought that the left foot I kept in a box under my
bed … for safe keeping, for later … and that solved the
problem … It’s all very well to laugh at it now, but at the
time it was pretty bloody terrifying, to say the
least.’ (Halligan et al. 1995)
(p.224) Since Zingerle’s (1913) early work, disorders related

to spatial neglect, collectively labelled as dyschiria, have been
viewed as a consequence of a disturbance of the conscious
representation of one side of the body and (though with less
Page 13 of 32
emphasis, as Bisiach and Vallar 2000 have noted) of the

extrapersonal environment. The appeal to the notion of the
body schema as a cue to the understanding of the conditions
(e.g. Brain 1941; Critchley 1953; Gerstman 1942) has been
common in the past and, as Bisiach and Vallar (2000) have
noted, may be considered the basis for Bisiach’s own
representational account (Bisiach and Luzzatti 1978; Bisiach
1995, 1999).
All these phenomena, however, have also been interpreted in

terms of an attentional disorder. Whether attention is involved
per se or as attention to an internal representation is still an
open question (which, to a certain extent, reconciles
attentional and representational interpretation of the
phenomena). As Kinsbourne (1995) argued, if awareness of the
body derived from selective attention to somatosensory input
to various body parts, there would be no need for the ad hoc
construct of a separate ‘body schema’.
Whatever the interpretation, and despite the tradition of its

inclusion in body schema disorders, personal neglect and
related problems seem to say little about the content and the
format of bodily representation—except to prove the
independence of this representation from other
representational contents and to be indicative of an analogous
non-prepositional quality. This disturbance may be viewed as
complementary to phantom limb sensation. Taken together the
two disturbances may indeed be suggestive of a system,
hardwired somewhere in the brain, imparting signals that ‘this
is my body, it is part of me’. One such system is considered by
Melzack (1992) as a component of the ‘neuromatrix’
responsible for phantom sensations.
4.2 Clinical assessment

Patients with personal neglect may show the condition in
various degrees of severity. Sometimes only a careful
neuropsychological examination may detect the phenomenon.
In other cases the presentation is more dramatic. The patient
may be unable to dress properly, leaving one-half of the body
unclothed, and showing signs of personal care only on one
side, leaving the contralateral side very untidy. Proper
assessment should contain at least a checklist of these
behavioural anomalies related to body usage.
Page 14 of 32
◆ When not so severe, the presence of personal neglect may

be assessed by asking patients to touch contralesional body
parts using the unaffected ipsilateral hand, or through tasks
involving the patient’s body, such as using a comb. Light
touches or even pinprick stimulation of the afferent side
may also be used. Patients may still deny pinprick
stimulation while showing movements aimed at avoiding it.
◆ Motor neglect may be assessed (Bisiach and Vallar 2000)

by requiring the patients to extend their hands or to
squeeze the examiner’s fingers placed within the palms of
their hands. Motor neglect may vanish if the patient is
invited to attend the neglected limb or is actively prevented
from moving the non-neglected one.
◆ In order to systematically assess personal neglect,

Cocchini et al. (2001) recently developed the Fluff Test. This
test requires subjects to remove white cardboard circles
(p.225) (2 cm in diameter) attached by velcro, at regular
intervals, located to the front of their clothes. These
stickers are distributed, on both the right and the left side,
along the central body areas, the legs, and the arm that is
not performing the task. The subject sits blindfolded whilst
the circles are attached. Still blindfolded they are asked to
remove all the stickers. The percentage of targets detached
from each side is then calculated. Normative data are
available.
Somewhat surprisingly, Cocchini et al. (2001) found no

correlation and a double dissociation of the Fluff Test with the
Comb and Razor/Compact Test (Beschin and Robertson 1997),
a test requiring exploration of the face area. Their
interpretation for this dissociation is still speculative. Further
research is required to clarify this issue as well as the role of
motor neglect in failing the test.
◆ Self-evaluation tests (Marcel and Tegner 1994; Berti et al.

1996) and structured interviews (e.g. Cutting 1978) that
require the patient to carefully describe their problem may
be useful in cases of anosognosia and somatoparaphrenia.
Patients affected by these disorders may show dissociations
in verbal reports on their abilities. They may consistently
exhibit the belief that their affected limbs are perfectly
functioning while showing, in contrast, a realistic self-
evaluation. For example Berti et al.’s (1998) patient, C.C.,
Page 15 of 32
assigned a score of 2/10 to her own ability to lift a glass

with her left hand but, at the same time, claimed that she
could perform the task perfectly.
As Halligan et al. (1995) pointed out, it is of the utmost

importance to elicit full accounts of what such patients believe
their condition to be. Such irrationalities may be important
cues to the patients’ mental contents. The evolution of
symptoms over time may also be revealing. Halligan et al.
(1995), reporting detailed abstracts of subsequent interviews
with a somatoparaphrenic patient, showed how most
symptoms could be interpreted as a delusional way of coping
with new, unfamiliar sensations.
◆ Extinction is generally assessed by symmetrically

presenting two identical stimuli at the same time. However
(Critchley 1953), the phenomenon may appear even with
different and asymmetrical stimulation (see, for instance,
the ‘face–hand test’; Fink and Bender 1952). Sometimes the
contralesional stimulus is not entirely neglected, but just
misperceived. Different types of material have been also
used. Schwartz and co-workers (1979) used the Quality
Extinction Test, which consisted of two sets of various
common materials such as sandpaper, tin foil, velvet, etc.
One set consisted of test items each of which was made
entirely of the same material (‘whole items’) while the other
consisted of items made up of two different materials side-
by-side (‘half and half items’). In the test, each item is
brushed against the subject’s fingers so that both hands are
stimulated simultaneously. Stimulation with the ‘half-and-
half’ is arranged so that a different material stimulates
each hand at the same time. An ‘extinction’ trial is recorded
if the subject names only one when in fact two have been
presented. The total score is derived by subtracting the
number of omissions made by the other hand and
converting the difference into a percentage. Errors in
naming are not scored.
(p.226) 4.3 Rehabilitation (see Chapter 6)
Patients with severe and persisting unilateral neglect are
seriously handicapped in everyday life and rehabilitation
should therefore be attempted as soon as possible. Neglect is
not only handicapping, but it has been demonstrated (Denes et
al. 1982) to interfere in general rehabilitation. A major
Page 16 of 32
obstacle to rehabilitation efforts is the frequent co-occurrence

of anosognosia.
Rehabilitation of unilateral neglect has been attempted with

different techniques and different success (see Zoccolotti
1999; and Robertson and Halligan 1999 for comprehensive
reviews). They mostly consist of repeated lateralized
stimulation to the affected side and, in general, employ a
series of sensory suggestions orientating or anchoring the
patient’s attention to the side of the target stimuli.
Visual stimuli have been most frequently used but

somatosensory-proprioceptile and vestibular stimulation has
also been employed with some improvement. Vestibular
stimulation, in particular (Rubens 1985; Cappa et al. 1987;
Vallar et al. 1990; Bisiach et al. 1991; Rode et al. 1992), has
been shown to temporarily reduce remission of unilateral
neglect phenomena, including somatoparaphrenic delusions
and even associated motor deficits.
Most current attempts are made on patients affected by both

personal and extrapersonal neglect, without clear efforts to
distinguish the two conditions. Positive results are (with some
notable exceptions, e.g. Halligan et al. 1992) generally
reported. The effects of treatment have been shown to surpass
those of spontaneous recovery, to be specific for neglect, to be
stable over time after dismissal, and to extend to tasks not
involved in treatment, at least when rehabilitation is
protracted enough (Antonucci et al. 1995; see Chapter 6, this
volume).
4.4 Distal extinction to unilateral double tactile stimulation

Patients may show extinction of the distal stimulus on
unilateral tactile double stimulation (Denny Brown et al. 1952;
Bender et al. 1948). This phenomenon is relatively little
known, although it has been considered an early sign of
diffuse brain damage (e.g. dementia). Cohn (1951), however,
described it as a common finding in 3–5-year-old normal
children. Typically, subjects are stimulated on the face and on
the hand, the face stimulus being invariably the one resistant
to the extinction. Other locations (e.g. shoulder and hand) may
be chosen and a rostral dominance is invaed, the foot will be
dominant (Bender et al. 1948).
5 Alien hand syndrome (see Chapter 20)
Page 17 of 32
The alien hand syndrome is a loosely defined cluster of

symptoms, characterized by involuntary movements of a limb
in conjunction with an experience of estrangement from and
personification of the limb itself (see Blakemore et al. (2002)).
The limb is perceived as having a will of its own, though
ownership is seldom denied. While the syndrome concerns
upper limbs, it may affect the legs.
(p.227) The underlying pathology involves lesions of two

types.
◆ In the anterior type, the damage is either to the left

frontal lobe and to the anterior corpus callosum or to the
corpus callosum alone. In the first case the right, dominant
limb is affected, while in the second case the
symptomatology is found in the left limb.
◆ In the less frequent, posterior type, the damage consists

of corticobasal degeneration or, in a few cases, of posterior
vascular damage. The anatomical substrate is the parietal
and posterofrontal cortex and the corresponding
subcortical areas, bilaterally. Recently, however, Martì-
Fabregas et al. (2000) have described a patient with a
vascular lesion limited to the right parietal lobe. Generally,
if not exclusively, posterior cases have been found to involve
the nondominant limbs.
The clinical presentation includes several phenomena. The

following is taken from Fisher (2000).
◆ Failure to identify an upper limb as one’s own on

palpating it behind the back or with the eyes closed. As
Fisher (2000) observes, this was the original definition.
◆ Movement of a limb that the patient regards as foreign,

unwilled, strange, uncooperative. The limb seems to act on
its own, outside the patient’s control. It may actively
contradict the other limb (see Della Sala et al. (1991)).
◆ Stereotyped ‘reflex’ motor activity of the ‘frontal’ type:

reaching out, groping and grasping with inability to release,
utilization behaviour, tactile and visual oral reactions.
◆ Other: withdrawal of a limb; flinging movement of optico-

sensory ataxia.
Page 18 of 32
Alien hand symptoms following corticobasal lesions may be

distinguished insofar as involuntary movements are typically
non-purposeful and non-conflictual, and include such
behaviours as arm levitation and finger-writhing (Bundick and
Spinella 2000). The corticobasal, posterior variety, therefore,
does not include ‘frontal’ symptoms.
Patients with alien hand are usually alert, cooperative,

interested, and aware of the movements requested. Their
reaction to their symptomatology varies from frustration and
torment to amusement. Concrete examples of alien hand
behaviour described in literature are provided in Table 12.4.
6 Altered muscular proprioception

The role of muscular proprioception and its contribution to
bodily representation emerges from observations of patients
suffering from proprioceptive deafferentation due to
peripheral pathologies and deafferentation due to central
lesions. These patients are extremely rare and no routine
clinical assessment is available. However, existing detailed
descriptions of the phenomenon suggest the framework for
proper testing procedures (Cole and Paillard 1995; Paillard et
al. 1983).
One type of patient has been observed with a very selective

and complete loss of large sensory fibres, while motor and
small sensory fibres are left intact. Muscular proprioception
(p.228)
Table 12.4 Examples of alien hand behaviour
◆ [On order to pick an object with the right hand] Picking

the object, the right hand approaches it and pauses, the
left hand comes over to approach the object, and then
both hands pick the object (left hemisphere infarction;
Liepmann 1900).
◆ Put on clothes with the right hand and pull them off
with the left hand.
Open a drawer or a door with the right hand and

simultaneously push it shut with the left hand. Dry the
clean dishes and then put them back in the pan to be
washed again.
Page 19 of 32
When thirsty fill a glass with water and then pour it out
(following callosotomy; Akelaitis 1945).
◆ Inability, on verbal command, to place the left hand

behind the head or to use it to point to something.
Reaching across with the right hand to grab the left

hand and place it in proper position (following
callosotomy; Gazzaniga et al. 1962).
◆ Failure to recognize as one’s own one of the hands,

usually the left, when the hands were out of sight
(callosal tumour; Brion and Jedynak 1972).
◆ Hands fighting each other: holding an envelope, each

hand independently and simultaneously tries to hold
and to release it, tugging at it, sometimes for as long as
10 minutes (anterior cerebral artery infarction; Watson
and Heilman 1983).
◆ The right hand pays for an item in a store, the left hand
withdraws the money; while purchasing something else
the left hand picks up an orange (ruptured anterior
cerebral artery; Papagno and Marsile 1995).
◆ While the left hand takes food to the mouth with the
fork, the right hand brings the knife towards the eye
with the risk of injury (corticobasal degeneration;
Lhermitte et al. 1925).
◆ The left hand has a tendency to levitation and the

fingers wander ‘like the tentacles of an
anemone’ (corticobasal degeneration; Gibb et al. 1989).
is lost but vestibular information as well as the senses of pain and

temperature is retained.
These patients express the feeling of using their bodies as
tools, relying heavily on visual feedback, concentration, and
intellectual effort. Motor automatism is apparent to them. If
their vision is precluded, their ability to preshape the grip
posture to the size and shape of a target would be absent.
On clinical examination, these patients may be asked, when

blindfolded, to point to a part of their skin where a thermal
stimulus (which they perceive) had been delivered. They could
not carry out such a task. In dramatic contrast, however, they
Page 20 of 32
would be able to verbally designate the point (‘over my elbow’)

and later to show it precisely on the picture of a human body.
Patients with parietal lesions may suffer from deafferentation

of a body area. For instance, in the case reported by Paillard et
al. (1983), a parietal lesion provoked deafferentation of the
forearm. The patient was unable, when blindfolded, to detect
the presence of a tactile stimulus on the affected area, but was
surprisingly able to indicate the place of stimulation with the
other hand. Paillard et al. considered this phenomenon to be
the equivalent of blindsight in the tactile modality.
(p.229) 7 Phantom limb and related phenomena
Page 21 of 32
Most amputees experience the continued existence of the

amputated limb or body part. Detailed descriptions of all
aspects of this phenomenon, including the history of condition,
may be found in Ramachandran and Hirstein (1998),
Ramachandran and Rogers Ramachandran (2000), Semenza
(2001) and Halligan (2002). This chapter is only concerned
with clinical assessment and attempts at rehabilitation.
Phantoms involve not only limbs but also other body parts
such as breasts, male genitalia, or facial parts like the jaw.
Amputation is not essential for the occurrence of such
phantoms. They have been reported in conditions such as
brachial plexus avulsion, spinal cord damage, and even single
spinal anaesthesia. Even patients with congenital absence of
limbs experience phantoms.
Phantom sensations are spontaneous but may also be evoked

with appropriate stimulation not only of the stump but also of
distant body areas. For instance, the stimulation of the
ipsilateral side of the face may evoke sensations in phantom
hands (e.g. Halligan et al. (1993) and Halligan et al. 1999).
Referred sensations are often topographically organized and
may be modality-specific. Thus, for example, hot, cold,
vibration, rubbing, metal, or massage are felt as hot, cold,
vibration, rubbing, metal, or massage at precisely localized
points of the phantom limb. Such sensations can occur even
hours after amputation.
A thorough interview should be carried on to assess phantom

limb phenomena, considering all the main factors
characterizing phantoms. (see Fraser, Halligan, Robertson and
Kirker 2001) Phantom sensations seem to vary considerably in
their intensity and veridicality. The size and form of missing
parts may change over time. The vividness of the phantom
sensation is typically enhanced by imaginary tasks performed
with the phantom limb. The phantom may change in form or
disappear in consequence of particular movements, e.g.
bringing the stump near to a wall. Absent limbs seem to
coordinate with the rest of the body in movement.
Patients may be able to provide a correct evaluation of the

size, length, and weight of the missing part; in other cases the
missing part may be perceived as shortened or in a bizarre,
anatomically impossible position. ‘Islands’ of phantom
sensation may be all the patient feels, e.g. phantom hands may
Page 22 of 32
be felt as suspended in mid-air. A common distinctive

phenomenon that occurs over time is ‘telescoping’—a phantom
may gradually retract in such a way that, in the end,
peripheral parts seem to join to the stump.
Pain is the most typical feature of phantom sensation and

occurs in approximately 70% of cases. When severe it is
described as burning, cramping, or shooting. Complex
sensations may also accompany phantoms—patients with
lower cord injury may report the sensation of defecation;
phantom penises experience ejaculation.
A less frequent and less known phenomenon is the felt

presence of and hallucinatory belief in the real existence of
supernumerary body parts. Such a condition may
paradoxically coexist with denial of hemiplegia and feeling of
nonbelonging of the contralesional limb (Halligan et al. 1993).
(p.230) 7.1 Rehabilitation attempts

Phantom limb phenomena appear dependent on neural
reorganization after amputation or the equivalent (besides
already indicated references, see, on this point, Karl et al.
2001).
On the basis of findings that phantom limb pain is closely

associated with plastic changes in the primary somatosensory
cortex and on animal data that show that behaviourally
relevant training alters the cortical map, Flor et al. (2001),
have recently devised a sensory discrimination training
programme for patients with intractable phantom limb pain.
The programme consists of 10 daily 90-minute sessions of
feedback-guided sensory training, in which patients have to
discriminate the frequency or the location of high-intensity
nonpainful electric stimuli applied in a random fashion
through electrodes attached to their stump. After this training,
patients showed a significant improvement in discriminating
both the location and the frequency of the stimuli as well as a
significant reduction of pain.
Ramachandran and Rogers-Ramachandran (1996) required

phantom limb patients to look at the reflection of their intact
hand mirror-reflected on the felt location of their phantom
hand. The patients were thus able, while moving the intact
hand, to receive visual feedback that the phantom hand was
obeying commands. A number of patients appeared to benefit
Page 23 of 32
from repeated use of such procedures, in that they were

relieved of spasms and cramps, with elimination of associated
pain.
8 Body-specific cognitive biases in eating disorders

Mental anorexia and bulimia have been considered to be
disorders of body schema. Modern investigators, however,
quite rightly believe (see a review by Hsu and Sobkiewic 1991)
that this ida is unfounded. Nonetheless subjects affected by
eating disorders have been shown to be unable to correctly
judge the size of their bodies. This problem is nowadays
attributed to a ‘cognitive bias’ that is thought to commonly
accompany eating disorders (Thompson 1990).
Typically, patients with eating disorders have been found to

misjudge hip-to-hip, armpit-to-armpit, and cheekbone-to-
cheekbone distances or the size of the waist. Waist size and
hip-to-hip distance seem the most likely to be grossly
misjudged.
Despite the variety of detection techniques, surprisingly little

has been done so far to ascertain with proper control
conditions whether misjudgement of size is indeed body-
specific as has been always assumed. A few investigations (e.g.
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misjudgements are body-specific, the choice of measures is far
from being satisfactory, since in most investigations control
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Comparisons between different types of anorexia and bulimia
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No routine clinical instruments are, therefore, available for

evaluating cognitivebiases in eating disorders. Ideally,
however, their proper assessment should take into
consideration the above observations.
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The assessment of acquired spoken language disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The assessment of acquired spoken

language disorders
Claus-W. Wallesch
Helga Johannsen-Horbach
Gerhard Blanken
DOI:10.1093/acprof:oso/9780199234110.003.13

The acquired language and speech disorders comprise
aphasia, speech apraxia, dysarthria, and language
impairments in dementia and confusional states. This chapter
considers the first three conditions.
Keywords: comprise aphasia, speech apraxia, dysarthria, speech disorders
1 Introduction
The acquired language and speech disorders comprise
aphasia, speech apraxia, dysarthria, and language
impairments in dementia and confusional states. Only the first
three conditions will be considered here.
1.1 Definitions
Page 1 of 25
1.1.1 Aphasia
The aphasias are disorders of language processing resulting
from acquired focal brain pathology. The underlying pathology
affects the cerebral representations of linguistic rules and
language-specific information. In most instances, aphasia is a
supramodal deficit (i.e. both language production and
perception, both spoken and written, are affected). However,
due to the existence of cognitive pathways that only subserve
written, but not spoken language, written language disorders
will be treated separately (see Chapter 17). Also, disorders of
written language processing may occur in the absence of
aphasia (e.g. in pure alexia or neglect dyslexia). In its strict
use, the term ‘aphasia’ is reserved for patients who suffer from
circumscribed pathology, and in whom language dysfunction
constitutes a focus of cognitive impairment. (Therefore, the
frequent and characteristic language impairment with
dementia of the Alzheimer type would only be termed aphasia
in the broader sense.)
The aphasias affect the cerebral representation of a developed

language system. They are therefore separated from disorders
of language acquisition (‘developmental dysphasia’). (The term
‘childhood aphasia’ is restricted to the effects of brain damage
upon language functions that had been acquired previously.)
1.1.2 Speech apraxia

The existence and definition of speech apraxia have been
intensely debated. Today a majority of researchers and
clinicians accept its existence and Darley’s definition:
‘An articulatory disorder resulting from impairment, as a result
of brain damage, of the capacity to program the positioning of
speech musculature and the sequencing of muscle (p.236)
movements for the volitional production of phonemes. No
significant weakness, slowness, or incoordination in reflex and
automatic acts.’ (Darley, 1969, cited Rosenbek, 1993). Speech
apraxia very rarely occurs in isolation; usually it is combined
with Broca’s or global aphasia (see Chapter 15).
Page 2 of 25
1.1.3 Dysarthria
The term ‘dysarthria’ is used to describe the effects of a
sensorimotor disorder resulting from neurological pathology
on respiratory, phonatory and articulatory functions involved
in speech sound production. It has been argued that
‘dysarthrophonia’ or even ‘dysarthrophonopneumia’ may be
terminologically more adequate, but these terms have not
found entrance into clinical use. Dysarthria may co-occur with
aphasia, especially acute nonfluent, Broca’s, and global
aphasia.
2 Aphasia
2.1 Epidemiology
Aphasia is a common symptom of cerebral disease with an
incidence of about 1/1000 (not including transient aphasia as a
symptom of TIA), and a prevalence of about 2/1000. Its most
frequent cause is ischemic infarction in the territory of supply
of the left middle cerebral artery (about 75%). Other causes
are hemorrhage, tumor, trauma, infarctions in other
territories, cerebral infections (herpes encephalitis), and
circumscribed atrophic pathology.
2.2 Symptoms of aphasia

Clinically and in aphasia test batteries, the analysis and
description of an aphasic patient’s language performance is
based on two types of observations:
◆ the analysis of his/her linguistic and communicative

performance in conversation,
◆ the comparison of linguistic proficiency across modalities

using tasks such as repetition, oral and written naming,
writing to dictation, reading aloud, speech and script
comprehension.
2.2.1 Spontaneous speech

In spontaneous speech, deficits and errors are analyzed on the
levels of phonology, lexicon/semantics and syntax. Other
important dimensions are the fluency of language production
and the presence of repetitive speech. Usually, the accuracy
and speed of articulation and prosodic features are also
described. For a glossary of neurolinguistic terminology, see
Table 13.1.
Page 3 of 25
The phonological structure of an utterance includes the

appropriateness of phoneme selection and combination in
order to form the sound structure of words. Impairment of
phoneme production as such is not an aphasic symptom but
would indicate the presence of dysarthria or speech apraxia
(whether the interface between linguistic and sensorimotor
processes can be defined so rigidly, is being intensively
debated). (p.237)
Table 13.1 Glossary of aphasic symptoms
Speech the automatic and compulsive production

Automatism of the same phrase, word, neologism,
syllable or sound, contrary to intention
Agrammatism reduction of grammatical elem ents, such

as inflections and function words (e.g.
prepositions)
Echolalia repetition of utterances of the

communication partner, frequently with
adequate changes denoting the speaker
(‘How are you?’– ‘How am I?’).
Jargon, phonemic paraphasia occurs to an extent

phonemic or that speech is
neologistic incomprehensible
Jargon, semantic paraphasia occurs to an extent

semantic that speech is
incomprehensible
Neologism, a word is incomprehensible because of

phonemic phonemic paraphasia
Paraphasia, substitution, omission, addition, or

phonemic perseveration of a phoneme or error of
phoneme sequence
Paraphasia, substitution of a presumably intended

verbal word by another
Paraphasia, substitution of a presumably intended

semantic word by a meaning related one
Perseveration the recurrent production of a previous

response out of context
Page 4 of 25
Stereotypy the repetitive and stereotyped use of a

communicatively acceptable word or
phrase without propositional meaning
(e.g. ‘yes’, ‘my God’, ‘I don’t know’, ‘such
is life’) in the position of a pause
The phonological structure of a word may be altered by omissions,

substitutions, the addition of phonemes, errors of sequence and
perseverations. Some aphasics strenuously attempt to correct their
phonological output, be it comprehensible or not. Both
the production of phonemic paraphasias and disorders of output
monitoring and correction may result in the characteristic
behaviours of ‘conduite d’approche’ and ‘conduite d’écart’, (i.e.
approximations and digressions from the target: e.g. trurtle – tertle
– turtle – trullet (naming a turtle)). Words that are phonemically so
distorted that they are incomprehensible, are termed ‘phonemic
neologisms’. The term ‘phonemic or neologistic jargon’ is used,
when the patient‘s speech is incomprehensible because of
phonemic paraphasia.
The analysis of lexical and semantic structure includes the
processes of word access, word selection and the
differentiation of word meanings. Impaired word-finding is a
symptom of all types of aphasia, but also of more diffuse
pathology such as dementia and impaired consciousness. It
may also occur in normal speakers, especially under stress,
distraction, fatigue and intoxication. Word finding difficulties
may manifest themselves as pauses, in the use of
circumlocutions, or in the discontinuation of the phrase. The
term ‘verbal paraphasia’ describes the incorrect use of a word.
Verbal paraphasias can be related to the target by meaning
similarity, form similarity, or both. Also (seemingly) unrelated
verbal paraphasias can occur. Usually meaning related errors
(‘semantic paraphasias’) form the most frequent type of word
substitution. Semantic paraphasias typically stem from the
target`s semantic category (e.g. ‘bus’ for ‘lorry’ – close
semantic (p.238) paraphasia), or can be otherwise
semantically associated (by situation, function etc.).
If productions are rendered incomprehensible by semantic
paraphasia, the term ‘semantic jargon’ is used.
Traditionally, syntactic errors in aphasia are classified as

‘agrammatic’ and ‘paragrammatic’. Because pathological
stereotypies may be grammatically appropriate, the analysis of
the use of syntax is based only on newly created propositional
utterances. An error is classified as agrammatic when a
necessary grammatical element, such as a bound inflectional
Page 5 of 25
morpheme, a function word, or an auxiliary verb in a complex

verb phrase is missing. In severe cases of agrammatism, the
patient almost exclusively uses nouns, verbs in the infinite
form such as the present and past participles, adjectives and
adverbs. Function words, such as prepositions, and inflections
are greatly reduced or lacking. In paragrammatism,
grammatical rules are applied. Patients inflect nouns and
verbs and use function words, but their speech deviates from
the grammatical norm. Sentence structures are typically long
and complex. Sentence boundaries may become obscured
(‘when I came home is my favourite place’).
Fluency and nonfluency (Kertesz, 1979) denote two prototypes

of aphasic patients:
◆ the nonfluent aphasic struggles with every word and

gives the impression of great effort required for speech
production;
◆ the fluent aphasic exhibits little or no effort but usually

produces many empty phrases or many paraphasic errors.
The fluency/nonfluency dimension is especially helpful for the

description of acute aphasia.
There are various types of repetitive speech that may occur in

aphasic language productions. The most common are speech
automatism (recurring utterances), echolalia, perseveration
and stereotypy (for definitions, see Table 13.1). From a clinical
point of view, it is important to note that speech automatisms
almost exclusively occur in aphasia, whereas echolalia,
perseveration and stereotypy also occur with non-aphasic
brain pathology and even in non brain-damaged persons (cf.
Wallesch, 1990).
2.4 Performance in language modalities

Although it is a great simplification in view of neural networks,
the Wernicke (1874) - Lichtheim (1885) model (Fig. 13.1) has
had a great influence upon aphasiology. In this model,
(spoken) language is processed by three interconnected
components: a sensory center for auditory word forms, a
center for speech-motor word forms, and a (semantic) concept
center. Wernicke did not localize the concept center in a
circumscribed brain region, but assumed its representation in
the interconnection of various association areas. The assumed
connection between the sensory and the motor speech centers
Page 6 of 25
provided the ability to repeat without semantic analysis, and

also control and monitoring of speech output. The link
between sensory and concept center, was necessary for
comprehension, and that between concept and motor speech
center for naming. With the exception of the concept center, a
parallel (or subordinate construction) was hypothesized for
written language processing. On the historical basis of the
Wernicke-Lichtheim model, (p.239)
Table 13.2 Error types in visual confrontation

naming and their functional basis (based on
Linebaugh, 1990)
Type Functional basis
Delayed naming slowed activation or selection of lexical

target
Self-correction recognition of error
Circumlocution failure to retrieve lexical target,

alternative production of semantic
information
Near semantic retrieval of a lexical entry semantically

paraphasia related to the target
Unrelated word failure to access appropriate target
Visually related error in visual object analysis

word
Perseveration failure to inhibit a previous response
Gesture compensation for failure to retrieve

lexical target
No response
the vast majority of aphasia assessment batteries include the tasks

of repetition, naming, and comprehension, in most instances both
at the word and the sentence level.
Table 13.2 summarizes error types in visual confrontation
naming. For neurolinguistic analysis, naming has the
advantage that the lexical target is known and errors can be
more easily analyzed linguistically than in spontaneous
speech. Naming contains fewer degrees of freedom than
spontaneous speech. Therefore, some aphasics may find
naming comparatively easy. On the other hand, in most
naming situations, only one response is appropriate. Aphasics
Page 7 of 25
with prominent disturbances of word access (e.g. with anomic

aphasia) may be particularly impaired in naming (e.g. ‘I cannot
tell its name, but we have similar chairs at home’). Some
patients have a specific impairment of visual object naming as
compared to naming with other presentation modalities. This
condition is called ‘optic aphasia’ (Coslett and Saffran, 1989).
Its functional basis is a disconnection of the language region
from the visual association cortex as it may occur with
posterior watershed infarctions. These patients can easily be
identified by their ability to produce names in response to
questions (e.g. ‘what do you open a lock with?’).
In repetition, semantic and lexical search processes are

usually not critically involved. Some patients however, may
have to rely on a semantic route in this task (Katz and
(p.240)
Goodglass,
1990); they
cannot repeat
nonwords
(phoneme
sequences that
do not
constitute a
meaningful
word in the Fig. 13.1 The Wernicke-Lichtheim model.
respective
language). The
assessment of repetition should include stimuli of varying length,
and lexical as well as nonlexical items. A focal deficit of repetition
may indicate a deficit of auditory-verbal short term memory; an
impairment of the memory for sequence, or of the transformation of
a phonological representation into a phonetic string. The latter
explanation is similar to the anatomical assumption of a
disconnection between receptive and expressive speech areas to
account for repetition deficits (Geschwind, 1965).
Intactness or only mild impairment of spoken language
comprehension is often wrongly assumed in aphasic patients,
as the patient may make use of situational cues. In formal
assessment, forced choice decision tasks are often easier for
the patient than those that demand production, both with
respect to linguistic and neuropsychological processing
demands (Wallesch and Kertesz, 1993). To compensate for this
effect, aphasia test batteries such as the Boston Diagnostic
Page 8 of 25
Aphasia Examination (Goodglass and Kaplan, 1972), the

Western Aphasia Battery (Kertesz, 1979), or the Aachen
Aphasia Test (Huber et al., 1983/1984) use norms derived from
aphasic patients to assign scaled scores or values.
2.5 Syndromes of aphasia

The term ‘syndrome’ denotes the statistical co-occurrence of a
cluster of symptoms. It is not imperative that all symptoms of a
syndrome be present in a given patient. The statistical cluster
is supposed to indicate an underlying cause of the various
symptoms. Poeck (1983) pointed out that the underlying
pathophysiological basis of the aphasia syndromes may rather
be the vascular anatomy of the cerebral language
representations rather than ‘natural’ linguistic structures.
Statistical cluster analysis reveals that most (about 70 to 80%)

of aphasic patients are grouped together and that these
clusters relate to the clinical syndromes of acute and chronic
aphasia (Kertesz, 1979, Huber et al., 1983, Wallesch et al.,
1992). Generally, patients with non-ischemic aphasia
syndromes correspond much less both to the clusters and
clinical syndromes of chronic aphasia than do patients with
ischemic stroke.
To increase confusion even further, a number of different

classification systems are used. These can be grouped into
three types:
◆ modality – oriented: Syndromes are distinguished on the

basis of assumed dissociations across modalities, resulting
in categories such as ‘motor’/‘sensory’ or
‘expressive’/‘receptive’. Recent examples are the
classification systems of Goodglass and Kaplan (1972), and
Kertesz (1979).
◆ Anatomically-oriented with syndromes such as ‘anterior’

vs. ‘posterior’ (Benson, 1967). Often, atypical aphasia
syndromes are denoted by anatomical terms, e.g.
‘subcortical’ or ‘thalamic’ aphasia.
◆ According to the linguistic deficit. A very simple

classification into ‘fluent’ and ‘nonfluent’ aphasia (Benson,
1967) is based upon speed of production and phrase length.
The classification system described in more detail below is
Page 9 of 25
based on cluster analyses of the results of aphasia tests,

and therefore on the linguistic deficit. (p.241)
Table 13.3 Differences between acute and

chronic vascular aphasia
acute chronic
Time post onset few weeks many months
Pathophysiology penumbra and cerebral

diaschisis enlarges reorganisation
functional lesion reduces functional
deficit
Neuropsychology additional compensation,

disorders of reorganisation
consciousness,
attention
and awareness
Psychology distress coping
Social role illness handicap
The syndromes of acute and chronic aphasia will be treated

separately. Obviously, there is no dichotomous distinction. However,
acute aphasia (i.e. aphasia syndromes seen in the acute hospital),
differs in many ways from chronic aphasia, seen in rehabilitation
and afterwards (Table 13.3). These differences explain the
syndromatic instability of some types of acute aphasia.
2.5.1 Syndromes of acute aphasia
Patients suffering from acute aphasia present symptoms of
acute focal pathology in combination with the effects of diffuse
cerebral dysfunction (Table 13.3), such as reduced
consciousness, attentional impairment and rapid fluctuations
in performance. The deficits preclude detailed linguistic and
neuropsychological assessment. Kertesz (1979) and Wallesch
et al. (1992) analyzed groups of patients 3 to 6 weeks after
onset of aphasia by means of cluster analysis. The results of
both studies converge with respect to syndromes of acute
aphasia by finding clusters of
1 mild aphasia with prominent word-finding difficulty,

2 mild aphasia with prominent comprehension deficit,
3 moderate aphasia with prominent repetition
impairment (‘acute condution aphasia’),
Page 10 of 25
4 marked aphasia with preserved repetition (‘acute

transcortical motor aphasia’),
5 severe aphasia with preserved comprehension,
6 severe aphasia with deficits in all modalities.
Clusters 1) and 2) are usually fluent, 4) 5) and 6), nonfluent.

Type 3) is fluent in stereotypies and mainly nonfluent in
propositional utterances and repetition (‘acute conduction
aphasia’). A development towards chronic Wernicke’s aphasia
occurred in clusters 3) and 5), but not in 2) (Wallesch et al.,
1992). A large number of patients from cluster 6) develop
Broca’s aphasia, and most patients from cluster 5) become
anomic (Kertesz, 1984). The frequency of a change of
symptomatology (‘Syndromwandel’) speaks against the use of
the terminology of chronic aphasia syndromes in the acute
stage.
Notwithstanding, Pedersen et al. (2004) applied the Western

Aphasia Battery (Kertesz 1982) to 270 consecutive clinically
aphasic patients within the first week after stroke and (p.
242)
Page 11 of 25
Table 13.4 Change in type of aphasia from first week to one year follow-up in survivors (data from Pedersen et al.
2004)
At follow-up Global Broca’s Wernicke’s Transcort. Conduction Anomic No aphasia

Motor
Within first
week:
Global 22% 35% 7% 22% 15%
Broca’s 18% 9% 36% 36%
Wernicke’s 18% 36% 27% 18%
Transcort. 17% 83%

Sensory
Conduction 14% 14% 71%
Anomic 38% 62%
Page 12 of 25
also the battery’s scoring system that forcibly assigns each patient
to an aphasic syndrom. Table 13.4 shows that there were great
changes in syndrome allocation between first week and one-year
follow-up. Each aphasia syndrome encountered during the first
week was compatible with full recovery. Except for those classified
as global within the first week, a majority of each other syndrome
recovered fully or changed into anomic aphasia within one year
post stroke.
Among the acute aphasias, one may encounter syndromes that
do not occur in the chronic stage. One of these is acute
phonemic paraphasia with sometimes largely
preserved comprehension, which is a rare but not unusual
finding with subcortical infarctions involving the ventrolateral
(Wallesch, 1997) or anteromedian (Carrera et al., 2004)
thalamus. Language disorders resulting from thalamic lesions
are often confounded by perseveration and fluctuating
impairments of attention and consciousness that are
particularly frequent with lesions of the nonspecific thalamic
nuclei. Acute semantic paraphasia with variable degrees of
comprehension deficit have been described with lesions of the
left head of caudate and anterior limb of the internal capsule
(for a review, see Wallesch, 1997). The underlying
pathophysiology has been related to the lesion of
thalamocortical projections involved in gating the processing
of multiple lexical choices.
In the first hours and day after stroke or trauma, many

patients are mute. Neurological mutism can result from
aphasia, but also from severe apraxia, paresis, akinesia or
disorders of attention or motivation. An analysis of nonverbal
communication and comprehension may guide the initial
differential diagnosis.
2.5.2 Syndromes of chronic vascular aphasia

As has been pointed out, the classical aphasia syndromes
describe best the symptomatology of stroke patients who have
suffered a functional deficit due to a circumscribed lesion at
one point in time and who have developed adaptive and
maladaptive compensatory strategies consequently.
(p.243) Global aphasia
The term ‘global’ denotes that all language processes are

severely affected. Propositional language is either almost
absent, or reduced to single words or phrase fragments and is
produced with great effort. Few stereotyped phrases may be
Page 13 of 25
preserved and used adequately in some situations. A subgroup

of patients are able to produce highly overlearned sequences
such as prayers, series such as the days of the week, or
popular songs. With echolalia as an additional syndrome-
nonspecific symptom, repetition may be quite good. Speech
automatisms (recurring utterances) can frequently (though not
necessarily) be observed in global aphasia and seem to
supersede intended more adequate utterances which in some
cases can be realized by superior writing performance (see
Blanken et al., 1990).
Global aphasia is the result of severe damage to the cerebral

language representation in the area of supply of the left
middle cerebral artery. Lesions of the deep periventricular
white matter and/ or the basal ganglia seem to be of special
importance. Global aphasia is a syndrome of older patients;
subjects below the age of about 40 are likely to develop
Broca’s aphasia even with very large infarcts.
Broca’s aphasia
The syndrome of Broca’s aphasia is different from the clinical

status (global aphasia) and functional interpretation (similar to
the modern concept of speech apraxia) of Broca’s original
patients. The principal feature of Broca’s aphasia is a
reduction of linguistic proficiency on the phonological
(simplification of phonemic structure), lexical (word-finding
difficulty) and syntactic (agrammatism) levels. Of these, the
agrammatic deficits are quite specific for the syndrome and
have been proposed to constitute an axial symptom. Severe
agrammatism leads to the so-called ‘telegraphic style’ with a
lack of function words and inflection forms (‘skiing – bang –
head – sick’). In mild cases, the patients’ productions may be
characterized only by a reduction in the use of subordinate
clauses, multiple objects, or complex verb forms. In these
cases, a premorbidly more elaborate use of language should
be established. Case reports of patients with quite specific
morphological or syntactic deficits however, contradict a
unitary view of agrammatism (Nadeau, 1988).
Patients suffering from Broca’s aphasia exhibit a deficit of

lexical retrieval with time-consuming, laborious attempts at
word finding. Phonological assembly and articulation are
slowed down. A combination with speech apraxia is common.
In a clinical situation, the comprehension deficit is mild. It has
Page 14 of 25
been shown that most patients have comprehension problems

similar to their expressive symptomatology, namely a
prominent impairment with the understanding of grammatical
constructions (Grodzinsky et al., 1999).
In the majority of cases, Broca’s aphasia develops from a very

severe deficit in all modalities, in most instances in a youngish
(younger than 60 years) patient who suffers from a large
infarct in the territory of the left middle cerebral artery. Their
improvement indicates that reorganisation (activation of
lexical representations outside the damaged language region)
and compensatory strategies (e.g. telegraphic style) contribute
to the syndromes phenomenology.
Wernicke’s aphasia
This syndrome is characterized by its prominent ‘para-

symptomatology’, phonemic and semantic paraphasia,
neologisms or jargon, and paragrammatism. (p.244) Speech
production is usually fluent, with few attempts at error
correction. With phonemic jargon, the syntactic structure
cannot be analyzed, although the presence of such structure
can often be inferred, as undistorted function words frequently
stand out and segment the utterance (Buckingham & Kertesz,
1976) and inflectional morphemes may be used on neologisms.
If the lexical content is sufficiently comprehensible, syntactic
violations such as sentence blendings, choice of inadequate
functors and inappropriate inflections can be detected.
Generally, language comprehension is more impaired in
Wernicke’s than in Broca’s aphasia, although jargon may occur
with little comprehension deficit.
Fluent paraphasic aphasia is frequent in the first two weeks

post onset (20% - Willmes and Poeck, 1984) but rare among
chronic aphasics (3% in the same series). Most patients
develop towards anomic or unspecific residual aphasia. This
finding probably also indicates a process of reorganisation by
reestablishing monitoring and output control. The most
common cause of chronic Wernicke’s aphasia is posterior
cerebral infarction in patients who are either elderly or have
diffuse or multifocal brain pathology in addition.
Anomic aphasia
Page 15 of 25
The core symptom of anomic aphasia is deficient lexical access

and/or retrieval. Phonology and syntax are only mildly
affected. The word-finding impairment results in pauses,
circumlocutions, closely related semantic paraphasias, evasion
of the target word by use of empty phrases or fillers without
specific meaning (‘thing’), circumscriptions by verbal or
nonverbal means, or discontinuation of the ongoing phrase
followed by variation of the statement. Most of these
strategies are communicatively acceptable. The deficit
becomes striking, when only one lexical response is
acceptable, such as in naming.
Anomic aphasia usually results from a lesion in the posterior

border regions of the core language area. In most cases, the
temporoparietal junction or the inferior parietal lobe
is affected. Anomic aphasia is relatively frequent with non-
ischemic pathology, such as tumor or trauma.
Conduction aphasia
Conduction aphasia was predicted by the Wernicke-Lichtheim

model (Fig. 13.1) as a disconnection between the sensory and
motor language centers. Wernicke predicted rather a deficit of
output monitoring and control than a disorder of repetition
(Köhler et al., 1998). Within the diagnositic category of
conduction aphasia, two different types of patients have been
distinguished (Shallice and Warrington, 1977):
◆ those with a prominent repetition deficit due to an

impairment of phonological short-term memory (Caramazza
et al., 1981)
◆ those with an impairment of phonological output

programming for single words which together with
relatively preserved monitoring results in frequent attempts
at correction (conduites d’approche) which can be most
prominent in repetition (Kohn, 1984).
Only the latter patients form ‘pure’ cases of conduction

aphasia. However, many conduction aphasics show deficits at
both levels of performance. Conduction aphasia is frequent in
the acute and rare in the chronic stage. When encountered
with acute aphasia, (p.245) its prognosis is good. Its
association with a lesion of the arcuate fascicle, the
Page 16 of 25
anatomical connection between Wernicke’s and Broca’s area,

is disputed.
The transcortical aphasias
The syndromes of transcortical motor, sensory and mixed

transcortical aphasia are characterized by their preserved
ability to repeat. They were predicted by the Wernicke-
Lichtheim model as disorders in which the direct connection
between sensory and motor speech areas was left intact.
Patients suffering from transcortical motor aphasia show

greatly reduced language production, except for repetition,
and rather preserved comprehension. This syndrome is usually
encountered with lesions of the left frontal lobe outside
Broca’s area, especially in the vicinity of the supplementary
motor area on the medial surface, and with lesions of the left
basal ganglia. It has been related to a nonlinguistic
mechanism involving initiative for speech. Repetition is least
affected, because it involves the fewest degrees of freedom
(Goldberg, 1985).
Both transcortical sensory and mixed transcortical aphasia are

rare. Patients are characterized by disinhibited echolalia. Most
patients decribed in the literature have been demented. In
transcortical sensory aphasia, language output is fluent with
mainly semantic paraphasia. In mixed transcortical aphasia,
language production is reduced to echolalia. Naming and
comprehension are severely impaired in both syndromes.
Mixed transcortical aphasia has been interpreted as an
‘isolation of the speech area’ (Geschwind et al., 1968), as these
patients exhibit signs of linguistic processing in the absence of
semantic analysis.
2.6 Diagnostic instruments

The experienced clinician does not require a formal test to
detect the presence of aphasia and diagnose the syndrome.
Tests subserve mainly three functions:
◆ establishing the severity of aphasia,
◆ analyzing the neurospychological or neurolinguistic

structure of the patient’s deficits as a basis for treatment
planning and evaluation by a test battery,
Page 17 of 25
◆ analyzing the effect of aphasia upon a patient’s

communication performance.
An overview over aphasia tests and their psychometric

properties and problems is given by Willmes (1993).
The Token Test (de Renzi and Vignolo, 1962) is a simple and
valid instrument to assess the severity of aphasia. It was
originally designed as a test of language comprehension that
would not include redundant information. The test consists of
circles and squares of two different sizes and five different
colours (Fig. 13.2), which the subject is required to point at or
perform operations with at the request of the investigator.
Contrary to the authors’ intuition, the test scores correlate as
highly with performance in expressive as in receptive
language tasks.
The most frequently used aphasia test is probably the Boston

Diagnostic Aphasia Examination (Goodglass and Kaplan,
1972). This battery includes 27 subtests that assess spoken
and written language and associated functions. It provides
norms from a collective (p.246)
of aphasics as
Z-scores and
assigns the
patient’s
aphasia
syndrome on
the basis of
test results.
The Aachen
Aphasia Test
(Huber et al.,
1984) assesses
a more limited
number
of functions,
but has
psychometrical
advantages, as Fig. 13.2 The Token Test.
it supports
single-case
statistics. Its English version has not been published. A brief,
clinically oriented aphasia battery for nonspecialist use is the
Frenchay Aphasia Screening Test (Enderby et al., 1987).
Page 18 of 25
A very detailed instrument for the assessment of aphasic

symptoms is the PALPA (Psycholinguistic Assessment of
Language Processing in Aphasia, Kay et al., 1992). It provides
an assessment of a wide variety of language processes
intended for a mapping of single case deficits and dysfunctions
on to a psycholinguistic model of normal language processing.
The Amsterdam-Nijmegen Everyday Language Test (ANELT,

Blomert et al., 1987) uses standardized everday situations in
the form of role-plays to assess aphasics’ communicative use
of verbal and nonverbal means of communications.
3 Speech apraxia
Speech apraxia describes the pathology of brain-damaged
persons whose speech is more affected by articulatory
symptoms such as distortions, substitutions and dysprosody,
than is explained by sensorimotor, language and cognitive
deficits. The phenomenological boundaries of the apraxic
dysfunction (e.g. towards dysarthria and conduction aphasia),
remain unclear. The structure of the interface between
linguistic and speech-motor processes is still unresolved.
Speech apraxia has to be differentiated from oral (buccofacial)
apraxia. Both conditions may co-occur but also occur
separately.
Theoretically, speech apraxia denotes a deficit on the level of

motor programming and execution that affects only speech-
related movements. Sensomotorically, speech is organized
differently from other motor acts, in that sensorimotor
feedback plays only a (p.247) neglegible role. On the
phonetic level, speech apraxia is characterized by inconsistent
errors variably related to the phonemic target, such as
omission, substitution, distortion, addition and errors of
sequence. The errors are influenced by articulatory
complexity. There are also effects of propositionality:
stereotyped productions, such as expletives, are less affected.
Usually, the beginning of a word is more impaired than sounds
within a word. This finding can be explained on the level of
motor processing, because the transition probabilities from
one phoneme to the next are smaller within words than at
word onset.
A very characteristic symptom of speech apraxia is the

occurrence of parapraxia. Parapraxia is defined as errors on
the level of movement elements (e.g. omission of a necessary
Page 19 of 25
element, addition, permutation, substitution or perseveration).

Without technical investigations, parapraxias can only be
observed with the anterior articulators and inferred from the
phonetic signal by an experienced examiner. Other typical
symptoms are probed in order to check auditorily and
somatosensorily whether type and place of articulation are
correct.

There is no generally accepted clinical instrument for the
assessment of speech apraxia (see Collins, 1989, and
Rosenbek, 1993, for discussions). The same technical
investigations may be used as with dysarthria (see below).
4 Dysarthria
The dysarthrias are disorders of the sensorimotor performance
of speech acts which are characterized by disturbances in
speech musculature control due to paresis, slowness,
incoordination, altered tone or additional (dyskinetic)
movements. They affect the respiration pattern required for
speech, phonation, resonation, articulation and prosody.
As with the sensorimotor speed and quality of other (e.g.
hand) movements, a number of neurological impairments can
cause dysfunction: lesions of the first (spastic paresis) and
second (flaccid paresis and atrophy) motor neuron, ataxia,
akinesia, dys- and hyperkinesia and sensory impairment.
Accordingly, the dysarthrias are classified into a central and a
peripheral paretic, a hypokinetic, an ataxic and a dyskinetic
variety. Clinically, some frequent neurological diseases result
in mixed forms, as more than one sensorimotor mechanism is
affected, e.g. amyotrophic lateral sclerosis (ALS) combines
first and second motoneuron degeneration and Multiple
Sclerosis frequently includes both spastic and ataxic
symptoms.
4.1 Types
Bilateral lesions of the first motoneuron of the corticobulbar
tracts results in spastic (or central paretic) dysarthria; there is
little spasticity in the involved muscles. It is characterized by
impaired diadochokinetic motility of the articulatory
musculature and a disinhibition of reflectory mass movements
and synergisms (pathological laughter and crying, sucking
etc.). Speech is laboured, monotonous and slow with imprecise
consonants as the most (p.248) prominent feature. It occurs
Page 20 of 25
in neurological diseases with prominent first motor neuron

pathology, mainly diffuse or multifocal cerebrovascular disease
(‘pseudobulbar palsy’).
The symptomatology of lesions of the second (peripheral)

motor neuron (or the neuromuscular junction- myasthenia
gravis, or diseases of the relevant musculature – e.g. muscular
atrophy and dystrophy, polymyositis) depends on the affected
nerves or muscles. With diffuse disease, such as in one form of
ALS (‘bulbar palsy’), bilateral affection of cranial nerves (e.g.
Miller-Fisher syndrome) and mysathenia, speech is reduced in
volume, monotonous, imprecise and hypernasal.
Hypokinetic dysarthria is phenomenologically similar to

spastic dysarthria with imprecise articulation, slow speech,
decreased prosody and often decreased loudness. Speech in
Parkinson’s Disease, the most frequent cause of hypokinetic
dysarthria, is additionally characterized by variations in
speech rate (tachyphasia) and rapid repetition of speech
elements (palilalia).
Ataxic dysarthria is characterized by variable articulatory

errors and imprecisions with frequent omissions, rapid
changes in speech rate, pitch and loudness (‘scanning speech’)
and inadequate respiratory patterns.
With dys- and hyperkinetic dysarthria, there is also a variable

pattern of errors dictated by the involuntary movements. In
view of the amount of dyskinesia, most patients articulate
surprisingly well. A dissociation from respiration is typically,
with phonation on inspiration, involuntary phonation and
diminished control of pitch and loudness.
For a detailed description of the dysarthrias, Darley et al.

(1975) is still a most valuable source.

Clinically, the most frequently used assessment instrument is
the Frenchay Dysarthria Assessment (Enderby, 1983). It
consists of a standardized investigation of speech and
nonspeech motor acts of respiration, phonation, and speech
and nonspeech movements of the articulators together with a
rating of comprehensibility of the production of words,
sentences and spontaneous speech. Normative data for groups
of patients are provided and aid differential diagnosis.
Page 21 of 25
In addition, speech related movements can be investigated by

technical means, such as electroglottography, endoscopy, X-ray
microbeam, and electromagnetic articulography, and phonetic
signals by sound spectrography.
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Page 25 of 25
Motor speech disorders: an overview


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Motor speech disorders: an

overview
Nick Miller
DOI:10.1093/acprof:oso/9780199234110.003.014

‘Motor speech disorders’ represents a general label applied to
a set of distinct disruptions to speech output associated with
neurological illness. There exists an array of subtypes of motor
speech disorder, irrespective of whether one bases taxonomies
on anatomy and physiology, neuropathology, acoustic-phonetic
parameters, or models of speech output. This chapter
discusses how normal speech production takes place, motor
speech disorders, assessment of motor speech disorders,
common neurogenic speech changes, and development of a
foreign accent.
Keywords: speech disorders, speech production, motor speech disorders,

taxonomies, speech changes
1 Motor speech disorders: what are they?

‘Motor speech disorders’ represents a general label applied to
a set of distinct disruptions to speech output associated with
neurological illness. There exists an array of subtypes of motor
speech disorder, irrespective of whether one bases taxonomies
Page 1 of 39
on anatomy and physiology, neuropathology, acoustic-phonetic

parameters, or models of speech output.
Motor speech disorders may arise from lesions of an isolated

cranial nerve affecting a single articulator through to major
systemic disorders implicating all movements of the vocal
tract. The speech disorder can occur in isolation or present as
one aspect of a complex cognitive-motor picture. Onset can be
sudden (e.g. stroke; head-injury) or insidious (e.g.
degenerative disorders, neoplams) over months or years.
Speaking changes may emerge as late rare effects of some
disorders, be an inevitable sequel of others, or constitute a
sole or early harbinger of neoplastic, inflammatory, infectious,
atrophic, metabolic or neurochemical changes (see below). In
some cases one might expect recovery towards (not
necessarily full) premorbid levels, in others decline is
inexorable over longer or shorter time spans.
From the perspective of speech output processes or models,

the label broadly encompasses two major subtypes of disorder:
a) problems with higher cortical planning, supervision and
execution of ‘programmes’ for speech movements; b)
neuromuscular impairment of movements of the articulators
(diaphragm, rib cage, larynx, soft palate, tongue, lips, jaw).
Neuromuscular disorders arise from disturbances of neural
transmission, problems with the electrochemistry of the nerve-
muscle synapse and dysfunctions of muscles themselves.
Cortical disturbances are claimed to underlie apraxia of
speech and phonemic paraphasia, neuromuscular changes are
associated with dysarthria. These terms are elaborated later. It
will also become clear later that the distinction between
cortical versus subcortical and peripheral impairments is an
oversimplification. In particular, lesions associated with the
cerebellum and basal ganglia may impact on programming
and online monitoring of speech motor execution in addition to
consequences for muscle tone, power and coordination
(Spencer and Rogers, 2005, Ackermann et al., 2007, Booth et
al., 2007).
Severity ranges from mild alterations perceptible only to the

speaker or on sensitive instrumental analyses, through
intelligible but non-normal sounding speech to total
unintelligibility or muteness. One should add the rider that
definitions of severity linked to objective assessments do not
necessarily reflect perceived impact of changes by the (p.
Page 2 of 39
252) speaker or their social circle. An apparently mild change

judged on objective measures may produce severe
psychosocial consequences for one speaker; an apparently
severe impairment may be scarcely noticed by another.
An awareness of motor speech disorders is paramount not just

for understanding them in their own right. They are important
in neuropsychological assessment in that ignoring them may
lead to an inaccurate picture because changes to speech
mimic the presentation of certain cognitive, affective and
neurobehavioural disorders (e.g. O’Keeffe et al., 2007,
Cannizzaro et al., 2004, Duffy, 2006, Gorno-Tempini et al.,
2006, O’Sullivan et al., 2008). On the other hand they may
mask or distract from changes in these domains. Either way
erroneous diagnoses will lead to mismanagement.
To provide a backdrop for discussion of assessment and

differential diagnosis the following section offers a brief
exposition of how normal speech production takes place.
2 Speech production
Essentially speech is produced by blowing air between the
vocal cords and using the velum (soft palate), tongue and lips
to shape the resultant sound into speech. More specifically,
speech is produced through the muscles of the diaphragm,
abdomen and ribcage modifying the rate and volume of
inspiration and duration and pressure of expiratory airflow
from the lungs. This air is used to drive the vocal cords,
generating sound (phonation, voice) by causing the tensed,
approximated vocal folds to vibrate (in the region of 130–140
times per second for adult males, 210–230 Hz for females).
The sound directly from the larynx is akin to the sound
produced from blowing two pieces of paper together or
humming with tissue paper on a comb. This is transformed
into what we hear as speech by amplification of the signal in
the resonating chambers of the nasopharynx and oral cavity
and modification of the signal by constricting (for continuant
sounds such as f, v, s, l) or blocking (for plosive sounds such as
p, b, t, g) the flow of air, or altering the shape and resonance
of the oral cavity (for vowels).
The contrast between nasal and oral sounds (e.g. pairs such as
m-w, m-b, n-d, n-l) is achieved by lowering or raising the velum
to divert air predominantly through the nasal or the oral
cavity. So-called voiced (e.g. b, d, g, v, z) and voiceless
Page 3 of 39
cognates (p, t, k, f, s) are contrasted in word initial positions

(pea vs bee) in English according to millisecond differences in
lag (voice onset time) between release of closures in the
mouth and restart of vocal cord vibration. In word final
position (lock vs log) perceived differences relate to duration
of the preceding vowel. In some languages, standard British
English for instance, an added perceptual clue for pairs such
as b-p, t-d derives from the degree of aspiration that
accompanies release, easily demonstrated by saying ‘pea’ and
‘bee’ onto the back of ones hand, where there should be a
noticeable puff of air with ‘pea’ but not ‘bee’.
Vowel contrasts rely on differing settings of the tongue tip and

dorsum. For instance in standard British English the series
‘heed, hid, head, had, hard, horde, hood, who’d’ entails
starting with the tongue tip raised, lowering it and switching
to the dorsum gradually rising. Notice too the modifications to
lip rounding-spreading that coordinate with the tongue
changes and how ‘abnormal’ the vowels sound if one says
‘heed’ with rounded instead of spread lips and ‘who’d’ with
spread instead of rounded.
(p.253) Pitch (and changes in pitch, the intonation pattern of

phrases) and voice quality are largely determined by the
(changing) length, degree of tension and pattern of
approximation of the vocal cords. Loudness (and contrasts in
loudness for stressed versus unstressed syllables/words)
derives from the balance between the respiratory driving force
of the air (subglottal air pressure) and the level of resistance
offered by the vocal cords (greater the pressure, tighter the
cords, louder the voice). Voice quality (e.g. harsh, breathy,
rich) is predominantly a function of the setting of the vocal
cords and control of pharyngeal and oral resonance.
Respiration for speech is different to vegetative patterns. In

the latter the ratio of inspiratory to expiratory phases is
roughly 1:1. For speech this vegetative pattern must be
overridden to effect a ratio of roughly 1:6–10 depending on the
length, loudness and rate of the utterance. Inability to
coordinate breathing with speech and with morpho-syntactic
planning (Hixon and Hoit, 2005) can severely compromise
intelligibility.
Page 4 of 39
While the above schema has a neat simplicity to it, the process
is actually highly complex. Speech motor control is the most
complex activity humans (and probably any species) can
achieve, in terms of the number of muscles and muscle groups
needing to be coordinated; the rate and precision at which
they have to be adjusted to sustain intelligible speech; the
complex interaction at a minimum with phonological (sound
system) processing to generate the right sound targets for
required words, sentence level processing to produce correct
breathing, stress and intonation patterns; and affective control
to convey correct tone and feeling.
Table 14.1 summarises the chief changes one might hear when
different parts of the vocal tract are impaired. As a rule of
thumb impairments of respiration and phonation (larynx)
compromise suprasegmental features of speech (loudness;
pitch; stress patterns across words and phrases; intonation
patterns; voice quality; affective expression), whilst tongue
and lip disturbances perturb production of individual sounds
(articulation). Given that there is a considerable amount of
motor equivalence possibility in articulatory movements and
redundancy in perception of speech sounds, a degree of
compensation across the vocal tract on the part of the speaker,
or ear of the listener may mask or neutralise disruptions to
isolated speech subsystems. Where systemic conditions or
extensive lesions affect multiple subsystems or where the
underlying disruption is precisely to the ability to coordinate
and compensate across subsystems, the ensuing speech
disorder is liable to be correspondingly more pervasive and
severe.
One must emphasize that communication is more than just

speech and language. Facial expression and hand and arm
gestures accompanying speech constitute an important
component. Compromise to these can also have an effect on
the intelligibility and acceptability of what is said (Munhall et
al., 2004, Garcia et al., 2004).
3 Motor speech disorders

A broad distinction was made above between planning versus
neuromuscular disorders of speech, with the former subsumed
under the label apraxia of speech, the latter under dysarthria.
The following sections look further at these distinctions and
introduce some (p.254)
Page 5 of 39
Table 14.1 Broad associations between changes

to articulator function and perceived voice and
speech changes
Articulator Possible changes Possible speech

affecting speech changes heard by
listener
Lungs, chest reduced breath frequent breaths,

wall, capacity; problems shorter phrases,
diaphragm: controlling slow reduced loudness or
respiration expiration; lack of sudden bursts of
coordination loudness; speaking on
breathing-speech residual air or on
inspiration
Balance imbalance between impaired control of

vocal cords- normally well poised loudness, stress
respiration subglottal air patterns, intonation
pressure and
laryngeal resistance
Larynx: uni- or bilateral cord control of pitch,

voice weakness/paralysis; loudness; altered voice
abrupt or persistent quality towards
alterations to tone whispery, weak or to
and stiffness in strained, harsh,
laryngeal muscles hoarse; inappropriate
bursts of excessive
loudness or whispers
or inappropriate
sudden pitch change
Velum (soft velum unable to altered degree of

palate): raise-lower (fast nasality, more
resonance enough/sufficiently) commonly to
to switch airstream hypernasality
from nasal to oral
flow or vice versa
Tongue hyper- or perceived distortion,

hypotonus; hyper- omission, addition,
or hypokinesis; substitution of tongue
tremor; sounds (t, d, n, l, r, s,
incoordination z, sh, ch, j, k, g,
vowels)
Page 6 of 39
Articulator Possible changes Possible speech

affecting speech changes heard by
listener
Lips hyper- or perceived distortion,

hypotonus; hyper- omission, addition,
or hypokinesis; substitution of lip
tremor; sounds (p, b, f, v, m, w)
incoordination
Mandible hyper- or disordered movement

hypotonus; hyper- unlikely to directly
or hypokinesis; impact speech; may
tremor; have significant knock-
incoordination; on effect on tongue
hangs too far open and lip control,
especially if they too
are affected and
unable to compensate
for mandibular
perturbation
of the subtypes within these categories that may pose particular

differential diagnostic conundrums.
3.1 Apraxia of speech and phonemic paraphasia
The characteristic picture in apraxia of speech is of a person
who knows what they want to say (no aphasia or general
intellectual impairment; though usually apraxia of speech does
co-occur with aphasia). They know the sounds they are trying
to speak (no dissolution or inaccessibility of the sound system/
phonology). They have full range, rate and power of
movements of the articulators (no primary sensory-motor
impairment). Yet, they are unable to combine these
movements into an overall action plan and realisation of
movements to produce the desired sounds for an utterance. In
severe cases the person may be rendered mute. In less severe
cases speech sounds are slow, laboured, hesitant, dysfluent,
with visible groping movements of the tongue and lips and
audible repeated attempts at starting a word as the person
struggles to overcome the misdirected articulatory
movements. In the mildest cases the problem may only be
manifest when the person (p.255) is fatigued, under time or
emotional pressure, or on articulatorily more complex motor
sequences.
Page 7 of 39
Diagnosis represents a challenge, calling for referral to speech

language pathology/therapy. Apraxia represents a disorder of
learned, volitional action control (McNeil et al., 2008).
Consequently the apparent inability to produce target sounds
and words and the relatively effortful, dysfluent speech in a
consciously controlled, propositional context contrasts with
the ability to utter the same targets more fluently and
accurately in more reflexive, automatic, non-propositional
contexts. The person cannot repeat after the examiner ‘me’ or
‘tea’ but shouts them clearly in response to ‘Which of you’s
Jean?’, ‘Would you like coffee or tea?’ The person can say
1-2-3-4-5 in the nursery rhyme, but fails to say 5-4-3-2-1;
pronounce ‘that’s hard’ clearly as an aside whilst struggling on
a particular word, but then cannot repeat after the examiner
‘that’s hard’ a minute later.
Perceptually, to the naked ear, the impression is that sounds

are distorted (right target sound, but spoken in an atypical
fashion, ‘tea’ is produced with heavy aspiration after the ‘t’),
substituted (‘table’ sounds like ‘kable’), omitted (‘stamp’
sounds like ‘sam’, ‘magazine’ like ‘mazine’), added (‘pay’
sounds like ‘pfay’ or ‘pshay’). The apparent substitutions may
themselves sound distorted (‘table’ sounds like ‘kyable’).
Misorderings, anticipations or perseverations may occur
(telephone is produced as ‘feletone, felephone, teletone’).
Parapraxic perseverations spread across utterances. In
naming successive pictures of ‘bus, car, horse’, for instance,
the person may pronounce them as ‘bus, bar, brarse’. Stress
and intonation patterns may also be disrupted – canOE is
misstressed as CAnoe, magaZINE as maGAzine or with
syllables separated off from each other – ma..ga..zine. Sound
derailments are prominently inconsistent – e.g. the speaker is
unable to say ‘tea’ on one occasion, can on another, one time it
is mispronounced as ‘key’, another time as ‘chee’, another as
‘stee’.
Contrary to earlier claims, these are not indications that the

person has lost the concept of particular sounds, has
misselected or misordered sounds. Rather the underlying
cause is in the breakdown of planning and regulation of the
movements to produce the auditory targets, in misphasing,
misscaling the fine distinctions alluded to above (e.g. voice
onset time, degree of aspiration, alternation of tongue tip and
Page 8 of 39
tongue dorsum gestures) that help distinguish between

different sounds (Ziegler and von Cramon, 1986, Itoh et al.,
1982, Ziegler, 2001).
As well as contrasting with neuromuscular aetiologies, apraxia

is traditionally seen as different to speech problems arising at
the level of phonological impairment, variously labelled
phonemic paraphasia, phonological output disorder or similar
(Buckingham, 1998). There are indeed speakers who sound as
if they make the same substitution, misordering, omission and
addition derailments as apraxic speakers, with repeated run-
ups at a word to try and reach the correct sounds, but who
otherwise show normal rate of speech and intonation and in
whom there is little or no perceptible distortion of sounds. This
invites a distinction between a phonological, paraphasic,
premotoric disruption to output planning versus a motoric
apraxic breakdown.
Guidelines exist for how one might differentiate speakers

clinically (McNeil et al., 2008). However, none has found
universal acceptance and application of principles to
individual speakers in clinic remains more often than not
decidedly problematic (McNeil (p.256) et al., 2008).
Distinguishing the putative disruptions is fraught with
controversy. This stems from competing theoretical positions
on the relationship, interface (or not) between phonological,
premotoric processes in speech planning and phonetic motoric
processes, all further clouded by decades of terminological
confusion (Lebrun, 1989). The result is opposing predictions
from contrasting models of speech output (Levelt et al., 1999,
Ziegler, 2002a, Schwartz et al., 2004, Kingston, 2007) and
divergent approaches to assessment (Miller, 2002, McNeil et
al., 2008). Furthermore, with few exceptions (Guenther, 2006)
models are highly underspecified concerning the nature of the
premotor-motor interface and what constitutes (speech)
motoric control. Current front runners for viable models that
might inform the differentiation between planning type
breakdowns come from views rooted in articulatory and
gestural phonologies (Browman and Goldstein, 1992, Kingston,
2007).
The role of mirror neurons and new understandings of the

relationship of input-output processes in phonology and the
links between perception and action will doubtless advance
Page 9 of 39
understanding of what breakdowns underlie phonemic

paraphasia and apraxia of speech and what their relationship
is (Poeppel and Hickok, 2004, Arbib, 2006).
Table 14.2 offers some general rules of thumb hinting in the

different directions. They do not represent a definitive
diagnostic key. Detailed differential diagnosis would be the
remit of speech language pathologists/therapists.
3.2 Dysarthrias
Dysarthria denotes a problem with articulation due to
neuromuscular impairment (Duffy, 2005, McNeil, 2008,
Yorkston, 2007). Neuromuscular disorders affect the tone,
power and coordination of movements. The precise
constellation of changes depends on site(s) of lesion. In turn
the neuromuscular changes impact on the initiation, range,
speed, strength, sustainability, steadiness and coordination of
movements for speech. These changes are in turn associated
with alterations to voice quality, pitch, loudness, stress
patterns and intonation of words and phrases, resonance,
articulation of speech sounds and the facial and gestural
movements that accompany speech. They impact on the
intelligibility and acceptability of speech and determine the
willingness or ability of an individual to engage in
communication.
Table 14.3 summarises the main areas of the central and

peripheral nervous system more directly involved in speech
motor control and the disruptions to speech associated with
lesions in these areas following this medical model. In as far as
speech motor control is dependent on or interacts with
broader motor and cognitive processes – for example arousal,
attention, memory, language – clearly more structures and
pathways are involved than this, but these are considered the
core components for speech. Given the rich bilateral crossed
and uncrossed innervation of the speech musculature
persisting and more severe disorders linked to upper motor
neurone lesions are more likely to occur with bilateral insults,
but lasting defects with unilateral lesions do happen (Duffy,
2005).
Dysarthric alterations to voice and speech are prominent

aspects of several degenerative disorders – including
Page 10 of 39
Parkinson’s disease, motor neuron disease/amyotrophic lateral

(p.257)
Table 14.2 Rules of thumb for differentiating

between paraphasic and apraxic type speech
More to ‘speech apraxic’ More to ‘phonemic

picture paraphasic’ picture
Perceived errors are Lot higher proportion of

predominantly distortions, displacement errors and
close substitutions or apparent distant
distorted substitutions that substitutions
differ minimally from the
target sound
On diadochokinetic (DDK) on DDK tasks perform

tasks difficulties are apparent normally on single syllable
already on single syllable repetition, once the person
(/’ta’ta’ta/) repetitions (altered has latched onto correct
rhythm, drifting on and off target, but fall down on
target, effortfulness) alternating tasks
(/’pa’ta’ka/)
On alternating tasks more alternating tasks tend to

likely to have perseveration be disrupted by sequence
errors (stuck on one target) errors or distant
substitutions
Perceptually involves all word tends to be restricted to

classes nouns, verbs, adjectives
(content words)
If no aphasia, written spelling errors generally

language is fine. Aphasia accompany the speech
usually present though, so not problem
good differentiator
Performance to reading or reproduction conduction

repetition may be better than aphasic speakers are
spontaneous speech, but this significantly worse on
is not a reliable diagnostic repeating words and
feature for all speakers sentences compared to
spontaneous speech
Slow rate, even in on-target (near) normal rate in on-

utterances target utterances
Page 11 of 39
More to ‘speech apraxic’ More to ‘phonemic

picture paraphasic’ picture
Inability to increase rate variable ability to increase

whilst maintaining sound rate and maintain sound
integrity accuracy, but rate within
normal limits
Variable, but overall variable, but in normal

prolonged movement limits movement transition
transitions durations
Variable, but abnormally long variable but normal limits

vowels in multisyllable vowel duration in
utterances multisyllable utterances
Variable but increased variable, but within normal

movement durations for limits durations
individual speech gestures in
connected speech
sclerosis, Friedreich’s ataxia, Huntington’s disease, multiple system

atrophy, and progressive supranuclear palsy (Hartelius et al., 2006,
Hillel et al., 1999, O’Sullivan et al., 2008, Sapir et al., 2008, Tjaden,
2008, Yorkston, 2007). Changes to speech and voice may even be
detectable in the prodromal phase or be the initial indication that
something is awry (Stewart et al., 1995, Harel et al., 2004, Hillel et
al., 1999, Penner et al., 2007, El Badawey et al., 2008, Richter et al.,
2005). Dysarthria is common too in multiple sclerosis, several
cerebellar disorders as well as some muscular dystrophies (de
Swart et al., 2004) (though these strictly speaking are not
neurogenic speech disorders). In traumatic brain injury and stroke
it may be one of many consequences of the incident or manifest as
a sole sequel. Dysarthria can be found in association with viral (e.g.
encephalitis), infectious (e.g. rheumatic fever, meningitis),
metabolic (e.g. Wilson’s disease) or iatrogenic conditions (recurrent
laryngeal nerve damage during surgery; drug induced). (p.258)
Table 14.3 Broad changes to speech associated

with varying central and peripheral nervous
system lesion sites
Page 12 of 39
Neurological Speech motor Associated disruption to

component control speech
component
affected
dominant planning, phonological

temporal- supervision/ disturbances, apraxia of
parietal, execution of speech (see text)
insular, movements for
frontal cortex speech
right control of aspects a-dysprosody (see text)

temporal- of intonation
parietal,
frontal cortex
upper motor transmission of spastic dysarthria;

neuron, impulses from hypertonus and
pyramidal primary motor spasticity of muscles;
pathways cortex via cortical slowed, effortful
bulbar and voluntary movements,
cortical spinal harsh ‘strain-strangled’
tracts to lower voice
motor neurons
(LMN)
basal ganglia initiation, scaling, depending on which

maintenance, structures and
alternation and functions affected:
smooth hypokinetic dysarthria:
concatenation of bradykinesia, rigidity,
movements slowed, quiet,
monotone, monoloud
speech; hyperkinetic
dysarthrias: chorea,
dystonia, ballism,
athetosis, tics,
associated with erratic
alterations to loudness,
rate, articulation;
tremor brings unstable
tremulous voice or
speech; palilalia
Page 13 of 39
Neurological Speech motor Associated disruption to

component control speech
component
affected
cerebellum feedforward ataxic dysarthria:

control and dysmetric (under-
coordination and overshooting of
integration of movements),
movements; dysrhythmic,
cognitive discoordinated,
affective disintegrated flow of
component speech movements
lower motor transmission of flaccid dysarthria:

neuron nerve impulses hypotonus of muscles:
from upper motor bilateral: weak, slowed,
neuron to easily fatigued or
muscles absent movement
unilateral: diplophonic
voice, compensatory
mechanisms may mean
articulation not majorly
affected
synaptic transmission of flaccid dysarthria:

junction and nerve impulses weak, slowed, easily
muscular from LMN to fatigued or absent
disorders muscles; muscle movement
contraction
The time course of speech changes in relation to other involvement

may be diagnostically significant. Speech-voice examination may
therefore offer a means of early detection and/or differentiation of
underlying disorders.
4 Assessment of motor speech disorders
One’s precise approach to assessment is shaped by the
purpose of the exercise. It may be to establish if some kind of
disorder is present; determine the type of disorder in terms of
(p.259) underlying neurological, neuromuscular,
neuropsychological or neurolinguistic breakdown; differential
diagnosis of which parts of the vocal tract are impaired and to
what degree; identification of variables to target in
intervention; or gauge the effects of a disorder on the
individual’s behaviour and quality of life. The following
outlines some broad approaches to assessment that can
Page 14 of 39
accomplish these ends. It is taken as understood that a

comprehensive examination sites speech within a broader
investigation of affective, language and other relevant
cognitive processes. In Britain and North America at least the
person likely to undertake detailed speech investigations is the
speech language pathologist/therapist.
Assessments can be divided according to ICF levels of

measurement (Threats, 2008). This framework is followed
here. More extensive expositions of assessment can be found
elsewhere (Duffy, 2005, McNeil, 2008).
4.1 Impairment level assessment

This entails the assessment of the tone, power, rate and range
of movements of the articulators for speech, as well as
measures of steadiness (e.g. rhythmic or arhythmic tremor;
athetosis) and consistency (patterns of (ir)regularity of
changes in specific parameters over time, from second to
second or different times of day).
There is some debate over whether the tasks best suited to

accomplish impairment assessment are nonverbal tasks (e.g.
stick tongue in and out; blow out cheeks), or whether speech
and speech-like items are more valid (e.g. repeat word ‘tea’ 10
times as fast as possible; alternate between tea-key as fast as
possible (Ziegler, 2003a, Ziegler, 2003b, McNeil, 2008). The
objection to the former is that they may well disclose muscle
weakness, altered range of movement and so forth, but these
correlate only weakly with success or not on movements for
speech. Hence the latter are generally preferred as delivering
a more ecologically valid evaluation. Table 14.4 summarises
some main techniques in appraisal of speech impairment.
Usual practice is to evaluate parameters in varying contexts,

since performance can vary according to whether elicitation
entails spontaneous speech, repetition or reading (Kempler
and Van Lancker, 2002). Furthermore differences across these
domains may be diagnostically relevant (McNeil 2008). Ideally,
one assesses under varying cognitive loads. Performance may
significantly deteriorate when competing tasks have to be
carried out (Ho et al., 2002, Bunton and Keintz, 2008).
Helpful information may be obtained by observing the

speaker/articulators at rest when not necessarily engaged in
speaking. Can the speaker attain and sustain adequate posture
Page 15 of 39
for optimal breathing; are respiration and phonation impeded

in other ways by e.g. hemiplegia, contractures, skeletal
deformities, inappropriate seating/bed? Pain from whatever
source may influence overall body posture as well as
articulator positioning and movement. In- or expiratory stridor
can point to particular pathologies and may indicate a referral
for laryngoscopic or neurological investigation.
Tremor, writhing, and ballistic movements may interfere with

any articulators. One records whether these are (ir)regular
and (un)predictable; what triggers them; the degree of
voluntary control the person has over them; whether they
overflow from/to other articulators/body parts. (p.260)
Table 14.4 Main approaches to assessment of

speech impairment
Articulatory Main Instrumental Non

function parameter(s) assessments instrumental
assessments
respiration capacity, Ability to Frequency of

control of sustain breath breaths on
expiration out for 5" with standard
straw at 5cm reading
depth on water passage or
manometer counting to 30
(Hixon et al., at fixed rate.
1982). Length of
Respiratory sustained /a/
kinematics. sound
Respiratory
function.
voice and vocal cord Acoustic Perceptual

prosody closure analyses of ratings of voice
patterns; pitch and quality (e.g
loudness, amplitude Karnell et al.,
pitch, voice perturbation; 2007), loudness
quality harmonics to and pitch
noise ratio; variation
range, mean suitability;
and standard ratings of
deviation of ability to signal
fundamental intonation
Page 16 of 39

assessments
frequency and patterns and
loudness stress contrasts
resonance ability to Nasality meter; Ability to

produce acoustic sustain
nasal vs oral measures of differentiation
resonance nasality of nasal-oral
and sounds sounds on 10
repetitions of
minimal pairs –
e.g. no-doe, by-
my, any-Eddie
tongue ability to Strain gauges, Diadochokinetic

control reach and force (DDK,
maintain transducers; (Gadesmann
articulatory acoustic and Miller,
contacts and measure of 2008; Ziegler,
precision articulation; 2002b)
duration, measures of
closure and rate, range,
consistency on sustainability
diadochokinetic and alternation
tasks; acoustic of contacts for
vowel space tongue tip and
back – e.g.
repetition of
tea; key, tea-
key; tea-see;
see-she; pea-
tea-key
lip control as for as for tongue as for tongue,

tongue, using words
mutatis involving lip
mutandis movements:
pea, fee, be, V,
we
Coordination breathing acoustic ability to make

across with measures of and sustain
articulators phonation; voice onset voiced-voiceless
oral with time; timing of distinctions;
Page 17 of 39

assessments
laryngeal voice and articulatory
gestures; respiration rate (syllables
inter- and onset-offset; per minute),
intra measures of pause duration
articulator coarticulation and frequency
timing (e.g. and on standard
tongue tip- syllabification tasks give
dorsum) rough measures
of overall
fluency
Food left in the mouth and/or round the lips may indicate the
speaker is unable to clear it because of a weak tongue, poor
swallow, because they are not aware it is there from poor sensory
awareness, or lack of attention or motivation.
4.2 Activity limitation
Measures here examine the consequences of impairment
alterations for speech intelligibility and naturalness. Rating
scales deliver rough and ready estimations of intelligibility but
(p.261) suffer from very poor intra- and inter-rater reliability
(Schiavetti, 1992, Kreiman and Gerratt, 2000) and are wholly
uninformative regarding targets for rehabilitation. Diagnostic
intelligibility testing (Kent et al., 1989) provides both a metric
for overall severity and (the diagnostic part of the label)
indications for therapy.
A speaker may have unimpaired or viable intelligibility, but

alterations to how natural or disordered their voice,
resonance, prosody and rate of speech are perceived, may act
as limitations on activity. Presence of disruptive struggle to
achieve intelligible speech may represent an additional feature
curtailing communication either from the point of view of the
speaker and how it impacts on them and their ability to adapt,
or from the point of the listener and their ability to tolerate or
adapt to the altered speech characteristics.
Whilst these factors can be assessed objectively (Table 14.4),

their combined or separate effects on activity are typically
rated on general scales of acceptability, disorderedness or
naturalness, or more specific scales examining elements of
prosody, voice quality, resonance (Karnell et al., 2007).
Page 18 of 39
4.3 Participation restriction and impact

Speech and voice changes, even mild, may alter a person’s
ability to enter into roles, places and activities they previously
were able to, and/or alter listeners’ reactions to the speaker
with consequences for social participation (Miller et al., 2006b,
Yorkston et al., 2007). Assessments of participation restriction
gauge these factors. Well validated and reliable instruments
specifically for speech are currently only under development
(Eadie et al., 2006, Walshe et al., 2009). Some evaluations for
voice impact exist (Karnell et al., 2007). The semantic
differential technique has been employed to effectively
measure status and change in relation to communication
(Miller et al., 2008).
5 Other speech changes

Speech may be disrupted by a wide variety of neurological
disturbances (Table 14.4). The following sections sketch a
broad overview of some more common neurogenic speech
changes, with a bias towards ones that may present some
diagnostic conundrums, especially where the speech
alterations occur in (relative) isolation from other signs and
symptoms.
5.1 Dystonias
Dystonia is a neurogenic movement disorder characterized by
repetitive, involuntary, sustained muscle contractions
(Albanese, 2007). These can be limited to one area of the body
or muscle (group), as in e.g. laryngeal or mandibular
dystonias; involve two or more adjacent or non-contiguous
areas of the body; or be generalized in nature. Movements
may arise without apparent trigger, may be elicited as an
overflow reaction to movements in unaffected body parts, or in
action dystonias (below) only appear in response to highly
specific eliciting conditions.
Although dystonias typically resolve over seconds or minutes,

more severe fixed dystonias may lead to long term abnormal
postures and contractures in the affected region. (p.262) Any
focal dystonia involving muscles of speech (including
breathing, larynx, jaw, soft palate, not just the more obvious
facial and tongue sites) may compromise spoken output.
Typically reactions involve a consistent movement pattern.
Thus, an individual with mandibular dystonia, depending on
which muscle (group) is affected, experiences the same
Page 19 of 39
opening, closing or lateral movement of the jaw, in the same

direction, to the same degree.
Dystonic spasms are usually worsened by stress, emotional

upset, or fatigue and improved with rest or sleep. A
characteristic of dystonia is that patients may be able to
temporarily suppress dystonic movements or feel they can
release spasms by various compensatory tricks (sometimes
termed gestes antagonistes) such as touching an affected or
adjacent body part.
Task specific dystonias are triggered or severely exacerbated

in response to specific voluntary movements. These highly
specific or hidden triggers can lend a decidedly psychogenic
air to the presentation, especially when they are combined
with apparently ‘bizarre’ gestes antagonistes.
Amongst reported action dystonias several illustrate speech or

facial movement related factors, including in response to wind
instrument playing, auctioneering, praying, writing (Frucht et
al., 2001, Rosset-Llobet et al., 2007, Das et al., 2007, Gaig et
al., 2007, Scolding et al., 1995, Ilic et al., 2005). One cause of
bruxism (teeth grinding) is dystonia (Singer and
Papapetropoulos, 2006, Tan et al., 2004). Task specific
dystonias may remain as such or may later emerge in other
activities as the condition deteriorates (e.g. writers cramp
spreads to eating behaviour or other activities involving arm
control).
5.2 Spasmodic dysphonia

Probably the most prevalent action dystonia in relation to
speech is spasmodic dysphonia (Baylor et al., 2007, Bender et
al., 2004). The act of speaking induces dystonic spasms that
either involuntarily draw the vocal cords together (adductor
spasmodic dysphonia or adductor laryngeal dystonia) or apart
(abductor variety). Whilst these varieties sometimes occur
independently, most speakers evidence both ad- and abductor
spasms.
Perturbations range from barely perceptible to severely

debilitating. In mild cases in the adductor type the listener
hears what sounds like a sudden hiccup or catch in the voice,
or the ‘huh’ one might exclaim if suddenly experiencing a
sharp pain. The more severe the state, the more symptoms
resemble a strained voice quality, stuttering like blocks, right
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up to complete voice arrest as the speaker struggles to

overcome hyperadduction. In the abductor variety in mild
cases the listener may perceive voice breaks, sudden intrusive
whispers or intermittent loss of volume and voicing, whilst at
the severe end of the spectrum every endeavour to vocalise
elicits an abductor spasm leading to complete voice loss.
In contrast to speech, vegetative functions such as laughing,

throat clearing, yawning are frequently performed normally.
As the problem is action induced, laryngoscopic examination
of the larynx at rest demonstrates no abnormality. Requests to
whisper, sing a note, say a high pitched /i/ may also not trigger
a spasm. It is only during natural and sustained speech that
the dystonic disruptions are likely to reveal themselves.
(p.263) Such suggestions of normality may strengthen the

impression of a psychogenic aetiology. This may be reinforced
by the compensatory suppression or release gestures the
individual has developed. Personal cases seen have performed
a shaking movement of the head, pushed or pinched the
thyroid cartilage, made a blowing movement with over
rounded lips when their voice arrests, preceded utterances
with a /hmm/ or a sniff, or ‘covered’ breaks with a cough.
Others report patients who pressed their hand against the
back of their head, or abdomen, or pulled their ear.
Onset is commonly in middle age. Symptoms gradually

deteriorate over a few years. The person notices first what
they might describe as catches of breath, little coughs or
gasps. These progress to what are perceived as a more
general hoarseness, or increasing whisperiness, eventually
ending in the spasmodic disruptions described above. In
association with nervous system damage onset may be sudden.
Apparent remission of symptoms followed by relapse is not

uncommon. Speakers may report spasms are less or more
severe at certain times of the day, week, or month, or in
particular speaking situations, or with specific interlocutors.
Symptoms may be ameliorated by tranquilizers or when under
the influence of alcohol. While suggestive of a psychogenic
origin, these features are all common findings in the dystonias
and should not be used to confirm a psychiatric problem.
Page 21 of 39
Whilst spasmodic dysphonia, contrary to earlier suppositions,

is not of psychological aetiology speakers may nevertheless
present with an overlay of psychological symptoms. Surveys
unanimously point up the affective consequences of the
disorder (Baylor et al., 2005, Baylor et al., 2007). Facing up to
frightening progressive changes which you yourself seem
unable to control, but which people, including medical staff,
are only too willing to tell you is all in the mind; living with the
stigma that attaches to such voice characteristics and
associated ‘bizarre’ behaviours; loss of employment, loss of
social standing; doubts about ones personal integrity and state
of mind can for some all add together to foster depression,
personality changes, breakdown of communication within the
family, social circle and workplace.
Behavioural voice therapy has no effect on the underlying

dystonia symptoms. Indeed, success from behavioural therapy
is one indication of a likely psychogenic origin. The current
treatment of choice is botulinum toxin injection of the affected
muscles (Bender et al., 2004). This can bring 4–6 months of
symptomatic relief before a repeat injection is required.
5.3 Speech tics

Tics are recurrent, brief, intermittent, stereotypical
movements which arise outside of or only under partial control
of the individual – a blink of the eyes, shrug of the shoulders,
twisting of the head, shouting of a sound or word. Tics that
involve verbal or speech like behaviours, and/or nonverbal tics
may interfere with speech production and communication
generally.
Tics contrast with myoclonic conditions and seizures, and

compulsive or ritualistic behaviours which may show
themselves as compulsive spitting, touching, shouting, (p.
264) reciting over and again of words or sequences of words
or sounds. They contrast with the repetitive stereotypies found
in autism, some psychiatric disorders and in some post brain
injury cases. Tics are not acquired habits or mannerisms,
though it is important to be alert to the possibility that an
apparent mannerism is a compensatory mask for an
underlying tic or other movement disorder.
Simple tics involve one (uni- or bilateral) group of muscles

(eye wink, pouting of the lips, sticking the tongue out),
complex ones several groups, or indeed a whole behavioural
Page 22 of 39
sequence resembling a normal motor act (writing gesture,

utterance of whole phrase, throwing, shaking the fist). Tic
episodes can involve a sudden and rapid jerking movement
(clonic tics) or a slower, held postural change (dystonic tics) or
isometric contraction (tonic tics). Depending on the aetiology
and severity they may be more or less constant, or
intermittent – several times per day, per week, per month, or
less frequent. The course may be transient (passes within a
year) or stretches out chronically.
One of the commoner disorders linked to tics is Tourette

syndrome (TS), a neurological disorder in which motor and
phonic tics (Albin and Mink, 2006) are prominent. Phonic tics
is a label coined to cover the fact that people with TS may
manifest vocal (throat clearing, shouting, crowing, barking,
squealing, gargling….) and speech (uttering specific speech
sounds or words) behaviours, but tics may also include
nonverbal sounds such as sniffing, lip smacking, clicks,
blowing, sucking, raspberries. The repertoire of motor tics can
encompass face twitching, nodding, shoulder shrugging, eye
rolling and many more. Outbursts of foul language (coprolalia)
(Van Lancker and Cummings, 1999) or obscene gestures
(copropraxia), occur in around a third of patients. The mean
age of onset is around 7 years (range ca. 3–12 years) though
phonic tics commonly emerge somewhat later. For most people
there is a lessening of tic severity or remission in late
adolescence or adulthood.
Typically a sufferer shows multiple tics, either simultaneously,

or over a short period of time, usually in bouts. The anatomical
site (eyes, neck, face…) and type (e.g. vocal, speech) may alter
over time, as can the frequency and complexity of the tics. Tics
are involuntary in as far as at some stage the person is no
longer able to resist their expression. However, around 4 out
of 5 patients experience premonitory sensations. They have
the feeling they need to blink, cough, shout, touch, or
whatever, but are able for a period (minutes, an hour even) to
suppress the compulsion. At the end of that time they have the
urge they must perform the behaviour to release the tension.
The precise timing of this release can have a degree of
voluntary control.
One or more neuropsychiatric disturbances commonly coexist

with the tics – including obsessive-compulsive thoughts or
behaviour, attention deficit hyperactivity disorder, anxiety,
Page 23 of 39
depression, self injurious behaviour, and possibly personality

disturbance. Whether they represent the expression of a
common underlying factor with the tics or are comorbid for
some other reason remains an ongoing debate. Language
delay, reading disorder, and stuttering may also accompany
the tics. Whether what is observed as stuttering is separate or
coterminous with the tic behaviour is disputable (Ludlow and
Loucks, 2003, Mulligan et al., 2003).
(p.265) Speech tics in TS seldom impair intelligibility, in so

far as they appear only in self-limiting bouts. However, in that
they represent socially unacceptable behaviours and the
height of symptoms peaks during the school years, the broader
effects on communication may be considerable.
5.4 Palilalia
In palilalia a speaker appears to become stuck on a sound,
word or phrase, repeating it over and over, typically a few
times, but 15–20 repetitions in a row are not unknown.
Generally repetitions are of final words, sounds or syllables. In
attempting to say ‘Pass me the salt’ the person says ‘pass me
the salt the salt the salt the salt….’; ‘I need the nurse’ appears
as ‘I need the nurse-urse-urse-urse-urse. Characteristically
iterations occur with a fixed, stereotypic intonation, with
fading loudness and excursion of articulatory movements, and
at least the perception that each successive repetition is faster
than the previous (Borsel et al., 2007, Benke and Butterworth,
2001). Speakers appear fully aware of the behaviour but are
unable to inhibit it. The degree to which palilalia appears in a
person’s speech can vary according to task and linguistic unit,
being more often heard in conversation, less so when
repeating phrases after the examiner or on reading and
automatic sequences.
Although the classical picture is the one just described, some

writers have included under the label of palilalia all sorts of
iterations of whole utterances, word initial sounds, and whole
word repetitions (Benke and Butterworth, 2001) that more
appropriately should be viewed as indicative of underlying
language processing, apraxic, phonological or dystonic
difficulties rather than the type of motor disruption causing
the classical palilalic picture.
5.5 Tremor
Page 24 of 39
Tremors of one kind or another occur as part of many

neurological conditions, classically Parkinson’s disease and
essential tremor. Relatively isolated tremor like behaviours
more liable to have a bearing on speech and voice are
essential tremor and myoclonus of the palate, tongue or jaw
(Silverdale et al., 2008, Samuel et al., 2004).
Essential tremor labels an isolated (i.e. not part of a more

general condition), slowly progressive, chronic condition
involving involuntary, rhythmic tremor of a body part.
Commonly it commences in the hands or arms, but may go on
(or rarely start) to involve the head, vocal cords and tongue.
When the latter are involved, seldom before the seventh
decade, disruption to speech and voice is possible. Hand
tremor may impair writing or typing or render it entirely
impossible.
Palatal myoclonus presents as a rhythmic contraction of either

or both sides of the soft palate (Samuel et al., 2004). Adjacent
structures, and sometimes distantly the diaphragm and eyes,
may also be involved, giving lingual or laryngeal myoclonus. At
first the movement may be reported by the sufferer as a
clicking in the ears (from contraction of the tensor veli palatini
muscle which also opens the Eustachian tube). It may arise as
an idiopathic, essential condition, typically in the 30–40 year
age range, or symptomatically at (p.266) any time after
infarcts, trauma, tumour or infections, usually of the
brainstem. Emergence of the myoclonus may be as long as one
year post onset of the responsible illness. In essential palatal
myoclonus the individual may be able to modify the tremor by
intention or adopting compensatory neck positions, or mouth
opening. It does not usually constitute a major cause of
intelligibility loss.
5.6 Whisper and Mutism

Whispering and mutism do not constitute diagnostic entities.
They are though a (occasionally sole) feature of numerous
neurological aetiologies. Elective (sometimes termed selective)
mutism, functional voice disorders and severe depression
represent likely non-neurological aetiologies here contrasting
with the neurological causes.
Mutism is present in the aptly named akinetic mutism, a

condition linked to frontal lobe damage and characterized by a
pronounced diminution of nearly all motor functions, including
Page 25 of 39
facial expression, gestures, and speech output. The person

nevertheless remains apparently alert. Less extreme forms
may be associated with a whispered voice. An isolated apraxia
of the larynx has been claimed (Marshall et al., 1988, Sieron et
al., 1995) where voluntary movements of the oral articulators
remain intact but the person is unable to consciously initiate
phonation. Non-conscious, spontaneous laryngeal sounds (e.g.
cough, sigh, yawn) remain intact.
In what has been described as dynamic aphasia (Robinson et

al., 2006) attempts to elicit a spoken (or any) response from
the individual may be met with muteness, or a severely
delayed response that then appears in just a whisper, with the
person apparently unable to sustain output beyond a few
words before it fades again into silence. Whether dynamic
aphasia represents a separate diagnostic entity or is merely a
sign of frontal involvement remains unresolved. Progressive
loss of voice ending in mutism is a profile reported in some
cases of frontal and frontotemporal atrophy.
People with locked in syndrome (Smith and Delargy, 2005,

Chisolm and Gillett, 2005) are unable to move any part of their
body, including the vocal cords, except for eye movements and
blinking. Hence they are mute. Being a disorder arising from
brain stem pathology, cognition is usually intact. Individuals
remain fully alert and may be able to acquire sophisticated
alternative means of communication employing the intact eye
and blinking movements.
A period of mutism is a common sequel early after stroke or

head injury, especially frontal lesions. Over days or weeks this
may resolve via a whispered voice (with or without aphasia) to
dysarthric, apraxic or normal speech. Muteness arises as a
transient and longer term sequel after some surgical
interventions (e.g. commisurotomy, posterior fossa operations,
especially in children). Transient muteness may be a
manifestation of epileptiform seizures, either as one element
of a complex pattern or as an isolated speech arrest.
Uni- and bilateral opercular lesions can cause muteness

(Kuroda, 2007). The Francophone label – labio-facio-glosso-
pharyngo-laryngo-paralysis (Foix Chavany Marie syndrome) –
is more illustrative of the presenting motor picture of what
some consider a cortical version of pseudobulbar palsy. There
is paralysis of the lower face, masticatory, (p.267)
Page 26 of 39
pharyngeal and laryngeal muscles, but, when it occurs in

isolation, all other language (including writing) and
neuropsychological functions remain intact. Characteristically
there is no paralysis of upper or lower limbs and there is an
automatic-voluntary dissociation. For instance the person is
able to smile, swallow, lick their lips spontaneously, but not to
command. Onset may be sudden (e.g. stroke) or progressive
(e.g. frontal atrophy).
Whispered voice or total mutism may be present in the end

stages of several degenerative neurological conditions,
including motor neurone disease/amyotrophic lateral sclerosis,
some cases of multiple sclerosis, multiple system atrophy,
progressive supranuclear palsy and Parkinson’s disease. In the
latter three weak(ening) voice, problems with initiation or
sustaining of phonation may be early signs of disease.
Bilateral vocal cord palsies render the speaker mute (Rubin

and Sataloff, 2007). Unilateral cord palsies produce
biplophonic phonation, but in an attempt to avoid the resultant
unnatural sounding voice, speakers may compensate by
speaking in only a whisper.
5.6.1 Prosody
Prosody refers to the general melody of speech derived from
variation in the components of pitch, loudness, rate/duration.
Linguistic prosody concerns the use of prosody to signal
grammatical contrasts (e.g. ‘That’s MY coat’ vs ‘THAT’S my
coat’; TOYshop vs toy SHOP; ‘you’re coming tomorrow!’ vs
‘you’re coming tomorrow?’). Affective prosody concerns the
emotional content of utterances expressed through
manipulating pitch, loudness, duration (e.g. ‘The sausage has
fallen in the custard’ spoken with an angry vs laughing vs sad
tone; ‘You’re so kind’ intended as a sincere vs ironic
comment).
Linguistic a- or dysprosody may arise after left or right

hemispheric lesions and can be disrupted by dysarthric and
apraxic speech. Typically in phonemic paraphasia prosody is
preserved. Affective aprosody is associated with right
hemisphere lesions and some neurodegenerative conditions.
In expressive a- or dysprosody speakers are unable to signal

the linguistic contrasts noted above and/or cannot convey
emotional content. Speech may sound monotone, monoloud,
Page 27 of 39
monorate, or inappropriate stress and intonation patterns may

appear. In receptive prosodic disturbances individuals fail to
pick up or misunderstand prosodic cues to linguistic or
affective meaning. Thus breakdowns in communication occur
because the person fails to understand/produce the necessary
linguistic marker to correctly convey/apprehend the meaning
of an utterance or they misconstrue or listeners misinterpret
the emotional intention – an ironic ‘you’re so kind’ is taken as
sincere; intended enthusiasm is heard as indifference.
An awareness of prosodic disturbances is important as a

possible source of comprehension or expression problems and
broader communication and interaction breakdown. It is also
important as the flattened intonation and quiet, slow speech
common in aprosodia, or instances of getting the ‘wrong end
of the stick’ may be misinterpreted as signalling an underlying
affective or neurobehavioural disorder when none is present.
Alternatively changes may be falsely put down to disorders of
attention, cognition or motivation (Blake et al., 2003).
(p.268) 6 Development of a foreign accent

People may be referred to clinic because they have acquired
what appears to be a foreign accent. The vast majority of
published cases are neurogenic, though psychogenic origins
have recently been reported (Gurd et al., 2001, Reeves et al.,
2007).
6.1 Re-emergence of a previous foreign accent

Speakers who migrated from one country to another, or even
from a different part of the same country, may have lost the
accent of their place of origin, yet after stroke or head injury
they speak again with their former accent (Roth et al., 1997,
Seliger et al., 1992). A possible neurolinguistic explanation
given for this phenomenon is that it ‘costs’ someone
(especially if they moved after the teenage years) in terms of
processing resources, to alter a previous accent and maintain
a new one. The new one may never become fully automatised.
When processing resources are compromised from
neurological damage, the ability to pay this cost is affected
and the previously less costly pattern reemerges.
6.2 Acquired foreign accent syndrome

Here, after a neurological episode a person is perceived as
speaking their native tongue with a foreign accent or different
regional accent, despite the fact that they have never lived in
Page 28 of 39
that place, have no knowledge of the alleged base language

and know no one who speaks with that accent. This is totally
unrelated to issues of language change in bilingual or polyglot
aphasia. FAS is as likely to be found in absolutely monolingual
speakers as any others. The accent may be heard transiently
for a few days or weeks or be permanent, unmodifiable by the
speaker. Most reported cases have arisen from left hemisphere
lesions, cortical and subcortical, but right hemisphere
aetiologies are recorded (Dankovičová et al., 2001, Miller et al.,
2006a). Aetiologies have included stroke, head injury, multiple
sclerosis, vasculitis, and dystonia.
Sometimes listeners perceive a definite geographical accent.

More usually listeners perceive only some generic ‘Slav’ or
‘Southern’ accent or disagree on where the accent comes from
(Christoph et al., 2004, Di Dio et al., 2006). Typically speech
does not contain all the features that might be linked to a
given perceived accent and even features present may not
necessarily appear constantly or consistently. Rather,
impressions of being Italian, French or whatever can hinge on
key features picked up by the listener (Gurd et al., 1988). In as
far as different listeners may focus on separate features, not
every listener hears the same accent (one thinks it is French,
the other Polish). In so far as features may be more or less
prominent on different occasions, the same listener may judge
an Italian accent one day, a German one the next. Hence the
ease with which such behaviour is dismissed as psychiatric.
Detailed acoustic studies of people with FAS reveal a

catalogue of changes associated with the altered accent.
Changes can involve syllable structure (e.g. ‘spy’ sounds like
‘suhpy’; ‘big dog’ like ‘biguhdog’, ‘string’ like ‘trin’), prosodic
alterations, or individual sounds (e.g. w sounds like v, r is
rolled instead of burred). Many cases also have an
accompanying mild agrammatism, word finding difficulty and
slowed, hesitant speech, which (p.269) lend an air of
foreignness. No unifying factor explains all cases, except in
most general terms that there are subtle perturbations to the
speech output mechanism, at the level of planning or
execution in either or both segmental (individual sounds) or
suprasegmental (prosodic) features. The common denominator
appears to be that the prominent changes to a speaker’s
speech are ones that listeners associate with an extant
Page 29 of 39
different accent or language. It is the disorder in the ear of the

listener par excellence.
FAS is seldom linked with impaired intelligibility. This does not

mean people with FAS do not experience problems with
communicating. They may despair at the readiness of others to
brand them as psychiatric cases, malingerers, posers; tire of
the condescending ‘foreigner talk’ addressed to them; no
longer tolerate the endless quips of family, friends and
strangers at their expense; and most of all, mourn for their
lost accent and what it meant for their identity and feeling of
belonging (Miller, 2009).
7 Treatment
Medical and or surgical interventions can influence speech to
a degree in some medical conditions (Duffy, 2005, McNeil,
2008), though in others may have no or a detrimental effect
(Schulz, 2002, Sapir et al., 2008). Speech language therapy
can improve communication for most people with neurogenic
motor speech disorders, including with degenerative
conditions and with longstanding changes, even if
improvement is seldom to a premorbid state.
Gains may be made through specific direct work on

respiration, voice, resonance and articulation. Progress may
come from introduction of techniques that influence speech
overall (e.g. rate control techniques). On occasion, spoken
communication has to be augmented by gestural, written or
other instrumental means; or alternative non-verbal methods
of communication sought.
While some treatment approaches for some conditions have

well developed evidence bases for what works for whom when
and how, definitive large scale studies or well controlled case
series demonstrating efficacy for others have still to be carried
out.
Ackermann, H., Mathiak, K. and Riecker, A. (2007) The

contribution of the cerebellum to speech production and
speech perception. The Cerebellum, 6, 202–213.
Page 30 of 39
Albanese, A. (2007) Dystonia: clinical approach. Parkinsonism

and Related Disorders, 13, S356–S361.
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Treatment of spoken language disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Treatment of spoken language

disorders
Jane Marshall
DOI:10.1093/acprof:oso/9780199234110.003.15

There are three broad types of speech disorder that can arise
from brain damage: dysarthria; apraxia (or dyspraxia); aphasia
(or dysphasia). The first two affect the muscular control or
coordination of speech. In contrast, aphasia is a language
disorder. Here the speech impairment is part of a complex of
symptoms, typically involving several aspects of
communication. This chapter discusses therapies for people
with dysarthria and apraxia of speech, and remediation of
spoken language impairments in aphasia.
Keywords: speech disorders, dysarthria, apraxia, aphasia, brain damage,

language impairment
1 Introduction
There are three broad types of speech disorder that can arise
from brain damage: dysarthria; apraxia (or dyspraxia); aphasia
(or dysphasia).
The first two affect the muscular control or coordination of

speech. In contrast, aphasia is a language disorder. Here the
Page 1 of 41
speech impairment is part of a complex of symptoms, typically

involving several aspects of communication (see Chapter 13).
The different speech disorders can coexist, e.g. a person may

have both aphasia and dysarthria, or aphasia and apraxia.
Also, the speech problem may be just one aspect of a more
global neurological condition that carries further implications
for communication. For example, dysarthrias often co-occur
with generalized motor difficulties that make it difficult for the
person to write or use technological aids.
Numerous treatments for neurological speech problems have

been attempted, a selection of which are summarized below.
Although diverse, these are underpinned by some common
principles.
◆ Many therapies aim directly to recover lost skills or

functions, e.g. through repeated and structured practice. If
successful, these treatments may work by promoting a
degree of neural reorganization.
◆ Alternatively or additionally, treatments may aim to

compensate for the difficulties. Such compensations may be
made by the person with the speech problem, by
drawing upon retained skills, or they may be employed by
those in the person’s environment.
◆ The role of the environment in creating barriers for

people with speech problems has been particularly
emphasized in the therapy literature (e.g. Pound et al.
2000). As a result, many treatments focus as much on that
environment as on the individual with the disorder.
2 Therapy for people with dysarthria

Dysarthria ranges from a mild loss of intelligibility, e.g. due to
damage to a single cranial nerve, to complete anarthria, due to
a severe loss of the neuromuscular control of speech.
Prognosis is equally varied. Some individuals, e.g. those with
vascular aetiology, may expect a good recovery, while others
are coping with progressive and terminal conditions. (p.275)
The social effects of dysarthria are wide-ranging, with
implications for the person’s working life, personal
relationships, and family roles. There is no single ‘dysarthria
therapy’. Rather, clinicians employ a range of approaches,
Page 2 of 41
which vary across individuals, and within the treatment of the

same individual over time.
2.1 Goals of therapy

Therapy aims to maximize the effectiveness, efficiency, and
naturalness of communication (Duffy 1995). This entails a
number of component aims.
◆ To restore or improve particular muscular functions, such

as vocal cord closure. This is particularly relevant for those
who can expect a degree of physiological recovery.
◆ To maintain neuromuscular function for as long as

possible, e.g. in the case of some progressive disorders.
◆ To compensate for lost function, particularly when

improvement of neuromuscular function is not achievable.
◆ To provide psychological support, e.g. to help the person

deal with the profound life changes associated with
dysarthria and, in some cases, plan for the progressive loss
of speech. Support may consist of counselling, information
and advice, and contact with relevant social and disability
organizations.
2.2 Therapy regimes
Dysarthria calls for flexible therapy regimes. Some may be
catered for in a single episode of intervention, while others
require ongoing support, which changes in nature as the
disease progresses. Therapy regimes should take account of
the needs of family members, e.g. through relatives’ support
groups. Therapy settings should also be flexible. For example,
therapy aiming to modify the person’s environment is best
conducted in that environment, some individuals may benefit
from group therapy.
Individuals with complex neurological conditions typically

receive input from a range of professionals. Coordination of
multidisciplinary input is crucial.
2.3 The role of assessment in planning therapy

Assessment has many roles.
Page 3 of 41
◆ To probe the individual’s view about their problem, e.g.

about what impairs intelligibility, what helps, what
situations are most difficult, what strategies they are
already using, and the role of others in either easing or
exacerbating the problem. Ideally, therapy is client-driven,
e.g. by targeting the aspects of speech that most concern
them, or by building upon strategies that they have already
started.
◆ To identify a target for intervention, e.g. by indicating

which impairment to the speech mechanism most reduces
intelligibility.
◆ To identify an approach, e.g. focal or mild impairments

may benefit from a speech-orientated approach, while
degenerative conditions usually call for compensatory
techniques.
◆ To identify factors that influence management decisions.

These include medical or personal factors such as fatigue
that are likely to impact upon the individual’s response to
therapy.
(p.276)
◆ To evaluate environmental factors. Here client’s insights
can be supplemented with clinician observation, e.g. of the
person’s communication with significant others, and by
structured questioning, e.g. about the layout of the home,
social activities undertaken, and barriers confronted during
those activities. This assessment is particularly crucial in
planning communication-oriented approaches.
◆ To provide a baseline against which to measure progress.

Baseline data may comprise quantitative or instrumental
measures and/or intelligibility ratings. It should include
measures of the dysarthric person’s perspective, such as
qualitative evaluations of their communication experiences.
2.4 Therapy approaches
2.4.1 Speech-orientated behavioural approaches (see examples in
Table 15.1)
These involve exercises and drills aiming directly to improve
neuromuscular function and hence speech. Tasks are
hierarchically organized, progressing from readily attainable
to more ambitious goals, and involve repeated and frequent
Page 4 of 41
practice. To achieve the latter, clinicians normally provide

homework exercises. Ideally, the task is developed in
Table 15.1 Examples of speech-oriented

approaches for dysarthria
Target Example Aim/rationale Relevant

parameter exercises dysarthria
types
Respiration Inspiritatory To improve Flaccid

checking breath support Ataxic
(Netsell 1992); for speech and Hypokinetic
the person is prevent air
instructed to wastage, e.g.
‘take a deep where there is
breath’ and reduced vocal
‘now let the cord adduction;
air out slowly’ uses the
inspiratory
muscles to
maintain
relatively
constant
subglottal air
pressure
Phonation Pushing, To maximize Flaccid

pulling, and vocal cord dysarthria
lifting adduction and only
exercises (e.g. possibly
Aronson improve vocal
1990); cord strength;
effortful appropriate for
movements, people with uni
such as or bilateral
pushing vocal cord
against the weakness
arms of a
chair, are
coordinated
with
phonation
Page 5 of 41
Target Example Aim/rationale Relevant

parameter exercises dysarthria
types
Phonation Lee Silverman To raise speech Hypokinetic

Voice Therapy volume by dysarthria
(e.g. Ramig et improving self associated
al, 2004) monitoring of with
vocal intensity Parkinson's
and control over Disease
this parameter
Articulation Drill To improve Flaccid

(Rosenbek and accuracy and Spastic
LaPointe intelligibility in Ataxic
1985); an articulation; Hypokinetic
individual may promote Unilateral
hierarchy of compensatory upper motor
speech sounds strategies, e.g. neuron
is developed; by helping the
targets are person to attain
modelled by acceptable
the clinician articulatory
and cued, e.g. substitutions for
with problem sounds
illustrations of
their
production
and hands on
assistance
in reaching
articulatory
placements;
targets are
practised and
consolidated
through drills
(p.277) consultation with the dysarthric person, since self-

directed therapy achieves better retention and generalization than
purely clinician-led approaches (e.g. Wertz et al. 1984). Feedback is
important, with specific feedback, outlining the type and locus of
errors, being more useful than general comments about
intelligibility (Till and Toye 1988). In some settings, feedback may
include instrumental techniques (see Section 2.4.6).
Page 6 of 41
A typical therapy cycle involves:
◆ discussion and explanation, including the rationale for the

exercise and how it relates to the person’s problem;
◆ practice with hierarchically structured tasks;
◆ feedback and self-evaluation;
◆ repeated practice, possibly at a more demanding level;
◆ practice of the target skill in communicative/

conversational tasks.
2.4.2 Compensatory behavioural approaches (see examples in

Table 15.2)
These aim to improve intelligibility without necessarily
changing neuromuscular function. A good example is therapy
that compensates for poor articulation by reducing speech
rate.
2.4.3 Communication-oriented approach (see examples in Table

15.3)
This approach may be offered in isolation, or as a supplement
to behavioural therapy. It aims to develop strategies, which
can be adopted by both the dysarthic person and their listener,
to facilitate communication, despite continuing problems with
intelligibility. Strategies should be developed in the light of
environmental assessment findings. The client, and significant
others, should play a major role in developing the ideas and
should be provided with opportunities to practise and modify
the strategies in therapy sessions.
Page 7 of 41
2.4.4 Prosthetic devices used in dysarthria therapy

A number of prostheses play a role in dysarthria therapy,
ranging from ‘low tech’ materials, such as alphabet boards, to
more sophisticated devices, such as artificial larynxes. Some
prostheses are recommended when direct, behavioural
therapy is unlikely to work. For example, hypernasality, due to
velopharyngeal inadequacy, typically responds poorly to
behavioural management (Duffy 1995; Theodorus and
Thompson Ward 1998), but positively to palatal lifts (see
Yorkston et al. 1988). These consist of a metal plate, fitting
rather like a denture, with a posterior flap that aids elevation
of the velum. Similarly, reduced volume, as occurs in
hypokinetic dysarthria, may not be amenable to behavioural
management, but might be assisted by a portable amplifier.
Other devices can supplement behavioural approaches. A good
example is a pacing board, which is a strip of wood marked
with regular slots. This helps the client regulate speech rate
by pointing to each slot as every word or syllable is produced.
2.4.5 Alternative and augmentative communication (AAC)

AAC includes some of the strategies and protheses that have
already been discussed. Other tools include: symbol charts;
photographic communication books; icons; word and alphabet
charts; word-processing software; e-mail; speech synthesizers;
portable, commercially available computer aids. (p.278)
Table 15.2 Examples of compensatory

behavioural approaches for dysarthria
Page 8 of 41
Target Approach Aim/rationale Relevant

parameter dysarthria
types
Respiration Optimal breath Improve Flaccid

group coordination Spastic
(Linebaugh between Ataxic
1983); speech and Hypokinetic
Assessment respiration
establishes the
number of
syllables that can
be produced
comfortably on
one breath; the
client practises
segmenting
utterances
according to this
figure; drills may
aim gradually to
increase the
optimal breath
group
Rate Pause Rate Flaccid
modification reduction Spastic
(Yorkston et al. improves Ataxic
1988); pause intelligibility Hypokinetic
boundaries are by allowing Unilateral
identified, e.g. in more time for upper
a written articulation; motor
sentence or modifying neuron
passage; the pauses All
client practises reduces rate
saying the target but preserves
passage with the natural
identified pauses; speech
pauses are rythms;
sustained for a pauses are
given time easier to
Alphabet board modify than
supplementation speech
(Beukelman and duration
Yorkston 1977;
Page 9 of 41
Target Approach Aim/rationale Relevant

parameter dysarthria
types
Crow and The alphabet
Enderby 1989); board helps
the person points the person
to the 1st letter controlspeech
of each word as rate; aided
they say it, using speech is
an alphabet more
board; the intelligible
technique is than unaided
practised with speech, both
utterances of because rate
increasing length is reduced
and in and additional
conversational information
contexts supplied by
the letter cue
Selection of AAC methods involves numerous factors such as client

choice, attitudes to technology, cognitive and literacy skills, motor
skills, and communicative need. The role of AAC for any individual
may change over time. For example, people with progressive
disorders may become increasingly dependent on AAC. In such
cases, it is desirable to discuss and introduce possible methods
before speech becomes unintelligible, so that the client is involved
in the decision-making process.
2.4.6 Instrumental contributions to therapy
Dysarthric people have to regain control over a mechanism
that, prior to the onset of their disabilities, was rapid and
automatic. Such learning benefits from feedback, one source
of which is instrumentation. A selection of instrumentation
used in dysarthria therapy is summarized in Table 15.4.
Therapies incorporating instrumentation can bring about

significant gains. For example, Thompson and Murdoch (1995)
used kinematic instrumentation to provide a patient with
feedback about respiration patterns, and so improved
phonation times. Electromyographic (EMG) feedback has been
used positively in the treatment of impaired velar fuction, and
Visispeech in the treatment of parkinsonian dysarthria
(Johnson and Pring 1990 and see (p.279)
Page 10 of 41
Table 15.3 Examples of communication-oriented

strategies
Strategies adopted by the dysarthric speaker
♦ Convey how communication is to take place, e.g. by

showing a card explaing the dysarthria and outlining
the person’s preferred communication method
♦ Establish the topic of conversation, e.g. by pointing to

an icon or spelling the topic on an alphabet board;
signal changes in topic
♦ Modify content and length of utterances, e.g. by

limiting production to key words or by increasing
redundancy
♦ Monitor listener’s comprehension and check whether

utterances have been understood
Strategies adopted by the listener
♦ Reduce environmental obstacles, such as background

noise
♦ Adopt active listening, e.g. feed back what has been

understood so far; be prepared to initiate repair when
comprehension fails
♦ Encourage the dysarthric person to employ

alternative approaches to communication, e.g. ‘can you
spell that word out for me?’
Strategies adopted by both the speaker and listener
♦ Maintain good eye contact
♦ Agree upon methods of feedback, e.g. some diads

may adopt a gesture to signal when comprehension has
failed;
♦ Agree upon repair strategies, e.g. some dysarthric

speakers may ask listeners to guess targets, while
others may prefer that they remain silent and wait for
clarification. Some speakers may value explicit
feedback about where speech intelligibility broke down
Page 11 of 41
Theodoros and Thompson-Ward 1998 for review). Despite this, the

application of instrumentation, at least in Britain, seems limited
(Coventry et al. 1997).
2.4.7 Surgical and pharmacological approaches
In some settings treatments provided by speech and language
therapists are supplemented by medical interventions,
involving surgery or pharmacology.
Many surgical procedures are for disorders of phonation, and

aim either to facilitate cord approximation, in the case of
flaccid dysarthrias, or prevent hyperadduction, in the case of
spastic dysarthrias (see summary in Table 15.5).
Hypernasality, as a result of velopharyngeal incompetence,
may be helped by phyaryngeal flap surgery, which, in effect,
builds up the posterior pharyngeal wall and so facilitates
closure with the velum (although the efficacy of this surgery is
disputed; see Duffy 1995 for review).
Recent years have seen the increasing use of Deep Brain

Stimulation as a treatment for Parkinson’s Disease. This
involves the surgical implantation of electrodes into the brain.
These emit electrical pulses, in an attempt to inhibit abnormal
brain signals. Although results have been encouraging for
movement, effects on speech are variable and may even be
negative (e.g.Farrell et al 2005; Gentil et al 2000; Tripoliti et al
2008). (p.280)
Table 15.4 Examples of instrumentation used in

dysarthria therapy
Page 12 of 41
U Tube manometer Measures air pressures generated

by exhalation; used in therapy
aiming to improve breath support
for speech (e.g. Rosenbeck and
LaPointe 1991)
Kinematic Records movement of the chest

instrumentation wall; can help dysarthric people
improve respiratory function
(Theodoros and Thompson-Ward
1998)
Visipitch, Visispeech, Provide visual feedback about

Speech viewer various vocal parameters, such as
fundamental frequency, intensity,
and duration; used in therapy for
phonatory and prosodic disorders
(e.g. Johnson and Pring 1990; Le
Dorze et al. 1992)
Nasopharyngoscopes Positioned in the nasal cavity to
provide a view of the
velopharyngeal sphincter from
above during speech, and so offer
feedback about the elevation of the
velum; used in therapy for
velopharyngeal disorders
Nasometer Measures nasal and oral accoustic

energy and so provides the patient
with feedback about the degree of
nasal resonance during speech;
used in therapy for velopharyngeal
disorders
EMG feedback Provides feedback about muscle

activity, e.g. of tongue, lip, and
other facial muscles; used in
therapy for articulation disorders
Page 13 of 41
Many neurological conditions are managed with drug treatments

that have associated benefits for speech, such as mestinon for
myasthenia gravis. The specific pharmacological management of
dysarthric speech requires further investigation, but might involve
antispasticity medications and interventions to combat tremor and
choreiform movements (see Rosenfield 1991). Clinicians need to be
aware of the medication taken by patients and any associated side-
effects for speech.
3 Therapy for apraxia of speech
There is a huge debate about the nature of speech apraxia (see
Ballard et al. 2000). However, most agree that it is an
impairment of volitional speech production in the face
Table 15.5 Examples of surgical procedures used

in the treatment of dysarthria
Disorder Treatment
Hyperadduction Laryngeal nerve section (Dedo 1979).

of vocal cords Paralyses one vocal cord and so
prevents hyperadduction
Injection of botulinum toxin into
tyroarytenoid muscle (Aronson 1990)
blocks release of acetylcholine from
nerve endings, so denervating some of
the thyroarytenoid muscle and
preventing hyperadduction
Hypoadduction Laryngoplasty (Koufman 1986).

of vocal cords Implants cartilaginous material
between the thyroid cartilage and inner
thyroid perichondrium, so displacing
the paralysed cord medially and
facilitating cord approximation
Teflon/collagen injection into
submucosal tissue of paralysed vocal
cord. Increases the bulk of cord and so
facilitates approximation
Velopharyngeal Pharyngeal flap surgery (Johns 1985)

incompetence
(p.281) of preserved linguistic and motor execution abilities. It

differs from dysarthria in that there is no loss of strength or
neuromuscular control. Rather the disorder is specific to the
planning of speech movement.
Page 14 of 41
Apraxia varies in severity. In mild cases, intelligibility may only

be affected for long, phonologically complex words, or when
rapid speech is attempted; while, severe apraxia can cause
complete loss of speech.
Apraxia may occur in isolation, or with other communication

problems, particularly aphasia. When other disorders are
present the clinician has to decide which problem to treat. If
the language problem is severe, this should be the focus of
therapy. Conversely, apraxia should be treated if poor
intelligibility is the main barrier to communication and if the
person has sufficient language to benefit from improvements
in speech.
Therapy for apraxia can aim to improve speech planning, and

hence intelligibility, or to facilitate communication despite the
speech problems. The former requires client-centred
behavioural approaches. The latter takes more account of the
communication environment and typically involves both the
client and his or her key interactants. With many individuals,
therapy tackles both aims, in sequence or parallel.
3.1 Therapies aiming to improve speech planning

Speech planning therapies typically involve repeated and
structured practice of a hierarchy of speech sounds, normally
progressing from single syllables/words, to phrases and more
extended utterances. Therapy also seeks to extend skills from
structured tasks to spontaneous production. A general
hierarchy of difficulty is known to apply in apraxia (Darley et
al. 1975). For example, within the consonants nasals are
typically easiest, while affricates are more difficult, and
clusters particularly so (although personal hierarchies may
differ from the typical pattern). Therapy stimuli are designed
in the light of this hierarchy. So, for example, drills may
progress from /m/ + V words (May, more); to /m/ + V + /m/
words (maim, mime); to /m/ + V + C words (man, mine) and so
on.
Some individuals with severe apraxia need help to phonate,

before articulation drills can begin. Various techniques can be
applied here, such as using a cough or sigh to elicit voice.
Some may be able to use familiar songs or intoned speech, or
automatic utterances such as counting or reciting the days of
the week. One therapy for severe apraxia, the Voluntary
Page 15 of 41
Control of Involuntary Utterances, seeks to exploit islands of

automatic speech, by bringing these under more conscious
control.
A selection of programmes used in apraxia therapy is

summarized in Table 15.6. Efficacy data for these programmes
are variable. For example, Wambaugh and Doyle (1994)
reviewed 28 treatment studies for apraxia of speech, and
conclude that only eight achieved posttreatment retention of
target skills, although since this review other studies have
reported more positive outcomes (e.g. Freed et al. 1997;
Wambaugh et al. 1998). One paper suggests that therapy
should take more account of principles of motor learning, e.g.
in the presentation of stimuli and feedback. When such
principles are applied, better maintenance of effects may be
achieved (Ballard et al. 2000). The most recent and
comprehensive review of the Apraxia therapy literature also
found variable outcomes (Wambaugh et al 2006 a & b) and
substantial weaknesses that need to be addressed in future
research (Wambaugh 2006). (p.282)
3.2 Communication-oriented approaches
Table 15.6 A selection of programmes used in

treating apraxia of speech
Programme Brief description References
8 Step Continuum A hierarchy of stimulus Rosenbeck et

presentation ranging al. 1973
from imitation of the
therapist to question/
answer responses
Melodic Uses preserved singing Sparks et al.

Intonation skills to elicit speech, 1974
Therapy (MIT) e.g. via ‘intoned’
utterances
Prompts for Uses physical prompts Square et al.

Restructuring on the patient’s face to 1985; Freed
Oral Muscular facilitate articulation et al. 1997
Targets (PROMPT) (e.g. tapping nose for
nasal sounds)
Minimal Pairs Organized practice of Wambaugh

Treatment minimal pair contrasts et al. 1998
Page 16 of 41
Programme Brief description References

(e.g. ‘sheet’ versus,
‘seat’; ‘shame’ versus,
‘same’, etc.)
Intersystemic Uses relatively intact See account

Facilitation/ systems to facilitate in
Reorganization impaired systems; Wambaugh
typically involves et al. (2006
coupling speech with b)
meaningful gestures,
such as Amer-ind signs
or finger tapping
These approaches aim to facilitate communication despite the

impairment, and are rather similar to those used with
dysarthric clients (see Table 15.3).
What are the clinical effects of apraxia therapy? As outlined

above, some treatments may improve speech intelligibility, e.g.
so that the person can clarify problem words or make better
use of the phone. Compensatory approaches may enable
apraxic people to participate more in conversation despite
their problems, albeit in a new way. These approaches may
also help the person recover from, or repair, communication
breakdowns when they occur.
4 Remediation of spoken language impairments in aphasia

Aphasia causes diverse problems with spoken language. Some
people cannot speak at all, or produce nothing but
incomprehensible jargon. Those who can speak, may be
frustrated by frequent word-finding blocks or problems in
building sentences. Many aphasic people have reasonable
comprehension, although not of abstract language or complex
sentences; while others have virtually no understanding of
speech. Aphasia also typically involves reading and writing
problems (see Chapters 8 and 16).
Aphasia is typically a chronic condition, with initial severity

being a strong predictor of outcome (Pedersen et al. 1995). A
longitudinal study of 119 aphasic patients found that 43% still
had significant aphasia at 18 months post onset; whereas only
24% had recovered (Laska et al. 2001). Clearly, therapy needs
to respond to the long-term nature of the problem.
4.1 Setting goals in aphasia therapy
Page 17 of 41
Goal-setting in aphasia therapy should start with the person

(see Pound et al. 2000).
◆ What communication are they attempting, and what

difficulties do they encounter?
◆ What would they like to be able to do?
◆ What do they see as their main skills?
(p.283) Care-givers’ views are also crucial, e.g. about what

most impairs communication, and what strategies are being
adopted by the aphasic person or by family and friends.
Through such questions, the therapist and aphasic person

start to pinpoint likely goals for intervention. Assessment is
conducted in the light of these goals, i.e. it aims to identify
obstructions to realizing the goals and useful skills. This may
well involve investigations of the person’s language, but also
evaluation of their environment and those in contact with the
person. At the end of the process we should arrive at goals
that are specific, realistic, measurable, and of benefit to the
person’s daily communication (see box below for an example
of goal setting).
Goal setting in aphasia therapy: a case example

(Maneta et al. 2001)
Page 18 of 41
Phillip was 84 and had jargon aphasia following a stroke 5

years ago. Previous therapy aimed to improve his speech,
but with little progress. Phillip lived with his wife, Florrie,
but had few other social contacts.
In the initial discussion Florrie said that telling Phillip

anything was a ‘nightmare’. She had to repeat information
several times, and even then could not be sure that he had
got it. Misunderstandings were common and could lead to
conflict, e.g. when Phillip felt that Florrie was keeping
things from him. It was agreed that therapy should aim to
reduce communication breakdowns at home.
Assessment aimed to identify the nature of Phillip’s input

problem, e.g. using tests of word discrimination and
comprehension, and to explore reading, to see whether
this could compensate for the difficulties. An interactive
assessment also looked at how Phillip and Florrie were
dealing with communication. Florrie was given a number
of written questions to convey to Phillip, using any method
of communication that she liked. The transaction was
videoed and analysed.
Here are the main assessment findings.
♦ Phillip’s auditory input was severely impaired.

Although he could discriminate environmental sounds,
he could not discriminate, recognize, or understand
spoken words.
♦ Phillip’s reading was much better than his auditory

input. For example, he could match written words to
pictures, but failed when the same words were spoken.
♦ The interactive assessment confirmed that

communication often broke down. Florrie tried to help
Phillip, e.g. by repeating words and phrases, but often
this did not work. She rarely wrote information down,
despite Phillip’s good reading.
♦ The therapy goals were specified in the light of these

findings.
♦ To improve Phillip’s discrimination of speech sounds,

at least in single words; If successful, this should enable
Page 19 of 41
him to recognize and comprehend spoken words more

reliably, and so ease communication at home.
♦ To modify Florrie’s communication with Phillip, e.g.

so that she made more use of writing. This should
reduce breakdowns and make exchanges between them
more efficient and enjoyable.
(p.284) 4.2 Therapy for word comprehension problems

As suggested in the box, therapy may aim to alleviate the
problems arising from a comprehension deficit. One approach
aims directly to improve the person’s input processing. The
other aims to compensate for the problem, by changing the
behaviours of those in the person’s environment.
4.2.1 Direct therapy approaches

Therapy to improve word sound discrimination (Morris et al.
1996; Morris 1997)
Some comprehension problems arise from deficits in sound

discrimination. This is signalled by difficulties with all auditory
input tasks, including repetition, and particularly by an
inability to discriminate minimal pairs, such as ‘cat’ and ‘bat’.
People with this problem benefit from visual cues, such as lip
reading (Shindo et al. 1991).
The therapy developed by Morris et al. (1996) aimed to

improve discrimination, using carefully structured minimal
pair tasks and lip reading cues (see the box for examples of
tasks). After therapy, both participants demonstrated gains,
e.g. in repeating words, but not in comprehension. A similar
approach was attempted by Maneta et al. (2001, and see the
box below), but again with disappointing results. To date,
studies suggest that improving sound discrimination is difficult
and, even if progress is made, this may not benefit
comprehension.
Examples of therapy tasks to improve word sound

discrimination
Same/different judgements
Page 20 of 41
♦ Two CV syllables are spoken by the therapist, e.g. /

ka/ /ta/. The aphasic person indicates whether they are
the same or different.
♦ Two VC syllables are spoken, e.g. /ak/ and /at/. The

aphasic person indicates whether they are the same or
different.
Matching spoken to written words
♦ The aphasic person is given a written word (e.g.

‘car’). The therapist says a word that is either the same
as the written word or minimally different (e.g. ‘tar’).
The aphasic person indicates whether the spoken word
matches the written word.
♦ The aphasic person is given several rhyming written

words (e.g. car, tar, par, etc.). The therapist says one
word that then has to be matched with its written
target.
Matching sounds to letters
♦ The aphasic person is given several written letters,

e.g. T, K, B, etc. The therapist says a sound (e.g. /t/) that
then has to be matched to one of the letters.
All the above tasks are presented first with lip-reading

information (where the aphasic person is encouraged to
watch the therapist’s face), then with ‘free voice’ (where
the aphasic person looks away).
(p.285) Therapy to improve semantic processing
Some comprehension problems appear to be due to a semantic

disorder, as indicated by poor written and spoken
comprehension, and comparable problems in production. In
such cases, a semantic approach might be attempted, e.g.
involving word to picture matching, picture and word
categorization, and word association tasks. This approach was
adopted by Grayson et al. (1997) with successful results. A
subsequent stage of therapy successfully combined semantic
and auditory therapy. For example, now the person had to
match spoken words to pictures, but with rhyming foils
(target: beer; distractors: deer and tear).
Page 21 of 41
Another treatment study involved a client who could not

access semantic information from spoken words, even though
his comprehension of written words was good (Francis et al.
2001). Two forms of therapy were attempted. One only
involved written words, e.g. a written word is presented with a
written definition and then has to be copied. The other
involved comparable tasks, but now with spoken words. Both
treatments were effective, in that treated words were
understood better after therapy than untreated words.
However, the spoken word tasks produced more durable
effects.
4.2.2 An indirect approach to comprehension therapy

Indirect therapies aim to advise friends and relatives about the
aphasic person’s difficulties, and help them communicate in
ways that tap into their strengths (e.g. Lesser and Algar 1995).
A good example can be found in Maneta et al. (2001; see the
first box, this chapter). Phillip had much better reading than
auditory comprehension. Despite this, his wife Florrie rarely
wrote things down for him and, when she did, she tended to
produce long sentences that were hard for Phillip to
understand. Therapy demonstrated how to simplify
information, using strategies like chunking information and
writing only key words. In post therapy assessment there were
fewer communication breakdowns between Phillip and Florrie
and those that did occur were resolved more rapidly.
4.2.3 Summary and conclusions

Comprehension problems are difficult to treat, not least
because the impairment may obscure the person’s
understanding of therapy. There is some evidence that input
skills can be enhanced through treatment, but often such
direct work needs to be combined with indirect interventions
with friends and relatives. Maneta et al. (2001) show that
simply advising friends and relatives to change their
communication is often not enough. Family members need
time, guidance, and practice to develop new skills.
4.3 Therapy for production problems
Page 22 of 41
An almost ubiquitious production problem is anomia, or a

word-finding deficit. Research has shown that word-finding
can fail for different reasons (e.g. Howard and Orchard Lisle
1984, Kay and Ellis 1987), which suggests that therapy should
be tailored to the particular processing needs of the individual.
Another important finding is that anomia usually reflects
problems of access rather than loss of vocabulary. We know
this because people may achieve a word on one occasion, but
not another. Also, aphasic people often benefit from cues (e.g.
Howard et al. 1985), which may consist of the first sound of
the (p.286) word (phonological cues) or information about its
meaning (semantic cues). This suggests that practice may
recover more permanent access to words. Finally, we know
that production is affected by numerous variables, such as
word frequency, imageability, and age of acquisition (see
Nickels 1997), which has implications for the selection of
vocabulary in therapy.
4.3.1 Word finding therapy

A typical programme of word finding therapy entails repeated
practice with a target group of words. These are carefully
selected for their personal relevance, e.g. they may be
associated with a particular interest or life goal. A second
control group of words may be tested but not treated. The
content of therapy reflects a person’s skills and weaknesses.
For example, semantic approaches might be used if there are
felt to be semantic difficulties or if semantic cueing seems to
prime access to words. The programme should be intensive,
e.g. at least two sessions a week. After this, retention of the
vocabulary is tested, typically with a picture naming
assessment. This may be administered again, after a pause, to
see whether gains have been maintained. Approaches to
naming therapy are summarized below.
Semantic approaches
Semantic tasks require the person to reflect upon the meaning

of words, with the rationale that improved semantic
processing may lead to better recovery of word forms (see
examples in the box below). A number of studies demonstrate
that repeated administration of such tasks can improve
naming of the treated vocabulary, and with good maintenance
of effects (e.g. Marshall et al. 1990; Nickels and Best 1996a ,
b). Best outcomes occur when semantic tasks are combined
Page 23 of 41
with exposure to target word forms (Le Dorze et al. 1994;

Drew and Thompson 1999), i.e. the aphasic person should hear
or see the target word, and think about its meaning.
Examples of semantic tasks to aid word finding
♦ Word to picture matching (e.g. Marshall et al. 1990).

The person is given a picture, together with 5 written
words comprising: the target, 2 words with similar
meanings, and 2 words with similar forms. For example,
the picture shows a television and the words are
television, radio, computer, telescope, telephone. The
person has to select the word that matches the picture
and (optionally) read it aloud.
♦ Semantic questions (e.g. Barry and McHattie 1991).

The person hears a question about each target word,
which requires a yes/no answer. For example, ‘is a
microwave used for cooking food?’; ‘does a microwave
do the washing?’
♦ Semantic associations (Jones 1989). A target word is

written in the centre of a piece of paper. Surrounding
this are a number of other words that are either related
or unrelated to the target. The person has to select the
related words and explain their selection. For example,
target word: car; words for selection: petrol, paraffin,
garage, stable, wheels, rails, Ford, Microsoft.
(p.287) Phonological therapy
Phonological therapies work on the premise that exposure to

the phonological properties of a word will prime access. Tasks
typically involve repeated naming with phonological cues, i.e.
ones that provide the first sound of the word or its rhyme (see
box for an example). Phonological therapies can improve
access to words and with good maintenance of effects (e.g.
Raymer et al. 1993; Robson et al. 1998b).
Page 24 of 41
A phonological therapy programme (Robson et al.

1998a)
Gillian had jargon aphasia with incomprehensible speech

and severe word-finding problems. Speech was her priority
for therapy, a decision endorsed by her husband.
The speech problem seemed due to impaired phonological

access, in that comprehension was good and naming
benefited from phonological cues. Gillian suggested that
some phonological recovery might be taking place, which
was rapidly fading, e.g. she said of one word-finding block:
‘I had it there and then it went’. Gillian had good
phonological skills on input, e.g. could discriminate
minimal pairs like ‘bat’ and ‘hat’ and could repeat words.
Therapy aimed to build up her phonological knowledge

about words. If successful, naming should improve.
♦ Stimuli. 50 words were chosen for personal relevance.

They all began with one of 8 phonemes and had one or
two syllables. Fifty untreated words acted as controls.
♦ Materials. Pictures of therapy items, a chart providing

the written form of the 8 initial phonemes.
Task 1. Syllable structure
♦ The therapist said the target word and Gillian had to

indicate whether it had 1 or 2 syllables, by pointing to
the numbers on a sheet of paper
♦ Gillian was given a target picture. She had to think of

its name and indicate how many syllables were
contained in the name, by pointing to the numbers on
the paper.
Task 2. Initial phoneme
♦ The therapist said a target word and Gillian had to

point to its first phoneme on the chart.
♦ Gillian was given a target picture. She had to think of

its name and point to its first phoneme on the chart.
Page 25 of 41
♦ As in the previous step, but now Gillian was asked to

say the name of the picture.
Outcome
Gillian’s naming of both treated and control words

improved and this was well maintained. Other language
tasks that were unrelated to therapy were unchanged.
(p.288) Relay therapy
Therapy may use intact skills to access words ‘in a new way’. A
good example is given by Nickels (1992). T.C. had severe
problems both in naming and reading aloud, although his
writing was better. Therapy helped him to develop letter to
sound matching skills, i.e. he learned to associate the letter ‘t’
with the sound /t/, ‘k’ with /k/, and so on. One effect of this was
to improve his reading. Another was to give him a new route
to naming, in that he could imagine the written name of an
object, think of its first letter, convert that into a sound, and so
give himself a phonological cue. Sure enough, after therapy,
T.C.’s spoken naming became almost as good as his written
naming (for a similar approach, see White-Thomson 1999).
4.3.2 Therapies aiming to compensate for speech production

problems
Some individuals may be unable to improve their word finding
at all and, even when therapy is effective, often only treated
words improve. Therefore, therapy should also develop
strategies to compensate for the word-finding problem.
Strategies typically engage alternative forms of output. One

candidate is writing, which has been used successfully even
with severely aphasic people (e.g. Robson et al. 1998a, 2001;
Beeson 1999). When writing is even more impaired than
speech, nonverbal strategies, such as gesture and drawing,
may be favoured (e.g. McIntosh and Dakin 1989; Sacchett et
al. 1999; Rose, 2006).
A more comprehensive approach involves ‘total

communication’ (Lawson and Fawcus 1999; Pound et al. 2000).
Here the aphasic person is encouraged to communicate using
any technique available to them, including speech, writing,
drawing, communication books, facial expression, and gesture.
Developing total communication is complex. Typically, the
Page 26 of 41
person is first made aware of the various communication

options. They may need help with particular skills, e.g. to
produce recognizable drawings or gestures. Constrained
tasks, e.g. ones in which the person has to communicate a
hidden word or picture using total communication, can further
develop the skills. Finally, therapy often needs to encourage
the generalization of skills to settings beyond the clinic, e.g. by
involving relatives or through communication assignments.
4.3.3 Summary and conclusions

Therapy can help aphasic people recover access to words and
with good maintenance of effects. Furthermore, aphasic
people can take considerable control of this aspect of their
therapy, since self-administered tasks can be very effective
(Marshall et al. 1990; Nickels and Best 1996a , b). The aphasic
person should also select the vocabulary for therapy.
Other findings are less encouraging. For example, naming

therapy often only benefits treated words, with no carry-over
to controls. This result is still useful, particularly if the words
are carefully chosen. However, it indicates that therapy should
include compensatory strategies such as total communication,
which provide aphasic people with a resource for what is likely
to be a chronic problem.
(p.289) 4.4 Connected speech and conversation

Aphasia may leave single-word processing relatively
unscathed, but severely impair sentences. This makes it
difficult for the person to deal with language about events and
relationships, the typical subject of most conversations.
Sentence processing can fail for different reasons, e.g. some

people have problems with the meaning relationships of
sentences, while others have problems in building surface
forms (see Marshall et al. 1999). Such variations have
stimulated a range of sentence therapies, a selection of which
are summarized in Table 15.7.
There is evidence that therapy can improve sentence

production and comprehension. However, the extent of change
is variable. Some studies only improved treated structures,
while others also benefited untreated forms, and, while some
treatments changed spontaneous production, this was not
Page 27 of 41
always the case (see Marshall, 2002 for a review of sentence

therapy outcomes).
The above limitations suggest that sentence therapy alone may

not necessarily improve the aphasic person’s ability to
converse. An alternative, or additional approach is to create
conversational environments that are accessible to aphasic
people despite their impairments. Typically, this involves
training conversational partners, who may be volunteers or
friends and relatives of the aphasic person (e.g. Kagan and
Gailey 1993; Pound et al. 2000). Such trained interactants can
make it possible for even severely aphasic people to
participate in conversations, and so regain access to one of the
primary social functions of language.
Another response to the problem of change is to provide

aphasic people with a communication aid that enables them to
capitalise on whatever language skills remain. One such aid is
the ‘Sentence Shaper’ (Linebarger et al 2000). This computer
device enables the person to record and other fragments of
speech, so building up connected production. Practice with the
aid has been shown to improve the grammatical cohension and
complexity of speech, and to make it more informative
(Linebarger et al 2007, McCall et al 2009).
4.5 Constraint Induced Aphasia Therapy

The above sections have outlined treatments for specific
aphasic symptoms. A more generalist approach is Constraint
Induced Aphasia Therapy (Pulvermuller et al 2001). Drawing
on constraint therapies in other domains, this approach
inhibits the use of compensary strategies, such as gesture, so
requires the person to target speech. It involves practice of
increasingly demanding speech acts within a highly intensive
regime, i.e. at least 3 hours per day. Evaluations suggest that
CIA may outperform other approaches, although it is difficult
to know whether this is due to the constraint or intensity of
practice.
4.6 Concluding comments

Aphasia therapy works. That is not to say that we can cure
aphasia, but we can bring about numerous valuable changes,
such as improved comprehension, word finding, and (p.290)
Page 28 of 41
Table 15.7 Examples of treatments for sentence

processing disorders in aphasia
Approach Rationale Brief References

description of
therapy content
Event The aphasic Making Marshall et

Therapy person cannot decisions about al. (1993)
determine the events shown Marshall
role structure on video, such (2009)
of events, or as who
who is doing instigated the
what to whom action and who
or what was
changed by it
Mapping The aphasic (i) Analysing Jones (1986)

Therapy person has written Schwartz et
some syntactic sentences, eg to al. (1994)
skills, but find the verb, Mitchum et
cannot relate agent al. (1995)
sentential (instigator of Rochon et
word order to action) and al. (2005)
meaning patient (person Byng (1988)
or object Nickels et
Changed by an al. (1991)
action) Marshall et
(ii) Matching al. (1997)
reversible
sentences to
pictures, such
as ‘the woman
chases the man’
(iii) Ordering
sentence
fragments to
describe
pictures
(iv) Interpreting
and ordering 3
argument
sentences, such
Page 29 of 41
Approach Rationale Brief References

description of
therapy content
as ‘Bob lends
£5 to John’
Verb The sentence Naming verb Fink et al.

Access disorder is at pictures with (1992)
Therapy least partly cues; carrying Mitchum
attributable to out semantic and Berndt
an impairment tasks with (1994)
in verb verbs, such as Marshall et
retrieval odd one out al. (1998)
tasks Marshall
(1999)
Syntax The aphasic Hierarchical Doyle et al.

Training person has a and cued (1987)
morpho- production of Helm
syntactic target sentence Estabrooks
impairment, or structures et al. (1981)
cannot Helm
generate the Estabrooks
surface forms and
of sentences Ramsberger
(1986)
Treatment The aphasic Practising the Thompson et

of person cannot production of al. (1993)
Underlying process complex forms, Thompson
Forms complex such as and Shapiro
structures, like questions and (1995)
questions and clefts; forming Thompson et
passives, complex al. (1997)
where sentences from Ballard and
sentence simple ones Thompson
elements have (1999)
been moved Thompson
from their 2008
deep structure
positions
Page 30 of 41
sentence building. We can also change the behaviours of those in

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Page 41 of 41
Neuropsychological assessment and treatment of disorders of reading


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Neuropsychological assessment and

treatment of disorders of reading
J. Richard Hanley
Janice Kay
DOI:10.1093/acprof:oso/9780199234110.003.16

Brain injury can disrupt the reading abilities of individuals
whose performance was previously quite normal in a variety of
different ways. This chapter discusses some of the most
common and the most theoretically important types of reading
impairment. It begins with descriptions of the peripheral
dyslexias (pure alexia, letter-by-letter reading, neglect
dyslexia) in which reading appears to be affected prior to the
point at which the word is recognized as a familiar visual form.
Descriptions then follow of central dyslexic impairments (deep
dyslexia, phonological dyslexia, surface dyslexia, and reading
in dementia) in which reading processes generally appear to
be intact up to the point at which the meaning or
pronunciation of a word must be generated.
Keywords: reading disorders, neuropsychological testing, brain injury,

dyslexia, central dyslexic impairments
1 Introduction
Page 1 of 46
Brain injury can disrupt the reading abilities of individuals

whose performance was previously quite normal in a variety of
different ways. In the sections that follow, some of the most
common and the most theoretically important types of reading
impairment are discussed. The review starts with descriptions
of the peripheral dyslexias (pure alexia, letter-by-letter
reading, neglect dyslexia) in which reading appears to be
affected prior to the point at which the word is recognised as a
familiar visual form. Descriptions then follow of central
dyslexic impairments (deep dyslexia, phonological dyslexia,
surface dyslexia, and reading in dementia) in which reading
processes generally appear to be intact up to the point at
which the meaning or pronunciation of a word must be
generated.
A summary of these different types of acquired dyslexia

together with some of their most important associated
attributes can be found in Table 16.1. Although grouping
patients into categories such as these provides an economical
way of summarising a large body of literature, the extent to
which they represent groupings that are scientifically useful is
highly controversial. For example, the nature of the reading
problems suffered by two individual patients who both fit the
criteria for surface dyslexia may differ in fundamental ways
(see section on surface dyslexia). Consequently, we would
encourage clinicians to discover the precise point(s) at which
an individual’s reading ability has broken down rather than to
worry unduly about precisely which type of acquired dyslexic
label best fits them.
It must be acknowledged that at the present time there is

considerable controversy as to which model is best to use
when attempting to explain the reading impairments observed
in acquired dyslexia. Coltheart (1985) advocated a three-route
model that incorporated a nonlexical reading route and two
separate lexical reading routes.
◆ The nonlexical route computes the pronunciation of a

word on the basis of sub-lexical grapheme-phoneme
correspondences (e.g. letter-sound associations). It is
capable of reading accurately familiar and unfamiliar words
whose pronunciation is consistent with those
correspondences (often referred to as “regular” words).
Page 2 of 46
◆ The lexical reading routes can recognise a previously

learnt word by activating its representation in a store of
familiar visual word forms (“orthographic lexicon”).
(p.297)
— The lexical-semantic route involves accessing the
word’s meaning, and would be heavily involved in
silent reading of text. If required, the pronunciation
of the word can be accessed from its meaning.
— The direct-lexical route is based on direct

connections between a word’s visual form and its
representation in a phonological lexicon. It would be
heavily involved in reading aloud.
The lexical routes are equally capable of processing regular

and irregular words so long as they have already been learnt,
but are unable to deal with nonwords or unfamiliar words.
The status of the three-route model has been significantly

strengthened by its successful implementation as a
computational model capable of providing the pronunciation of
written words (Coltheart et al. 1993, 2001) and simulating the
effects of brain injury on word recognition. Nevertheless, the
existence of the direct-lexical route is controversial; Hillis and
Caramazza (1991) claim that the functions it provides can be
performed by the interaction of the lexical-semantic and
nonlexical routes.
A more radical alternative to the three-route model is provided

by a connectionist computational model that is often referred
to as the triangle model (Plaut et al. 1996;
Page 3 of 46
Table 16.1 A summary of the impairments associated with different types of acquired dyslexia
Type of dyslexia Impaired at reading Characteristic responses Ability relatively Common area(s) of brain
to printed words preserved injury
Pure alexia All letters and words No response or responds Writing, recognition of Left occipitotemporal,
with unrelated words orally spelled words callosal Lesions
Letter-by-letter reading Long words; individual Very slow responses; Writing; recognition of Left occipitotemporal,
letters speed affected by orally spelled words callosal Lesions
number of letters
Neglect dyslexia Words and/or text Omissions or Right parietal

substitutions of letters
on one side of word
Deep dyslexia Nonwords; function Semantic errors; visual Reading of content Left
words; words of low errors; morphological words frontotemporoparietal
imageability errors
Phonological dyslexia Nonwords Visual errors Reading of familiar Left anterior perisylvian
words
Surface dyslexia Irregular words Regularization errors; Reading regular words; Left temporal lobe
visual errors high frequency words,
and nonwords
Dementia Irregular words; unusual Regularization errors Reading regular words Left temporal lobe
nonwords
Page 4 of 46
(p.298) Seidenberg and McClelland, 1989). Its advocates claim

that it is not necessary to incorporate a separate nonlexical reading
route. Plaut et al. argue that nonwords and regular words are
generally read aloud via a direct orthography to phonology route
(the triangle’s first arm). Reading aloud of irregular words relies
heavily on an orthography to semantics route (the triangle’s second
arm) and on the connections between semantics and phonology
(the final arm of the triangle). Advocates of the triangle model (e.g.
Patterson and Lambon Ralph, 1999) dispute the view that reading
impairments reflect damage to mechanisms that are specific to
reading. For example, Patterson and Lambon Ralph argue that:
◆ letter-by-letter reading reflects a primary visual
impairment;
◆ surface dyslexia is caused by a semantic impairment;
◆ phonological dyslexia is the result of a phonological

processing deficit.
The triangle model is clearly more parsimonious, but it is

debatable whether its explanations of acquired dyslexia are
equally plausible. For example, the triangle model has not
provided a convincing account of why certain patients can
read irregular words despite being ignorant of their meaning
(see section on reading impairment in dementia).
Many of the conditions discussed in this chapter will affect

profoundly how much pleasure can be derived from reading
books or newspapers. This is particularly likely to be true of
the peripheral dyslexias and of those central dyslexias that
affect retrieval of a word’s semantic representation. Where
reading problems reflect a primary phonological impairment
or word finding difficulty, however, individuals may continue to
read books avidly (e.g. Hanley and McDonnell, 1997). Such
cases demonstrate that comprehension of print can be entirely
preserved even though the pronunciation of many familiar
words can no longer be accessed when reading aloud.
In the sections that follow, we have included studies that

attempt remediation of acquired reading problems. In
determining whether to make use of any of these strategies,
clinicians should bear in mind that they are likely to be time
consuming and should be tailored precisely to the needs and
abilities of the individual concerned. In addition, it must be
borne in mind that statistically significant gains in terms of
increased reading speed or accuracy do not necessarily reflect
clinically significant improvements that will increase a
Page 5 of 46
patient’s quality of life. It is also the case that the reading

impairments experienced by some patients will improve
spontaneously in the months that follow their illness or injury,
although those of others appear to remain stable across all the
years that they have been studied.
2 ‘Pure alexia’ or ‘alexia without agraphia’

2.1 Impairment
Detailed documented accounts of the impairments observed in
pure alexia have been available since the end of the nineteenth
century (Dejerine, 1892; Hinshelwood, 1895). Following a
stroke, both of the patients described in these reports
experienced sudden and complete loss of the ability to read
any words despite intact speech production and (p.299)
comprehension, normal object recognition and apparently
unimpaired general intellectual functioning. Writing was
entirely preserved in both patients (hence the term ‘pure’
alexia), although neither of them was subsequently able to
read back what they had written. The reading problems did
not appear to be the consequence of a basic visual problem
since acuity, colour vision and object naming were good when
objects were presented in the preserved left visual field.
Dejerine’s patient could see letters clearly because he could
accurately copy and describe their visual form (e.g. he said
that the letter Z looked like “a serpent”) but was completely
unable to name them. Extremely poor naming of visually
presented letters has consistently been observed in more
recent reports of pure alexic patients who are unable to read
words aloud (Caplan and Hedley-White, 1974; Coslett and
Saffran, 1989 1992; Miozzo and Caramazza, 1998; Mycroft et
al. 2002). However, all of these patients retained some ability
to process letters:
◆ Caplan and Hedley-White’s (1974) patient could correctly

realign letter tiles that had been rotated away from their
normal orientation.
◆ Coslett and Saffran’s (1992) patient scored 10/10 at

cross-case letter matching.
◆ Miozzo and Caramazza’s (1998) patient was able to

distinguish real letters from pseudo-letters and could
identify canonical letter orientations.
Page 6 of 46
◆ Mycroft et al.’s (2002) patient could perform cross-case

matching of visually presented letters despite a complete
inability to name them. This did not occur because the
patient was suffering from an anomia for letter names
because she was able to name letters perfectly when asked
to recite the alphabet or spell words orally. This suggests
that some pure alexic patients can access the abstract
identity of visually presented letters despite being unable to
name them.
2.2 Anatomical issues
The classical account of the anatomical correlates of pure
alexia derives from Dejerine (1892) and Geschwind (1965). A
left hemisphere lesion produces a right-sided hemianopia
which means that visual information from the right visual field
cannot be processed by the reading system in the left
hemisphere. Dejerine argued that the location of the left
hemisphere lesion also made it impossible for visual
information from the occipital lobe in the right hemisphere to
access the reading system. More recent accounts following
Geschwind (1965) argue that it is a lesion of the corpus
callosum that prevents visual information from the left visual
field crossing from the right to the left hemisphere.
This view has been developed by Coslett and Saffran (1989,

1992). They demonstrated that some patients are able to make
lexical decisions (is this a word or a nonword?) and retrieve
some basic semantic information (e.g. is this word the name of
an animal?) about written words at above chance levels
despite a complete inability to read words aloud. Coslett and
Saffran claim that there is a rudimentary right hemisphere
reading system that can perform lexical decisions and retrieve
semantic information from visually presented words despite
being unable to name any words or letters. An intact right
hemisphere reading system would also explain why some pure
alexic patients who cannot name written (p.300) letters can
access their abstract identity (see above). If words or letters
are to be named, information about letter identity must be
transferred across the corpus callosum to the left hemisphere
(extremely difficult for pure alexics because of their callosal
lesions).
Dejerine (1892) believed that the angular gyrus in the left

hemisphere contained visual representations of words and
letters. However, recent functional imaging suggests that the
Page 7 of 46
fusiform gyrus is more likely to be the locus of the visual word

form area (Cohen et al. 2002), although there is controversy
over its precise role in reading relative to other visual
recognition tasks (Price and Devlin, 2003).
2.3 Remediation
Dejerine’s patient died just over four years after his initial CVA
never having recovered any ability to read words aloud. The
only occasions when he correctly named a letter were when he
traced over their visual form with his finger. The speed at
which he could name letters this way was unfortunately too
slow to allow words to be recognised during reading. This
strategy has sometimes been reported in more recent
accounts of pure alexia. For example:
◆ Case 3 (Benson et al. 1971) sometimes correctly identified

a previously misnamed letter by tracing it with his finger.
◆ Maher et al. (1998) reported that a treatment for pure

alexia based on finger spelling led to a 50% increase in
reading speed with 100% accuracy.
An alternative remediation strategy is to attempt to teach pure

alexic patients to name visually presented letters. If
successful, this treatment should enable them to become
letter-by-letter readers (see next section). Greenwald and
Rothi (1998) report a successful therapy programme of this
kind. They suggest that this remediation strategy is likely to be
beneficial so long as the patient’s ability to recognise orally
spelled words is preserved. It is worth adding a cautionary
note however. Hinshelwood (1900) subsequently reported that
after approximately 6 months, his alexic patient started to
attempt to relearn the alphabet. He practiced daily, and
gradually came to read words “slowly and laboriously, spelling
out the words letter by letter” (Hinshelwood 1900, page 13).
Unfortunately, Hinshelwood (1917, page 5) finally reported
that this man did not persevere with reading in this way
because it “required such intense mental effort”. Remediation
strategies attempted by Mycroft et al. (2002) included an
attempt to teach a patient a small set of high frequency words
by sight, and an attempt to teach her to recognise groups of
letters that co-occur frequently in English words. She was also
taught to recite the alphabet in an attempt to find the name of
the letter that she was looking at. Unfortunately, none of these
Page 8 of 46
strategies proved effective despite the patient’s high

motivation.
2.4 Assessment
Pure alexic patients will have great difficulty in reading aloud
even simple lists of words (e.g. PALPA Test 29, Kay et al. 1992)
or letters (e.g. PALPA Test 22). Writing of the same items to
dictation should be preserved.
(p.301) 3 Letter-by-letter reading

3.1 Impairment
It is widely assumed that the nature of the deficit observed in
letter-by-letter (LBL) reading is qualitatively similar to that
found in pure alexia (see previous section), although there is
little direct evidence to substantiate this claim. In LBL
reading, words are often read aloud accurately but slowly and
laboriously. Reading times increase in line with the number of
letters in a word. For example, Patient DC (Hanley and Kay,
1996), who read relatively quickly for an LBL reader, took just
over two seconds to read 3-lettter words aloud and
approximately five seconds to read 9-letter words aloud.
Patterson and Kay (1982) reported 3 patients who all took over
10 seconds on average to read a 3–4 letter word and over 30
seconds to read a 9–10 letter word. Nevertheless, the
overwhelming majority of words were read correctly by these
patients. The linear relationship between number of letters
and reading times that is observed in LBL reading is not found
in reading aloud by unimpaired individuals (Weekes, 1997). It
suggests that, unlike normal readers, LBL readers are
attempting to recognise a word by first naming its component
letters. Consistent with this idea, some (though not all) LBL
readers say the letter names aloud before the word is read.
There is widespread evidence that LBL reading is associated

with severe letter recognition deficits. In a major review of
LBL reading, Behrmann et al. (1998) found that 50/57 of the
cases showed slow and error prone letter processing when
letters were presented outside the context of words. The other
seven were not tested on speeded tasks. As a consequence,
they suggested that a letter processing deficit is of itself the
cause of LBL reading. Nevertheless, there are at least two
reasons why it appears unlikely that the key deficit is to the
processing of single letters:
Page 9 of 46
◆ LBL readers reported by Rosazza et al. (2007) and

Warrington and Langdon (2002) were able to process single
letters as accurately and quickly as controls.
◆ Lambon Ralph and Ellis (1997) and Crutch and

Warrington (2007) reported individuals with visual dyslexia
whose single letter processing was very poor and seemed to
impair their ability to access visual word forms. Although
these patients made a large number of errors in which the
response was visually similar to the target word, neither of
them showed any signs of LBL reading.
Following Patterson and Kay (1982), others have argued that

the core impairment is a problem in recognising letters in
parallel rather than a problem in recognizing single letters.
There is a great deal of evidence which is consistent with this
claim:
◆ Osswald et al.’s (2002) LBL reader found it more difficult

to recognize words when letters were presented
simultaneously than when they were presented sequentially.
◆ Kay and Hanley’s (1991) LBL reader was slow at

comparing the identities of visually presented letters when
they were presented simultaneously but performed
relatively quickly when the letters were presented
sequentially.
(p.302)
◆ Despite being good at single letter processing, the LBL
readers described by Behrmann and Shallice (1995),
Rosazza et al. (2007) and Warrington and Langdon (2002)
had difficulty in recognizing and naming sequences of
letters.
Arguin et al. (2002) suggested that LBL readers tend to

confuse the identity of letters in a word when attention must
be directed to several letters simultaneously during parallel
processing. Consistent with this claim, they showed that
reading speed increased for LBL readers, but not for controls,
when words were comprised of visually similar letters of high
confusability. Conversely, the visual similarity of letters did not
affect performance in LBL readers when letters in words were
presented sequentially (Fiset et al. 2006). This finding
suggests that the LBL strategy in which patients focus their
Page 10 of 46
attention on individual letters one at a time is employed to

prevent confusion between simultaneously presented letters.
There are some similarities between LBL readers and patients

with attentional dyslexia because, like LBL readers, attentional
dyslexics are better at recognising letters that are presented
singly than in arrays, and have been shown to read long words
less accurately than short words (Price and Humphreys, 1993).
However LBL readers do not typically make transpositional
errors of the kind seen in attentional dyslexia (Shallice and
Warrington, 1977) when reading simultaneously presented
words (e.g. win fed > fin fed).
It has sometimes been claimed that the core impairment in

LBL reading is a word-level deficit rather than a letter-level
impairment, and that LBL reading reflects the compensatory
use of the spelling system to read words aloud (Warrington
and Shallice, 1980). Indeed Warrington and her colleagues
have referred to LBL reading as “spelling dyslexia” (e.g.
McCarthy and Warrington, 1990; Warrington and Langdon,
2002). The discovery of letter processing impairments (see
above) and word superiority effects in some LBL readers (e.g.
Bub et al. 1989; Reuter-Lorenz and Brunn, 1990) has cast
doubt on this claim as a general account of LBL reading.
Furthermore, spelling is severely impaired in some LBL
readers, and it is sometimes impaired in a quite different way
from reading (Hanley and Kay, 1992; Rapcsak, et al. 1990). It
is conceivable, however, as Crutch and Warrington (2007)
have argued, that there exists a small minority of LBL readers
with good letter processing skills who adopt a serial letter
processing strategy because of damage to visual word forms.
Some LBL readers appear to suffer from a clear word level

deficit in addition to their parallel letter-processing deficit.
Whereas some patients (termed “Type 1” LBL readers by
Patterson and Kay, 1982) read words accurately given that
they named the letters correctly, other patients (termed “Type
2” LBL readers by Patterson and Kay, 1982) made errors even
when letters were named correctly. This suggests that Type 2
LBL readers have an additional impairment at the word form
system level that is superimposed on top of their parallel letter
processing problem. An additional lexical or post-lexical
impairment can explain why LBL reading is sometimes
associated with visual errors (Hanley and Kay, 1992),
Page 11 of 46
regularisation errors (Friedman and Hadley, 1992), semantic

errors (Buxbaum and Coslett, 1996), and imageability effects
(Behrmann et al. 1998).
(p.303) There is considerable controversy over whether or

not the parallel letter processing impairment in LBL reading is
the consequence of a more basic visual processing impairment
(see Patterson and Lambon Ralph, 1999; and Farah, 2000, for
discussion). Crutch and Warrington (2007) suggested that
visual crowding is an example of such a deficit. They reported
an LBL reader who was much worse at letter naming when
letters were flanked by additional letters or simple visual
forms. Effects of flankers are observed in attentional dyslexia
(Shallice and Warrington, 1977). However, unlike attentional
dyslexics, Crutch and Warrington’s LBL reader performed
equally poorly when the flankers were drawn from categories
such as numbers, consistent with the view that his letter
processing deficit was caused by foveal crowding.
Page 12 of 46

As is the case with pure alexic patients of the kind described
in the previous section, LBL reading is frequently associated
with lesions to the posterior part of the left hemisphere.
Damage to the left occipito-temporal junction has been
implicated as a probable cause of the difficulties experienced
in recognising words as wholes (Leff et al. 2001). Additional
left hemisphere injuries, it is assumed, will produce a right
sided hemianopia. LBL reading is usually, though not
invariably, also associated with lesions to the splenium of the
corpus callosum (see Binder and Mohr, 1992 for further
anatomical evidence concerning alexics who do and do not
read words letter-by-letter).
Leff et al. (2001) have claimed that a right hemianopia that is

caused by a lesion “affecting either primary visual cortex on
the left, or its geniculostriate afferents” can of itself produce a
reading impairment in patients with no left occipitotemporal
damage, that can be confused with letter-by-letter reading.
The impairment occurs because words can fall outside the
patients’ visual field and require one or more saccades before
recognition is possible. In hemianopic alexia, they claim,
reading times may show word length effects, but are quicker
than for LBL readers (Leff et al. calculate a range of 51–162
msec. per letter) particularly with shorter words. They argue
that it is important to diagnose hemianopic alexia accurately
because there are remediation techniques available that can
increase reading speed in these patients (Kerkhoff, 1992; Leff
et al. 2000).
As in pure alexia, debate has centred on the precise role

played by the left and right hemispheres in LBL readers.
Shallice and Saffran (1986) showed that some LBL readers
could make accurate lexical decisions and semantic
classifications about visually presented words even when the
words were presented so quickly that they could not be read
by a LBL strategy. Similar abilities have been documented in
some (but not all) LBL readers with whom these tasks have
been attempted (Behrmann et al. 1998). Saffran and Coslett
(1998) argue that LBL are using their right hemisphere
reading system (see previous section) when they show these
‘covert’ effects. They claim that LBL reading involves the use
of the damaged primary left hemisphere reading system, and
that the left hemisphere inhibits the intact right hemisphere
reading system. Behrmann et al. (1998), on the other hand,
Page 13 of 46
argue that residual activation within a damaged single reading

system subserved by both left and right hemispheres could
explain these effects so long as it is (p.304) assumed that the
system operates according to the principles of interactive-
activation-and-competition models. McKeeff and Behrmann
(2004) have shown that ‘covert’ effects are fairly fragile,
consistent with the idea that they reflect the output of a
damaged system. Lambon Ralph et al. (2004) provided
evidence that preserved performance by Saffran and Coslett’s
(1998) LBL readers on ‘covert’ tasks may be due to the
different nature of the response demands in tests of
classification and overt word identification.
3.3 Remediation
A number of different remediation strategies have been
attempted with LBL readers.
◆ Moyer (1979) and Moody (1988) employed multiple oral

re-reading (MOR) in which the patient was encouraged to
read the same passages of prose over and over again.
◆ Arguin and Bub (1994) employed a more theoretically

driven technique by focusing on letter processing. They
trained their patient to make cross-case matching decisions
about pairs of letters in different sized letter fonts.
◆ Behrmann and McLeod (1995) attempted to treat their

patient by encouraging her to identify the letters at the end
of a word before saying it aloud.
These techniques generally led to increased reading speeds

that were statistically significant. Unfortunately, none of them
produced clinically effective increases in the time it took to
read words aloud; reading speeds remained disappointingly
slow.
◆ Sage et al. (2005) used an errorless learning technique in

which an LBL reader was presented with a written word
and listened to five presentations of the word’s spoken form
which he then repeated aloud. Strikingly, word level
remediation led their patient to abandon the LBL strategy
and start reading more quickly. However the new strategy
also produced many more visual and semantic errors than
had been observed prior to the treatment.
3.4 Assessment
Page 14 of 46
Measure reading speed on a word list which manipulates

letter length (e.g. PALPA Test 29, Kay et al. 1992).
4 Neglect dyslexia
Page 15 of 46
4.1 Impairment
In neglect dyslexia, portions of the left side of text are
sometimes omitted when passages are being read. When
individual words are being read, initial letters may be
◆ omitted (e.g. cage > “age”);
◆ substituted (e.g. elate > “plate”);
◆ added (e.g. pan > “span”).
Ellis et al.’s (1987) patient defined words consistent with her

neglect error: (e.g. rice > “price . . . how much for a paper or
something in a shop”). It is often assumed that neglect (p.
305) dyslexia is just one of a number of features associated
with a more general neglect of contralesional space. However,
neglect dyslexia has been observed in a number of cases
without other features of neglect (e.g. Baxter and Warrington,
1983; Patterson and Wilson, 1990). In discussing these studies,
Riddoch (1990) has pointed out that reading may be
a particularly demanding task and that evidence of
generalised neglect might have emerged with more stringent
testing of other visual stimuli. Whether or not neglect dyslexia
co-occurs with neglect of objects remains a controversial issue
(Caramazza and Hills, 1990; Haywood and Coltheart, 2000).
There is clear evidence of fractionation of deficits within

neglect dyslexia itself. Although word and text reading may
both be affected in some patients, (e.g. Ellis et al. 1987),
reading of single words can be impaired selectively (e.g.
Costello and Warrington, 1991; Miceli and Capasso, 2001), and
reading of text can be impaired selectively (Kartsounis and
Warrington, 1989). Some patients make more neglect errors
on nonwords than words (Arguin and Bub, 1997), but others
show no lexicality effect (e.g. Ellis et al. 1987). When Ellis et
al. (1987) rotated the page by 90 degrees, their patient no
longer made any neglect errors. In contrast, patient NG
(Caramazza and Hillis, 1990) continued to make errors
affecting the initial letters in a word regardless of whether it
was presented in vertical orientation, mirror image or
inverted. Miceli and Capasso (2001) compared the
performance of two neglect dyslexic patients using the same
test materials and found that one of them (SVE) made
approximately the same number of errors regardless of
whether words were presented horizontally or vertically,
Page 16 of 46
whereas the other (MR) made much larger numbers with

horizontal presentation, but no errors at all with vertical
presentation.
Caramazza and Hillis (1990) suggested that any one of three

distinct levels of representation (retina-centred, stimulus-
centred, word-centred) involved in the early stages of word
recognition might be affected in neglect dyslexia.
◆ The retina-centred level represents the visual shape and

location of visual forms (letters) within the viewer’s visual
field. Patients with retina-centred impairments will make
errors only to words that are presented in the left hemifield
so long as central fixation is maintained.
◆ Stimulus-centred representation maintains orientation

but codes the location of letters relative to each other
irrespective of their absolute location in visual space.
Patients with left-sided neglect associated with stimulus-
centred impairments will make errors regardless of
whether or not a word is presented to the left or right of
fixation, but will not make errors on vertically presented
words.
◆ The word-centred level represents the position and

abstract identities of letters within a word irrespective of
physical location (e.g. orientation). Patients such as SVE
(Miceli and Capasso, 2001), who made neglect errors
regardless of horizontal or vertical presentation, and
whether or not the word was presented to the left or right
of a fixation point, are considered by Caramazza and Hillis
to have a word-centred neglect.
Haywood and Coltheart (2000) reviewed the performance of

14 previously reported neglect dyslexic patients who had been
administered with suitable tests. They found that Caramazza
and Hillis’ theory provided a satisfactory account of all 14 of
them.
(p.306) 4.2 Anatomical issues

Neglect dyslexia affecting the left side of text or words is
generally associated with right occipito-parietal lesions.
However, cases reported by Caramazza and Hillis (1990),
Sieroff (1990), and Warrington (1991) all had left hemisphere
Page 17 of 46
lesions that correspondingly affected word endings and the

right side of text.
4.3 Assessment
In neglect dyslexia, errors when reading words are visually
related to the target word and consistently affect just one side
of the word. In a patient with left-sided neglect, it is a good
idea to use items that remain words when the first letter is
omitted, and where the first letter can be substituted to make
another word (e.g. cage, elate, peach, lever). Ellis et al. (1987)
used a list of this kind.
5 Deep dyslexia
5.1 Impairment
Although the term “deep dyslexia” was first used by Marshall
and Newcombe (1973), the first cases were reported as long
ago as Low (1931) and Goldstein (1948) (see Marshall and
Newcombe, 1980, for an historical review). Marshall and
Newcombe (1966, 1973) investigated the types of word that
their patients found most difficult to read, and examined
systematically the nature of the errors that they made. They
also attempted to explain their pattern of performance in
terms of a model of reading derived from research in cognitive
psychology. In so doing, Marshall and Newcombe provided a
blueprint for subsequent cognitive neuropsychological
investigations of acquired dyslexia.
Several decades of research into deep dyslexia have revealed a

strikingly consistent pattern of reading impairment and
associated language deficits (including agrammatism and
phonological short-term memory problems). Deep dyslexics
are almost completely unable to read nonwords and novel
words aloud. They either respond with a visually similar real
word or they make no response at all. The errors made by
Marshall and Newcombe’s patient (GR) included the following
responses: wux > “don’t know”; nol > “no idea”; Zul > “Zulu”;
wep > “wet”; dup > “damp”.
The probability that a familiar word can be read aloud

correctly is closely related to its concreteness/imageability
rating, with concrete words being much easier to read than
abstract words. For example, LW (Newton and Barry, 1997)
read correctly 19/30 highly concrete words (e.g. house, snake),
but only 1/30 medium concrete words (e.g. friend, joke), 2/30
medium abstract words (e.g. life, hint), and 4/30 highly
Page 18 of 46
abstract words (e.g. fate, hope). Visual errors are most

common on abstract words, with the incorrect response
typically being of higher imageability than the target word
(Shallice and Warrington, 1975). According to Paivio et al.
(1968) imageability ratings are based on the capacity of a
word to arouse sensory experiences of objects, materials or
persons, whereas concreteness ratings are based on the extent
to which a word refers to objects, materials or persons
experienced in the physical world. According to Paivio et al.
concreteness and imageability are (p.307) highly
intercorrelated (r = .83) and in deep dyslexia, they are almost
certainly capturing the same dimension.
Several competing theoretical accounts have been proposed to

explain the imageability effect in deep dyslexia:
◆ In Plaut and Shallice’s (1993) influential computational

model of deep dyslexic reading, it was assumed that
abstract words contain fewer semantic features, and are
therefore less resistant to semantic feature loss following
brain injury than concrete words.
◆ Newton and Barry (1997) argued that abstract words

tend to be more ambiguous than concrete words. They
believe that ambiguity makes lexicalisation (the process
whereby the phonological form of a word is accessed from
its meaning) more difficult for abstract words.
◆ Crutch and Warrington (2005) suggest that abstract

words tend to be represented in semantic memory in terms
of their associations with related concepts (e.g. robbery-
punishment). Concrete words, they argue, tend to be
represented in terms of their similarity to other members of
the same category (e.g cow-sheep). Consistent with this
conceptualization, Crutch (2006) showed that in some deep
dyslexics, semantic errors for abstract words tend to be
associative errors (e.g. police > “evidence”), whereas
semantic errors for concrete words tend to share more
semantic features with the target word (e.g. bough >
“branch”). Because they believe that concrete and abstract
words are represented in qualitatively different
representational systems, Crutch and Warrington’s (2005)
account can accommodate the double dissociation between
deep dyslexia, and a patient who is better at reading
abstract than concrete words (Warrington, 1981).
Page 19 of 46
There is also a part of speech effect in deep dyslexia, whereby

nouns are read better than adjectives, and adjectives are read
better than verbs. However there is strong evidence that this
effect only occurs when part of speech is confounded with
imageability and/or frequency (Allport and Funnell, 1981;
Barry and Richardson, 1988). Deep dyslexics also have
particular problems with function words, often responding
with a different function word (e.g. for > “and”; in > “the”; as
> “he”). This problem occurs despite the fact that many
function words are amongst the most common words in
English. Deep dyslexic patients appear to have lost knowledge
about the syntactic role of function words (e.g. Morton and
Patterson, 1980).
The errors made by deep dyslexics when reading content

words include:
◆ semantic errors, which are generally considered to be the

hallmark of deep dyslexia. Examples include uncle read as
“cousin” (Marshall and Newcombe, 1966), hurt read as
“injure” (Shallice and Warrington, 1975) and grass read as
“lawn” (Saffran and Marin, 1977). Semantic errors appear
to occur with equal frequency in readers of shallow and
deep orthographies (Beaton and Davies, 2007).
Semantically related responses have been shown to be
words that are earlier acquired than the targets (Gerhand
and Barry, 2000). The majority of errors made by GR
(Marshall and Newcombe, 1966) were semantic.
(p.308)
◆ visual errors in which a word is read as a word that
shares letters with the target word. Examples include
crowd read as “crown” (Marshall and Newcombe, 1966),
fixed read as “mixed” (Shallice and Warrington, 1975), and
proof read as “roof” (Saffran and Marin, 1977). Visual
errors are the most common form of errors made by many
deep dyslexic patients.
◆ Sometimes errors are both visual and semantic. Examples

include earl read as “deaf” (Marshall and Newcombe,
1966), and stream read as “train” (Saffran and Marin,
1977).
◆ derivational errors (Marshall and Newcombe, 1966) in

which the errors share a root morpheme with the target
word (e.g. heat > “hot”). However, it must be borne in mind
Page 20 of 46
that morphological errors are also visually and semantically

similar to the target word (for discussion of this issue, cf.
Funnell, 2000).
In terms of the triangle model (Crisp and Lambon Ralph,

2006), deep dyslexia is associated with a severe general
phonological processing deficit that affects reading, auditory
repetition, and rhyme judgement. It follows that reading must
rely on the orthographic to semantic route. In terms of the
three-route model (Coltheart et al. 1993) deep dyslexics have
suffered
◆ severe damage to the nonlexical reading route (hence

abolished nonword reading).
◆ severe damage to the direct-lexical route whereby

familiar words are connected with their pronunciation in a
phonological lexicon because availability of this route would
have allowed them to read aloud function words and words
of low imageability.
It follows from both models therefore, that reading in deep

dyslexia relies on semantic mediation. Newcombe and
Marshall (1980) argued that semantic errors might be an
automatic consequence of the output of the semantic route
when it must operate in isolation. However, unimpaired
individuals do not make semantic errors in picture naming
(where the semantic route must also be operating without any
phonological assistance) to anything like the same extent as a
deep dyslexic patient such as GR (Marshall and Newcombe,
1966) made during reading.
This raises the important question of where precisely the

impairment to the semantic reading route in deep dyslexia
lies. Shallice and Warrington (1980) argued that at least three
different types of deep dyslexia might exist.
◆ input deep dyslexia in which there is a difficulty in

accessing intact semantic representations of low
imageability words. Consistent with this account, Shallice
and Coughlan (1980) described a deep dyslexic patient who
was much better at auditory than written comprehension of
low imageable words. Even though this patient performed
poorly at visual lexical decision (Shallice and Coughlan,
1980), it seems unlikely that the primary cause of deep
dyslexia could have a pre-semantic locus. As Shallice (1988)
Page 21 of 46
pointed out, if the impairment was to the word form system,

it is difficult to see how imageability/concreteness could
exert such an effect on deep dyslexic reading.
◆ central deep dyslexia in which there is said to be an

impairment that affects the semantic representations
themselves. Plaut and Shallice’s (1993) computational
model of (p.309) deep dyslexic reading hypothesises that
semantic features have been lost from semantic memory.
There clearly are patients with central semantic deficits
who make semantic errors on a variety of tasks (e.g. Hillis
et al. 1990). However, although Crisp and Lambon Ralph
(2006) did reveal evidence of written and auditory
comprehension problems in three deep dyslexic patients,
these impairments seemed to be too mild to be the sole
cause of their semantic errors, and poor reading of abstract
words. Moreover, Newton and Barry’s (1997) review of the
literature revealed that deep dyslexics often perform well at
written comprehension so long as they are tested
appropriately.
◆ output deep dyslexia in which there are problems in

accessing the speech output system from intact semantic
representations. Newton and Barry’s review revealed
widespread evidence of speech production problems in
deep dyslexia. Consequently, they suggested that output
problems are the primary cause of deep dyslexia.
In conclusion, the impairment to the semantic reading route in

most cases of deep dyslexia is either to the semantic system
itself or else to the connections between semantics and
phonology. The relative importance of these two types of
impairment remains controversial.

Extensive left hemisphere damage is frequently observed in
brain scans of deep dyslexic patients. Lambon Ralph and
Graham (2000) reviewed 48 articles examining deep dyslexia
and found evidence of damage to the left fronto-temporo-
parietal region in 44 of them. The lesions were generally large
“encompassing at least the perisylvian area and often
extending to include much of the left hemisphere”. Their
review also revealed that the majority of cases occurred as a
consequence of cerebrovascular accident, although there were
Page 22 of 46
a small number of cases with head injury. There were no cases

associated with dementia.
A crucial issue is whether the extensive left hemisphere

damage means that reading depends on a secondary right
hemisphere reading system. Coltheart (2000) pointed out that
the right hemisphere hypothesis does not require that
orthographic processing, semantic processing, and
phonological processing are all carried out by the right
hemisphere: “as long as any one of these three stages cannot
be carried out by the left hemisphere, then some kind of right-
hemisphere reading mechanism will be required if reading
aloud is to be achieved.” In fact, Coltheart claims that the
results of brain imaging studies of deep dyslexic patients
(Price et al. 1998; Weekes et al. 1997) are consistent with the
view that orthographic processing and semantic processing
are carried out initially in the right hemisphere. There is then,
he argues, transmission of information from semantic areas in
the right hemisphere to semantic areas in the left hemisphere
followed by phonological processing in the left hemisphere
leading to spoken word production.
5.3 Remediation
◆ De Partz (1986) attempted to improve the nonlexical
reading skills of a French deep dyslexic patient. She taught
him to blend phonemes to make words and nonwords, (p.
310) and re-taught him grapheme-phoneme
correspondences by associating letters with the phonemes
at the start of familiar words. Phonemes that are
represented by more than one grapheme were taught by an
ingenious series of mnemonics that made use of the
patients preserved knowledge of whole word phonology.
After nine months of intensive therapy, the patient’s reading
accuracy for nonwords had improved from zero to 90%.
Reading of all types of familiar words also improved
dramatically, although irregular words were often
regularised (see section on surface dyslexia).
◆ Nickels (1992) used a similar technique with an English

speaking patient. Unfortunately, he did not learn to blend
phonemes together and so was unable to improve his ability
to read nonwords and words of low imageability. The
technique did, however, improve his ability to read words of
high imageability, perhaps because knowledge of
grapheme-phoneme associations enabled him to generate
Page 23 of 46
his own phonemic cues. These, in turn, may have enabled

him to overcome word finding problems when trying to read
high imageability words.
◆ Stadie and Rilling (2006) retrained a patient to blend

phonemes who subsequently did show improved reading of
trained words, untrained words and untrained nonwords. A
separate lexically based treatment also improved reading of
trained and untrained words.
◆ Hillis and Caramazza (1994) presented a series of theory-

based studies that attempted to remediate lexical
processing skills in patients who made semantic errors.
◆ The programmes used to improve phonological skills in

phonological dyslexia (see next section) might also be
effective with deep dyslexic patients.
5.4 Assessment
Investigate reading accuracy on words of low and high
imageability (e.g. PALPA Test 31, Kay et al. 1992). Examine
responses for evidence of semantic errors in particular.
Examine reading accuracy on functors (e.g. PALPA Test 32)
and nonwords (e.g. PALPA Test 36).
6 Phonological dyslexia
Page 24 of 46
6.1 Impairment
The defining characteristic of phonological dyslexia is a
selective impairment of the ability to read nonwords relative to
real words. Relative preservation of the ability to read familiar
words is probably the reason why phonological dyslexia was
first reported relatively recently (Beauvois and Derouesne,
1979). Since then, cases of phonological dyslexia have been
reported even in countries such as Spain which use a shallow
alphabetic orthography (Cuetos et al. 1996), and Japan where
a patient was described who could read familiar but not
unfamiliar words that were written in the transparent syllabic
script Kana (Sasanuma et al. 1996).
The level of the impairment in nonword reading ability can

vary from one patient to another. For example, WB (Funnell,
1983) virtually never read a nonword correctly, (p.311)
whereas JD (Farah et al. 1996) read 25-30% of nonwords
correctly. In general, however, nonword reading is somewhat
better preserved in phonological dyslexia than it is in deep
dyslexia, with some patients making errors that are
phonologically similar to the target item. Detailed
investigations of the nature of the nonword reading problem in
11 phonological dyslexics (Berndt et al. 1996) revealed that all
of them experienced problems in:
◆ graphemic parsing (how many phonemes does “auk”

contain?).
◆ grapheme-phoneme knowledge (providing the phonemes

associated with single letters).
◆ blending auditorily presented phonemes.
As phoneme blending does not involve reading, some have

argued that phonological dyslexia is primarily the
consequence of a phonological processing deficit that affects
reading, rather than the consequence of an orthographic
deficit per se (e.g. Friedman, 1995; Patterson and Marcel,
1992). Because nonwords have an unfamiliar phonological
form relative to familiar words, these authors argue that
nonwords will be particularly difficult for an impaired
phonological system to generate from print. Consequently
a purely phonological deficit will make reading of nonwords
much more error prone than reading of familiar words. It is
true that many individuals with phonological dyslexia do
appear to suffer from a general phonological deficit that
Page 25 of 46
affects tasks that do not involve reading (for discussion, see

Coltheart, 1996). However, recent studies by Caccappolo-van
Vliet, Miozzo and Stern (2004), and Tree and Kay (2006)
report exceptions to this pattern. Despite impaired nonword
reading, Tree and Kay’s patient performed well at phoneme
segmentation and blending in the auditory modality, and
appeared to have preserved phonological short-term memory
skills. This patient’s ability to read familiar words also
appeared to be entirely preserved. Such a pattern of
performance is clearly consistent with a selective orthographic
impairment to a non-lexical reading route.
It is unusual for reading of familiar words to be entirely

preserved in phonological dyslexia. Some patients show
imageability effects (Farah et al. 1996), and patients such as
AM (Patterson, 1982) are worse at reading function word than
content words. The errors made by AM on content words were
visual/morphological, and on function words
were substitutions. Comprehension of familiar written words
appeared to be entirely normal in AM (Patterson, 1982), who
was able to make visual lexical decisions and make semantic
classifications about written words as accurately as control
subjects, despite poor nonword reading. WB (Funnell, 1983),
on the other hand, was above chance but severely impaired on
written comprehension tasks using words she could
read aloud. In terms of three route models of reading
(Coltheart et al. 1993), the obvious interpretation of these
differences is that patients such as AM are reading via the
lexical-semantic route whereas WB was reading via the direct-
lexical route. However, advocates of two route models such as
Hillis and Caramazza (1991), and Plaut et al. (1996) have
attempted to argue that WB’s reading of words might be
explicable in terms of a partially functional semantic route and
a partially functional phonological reading route.
(p.312) Patients who recover from deep dyslexia sometimes

turn into phonological dyslexics, consistent with the view that
these two types of deep dyslexia are closely linked. For
example, Klein et al.’s (1994) deep dyslexic patient remained
bad at reading nonwords (though nonword reading did
improve over time), but the semantic errors and imageability
effect disappeared with reading of words returning close to
normal levels. Several research groups have suggested that
Page 26 of 46
deep and phonological dyslexia may reflect opposite ends of a

continuum of severity from deep dyslexia (relatively severe) to
phonological dyslexia (relatively mild):
◆ Hanley and Kay (1997) suggested that the continuum may

represent the severity of the impairment to the nonlexical
route and that, as Hillis and Caramazza (1991) argue, even
a partially functioning nonlexical route is able to inhibit
semantic errors in phonological dyslexia.
◆ Friedman (1996) claimed that the continuum represents

the severity of a semantic impairment.
◆ According to advocates of the triangle model (Crisp and

Lambon Ralph, 2006), the severity of both the phonological
deficit and the semantic deficit is critical. At one end of the
continuum, isolated phonological impairments will produce
nonword reading deficits (mild phonological dyslexia).
Additional semantic deficits, or impaired semantic-
phonological interactions, will lead to semantic errors and
effects of imageability in reading (deep dyslexia).
In a review of 37 papers on phonological dyslexia, Lambon
Ralph and Graham (2000) found consistent evidence of
“damage focussed on the anterior perisylvian areas ranging
from relatively circumscribed lesions typically of the left
inferior, posterior frontal lobes to those patients with more
extensive damage involving fronto-temporo-parietal areas”. A
small number of patients had posterior left hemisphere lesions
affecting the occipito-temporo-parietal junction, and two had
right hemisphere lesions. Apart from one case with head
injury, one with Alzheimer’s disease, one with Pick’s disease,
and one with hemispherectomy, all were associated with some
form of cerebrovascular accident.
6.3 Remediation
Remediation is obviously a less pressing issue in a patient
whose ability to read familiar words is relatively well
preserved. Nevertheless, successful therapy programmes
based on teaching of grapheme-phoneme correspondences
(Kendall et al. 1998) and on teaching phonological awareness
skills (Conway et al. 1998) have been reported. Gains were
observed in both real word and nonword reading in these
studies.
Page 27 of 46
6.4 Assessment
Investigate reading accuracy on nonwords (e.g. PALPA Test 36,
Kay et al. 1992). Compare reading aloud accuracy on matched
words and nonwords (e.g. the items from PALPA 25).
(p.313) 7 Surface dyslexia

7.1 Impairment
Early accounts of surface dyslexic reading were provided by
Marshall and Newcombe (1973) and have been the focus of
intensive investigation ever since. Because English does not
employ a transparent alphabetic writing system, written
English contains many irregular words whose pronunciation
cannot be reliably generated on the basis of grapheme-
phoneme rules. The two cardinal features of surface dyslexia
are greater problems in reading irregular words than regular
words (a “regularity” effect) and regularised pronunciation of
irregular words known as “regularisations” (e.g. island >
“izland”; trough > “truff ”; come > “comb”). For example, JC
(Marshall and Newcombe, 1973) correctly read 67/130 (52%)
regular words (e.g. bite), but only 41/130 (32%) irregular
words (e.g. come). MK (Howard and Franklin, 1988) correctly
read 90% of regular words (e.g. shrug,) and 67% of irregular
words (e.g. shove). MP (Behrmann and Bub 1992) correctly
read 100% regular words (e.g. summer), and 80% irregular
words (e.g. island). Most of the errors made by MK and JC
were regularisations, but JC also made some visual errors (e.g.
reign > “region”, bargain > “barge”, bike > “bik”). It is
therefore clear that the lexical reading route is impaired in
surface dyslexia.
The nature of the impairment to the lexical route appears to

differ from one patient to another (see Ellis et al. 2000, for
detailed discussion). As Ellis et al. point out:
◆ some patients such as NW (Weekes and Coltheart, 1996)

who was poor at distinguishing written words from
nonwords, appeared to have difficulties in gaining access to
the meaning of irregular written words.
◆ Others, such as MP (Behrmann and Bub, 1992), who had

difficulties in understanding both spoken and written
words, appeared to have a central semantic deficit.
◆ Finally, there appear to be surface dyslexic patients such

as EST (Kay and Patterson, 1985), FM (Graham et al. 1994),
Page 28 of 46
and MK (Howard and Franklin, 1988) whose problems

reflect a lexicalisation/word finding problem rather than a
semantic deficit.
All surface dyslexics so far tested could read some irregular

words correctly, however. In the case of MP (Behrmann and
Bub, 1992), the ability to do so appeared to be related to word
frequency. MP’s ability to read regular words was unaffected
by word frequency, but less common irregular words such as
anchor and echo were read less accurately than more common
irregular words such as trouble and heart.
It is sometimes claimed that nonword reading is normal in

surface dyslexia, but this is true in only some of the published
cases (e.g. Bub et al. 1985; Shallice et al. 1983; Weekes and
Coltheart, 1996). MP, for example, read 42/44 nonwords
correctly, but MK (Howard and Franklin, 1987) read only
25/30 nonwords correctly, and JC’s nonword reading (Marshall
and Newcombe, 1973) was poorer still. There is therefore no
guarantee that surface dyslexia will be associated with an
unimpaired nonlexical reading route. Nevertheless, the finding
that nonword reading can be unimpaired in a patient such as
MP despite poor reading of irregular words is of considerable
theoretical significance. This is because it represents a double
dissociation with phonological dyslexics such as WB (p.314)
(Funnell, 1982) and provides evidence consistent with the
view that the reading system contains functionally distinct
lexical and nonlexical reading routes. MP has posed a severe
challenge to computational models of reading that dispense
with a separate nonlexical phonological reading route such as
the triangle model (e.g. Plaut et al. 1996). It has not proved
possible for the triangle model to reproduce the surface
dyslexic symptoms observed in MP by lesioning a single
phonological reading route. If a lesion to the phonological
route is large enough to reduce performance on irregular
words to the levels observed in MP, it will also severely
damage reading of regular words and nonwords. Advocates of
the triangle model therefore believe that irregular words are
usually read aloud via the semantic pathway (see section on
reading impairments in dementia).
Some surface dyslexics appear to comprehend words on the

basis of the pronunciation that they assemble. For example, JC
(Newcombe and Marshall, 1973) read begin as “beggin” and
defined it as “collecting money” and made comprehension
Page 29 of 46
errors on homophones (Newcombe and Marshall, 1981). MK

(Howard and Franklin, 1987), on the other hand, whose
surface dyslexia appeared to reflect a post-semantic
impairment read only 52% of a set of irregular words correctly
but defined 88% of them accurately. For example, he defined
steak as “good beef ” but pronounced it as /stik/.

In a review paper, Vanier and Caplan (1985) found that surface
dyslexia could occur following tumour, head trauma and
stroke. Vanier and Caplan found that there was consistent
evidence of damage to left temporal regions in published cases
of surface dyslexia. Damaged areas frequently included the
insula and the putamen. It is also closely associated with left
temporal pole atrophy in dementia (Gold et al. 2005) (see
section on reading impairments in dementia).
7.3 Remediation
◆ A successful technique for treating the symptoms of
surface dyslexia is to repeatedly present words that the
patient cannot read together with a picture that provides
information about what the word means (Byng and
Coltheart, 1986; Coltheart and Byng, 1989). This technique
might help strengthen representations within the
orthographic lexicon and\or strengthen connections
between the orthographic lexicon and the semantic system.
Such a technique is less likely to achieve improvement in a
patient whose reading difficulty is associated with speech
production problems.
◆ Ellis et al. (2000) describe a technique in which the

patient immediately hears a word’s spoken form whenever
the word is read incorrectly. The patient must then repeat
the word whilst thinking about its meaning. Such a
technique might prove successful in treating a number of
different types of surface dyslexia.
7.4 Assessment
Compare reading accuracy on regular and irregular words
(e.g. PALPA Test 35, Kay et al. 1992). Examine responses for
evidence of regularisation errors.
(p.315) 8 Reading impairments in dementia

8.1 Impairment
Page 30 of 46
The results from a number of studies reveal a very strong

association between semantic dementia (progressive aphasia
affecting semantic memory accompanying the temporal
variant of fronto-temporal dementia) and surface dyslexia (see
section on surface dyslexia). All 51 semantic dementia cases
studied by Woollams et al. (2007) became surface dyslexic as
their disease progressed. Graham et al. (1994) found that
irregular words could be read aloud only if they could be
matched with their appropriate picture; irregular words that
could not be matched with pictures were not read accurately.
These researchers claim that for most people oral reading of
an irregular word requires access to the word’s semantic
representation, and that if the semantics for an item are
missing or corrupted, it will not be read accurately. There is
evidence that poor reading of irregular words in semantic
dementia is associated with atrophy of the left temporal pole
(Gold et al. 2005). As Gold et al. point out functional imaging
studies have not shown this to be an area involved in reading
aloud single words. They suggest therefore, that the left
temporal pole provides a gateway to semantic representations
which allow irregular words to be read aloud (Gold et al.
2005).
Nevertheless, there are a small number of patients with

Alzheimer’s disease (Lambon-Ralph et al. 1995; Schwartz et al.
1980) and semantic dementia (Cipolotti and Warrington, 1995;
McKay et al. 2007) who are not surface dyslexic, despite
semantic impairments. For example DC (Lambon Ralph et al.
1995) read correctly 40/42 of a list of irregular words but
defined only 24/42 of them correctly, even though a fairly lax
criterion was used for accepting definitions. Blazely et al.
(2005) reported two patients with equivalent degrees of
semantic memory loss, one of whom was, and one of whom
was not, surface dyslexic. Woollams et al. (2007) believe that
the semantic dementia patients who do not suffer from surface
dyslexia reflect a small subset of the population who learned
to read exception words without semantic mediation via direct
orthographic to phonological connections. Unfortunately this
claim is hard to test in the absence of any assessment of the
way in which patients read exception words pre-morbidly.
Conversely, the existence of such patients has been taken (e.g.

Blazely et al. 2005) to provide evidence that the reading
system contains a direct-lexical reading route that does not
require access to a word’s meaning. Blazely et al. claim that
Page 31 of 46
the correlation between semantic dementia and surface

dyslexia comes about because this route becomes
incapacitated as the disease progresses. Only after the direct
route is lost, they argue, will a patient’s reading of exception
words require semantic mediation. This account requires that
the anatomical location of the direct lexical route is such that
it will also be damaged around the time that semantic
representations of words are disrupted by atrophy of inferior
and anterior areas of the left temporal lobe. Opponents
(Woollams et al. 2007) point out that no neuro-anatomical
evidence currently exists to support this claim.
Two studies have reported effects of word length on the

reading speed of patients with semantic dementia (Gold et al.
2005; Cumming et al. 2006). Cumming et al. reported that
these effects are not as large as those observed in LBL reading
(see earlier section), and that (p.316) the dementia patients
who showed length effects were less impaired on letter
processing tasks and visuo-spatial tasks than LBL readers. As
the semantic dementia patients were all surface dyslexic, it is
likely that the length effect is a direct consequence of reading
via the non-lexical route, rather than impaired parallel letter
processing. Gold et al. did not observe abnormal word length
effects in the reading of patients with Alzheimer’s disease.
8.2 Assessment
The National Adult Reading Test (Nelson, 1982) was designed
to provide a measure of pre-morbid IQ based on the
assumption that irregular word reading is relatively immune to
the effects of dementia. However, it is clear that performance
on the NART is correlated with dementia severity (Patterson et
al. 1994) and there are a number of reports of a decline on this
test as the disease develops (e.g. Fromm et al. 1991; Paque
and Warrington, 1995). Strain et al. (1998) suggest that
decline on the NART can be observed as soon as the disease
develops past the early stages, and Storandt et al. (1995)
report a decline even in mild patients. Alzheimer patients have
been shown to perform well at reading nonwords unless they
are orthographically unusual (Friedman et al. 1992), or
phonologically unusual (Glosser et al. 1998).
Page 32 of 46
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Neuropsychological assessment and rehabilitation of writing disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Neuropsychological assessment and

rehabilitation of writing disorders
Pélagie M. Beeson
Steven Z. Rapcsak
DOI:10.1093/acprof:oso/9780199234110.003.017

Written language provides a means to transform speech into
durable, static visual representations, allowing communication
of specific thoughts and ideas to transcend time and place. As
literate adults, we tend to take for granted our ability to
receive and transmit written messages, but this skill requires
the integrated function of cognitive, linguistic, and
sensorimotor processes that are vulnerable to the effects of
acquired brain damage. The goal of neuropsychological
assessment of writing is to examine the status of the
component processes necessary to support written
communication. An understanding of the nature and degree of
impairment to specific processes, as well as the availability of
residual abilities, provides guidance for the design and
implementation of a behavioural rehabilitation plan that is
appropriate for a given individual. This chapter provides an
overview of the cognitive processes that support writing and a
description of the major acquired agraphia syndromes,
Page 1 of 41
followed by a review of evidence-based treatment approaches

for these writing impairments.
Keywords: writing disorder, cognitive processes, agraphia syndromes, residual

abilities, behavioural rehabilitation
1 Introduction
Written language provides a means to transform speech into
durable, static visual representations, allowing communication
of specific thoughts and ideas to transcend time and place. As
literate adults, we tend to take for granted our ability to
receive and transmit written messages, but this skill requires
the integrated function of cognitive, linguistic, and
sensorimotor processes that are vulnerable to the effects of
acquired brain damage. The goal of neuropsychological
assessment of writing is to examine the status of the
component processes necessary to support written
communication. An understanding of the nature and degree of
impairment to specific processes, as well as the availability of
residual abilities, provides guidance for the design and
implementation of a behavioral rehabilitation plan that is
appropriate for a given individual. In this chapter, we provide
an overview of the cognitive processes that support writing
and a description of the major acquired agraphia syndromes,
followed by a review of evidence-based treatment approaches
for these writing impairments.
2 A cognitive model of writing

The cognitive-linguistic and sensorimotor processes necessary
for writing single words are specified in Figure 17.1.
2.1 Central processes engaged during written language production

◆ Semantic system: knowledge of word meanings stored in
long-term memory.
◆ Orthographic lexicon: memory store of learned spellings.
◆ Phonological lexicon: memory store of sound-based

representations for familiar words.
◆ Graphemes: single letters or letter combinations that

represent a single sound (i.e., phoneme) of a language.
◆ Phonemes: the smallest meaningful units of sound in a

language. (p.324)
2.2 Peripheral writing processes
Page 2 of 41
Fig. 17.1 A dual-route model of written

language processing indicating lexical
(whole-word) and sublexical (phoneme-
grapheme conversion) spelling routes.
Allographic conversion: the process by which abstract

orthographic representations are converted into
appropriate physical letter shapes.
◆ Graphic motor programs: spatio-temporal codes for

writing movements which contain information about the
sequence, position, direction, and relative size of the
strokes necessary to create different letters.
◆ Graphic innervatory patterns: motor commands to

specific muscle effector systems involved in the production
of handwriting.
Page 3 of 41
2.3 Lexical-semantic and sublexical spelling routes

According to the dual-route model of written language
processing that will provide the framework for our discussion
(see Figure 17.1), orthographic information is processed in
parallel by both lexical and sublexical procedures that operate
in an interactive manner. Access to the orthographic lexicon
via the semantic system, either directly or with concurrent (p.
325) input from the phonological lexicon, is referred to as the
lexical-semantic spelling route. This is the most common
manner of spelling familiar words. Spelling can also be
assembled in a sublexical (or non-lexical) manner on the basis
of sound-letter correspondence rules (Ellis 1993; Rapcsak and
Beeson 2002; Tainturier and Rapp 2001). Using the sublexical
route, plausible spellings can be generated for both words and
nonwords by the conversion of phonemes to graphemes as
depicted in Figure 17.1. Assembled spellings are likely to
reflect common sound-spelling correspondences, so that
irregularly spelled words with exceptional phoneme-grapheme
mappings might be regularized (for example, “tough” might be
spelled as tuff ). The sublexical route can provide an important
compensatory spelling strategy when the lexical-semantic
spelling route is impaired. This route is also critical for
spelling pronounceable nonwords (e.g., chulf) that do not exist
in the orthographic lexicon.
Spellings generated by the lexical-semantic and sublexical

spelling routes are held in short term storage while they are
converted into output for handwriting (or typing or oral
spelling). This working memory system for orthographic
information is referred to as the graphemic buffer, and it
serves as an interface between central spelling processes and
the peripheral procedures that support the production of
handwriting. Peripheral writing procedures are accomplished
through a series of hierarchically organized stages that
include allographic conversion, motor programming, and the
generation of graphic innervatory patterns.
3 Clinical assessment of spelling and writing

The initial goal of writing assessment is to determine whether
an individual can meet their daily needs for written language
production. Writing abilities should be considered relative to
premorbid language skills. When agraphia is evident, careful
assessment should be performed to determine the functional
Page 4 of 41
integrity of the various processing components involved in

writing.
A variety of tasks can be used to sample writing performance,

and the comparative performance across tasks allows for the
relative isolation of the damaged components (see Table 17.1).
Conceptually mediated writing can be sampled by asking the
patient to compose a written narrative on a specific topic or
using picture description tasks from standardized tests, such
as the Western Aphasia Battery (WAB; Kertesz 1982) or the
Boston Diagnostic Aphasia Examination (BDAE; Goodglass
2001). Written narratives require grammatical and syntactic
knowledge, as well as higher level conceptual organization.
Written naming can be assessed by using pictured stimuli or
objects from standardized tests, such as the WAB, BDAE, the
Boston Naming Test (BNT; Kaplan et al. 2001) or the
Psycholinguistic Assessments of Language Processing in
Aphasia (PALPA; Kay et al. 1992). Writing single words to
dictation allows examination of various linguistic variables
known to affect spelling performance including word length,
orthographic regularity, word frequency, concreteness,
grammatical class, morphological complexity, and lexical
status (word vs. nonword). Word lists controlled for such
variables are available in published tests like the PALPA (Kay
et al. 1992) or in the literature (e.g., the Johns Hopkins
Dyslexia (p.326)
Page 5 of 41
Table 17.1 Tasks used for the assessment of spelling. Check marks indicate those processes or representations
that are necessary to accomplish the various tasks. (See discussion in text.)
Tasks Lexical-semantic processes Sublexical Central- Peripheral spelling processes

processes peripheral
interface
Syntax/ Semantic Orthographic Phoneme- Graphemic Allographic Graphic Letter Name

Grammar representatio representatio grapheme buffer conversion Motor selection
rules n n conversion programs
Conceptual √ √ √ √ √ √
Written
narrative or
picture
description
Written √ √ √ √ √
Naming
Dictation √ √ √ √ √
Writing to
Dictation
Writing √ √ √ √ √
Homophones
Typing or √ √
Anagram
Spelling
Page 6 of 41
Tasks Lexical-semantic processes Sublexical Central- Peripheral spelling processes

processes peripheral
interface
Syntax/ Semantic Orthographic Phoneme- Graphemic Allographic Graphic Letter Name

Grammar representatio representatio grapheme buffer conversion Motor selection
rules n n conversion programs
Oral Spelling √ √ √
Writing √ √ √ √
Nonwords
Copy
Case √ √
Conversion
Direct Copy √
Page 7 of 41
(p.327)
Page 8 of 41
Table 17.2 Summary of the primary features of various central agraphia syndromes
Central Effect
agraphia
Word length Spelling Word freq Concrete Word class Inability to Characteristic
syndrome
short>long regularity HF>LF con>abstr cont>func spell nonwords errors
reg>irreg
Lexical (or √ √ phonologically

Surface) plausible
Agraphia misspellings;
homophone
confusions
Phonological/ √ √ √ √ phonologically
Deep implausible
Dysgraphia errors; functor
substitutions;
morphological
errors;
semantic
errors (deep
dysgraphia)
Graphemic √ letter
Buffer omissions,
Agraphia substitutions,
additions,
transpositions
Page 9 of 41
√ = significant effect; Reg = regular spelling; Irreg = irregular spelling; HF = high frequency words; LF = low frequency words;
Concrete = concreteness; Con = concrete; Abstr = abstract words; Cont = content words; Func = functors.
Page 10 of 41
and Dysgraphia Batteries; Goodman and Caramazza 1984/2001).

Certain linguistic features and characteristic error types are
associated with damage to particular spelling processes and may
result in specific agraphia syndromes (Table 17.2).
3.1 Central processing components assessed by various writing
tasks
◆ Semantic processing is necessary for the composition of
written narratives, written naming, and spelling words that
sound the same but have different meanings (i.e.,
homophones, such as bear – bare). Although semantic
activation typically occurs when words are spelled to
dictation, these tasks may be accomplished by transcoding
directly between corresponding representations in the
phonological and orthographic lexica (and also by phoneme-
grapheme conversion), therefore bypassing semantics.
◆ Activation of orthographic representations is necessary to

support spelling of familiar words regardless of output
modality (i.e., written spelling, oral spelling, typing, or
spelling with anagram letters).
◆ Sublexical spelling procedures rely on knowledge of

phoneme-grapheme correspondence rules. These skills can
be tested directly with the spelling of pronounceable
nonwords (e.g. merber) that do not have representations in
the orthographic lexicon.
(p.328)
◆ The graphemic buffer holds orthographic information in
short term memory as sequential letters are written, typed,
or spelled aloud. The capacity of the graphemic buffer is
examined by spelling words of increasing length.
3.2 Assessment of peripheral writing processes
Peripheral writing processes serve to transcode abstract
orthographic representations into actual letter shapes. These
abilities can be examined using any of the writing tasks shown
in Table 17.1. Performance on these tasks may be compared to
oral spelling, typing, and spelling by arrangement of letters
(i.e., anagrams) in order to identify potential dissociations
between the various output modalities.
◆ Allographic conversion refers to the ability to assign each

grapheme to the appropriate physical letter shape. This
ability can be assessed by asking patients to transcribe
Page 11 of 41
letters from upper to lower case and vice versa, or to copy

words in a different case or style (e.g., print vs. cursive).
◆ Graphic motor programs and graphic innervatory

patterns control the motor execution of handwriting
movements affecting the overall legibility, size, and
morphology of handwriting. Poor control of movement
speed, force, and amplitude may be readily apparent as the
patient is observed in the act of writing. Peripheral writing
processes may also be examined by asking the patient to
copy words or single letters. Keep in mind that copying may
be accomplished without activation of the orthographic
lexicon, letter shape selection, or graphic motor programs if
it is performed in a manner that is more like drawing a
picture than writing.
3.3 Comparison of writing abilities with related language and motor
skills
Writing abilities should be contrasted with performance on
other language comprehension and production tasks and
relative to the performance of other skilled limb movements.
◆ Examine single-word auditory comprehension (point to

picture in response to spoken word). Impairment will
negatively affect performance on writing to dictation tasks.
◆ Examine single-word reading comprehension (match

written word to picture) and the ability to recognize
correctly spelled real words versus pseudowords, such as
flig (visual lexical decision task). Poor word recognition
abilities will impair the ability to detect spelling errors.
◆ Examine reading aloud to determine whether written

words provide access to appropriate entries in the
phonological lexicon. Good oral reading skills may provide
strategies for self-detection of spelling errors.
◆ Examine spoken picture naming and compare it to written

naming of the same items to identify modality-specific
impairments of lexical retrieval.
◆ Examine limb praxis for tasks other than handwriting

using an apraxia screening test or praxis subtests from
comprehensive aphasia batteries, such as the WAB or
BDAE.
(p.329) 4 Principles of agraphia classification and

treatment
Page 12 of 41
The assessment of impaired and preserved writing processes

should allow for the determination of whether a patient’s
performance fits the diagnostic criteria for a specific agraphia
syndrome.
4.1 Acquired disorders of writing can be subdivided into central

and peripheral types.
◆ Central agraphia syndromes reflect damage to the lexical-
semantic or sublexical spelling routes, or the graphemic
buffer, and result in similar impairments across different
modalities of output (e.g., written spelling, oral spelling,
typing). Central agraphia syndromes include lexical (or
surface) agraphia, phonological agraphia, deep agraphia,
and graphemic buffer agraphia (Table 17.2) (Ellis 1988;
Rapcsak and Beeson 2000; 2002; Roeltgen 1993).
◆ Peripheral agraphia syndromes reflect damage to writing

processes that are distal to the graphemic buffer.
Dysfunction primarily affects the selection or production of
letters in handwriting. These syndromes include allographic
disorders, apraxic agraphia, and non-apraxic disorders of
neuromuscular execution (Table 17.3) (Rapcsak 1997;
Rapcsak and Beeson 2000; 2002).
Individual agraphia syndromes and appropriate treatment

approaches are detailed in Sections 5–10. The presumed
neuroanatomical correlates of these syndromes are drawn
from careful examination of lesions in patients with well-
defined agraphia profiles (Henry et al. 2007; Hillis and Rapp
2004; Rapcsak and Beeson 2002; 2004; Roeltgen 1993).
Table 17.3 Summary of the primary features of

various peripheral agraphia syndromes.
Peripheral Distinctive features

agraphia
Impairment Spared Characteristic
syndrome
abilities errors
Allographic Inability to oral Substitution of

Disorders generate or spelling physically
select correct similar letter
letter shapes in forms; case
handwriting mixing errors.
May be specific
to case (upper
Page 13 of 41
Peripheral Distinctive features

agraphia
Impairment Spared Characteristic
syndrome
abilities errors
vs. lower) or
style (print vs.
cursive)
Apraxic Poor letter oral Gross errors of

Agraphia formation not spelling, letter
attributable to typing, morphology,
allographic spelling spatial
disorder, with distortions,
sensorimotor, anagram stroke
cerebellar, or letters insertions and
extrapyramidal deletions.
dysfunction Writing may be
completely
illegible
Nonapraxic Defective oral Micrographia

Disorders regulation of spelling, (Parkinson’s
of Motor movement spelling disease);
Function force, speed, with disjointed and
and amplitude anagram irregular
in handwriting letters writing
(typing movements
may be (cerebellar
impaired disorders)
due to
disordered
motor
function)
(p.330) When an individual’s agraphia profile does not conform to

a recognized agraphia syndrome, it can be characterized by a
description of the status of impaired and preserved processes.
Page 14 of 41
4.2 Treatment principles and supporting evidence

A review of the literature yields about 45 empirical studies of
treatment for acquired impairments of spelling and writing in
adults. One randomized controlled trial conducted with a
diverse group of 94 individuals with aphasia (and alexia and
agraphia) showed that patients who received treatment for
spoken and written language made significantly greater
improvement in writing than patients who did not receive
treatment (Wertz et al. 1986). In addition, several group
studies demonstrated a therapeutic effect of behavioral
treatment for written spelling (Schechter et al. 1985; Schwartz
et al. 1974; Sugishita et al. 1993), and words typed on a
keyboard (Deloche et al. 1992; Katz and Nagy 1984;
Pizzamiglio and Roberts 1967). The majority of the writing
treatment studies are controlled single-subject experiments
(including 1 to 8 participants) that examine the effects of
specific treatment approaches on well-described writing
impairments. To date, these studies provide the clearest
evidence regarding the influence of treatment on specific
cognitive processes for spelling and writing (cf. Beeson and
Hillis 2001; Beeson and Rapcsak 2002; 2006; Behrmann and
Byng 1992; Carlomagno et al. 1994; Luzzatti et al. 2000;
Patterson, 1994).
Agraphia treatment may target central or peripheral

components of the writing process. Treatments for central
agraphias may be directed toward the lexical-semantic or
sublexical spelling routes, or the interaction between these
complementary spelling procedures. Lexical-semantic
treatments focus on strengthening specific orthographic word
forms and their links to meaning, whereas sublexical
treatments focus on the links between phonology and
orthography (i.e., sound-letter correspondences). Treatments
for peripheral agraphias are designed to improve the selection
and implementation of graphic motor programs for
handwriting. In general, treatments are designed to
strengthen damaged processing components and to take
advantage of residual abilities. Treatment examples are
described below relative to specific agraphia profiles. For a
more detailed description of agraphia treatment procedures,
see Beeson (2004) or Beeson and Henry (2008).
5 Lexical agraphia (also called surface agraphia)
Page 15 of 41
Lexical agraphia is a central agraphia syndrome that results

from damage to the lexical-semantic spelling route. It is
characterized by the loss or unavailability of word-specific
spelling knowledge so that patients are forced to rely on
spelling by a sublexical strategy (i.e., phoneme-to-grapheme
conversion) and they tend to spell words as they sound.
Relative to the processes depicted in Figure 17.1, lexical
agraphia results from damage to the orthographic lexicon and/
or the semantic system.
5.1 Distinctive features

Spelling accuracy is strongly influenced by orthographic
regularity in that regular words (e.g., chart) and nonwords
(e.g., floke) are spelled better than words with irregular (p.
331) spellings (e.g., choir). This profile is shown in Figure
17.2 reflecting the average performance of a group of 8
individuals with lexical agraphia (Rapcsak and Beeson 2004).
Attempts to spell irregular words often result in effortful,
deliberate attempts to assemble spelling on the basis of sound-
to-spelling relationships, and result in phonologically plausible
errors, such as tomb written as toom (see examples in Figure
17.2). Low frequency irregular words are especially vulnerable
to error. In addition, the loss of semantic influence on spelling
creates difficulties in writing homophonic words that cannot
be spelled correctly without reference to the word’s meaning
(e.g. dear – deer).
Page 16 of 41
(p.332) 5.2
Locus of
Fig. 17.2 a. Spelling profile of a group of
neurological individuals with damage to left temporo-
damage occipital regions resulting in lexical
Lexical agraphia characterized by greater
agraphia is difficulty spelling irregular words relative
typically seen to regular words and nonwords (from
following Rapcsak & Beeson, 2004). b. Left inferior
focal damage temporo-occipital damage in an individual
to left with lexical agraphia. c. Phonologically
extrasylvian plausible spelling errors made on
temporo- irregularly spelled words and correct
parieto- spelling of nonwords by an individual
occipital with lexical agraphia. d. Example of self-
regions, as detection and correction of spelling
shown in errors in an individual with lexical
Figure 17.2. agraphia.
The syndrome
has also been
described in patients with damage to these cortical regions
due to neurodegenerative disorders such as Alzheimer’s
disease (Rapcsak et al. 1989; Croisile 1995; Hughes et al.
1997; Lambert et al. 2007) and semantic dementia (Graham et
al. 2000).
5.3 Treatment
Treatment for lexical agraphia may be directed toward
improving the spelling of irregular words and homophones by
strengthening word-specific links between the semantic
system and the orthographic output lexicon. Another approach
involves maximizing the interactive use of residual lexical and
sublexical knowledge.
5.3.1 Strengthening interactive use of sublexical and lexical

knowledge
◆ Goal. To promote interactive use of residual orthographic
and sublexical (i.e., phoneme-grapheme conversion)
knowledge.
◆ Task example(s). Using a problem-solving approach,

patients are trained to self-detect and correct spelling
errors. Individuals with lexical agraphia often have partial
word-form knowledge, as well as relative preservation of
sublexical spelling abilities that allow them to assemble
plausible spellings for difficult words. Interactive treatment
procedures guide patients to self-evaluate assembled
Page 17 of 41
spellings relative to their residual orthographic knowledge,

and then to self-detect and correct errors. An electronic
speller that is sensitive to phonologically plausible errors,
such as the Franklin Spelling Ace® can be used to check
spelling. Such a device offers alternative spellings on the
basis of phonological plausibility, allowing patients to select
from several written choices.
◆ Expectation. Although this approach involves a

compensatory strategy for spelling that is supported by an
external aid (the electronic speller), treatment also results
in improved spelling accuracy that is not specific to
particular words, and improved ability to resolve spelling
difficulties (Beeson et al. 2000).
5.3.2 Strengthening lexical-semantic spelling abilities

◆ Goal. To strengthen specific orthographic representations
for writing and their links to semantic meaning.
◆ Task example(s). Hierarchically ordered tasks with

progressively increasing demands on spelling knowledge
can be used to strengthen spelling of specific words. Such
tasks include, for example, the arrangement of component
letters (i.e., anagram task), direct copying of the target
word, and delayed copying (after 10–15 second delays) of
target words. A critical component of these treatment
protocols is repeated, corrected spelling of the targeted
words. The re-training of orthography should take place in
the presence of pictured stimuli or in response to semantic
information about the word, (p.333) so that the link
between semantics and restored orthographic
representations is also strengthened. To emphasize the
semantic meaning of written word forms, some researchers
have used words with embedded drawings to evoke imagery
associated with the target words (de Partz et al. 1992).
The direct training of homophone pairs (e.g., red vs. read) may
be approached using word-to-picture matching tasks with
corrective feedback stressing the orthographic and semantic
differences between words in each pair (Behrmann 1987).
These tasks are typically supplemented by repeated copying
and writing to dictation of target words, and homework may
include looking up target words in the dictionary and copying
the spelling and definitions as a means to strengthen links
between spelling and meaning.
Page 18 of 41
◆ Expectation. Spelling for targeted words improves, but

may have limited generalization to untrained words
(Carlomagno et al. 1994; de Partz et al. 1992; Hillis and
Caramazza 1987; Weekes and Coltheart, 1996). However,
generalized improvement in spelling irregular words has
been shown to result if self-detection and correction of
errors improves (Behrmann 1987). Patients with lexical
agraphia may be able to abandon sublexical spelling
strategies as representations in the orthographic lexicon
are restored. Other patients may combine partially spared
(or recovered) orthographic knowledge with sublexical
procedures to actively resolve spelling difficulties (Beeson
et al. 2000).
6 Phonological agraphia and deep agraphia

Phonological agraphia and deep agraphia are central agraphia
syndromes attributable to dysfunction of the sublexical
spelling route. In both syndromes, spelling is accomplished
primarily via a lexical-semantic strategy and patients have
difficulty spelling nonwords. This profile of markedly impaired
nonword spelling relative to real word spelling is shown in
Figure 17.3a. In mild cases of phonological agraphia, the
spelling of familiar words (both regular and irregular) is
relatively spared; however, in most instances the decreased
input from phonology to orthography results in reduced
spelling accuracy for real words as well (see Figure 17.3).
Within the framework of the cognitive model presented in
Figure 17.1, phonological and deep agraphia result from
damage to sublexical processing (phoneme-grapheme
conversion), and deep agraphia reflects additional damage to
semantics or the links between semantics and the
orthographic lexicon.

In both phonological and deep agraphia, spelling accuracy is
influenced by lexical-semantic variables (concreteness, word
class, and frequency), consistent with reliance on a lexical-
semantic strategy. Individuals with deep agraphia also
produce semantic errors (e.g. boy – girl, and see examples in
Figure 17.3), indicating additional impairment of the lexical-
semantic spelling route. Other spelling errors may include
morphological errors (p.334)
Page 19 of 41
(p.335)
Fig. 17.3 a. Spelling profile from a group

of individuals with left perisylvian
damage and phonological agraphia
showing greater difficulty with nonword
spelling relative to regular and irregular
words (from Henry, Beeson, Stark, &
Rapcsak, 2007). b. Left perisylvian
damage in an individual with
phonological agraphia. c. Spelling
examples from an individual with
phonological agraphia showing preserved
spelling for irregular words and markedly
impaired spelling of nonwords. d.
Semantic errors characteristic of deep
agraphia made by patient with large left
perisylvian lesion.
Page 20 of 41
(walked –
walking),
functor
substitutions
(while – into),
and
substitution of
unrelated
words (table –
shoe). As in
any of the
central
agraphia
syndromes,
patients may
recall only
some of the
letters of the
target word.
Phonological
and deep
agraphia have Fig. 17.4 a. Characteristic spelling
been profile of an individual with global
agraphia showing limited residual
spelling knowledge for real words and
nonwords. b. Large left perisylvian lesion
resulting in Broca’s aphasia and global
agraphia. c. Limited residual spelling
knowledge for words and nonwords in
patient shown in figure b. d. Spelling of
trained words following lexical treatment
(in same individual).
conceptualized as representing endpoints along a continuum

of increasingly severe phonological and lexical-semantic
spelling deficits (Rapcsak and Beeson 2000; 2002). Consistent
with this view, mild phonological (p.336) agraphia may have
limited clinical significance, whereas deep agraphia typically
is associated with severe limitations in written communication.
The severity continuum can be extended to include global
agraphia in which there is little to no residual ability to write
words (see Figure 17.4.).
6.2 Locus of neurological damage
Page 21 of 41
Phonological and deep agraphia are associated with damage

to the perisylvian language areas including Broca’s area,
Wernicke’s area, and the supramarginal gyrus (see Figure 17.3).
Deep agraphia in patients with extensive left-hemisphere
lesions may reflect reliance on the right hemisphere for
writing (Rapcsak et al. 1991). Global agraphia is also
associated with extensive left hemisphere lesions, which may
be indistinguishable from those associated with deep agraphia
(see Figure 17.4).
6.3 Treatment
Treatment for phonological or deep agraphia may be directed
toward improving the availability and use of sublexical spelling
procedures. In deep agraphia, additional treatment is required
to restore the dysfunctional lexical-semantic spelling route in
order to eliminate semantic errors. Similarly, treatment for
individuals with global agraphia may be directed toward
sublexical or lexical-semantic spelling routes, or both
(Greenwald 2004).
6.3.1 Strengthening sublexical spelling abilities

◆ Goal. To re-establish phoneme-grapheme conversion skills
so that lexical-semantic spelling procedures are supported
by phonological input, and to allow reliance on sublexical
spelling procedures as needed. Strengthening of the
sublexical spelling route may also help constrain the output
of the unstable lexical-semantic spelling route thus
reducing the potential for semantic errors in deep
dysgraphia. Partial orthographic information derived by the
application of sound-to-letter correspondences can also
serve to cue the retrieval of word-specific spellings from the
orthographic output lexicon.
◆ Task example(s). Sound-to-letter correspondences may be

trained directly using structured drill and corrective
feedback procedures. This treatment may also require
specific training of phonological segmentation of the
syllables and individual sounds of words, as well as sound
blending skills to assist in self-evaluation of assembled
spellings. It is often necessary to establish a corpus of key
words (also called “relay words”) that can be used to derive
orthography from phonology. For example, if the patient is
able to say and spell the word baby then this will be used as
the ‘key word’ to derive ‘b’ when spelling other words. Key
words may include proper or common nouns that are
Page 22 of 41
preserved for a given individual, and are used to retrieve

the spelling of consonants and vowels. Retrieval of the first
letter or two of a word may serve to cue retrieval of word-
specific spellings and to block semantic errors in writing.
Given that sound-to-letter correspondences for consonants
are more predictable (i.e., less variable) than for vowels, it
is best to begin with the establishment of key words for
consonants (see suggested sequence in Beeson and Henry,
2008).
(p.337)
◆ Expectation. The retraining of sound-letter
correspondences typically improves the spelling of regular
words, as well as single-word reading (Luzzatti et al. 2000).
Using a lexical relay strategy, patients have been able to
derive the spelling of untrained words, or to cue the recall
of orthographic representations (Carlomagno and Parlato
1989; Hatfield 1983; Hillis Trupe 1986; Hillis and
Caramazza 1991; 1994). The establishment of key words to
derive sound-to-letter correspondences may be a tedious
process, however daily homework may be implemented to
accomplish the goal efficiently. Self-correction of
phonologically plausible spellings may be trained using
electronic devices such as a portable computer that
provides synthesized speech for communication (Hillis
Trupe 1986), or an electronic spell checker that offers
possible correct spellings (Beeson et al. 2000).
6.3.2 Strengthening (and improving access to) orthographic

representations
◆ Goal. To strengthen memory for specific orthographic
representations, and to strengthen the link between
semantic and orthographic representations in patients who
make semantic errors as a result of faulty transmission of
information between semantics and orthography.◆
Task example(s). A cueing hierarchy for written naming of
pictured stimuli may include tasks such as arrangement of
component letters (i.e., anagram task) combined with direct
and delayed copying of target words (referred to as
Anagram and Copy Treatment, or ACT; Beeson 1999; 2004).
Lexical treatment may focus exclusively on the repeated
copying and recall of targeted words (referred to as Copy
and Recall Treatment, or CART; Beeson 1999; 2004). These
procedures should include corrective feedback to retrain or
stabilize the association between concepts and written
Page 23 of 41
words, and to strengthen word-specific spellings. A

relatively small set of words (about 5) should be trained to
mastery, with additional groups of words subsequently
targeted for treatment. When semantic errors arise,
corrective feedback may be provided to highlight the
distinctive features of the target in contrast to other
members of the semantic category. For example, if ‘apple’ is
written for ‘orange’ the distinguishing features of color
would be highlighted for the two semantically related
words. Thus, treatment tasks are directed toward semantic
specification.
◆ Expectation. Improved written naming of targeted items

(Aliminosa et al. 1993; Beeson 1999; Beeson et al. 2002;
Hillis 1989; Rapp and Kane 2002). Generalization to
untrained items in the same semantic category may also
occur when semantic representations are strengthened in
addition to reinforcing functional links between semantics
and orthographic lexicon (Hillis 1990). Such generalization
is not likely in severely agraphic individuals for whom
orthographic representations are degraded to the extent
that they must be rebuilt one word at a time. However, even
globally agraphic individuals can relearn the spellings of
specific words, as shown in Figure 17.4d, and single-word
writing can provide a much-needed communication
modality for individuals with severe impairments of spoken
language (Beeson et al. 2003; Clausen and Beeson 2003;
Robson et al. 2001).
The lexical-semantic treatment can also be combined with

phonological treatment so that sound-letter correspondences
are re-trained in the context of specific regular words targeted
for treatment. Such treatment has been shown to result in
generalization to (p.338) spelling of other regular words in
some individuals (Kiran 2005). Lexical spelling treatment can
also be paired with spoken repetition of target words, which
results in improved spoken naming as well as written naming
in some individuals (Beeson and Egnor 2006). Another
variation of lexical treatment involves training target
sentences rather than isolated words; this approach has
potential value for communication via email (Greenwald 2004).
7 Graphemic buffer agraphia
Page 24 of 41
Graphemic buffer agraphia reflects impairment of the ability

to retain orthographic representations in short-term memory
as the appropriate graphic motor programs are selected and
implemented. Damage to the graphemic buffer leads to
abnormally rapid decay of information relevant to the serial
order and identity of stored graphemes. Relative to Figure
17.1, the graphemic buffer is conceptualized as the
maintenance of activated graphemes generated by lexical or
sublexical spelling routes.

Spelling accuracy is notably affected by word length because
each additional grapheme increases the demand on limited
storage capacity. This word-length effect is shown in Figure
17.5. Spelling is not significantly influenced by lexical status
(words vs. nonwords), lexical-semantic features (concreteness,
word class, frequency), or orthographic regularity (see Table
17.2). Dysfunction of the buffer results in loss of the
information regarding serial order and identity of graphemes
leading to letter substitutions, additions, deletions, and
transpositions (e.g., flower – florew; see examples in Figure
17.5). These errors are observed in all spelling tasks and
across all modalities of output (handwriting, typing, oral
spelling). Individuals with graphemic buffer agraphia may
have relatively good spelling for words up to about four
letters, but have increasing difficulty with longer words.

Lesion sites in patients with graphemic buffer agraphia have
been variable and include left fronto-parietal networks that
are implicated in working memory functions (see example
lesion in Figure 17.5).
7.3 Treatment
Although it is not clear whether the graphemic buffer itself
can be restored, several successful treatments have been
documented that reduce spelling errors associated with
graphemic buffer agraphia.
7.3.1 Lexical treatment for graphemic buffer impairment

◆ Goal. To strengthen specific orthographic representations
so they are less subject to decay and to develop strategies
to compensate for the limited short-term memory for
orthographic information.
Page 25 of 41
(p.339)
◆ Task
example(s).
Lexical
spelling
treatments
that serve
to
strengthen
Fig. 17.5 a. Characteristic spelling

profile of an individual with graphemic
buffer agraphia showing decreasing
accuracy as word length increases (left),
and showing improved spelling
performance and loss of word-length
effect following spelling treatment. b.
Surface rendering of cortical damage to
frontal and parietal lobes in the individual
whose spelling performance is shown in
a. c. Example spelling errors from this
individual with graphemic buffer
agraphia.
orthographic representations, such as ACT and CART

(described above), are also appropriate for treatment of
graphemic buffer agraphia. Another approach involves the
segmentation of long words into shorter units that can be
retained in the graphemic buffer. For example, long words
that contain embedded words, such as pencil or basement,
are selected as target words in order to train the
segmentation of words into smaller units. The lexical sub-
segments (i.e. embedded words) are underlined as the
words are presented for study. Delayed copying of the
target word is used to test recall of spelling using the
segmentation strategy. Homework involves studying and
copying the segmented words.
Individuals with graphemic buffer impairment also benefit
from training to improve their ability to self-detect and
correct spelling errors. A search strategy should be used to
Page 26 of 41
detect errors, with each word sounded out as it is written to

call attention to phonologically implausible misspellings.
◆ Expectation. Improved spelling of words targeted for

treatment, so that the word-length effect is diminished
(Cardell and Chenery 1999; Hillis 1989; Raymer et al.
2003). Ideally, treatment effects generalize to untrained
words, confirming improved capacity (p.340) of the
graphemic buffer to maintain the activation of orthographic
representations (Rapp and Kane 2002; Rapp 2005; Raymer
et al. 2003). This effect is demonstrated by the pre-post
treatment profile for the patient shown in Figure 17.5
(Ramage et al. 1998). Spelling improvement is also likely to
generalize to untrained words if self-detection and
correction of spelling errors is enhanced (Hillis and
Caramazza 1987; Sage and Ellis 2006). Improvement for the
spelling of long words that contain embedded short words
has been documented for words trained using a
segmentation strategy (de Partz, 1995).
8 Allographic writing impairment

Allographic disorders are peripheral writing impairments that
reflect the breakdown of procedures by which orthographic
representations are mapped onto letter-specific graphic motor
programs (see Figure 17.1).

Allographic disorders are characterized by an inability to
activate or select letter shapes appropriate for orthographic
representations held in the graphemic buffer. Patients may
have selective difficulty in writing upper- or lower-case letters,
or they may produce case-mixing errors (e.g., tAblE). Other
patients produce well-formed letter substitution errors that
may or may not bear physical similarity to the target (see
examples in Figure 17.6a). Allographic disorders are typically
observed in the presence of preserved oral spelling.

Allographic disorders are usually associated with damage to
the left temporo-parieto-occipital region (Rapcsak and Beeson
2002).
8.3 Treatment for allographic disorders
Page 27 of 41
◆ Goal. To improve letter selection and implementation of

letter shape, or to develop compensatory strategies to
overcome the allographic impairment.
◆ Task example(s). An alphabet card may be used to assist

the patient when a model is needed for letter shapes, but
treatment may be necessary to achieve effective use of this
strategy. If oral spelling is preserved, self-dictation may
provide a means to monitor letter selection and promote
self-correction of errors. Repeated copying of target words
followed by writing the word from memory, and case
conversion tasks (e.g., transcoding words written in upper
case into words written in lower case) also may be used to
strengthen allographic conversion.
◆ Expectation. Use of the self-dictation strategy to prevent

and self-correct errors has the potential to support
generalized improvement in letter selection (Pound 1996).
Repeated copying of target words may result in item-
specific improvements, but has the potential for generalized
improvement as allographic skills are strengthened.
(p.341) 9 Apraxic agraphia

Apraxic agraphia is a peripheral writing impairment caused by
damage to graphic motor programs (see Figure 17.1), or it
may reflect an inability to translate information contained in
these programs into specific motor commands.

Apraxic agraphia is characterized by poor letter formation that
cannot be attributed to sensorimotor (i.e., weakness,
deafferentation), basal ganglia (i.e., tremor, rigidity) or
cerebellar (i.e., ataxia, dysmetria) dysfunction affecting the
writing limb. Errors of letter shape include spatial distortions,
stroke additions or deletions, frequently resulting in
production of illegible handwriting (see example in Figure
17.6b). Oral spelling is typically preserved and, in some cases,
typing remains intact.

In right-handers, apraxic agraphia is associated with damage
to a left-hemisphere cortical network dedicated to the motor
programming of handwriting movements. The major functional
components of this neural network include posterior-superior
parietal cortex
Page 28 of 41
(p.342) (i.e.,
the region of
the
intraparietal
sulcus),
dorsolateral
premotor
cortex, and the
supplementary
motor area
(SMA). Callosal
lesions in
right-handers
may be
accompanied
by unilateral Fig. 17.6 a. Letter selection errors
apraxic (allographic dysgraphia) following
agraphia of the damage to left temporo-parietal cortex
left hand. due to stroke. b. Apraxic agraphia
9.3 Treatment
for apraxic associated with focal cortical atrophy
agraphia affecting left superior parietal cortex. c.
Treatments Micrographia associated with Parkinson
for apraxic disease.
agraphia have
not been well
documented in the literature, so rehabilitation may be
considered on a trial basis. When central spelling processes
are intact, it may be possible to circumvent handwriting
difficulties by using a keyboard for written communication.
◆ Goal. To re-establish the ability to control hand

movements necessary to write letters and words.
◆ Task example(s). When copying skills are relatively

preserved, treatment should include repeated direct and
delayed copying tasks to re-establish the ability to write
letters and words. A task hierarchy should initially include
deliberate and feedback-dependent writing to regain
graphomotor control, with repeated productions to improve
the automaticity of motor execution.
◆ Expectation. Limited evidence of improvement in apraxic

agraphia is available. Several sessions of trial therapy
should provide an indication of a patient’s responsiveness
to treatment.
Page 29 of 41
10 Writing disorders due to impaired neuromuscular

execution
Damage to motor systems involved in generating graphic
innervatory patterns results in defective control of writing
force, speed, and amplitude.

Writing disorders due to impaired neuromuscular execution
reflect the specific underlying disease or locus of damage. In
the case of Parkinson’s disease, reduced force and amplitude
of movements of the hand result in micrographia (see example
in Figure 17.6c). In patients with cerebellar dysfunction,
movements of the pen may be disjointed and erratic. Patients
with hemiparesis often have weakness and spasticity of the
hand and limb that markedly impairs their ability to write with
the preferred hand.

Breakdown of graphomotor control in these neurological
conditions suggests that the basal ganglia and the cerebellum,
working in concert with dorsolateral premotor cortex and the
SMA, are critically involved in the selection and
implementation of kinematic parameters for writing
movements.
10.3 Treatment
Although there are a variety of causes for impaired
graphomotor control, there are relatively few rehabilitation
reports. Successful rehabilitation strategies have been
demonstrated for some patients with micrographia, and some
with hemiparetic writing.
(p.343) 10.3.1 Treatment for micrographia

◆ Goal. To increase graphomotor control and thus improve
legibility of handwriting.
◆ Task examples(s). An increase in letter size may be

accomplished by the provision of parallel lines or a template
to facilitate the re-calibration of the range and force of
movements for writing. Another approach to facilitate
increased amplitude of the motor movements for writing in
Parkinson disease involves training to self-monitor by
thinking “WRITE BIG” (Farley et al. 2006). This cognitive
approach is analogous (and can be combined with) a voice
treatment for Parkinson disease that involves a
Page 30 of 41
recalibration of speech effort by training individuals to

“THINK LOUD” (Farley et al. 2008; Volume 24, pp. 99–114;
Ramig et al. 2001).
◆ Expectation. Improved letter formation is expected with

provision of external cues (Oliveira et al. 1997).
Maintenance of increased letter size is dependent upon
establishing adequate self-monitoring abilities so that
adjustments are made as legibility declines.
10.3.2 Hemiparetic writing

Writing with the nondominant hand can be mastered with
practice, however, several investigators have reported on the
use of various prosthetic devices to support the paralyzed
right hand during writing.
◆ Goal. To learn to write with the paretic dominant hand

using a prosthesis.
◆ Task example(s). Using a custom-made splint with wheels

that allows easy movement across the writing surface, the
patient learns to move the affixed pen to form letters.
◆ Expectation. Some researchers have found that writing

produced with the aided hemiparetic right hand proves to
be linguistically superior to that written with the
nondominant left hand (Brown et al. 1983; Leischner 1983;
Lorch 1995).
11 Treatment schedule
11.1 Initiation of treatment
The majority of empirical studies document improved spelling
and writing following agraphia treatment initiated long after
onset of the neurological damage, suggesting that there is not
a “critical period” for the implementation of treatment.
11.2 Frequency of treatment

Reviews of the agraphia treatment literature reveal
considerable variability in the frequency of treatment sessions
that resulted in improved writing. Treatment schedules range
from twice daily to once a week or even biweekly; however,
daily practice is often incorporated in the treatment plan and
appears to be important for bringing about enduring changes
in writing. Therefore, regardless of the frequency of clinical
treatment sessions, appropriate daily homework should
accompany writing treatment protocols whenever possible.
(p.344) 11.3 Response to treatment
Page 31 of 41
The likelihood that a patient will respond to a given treatment

is based on several factors including the severity of the deficit,
the status of the impaired and residual abilities, the nature of
the neurological illness, as well as the patient’s motivation. In
some cases, patients who appear to have similar functional
deficits may respond differently to the same treatment. A
patient’s response to treatment may further clarify the nature
of the writing impairment, and subsequently prompt
modification of procedures, determination of the next stage of
treatment, or indicate that treatment should be terminated.
12 Functional impact of treatment

This chapter has focused on the nature and treatment of the
cognitive and sensorimotor processes necessary for written
communication. It is important to emphasize that the
assessment and treatment of individuals with spoken and
written language impairment should be tailored so that the
functional needs of the person with agraphia are taken into
account. In a clinical context, the selection of skills and
specific lexical representations that will be the focus of
treatment should be individualized and determined jointly with
the patient (see Panton and Marshall 2007, for a recent
example). In other words, treatment planning and
implementation should be guided by a strong understanding of
the cognitive neuropsychology of the impairment, but should
also be influenced by the needs, desires, and goals of the
individual. Ultimately, the rehabilitation of writing should lead
to enhanced communication skills and an improved quality of
life.
Acknowledgement
This work was supported by RO1DC007646 and
RO1DC008286 from the National Institute on Deafness and
other Communication Disorders. The authors thank Sarah
Andersen for her assistance in the preparation of this
manuscript.
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Page 41 of 41
Assessment of executive function


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001

Paul W. Burgess
DOI:10.1093/acprof:oso/9780199234110.003.018

Executive function is probably the newest of the fields of
neuropsychology. Although observations of patients showing
symptoms of executive dysfunction have existed for over 150
years, and experimental investigation for at least half of that
time, the area has only really become the focus of very
widespread investigation in the last twenty years or so. And,
since the translation of scientific findings into clinically useful
techniques occurs relatively slowly, it is only recently that the
experimental findings are being translated into procedures for
clinical use. As a consequence, the practising clinician should
take special care to follow the latest developments in this fast-
moving field. This chapter describes some of the most
commonly used tests of executive function. The principal aim
is to outline the philosophy of the assessment procedure, so
that the reader can know what to look for, decide which tests
to use, and understand the issues surrounding the possible
choices of assessment procedure.
Keywords: executive function, neuropsychological assessment, assessment

procedures, executive dysfunction
1 Introduction
Page 1 of 29
Executive function is probably the newest of the fields of

neuropsychology. Although observations of patients showing
symptoms of executive dysfunction have existed for over 150
years, and experimental investigation for at least half of that
time, the area has only really become the focus of very
widespread investigation in the last 20 years or so. And, since
the translation of scientific findings into clinically useful
techniques occurs relatively slowly, it is only recently that the
experimental findings are being translated into procedures for
clinical use. As a consequence, the practising clinician should
take special care to follow the latest developments in this fast-
moving field.
This chapter does not provide an exhaustive description of all

the various tests of executive function available to the
neuropsychologist since excellent summaries appear
elsewhere (e.g. Lezak 1995; Spreen and Strauss 1998;
Alderman and Burgess 2002). Instead, while we do briefly
describe some of the most commonly used tests, the principal
aim is to outline the philosophy of the assessment procedure,
so that the reader can know what to look for, decide which
tests to use, and understand the issues surrounding the
possible choices of assessment procedure. This information is
much harder to come by.
1.1 What are executive functions?

At the most basic level, executive functions are the abilities
that enable a person to establish new behaviour patterns and
ways of thinking, and to introspect upon them. This is required
most in unfamiliar situations, where one doesn’t know what to
do, or in situations where established ways of behaving are no
longer useful or appropriate. As such, the term ‘executive
function’ refers to a whole range of adaptive abilities such as
creative and abstract thought, introspection, and all the
processes that enable a person to analyse what they want, how
they might get it (i.e. form a plan, based often on recollections
of past experience), and then carry that plan out. It is also
widely accepted that executive functions play a critical part in
complex social behaviour, such as understanding how others
see us, being tactful, or deceitful. Therefore, there is probably
no activity beyond the most routinized and practised ones that
does not to some extent involve ‘executive processing’. It is
not clear, however, how much overlap there is between the
Page 2 of 29
processes underlying these various abilities. Identifying the

processes and working out how they may relate to each other
is the current focus of much exciting research, but we are just
in the early stages.
(p.350) These abilities are collectively referred to as

‘executive functions’ because it is believed that the region of
the brain that supports them (the frontal lobes) operates in a
‘supervisory’ (Shallice 1988) or ‘executive’ (Pribram 1973)
capacity over the rest of the brain. For many researchers,
‘executive function’ is synonymous with ‘frontal lobe function’.
However, the latter term is of little use to the practising
clinician for two reasons.
◆ What is important clinically is the function that is

impaired rather than the brain region that is damaged.
◆ Recent advances in cognitive neuroscience show that,

whilst the frontal lobes play an important part in executive
functions such as planning and organization of behaviour,
the frontal lobe contribution is just one part of a wider
network of brain involvement.
In the 1980s there was a move away from discussing ‘frontal

lobe function’ towards use of the terms ‘executive function’
and ‘dysexecutive symptoms’ (to describe executive function
impairments) in order to reflect this more function-oriented
focus.
1.2 Symptoms of executive dysfunction

The 20 most commonly reported symptoms of executive
dysfunction are shown in Table 18.1. This is by no means an
exhaustive list, however, and there are also many other,
generally less frequently encountered dysexecutive symptoms
(e.g. utilization behaviour, alien hand sign).
Recent evidence suggests that at least some executive abilities

may be impaired in neurological patients when others are not.
The term ‘dysexecutive syndrome’, which is commonly used as
shorthand to refer to executive function impairments, can
therefore be misleading since it suggests that symptoms are
invariably seen together. This is not the case. However, it is
equally true to say that in normal clinical practice it is less
common to see people with isolated problems than with
clusters of them. There are probably two main reasons.
Page 3 of 29
◆ Even apparently quite localized brain dysfunction is

unlikely to affect only one brain system and, because of the
highly interconnected nature of the brain, dysfunction in
one region in any case can probably cause disruptions in
others.
◆ Some researchers contend that there are some executive

processes that are used in many situations (e.g. Duncan et
al. 2000), e.g. those that govern attention and arousal, as
well as others that are required in more specific situations,
e.g. those requiring multitasking (Burgess et al. 2000).
1.3 The impact of executive dysfunction on everyday life
Even apparently quite mild deficits of executive function can
have a devastating impact upon an individual’s effectiveness in
everyday life and their relationships with others. A key reason
for this is the attributions that observers make about the
causes of the behaviour they see. Many dysexecutive
symptoms mimic exaggerated versions of behaviour that are
sometimes seen in healthy people and therefore can easily be
misunderstood. (p.351)
Table 18.1 Frequency of 20 of the most common

symptoms of executive dysfunction (adapted
from Burgess and Robertson, 2002)
Symptom Percentage reporting

problem
Patients Carers
Poor abstract thinking 17 21
Impulsivity 22 22
Confabulation 5 5
Planning 16 48
Euphoria 14 28
Poor temporal sequencing 18 25
Lack of insight 17 39
Apathy 20 27
Disinhibition (social) 15 23
Variable motivation 13 15
Page 4 of 29
Symptom Percentage reporting

problem
Patients Carers
Shallow affect 14 23
Aggression 12 25
Lack of concern 9 26
Perseveration 17 26
Restlessness 25 28
Can’t inhibit responses 11 21
Know–do dissociation 13 21
Distractibility 32 42
Poor decision-making 26 38
Unconcern for social rules 13 38
Take, for example, confabulation. All ordinary, healthy people at

some time or another tell lies. This is a common event. So when a
patient says something that is quite obviously untrue, it is easy for
observers to assume that the patient is deliberately lying. Of
course, this is not the case. Confabulation is caused by a problem
with the cognitive control processes that govern recollection,
leading to memories and thoughts becoming jumbled up with each
other (see Burgess and Shallice 1996b). The patient can’t help it.
However, if one doesn’t know this and has not seen confabulation
before (as most spouses or relatives of neurological patients will
not have), it is easy to make this mistake, and get irritated with the
patient for ‘lying’ or ‘making things up’. The same point can be
made about many of the dysexecutive symptoms shown in Table
18.1. Especially difficult to live with are the social changes such as
lack of concern or increased aggressive reactions to troublesome
situations. Relatives or partners might quite justifiably claim that
these ‘personality changes’ mean that the patient ‘is no longer the
person she/he used to be’.
The non-social changes can also be a severe handicap,
especially in the work situation. A good example is those
patients who show relatively isolated multitasking deficits. (p.
352) These people may still be extremely intellectually gifted,
with little or no (retrospective) memory, language, or other
problems, and some are even very competent on most tests of
executive function. However, for all reported cases in the
literature, their return to work has been tragically
unsuccessful, with employers complaining of tardiness and
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disorganization (see Burgess 2000 for review). Common

complaints from the employers of these cases are that the
patient starts many jobs but never completes any of them, and/
or shows no awareness of the relative priorities of different
jobs, treating the most trivial (e.g. the sticky tape needs
replacing) as equally pressing as the most important (e.g.
delivering an important letter to the company chairman). It is
simply very difficult to work with someone who shows these
sorts of symptoms—certainly more so in many contexts—than
with a more predictable and obvious handicap (e.g. a language
or visual impairment) for which compensatory methods exist
and that can be readily understood by co-workers.
A further complication of executive dysfunction is that the

associated problems are exactly the kinds of problems that
interfere with learning new ways of behaving, or prevent
patients from benefiting from therapy aimed at ameliorating
other sorts of problems (e.g. physiotherapy). For this reason,
combined with the typical lack of insight that accompanies
these symptoms, dysexecutive problems present a real
challenge for rehabilitation. (For further information see
Burgess and Robertson, 2002.)
1.4 Prognosis for executive deficits

One of the reasons why the functions of the frontal lobes were
described by a leading researcher over 30 years ago as a
‘riddle’ was that some apparently severe symptoms could
resolve well in time, whereas other apparently milder
problems could persist. This is just as true today: symptoms
such as confabulation typically (but not always) resolve quite
well on their own within a few weeks or months, but others
(e.g. multitasking problems) when they persist beyond the
initial stage of medical trauma are often best considered
permanent handicaps requiring intervention before
improvement will occur. We still do not understand why this
should be the case, and this is an underresearched area. The
wise clinician will freely admit this lack of knowledge to
relatives, carers, or the patients themselves. There should be
no embarassment in not knowing when there is nothing to
know. Freely admitting that no one knows the answer has the
advantage of removing the temptation to speculate whilst also
avoiding seeming obscure or evasive.
2 Choosing the assessment approach
Page 6 of 29
The ideal assessment would obviously attempt to assess all of

the symptoms shown in Table 18.1, plus the less common signs
of executive dysfunction (e.g. utilization behaviour, alien hand
sign, subtle attentional changes). However, this is impractical
in most clinical settings, and formal assessment measures do
not yet exist for many of the symptoms. Moreover, relatively
little is known about what many of the tests shown to be
sensitive to frontal lobe lesions are actually measuring in these
cases. (This is a theoretical (p.353) problem that is far more
complex than it seems at first.) One is left therefore with five
choices of how to proceed:
◆ Time. Administer the greatest number of tests possible in

the available time.
◆ Psychometrics. Base your choice of measures on test-

based factors such as ease of use and cost, psychometric
validity, how widely the tests are used, how often they have
been used with a particular client group, etc.
◆ Expectation. Base assessment on what you expect to find,

given knowledge of the medical history and/or previous
assessments.
◆ Observation. Base assessment on symptoms already

observed by carers or relatives.
◆ Theory. Adopt a particular theoretical stance and choose

the tests that make most the sense according to it.
These methods are of different merit. Remarkably, perhaps,

none is entirely meritless and, in practice, most experienced
clinicians develop their own assessment procedure based on a
personal weighting of these methods. In principle, this is
appropriate. Too often, however, this choice has merely
evolved haphazardly over time. Instead, the choice should be
made deliberately and with good justification. If the same
battery of tests is given to all clients, this choice should be
reviewed regularly. The clinician should always be able to
clearly articulate and defend the reasons behind his/her choice
of procedures.
In practice, I have observed a further method of determining

the assessment procedure: to just use whichever tests are
most familiar and/or everyone else is using. This method might
in some circumstances be most appropriate for students, but it
Page 7 of 29
would be dubious indeed for a qualified clinician, and this

method will be considered no further.
Let us consider the legitimate approaches in turn.
2.1 Method 1. Time

This is not as unjustifiable as it might at first seem, for two
reasons.
◆ As mentioned above, we know little about many of the

traditional tests of executive function (e.g. Wisconsin Card
Sorting Test, Stroop Test) or what they measure.
◆ The ecological validity of these tests (i.e. the extent to

which they are indicators of real-world impairment) has not
yet been clearly established. (It does, however, seem at
present that the more modern tests designed to be more
like real-life activities are often—but not always—better in
this respect.)
Thus one solution to this problem is just to give as many tests

as one can in the available time, in the hope of covering as
many possible functions/situations as possible. The
disadvantages of this approach are the following.
◆ As the number of tests administered rises, so does the

likelihood of a false-positive result (unless the clinician
statistically corrects for the number of tests administered,
which is uncommon).
(p.354)
◆ Unless the clinician has at least some hypothesis about
what he/she is measuring, it is difficult to know what might
be usefully concluded from a task failure. Clinically, it is
rarely sufficient to just baldly state ‘this person failed this
test’, without further interpretation.
2.2 Method 2. Psychometrics
All people involved in the administration of psychometric tests
should have at least some basic grounding in psychometric
theory. This allows them to understand the relative merits of
the measurement aspects of different tests, and to select
accordingly. In particular, there may be times when some
aspect of the psychometric dynamic of relative tests might
strongly influence the clinician’s choice, e.g. where parallel
forms are required, where there is to be repeated testing
Page 8 of 29
using the same measure, or where various different people

may make assessments on the same person.
In general, however, it is harder in the field of executive

function to use psychometric values (e.g. test–retest and
interrater reliability; interitem consistency, etc.) as a guide to
test choice. This is because the tests are often measuring
abilities such as response to novelty or strategy formation.
These can subvert the theory behind traditional
psychometrics, and render the values a poor guide to a test’s
actual clinical utility (see Burgess 1997 for more detail). In
addition, there is another problem that is applicable to the use
of most psychometric tests with pathological populations. This
is that the construct validity of a task (i.e. the extent to which
you are measuring what you intend to measure) alters with
level of performance. Overall, these matters present a highly
complex theoretical problem for someone trying to base their
choice of assessment procedure upon psychometric values,
especially when they are derived from the performance of a
different population than the one you intend to test (e.g.
healthy control subjects). In summary, all other things being
equal, one should choose the test with the best psychometric
validity. However, all other things are unlikely to often be
equal.
2.3 Method 3. Expectation

If we knew more about what executive tests measure, this
would probably be the most frequently appropriate single
method. For success it does, however, rely upon at least four
variables:
◆ The quality of the information, case history, or previous

assessment that you have received.
◆ Your knowledge of the test’s performance in different

populations.
◆ How the test is affected by a variety of background

variables (e.g. education, culture, age, etc.).
◆ The ecological validity of the task (i.e. how strongly you

can make a prediction that your test measures the function
that was observed to be impaired elsewhere).
This method therefore requires a high degree of knowledge

and clinical judgement. This requirement should decrease as
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our knowledge of the performance of the tests and what they

measure increases.
(p.355) 2.4 Method 4. Observation

Although the examinee should always be asked about the
symptoms they notice since it is important to assess the
patient’s degree of insight and knowledge about their
condition, it is unwise to base your assessment upon this
report. Self-report of dysexecutive difficulties is notoriously
inaccurate (e.g. Burgess and Robertson 2002). However, the
reports of carers, relatives, or other people who know the
examinee well can be very useful indeed, and should always be
sought if possible.
The best witnesses are usually those who knew the person
premorbidly, since change in behaviour is usually more
instructive than comparisons of current behaviour with some
population norm. This is important for executive function
assessment since the behaviours under examination are often
at the extreme of the range of behaviours that might be
observed occasionally in the normal population. This is one of
the important ways in which executive function assessment
differs from assessment of other functions in neuropsychology.
In, say, language assessment, or assessment of visuospatial
skills, pathological symptoms (e.g. jargon aphasia, neglect) are
rarely or never seen in the healthy normal population.
However, many of the symptoms of executive dysfunction are
seen occasionally in the healthy population, albeit perhaps
under special circumstances, and in a milder form (e.g.
confabulation (Burgess and Shallice 1996b), impulsivity,
disinhibition). Since, therefore, it is often the extremity (i.e.
severity, frequency) of the behavioural sign rather than its
type that is at issue, it is important if possible to have an
observer ‘baseline’ with which to compare current behaviour.
Once the clinician has collected the observations, however, he/

she is faced with the challenge of interpreting them for the
purposes of the examination procedure. There is no substitute
for experience and knowledge in this respect. The job is made
easier by some of the newer assessment procedures that are
more like real-world situations, since one can ask the observer
about situations in which the examinee experiences problems
and then choose the closest test situations. However, for
Page 10 of 29
experienced examiners, more experimentally derived

procedures also have their merits.
◆ Often the theory of how they work is more developed.
◆ They may be more specific in what they measure.
◆ The link with damage to certain brain regions may be

more direct.
These factors can add up to a strong advantage if you have a

clear idea what it is that you are looking for and have
experience in interpreting the observations of others.
2.5 Method 5. Theory

All assessment and treatment has to start with some theory of
what it is that is being studied, even if this is very basic. The
assessment implications of all theories of executive function
cannot be covered here. However a few of the leading ones
will be selected as examples.
(p.356) 2.5.1 Single-process theories

These hold that damage to a single process or system is
responsible for a number of different dysexecutive symptoms.
An example is the theory of Cohen (e.g. Cohen et al. 1990).
This holds that prefrontal cortex is used to represent ‘context
information’, which is the ‘information necessary to mediate
an appropriate behavioural response’ (Cohen et al. 1998, p.
196). Two functions of the prefrontal cortex may be effected
by this system—active memory and behavioural inhibition—
with both functions reflecting the operation of the context
layer under different task conditions. Under the conditions of
response competition the context module plays an inhibitory
role by supporting the processing of task relevant information.
But, when there is a delay until the execution of a response,
the context module plays a role in memory by maintaining that
information over time.
Following this theory, clinical assessment would include tests

of response suppression (e.g. Hayling Test, Stroop) plus tests
with a ‘working memory’ component (e.g. Wisconsin Card
Sorting Test (WCST), Cambridge Neuropsychological Test
Automated Battery (CANTAB) spatial working memory test).
2.5.2 Construct-led theories
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Construct-led theories are those that propose a construct (i.e.

a theoretical ability) such as ‘working memory’ or ‘fluid
intelligence’ as a key function of the frontal lobe executive
system.
Working memory theories
Two leading theorists in this area are Petrides and Goldman-

Rakic.
◆ Petrides believes that the mid-dorsolateral prefrontal

region (areas 9 and 46) supports a brain system ‘in which
information can be held on-line for monitoring and
manipulation of stimuli’ (Petrides 1998, p. 106). The mid-
ventrolateral region, however, is used in explicit encoding
and retrieval of information. Obvious suggested tests are
therefore Petrides and Milner’s (1982) Self-Ordered
Pointing Test, and other memory tests that particularly
stress explicit encoding and retrieval (e.g. recall of complex
figures such as the Rey figure; recall of short stories or
word lists).
◆ Goldman-Rakic’s position is different in that she believes

that the various different frontal lobe regions all perform a
similar role in working memory, but that each processes a
different type of information (Goldman-Rakic 1995). She
suggests that dysfunction of this system can cause a variety
of deficits on e.g. verbal fluency and Stroop tasks due to an
inability to use working memory to initiate the correct
response.
Duncan’s theory of ‘g’ (e.g. Duncan et al. 1995, 2000)
Duncan suggests that the principal purpose of the frontal

executive system is to support a single function that is used in
many situations, called ‘fluid intelligence’ or Spearman’s g. Of
the commercially available tests, he believes Cattell’s Culture-
Fair Test and (by implication from his studies) the Six Element
Test of the Behavioural Assessment of the Dysexecutive
Syndrome (BADS) measure this function.
(p.357) 2.5.3 Multiple-process theories

These propose that the frontal lobe executive system consists
of a number of components that typically work together in
everyday actions.
Fuster’s temporal integration framework (Fuster 1997)
Page 12 of 29
This holds that the frontal lobe executive system performs

three functions:
◆ working memory;
◆ set attainment;
◆ inhibition.
Suggested tasks are, therefore, WCST or CANTAB working

memory tests, Brixton Test, Hayling Test, or Stroop.
Stuss’s anterior attentional functions (e.g. Stuss et al. 1995;

Stuss and Alexander 2000)
The focus of Stuss et al.’s theoretical approach is attention.

They propose seven different attentional functions. The closest
clinical test is probably the Test of Everyday Attention (TEA).
Shallice’s supervisory attentional system (e.g. Norman and

Shallice 1986; Shallice 1988; Shallice and Burgess 1991a ,b,
1996; Burgess et al. 2000)
This is one of the longest established and best known theories.

In this model, the frontal lobes support a cognitive system
known as the supervisory attentional system (SAS). This plays
a part in at least eight different processes, each of which may
be impaired in isolation:
◆ working memory;
◆ monitoring;
◆ rejection of schema;
◆ spontaneous schema generation;
◆ adoption of processing mode;
◆ goal-setting;
◆ delayed intention marker realization;
◆ episodic memory retrieval.
On these grounds, and as the result of a study that examined

the relationship between symptoms in everyday life and
executive test performance, Burgess et al. (1998) recommend
that at the very least an assessment of a dysexecutive patient
should include the following.
Page 13 of 29
◆ A general measure of inhibitory abilities (e.g. Hayling

Test; however this function is probably also measured to
varying degrees by many other tests, e.g. verbal fluency,
Trail-Making).
◆ Measures of executive memory abilities both in the short-

term (i.e. working memory tests) and long-term (i.e.
accuracy of episodic recollection). Suggested tests would be
WCST; Brixton Test; story, figure, and word list recall; and
also observation of real-life ability to recollect events
accurately.
(p.358)
◆ A measure of multitasking ability, e.g. Six Element Test
from the BADS; Multiple Errands Test (Shallice and Burgess
1991a; Burgess et al. 1996b, 2000; Alderman et al. in
press).
However, Burgess et al. (1998) make two further points.
◆ Neuropsychological tests of executive function do not

measure well many of the emotional changes that can be
part of the dysexecutive syndrome (e.g. euphoria, apathy).
The formal tests need therefore to be supplemented by
more general observation, preferably using a structured or
semistructured interview, perhaps based around a symptom
checklist or questionnaire such as the Dysexecutive
Questionnaire (DEX; Burgess et al. 1996a) from the BADS
test battery.
◆ Since many impairments can be seen in isolation, a true

assessment will be as comprehensive as possible—the list
above could be considered only as a basic screening
assessment. For instance, one might also wish to
supplement it routinely with measures of planning (e.g.
Zoo-Map test of the BADS; abstract reasoning and
judgement (e.g. proverb interpretation, cognitive estimates,
or similar); initiation (e.g. Hayling Test section 1); problem-
solving and strategy formation (e.g. Action Program and
Key Search tests from the BADS); rule attainment and
following (e.g. Brixton Test).
2.5.4 Single-symptom theories

These are theories of specific symptoms, such as confabulation
(e.g. Burgess and Shallice 1996b; Burgess and McNeil 1999)
or multitasking deficits (e.g. Burgess et al. 2000). In general,
Page 14 of 29
however, there are not tests specifically marketed to measure

single symptoms. Clinicians therefore typically just make
observations, or copy an experimental method.
3 Types of executive function test

The perfect test for most clinical applications would probably
have the following characteristics (in addition to those that
would be desirable in any psychometric test):
◆ perfect, and known correspondence to everyday life

impairment;
◆ strong proven link to operation of one particular brain

region or system;
◆ well understood psychometric dynamics;
◆ comprehensive theory as to what the test measures.
However as can be inferred from the discussions above, there

is currently no test that could be said to have all these
characteristics. Take for instance, probably the best-known
executive test: the Wisconsin Card Sorting Task (WCST). This
test was not originally designed for use with neurological
patients (Berg 1948). Impairment of dorsolateral prefrontal
lesioned patients was first demonstrated by Milner (1963), but
there are few replications of this finding (see Stuss et al. 2000
for possible explanations). More positively, there is some early
evidence about its relationship with everyday life impairments
(Burgess et al. 1998), and there are various theories about
what the test measures.
(p.359) Similarly, the Stroop test, although widely used for

the assessment of executive functions in neurological patients,
was not designed with this purpose in mind. Moreover, in my
opinion there is only one convincing demonstration of its
sensitivity to frontal lesions (Perret 1974), and one convincing
failure to replicate (Shallice 1982). There is disagreement
about what the test measures (see MacLeod 1991), although
there are some theories that have been made relevant to the
assessment of executive functions, as outlined above.
Moreover, there is little information that would allow one to
predict from test impairment what deficits in real life might be
expected.
Page 15 of 29
Some of these shortcomings no doubt stem from the fact that

the procedures were not designed with neuropsychological
assessment in mind. In recognition of this situation, there have
recently been tests invented for this specific purpose (e.g.
BADS battery, Hayling and Brixton tests, CANTAB battery).
Due to their newness, these tests have not, of course, yet been
thoroughly put to the test of time (although there has been
considerable work using the CANTAB in different populations),
and it is possible that they will turn out not to fulfil the criteria
above in any greater fashion than the older tests. However
they do start with the advantage of being purpose-built.
3.1 Specificity and sensitivity

The specificity of a task refers to the degree to which a test
measures the particular process or function of interest
compared with other processes or functions that are not
intended to be measured. The sensitivity of a task in this
context refers to the degree to which any cognitive
impairment can cause impairment on the task. There is some
evidence that the different executive tasks differ greatly along
these dimensions. For instance, the Cognitive Estimates Test
does not seem to be particularly sensitive to any kind of
neurological dysfunction per se (Burgess et al. 1998), but it
does show consistent correlations with specific symptoms (e.g.
fantastic confabulation), which suggests that it has good
specificity. By contrast, the WCST appears to be more
generally sensitive to cognitive decline, as well as to
dysexecutive problems (e.g. Stuss et al. 2000). There is not
room here for a discussion of the specificity and sensitivity of
every test. However the clinician should consider matching the
test to the clinical question under consideration. Using the
current examples, for instance, the Cognitive Estimates test is
probably not the best choice as a general screening measure
for dysexecutive problems. However, its ecological validity is
excellent and, if the clinical question instead concerns whether
a patient has a specific executive problem rather than more
general cognitive dysfunction, then the test is well suited to
that application.
In many clinical settings the ideal test would have a

combination of both characteristics, i.e.:
◆ sensitivity to a range of executive problems;
Page 16 of 29
◆ relative insensitivity to non-executive cognitive

impairments.
This compromise is generally closest in those tests that have

been shown to be impaired in group studies of frontally
lesioned patients compared with patients whose lesions were
elsewhere in the brain (e.g. Hayling and Brixton Tests,
Burgess and Shallice 1996a ,c, 1997). (p.360) Some tests
appear to be both locally specific and more generally sensitive.
For instance, impairment on the Six Element Test (a test of
multitasking ability; see below) has been demonstrated in
neurological patients with frontal lobe lesions who show no
impairment on other executive function tests (e.g. Shallice and
Burgess 1991a). However, this type of test is also more
generally sensitive to executive (and to a lesser extent non-
executive) impairments (Burgess et al. 2000). This combination
of characteristics can make a test particularly useful in a wide
range of settings. However, once a patient has failed a task, it
generally requires that one should consider performances on
other tasks in its interpretation (using this example, for
instance, to find out whether the locus of the problem is a pure
multitasking failure or, for instance, a more basic memory
problem that prevents the examinee from learning the task
rules).
3.2 Summary
Assessment of executive functions is probably the most
technically and theoretically complex aspect of
neuropsychological assessment. Executive test scores should
always be administered in the context of a wider
neuropsychological assessment since executive test
performance can be affected by dysfunction in other cognitive
systems (e.g. memory, etc.). The clinician’s choice of tests and
procedure should be made with careful consideration of the
factors outlined above and, if not made on a case-by-case
basis, they should be reviewed regularly.
Executive function as a subject area is one of the newest and

fastest developing in neuropsychology, and there are still many
gaps in our knowledge. However, since even relatively mild
executive dysfunction has repeatedly been shown to greatly
affect the long-term outcome of rehabilitation and recovery,
any neuropsychological assessment is not complete without at
least a basic evaluation of executive function abilities. New
procedures and tests are appearing at a rapid rate. The
Page 17 of 29
assessment professional would therefore be wise to be

circumspect when interpreting executive test scores, and
make every attempt to benefit from the latest developments in
the area as they appear.
4 Description of some key tests

There are many tests of executive function. A brief description
of a few of the most commonly used is given in Sections 4.1–
4.11. However, lack of inclusion in this list should not be seen
as a failure of endorsement. There are a number of tests (e.g.
the Test of Everyday Attention; Rey Complex Figure Recall)
that could be seen as falling under the heading of ‘executive
function’ but that have not been included since they also fall
under other topic areas (e.g. attention, memory). There are
also other methods that combine tests or aspects of them to
increase specificity or sensitivity (e.g. the Frontal Lobe Score,
see Ettlin et al. 2000; Wildgruber et al. 2000) and are worthy
of consideration. Excellent summaries of the range of
executive tests can be found in Lezak (1995) and Spreen and
Strauss (1998) and, where publisher information etc. is not
given below, it can be found in these texts. It should be borne
in mind that dysexecutive problems demonstrate themselves
as impairment on a wide range of neuropsychological tests,
not just (p.361) those specifically aimed at measuring
‘executive function’, so the manner of failure on a test can also
be instructive.
4.1 Behavioural Assessment of the Dysexecutive Syndrome (BADS)

◆ Original reference. Wilson et al. (1998). Commercially
available from various distributors worldwide. For details
contact the Thames Valley Test Company, 7–9 The Green,
Flempton, Suffolk, IP28 6EL UK. ([email protected])
◆ Test description. The BADS is a test battery aimed at

predicting everyday difficulties arising from the
dysexecutive syndrome. It contains six tests (and a
questionnaire (the DEX) that has two versions, one to be
filled in by the patient and one by an independent rater,
which can be used as the basis for a semistructured
interview). The six different tests (Rule Shift, Action
Program, Key Search, Temporal Judgement, Zoo-Map, and
Six Elements Test) are designed to have high ecological
validity, and scores from the tests can be combined to give
Page 18 of 29
an overall executive function measure that can be

compared with measures of cognitive functioning.
4.2 Cambridge Neuropsychological Test Automated Battery
(CANTAB)
◆ Original reference. Robbins et al. (1994).
◆ Test description. A computerized battery of 13 tests that

evaluate more than executive functions alone. However, it
contains two tests that are particularly oriented towards
executive function assessment: ID/ED Shift and the
Stockings of Cambridge test, which are developments of the
WCST and Tower of London (Shallice 1982) tests,
respectively.
4.3 Cognitive estimates test
◆ Original reference. Shallice and Evans (1978).
◆ Test description. Patients are asked 15 questions about

everyday magnitudes where no rote knowledge or routine
method seems available. Axelrod and Millis (1994) issued a
shorter version (10 questions) adapted to the North-
American population.
◆ Scoring method. Answers rated as normal, quite extreme,

extreme, and very extreme according to how much they
vary from the estimates of a control group.
4.4 Hayling and Brixton tests
◆ Original references
— Hayling: Burgess and Shallice (1996c).
— Brixton: Burgess and Shallice (1996a).

Commercially available from various distributors
worldwide; for details contact the Thames Valley Test
Company, 7–9 The Green, Flempton, Suffolk, IP28
6EL UK. ([email protected])
(p.362)
◆ Test description.
— Hayling: Patients have to complete 30 sentences

from which the last word was omitted. In the first
half (initiation condition), they complete the
sentences with a word that makes sense. In the
second half (inhibition condition) they have to supply
Page 19 of 29
a word that makes no sense in the context of the

sentence (e.g. ‘London is a very busy banana’).
— Brixton: A nonverbal test of set attainment and

rule detection. The patient is shown a 56-page
stimulus book, one page at a time. All pages contain
10 circles in the same basic array (see Fig. 18.1(a)).
Only one circle is filled on each page and the patient
has to predict where the next filled position will be,
based on what they have seen in the previous pages.
◆ Scoring method.
— Hayling: Sum of all response latencies for part 1;

sum of all response latencies and error score for part
2.
— Brixton: Total number of errors (maximum is 54).

(p.363) 4.5
Multiple
Errands Test
(MET)
◆ Original
reference.
Shallice
and
Burgess
(1991a).
◆ Test
Figure 18.1 (a) Sample sequence from
the Brixton Test. Here one might
reasonably expect the filled circle to be at
number 4 on the next page (on the
testing booklet, circles are numbered
from 1 to 10 on each array to make it
easier to refer to their position). (b)
Materials used for the Six Elements Test.
description. The test with probably the most obvious

ecological validity in current use, this is a formalized
version of a shopping task. It is conducted in a real
shopping centre or mall, so a specific version has to be
adapted to the local circumstances available to the
clinician. There is also a version that can be carried out in
most hospital environments (Knight et al. 2002). Appears to
Page 20 of 29
be highly sensitive both to brain damage in general, and to

specific dysexecutive problems. Details of how to set up the
test for your own local environment can be obtained from:
Dr Nick Alderman, Consultant Clinical Neuropsychologist,
Kemsley Brain Injury Rehabilitation Centre, St. Andrew’s
Hospital, Billing Road, Northampton, NN1 5DG, UK. (See
also Alderman et al. 2003.)
◆ Scoring method. A number of different types of error are

collected: rule-breaks; social rule-breaks; interpretation
failures; inefficiencies; task failures.
4.6 Proverbs test
◆ Original reference. Gorham (1956).
◆ Test description. Patients are asked to recognize and

interpret a certain number of proverbs (e.g. ‘Rome wasn’t
built in a day’) in two different ways. In the first part, they
must provide free verbal interpretations of each proverb. In
the second part, they must choose one out of four possible
answers provided for each proverb.
◆ Scoring method. Free verbal interpretations are scored

on a 3-point scale according to their degree of
‘concreteness’. In the multiple-choice test, there is only one
correct response for each proverb (the other three are
either wrong, partial, or concrete).
4.7 Six Elements Test (SET)
◆ Original reference. Shallice and Burgess (1991a).
◆ Test description. A modified version of this multitasking

test for general clinical use (Burgess et al. 1996b) is
commercially available as part of the BADS battery (see
Section 4.1). Additionally, there are other versions of this
test that have recently been developed by groups in
Cambridge and Toronto, plus more extensive versions by
the original authors (Burgess et al. 2000). Patients have 10
minutes to do three tasks (dictation, arithmetic, and picture
naming; see Fig. 18.1(b)). Each task has two parts, called A
and B. The two parts of each task cannot be carried out one
after the other (for instance, dictation A immediately
followed by dictation B, or vice versa). There are more
items in the six tasks than can possibly be completed in the
time allowed, so the aim is to do a bit of each part of each
task within the 10 minutes and thus patients have to plan
their time accordingly. The original, and some later versions
Page 21 of 29
also use weightings for certain items which gives them

particular significance, but this is not used in the most
widely used BADS subtest version of the SET.
(p.364)
◆ Scoring method. In the BADS version, a profile score is
calculated from the number of tasks attempted minus the
number of tasks where rule breaks were made. A further
point is deducted if the maximum time on any one task is
more than 271 seconds.
4.8 Stroop test
◆ Original reference. Stroop (1935).
◆ Test description. In the Victoria version, patients are

presented with three cards, each with a different stimulus:
24 coloured dots where one is asked to name their colour;
24 common words where one has to name the colour of the
ink in which the words are printed; and 24 colour names,
where the task is again to name the colour of the ink. There
are other versions, for instance, using an additional card on
which words are printed in black ink. Another version
includes only two cards, both with colour names printed in
different colour inks (first card, names are read; second
card, the ink colour is named).
◆ Scoring method. For each card, the time to complete the

task and the number of errors are recorded. The amount of
time required for the interference card (name ink colour) is
typically compared to the amount of time required in the
other conditions(s).
4.9 Trail making test
◆ Original reference. Originally, the test was one of the
Performance subtests of the US Army Individual Test
Battery, published in 1944. Earliest use with neurological
patients: Armitage (1946).
◆ Test description. In part A, examinees draw lines to

connect consecutively numbered circles from 1 to 25 on a
sheet of paper. Part B follows the same principle but this
time the lines drawn must connect consecutively numbered
and lettered circles (also 25 circles) by alternating between
the two types of sequences (see Fig. 18.2(a)). There are
various forms of this test.
Page 22 of 29
◆ Scoring method. There is a separate score for Part A and

Part B, which is the amount of seconds taken to complete
each task.
4.9 Verbal fluency test
◆ Original reference. Thurstone (1938).
◆ Test description. Patients are asked to say as many words

as they can, beginning with the letters F, A, and S (usually 1
minute per letter). They are asked not to give proper nouns
or alternative forms of the same word (e.g. ‘made’ and
‘making’). There are many alternate versions: written;
semantic categories (e.g. animals); different letters.
◆ Scoring method. Total number of correct words; number

of correct words for each letter.
4.11 Wisconsin card sorting test
◆ Original reference. Milner (1963). (Originally invented by
Berg 1948.)
◆ Test description. The patients sort 128 response cards

under four stimulus cards according to colour, form, and
number (see Fig. 18.2(b)). The aim is to work out the (p.
365)
sorting
category
according to
feedback
from the
examiner.
Nelson
(1976)
introduced
a shorter
version with
48 cards,
quicker
shifts, and
more
feedback to
the Figure 18.2 (a) Practice samples of the
examinee. Trail Making Test. (b) Examples of
◆ Scoring materials from the Wisconsin Card
method. Sorting Test.
Number of
categories
Page 23 of 29
achieved; total number of errors; nonperseverative errors;

perseverative errors (definitions vary).
Acknowledgements
Paul Burgess is supported by Wellcome Trust grant ref:
049241/Z/96/Z/WRE/HA/JAT. I am grateful to Laure Coates,
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Page 29 of 29
The natural recovery and treatment of executive disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The natural recovery and treatment

of executive disorders
Andrew D Worthington
DOI:10.1093/acprof:oso/9780199234110.003.19

This chapter provides an overview of the context and content
of the management of executive dysfunction. Traditional
approaches to this field tend to be structured in terms of
intervention type such as restorative versus compensation
techniques. By contrast, the chapter is organized around a
basic conceptual framework of normal executive functioning,
and disorders that occur at each stage of the processing
continuum are addressed in turn.
Keywords: executive dysfunction, rehabilitation, treatment, restorative

techniques, compensation techniques
Page 1 of 26
1 Introduction
Consider a typical household at breakfast time and it becomes
easy to appreciate the organisational or executive skills that
we normally take for granted. To prepare breakfast one needs
to decide what to eat, to search for the relevant food items;
recall how to boil an egg, make toast, or fry bacon, and carry
out the steps in sequence so that everything is cooked safely
and is ready to eat at the same time. During this activity other
aspects of the environment are very likely being monitored
too: keeping a check on the time; perhaps listening to the
television news, while simultaneously trying to stop the
children squabbling and ensuring they are ready for school;
mentally preparing for an important meeting at work; or trying
to anticipate whether you will have time visit the bank in your
lunch break. As if this were not complex enough, a barrage of
irrelevant stimuli assault the senses – an advertisement on the
radio, a stray dog barking at the postman, a neighbour trying
to start their car. All this information is processed, evaluated
and then discarded or accommodated within on-going
behaviour. The ability to carry out such naturalistic activities
successfully requires the co-ordinated and regulated
implementation of many cognitive operations, especially those
which have come to be associated with the term executive
functioning. These include skills such as goal setting,
planning, action initiation, self-monitoring and behavioural
inhibition. Disruption to any of these underlying processes as a
result of brain injury produces characteristically impaired
performance on many complex tasks that are fundamental to
daily living.
Consequently treatment of executive functioning may be, not

only the most important part of an individual’s rehabilitation,
but also the most difficult, affecting the highest levels of
cognitive ability, awareness and self-regulation. If intervention
is undertaken successfully a person’s life may be transformed
in a manner more familiar to transplant surgeons than to
psychologists. Effective treatment of severe executive disorder
can enable a person to sustain a degree of employment,
leisure activity and family integrity previously inaccessible to
them. In contrast, persistent dysexecutive problems may
render an otherwise intelligent individual unable to undertake
even the most rudimentary of everyday activities.
Page 2 of 26
(p.370) For practitioners, three facts make rehabilitation of

executive skills particularly problematic:
◆ The manifestations of executive dysfunction are diverse,

affecting cognition, mood and behaviour;
◆ The problems are not readily encapsulated in the manner

of traditional psychological assessment;
◆ There is no consensus regarding a conceptual or

methodological approach to either investigation or
treatment.
Effective rehabilitation depends on the therapist’s skill in

overcoming these fundamental difficulties. This chapter is
intended to assist by providing an overview of the context and
content of the management of executive dysfunction.
Traditional approaches to this field tend to be structured in
terms of intervention type such as restorative versus
compensation techniques (Sohlberg et al.1993; Evans, 2001).
By contrast, this chapter is organised around a basic
conceptual framework of normal executive functioning, and
disorders that occur at each stage of the processing
continuum are addressed in turn. This is not a ‘cookbook’
approach to treatment, and its coverage is certainly not
exhaustive, but the reader will find that this structure permits
systematic discussion of practical intervention strategies for
each of the most common executive dysfunctions. Repetition of
interventions is limited to cross-references. The chapter has
been organised pragmatically to help clinicians who are
typically faced with problems and want to know what methods
are available to manage the difficulties presented.
2 Natural recovery of executive disorders

Disorders of executive functioning are amongst the most
persistent sequelae of brain injury. Paradoxically they are
often difficult to identify in hospital due to the presence of
ward routine, the limited behavioural demands on patients and
the usual absence of skilled observers. Furthermore, when
they are apparent, executive disorders often exclude people
from rehabilitation, leading to overly pessimistic prognoses.
Finally, the manifestations of executive dysfunction are
typically misunderstood in the community, with the result that
many people fall by the wayside or come to the attention of
psychiatric or forensic services. Many of the personality
changes that follow serious brain damage are attributable to
Page 3 of 26
disorders of executive functioning, and it is these changes,

rather than physical or specific cognitive deficits, which cause
long-term breakdown of relationships and status. The true
severity of executive dysfunction may be apparent only after
formal rehabilitation has ended and a person has returned
home or back to work. However, significant improvements in
everyday functioning can be made, even several years after
the original injury, largely through compensatory
interventions.
Clinicians should be aware of factors that influence prognosis.

Important positive signs are:
◆ Brain injury occurring as an adult rather than as a child.
◆ Single incident brain injury without complications.
(p.371)
◆ Circumscribed rather than diffuse cerebral involvement.
◆ Motivation to participate in treatment. (NB. this is not the

same as motivation to go home or return to work, which can
be counter-productive).
◆ Awareness of problems in thinking or personality.
◆ Absence of severe behaviour disorders.
◆ No previous history of alcohol or substance abuse.
◆ No premorbid psychiatric history.
◆ Supportive social and family circumstances.
3 A conceptual basis for the treatment of executive

dysfunction
Investigating rehabilitation potential for executive

disorders
◆ Establish the organic basis for an executive

disorder, then considering non-organic confounding
factors.
◆ Certain neuropathology is especially likely to
cause executive disorders: traumatic brain injury,
herpes simplex encephalitis, aneurysms of the
Page 4 of 26
anterior communicating artery, certain tumours,

dementia of fronto-temporal type, subcortical
infarcts involving the thalamus, basal ganglia or
internal capsule.
◆ Severe executive dysfunction in everyday life can
occur in the absence of structural frontal lobe
pathology on an MRI scan.
◆ Basal skull fractures / cerebellar lesions may be
associated with significant executive deficits.
◆ Behaviour at home or work is a better index of
executive problems than behaviour in hospital or
formal assessment in a consulting room.
◆ Listen to what friends and family members say –
give them permission to report changes in
personality or behaviour.
Clinicians can be forgiven for feeling that the burgeoning

literature on executive functions and ‘frontal lobology’ is
abstruse and bewildering. Even so, when faced with multiple
executive problems a simple framework is helpful in
structuring treatment interventions, as diverse disorders of
cognition and behaviour may be manifestations of the same
underlying deficits. Below is a rudimentary but robust
framework for clinicians. The role of action schemas is central
to this model. An action schema is a representation of basic
action, which, when arranged in hierarchical fashion with
lower-level motor acts and higher-level organisational
processes, forms part of the executive system for governing
behaviour. For example, in the model below, planning occurs
at the level of assembly of action schemas relevant to a task.
(p.372)
A wide range of action and behaviour disorders can be

encompassed within this simple scheme. Effective intervention
requires identification of the level of dysfunction. Therefore
clinicians should consider how well a person can carry out
each of the following key stages in turn:
◆ Generating an intent to act (goal articulation) and

formulating a plan.
◆ Activating the plan and implementing the action to

achieve the desired goal.
Page 5 of 26
◆ Monitoring progression towards the goal and regulating

behaviour accordingly.
A three-stage framework for prioritising deficits for

treatment
Cognitive Behavioural manifestation

process at work
I Schema Disorders of goal articulation

assembly and planning
formulating intentions, clarifying
goals, planning and anticipation
II Schema Disorders of initiation and

activation sequencing
aspontaneity, action sequencing,
prospective remembering
III Schema Disorders of inhibition and

regulation control
Utilisation behaviour, impulsiveness,
perseveration, disinhibition,
aggression
Disorders of monitoring and

evaluation
attention and awareness, reasoning,
judgment, decision making, problem
solving, confabulation
We turn now to consider rehabilitation methods. Most

techniques can be considered to conform to one of three broad
types, loosely based on putative mechanisms of effectiveness,
as illustrated. However such taxonomies are mostly intuitive,
atheoretical, and not mutually exclusive (Worthington, 2005).
In preference therefore this chapter reviews intervention
methods in terms of their utility for disorders at each of the
above stages.
Page 6 of 26
A broad taxonomy of intervention types
Environmental modification
Essentially a compensatory means of therapeutic

intervention - changing the physical or social setting and
modifying the contingencies of reward. (eg. changing
layout of a room, using notebooks, diaries, pagers). Much
under-rated, often unfairly regarded as the therapist’s last
ditch option. Consider using for: (a) deficits in initial goal
setting, or in task execution, (b) in situations of stimulus
overload/competition, (c) context-driven behavioural
deficits, in the presence of other cognitive impairment.
Cognitive remediation techniques
Tasks aimed at restoring impaired cognitive processes -

repetitive practice of a specific (sometimes rather
contrived) task. Intervention delivered on structured
exercises in set treatment sessions. Some promising
results in the treatment of attentional deficits, but yet to
demonstrate wider utility for executive problems
(generalisability of treatment gains is poor). Be sceptical of
interventions claiming to restore underlying cognitive
processes (eg. memory process training, organisational
skills training, problem solving therapy).
Specific skills training
Variety of methods from cognitive and behavioural

psychology intended to teach people how to perform very
specific everyday activities. Often used in conjunction with
environmental modifications to good effect. Includes
training of metacognitive skills (eg. monitoring, evaluation,
feedback and awareness). Not limited to classroom
activities, can be employed in real life settings. Most of the
active interventions in this chapter conform to some kind
of skills training approach.
(p.373) 4 Interventions for deficits in the creation of

action plans
4.1 Impairments of planning and goal formulation
Page 7 of 26
Difficulty in formulating intentions or clear objectives before

starting a task. Caused by inability to devise an appropriate
action plan - commonly occurs with complex multi-stage tasks
(Shallice, 1982). The clinician should educate (reiterate the
importance of planning to eventual outcome) and moderate
(consider changes in routine or the task environment). Some
apparent planning impairments are in reality, impulsive
behaviours, which respond to self-instructional or verbal
mediation interventions (eg. Cicerone and Wood, 1987). Poor
planning may be improved by generating an appropriate
action script by asking people to verbally rehearse what is
required for a task (Zalla et al., 2001) or cueing
autobiographical memories (Hewitt et al., 2006). Task-based
checklists can also provide an explicit framework for
developing plans (Burke et al., 1991). For complex deficits of
strategic planning, consider training programmes with an
early emphasis on goal articulation and planning (see Goal
Management Training, stages 1–3; and Problem Solving
Therapy below). Alternatively, where time constraints are
important, Time Pressure Management (TPM) training (Fasotti
et al., 2000) offers a problem-solving framework which can be
linked to self-instruction to help individuals plan more
effectively.
4.2 Degradation of everyday action schema

Problems in carrying out everyday routine activities; this is not
really an executive deficit but manifests as one. It is caused by
the breakdown of conceptual knowledge or ‘schema
assemblies’ (Schwartz et al., 1991) for well-established actions
– may manifest as part of (p.374) an ideational or frontal
apraxia. It may be associated with semantic impairments.
Treatment as for action disorganisation (below): Ensure a good
understanding of the task objectives and operations before
commencing action. Follow this with on-line assistance (verbal
prompts, physical cues) as necessary.
5 Interventions for deficits in the activation and

implementation of everyday action schema
Deficits in activating intentions or initiating behaviour cause
poverty of action, an extremely debilitating condition.
Manifestations may vary.
5.1 Aspontaneity
Page 8 of 26
A marked reduction in spontaneous purposeful activity; this

must be distinguished from the neurological conditions of
abulia and akinesia, and the neuropsychiatric syndromes of
apathy and depression. Environmental cues and verbal
prompts are often ineffective because the problem is not one
of goal clarity but represents a difficulty putting plans into
action. Solutions are as follows:
1 Modify the environment to increase the salience of

antecedent stimuli and reduce the significance of
irrelevant stimuli (see discrimination training below);
2 self-prompting schedules can also be beneficial
(Burke et al., 1991) but only if linked to clear rewards
for the individual. Too often intervention fails because
the person has no desire to engage in particular
activities.
3 Pharmacological agents may help (eg. dopamine
agonists).
5.2 Action disorganisation

Problems with common everyday tasks (eg. making a cup of
tea); this is not a pure executive disorder, but is caused by
disruption to the procedural knowledge base for over-learned
actions (such as brushing one’s teeth), rendering the activity
dependent on inadequate executive control.
Intervention should ensure conditions are optimal for action

schema activation, and include procedures to improve
behavioural regulatory functions, to ensure efficient operation
of the relevant action schema once activated. Treatment
options include:
1 environmental simplification to minimise off-task

errors;
2 provide a visual sequence of correct action stages to
be followed;
3 use behavioural techniques: where a desired response
does not occur spontaneously such an action can be
developed using the technique of shaping, which
involves positively reinforcing successive
approximations to the desired behaviour. Chaining
techniques are recommended if the primary problem is
in action sequencing;
4 use verbal self-regulation methods.
Page 9 of 26
Clinicians usually select whatever seems likely to work, and

then modify accordingly (see Wilson, 1999).
(p.375) 5.3 Prospective remembering

The inability to carry out an intention to act at some future
time; this is commonly associated with other executive
deficits, but not necessarily with other memory problems. It
needs to be distinguished from initiation disorder (see
aspontaneity above) and impairments of retrospective memory,
as memory for the intent to act may be preserved.
Therapeutically, internal memory strategies have limited
success. Likewise, the use of spaced retrieval methods
(increasing the time lag between encoding and execution of
intentions) has been disappointing (Sohlberg et al., 1992).
Instead, external cueing systems should be considered
(individualised checklists are a good example). As long as the
person can use the technology electronic aids can be effective
such as a pager (Evans et al. 1998; Emslie et al., 2004) or SMS
text message (Pijnenborg et al., 2007). A text message that
says ‘Stop’ may be sufficient to re-focus attention (Fish et al.,
2007). If severe anterograde memory problems are also
present, start with a very basic task and simple cues (eg.
prompt with telephone calls). Gradually a self-cueing
programme can be devised using a combination of checklists
and external prompts to use the checklists, in order to develop
a simple routine of action initiation. Many people develop their
own idiosyncratic methods. These should be respected, but
may be improved.
6 Interventions for deficits in the regulation of behaviour

For goal-oriented behaviour to be adaptive in the real world it
has to be efficiently regulated. The majority of cognitive and
behavioural disorders that characterise the dysexecutive
syndrome arise from disturbance to regulatory control
mechanisms. These comprise fundamental processes of
attention and awareness, judgment and inhibition.
6.1 Disorders of inhibition

Disorders of inhibition arise principally from a deficiency of
executive control over lower-level action schemas, leading to
unmodulated contention scheduling (see Chapter 18). The
manifestations of impaired inhibitory control are varied. In
some cases one observes a failure to exercise a socially-
acceptable degree of self-restraint in translating thoughts or
feelings into action. In other instances, behaviour is clearly
Page 10 of 26
driven by external stimuli without any apparent cognitive

mediation. Treatment of the most common manifestations is as
follows:
6.1.1 Utilisation behaviour

A non-planned and irrelevant response to an object that often
interferes with an existing activity; it is caused by automatic
activation of an action schema, usually triggered by a specific
object, resulting in behaviour that may be socially
unacceptable (drinking from someone’s cup, answering their
telephone). It is important to distinguish utilisation behaviour
from a simple frontal grasp reflex (objects do not have to be
within immediate grasping range to elicit utilisation
behaviour) and ‘alien hand’. Verbal prompting does not usually
help, as awareness may be preserved. Modifying the
environmental triggers offers a partial solution, though the
problem often resolves spontaneously.
(p.376) 6.1.2 Distractibility

Responding to external stimuli (noise, people) at the expense
of current activity; this is essentially a deficit in attentional
control, allowing attention to be captured by task-irrelevant
events. Can produce severe disability in everyday life, but is
amenable to treatment with cognitive and behavioural
techniques. [See Discrimination Training below and also
Chapter 5 on Attention]. Intermittent cues, such as periodic
auditory alerts (Manly et al., 2002), may help re-focus
attention to the task at hand.
6.1.3 Impulsiveness
A tendency to act without pre-planning or thinking through the
consequences; this is caused by inadequate executive control
over behaviour - unconstrained contention scheduling. It is
commonly associated with other signs of dysregulation
including mood.
The consequences of impulsive behaviour can be ameliorated

to a degree by removing temptation, a simple but effective
strategy at times. In treating impulsiveness itself, practical
(and perhaps ethical) constraints prevent more widespread
use of counter-conditioning methods, massed practice or
paradoxical intention. Consequential learning methods can be
used, where there is some incentive for demonstrating self-
restraint. In practice this is better tied to a concurrent verbal
task to capture attention (eg. counting 1–5 and then carrying
Page 11 of 26
out the action). A personal favourite is the cue word “WAIT!” –

short, clear and effective in interrupting action. It is also an
acronym for ‘What Alternative Is There?’ which can be
incorporated into a self-instructional programme.
6.1.4 Perseveration
A repetitive pattern of action that is no longer relevant to the
situation. Even if an action is triggered appropriately, there
comes a time when it is redundant due to changes in
circumstances (eg. a goal has been achieved). Inability to
change action schema accordingly leads to inefficient, often
highly inappropriate, behaviour.
The clinician should establish whether the behaviour is

exclusively organically-driven (frontal perseveration) or has
been learned (habitual behaviour). Awareness may be
preserved and the problem may improve within six to twelve
months after brain injury.
Training a person to use self-statements during perseverative

acts can reduce the problem. There is some evidence that
massed practice or ‘cognitive over-learning’ is effective in
reducing verbal perseverative behaviour (Alderman and Ward,
1991). Repetitive habitual behaviour needs a functional
analysis, followed by appropriate cognitive-behavioural
treatment to address the environmental contingencies helping
to maintain the behaviour. In this way Matthey (1996) reduced
perseverative behaviour, but effects did not generalise to the
home environment, presumably because the external
contingencies at home were different from the treatment
environment. This problem could be minimised if the therapy
specifically included the discharge environment as a legitimate
treatment arena.
6.1.5 Disinhibition
This is acting or speaking in a manner which contravenes
acceptable social conduct.
(p.377) Disinhibited behaviour can take many forms, from

mild over-familiarity with strangers to acts of sexual
indecency. Situations may vary and the first step in treatment
is to conduct comprehensive assessment of the circumstances
of the behaviour. Although organically-derived, the behaviour
is often exacerbated or sustained by reactions from others.
Therefore investigation should encompass social context,
Page 12 of 26
including antecedents and consequences, as the key to

successful treatment. Amelioration has typically been based on
principles of behaviour modification, including time-out from
positive reinforcement (Wood, 1990), though attention
constraints associated with dysexecutive impairment may
interfere with conditioning.
Intervention should therefore be immediate, providing a direct

feedback (usually a specific verbal response). For individuals
with adequate memory, additional delayed feedback (up to 1
hour later) encourages reflection on behaviour and provides
opportunity to rehearse alternative responses (thus developing
a more acceptable action schema). Here verbal mediation
methods can help towards the development of a self-
management approach (Wood and Worthington, 2001).
Example of a verbal mediation dialogue
How are you this morning?
Fed up, I missed my breakfast
What happened at breakfast?
I had an argument with Jason, because he was staring at

me
Why do you think he did that?
I don’t know, maybe he was trying to annoy me. He was

doing it on purpose
How did that make you feel?
I got angry, he was doing it on purpose to annoy me
What did you do then?
I started shouting and calling him names
What happened next?
He shouted back…we just kept shouting, until we got told

to leave the dining room
Page 13 of 26
What else could you have done?
I could have carried on eating my breakfast and ignored

him
How do you think Jason would have reacted then?
He would have got fed up as I was ignoring him
Would that have been better for you too?
Yeah, because he’s just a loser, but I would have had my

breakfast
So if you feel Jason is trying to wind you up at breakfast

tomorrow, what will you do?
I’ll take no notice, and carry on
(p.378) 6.1.6 Aggression

Aggression can be verbal or physical, towards objects or
persons, including self-directed anger, and has many causes. It
is often an attempt to intimidate rather than harm. Inability to
articulate goals, solve problems or communicate intentions
can lead to frustrations and, if unchecked, to aggression. It is
important to differentiate this from irritability and episodic
dyscontrol. Remember also that aggression is a normal
response to certain situations, but after frontal brain injury
impaired behavioural control mechanisms mean that it
becomes a default response in many situations. Once
triggered, aggression may not be constrained by normal
regulatory processes. There are several approaches to
treatment. Pharmacological intervention is usually necessary
in severe cases, and can augment psychological methods.
Medication alone is not a long-term solution. Modification of
the environment can help reduce trigger events, but this is
rarely adequate. The objective of treatment is usually to
restore a degree of self-control. This can be done using
behavioural methods alone, such as cost-response techniques
which link the anti-social behaviour to a meaningful sanction
(eg. failure to earn privileges). Some understanding of
response-consequence relationships is necessary for learning,
so ensure learning intervals are brief where cognition is
severely disturbed. Alderman and Burgess (1994)
Page 14 of 26
recommended cost-response techniques as especially useful in

such cases.
For higher-functioning individuals cognitive-behavioural

methods can be used, either in a self-instructional programme
or a problem-solving anger management intervention (Medd
and Tate, 2000). In all cases the aim is to encourage the
activation (consciously or otherwise) of an incompatible, more
acceptable action schema in response to identifiable trigger
stimuli. Caveat: change on self-report measures of anger is not
the same as spontaneous use of anger management strategies
in everyday life, and generalisation of treatment effects is
problematic, especially after group interventions.
6.2 Disorders of evaluation and judgment

The inability to make sensible decisions or express sound
judgments is a cardinal feature of executive dysfunction. In
extreme cases, otherwise intelligent individuals mix with bad
company, frit away their savings on fruitless ventures, and
generally go through life from one mishap to another, unless
supervision is imposed. In such cases the matter of
competency to manage one’s affairs becomes important. In
many other instances the deficiencies are subtle and may only
be apparent some time after rehabilitation has ended.
6.2.1 Impairments of judgment and decision making

First, establish whether impaired judgment is a specific or
more general defect. For example, poor road safety judgment
may be secondary to subtle perceptual deficits. Commonly,
generalised impairments of judgment are accompanied by
diminished self-awareness.
The type of intervention depends on the likely underlying

problem. Inability to select a single course of action from
plausible options can produce impairments in both judgment
and decision making, or may even result in deficits of
initiation. Therefore it is important to distinguish between
difficulty in making just about any kind of decision from a
tendency to make poor decisions. The former need
interventions aimed at clarifying the (p.379) issues and
generating solutions, whereas the latter requires focus on the
process of comparative evaluations and anticipated
consequences. Strategies used in training problem solving
(see next section) are valid in both cases.
Page 15 of 26
6.2.2 Impairments of reasoning and problem solving

Reasoning and problem solving are two high-level skills which
are often compromised as part of a dysexecutive presentation,
but often the full magnitude of the deficits is only evident on
real-life tasks (Shallice and Burgess,1991; Goel et al., 1997;
Goel and Grafman, 2000). Unfortunately, treatment for such
deficits is still largely classroom–based (see Evans, 2001). One
comprehensive programme is Problem Solving Training, or
PST (von Cramon et al., 1991; von Cramon and Matthes-von
Cramon, 1992). The essence of the treatment is to train
persons in key aspects of problem solving. This kind of mental
discipline training can improve performance on problem
solving exercises within a few weeks. However, the real
difficulty is that patients with executive disorders can acquire
knowledge and skills but may nevertheless fail to apply this
spontaneously outside the treatment environment. Evidence to
date suggests that effort would be better spent improving use
of such skills in specific everyday environments (von Cramon
and Matthes-von Cramon, 1994).
A related approach is employed in Goal Management Training.

This is really another form of verbal mediation training
intended to improve self-regulation, but with an abstract set of
principles that can be applied across situations. This method
can improve performance of everyday tasks (Levine et al.,
2000), but, as with PST, it is not clear whether all the
components are really necessary, and some stages may be
more relevant than others for particular deficits. (p.380)
Stages in Problem Solving Therapy
1 Problem formulation (defining the task objective)

2 Generation of solutions (brainstorming)
3 Deciding on a solution (weighing-up the options)
4 Verifying the outcome (recognising errors,
correcting mistakes)
Steps to Goal Management Training
Page 16 of 26
1 Problem orientation
2 Problem definition (specifying the goal)
3 Listing (breakdown goals into relevant stages -
subgoals)
4 Learning (encoding and retention of steps)
5 Monitoring (comparing outcome with intention)
6.3 Impairments of self-monitoring

6.3.1 Self-
awareness of
behaviour
Many
behavioural
interventions
work
successfully
without
specifically Fig. 19.1 Response-cost programme in
recruiting progress for verbal sexual disinhibition.
self-
awareness.
Other methods however explicitly target awareness as an
integral aspect of the rehabilitative process. Disruption to the
normal feedback mechanism linking conscious intentions with
the external world results in an inability to monitor one’s
behaviour and its effect on others. This is why social
disinhibition does not improve with experience alone. This is
usually treated by response-consequence methods, for
example, by linking this with subtle social reinforcement,
explicit feedback or tangible reward. Fig. 19.1 is a snapshot of
the gradual reduction in sexual comments taking place during
a social reinforcement cost-response programme for a 40 year-
old man with very severe traumatic brain injury. (p.381)
A self-instruction programme
Page 17 of 26
A self-instructional programme was employed to good

effect with a 29 year-old woman two years after her severe
head injury. She could take up to three hours to get
washed and dressed in the morning as a result of severe
distractibility and obsessive behaviour. A programme was
devised during which a support worker read out specific
action prompts. These were repeated by the client as she
performed the actions. These statements gradually came to
act as internal prompts, improving her attention to task
and increasing her speed to wash and dress to half an
hour. Fig. 19.2 shows the mean number of daily verbal
prompts in a two week baseline period and for four weeks
following withdrawal of the self-instructional programme.
To promote
generalisation
of gains
clinicians
should
remember to
include graded
exposure to
successively
more
challenging
stimuli or
situations. Self-
instructional or
Fig. 19.2 Self-instructional programme
self-
for washing and dressing.
management
approaches
have been
under-used in brain injury. True, many cognitive skills packages (eg
GMT) and behaviour modification techniques invoke an appeal to
self-awareness and thereby to self-monitoring. But, few deal
specifically with this crucial aspect of executive disorder.
An exception is Self-monitoring Training (SMT) reported by
Alderman (et al., 1995) to reduce to the frequency of
inappropriate utterances. This multi-stage programme is really
a hybrid for improving self-awareness in combination with a
procedure for reinforcing successively lower frequencies of
target behaviour (DRL), although DRL methods can be
effective without such self-monitoring (Knight et al., 2002).
Personal experience suggests that increased self-awareness
Page 18 of 26
can be achieved within a few weeks, at most, but does not

necessarily generalise to changes in behaviour.
Fig. 19.3 shows how this method was effective in reducing a

range of disinhibited verbal behaviours in a young woman
following herpes simplex encephalitis, first reported by
Worthington (2005). The technique is recommended for high
frequency problems, and can be enhanced by self-completion
of a daily record or diary (Burke et al., 1991). In many cases
however the problem is not one of self-evaluation, but an
inability to divide attention between the task in hand and other
pressures. In this case intervention should focus on the
temporal aspect of the task (see Time Pressure Management,
above).
6.3.2 Confabulation from memory

Confabulation is the production of false memories following
brain injury, which the person confuses for, and cannot
distinguish from, veridical recollection. It is generally
associated with frontal-subcortical damage, and is considered
to result from deficient executive control over memory
retrieval – (ie. faulty verification procedures). Improvement
often occurs spontaneously, and there are few treatment
studies. However Dayus and van den Broek (2000)
successfully employed self-monitoring training to reduce
debilitating delusional confabulations. (p.382)
7 Issues in
the
treatment of
executive
disorders
Fig. 19.3 Self-monitoring programme

with generalisation of behaviour across
settings. Key: I = interruptions; IC =
inappropriate comments; OT = off the
topic comments; G = generalisation
probe (second axis) reprinted with
permission.
Page 19 of 26
Components of self-monitoring training
1 Baseline assessment of frequency of target

behaviour
2 Spontaneous (ie. unprompted) self-monitoring of
target behaviour
3 Prompted self-monitoring, with assistance of
therapist
4 Independent self-monitoring (with reward
contingent on achieving a pre-determined level of
agreement in frequency ratings between therapist
and client)
5 Independent self-monitoring and reduction of
target behaviour (delivery of reward contingent
upon graded reduction in frequency of target
behaviour)
7.1 Evaluating clinical efficacy

Well-designed rehabilitation studies for executive skills are a
rare breed. The so-called dysexecutive syndrome encompasses
a wide range of deficits, some presenting as behaviour
problems, some manifesting as higher cognitive impairments.
Treatment efficacy has to be evaluated for specific subtypes of
executive disorder, indicating whether the behaviour or the
underlying the cognitive processes are the focus of
intervention. Evidence of effectiveness is limited to small
group studies or single cases. While many of these seem to
show good results (and clinical experience would support
this), it is difficult to infer who benefits from which
interventions. Comprehensive treatment packages may
contain much redundant material and need to be examined in
detail. In this light, studies comparing different interventions
(eg. Alderman and Burgess, 1994) are particularly instructive.
(p.383) 7.2 The role of attention and self-awareness

Recruitment of attention is critical to improving many high-
level executive skills, but attention is often impaired in
conjunction with executive processes. Brain injury can also
cause disorders of awareness and prevent use of attentional
resources in regulating behaviour. This is why techniques
based solely on positive reinforcement may be ineffective in
Page 20 of 26
modifying behaviour in the context of a dysexecutive

syndrome. Rehabilitation can be focussed on the attention
deficit or the behavioural manifestation - the clinician must
decide.
In terms of self-regulatory disorders, attention per se is rarely

the focus of intervention, but treatment does involve
techniques for modifying attention to what is therapeutically
important. This is the basis of discriminative attention training
that underpins much of the learning process in rehabilitation.
Treatment methods, involving either environmental
modification or manipulation of consequences of actions, focus
on alternative or incompatible reactions to a situation. This
allows selective reinforcement by therapists for certain actions
and thereby increases the likelihood of the desired behaviours
recurring. Such discriminative reinforcement techniques were
reviewed by Wood (1990). Attentional re-directing is also
integral to cognitive-behavioural approaches to improving
social and functional skills, and is central to the development
of self-monitoring programmes. Clinicians should establish
first whether there is a significant attentional contribution to
an executive disorder, as this is often the key to successful
treatment. For a comprehensive review of attention disorders
and remediation, the reader should refer to the chapter on
attentional disorders in this volume.
7.3 Designing effective interventions for executive disorders

The principles of sound clinical practice apply to rehabilitation
of executive dysfunction. Thus budding therapists need to:
◆ Carry out assessment of both spared and impaired

abilities (ie. a reliable baseline).
◆ Decide on priorities for treatment.
◆ Agree specific operational goals with family, client and

therapy team.
◆ Devise a clear explicit intervention, based on a hypothesis

of the nature of the executive dysfunction.
In addition, rehabilitation of executive deficits requires close

attention to the following aspects of treatment design:
◆ Consider the conceptual basis for a deficit in order to

rationalise choice of intervention strategy.
Page 21 of 26
◆ Select practical tasks as targets for intervention.
◆ Avoid tasks reliant on regurgitation of old knowledge.
◆ Avoid highly constrained tasks where responsibility for

correcting performance rests solely with therapist.
◆ Breakdown intervention into discrete stages.
(p.384)
◆ Consider most-to-least-prompts and spaced retrieval
(using errorless learning principles).
◆ Deliver treatment in different settings to facilitate

generalisation.
◆ Start with a simple analogue but work towards increasing

complexity of treatment environment.
◆ Assess similar non-treated tasks to investigate

generalisation of skills to related tasks.
◆ Assess non-treated domains of cognitive functioning to

control for natural recovery.
The treatment of executive dysfunction is one of the least

understood and most complex areas of brain injury
rehabilitation. It is not sufficient to show improvements on a
task with practice; to be effective an intervention must also
address the problem of spontaneous application and self-
evaluation of skills once acquired. The therapeutic techniques
described are largely in their infancy, there is much we still
have to learn about optimal methods for improving self-
regulation (Muraven and Baumeister, 2000). Nevertheless, if
intervention is undertaken sensitively and rationally, executive
functioning can be improved to the extent that real change can
be effected in quality of life.
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Schwartz, M.F., Reed, E.S., Montgomery, M.W., Palmer, C.

and Mayer, NH. (1991). The quantitative description of action
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Shallice, T. and Burgess, P.W. (1991). Deficits in strategy

application following frontal lobe lesions in man. Brain, 114,
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Sohlberg, M.M., Mateer, C.A. and Stuss, D.T. (1993).

Contemporary approaches to the management of executive
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Page 26 of 26
The neuropsychological assessment and treatment of disorders of voluntary
movement


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The neuropsychological assessment

and treatment of disorders of
voluntary movement
Georg Goldenberg
DOI:10.1093/acprof:oso/9780199234110.003.020

This chapter discusses the assessment and treatment of
incorrect awkward movements and disturbed voluntary control
of motor actions. Incorrect and awkward movements can
occur on one or both sides of the body. Kinaesthetic ataxia
affects the hand and optic ataxia affects the visual field
contralateral to the lesion. Face apraxia and limb apraxia are
bilateral disorders resulting from unilateral, mainly left sided,
lesions. Callosal apraxia disturbs movements of the left-sided
extremities. In disturbed voluntary control of motor actions,
the affected limbs either do not spontaneously participate in
an intended action (motor neglect) or do perform actions
which are not intended (all other syndromes).
Keywords: motor impairments, kinaesthetic ataxia, face apraxia, limb apraxia,

callosal apraxia
1 Introduction
Page 1 of 22
movement
Neuropsychology is concerned with ‘higher order’ rather than

‘elementary’ disorders of movement. The theoretical model
underlying such a distinction is questionable but it is useful for
delimiting a collection of disorders which deviate from other
motor symptoms of brain damage by marked dissociations
between normal and abnormal motor acts of the same body
part. One class of such disorders is characterized by incorrect
or awkward movements which differ from ‘elementary’ motor
disorders in that the same movements which give rise to
errors in one condition can successfully be performed in other
conditions and success or failure depend on non-motor factors.
Such factors may be the visual control of the movements, its
communicative meaning, or its relationship to tools and
objects. Another class of higher order motor problems is
constituted by well executed and apparently purposeful
movements which do not conform to the subject’s intentions.
Table 20.1 gives an overview of disturbances fullfilling these
criteria.
2 Incorrect and awkward movements

They can occur on one or both sides of the body. Kinaesthetic
ataxia affects the hand and optic ataxia affects the visual field
contralateral to the lesion. Face apraxia and limb apraxia are
bilateral disorders resulting from unilateral, mainly left sided,
lesions. Callosal apraxia disturbs movements of the left sided
extremities.
2.1 Kinaesthetic ataxia (parietal hand)

Patients need vision to compensate for insufficient processing
of kinaesthetic afferences. Shaping of the hand for grasp and
manipulations is clumsy and needs visual attention. When out
of visual control, the arm may involuntarily change its position
but it does not unintentionally perform goal directed action.
Kinaesthetic ataxia is a very disabling condition. The need for
visual control renders the hand unusable for manipulation of
objects in daily living because patients must concentrate their
attention on the affected hand rather than on the external
actions they want to accomplish.
(p.388)
Table 20.1 Higher level motor disorders resulting

from hemisphere damage*
Page 2 of 22
movement
Incorrect and awkward Movement out of voluntary control

movements
contralesional bilateral contralesional bilateral
Kinaesthetic Face Grasping & Motor

ataxia Optic apraxiaLimb gropinganarchic perseverationsImitation
Ataxia apraxia hand behaviourUtilization
behaviour
Parietal lesions Frontal lesions

*Callosal apraxia is not considered in this table
◆ Clinical diagnosis:
— Note involuntary displacement of the arm when

attention is directed elsewhere.
— Palpation of objects given for stereognosis is

awkward and when the patient is prevented from
seeing the hand the object may slip out of the hand.
— Ask blindfolded patient to replicate with the sound

arm a passively induced position of the affected arm:
they cannot do so because they lack kinaesthetic
information.
◆ Lesion. Anterior parietal lobe (Freund, 1987), lateral

thalamus, or fibre tracts connecting these structures.
◆ Therapy. Explaining the mechanisms of the disorder and

the importance of visual feedback can alleviate the patient’s
distress and help them to develop compensatory strategies
in daily living. Occupational therapy can train performance
of simple unimanual actions, like drinking or eating.
Success remains contingent on allocation of attention to the
affected hand. Integration of its movements into swift
bimanual actions is rarely achieved.
2.2 Optic ataxia
Patients are unable to exploit visual information for exact
guidance of goal-directed motor action of their hands.
Inaccuracy and hesitancy of reaching to visually presented
objects (e.g. the finger of the examiner) contrast with fast and
accurate reaching to parts of their own body (e.g. the tip of
the nose or the finger of the other hand). Experimentally it has
been demonstrated that accuracy of visual reaching improves
when a delay is interpolated between visual presentation and
Page 3 of 22
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start of the movement (Rossetti et al., 2005). Optic ataxia is

more severe in the periphery of the affected visual hemi-field
than in foveal vision. If optic guidance of eye movements is
preserved, patients can compensate for optic ataxia by making
a saccade to fixate a peripheral target and then reach it in the
centre of the visual field. Optic ataxia affects reaching with
either hand, but is sometimes more severe for the
contralateral hand.
Bilateral lesions can cause optic ataxia of the whole visual

field. Because of the proximity of responsible lesions, bilateral
optic ataxia can be associated with Balint’s Syndrome (see
Chapter 11). Left sided optic ataxia can be associated with
hemi-neglect, but most patients with hemi-neglect reach
accurately to targets on the neglected side once they have
noticed them.
(p.389) The ecological significance of optic ataxia depends

on whether it is uni- or bilateral and whether reaching in
central fixation is preserved. If only reaching in the periphery
of one visual field is inaccurate, the impact on everyday
functioning is moderate.
◆ Clinical diagnosis
— Sit opposite the patient and ask the patient to

fixate on your eyes (as in confrontation perimetry).
Raise a finger or a small object (e.g. a pencil) to
different locations and ask the patient to touch it
with their index finger.
— To document preserved non-visual pointing ask the

patient to touch their nose or fingers of the other
hand.
◆ Lesion. Superior parietal lobe and parieto-occipital

junction (Karnath & Perenin, 2005).
◆ Therapy. If visual fixation is preserved, the strategy of

self-cueing by visual fixation (see above) can be trained.
Page 4 of 22
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2.3 Face apraxia

Patients have difficulties in performing facial or oral
movements on command, although very similar movements
are carried out spontaneously. For example, a patient may be
unable to move the tongue into one cheek on command, but
can perform the same movement when cleaning the mouth
from remainders of a meal. Face apraxia may be associated
with contralesional facial paralysis but can also be
demonstrated on the ipsilesional side of the face. Face apraxia
is rarely noted by the patients themselves and has no impact
on life outside the testing situation. It may, however, constitute
an obstacle for speech therapy in patients with LBD and
apraxia of speech.
◆ Clinical diagnosis: To avoid confusion with problems of

language comprehension, movements are tested in
imitation. Table 20.2 provides a list of items arranged by
difficulty (Bizzozero et al., 2000).
◆ Lesion: Face apraxia can result from lesions of either

hemisphere, but tends to be more persistent and more
severe after left brain damage (LBD) than right brain
damage (RBD). In LBD patients it is predominantly caused
by inferior frontal and precentral lesions (Raade et al.,
1991).
◆ Therapy: Face apraxia per se does not need therapy.

2.4 Limb apraxia (see box)
Patients commit errors on performing some kinds of motor
actions even when using the hand ipsilateral to the lesion
which shows completely normal skill on other kinds of actions.
The affected domains of action are imitation of gestures,
performance of meaningful gestures, and use of tools and
objects which can be further subdivided into the use of single
tools or tool-objects pairs, and multi-step actions with several
objects.
2.4.1 Imitation of gestures

Patients understand the request to imitate (if they do not,
apraxia cannot be diagnosed) and try to provide a gesture
resembling the demonstration, but the resulting posture is (p.
390)
Table 20.2 Items for testing facial apraxia
Page 5 of 22
movement
A Lower face
B Easy
Open your mouth
Show your teeth
Blow
B Medium
Make a clip-clop noise with your tongue
Push the tip of your tongue against the inside of your left
cheek
Move your jaw to the right (and from right to left) three
times
B Difficult
Puff out your right cheek
Push out your lower teeth (prognathism)
Push your tongue against the inside of your lower lip
A Upper face
Wrinkle your forehead
Wrinkle your nose
Blink your right eye (tight)
Easy, medium, and difficult refer to the ease with which
normals perform these gestures. All upper face items are
medium to difficult. Performance should be considered
pathological if the patient produces random and amorphous
movements, if response is preceded by additional,
unsolicited movements, or if the required movement is
incomplete or not performed at all. Items are from
(Bizzozero et al., 2000) in which a complete list is given
together with normative data.
Bizzozero, I., Costato, D., Della Sala, S., Papagno, C.,

Spinnler, H., and Venneri, A. (2000). Upper and lower face
apraxia: role of right hemisphere. Brain, 123, 2213–2230.
Page 6 of 22
movement
(p.391) spatially wrong. The movement to the final position may

be hesitant and searching, but there are patients who attain the
wrong position by a quick and confident movement. The problem
concerns the definition of the target posture rather than its motor
execution, and patients also commit errors when asked to replicate
the gestures on a mannikin, or to match photographs of the same
gestures performed by different persons seen from different angles.
Imitation of meaningful gestures may be preserved, as patients
may be able to recognize the meaning of the gesture and reproduce
it without actually copying the shape of the gesture.
Box 20.1 Classification of apraxia
There is a traditional distinction between three forms of

limb apraxia:
◆ Ideational
◆ Ideomotor
◆ Limb-kinetic
This classification goes back to a hierarchical model of

motor control proposed by Liepmann about 100 years ago.
Liepmann thought that patients with ideational apraxia
could not generate the idea or, respectively, the mental
image of the intended action, whereas ideomotor apraxia
disrupts the transformation of this idea into appropriate
motor commands. Limb-kinetic apraxia should result from
loss of ‘motor engrams’ which each hemisphere possesses
and which direct overlearned routine actions of the
opposite hand.
It is difficult to define clinical criteria that unequivocally

distinguish between these variants of apraxia.
Consequently, they have received very different
interpretations. The theoretical model underlying the
classification does not accord well with current knowledge
of the physiology of motor control. There are thus no
convincing reasons for retaining the historical
classification.
Disturbed imitation of gestures is a very impressive and easily

demonstrable symptom of high theoretical interest, but as
imitation is rarely required outside the testing situation it has
Page 7 of 22
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little ecological significance. However, disturbed imitation may

be an obstacle for efficient therapy of other motor
impairments in physical and occupational therapy.
Clinical diagnosis
It is preferable to test meaningless gestures as they provide an

uncontaminated indication of the ability to imitate the shape of
gestures. The examiner sits opposite the patient and
demonstrates the gestures ‘like a mirror’ using the right hand
for left hand imitation and vice versa. Patients should always
use the hand ipsilateral to the lesion. The patient is allowed to
start imitation only immediately after demonstration. Figure
20.1 shows 10 hand postures and 10 finger postures for which
norms are available (Goldenberg, 1996).
Lesion
LBD disturbs imitation of hand postures more than finger

postures. RBD affects imitation of finger postures but spares
hand postures. Imitation of foot postures can be deficient in
both LBD and RBD. Within the left hemisphere, disturbed
imitation of hand postures is linked to inferior parietal, and
disturbed imitation of finger postures to inferior frontal and
precentral lesions (Goldenberg & Karnath, 2006).
Therapy
As it does not affect the patient’s independence in daily living,

disturbed imitation would not by itself justify therapeutic
intervention. It may, however, be useful to train imitation of
hand and finger postures as a prerequisite to acquiring the
use of meaningful gestures to compensate for aphasia.
2.4.2 Meaningful gestures

Patients are unable to demonstrate meaningful gestures on
command. Such gestures may either have a conventionally
agreed, more or less arbitrary, meaning like ‘somebody is
nuts’, ‘military salute’, or ‘okay’, or they may indicate objects
by miming their use. Outside the testing situation the deficit
can be observed when aphasic patients try to express
themselves in spite of severe language impairment. They
either do not employ gestures at all or produce amorphous,
stereotypic, or incomprehensible gestures. Because it restricts
the range of possible compensation for the language deficit,
this manifestation of apraxia has ecological significance.
Page 8 of 22
movement
Clinical diagnosis
Usually, diagnosis concentrates on miming of object use,

because aphasic patients may not understand the verbal label
of gestures with conventional meaning, whereas
comprehension of the object name can be facilitated by
showing either the object (e.g. a hammer, a key, a screwdriver)
or a picture of it. Even with this help, understanding (p.392)
Fig. 20.1 10 hand postures and 10

finger postures for testing imitation
of meaningless gestures.
Two points are given for correct imitation
on first trial, and 1 point for correct
imitation on second trial, scores of 18 for
hand postures and 16 for finger postures
are borderline and scores below these
values are pathological (Goldenberg,
1996). Illustration from (Goldenberg et al.,
2001).
Page 9 of 22
movement
the instruction may be problematic. The demand to demonstrate

the movements associated with object use without actually
handling the object, taxes not only speech comprehension but also
‘abstract attitude’ which is frequently compromised in patients with
aphasia. A diagnosis of apraxia should be made only if patients
respond to the presentation of the object with a movement of the
hand which can be clearly distinguished from spontaneous ‘baton’
movements accompanying attempts of verbal expression. A further
difficulty is posed by the great variability of gesture performance in
normal subjects. For example, the replacement of the absent object
by the hand (‘body part as object’: e.g. brushing teeth with the
index rather than demonstrating the manipulation of a toothbrush)
is a strategy frequently employed to indicate an absent object when
the verbal label is lacking (e.g. when trying to buy a toothbrush in a
country the language of which you cannot speak). There are,
however, errors which unequivocally indicate apraxia:
◆ Perseveration of a more or less amorphic movement (e.g.
a circling movement above the table or repeated hitting of
the fist against one’s chest)
(p.393)
◆ Pointing to the location where the object should be
applied (e.g. pointing to the mouth for a toothbrush or to
the table for a pencil)
◆ Searching movements of the hand and fingers which

eventually result in a recognizable pantomime (‘conduite
d’approche’)
Lesion
Apraxia for meaningful gestures is a symptom of LBD. It is

virtually always associated with aphasia, but the severity of
apraxia may differ from that of language impairment. Within
the left hemisphere, lesions of inferior frontal lobe and
underlying white matter are crucial. Contrary to a widely held
belief, parietal lesions do not interfere with pantomime of tool
use (Goldenberg et al., 2007). This independence is
corroborated by observation of patients in whom parietal
lesion causes “visuo-imitative apraxia”. These patients have
severe difficulties with imitation of meaningless gestures
(particularly hand postures) but perform pantomime of tool
use and other meaningful gestures to command flawlessly.
Therapy
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movement
In patients with severe expressive language problems it may

be worth while to train gesturing as an alternative channel for
communication. Training must take into account the loss of
‘abstract attitude’ and behavioural flexibility which frequently
accompany severe aphasia. Thus a first step in the training is
to familiarize patients with the possibility of using gestures for
replacing speech. A second step is the training of specific
gestures. Rarely do patients generalize to create and use
gestures which have not been explicitly trained. Even for
trained gestures, use outside the therapeutic setting may fail
because patients persist in fruitless attempts at verbal
expression rather than spontaneously changing to an
alternative means of communication (Purdy & Koch, 2006). It
is therefore advisable to concentrate on gestures which are
important for everyday communication (e.g. I am hungry or
tired, I need to go to the toilet etc), and to instruct the
patients’ partners to encourage use of gesture when verbal
communication fails.
2.4.3 Use of single tools and objects

Use of single familiar tools and objects can fail for two
reasons. Patients may have lost knowledge about the purpose
of the tool and the prototypical manner of its use. For example,
they may use a toothbrush for cleaning their jacket, because
they have lost knowledge about the special purpose of
toothbrushes. Conversely, they may know the purpose of the
tool but be unable to adapt their actions to the constraints and
affordances of the mechanical interaction between tool and
object. For example, they press a knife into a loaf without a
sawing movement, because they pursue the aim of dividing the
loaf but cannot adapt the manner of cutting to the resistance
of the loaf.
Clinical diagnosis
◆ Present familiar, easy to use, objects like a padlock with a

key, a hammer and a nail, a comb, or a pair of binoculars
and ask patients to use them. For examining hemiplegic
patients objects must be prepared for one-handed use (e.g.,
provide a wooden block with a hole in which the nail to be
hammered can be fixed).
◆ Examine one-handed tool use with the non-dominant left

hand in several control persons to obtain an estimation of
normal clumsiness of the non-dominant hand. (p.394) You
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will see that it is not difficult to distinguish apraxic errors

made by the left hand of patients with right sided
hemiplegia from normal variations of manual skill.
◆ Record errors and try to classify them according to

whether they betray preserved knowledge about the usual
purpose of the tool.
Lesion
In patients with circumscribed brain lesions (e.g. from

vascular accidents), misuse of familiar objects is due to left
brain lesions, associated with aphasia and other
manifestations of apraxia (Goldenberg & Hagmann, 1998).
Lesions involve the parietal lobe but are rarely restricted to it.
Loss of knowledge about the purpose and prototypical use of

tools in combination with preserved ability to infer possible
functions has been documented in patients with bilateral
temporal lobe lesions (e.g. from Herpes Simplex Encephalitis
or Semantic Dementia) (Hodges et al., 2000).
Therapy
Training the application of single tools and objects, forms part

of the therapy of multi-step activities of daily living (see 2.4.4).
2.4.4 Multi step actions with several tools and objects

(“naturalistic action”)
In daily life the use of the single tool is frequently embedded
in a chain of actions involving several tools and objects and
aiming at a superordinate goal transgressing and modulating
the purposes of each single action step. Proper sequencing of
actions and maintenance of the ultimate goal puts demands on
memory and attention which can lead to errors even in
patients who have no problems with use of single tools. In
patients who already have problems with single tools and
objects, the additional cognitive demands of multi-step
planning may unmask misuse of single tools which did not
appear during isolated testing.
Clinical diagnosis
A task which can easily be administered at the examiner’s

desktop is to provide a sheet of paper, a perforator, and a
folder, and to ask the patient to punch the paper and insert it
into the folder. Preparation of coffee or a meal and
Page 12 of 22
movement
performance of technical tasks can be observed in

occupational therapy.
Lesions
Errors and action slips in chains of actions with multiple tools

and objects have been documented in patients with LBD, RBD,
frontal, or diffuse brain damage (Rumiati, 2005). Although
systematic studies failed to find significant differences
between the error rates of these patient groups, clinical
experience suggests that the most severe and persistent
problems occur in patients with LBD and aphasia who also
have apraxia for use of single tools and objects.
Therapy
Patients can relearn use of tools and objects and even

performance of complex chains of actions by training, but it is
questionable whether improvement on trained activities
generalizes to non-trained activities (Goldenberg et al., 2001;
Geusgens et al., 2006). Possibly the flexibility of transposing
therapeutic gains to other tasks and other circumstances
depends on the presence and severity of other accompanying
neuropsychological problems. In patients with severe aphasia
as well as apraxia for use of single tools and objects, therapy
success may remain restricted not only to the task but even to
(p.395) the exemplars of tools and objects used in therapy.
Presumably, the most enduring way to enhance the
independence of such patients, is to train them within their
permanent environment, on tasks which they want to perform
every day.
2.5 Callosal apraxia

Callosal disconnection deprives the right hemisphere from left
hemisphere competence and renders the left hand apraxic.
Like bilateral apraxia from LBD, left hand apraxia from
callosal disconnection affects imitation, performance of
meaningful gestures and object use. Disturbed object use may
be restricted to objects not normally used by the right hand
(e.g. knife, but not fork). Because natural lesions destroying
the corpus callosum frequently encroach on neighbouring
mesial frontal regions, callosal apraxia can be associated with
disorders of voluntary control of motor actions such as motor
neglect, grasping and groping, or anarchic hand (see below).
On the other hand, destruction of callosal fibres is rarely
absolute. Particularly when there is no additional mesial
Page 13 of 22
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frontal lobe damage, imitation and object use by the left hand
may recover due to enhanced employment of remaining
callosal fibres or of ipsilateral motor pathways. (Goldenberg et
al., 2001).
Clinical diagnosis
The hallmark of callosal apraxia is a discrepancy between

apraxia of the left hand, and normal praxis of the right hand.
In addition, there are signs of sensory-motor, sensory-verbal,
and verbal-motor disconnection:
◆ Blindfolded patients cannot indicate the location of touch

on their left hand either verbally or by pointing with their
right hand, although they can point to the location with
their left thumb.
◆ They cannot name objects put into their left hand,

although the left hand palpates them skilfully.
◆ They cannot move single fingers of their left hand on

verbal command although they can do so on imitation (note
that imitation of finger postures depends less on the left
hemisphere than does imitation of hand postures).
Lesion
Callosal apraxia is contingent upon destruction of the middle

portion of the corpus callosum.
Therapy
Callosal apraxia is a fascinating syndrome of questionable

ecological validity. Patients will rarely feel handicapped by the
inability of their left hand to perform meaningful gestures on
command. However, the insufficiency of callosal transfer of
sensori-motor information may impede swift bimanual
coordination, and this may be worth a trial of occupational
therapy.
3 Disturbed voluntary control of motor actions

The affected limbs either do not spontaneously participate in
an intended action (motor neglect) or do perform actions
which are not intended (all other syndromes). Non-
performance of intended actions, and performance of non-
intended actions are not mutually exclusive.
(p.396) 3.1 Motor neglect
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movement
Patients need extra voluntary effort to make the affected limbs

comply with their intentions. The limb is not used
spontaneously although force and coordination are preserved.
In severe cases the affected limb may appear to be completely
paralyzed, although it may be raised and moved readily on
command. Motor neglect becomes worse when attention is
distracted. Thus patients with mild paresis of a leg who can
safely stand and walk, may fall when attention is directed
towards a simultaneous manual activity or external distractor.
Simultaneous movement of the opposite limbs may also
increase motor neglect, particularly if it is asymmetric.
If there has initially been paresis of an affected limb, it may be

difficult to distinguish motor neglect from ‘learned non-use’:
patients may have formed a habit of preferentially using the
unaffected limb even for tasks which could easily be
accomplished with the affected limb. Motor neglect is a
disabling condition as it prevents normal use of the affected
limb. Even very mild forms of motor neglect can be disastrous
when combined with hemiparesis. Patients who have partly
recovered from paresis and are able to stand and walk may
neglect the affected limb when distracted and consequently
fall and hurt themselves.
◆ Clinical diagnosis: Observe spontaneous motor behaviour

and compare it with explicit testing of motor function. Place
an object (e.g. a glass) in different locations on a table
before the patient and ask them to grasp it. They will use
the non-affected hand even if the glass is placed on the
affected side.
◆ Lesion: Extended lesions including the parietal lobes can

cause motor neglect together with perceptual and
representational neglect, but frontal or deep lesions can
cause pure motor neglect. Predominance of right sided
lesions is less conspicuous for motor than for sensory and
representational neglect (Siekierka-Kleiser et al., 2006).
◆ Therapy: Frequent reminders to use the contralesional

limbs are integrated in physio and occupational therapy. It
is questionable whether therapies aimed at alleviating
visuo-spatial neglect (see Chapter 6) have an effect on
accompanying motor neglect.
3.2 Grasping and groping
Page 15 of 22
movement
When getting in touch with an object, the affected hand grasps

it. It may also grope for visually perceived objects located in
its proximity and grasp them. Few patients are able to
suppress the grasp reaction by an effort of will. The majority
have to interfere with their sound hand to loosen the grasp.
They may sit on their hand or permanently place an object into
it to prevent it from grasping external objects. Groping and
grasping are embarassing and compromise the use of the
affected hand.
◆ Clinical diagnosis:
— Move your finger or a comparable object (e.g.

handle of reflex hammer) over palm exerting some
pressure on skin. If the patient grasps, advise them
not to do so and repeat the manoeuvre.
(p.397)
— To elicit groping, move an object (e.g. reflex
hammer) close to the patient’s hand and withdraw it
slowly if the hand moves towards it. If the hand
follows the object, advise the patient not to do so,
and repeat.
◆ Lesion: Medial face of superior frontal lobe (cingulate

gyrus and supplementary motor area). Unilateral lesions of
either side can cause bilateral grasping (De Renzi &
Barbieri, 1992).
◆ Therapy: Spontaneous recovery is frequent, particularly

when the lesion is unilateral. In collaboration with the
patient, therapists may try to devise strategies which
enhance the voluntary control of the afflicted hand.
3.3 Anarchic hand
One hand performs complex movements which are goal-
directed and well executed but unintended. These unwanted
movements cannot be voluntarily interrupted and may
interfere with desired actions carried out by the other hand.
Most of the unwanted actions are composed of seizing and
pulling objects (e.g. pulling away a sheet on which the other
hand is writing). Patients never deny that the hand is part of
their own body but may accuse it of being disobedient and
having a will of its own.
Page 16 of 22
movement
In the literature the term “alien hand” is frequently used

synonymously with anarchic hand, although originally it
referred to the failure to recognize one’s own hand when
placed into the other hand out of sight (Brion & Jedynak,
1972).
◆ Clinical diagnosis: Relies on complaints of patients and

observation of spontaneous behaviour of the hand.
◆ Lesion: Anarchic hand can result from mesial superior

frontal lobe lesion of the opposite hemisphere. In this case
it may be associated with forced grasping or motor neglect
(Marchetti & Della Sala, 1998). It has, however, also been
observed following thalamic lesions with sensory loss of the
afflicted hand which might be considered as a variant of
kinaesthetic ataxia (Coulthard et al., 2007). When lesions
encroach on callosal fibres, anarchic hand can be
associated with callosal apraxia of the left hand, but there
are cases of right-sided anarchic hand as well.
◆ Therapy: The unwanted actions of the anarchic hand can

be very embarrassing and a severe handicap for bimanual
actions in activities of daily life such as dressing or eating.
Experimental approaches to improving coordination, train
rhythmic switching of objects between hands, or use of a
mirror for enhancing visual control of the disobedient hand.
Some success has been seen during training session but it
rarely carries over to daily living (Brainin et al., 2008).
3.4 Motor perseverations
Patients continue a motor action although its original purpose
has been attained. For example, they may continue to peel all
the oranges in a basket after they have peeled one for eating,
or they may be unable to stop tooth brushing, or washing and
spend hours in the bathroom. Patients may experience
perseveration of actions as compulsive and against (p.398)
their own intentions, or they may justify them by ostensible
motives (e.g. hygienic reasons for perseverative washing).
◆ Clinical diagnosis: Rests mainly on history taking and

observation of the patient. In examination motor
perseveration can be provoked by asking patients to draw a
series of figures each consisting of three consecutive loops.
Patients will increase the number of loops.
Page 17 of 22
movement
◆ Lesion: Uni- or bilateral lesions of superior mesial frontal

lobe, similar to grasp reaction with which it may be
associated. Persistent and severe motor perseverations are
likely due to large bilateral frontal lesions or additional
diffuse brain damage.
◆ Therapy: If motor perseverations do not recover

spontaneously and constitute an obstacle for activities of
daily living, strategies for interrupting them may be
explored.
3.5 Utilization behaviour
Patients use objects which happen to be within their grasp in a
way which is appropriate to the object but not to the situation.
For example, they may take glasses which the examiner has
laid down and put them on their nose, or they may take a
stamp and repeatedly press it on a sheet of paper. If occurring
outside the test situation, utilization behaviour may be socially
disturbing.
◆ Clinical diagnosis: Care must be taken to distinguish

utilization behaviour from enhanced suggestibility of brain
damaged patients. If, for example, the examiner interrupts
testing and puts objects on the table without commenting
on their purpose and waits for the patient’s reaction
(L’hermitte, 1983), patients may understand this to be a
non-verbal invitation to use the objects. It is therefore
preferable to have attractive objects (e.g. glasses,
matchbox, cigarettes, a pack of cards, a filled bottle and a
glass.) already placed on the periphery of the table when
the patient enters the room, then to engage the patient in
unrelated conversation or testing, and observe their
spontaneous behaviour (Shallice et al., 1989).
◆ Lesion: Large, bilateral mesial frontal lesions. Lesions

must be associated with some diffuse brain damage to give
rise to utilization behaviour.
◆ Therapy: Methods from behavioural therapy may help to

reduce socially embarrassing utilization behaviour.
Page 18 of 22
movement
3.6 Imitation behaviour

Although not requested to do so, patients imitate gestures and
actions of the examiner or other persons. For example,
patients may take off their glasses when the examiner does so
or repeat back questions rather than answering them. An
explicit command not to imitate can stop imitation but
introduction of a pause is sufficient for reappearance of
imitation. When asked why they imitated patients are puzzled
and say nothing or they claim that they thought this was the
implicit request made by the examiner (De Renzi et al., (p.
399) 1996). Like utilization behaviour, imitation behaviour
may cause irritation when occurring outside the testing
situation.
◆ Clinical diagnosis: Rests mainly on observation of

spontaneous behaviour during conversation and testing.
Avoidance of non-verbal requests to imitate can be very
difficult when gestures are introduced explicitly for
provoking imitation behaviour.
◆ Lesions and therapy: As in utilization behaviour

3.7 Voluntary motor control and social demands
The classification of utilization and imitation behaviour as
disorders of voluntary control of movement can be called into
doubt. The particular actions are wrong only with respect to
the specific demands of the testing situation. The subtlety of
their deviance from appropriate behaviour is highlighted by
the fact that the very same actions – utilization of objects and
imitation of gestures – are explicitly asked for when the
examiner is interested in testing for apraxia (which may
happen in the same session!). The observation that normal
controls never utilize objects or imitate under the same
conditions proves that they can easily understand such subtle
distinctions, whereas patients with frontal lobe damage
cannot. It is, however, questionable whether this failure should
be classified as a disorder of motor control or as a
manifestation of the effects of frontal lobe damage on
comprehension and observance of social demands.
Page 19 of 22
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Spinnler, H., and Venneri, A. (2000). Upper and lower face
apraxia: role of the right hemisphere. Brain, 123, 2213–2230.
Brainin, M., Seiser, A., and Matz, K. (2008). The mirror

world of motor inhibition: The alien hand syndrome in chronic
stroke. Journal of Neurology, Neurosurgery, and Psychiatry ,
79, 246–252.
Brion, S. and Jedynak, C. P. (1972). Troubles de transfert

interhémisphérique (callosal disconnection). A propos de trois
observations de tumeurs du corps calleux. Le signe de la main
étrangère. Revue Neurologique, 126, 257–266.
Coulthard, E., Rudd, A., Playford, E. D., and Husain, M.

(2007). Alien limb following posterior cerebral artery stroke:
failure to recognize internally generated movements?
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De Renzi, E. and Barbieri, C. (1992). The incidence of the

grasp reflex following hemispheric lesions and its relation to
frontal damage. Brain, 115, 293–313.
De Renzi, E., Cavalleri, F., and Facchini, S. (1996).

Imitation and utilisation behaviour. Journal of Neurology,
Neurosurgery, and Psychiatry , 61, 396–400.
Freund, H. J. (1987). Abnormalities of motor behavior after

cortical lesions in humans. In V.B. Mountcastle, F. Plum, & S.
R. Geiger (Eds.), Handbook of Physiology Section 1: The
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Geusgens, C., van Heugten, C. M., Donkervoort, M., van

den Ende, E., Jolles, J., and van den Heuvel, W. (2006).
Transferf of training effects in stroke patients with apraxia: An
exploratory study. Neuropsychological Rehabilitation, 16, 213–
229.
Goldenberg, G. (1996). Defective imitation of gestures in

patients with damage in the left or right hemisphere. Journal
of Neurology, Neurosurgery, and Psychiatry, 61, 176–180.
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(p.400) Goldenberg, G., Daumüller, M., and Hagmann,

S. (2001). Assessment and therapy of complex ADL in apraxia.
Goldenberg, G. and Hagmann, S. (1998). Tool use and

mechanical problem solving in apraxia. Neuropsychologia, 36,
581–589.
Goldenberg, G., Hermsdörfer, J., Glindemann, R.,

Rorden, C., and Karnath, H. O. (2007). Pantomime of tool
use depends on integrity of left inferior frontal cortex.
Cerebral Cortex, 17, 2769–2776.
Goldenberg, G., Hermsdörfer, J., and Laimgruber, K.

(2001). Imitation of gestures by disconnected hemispheres.
Goldenberg, G. and Karnath, H. O. (2006). The neural basis

of imitation is body‐part specific. Journal of Neuroscience, 26,
6282–6287.
Hodges, J. R., Bozeat, S., Lambon Ralph, M. A.,

Patterson, K., and Spatt, J. (2000). The role of conceptual
knowledge in object use - evidence from semantic dementia.
Brain, 123, 1913–1925.
Karnath, H. O. and Perenin, M. T. (2005). Cortical control

of visually guided reaching: Evidence from patients with optic
ataxia. Cerebral Cortex, 15, 1561–1569.
Lhermitte, F. (1983). “Utilization behaviour” and its relation

to lesions of the frontal lobes. Brain, 106, 237–255.
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alien and anarchic hand. Cognitive Neuropsychiatry, 3, 191–
207.
Purdy, M. and Koch, A. (2006). Prediction of strategy usage

by adults with aphasia. Aphasiology, 20, 337–348.
Raade, A. S., Rothi, L. J. G., and Heilman, K. M. (1991).

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Page 22 of 22
The neuropsychology of acquired calculation disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The neuropsychology of acquired

calculation disorders
Marinella Cappelletti
Lisa Cipolotti
DOI:10.1093/acprof:oso/9780199234110.003.21

Acalculia is an acquired disorder of number processing and
calculation skills following cerebral damage. The inability to
use numbers can be very incapacitating as it interferes with
several everyday activities such as shopping, using bank
accounts, and telephones. This chapter presents the basic
components of the number and calculation system; discusses
cases of selective impairment of number processing and
calculation; discusses cases of selective preservation of
number processing and calculation; briefly outlines the brain
localization of number and calculation disorders; and proposes
some guidelines for the assessment and rehabilitation of
acalculia in neurological patients.
Keywords: acalculia, brain damage, number processing disorder, calculation

skills
Page 1 of 28
1 Acalculia
Acalculia is an acquired disorder of number processing and
calculation skills following cerebral damage (Henschen, 1919).
The inability to use numbers can be very incapacitating as it
interferes with several everyday activities such as shopping,
using bank accounts and telephones (Butterworth, 1999;
Dehaene, 1997). Acalculia is not a unitary disorder and can
take a variety of different forms: patients may present with
impairments in number processing, in calculation or both. The
incidence of acalculia in patients with left hemisphere lesions
has been estimated between 16% and 28%, and 90% of
patients at the early stage of Alzheimer disease present with
acalculia (Carlomagno et al., 1999). Knowing the incidence of
acalculia and its impact on everyday life has helped to improve
assessment techniques and it has recently promoted the
development of rehabilitation programs. In this chapter, we
will:
1 present the basic components of the number and

calculation system;
2 discuss cases of selective impairment of number
processing and calculation;
3 discuss cases of selective preservation of number
processing and calculation;
4 briefly outline the brain localization of number and
calculation disorders;
5 propose some guidelines for the assessment and
rehabilitation of acalculia in neurological patients.
2 The basic components of number and calculation

processing
2.1 Number comprehension and production
Number comprehension usually refers to the ability to
generate a semantic representation of numbers. This
commonly refers to the quantity associated with numbers, for
instance ‘21’ indicates the numerosity of 21. The
representation of quantity is thought to be abstract in nature
(Dehaene and Cohen, 1997; McCloskey et al., 1990 but see
Cohen Kadosh et al., 2005). The quantity expressed by
numbers is often processed when comparing numbers, for
instance when deciding which of two products is the most
expensive. In doing so, we are usually faster and more
accurate when two numbers (or two prices) are further apart,
(p.402) e.g. £1.20 and £2.55, relative to when they are close
to each other, e.g. £1.20 and £1.15. This phenomenon is
Page 2 of 28
referred to as the ‘distance effect’ (Moyer and Landauer, 1967).

Impairments in processing numerical quantity may result in a
‘reverse distance effect’, which indicates that the time needed
to process numbers increases as the numerical distance
between them increases (e.g. Delazer and Butterworth, 1995).
This is because the quantity associated with numbers can not
be accessed automatically and other strategies, for instance
counting, have to be used instead. Besides indicating
quantities, numbers can also have a ‘nominal’ function, for
instance ‘21’ may also indicate a house or a bus number or the
age of consent (Butterworth, 1999; Dehaene, 1997).
Number production refers to the process of converting a

numeral’s semantic representation into an output format. The
most commonly used formats are the Arabic, e.g. ‘21’ and the
verbal, e.g. ‘twenty-one’. The production of a number in one of
these formats is based on input and output processes. For
instance, reading Arabic numerals is based first on visually
identifying the string of digits, second on translating this
string of digits into a sequence of words according to a set of
rules, and third on producing an oral or written output. This
transformation of numbers from one format to another is
usually referred to as ‘transcoding’ (Dehaene and Cohen,
1995; Deloche and Seron, 1982; McCloskeyet al., 1986).
2.2 Calculation
Processing oral and written arithmetical operations require a
set of specific and independent processes including:
(i) The processing of arithmetical symbols (i.e. +, ×, –,

÷)
(ii) The retrieval of arithmetical facts, defined as a
vocabulary of ‘number combinations’, such as ‘3 + 3 =
6’ or ‘3 × 3 = 9’.
(iii) The execution of calculation procedures consisting
of the specific algorithms required to solve multi-digit
calculations, for instance carrying (e.g. in ‘234 + 159’)
and borrowing (e.g. in ‘234 – 159’) procedures.
(iv) Arithmetic conceptual knowledge, namely the
understanding of the principles underlying arithmetical
facts and procedures (e.g. the principle of
commutativity, such as a + b = b + a).
3 Selective impairment of number processing and

calculation
Page 3 of 28
Neurological patients may present with specific impairments

in the processing of numbers, in calculation, or in both. Table
21.1 provides an overview of the range of potential deficits
which can be observed in acalculic patients.
Here we will describe the impairments of:
1 number transcoding;
2 quantity processing;
3 calculation, which in turn may consist of impairments
in processing arithmetical signs, simple facts,
procedures, or arithmetical conceptual knowledge. (p.
403)
3.1 Impairments of number production
Table 21.1 Overview of the potential disorders of

(A) number processing and (B) calculation (right
column)
A. Disorders of number processing
Disorders of number production lexical processing

affecting
syntactical
processing
Disorders of number comprehension cardinal number

affecting meaning
sequence number
meaning
B. Disorders of calculation
affecting processing of
arithmetical symbol
processing
arithmetical fact
retrieval
calculation
procedures
conceptual
knowledge
Page 4 of 28
Studies have described patients with disorders in number

production have primarily focussed on reading and writing
numbers (e.g. Cipolotti et al., 1995; Deloche and Seron, 1982;
McCloskey et al., 1986; 1990; Sokol and McCloskey, 1988).
Some of these studies have looked at the errors made by
patients when reading or writing numbers. This permitted the
identification of two major cognitive mechanisms within
number transcoding: the syntactic, and the lexical number
processes.Syntactic processes involve the specification of the
relationship among the elements of the number, e.g. number
class, i.e. to read aloud 600, one needs to retrieve the correct
number class {hundred}. Syntactic errors are errors which
occur when the wrong number class is selected (e.g. stimulus:
‘5’, response: ‘fifty’ or stimulus: ‘two thousand and thirty
eight’, response: ‘2000308’). For example, patient SF’s
syntactic errors occurred in reading aloud Arabic numerals
and could best be classified as ‘quantity-shift’ errors (e.g. 207
→ ‘two thousand and seven’; 80 → ‘eight’) (Cipolotti, 1995).
Lexical processes involve the specification of individual

elements in the numeral, for instance to read aloud 600, has to
be retrieved once the correct class {hundred} has been
identified the correct element {6}. Lexical errors involve the
incorrect production of one or more of the individual elements
in a numeral (stimulus: ‘29’, response: ‘forty-nine’). Patient
HY’s errors in reading aloud Arabic numerals were mainly
lexical, for instance he read number ‘5’ as ‘seven’ and ‘29’ as
‘forty-nine’ (Sokol et al., 1991).
Other studies have demonstrated that transcoding skills can

be independent from other numerical abilities. For example,
patient HY was impaired in reading aloud Arabic numerals
(McCloskey et al., 1986). When attempting to read aloud an
Arabic numeral, he often made mistakes such as reading
number ‘5’ as ‘seven’, and ‘29’ as ‘forty-nine’. In contrast,
results from a series of number comprehension tasks showed
that patient HY was unimpaired in comprehending Arabic
numerals. Thus, his impaired performance in (p.404) reading
aloud Arabic numerals reflected his impairment in number
transcoding rather than a deficit in comprehending the Arabic
stimuli.
This pattern of performance has also been shown by other

patients (e.g. Cipolotti and Butterworth, 1995), and the
opposite performance, (i.e. poor performance in calculation
Page 5 of 28
and preserved transcoding has also been documented) (e.g.

Cipolotti and Butterworth, 1995; Sokol et al., 1991). This
suggests that transcoding skills are distinct from other
numerical abilities.
A frequent type of error in writing numbers to dictation or

from a written input has been referred to as ‘intrusion errors’.
These consist of reproducing part of the input code when
formulating the output one. This type of error has been
described in patients with dementia of the Alzheimer type as
well as in those with focal brain lesions (Della Sala et al., 2000;
Thioux et al., 1999). According to Thioux and colleagues
(1999), three different types of intrusion errors can be
distinguished.
◆ The first consists of producing a numerical output in the

same format as the source one, has been called ‘complete
lexical shift error’ or ‘perseveration’. For example when the
Arabic numeral ‘75’ is written as ‘75’ instead of as the
number word ‘seventy five’, (or conversely the ‘seventy five’
written as the number word ‘seventy five’ instead of as the
numeral ‘75’).
◆ The second type of intrusion error is called ‘partial lexical

shifting’, and occurs when only one part of the input is
transposed onto the output, (e.g. the Arabic numeral ‘75’
written as ‘seventy5’).
◆ Thirdly, ‘intra lexical shift’ errors consist of writing a

numeral in a mixture of verbal and Arabic formats, for
example, the Arabic numeral ‘70’ written as ‘7ty’.
Some authors explained these errors in terms of the

combination of impaired transcoding mechanisms on the one
hand, and impaired inhibitory processes on the other (Thioux
et al., 1999). Other authors have suggested that perseveration
and intrusion errors are attentional in nature and originate
from a unique impairment in selective attentional capacities
(Macoir et al., 2002).
3.2 Impairments of number comprehension

A few studies have reported patients with a basic failure of
understanding and processing the quantity indicated by
numbers (Cipolotti et al., 1991; Dehaene and Cohen, 1997;
Delazer and Benke, 1997; Delazer and Butterworth 1997;
Lemer et al., 2003; Noel and Seron, 1993; Polk et al., 2001).
Page 6 of 28
For example, patient NR showed impairment in understanding

Arabic numerals (Noël and Seron, 1993). Thus, she could no
longer point to the larger of two Arabic numerals (e.g. 345 vs
785 or 265 vs 237). Moreover, she lost the ability to match
spoken number names to the corresponding Arabic numeral. A
profoundly acalculic patients (CG) presented with an unusual
pattern of performance (Cipolotti et al., 1991). Although she
had retained the ability to process abstract quantities, she lost
the meaning of all numbers above 4. For example, she was
unable to say (p.405) how many days were in a week or
which was larger, 5 or 10. Her deficit was so pervasive that it
seriously limited her activities of daily living, for instance, CG
was unable to do her own shopping, deal with money, make
phone calls, use a calendar, or read the time, although her
intellectual skills, language, memory and visuospatial abilities
were largely preserved.
Recent studies have focused on quantity processing in neglect

patients. Two of these studies have shown that neglect
patients can correctly indicate the larger or smaller of two
numbers (Cappelletti and Cipolotti, 2006; Vuilleumier et al.,
2004). The patients’ performance in number comparison
indicated that even the numerical stimuli appearing in the
neglected hemifield could be processed even when not
reported (Cappelletti and Cipolotti, 2006). Moreover neglect
patients are typically slower to process numbers which are
located to the left of ‘5’, (i.e. ‘4’) relative to numbers located to
its right (i.e. ‘6’), suggesting that their number impairment is
consistent with their spacial impairment (Vuilleumier et al.,
2004).
Thus, the idea that the spatial impairments in neglect may

affect numerical processing has recently been explored in
studies, specifically, which tested whether neglect may affect
the mental ‘number line’; a metaphor used to represent
numbers as oriented from smaller to larger (Dehaene et al.,
1993). One way to test the integrity of a mental number line is
with the bisection task. This consists of orally presenting two
numbers, (e.g. ‘1’ and ‘5’) and asking which number falls in
the middle. Neglect patients typically select a number which is
larger than the middle one, for instance they say that ‘4’ and
not ‘3’ is mid-way between ‘1’ and ‘5’ (Cappelletti et al., 2007a;
Doricchi et al., 2005; Zorzi et al., 2002). This pattern of
Page 7 of 28
performance mirrors the classical leftward bias which neglect

patients show in bisecting physical lines, although their
performance also seems to depend on the line orientation of
the physical and numerical lines (Cappelletti et al., 2007).
3.3 Impairments of calculation

Each of the different cognitive processes involved in
calculation (i.e. processing arithmetic symbols, facts,
procedures and conceptual knowledge), appear to be
functionally independent as well as differentially susceptible to
brain damage. Examples of selective impairments in such
components of calculation are described below.
3.3.1 Disorders of arithmetic symbol processing

Very few patients with selective impairment in understanding
arithmetic symbols have been reported (e.g. Ferro and
Botelho, 1980; Laiacona and Lunghi, 1997). For example,
Laiacona and Lunghi (1997) investigated a patient who
misnamed and misidentified the arithmetic signs and
performed written arithmetic operations according to this
misidentification, for instance the patient systematically added
up instead of multiplying (See Fig. 21.1a). This deficit
however, was not specific to arithmetic symbols, but was part
of a more general impairment in processing also non-
arithmetic symbols such as punctuation marks. (p.406)
Page 8 of 28
3.3.2 Disorders of arithmetic fact retrieval

Several
patients have
been
documented
Fig 21.1a Disorders of arithmetric
with selective
processing symbols.
impairments
of arithmetic
fact retrieval. Typically, these patients have severe difficulties
in performing very simple single-digit addition, subtraction,
multiplication and division. They produce many errors such as
‘5 + 7’ = ‘13 roughly’ (e.g. Dehaene and Cohen, 1991), and
their response times are abnormally slow (e.g. >2 seconds).
An error classification has been proposed by McCloskey et al.,
(1991c). Errors can be classed as operand errors, if the
incorrect answer is the correct answer to a computation that
shares one of the operands (e.g. 6 × 5 = 25); as operation
errors, if the incorrect answer constitutes a correct answer to
another computation involving the same operands, but a
different operation (e.g. 3 × 4 = 12); as table errors, if the
incorrect answer represents the product of two different
single digit numbers (e.g. 4 × 4 = 25); and as non table errors,
if the incorrect answer is neither an operand, a table or an
operation error (e.g. 9 x 8 = 52). Patients who make these
errors often show intact knowledge of arithmetical principles
and procedures. Typically, they are able to retrieve and apply
the appropriate arithmetic steps required to solve complex
arithmetic problems and they are able to define arithmetic
operations (e.g. Delazer and Benke, 1997; Sokol et al., 1991;
Warrington, 1982). For this type of patient everyday activities
such as checking their change or their bank statements pose
great difficulties.
Impairment of arithmetic facts can also manifest in a highly

selective manner. Selectively preserved and impaired
arithmetic facts have been reported according to specific
types of operation. For example, patients have been
documented with selective impairments or selective
preservations of multiplication (e.g. Dehaene and Cohen,
1997; McCloskey et al., 1991b; Grafman et al., 1989; Delazer
and Benke, 1997), and subtraction facts (e.g. Dagenbach and
McCloskey, 1992; Pesenti et al., 1994; McNeil and Warrington,
1994; Lampl et al., 1994; Dehaene and Cohen, 1997). Selective
impairments of addition and division have also been reported.
Page 9 of 28
Cipolotti and de Lacy Costello (1995) described a patient who

could no longer solve ‘4 ÷ 2’, while being able to solve ‘27 ×
26’. Van Harskamp and Cipolotti (2001) described a patient
with selective addition impairment who could no longer add 2
+ 3, but was still able to solve 13 – 6 and 8 × 9.
3.3.3 Disorders of calculation procedures

There have only been a few reports of patients with selective
impairment of calculation procedures. Girelli and Delazer
(1996) described patient MT, who systematically subtracted
the smaller number from the larger one, irrespective of
whether the larger was at the top or the bottom line (see Fig.
21.1b). His impairment in solving multi-digit (p.407)
subtractions
was attributed
to a defective
knowledge of
calculation Fig. 21.1b Disorders of arithmetric
procedures. processing symbols.
This deficit
was selective
for subtraction, as the patient was able to correctly carry out multi-
digit addition problems involving the carry over procedure (such as
78 + 26).
Other impairments in the use of calculation procedures may
consist of misaligning the digit in multi-digit operations, of
errors using carrying procedures in addition problems, or of
not applying the problem-specific procedure in the correct
order. For example, in multi-digit multiplications this consists
of multiply digits in the upper number starting from the
rightmost, by digits in the bottom number starting from the
rightmost etc. (e.g. Benson and Weir, 1972; Grana et al., 2006;
Sokol et al., 1991; Sokol and McCloskey, 1991).
Page 10 of 28
3.3.4 Disorders of arithmetic conceptual knowledge

Delazer and Benke (1997) described a patient (JG) who had
lost arithmetical conceptual knowledge, which is defined as
‘An understanding of arithmetical operations and laws
pertaining to these operations’ (Hittmair-Delazer et al., 1994,
p. 117). JG could retrieve multiplication tables from memory
despite severe problems in all tasks requiring conceptual
knowledge. The patient could correctly calculate ‘3 x 3,’ but
did not know that ‘3 x 3’ equals ‘3 + 3 + 3’. The patient was
encouraged to use any ‘back-up strategies’, such as counting
on fingers for simple addition problems. Usually this strategy
is adopted spontaneously by patients with impairments in
arithmetic fact retrieval. However, JG never succeeded in
representing problems with her fingers (Delazer and Benke,
1997, p.705). She did not apply even very basic principles such
as commutativity in multiplication (i.e. 4 × 12 = 12 × 4), and
she was unable to recognize that multiplication can be
transformed into repeated addition (4 × 12 = 12 + 12 + 12 +
12).
The opposite side of the dissociation, namely intact conceptual

knowledge with impaired fact retrieval, has been reported in
two single-case studies (Hittmair-Delazer et al., 1994, 1995).
The first study described a patient who demonstrated
excellent conceptual knowledge despite a severe acalculia. For
example, when presented with arithmetic operations such as
8x6, he adopted the following strategy 8 × 10 = 80; 80:2 = 40;
40+8=48 (see Fig. 21.1c). Another patient who was no longer
able to solve simple elementary arithmetic such as 2 + 3,
showed excellent understanding and use of abstract equations
such as (b × a): (a × b)=1 and (cd + ed):d= c + e (Hittmair-
Delazer et al., 1994). Similarly, a semantic dementia patient
demonstrated well preserved understanding of arithmetic
concepts despite the loss of arithmetic facts (Cappelletti et al.,
2005). He spontaneously developed strategies which allowed
him to perform computations when he could not access simple
facts or use canonical procedures (e.g. using multiple
additions (p.408)
Page 11 of 28
to solve a Fig. 21.1c Disorders of arithmetric

multiplication
processing symbols.
problem, see
Fig. 21.1d).
These cases
demonstrate
that
conceptual
knowledge is a
functionally
independent
component of
calculation.
4 Selective
preservation
of number
processing
and Fig. 21.1d Disorders of arithmetric
calculation processing symbols.
It is now well
established
that numerical and calculation abilities can be largely
independent from other cognitive abilities, such as general
intellectual skills (e.g. Remond-Besuchet et al., 1999),
language (e.g. Rossor et al., 1995; Thioux et al., 1998), short-
term memory (e.g. Butterworth et al., 1995), and semantic
knowledge (e.g. Cappelletti et al., 2001; Crutch and
Warrington, ). For example, a patient with semantic dementia
(IH) presented with severe impairment in understanding the
meaning of words and the use of objects, but was nevertheless
able to understand numerical concepts and to perform
arithmetical operations (Cappelletti et al., 2001), even in the
later stages of illness (Cappelletti et al., 2005). This suggests
that a patient’s understanding of arithmetical concepts may
remain preserved despite severe inability to process the
meanings of words and objects. A similar pattern of
performance on numerical and calculation tasks has been
reported in other (p.409) semantic dementia patients (e.g.
Crutch and Warrington, 2002), suggesting that knowledge of
verbal concepts can be independent.
Page 12 of 28
5 Localisation of brain lesions in number and calculation

disorders
An overview of group and single case studies has indicated
that numerical skills may have discrete and independent brain
substrates (Cipolotti and van Harskamp, 2001). The majority of
patients with number production and/or number
comprehension impairments have left posterior lesions, often
involving the parietal lobe. Similarly, the majority of patients
with arithmetical fact retrieval impairments had lesions mainly
implicating the left parietal lobe. This is also the case for the
majority of patients with impairment of arithmetic fact
retrieval for specific types of operations. In particular, patients
with impairments of multiplication or subtraction typically
have lesions encroaching on the left parietal lobule.
The neuropsychological evidence indicating the involvement of

the parietal lobe in numerical processing has been
corroborated by neuroimaging studies (e.g. Cappelletti et al.,
2009; Dehaene et al., 1999, 2003; Pesenti et al., 2000), and by
studies using transcranial magnetic stimulation (TMS, e.g.
Andres et al., 2005; Cappelletti et al., 2007b). However, it is
important to note that not all parietal lesions result in
numerical impairments. For instance, only about 20% of
patients with left parietal lesions show numerical deficits (e.g.
Jackson and Warrington, 1986). Moreover, most patients with
right parietal lesions show preserved comprehension of core
numerical concepts (e.g. Cappelletti and Cipolotti, 2006;
Cappelletti et al., 2007; Cohen et al., 2007; but c.f. Rosselli and
Ardilla, 1989; Langdon and Warrington, 1997 for a different
pattern of results). Similarly, not all numerical impairments
are due to parietal lesions. For instance, deficits in
arithmetical procedures have been reported in patients with
more anterior lesions (e.g. Grana et al., 2006). Future research
will help to clarify the extent to which parietal regions are
critical for number and calculation processing, and elucidate
the role of the left and the right parietal lobes in these
processes.
6 Assessment and rehabilitation of acalculia

6.1 Diagnosis and assessment tools
The diagnosis of acalculia relies on the establishment of
appropriate tools to detect the presence of number processing
and/or of calculation impairment in subjects with intact
premorbid calculation skills. The diagnosis of pure acalculia
Page 13 of 28
needs to exclude that numeracy skills are not a secondary

consequence of other cognitive deficits such as language,
attention, and visuospatial functions.
Formal assessment of the patient’s numeracy skills requires

detailed evaluation of number processing and calculation
abilities. Number processing can be assessed using number
reading, writing to dictation, and repetition tasks. Numerical
stimuli can be (p.410) presented as either Arabic numerals
(e.g. 8), written ( eight) or spoken number names (‘eight’).
Patients can be simply asked to read, write or repeat the
numeral presented. Comprehension of number quantity is
usually assessed with magnitude comparison tasks, whereby
patients are asked to indicate the larger of two numbers (e.g.
which is bigger: 6 or 9?).
Another test of number comprehension is the number

composition task in which subjects have to compose the value
of a given number using poker chips which range in value
from 1 to 500. The ability to subitize is another way to test
comprehension of number quantity. Subitizing is the ability to
rapidly indicate the number of items contained in a small set
(usually up to 4 or 5). Larger sets of objects require additional
processing, such as counting. Patients’ subitizing can be
tested by presenting them with displays containing items
which vary in number and position. Patients can simply be
asked to report the number of items contained in each display.
Intact quantity processing is expected to correspond to the
ability to rapidly and correctly indicate the numerosity of the
set; the time required to produce an answer is expected to
increase with the number of items presented with a sharp
increase after number 4 or 5. This is because enumeration
over four items is slow, more error-prone, and thought to
require counting (e.g. Trick and Pylyshyn, 1993, Sathian et al.,
1999).
Calculation skills can be assessed with tasks exploring

knowledge of arithmetical signs, arithmetical facts, and
arithmetical procedures. To evaluate the ability to process
arithmetical signs, patients are usually required to read, point
to and write, the arithmetical signs. To test the ability to
retrieve simple arithmetical facts, patients are asked to
compute orally presented single-digit arithmetical calculations
(e.g. 4 + 2, 3 × 4 or 5 – 2). The access to arithmetical
procedures is usually assessed by performing multi-digit
Page 14 of 28
calculation, such as 294 + 12=306, either in the written or in

the oral modality. Both response hires and accuracy should be
recorded.
Error analysis, although usually not included in standardised

tests, adds useful extra information to the assessment, in so
far as it can provide further details about the nature of the
impairment. Thus, when patients have problems in reading
and writing numerals, a common analysis of errors is the
distinction between lexical or syntactical errors. When
patients have problems in the retrieval of arithmetical facts, it
is useful to distinguish between operand errors, operation
errors, table errors, and non-table errors.
6.2 Natural recovery from acalculia

Although acalculia is a frequent disorder in left-brain damaged
patients, relatively little is known about its prognosis. Only one
study has investigated the natural evolution of acalculia in
patients with left hemisphere vascular lesions (Caporali et al.,
2000). This study indicates that some patients recover
completely in the first months post-stroke even without
specific rehabilitation. Apparently, this improvement can also
present in severely acalculic atients. This would suggest that
initial severity of acalculia may not significantly influence
recovery.
The authors suggest that recovery might be due to the

resolution of the diachises in the first months after stroke (3-6
months post-onset). However, besides this more general (p.
411) and ‘passive’ recovery, the authors suggest that a more
specialised functional reorganisation might play a role several
months post onset (>7 months). This suggestion would
account for the fact that some patients continued to improve
even several months after stroke although it is not clear
whether the recovery was specific for acalculia. In fact, most
patients also improve in other cognitive domains, such as
language.
6.3 Rehabilitation of number processing and calculation skills

The high frequency and disabling consequences of acalculia
underline the importance of developing remediation
techniques and intervention for arithmetical disorders. A
complete and detailed assessment of the patient’s numerical
processing and calculation skills is essential to understanding
the nature of numeracy impairment and will continue the basis
Page 15 of 28
for designing suitable rehabiliation programs (Girelli and

Seron, 2001). According to the specific type of acalculia,
different kinds of rehabilitative intervention may be required.
Thus, a detailed assessment of a patient’s number processing
and calculation skills will constitute the basis for designing
suitable rehabilitation programmes. For example, a patient
may show a highly selective impairment in the retrieval of
simple multiplication facts. However, he/she may still be able
to perform simple addition and subtraction. The re-acquisition
of multiplication facts may then be facilitated by the use of
back-up strategies based on addition (e.g. counting-on
procedure: 3 × 6 = 6 + 6 + 6).
Recent reviews (e.g. Girelli and Seron, 2001; Lochy et al., in

press) have shown that very few studies have been devoted to
the rehabilitation of numerical skills. These few studies
concentrated on the rehabilitation of number transcoding
deficits (e.g. Deloche et al., 1989; Sullivan et al., 1996),
arithmetical fact retrieval (e.g. Domahs, 2003, 2007; Girelli et
al., 1996, 2002; Hittmair-Delazer et al., 1994; Whetstone,
1998), and the development of strategies for solving problems
(Fasotti et al., 1992).
Page 16 of 28
6.3.1 Rehabilitation of transcoding skills

The rehabilitation of transcoding skills has concentrated on
the ability to translate numerical stimuli into different codes
(e.g. ‘four’ → 4). As an example we will discuss an interesting
rehabilitation programme implemented by Deloche and
colleagues. (1989). They treated a patient with selective and
very severe difficulties in the production of written verbal
numerals from Arabic numerals (i.e. 7001 → seven thousand
zero one). This deficit was very severe. Indeed, the patient
showed a 45% error rate. His errors were mostly syntactic
(e.g. 114 → one hundred ten four). Deloche et al.’s
rehabilitation programme consisted of re-teaching a set of
explicit transcoding rules using a step-by-step procedure. They
used highly specific exercises which targeted a single
transcoding rule. There were several facilitation procedures
(e.g. colour cues, vocabulary panels) to help the patient with
his learning process. For example, they rehabilitated the
patient’s ability to transcode a 2-digit Arabic numeral such as
73 into the corresponding written number word seventy-three,
by explicitly stating the rule ‘transcode the left digit by a ten
name and the right digit by a unit name’. During training a
vocabulary panel with two coloured columns was placed in
front of him. The red part of the vocabulary panel contained
the TENS names (ten, twenty, thirty etc up to ninety), and the
blue part contained the UNIT names (one, (p.412) two, etc
up to nine). After 25 training sessions of 30 to 60 minutes
each, the patient’s performance was close to ceiling.
Interestingly, the long-term effects of the treatment were
reassessed 7 months post-training. Only a very small increase
in error rate relative to post-training evaluation was reported
(6%). Overall, the patient continued to perform better than
before training.
6.3.2 Rehabilitation of arithmetical facts

Rehabilitation of arithmetical fact retrieval consists primarily
of attempts to re-teach ‘lost’ arithmetical knowledge via
extensive practice. The underlying assumption is that practice
may ‘re-create’ or ‘re-strengthen’ lost associations between
problems and answers. Thus, for example, two patients (TL
and ZA) with specific impairment of multiplication fact
retrieval underwent twice-weekly training sessions over a
period of eight weeks (Girelli et al., 1996). During the training
session the arithmetical problems were presented in written
form and simultaneously read aloud by the examiner. The
Page 17 of 28
patients were asked to answer, either verbally whilst pointing

to the number on a table, or by writing the Arabic numeral.
Errors were always corrected immediately. Patient TL
relearned the answers as ‘labels’, by reciting one operand’s
table (e.g. 4 × 3 = 4, 8, 12,). Patient ZA relearned the answers
as serial additions (e.g.4 × 3 = 3 + 3 + 3 = 12).
At the end of the session, both patients improved considerably

and showed stable recovery at one month follow-up. Strikingly,
after treatment, their overall error rate dropped to 10% (from
pre-treatment error rates of 91% (TL), and 81% (ZA)). Not only
did the error rates decrease dramatically over the course of
remediation in both patients, but the nature of the errors also
changed. This change in error patterns was interpreted as
being due to different strategies used by the two patients in
relearning their facts. As described above, patient TL relied on
the recitation of Nx1 forward until she could access the
solution to the problem. Patient ZA relied on the strategy of
repeated addition of the second operand. Thus, back-up
strategies may certainly play a facilitative role in the re-
acquisition of simple arithmetic. Similar training programs for
the rehabilitation of arithmetical fact impairment have been
adopted in other cases as well (e.g. Hittmair-Delazer et al.,
1994; Whetstone, 1998).
The conventional ‘drill’ approach to rehabilitation of

arithmetical facts can be lightened by simultaneous
presentation of visual or auditory cues (Domahs et al., 2004,
2007). Another approach has been to rehabilitate arithmetic
facts based on conceptual knowledge rather than extensive
training. This method is based on inducing a meaningful re-
organisation of arithmetical facts according to the principles
underlying them, for instance the commutative law or
decomposition using known facts, (i.e. 10s, ties and 2s) (Girelli
et al., 2002).
Girelli and Seron (2001) also stressed the importance of

minimising the opportunity to make mistakes, since repeated
errors may strengthen the wrong associations between
problems and answers. Moreover, the use of back-up
strategies based on the principles underlying arithmetical
facts such as the order-irrelevant principle (e.g. 8 × 6 = 6 × 8 =
48), decomposition strategies (e.g. 4 × 8 = 2 × 8 + 2 × 8 = 32)
or repeated addition of the second operand (e.g. 3 × 5 = 5 + 5
+ 5 = 15) seem important in rehabilitation of arithmetical
Page 18 of 28
facts. (p.413) Overall, research has indicated that patients

benefit significantly from training, and that improvement is
retained over time (and in some cases, spontaneously
generalises).
7 Conclusions
This review described acalculia as a heterogeneous disorder
consisting of impairments in processing numbers, in
calculation, or in both. Specific components of number and
calculation have been presented in the context of both normal
functioning and impaired performance following cerebral
damage. This included disorders in transcoding processing,
quantity processing, calculation, and their sub-components.
Cases of selective preservation of number processing have
also been analysed. This review also offered a short outline of
lesions’ localization with respect to number and calculation
disorders, and indicated the parietal areas most relevant for
numeracy and its impairments.
Finally, we have proposed some guidelines for the assessment

of acalculia and discussed some of the rehabilitation
programmes for acalculia in neurological patients. These
programmes have indicated the importance of systematic
intervention in acalculia, but have also shown that there are
several important aspects of numerical skills for which no
specific interventions have been developed. Future studies are
needed to create treatments for different numeracy
impairments and to test whether these treatments generalise
to real-life situations; the purpose of any rehabilitation
programme.
Acknowledgments
This work was supported by a grant from the Wellcome Trust
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The assessment and treatment of emotional disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The assessment and treatment of

emotional disorders
Guido Gainotti
DOI:10.1093/acprof:oso/9780199234110.003.022

This chapter begins with a discussion of how emotional
disorders differ from other ‘neuropsychological’ disorders
such as language, memory, attention, visuospatial exploration,
etc. It then discusses taxonomies of emotions and their
underlying theoretical models; neurological, psychological,
and psychosocial factors causing disorders in brain-damaged
patients; the major types of emotional disorders following
brain damage; and assessment and treatment of emotional
disorders following brain-damage.
Keywords: emotional disorders, brain damage, neuropsychological disorders,

visuospatial exploration
1 Introduction
Page 1 of 34
The juxtaposition, in this and in most other books of

neuropsychology, of emotional disorders and disorders of
language, memory, attention, visuospatial exploration, etc.
could implicitly suggest that a basic similarity exists among all
these ‘neuropsychological’ disorders. This suggestion,
however, is misleading from both the conceptual and the
pathophysiological point of view. Conceptually, emotions
cannot be placed under the same general heading as the
above-mentioned cognitive functions. Pathophysiologically, the
relationship between brain damage and clinical
symptomatology is different in the cases of cognitive and of
emotional disorders.
1.1 Emotion as a general ‘adaptive system’

From the ‘conceptual’ point of view, language, memory,
attention, etc. must be viewed as components of a general,
phylogenetically advanced, adaptive system (the ‘cognitive
system’). Emotion, on the other hand, should be considered as
a second (more primitive) general adaptive system, also
composed of different functional subsystems. The adaptive
nature of both the emotional and the cognitive system has
been stressed by Oatley and Johnson-Laird (1987), who have
claimed that, in order to face a partially unpredictable
environment and to select the most appropriate response
pattern, the organism makes use of two operative (the
emotional and the cognitive) systems.
◆ The emotional system is considered as an automatic

emergency system, based on processes involved in the
quick appraisal of external events and the immediate
activation of a small number of innate operative patterns.
These action patterns correspond to a few basic emotions
(e.g. fear, rage, joy, sadness, surprise and disgust) that
reflect, at the level of interpersonal communication and of
proness toward action, the most important interactive
schemata for the human species.
◆ The cognitive system can be considered, in contrast, to be

a powerful propositional adaptive system, based on the
exhaustive computation of sensory data and on the
selection of complex strategic plans, but one that requires
much more time to carry out its adaptive function (see
Gainotti 2000).
Page 2 of 34
If we turn now to the different pathophysiology responsible for

cognitive and emotional disorders resulting from brain injury,
we can say that the relationship between brain (p.419)
damage and clinical symptomatology is immediate (and the
functional defect closely related to the anatomical locus of
lesion) in various kinds of cognitive disorders. This relation,
however, is at least in part indirect (and the behavioural
pattern only in part related to the anatomical locus of damage)
in the case of emotional disorders.
1.2 Emotional reactions to the consequences of a brain damage

According to most theorists of emotions (e.g. Lazarus 1982),
the process of emotional appraisal (or emotional evaluation) is
a fundamental step of every kind of emotional reaction and
consists of the subjective evaluation.
(a) of the personal significance of a situation or an

event;
(b) of the capacity to cope adequately with this event.
Now, since a stroke, brain trauma or other cause of brain

damage is an event that can have a tremendous personal
meaning for the patient, a significant emotional reaction to the
brain damage is to be expected, irrespective of the extent and
of the anatomical location of the brain lesion.
2 Taxonomies of emotions and their underlying theoretical

models
The theoretical debate between biologically and cognitively
oriented authors about the nature of emotions has been
dominated in recent years by a controversy on the
relationships between emotion and cognition. On the one
hand, authors such as Zajonc (1980), Panksepp (1982) and
LeDoux (1996) have stressed the biological foundations of
emotions, maintaining that emotion and cognition must be
considered as independent systems. On the other hand,
cognitively oriented authors, such as Lazarus (1982), Frijda
(1986) and Scherer (2000) have argued that there are not two
independent adaptive systems, but that cognition plays an
integral in emotion. This controversy stems from the facts that
human emotions are very complex, hierarchically organized
phenomena (Gainotti 2001) and that the levels of emotions
taken into account by biologically oriented and by cognitively
oriented authors, can be very different.
Page 3 of 34
◆ The biologically oriented authors, being interested in the

brain-behaviour relationships, and drawing on Darwin’s
(1872/1965) seminal work on the survival value of the social
aspects of emotions, focus their attention on the simplest
aspects of emotion, as they appear in animals and in the
early stages of human development.
◆ The cognitively oriented authors, attracted by the

complexity of emotional phenomena, focus their attention
on the subtleties of human interactions, consider the
biological approach as inappropriate and reductionistic, and
base their taxonomies of human emotions on various types
of situational antecedents and of appraisal criteria (Scherer
2000).
Biologically oriented authors are therefore right in considering

that, from the phylogenetic and from the functional points of
view emotion and cognition constitute two partly independent
adaptive systems, and are subserved by different brain
structures. However, cognitively oriented theorists are also
right in stressing the interaction that exists (p.420) between
the two systems and the integral role that cognition plays in
functions of emotional appraisal.
Trying to construct a bridge between these two different, but

not necessarily alternative positions, Leventhal (1974 and
19871987) has proposed an ontogenetic model of emotions
that implicitly acknowledges both the earlier autonomy and
the later dependency of emotionsl on the cognitive system. In
particular, Leventhal has proposed a model of human emotion
based on three functional levels:
◆ The sensori-motor level consist of a set of innate

expressive-motor programs, that are triggered
automatically by certain stimuli and which include
components of motor and autonomic activation, as well as
subjective emotional feelings. During an individual’s
psychological development, expressive-motor programs are
created through a process of linking conditioned learning to
situations within the individual’s experience - building an
‘emotional schemata’ for each person.
◆ The second schematic level consists of the units that

make up the emotional schemata for each individual. These
units determine spontaneous emotions as well as emotional
Page 4 of 34
feelings and these give each schemata the hallmarks of true

emotion.
◆ The last stage of this model is the conceptual level where

the individual does not store instances of concrete
emotional experiences but draws on conscious declarative
memory, abstract notions about emotions and social rules in
order to express emotion.
More recently, Rolls (2005) has examined aspects of the

Leventhal’s hierarchical model and has explored in some detail
how cognitive states can modulate emotions and, in turn, how
emotions can influence both cognition and decision-making.
The distinction between biologically grounded basic levels and
the more complex psychologically oriented levels of emotions
can allow us to understand why emotional disorders can
result, in some cases, as a consequence of neurological factors
and in other cases because of psychological or psychosocial
factors (Gainotti, 1993).
3 Neurological, psychological and psychosocial factors

causing disorders in brain-damaged patients
3.1 Neurological factors
Emotional disorders are due to neurological factors when they
result from the encroachment of the lesion upon ‘limbic’
structures (such as the fronto-orbital cortex, the cingulate
gyrus, the amygdala or the hypothalamus) specifically involved
in various aspects of emotions (see Gainotti 2006 for a survey
of this subject). A schematic representation of these
structures, mapped on to a medial view of a cerebral
hemisphere, is shown in Figure 22.1.
3.1.1 Emotional disorders as long-term sequelae of closed head

injury
Of the various categories of diseases which can provoke brain
damage, closed head injury is probably the one that shows the
most direct link between structural brain lesions and
emotional disorders. This is due to the fact that, in patients
who report a typical road accident of the acceleration-
deceleration type, the injury mostly involves the axial brain
structures and the mesiobasal parts of the frontal and
temporal lobes (Adams et al., 1980). Particularly damaged are,
therefore, are structures such as the fronto-orbital cortex, the
(p.421)
Page 5 of 34
anterior part of
the cingulate
gyrus and the
amygdala (Fig.
22.1), which
are critically
involved in
various aspects
of emotional
and
motivational
processes. The
clinical Fig. 22.1 A schematic representation of
counterpart of the fronto-orbital cortex, the cingulate
the gyrus, and the amygdala mapped on to a
preferential medial view of a cerebral hemisphere.
encroachment The hatched parts of the figure indicate
of the lesion the brain structures usually damaged in
upon these patients with a severe closed head injury
limbic
structures is a
prevalence of emotional and behavioural disorders (rather than of
motor, sensory or aphasic disturbances) as the the long-term
sequelae of severe head injury. These emotional disorders usually
consist of:
(a) a severe apathetic syndrome, with a lack of
emotional reaction to pleasant or unpleasant events
and of goal-directed behaviours;
(b) a marked inability to keep under control socially
unacceptable emotional reactions, such as aggressive
outbursts when experiencing frustrating situations;
(c) less specific anxious or depressive reactions.
According to Mega & Cummings (1994) the apathetic

syndrome and the disinhibition of emotional outbursts may be
due to loss of function in different pathophysiological
mechanisms within different parts of the frontal cortex. Here,
apathy is seen as the result of disruptions in dopaminergic
circuits (running from the mesencephalic ventral segmental
areas to the frontal cortex), reducing motivated behaviour. In
contract, disinhibition is seen as the result of a breakdown of
control activity exerted by the fronto-orbital cortex on the
amygdala.
From a theoretical point of view, the inability of patients with

fronto-orbital lesions to assimilate external stimuli results
from deficiencies s in the activation of the ‘somatic markers’
Page 6 of 34
which converge in the ventro-medial frontal cortex. (For an

examination of the autonomic emotional response within
appropriate social and cognitive context and proprioceptive
afferences associated with emotional consequences for
personal decisions see Damasio (1994). Results supporting
these views have been reported by Bechara et al. (1997, 2000)
using a gambling task, in which choices that yield high
immediate gains are followed by higher future losses. Contrary
to control subjects, who rapidly realized the need of changing
their initial options, patients with ventro-medial frontal (FO)
lesions were insensitive to future consequences and were
primarily guided by immediate reward.
(p.422) However, from a clinical point of view and

irrespective of the nature of the underlying disorder, mental
changes in patients with severe head injuries are extremely
important. Not least, because they usually affect young or very
young persons and are associated with important memory
disorders and poor awareness of cognitive and behavioural
disturbances. These mental changes hamper resumption of
gainful employment and place a heavy burden upon family
members, who must cope with the patient’s childishness,
impaired initiative, low tolerance of frustration, and impulsive
or aggressive reactions.
3.2 Psychological factors
Page 7 of 34
Emotional disorders due to psychological or psychodynamic

(rather than to neurological) factors result from the process of
appraisal:
◆ evaluating the personal significance that the

consequences of the brain damage will have for the subject;
◆ evaluating his/her capacity to cope with these

consequences.
A factor that critically contributes to the outcome of this

(implicit or explicit) appraisal process is the awareness of the
brain damage and of its consequences. When this awareness is
full and painful, as in many patients with Broca’s aphasia and
a right-sided hemiplegia, the emotional response often
consists of ‘catastrophic reactions’ following frustrating
attempts at verbal expression and a more stable anxious-
depressive disorder. When, in contrast, this awareness is poor
(as in patients with a frontal lesion resulting from a traumatic
brain injury, or in stroke patients with a right hemisphere
lesion and a syndrome of neglect for the left half of the body
and of extrapersonal space), then a lack of concern and an
apathetic behaviour are usually observed.
It must be acknowledged, however, that the relationship

between awareness of the disorder, the appraisal process and
the emotional reaction is not necessarily one-way, simple or
direct. According to Lambie and Marcel (2002), experience of
emotion can take various forms and phenomenological
knowledge can be distinguished from awareness. Marcel et al.
(2004) have shown that anosognosia for hemiplegia is not a
unitary phenomenon and that several factors underlie deficits
in bodily awareness. Sometimes, the (apparent) unawareness
of the functional defect and of the resulting disability
(‘anosognosia’) can be considered to be a primitive form of
coping mechanism, rather than as a factor influencing the
appraisal process. In this case it seems preferable to use the
term ‘denial of illness’, rather than the term ‘unawareness of
the disability’, to mean that the patient is somehow aware of
his/her disabilities, but is forced to verbally deny their
existence.
3.2.1 Anosognosia of left-sided hemiplegia

The more impressive form of ‘denial of illness’ is often
observed in patients who have sustained a massive stroke in
Page 8 of 34
the territory of the right middle cerebral artery but who

verbally deny their left-sided hemiplegia or behave as if this
side of their body is perfectly normal.
Patients exhibiting the syndrome of ‘denial of left-sided

hemiplegia’ have been included in psychoanalytically oriented
research studies (Kaplan-Solms and Solms, 2000; (p.423)
Turnbull et al., 2002) and the existence of a ‘denial syndrome’
due to general psychodynamic mechanisms and not resulting
directly from brain damage is suggested by several lines of
enquiry. One of these is that denial syndrome is often observed
in life-threatening conditions, such as cancer or miocardial
infarction where there is no evidence of brain damage.
Difficulty in determining whether an emotional behaviour is a

consequence of a process of emotional appraisal or is, instead,
due to a biologically determined factor that influences the
outcome of this process is frequently experienced in brain-
damaged patients (see Orfei et al., 2007). This problem raises
important methodological problems (see Ownsworth and
Clare, 2006) and may concern not only the awareness of the
disease, but also other important aspects of emotional
behaviour, such as a depressive mood or an apathetic state.
Page 9 of 34
3.2.2 Post-stroke depression

The syndrome of major ‘post-stroke depression’(PSD), that is
observed in a high proportion (20-25%) of stroke patients, has
been considered by Robinson et al. (1984, Robinson 2001) to
be a biological consequence of stroke, resulting from
disruption of monoaminergic pathways running from the
brainstem to the cerebral cortex. These conclusions, however,
have been criticized on methodological grounds by Gainotti et
al. (1997), who have reanalyzed the question using a new
instrument (the Post-Stroke Depression Rating Scale)
specifically constructed to take account of symptoms and
problems of stroke patients, and have shown that major PSD is
phenomenologically different from ‘endogenous’ forms of
major depression. On the basis of these data, Gainotti and
Marra (2005) conclude that PSD must be considered a
motivated form of depression, provoked by the serious
obstacles that the consequences of brain damage put in the
way of the patient’s attainment of personal goals. The
emphasis on the personal/ subjective nature of emotional
problems caused by brain damage underlies the weakness of
the main objection of supporters of the ‘neurological’ model to
the psychological interpretation of PSD, namely that since in
some studies no significant association has been found
between degree of disability and severity of PSD, no
relationship should exist between psychological factors and
PSD. The weakness of this argument consists in its assumption
that a linear and objective relationship must exist between
disability and emotional reaction. This assumption does not
take into account the subjective nature of the process of
emotional reaction. Emphasis on the subjective component
implies that a motivated form of depression does not result
from the objective consequences of brain damage, but from
the personal significance that the subject attributes to these
consequences, in terms of social roles and of personal goals.
3.3 Psychosocial factors

Emotional disorders can be due to psychosocial factors rather
than to the the appraisal of the immediate consequences of
brain damage, when they result from the long-term
consequences of this event on the full range of activities,
social roles and social relationships of the patient. (p.424)
The most important of these social consequences is perhaps
Page 10 of 34
represented by the process of social isolation,which increases

over time, extending from the patient to his or her family.
This process implies two major modifications in the patient’s

social network:
(1) a reduction in its size, as the number of people

interacting with the patient progressively decreases;
(2) an increase of its intensity, since the only persons
remaining in contact with the patient are those who are
committed to a lasting relationship with them, (i.e.
family members, closely related to each other)
(Gainotti, 1993).
From an emotional point of view, the first modification leads

patients to become apathetic, lonely and depressed, whereas
the second modification usually leads to an increasing strain
among the members of this isolated group, with development
of feelings of resentment and hostility.
3.3.1 Circular interactions between patients and their families

It is important to note in this context that the circular
interactions that can develop between patients and their
families can, not supprisingly, have either a positive or a
negative influence on the patient’s own emotional attitude
and, consequently, on the rehabilitation process and outcome.
Thus, if close relatives are unable to tolerate the emotional
problems of these patients and the associated role changes
that the patients’ disabilities introduce in the family system,
then their negative attitude will further decrease the self-
esteem of the patient and their motivation toward
rehabilitation. If, on the other hand, family members warmly
support their relatives and assume a realistically positive
attitude toward their condition, then this positive attitude will
be inculcated by the patient, restoring their self-esteem and
increasing motivation toward rehabilitation.
4 The major types of emotional disorders following brain

damage
Page 11 of 34
As mentioned in previous sections, depression, anxiety, apathy

and lack of control over disruptive emotional outbursts are
among the most prevalent and clinically relevant forms of
emotional disorders usually observed in brain-damaged
patients. The prevalence of these disorders and their clinical
characteristics are different, however, following different
categories of brain damage and during different stages in the
evolution of the same disease. The anatomical locus of lesion
and the time elapsed from onset are very important
determinants of this heterogeneity in the patterns of emotional
behaviour shown by different clinical categories of brain-
damaged patients.
In particular, the anatomical locus of lesion, which is the more

powerful source of variance from this point of view, probably
acts trough two main mechanisms:
(a) the encroachment of the lesion upon limbic

structures (or neurochemical circuits) crucially
involved emotional functions;
(b) the level of awareness of physical and cognitive
disorders provoked by the lesion of different functional
systems.
This Section we will analyze in some detail the emotional

disorders corresponding to some important clusters of
physical and cognitive disorders that are usually provoked by
(p.425) the encroachment of the lesion upon some well
defined cortical areas. The aim of this description will be
twofold:
(1) to illustrate how some of the most frequent

emotional phenomena present clinically;
(2) to show that these different kinds of emotional
reactions are mostly due to a different level of
awareness of physical and cognitive disorders.
The emotional disorders that will be discussed here

correspond to the early stages following infarcts affecting the
territories of:
(a) the anterior branches of the left sylvian artery;

(b) the posterior branches of the same artery;
(c) the right middle cerebral artery.
4.1 The ‘catastrophical reaction’ of patients with Broca’s aphasia
Page 12 of 34
Lesions involve the inferior part of the left frontal lobe and the
patient presents with a severe sensorimotor defect on the
right side of the body, affecting hand and face. From the
(cognitive) linguistic point of view, the most striking defect is
severe Broca's aphasia, characterised by difficulty in engaging
in any form of propositional speech, very low speech rate,
effortful speech production, and inability to produce fluent and
well formed verbal utterances, but relatively spared
comprehension of oral and written language. The emotional
counterpart of this cluster of motor and speech disorders is a
marked tendency to ‘catastrophical reactions’ (i.e. to show
increasing signs of anxiety and/or to suddenly burst into tears)
because of frustrating and repeated attempts at verbal
expression.
4.2 The anosognosic ‘excitement’ of patients with a severe

Wernicke’s aphasia.
Here, the vascular lesion encroaches upon the temporoparietal
areas of the left hemisphere, involving the Wernicke's area,
and produces a quite different pattern of sensorimotor,
linguistic and emotional disturbances. -Sensorimotor disorders
are absent or very mild, and usually only a partial visual defect
for the right half space can be detected. The verbal production
of these patients appears fluent, harmonious and well formed,
but its meaning cannot be understood, since the most
informative parts of speech (namely nouns and other content
words) are affected by phonemic or semantic transformations,
producing a quite incomprehensible jargon. Equally important
(and, if possible, even more striking) are disorders of
comprehension which hamper these patients’ understanding
not only of the content of verbal messages addressed to them,
but also of the pathological nature of their own verbal
production. The emotional behaviour of these subjects sharply
contrasts with the catastrophical attitude of patients affected
by a Broca's aphasia, since these patients usually appear
unaware of their language disorders and appear overtalkative,
excited and often even aggressive against people who appear
not to understand their verbal messages.
Page 13 of 34
4.3 The ‘indifference reaction’ of right-brain-damaged patients

This cluster of physical, cognitive and emotional disorders
results from a focal brain lesion that affects the territory of the
right sylvian artery, (particularly involving the right parietal
lobe). From the physical point of view, these patients usually
present with a severe (p.426) left-sided hemiplegia and a
marked deviation toward the right side of space of all the
components of their body-orienting apparatus, (i.e. trunk, head
and eyes). From the cognitive point of view, the most striking
defect consists of a strong tendency to neglect the left half of
the body and of extrapersonal space with an automatic
capture of attention by stimuli rising on the right half space.
Finally from the emotional point of view, these patients show a
composite pattern of emotional disorders that can be grouped
in three sets of emotional abnormalities.
◆ The first and most important set, ‘emotional indifference’,

includes an apparent lack of appropriate concern for the
disability and an attitude of indifference toward other kinds
of emotionally laden events.
◆ The second set, labelled ‘verbal disinhibition’, consists of

a tendency to joke in a fatuous ironic or sarcastic manner.
◆ The third set, includes the verbal denial of left-sided

hemiplegia (considered in Section 3.2.1) and other
phenomena that all suggest an implicit attitude of denial of
illness. These last features often suggest feelings of
rejection of the paralyzed limbs that are felt not to belong
to the patient (‘somatoparaphrenia’) or described with
expressions of hatred, couched in a grotesque or
exaggerated language (‘misoplegia’).
Page 14 of 34
4.4 Factors underlying the awareness of the disorder

From the pathophysiological viewpoint, one of the most
important factors that can explain the of brain-damaged
patients different patterns of emotional behavioural brain-
damaged patients is the different extent of awareness of the
defect following disruption of the functional systems
subserved by these different anatomical regions. This
awareness could in turn be related both to neurological and to
psychological factors (Ownsworth and Clare, 2006). From the
psychological point of view, the level of awareness of a defect
could result from the amount of attention and of effort
required by patients to overcome their functional defect. This
could explain why patients with Broca’s aphasia, being obliged
to make a sustained conscious effort to mobilize their
articulatory apparatus and to overcome their difficulties of
speech production, are acutely aware of their communication
difficulties, whereas patients with Wernicke’s aphasia, having
a fluent speech and a severe comprehension disorder, that do
not allow them to monitor their meaningless utterances, are
unaware of their language disorders. Analogously, right brain-
damaged patients with a left sided hemiplegia and an
ipsilateral neglect may be unable to automatically orient their
attention toward the paralyzed limbs and this fact could
explain the most important aspects of their emotional
disturbances.
Page 15 of 34
4.5 The stigma of language expression disorders

A final mechanism which can explain the various emotional
behaviours of patients with differing lesions pertains to the
varying meaning and psychosocial impacts which different
kinds of cognitive and communication disorders can have for
the patient. In particular, the high level of depression and of
discouragement often show by left brain-damaged patients
with expressive aphasia may be due to the feelings of
inadequacy, embarassment and self-depreciation that
communicative disorders provoke in these subjects. Several
authors (e.g. Sarno and Gainotti, 1998) have noted that
aphasic patients feel particularly stigmatized, and often report
lowered self-esteem accompanied by feelings of shame as a
consequence of their communication disorders.
(p.427) Obviously, it is not possible to consider here the

complex problem of the many other facets that emotional
disorders can have following various categories of brain
damage and during the various stages of evolution of the
diseases. For simplicity sake, Table 22.1 summarises the most
important points concerning the pathophysiology and
prevalence of three broad categories of emotional disorders
(anxiety and depression, apathy and poor control of disruptive
emotional outbursts) following three important kinds of brain
damage, namely stroke, closed head injury and Alzheimer’s
disease (see also Starkstein and Manes, 2001).
The data reported in Table 22.1 are relevant from both the
epidemiological and the pathophysiological point of view. On
one hand, they show that all these kinds of emotional
disorders are widely, although unevenly distributed in
different clinical forms of brain damage or in different stages
of evolution of the same disease. On the other hand, they
confirm that anxiety and depression are mostly due to
psychological factors, whereas apathy and disruptive
emotional outbursts usually result from properly neurological
factors. The relationship between anxiety/depression and a
painful realisation of the consequences of the disease is, in
fact, present not only in stroke patients but also in closed
Table 22.1 Pathophysiology and prevalence of the

most important kinds of emotional disorders in
various categories of brain damage
Page 16 of 34
Categories of Stroke Brain injury Alzheimer’s

brain damage disease
Pathophysiology
Anxiety and depression
Psychological Very Rather Rather

factors. common uncommon common
‘Painful’ (40–50%) in in the (40%) in the
awareness of hospitalized earliest first stages
the adverse patients and post- of the
effects of less common traumatic disease; tend
handicaps and (20–30%) in periods; to disappear
disabilities on community tend to in later
the patient’s Settings develop stages with
social role and with the the
personal goals increased progression
awareness of dementia
of
handicaps
and
disabilities
Neurological According to
factors? (major some
PSD). authors
Disruption of more
monoaminergic common
pathways after left
relaying the than right
brainstem to the hemisphere
cerebral cortex damage
Apathy
Neurological More Very frequent Very

factors. Lesions common and due to frequent
encroaching after right neurological (30–80%).
upon the mesial (20–25%) factors in the Its
parts of the than left earliest frequency
frontal lobes, (10–15%) stages and to and severity
the anterior hemisphere psychosocial increase
cingulate gyrus stroke factors in with the
and the late periods progression
mesolimbic of dementia
Page 17 of 34
Apathy
dopaminergic
System
Psychological
factors.
Can result from
the tendency to
avoid the
frustrations
resulting from
handicaps,
disabilities, and
communication
disorders
Lack of control over disruptive emotional outbursts
Neurological Very Very frequent Rather

factors uncommon after the common in
Lesions earliest the most
encroaching posttraumatic advanced
upon the periods stages of the
orbitofrontal disease
cortex and the progression
fibres
connecting
these
structures to
the amygdala
(p.428) head injury or in dementia of the Alzheimer’s type (DAT).

However, in the last two categories of brain damage, these
emotional disorders are only observed in the stage of evolution of
the disease characterized by the highest level of awareness, namely
in the earliest stages of DAT and in the late stages of brain injury.
This is very different to the context in which disruptive emotional
outbursts and apathetic disorders are usually observed.
◆ Disruptive emotional outbursts are mainly observed in
patients with a severe traumatic injury of the fronto-orbital
cortex (and in the most advanced stages of DAT).
◆ Apathetic disorders are particularly severe in patients

with lesions encroaching upon the anteromesial parts of the
frontal lobes, but are also observed in patients with an
Page 18 of 34
extensive infarct impinging upon the the right parietal

region and in the advanced stages of DAT.
5 Assessment of emotional disorders following brain-

damage
In recent years, behavioural and emotional disorders of brain-
damaged patients have attracted more and more attention in
the field of neurorehabilitation for two main reasons.
◆ These disorders constitute an important obstacle not only

to the resumption of productive activities, but also to the
rehabilitation process. They are indeed responsible for the
lack of collaboration of the patient, which impedes the
improvement of potentially treatable physical and cognitive
defects.
◆ The fact that emotional and personality disorders are the

consequence of brain damage is likely to be difficult to
accept for family members (Lezak, 1978; Brooks et al.,
1983, 1986). These disorders are, therefore, the factors that
more frequently trigger the negative circular interactions
between patients and their families briefly described in
Section 3.3.1.
A careful assessment of emotional and behavioural disorders

is, therefore, critical to the process of evaluation of the
specific needs of each brain-damaged individual and is crucial
when establishing comprehensive (holistic) rehabilitation
programmes. Furthermore, the recent development of
evidence-based rehabilitation medicine stresses the need for
using a large array of standard psychometric instruments that
could be appropriate to the assessment of emotional disorders
of brain-damaged patients and that could, in turn, be used as
outcome measures for various kinds and stages of
neuropsychological rehabilitation (see Fleminger and Powell
1999). Obviously, the in-depth assessment required to
understand individual problems and to establish personalized
rehabilitation programs overlaps only in part with the
standard psychometeric assessment required by the evidence-
based rehabilitation medicine. Consequently, this chapter will
only deal with two forms of evaluative processes:
◆ the personalized kind of assessment;
◆ the psychometric instruments currently used for a

standard assessment of emotional disorders.
Page 19 of 34
5.1 Personalized assessment of the significance of emotional

disorders
The subjective, personalized assessment of the significance of
emotional disorders consists of two main steps:
(a) distinguishing the neurological from the motivated

(psychological or psychosocial) components of these
disorders;
(b) delineating the main problems and psychosocial
resources of the patient.
(p.429) Snyder (1994) developed an interesting construct to

clarify this problem. He defined the the construct of ‘hopeful
thinking’ as a relatively enduring personality style that is
based on self-referential beliefs about:
(a) the development of personally meaningful goals;

(b) finding ways (around obstacles) to achieve these
goals;
(c) being motivated to implement these pathways.
‘Hopeful thinking’ is relevant to understanding the emotional

functioning of stroke patients because of the importance of
goals in their disability and recovery. Stroke patients who
remain hopeful believe that they can both overcome the
obstacles caused by the disability and attain their goals. They
are likely, therefore, to be less depressed and actually achieve
more goals than patients who are less hopeful. In his study
Gum et al. (2006) confirmed that three months after a stroke,
patients who are more hopeful were less likely to exhibit
symptoms of depression and more likely to show higher levels
of participation in general social activities.
5.2 The standard psychometric assessment of emotional

disturbances
The standard psychometric assessment is much less relevant
for the evaluation of individual problems and difficulties, but
has the virtue of being more objective and quantitative. It is,
therefore, much more reliable as a method of assessment for
the negative effects that emotional disturbances can exert on
the rehabilitation process. Important methodological
objections have been raised the use of these psychometric
measures of emotional and affective disorders. These will be
considerd briefly and Table 22.2 summarises some of the
Page 20 of 34
instruments commonly used for the assessment of anxiety or

depression, apathy and some disruptive behavioural disorders.
5.2.1 Methodologial objections

◆ One general problem for all of these scales, and in
particular for those assessing anxious-depressive disorders,
consists of the fact that they have usually been developed
for psychiatric patients and that their transfer into the field
of organic brain-damaged patients may produce misleading
results. It is for this reason that some authors have
developed instruments specifically constructed for well
defined groups of brain-damaged patients, such as the
already mentioned ‘Post-Stroke Depression Rating
Scale’ (PSDRS), designed by Gainotti et al. (1997) to clarify
the meaning of major depressive disorders frequently
observed in stroke patients.
◆ A different, but equally important, problem can be

recognised in the use of self-report instruments, such as the
‘Beck Depression Inventory’(1961), the Zung Self-Rating
Inventory’ (Zung et al., 1965), the ‘Hospital Anxiety and
Depression Scale’ (Zigmond & Snait, 1983) or the
‘Wimbledon Self-Report Scale’ (Coughlan & Storey, 1988).
Since patients with dementia or with severe brain injury
may well be unaware not only of their physical problems,
but also of their cognitive or emotional difficulties, the
assessment based on the use of self-report scales must be
considered quite unreliable. (p.430)
6 Treatment of emotional and behavioural disorders in

brain-damaged patients
Table 22.2 Main instruments used for the
standard neuropsychological assessment of the
most important kinds of emotional disorders
Anxiety Hamilton Anxiety Designed for

Scale (HAS: psychiatric
Hamilton, 1959) settings
Hospital Anxiety and Self report

Depression Scale. instrument for
See Balon (2007) for detecting
review anxiety and
depression in
hospitalized
Page 21 of 34

medical and
neurological
patients
Depression Hamilton Depression Designed for

Rating Scale (HDRS; psychiatric
Post-stroke Clinician rated

depression rating scale specifically
scale (PSDRS; constructed for
Gainotti et al. 1997) stroke patients.
Montgomery-Asberg Psychiatric scale

Depression Rating consisting of 9
Scale (MADRS; reported and 1
Montgomery & observed items
Asberg, 1979;
Demyttenaere and De
Fruyt (2003)
Wimbledon Self- Self report scale

report scale (WSRS; devised to
Coughlan e Storey, assess mood in
1988) brain-damaged
patients
Apathy Apathy evaluation Self-informant

scale (AES; Marin et and clinician
al., 1991) Glenn et al. rated versions of
(2002) this scale have
been developed
Disruptive Overt aggression Designed to be

behavioural Scale (OAS; rated by nursing
disorders Yudowsky et al., staff in
1986) psychiatric
setting, is also
used in brain
injury patients
Page 22 of 34

General Neurobehavioural Sensitive to

Neurobehavioural Rating Scale (NRS; behavioural
Levin et al., 1987) disorders
related to
frontal lobe
injury
Rating Scales Neuropsychiatric Clinician rated

Inventory (NPI; instrument
Cummings et al., developed as an
1994) assessment tool
Sink et al. (2005) for patients with
dementia
The treatment of emotional disorders in brain-damaged

patients is based on a large array of methods and techniques
from the pharmacological treatment in the most severe
emotional disorders, through behavioural management
techniques used to modify inertia or disruptive patterns of
social behaviour in patients with severe brain injury, to various
kinds of group treatments and of individual psychotherapies.
6.1 Management of unawareness of deficits

Several studies, summarized by Ownsworth and Clare (2006),
suggest that a lack of deficit awareness is often associated
with poor rehabilitation outcome, However, the usefulness of
treating these deficits remain a contested issue - primarily
because patients with these deficits may develop harmful
emotional distress very early in the adjustment process
(Langer and Padrone, 1992; Ownsworth, 2005). In contrast,
individuals with persistent unawareness of deficits are more at
risk of long-term emotional disorders, due to their unrealistic
expectations of recovery and inability to understand the
reason for restrictions imposed upon them. In these cases, the
need for therapeutic interventions seems very strong. Fleming
and Ownsworth (2006), in their review of a range of
awareness interventions in (p.431) brain injury
rehabilitation, makes an important distinction between
intervention approaches for unawareness due to
neurocognitive factors or psychological factors.
Page 23 of 34
6.2 Cognitive behavioural therapy in the treatment of post-stroke

depression
Lincoln et al. (1997) have considered the use of cognitive
behavioural therapy (CBT) (which is effective in the treatment
of late-life depression) in the treatment of PSD. In an initial
study Lincoln et al., (1997) implemented 10 sessions of CBT
treatment over a 4-week baseline period and found that there
was a tendency for improvement in the mood in some patients.
However, in a second, randomized controlled trial, Lincoln and
Flannaghan (2003) concluded that there were no significant
differences between groups in patients’ mood, independence,
handicap or satisfaction with care.
6.3 Group treatment of emotional and behavioural disorders

Group treatment of emotional and behavioural disorders of
patients with severe brain injury has several advantages:
(a) It increases the level of awareness of the patients’

defects and capabilities, allowing them to check the
adequacy of their current behaviour;
(b) It promotes interactions that, on one hand,
increases the level of initiative and of personal
involvement of patients and, on the other hand,
improves their control over irritability, overt aggression
or other disinhibited patterns of behaviour;
(c) It improves the level of participation to shared
activities, favouring some degree of competition and,
consequently, a more independent attitude.
6.4 Behavioural management techniques

Behavioural management techniques tend to induce an
implicit learning of the suggested behavioural modifications by
means of (classical or operant) conditioning methods. These
techiques make use of positive and negative reinforcements to
increase favourable changes (e.g. the development of
intentional action schemata in patients with inertia or severe
apathy) and to inhibit socially unacceptable emotional
outbursts. Wood (1987) has suggested, for example, the
systematic use of the ‘time out’ procedures (the complete
suspension of every kind of reaction to the onset of
undesirable behavioural patterns) since the patient implicitely
learns from this unexpected lack of response that his
provocative behavioural patterns are unable to produce any
effect on the external milieu.
Page 24 of 34
6.5 The pharmacological treatment of emotional disorders

With respect to the pharmacological treatment of patients with
severe forms of emotional disorders Table 22.3 indicate that
several drugs are able to ameliorate the depressive disorders,
apathy aand disruptive behavioural outbursts of brain-
damaged patients. For example, Fleminger et al. (2003) and
Deb and Crownshaw (2004) have provided systematic reviews
of the pharmacological treatment of agitation and aggression
in people withn brain injury, Yury and Fisher (2007) have
published a meta-analysis of the effectiveness of atypical
antipsychotics for treatment of behavioural problems in people
with dementia, (p.432)
Table 22.3 Drugs used for the treatment of post-

stroke depression, apathy and behavioural
disorders of brain-damaged patients
Emotional Therapeutic approach Reference

Disorder
Post-strokes Serotonine selective Andersen et

depression reuptake inhibitors al., (1993)
Citalopram Gainotti et al.,
Fluoxetine (2001)
Sertraline Fruehwald et
al., (2003)
Murray et al.,
2002
Hackett et al.,
(2005)
Other Reding et al.,

antidepressants (1986)
Trazodone Robinson et
Nortriptyline al., (2000)
Apathy Dopaminergic drugs Newburn et

Selegiline al., (2005)
Bromocriptine Campbell and
Pergolide Duffy (1997)
Modafinil Padala et al.,
(2007)
Stimulant drugs Marin et al.,

Methylphenidate (1995)
Page 25 of 34
Emotional Therapeutic approach Reference

Disorder
Deb and
Crownshaw
(2004)
Aggression and Atypical Perino et al.,

other antipsychotic (2001)
behavioural medications McAllister and
disorders Clozapine Ferrell (2002)
Risperidone Yury, C.A.,
Quetiapine Fisher, J.E.
Beta Blockers (2007)
Tiihonen,
(2009)
Fleminger et
al., (2003)
Deb and
Crownshaw
(2004)
and Hackett et al. (2005) have reviewed the effectiveness of

antidepressants for the treatment and prevention of post-stroke
depression.
In 2004, Given such strong data, the Committee for the Safety
of Medicines (CSM) in the UK issued a warning that
olanzapine and risperidone should not be given to elderly
patients with dementia, because of an increased risk of stroke
and Gill et al. (2007) have shown that there is an increased
risk of death with conventional antipsychotics as opposed to
atypical antipsychotics.
This does not imply, however, that purely biological methods

are sufficient to treat, in the long term, the emotional
problems and disorders of brain-damaged patients.
Pharmacological treatments are necessary to improve the
most severe emotional disorders of these patients and to re-
establish a physiological process of emotional appraisal, but
the emotional problems of these patients will lose their
dramatic nature only when the outcome of this process will
become more acceptable to them. From this point of view, it is
probably correct to say that the rehabilitation process is the
most powerful instrument that we can use to improve the long
term the emotional equilibrium of these patients.
Page 26 of 34
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Page 33 of 34
Page 34 of 34
Assessment of anosognosia for motor impairments


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Assessment of anosognosia for

motor impairments
Anne M. Aimola Davies
Rebekah C. White
Martin Davies (Contributor Webpage)
DOI:10.1093/acprof:oso/9780199234110.003.023

This chapter begins with a threefold distinction that organizes
the investigation of anosognosia: the distinction between
failure to experience a motor impairment (concurrent
unawareness); failure to acknowledge the impairment itself;
and failure to appreciate the consequences of the impairment.
It then reviews methods for the assessment of motor
impairments and anosognosia for motor impairments including
structured anosognosia interviews that have been published.
This literature review reveals considerable variation in the
methods by which patients with anosognosia have been
assessed. The development of a comprehensive and widely
accepted procedure for assessing anosognosia for motor
impairments would contribute to a better understanding of the
many factors in anosognosia and might also lead to
improvement in the clinical management of patients. The
chapter presents a structured interview that offers a
Page 1 of 60
theoretically motivated and relatively comprehensive approach

to the assessment of anosognosia for motor impairments.
Keywords: anosognosia, motor impairments, neuropsychological assessments,

structure interview
1 Introduction
Patients with anosognosia fail to acknowledge their motor
impairments. Anosognosia is usually assessed by means of a
structured interview, beginning with questions about general
health and moving to specific questions about the patient’s
motor impairment. A patient whose arm or leg is paralysed or
weak following a stroke may deny the weakness in response to
questions like ‘Is there anything wrong with your arm or leg?’
or ‘Is your limb weak, paralysed, or numb?’ (questions from
Cutting, 1978; Nathanson, Bergman and Gordon, 1952;
Starkstein, Federoff, Price, Leiguarda and Robinson, 1992),
and may continue to deny the impairment even when it has
been demonstrated. The examiner may ask the patient to raise
both arms and then demonstrate to the patient that one arm is
not raised as high as the other. Recognising that a patient has
anosognosia may be relatively straightforward, for example,
when the patient denies outright that there is anything the
matter. In many patients, however, a full assessment will
reveal a more complex profile.
In this chapter, we begin (Section 2) with a threefold

distinction that organises our investigation of anosognosia —
the distinction between failure to experience a motor
impairment (concurrent unawareness), failure to acknowledge
the impairment itself, and failure to appreciate the
consequences of the impairment (Aimola Davies, Davies,
Ogden, Smithson and White, 2009). Then, we review methods
for the assessment of motor impairments and anosognosia for
motor impairments (Section 3) including structured
anosognosia interviews that have been published (Section 4).
improvement in the clinical management of patients (Orfei,
Caltagirone and Spalletta, 2009). We present a structured
Page 2 of 60
interview (Section 5) that offers a theoretically motivated and

relatively comprehensive approach to the assessment of
anosognosia for motor impairments.
(p.437) 2 A threefold distinction

Two ideas figure in the Oxford English Dictionary definition of
anosognosia: ‘unawareness of or failure to acknowledge one’s
hemiplegia or other disability’. Unawareness suggests a failure
of experience (sensation and perception). Failure to
acknowledge suggests a failure of judgement (belief and
assertion). This important distinction is obscured if the term
‘unawareness’ is used interchangeably with ‘anosognosia’. We
regard anosognosia as a failure or pathology of belief: a
mismatch between the patient’s estimate of his or her abilities
and the reality of the impairment. The patient believes that he
or she does not have the impairment despite the fact that it is
clearly present. This incorrect belief will be manifested in the
patient’s failure to acknowledge the impairment verbally in
response to questions.
Consider a hypothetical case of a patient with hemiplegia

following right-hemisphere stroke. When the patient intends to
raise his left arm, proprioception and vision tell him that the
arm is still hanging by his side. When the patient tries to raise
his arm, a comparator within the motor control system detects
a mismatch between the expected movement of the arm and
what actually happens and the patient is alerted to his
paralysis. If the patient directs his attention to the left side of
his body, this only confirms that his left arm has not moved.
This hypothetical patient has immediate experiences —
concurrent awareness — of his motoric failure and these
experiences may lead him to abandon long-held beliefs about
his motor abilities. In contrast, patients with proprioceptive
loss (Levine, 1990), or unilateral neglect (Vuilleumier, 2004),
or with damage to the comparator in the motor control system
(Gold, Adair, Jacobs and Heilman, 1994; Heilman, 1991;
Heilman, Barrett and Adair, 1998), may not fully experience
their motoric failures. They may even seem to experience
motoric success — illusory limb movements (Frith, Blakemore
and Wolpert, 2000; Feinberg, Roane and Ali, 2000; Levine,
Calvanio and Rinn, 1991). Such patients, with concurrent
unawareness of motoric failure, may be more likely to
Page 3 of 60
maintain long-held beliefs that are now incorrect — beliefs

that overestimate their motor abilities.
It is plausible that concurrent unawareness often plays an

important role in the aetiology of anosognosia. But the
distinction between concurrent unawareness (a failure to
experience motoric failures when they occur) and anosognosia
(a failure of belief) is confirmed by thought experiments and
empirical findings (Marcel, Tegnér and Nimmo-Smith, 2004).
In principle, a patient with impaired proprioception might
have no immediate bodily experience of failure to move a
paralysed limb yet, on the basis of other evidence, the patient
might still reach the correct belief about his or her paralysis
(failure of experience without failure of belief). Conversely, a
patient with intact proprioception might have vivid bodily
experiences of failure to move a paralysed limb but, because
the information is not consolidated into more lasting
representations, the patient might fail to reach the correct
belief about his or her paralysis (failure of belief without
failure of experience).
Having an incorrect belief about the severity of an impairment

itself is also distinct from having an incorrect belief about the
seriousness of the consequences of the impairment for
activities of daily living. House and Hodges (1988) present an
example that is relevant to (p.438) this second distinction.
They describe an 89-year-old woman who suffered left-side
paralysis following a right-hemisphere stroke. When she was
examined six months after her stroke, she acknowledged that
her left arm was weak, and weaker than her left leg. When it
was demonstrated to her that her left arm was completely
paralysed and her left leg nearly completely paralysed, she
rated the strength of her left elbow and hand/wrist zero out of
ten and her left hip, knee and ankle/foot two out of ten. But
even while she acknowledged her motor impairments she
failed to appreciate their consequences, ‘she insisted that she
could walk upstairs unaided if she were allowed to’ (whereas,
in reality, she was restricted to a wheelchair) (House and
Hodges, 1988, p. 113). Marcel and colleagues (2004) also
report several patients who acknowledged that their left arm
was paralysed yet overestimated their ability to carry out
bimanual tasks such as tying a knot, clapping hands, or
shuffling cards. We might describe such patients as having
anosognosia for the consequences of their motor impairment
but not anosognosia for the impairment itself. They
Page 4 of 60
overestimate their ability to carry out activities of daily living

even if they do not, strictly speaking, overestimate their motor
abilities.
Thus, we reach the threefold distinction between concurrent

unawareness of an impairment, failure to acknowledge the
impairment itself, and failure to appreciate the consequences
of the impairment for activities of daily living. The first is a
failure of experience; the second and third are both failures of
belief.
In cases of mild motor impairment, where patients have

considerable residual movement in their impaired limbs, there
is less room for overestimation of motor abilities. It may be
difficult to classify such patients as having substantially
incorrect beliefs about their motor abilities. Even mild motor
impairments can, however, have serious consequences for
activities of daily living such as walking, washing, dressing,
grooming, and feeding. So patients who do not have complete
hemiplegia may still have dramatically incorrect beliefs about
their ability to carry out everyday activities. Assessment of
anosognosia, considered as a pathology of belief, should
investigate both failure to acknowledge the motor impairment
itself and failure to appreciate its consequences. Assessment
of the causes of anosognosia should extend to investigation of
concurrent unawareness of motoric failure.
3 Assessment of motor impairments and anosognosia

Before one can assess whether a patient has anosognosia for
motor impairments, it is necessary to establish that the patient
does have a motor impairment. In fact, some researchers (e.g.,
Berti, Spinazzola, Pia and Rabuffetti, 2007) have argued that
only patients with complete hemiplegia should be included in
studies of anosognosia because, otherwise, the patient’s belief
that he or she can move the affected limbs is at least partly
correct (see also Berti, Làdavas and Della Corte, 1996;
Bisiach, Vallar, Perani, Papagno and Berti, 1986; for
discussion, see Vallar and Ronchi, 2006, pp. 252–3).
3.1 Simple assessment of motor impairments and anosognosia

We now outline a procedure for establishing that the patient
has a motor impairment. If the primary purpose is to identify
patients with complete hemiplegia then a simple assessment
(p.439) of motor performance is sufficient. The examiner
might, for example, ask the patient to raise the affected limb,
Page 5 of 60
or to maintain a raised position following passive elevation by

the examiner. Three ordinal rating scales that can be used to
assess patient performance are presented in Table 23.1:
Medical Research Council (MRC) Scale (Guarantors of Brain,
2000), National Institute of Health (NIH) Stroke Scale (Brott,
Adams, Olinger, Marler, Barsan, Biller et al., 1989; Goldstein,
Bertels and Davis, 1989; Lyden, Lu, Levine, Brott and
Broderick, 2001), and the Bisiach Motor Impairment Scale
(Bisiach et al., 1986). Complete plegia corresponds to a score
of 0 on the MRC Scale, 4 on the NIH scale, and 3 on the
Bisiach scale. All three scales have been used in previous
studies of anosognosia.
Alongside the Bisiach Motor Impairment Scale (see Table

23.1), Bisiach and colleagues (Bisiach et al., 1986) introduced
the Bisiach Anosognosia Scale. A four-point scale is used for
assessment of anosognosia, ranging from 0 (no anosognosia)
to 3 (severe anosognosia):
0 The disorder is spontaneously reported or mentioned

by the patient following a general question about his
complaints (no anosognosia)
1 The disorder is reported only following a specific
question about the strength of the patient’s affected
limbs (mild anosognosia)
2 The disorder is acknowledged only after its
demonstration through routine techniques of
neurological examination (moderate anosognosia)
3 No acknowledgement of the disorder can be obtained
(severe anosognosia).
The distinction between moderate and severe anosognosia

depends on whether or not the patient acknowledges the
disorder ‘after its demonstration through routine techniques of
neurological examination’. This demonstration would be
provided by the assessment of motor impairments mentioned
in the previous paragraph. In the case of a patient with a score
of 3 for motor impairment of the left arm according to the
Bisiach Motor Impairment Scale, the demonstration would be
provided by the patient’s raised arm falling to the bed surface
within five seconds (see Table 23.1).
Many studies (including Bisiach et al., 1986; see also Baier and
Karnath, 2005; Berti, Bottini, Gandola, Pia, Smania, Stracciari
et al., 2005; Karnath, Baier and Nägele, 2005; Spalletta, Serra,
Page 6 of 60
Fadda, Ripa, Bria and Caltagirone, 2007) classify patients as

having anosognosia only if they receive a score of 2 (moderate
anosognosia) or 3 (severe anosognosia). In a recent study of
128 acute left- and right-hemisphere stroke patients, Baier and
Karnath (2005) found that twelve patients (9%) had a score of
2 or 3 (moderate or severe anosognosia). They also found that
sixteen of the seventeen patients with a score of 1 (mild
anosognosia) spontaneously mentioned other neurological
deficits or symptoms of stroke when asked a general question
and immediately acknowledged their motor impairments when
asked specifically about the strength of their limbs. Baier and
Karnath proposed that these patients had no problem
accepting their motor impairments but simply mentioned
‘subjectively more prominent’ symptoms (p. 361) in response
to a general question. The authors therefore argued that
patients with a score of 1 on Bisiach’s Anosognosia Scale
should not be classified as having anosognosia. (p.440)
Table 23.1 Assessment of Motor Impairments
Scale Instruction Rating scale
Medical Upper limb: 5. Normal power

Research The patient 4. Active movement
Council abducts the against gravity and
(MRC) upper arm resistance:
Scale* against 4+ strong
resistance. resistance
(Guarantors of 4
Brain, 2000, moderate
Fig. 21). resistance
Lower limb: 4 - slight
The patient lies resistance
on his or her
back and flexes 3. Active movement
the thigh at the against gravity
hip against 2. Active movement
resistance with with gravity
the leg flexed at eliminated
the knee and 1. Flicker or trace of
hip (Guarantors contraction
of Brain, 2000, 0. No contraction
Fig. 70).
Page 7 of 60
National Upper limb: 0. No drift; arm holds

Institute of The arms are 90° (or 45°) for full
Health placed in the 10 seconds
(NIH) appropriate 1. Drift; arm holds
Stroke position: arms 90° (or 45°) but drifts
Scale outstretched down before full 10
(palms down) at seconds; does not hit
90° if sitting, or bed or other support
at 45° if supine. 2. Some effort
Full effort is against gravity; arm
requested for cannot get to or
10 seconds. If maintain (if cued) 90°
consciousness (or 45°), drifts down
or to bed but has some
comprehension effort against gravity
are abnormal, 3. No effort against
cue patient by gravity; arm falls
actively lifting 4. No movement of
arms into arm
position as
request for 0. No drift; leg holds
effort is orally 30° position for full 5
given. seconds
Lower limb: 1. Drift; leg falls by
The leg is the end of the 5-
placed in the second period but
appropriate does not hit bed
position: while 2. Some effort
supine, the against gravity; leg
patient is asked falls to bed by 5
to maintain seconds, but has
weaker leg at some effort against
30° for 5 gravity
seconds. If 3. No effort against
consciousness gravity; leg falls to
or bed immediately
comprehension 4. No movement of
are abnormal, leg
cue patient by
actively lifting
the leg into
position as
Page 8 of 60

request for
effort is orally
given.
Bisiach Upper limb: 0. No defects or

Motor The supine minimal defects not
Impairment patient is asked scorable as 1
Scale to hold the 1. Appearance of at
following least one of the
position for 30 following signs:
seconds: arm finger
flexed at 45°, abduction,
forearm pronation
extended and of the
supinated, forearm,
fingers lowering
abducted. of limb
Lower limb: without
The supine reaching
patient is asked bed
to hold the surface
following within 15
position for 30 seconds
seconds: thigh
flexed at 90°, 2. Limb lowers and
leg flexed at reaches bed surface
90°. within 15 seconds
3. Limb reaches bed
surface within 5
seconds
0. No defects or
minimal defects not
scorable as 1
1. Lowering of limb
without reaching bed
surface within 15
seconds
2. Limb lowers and
reaches bed surface
within 15 seconds
Page 9 of 60

3. Limb reaches bed
surface within 5
seconds
*Medical Research Council Scale is different in two ways

from the NIH Stroke Scale and the Bisiach Motor
Impairment Scale: the assessment is for raising the limb (as
opposed to maintaining a raised limb) and scoring is in the
opposite direction, so that higher scores indicate better
motor function.
(p.441) This recent discussion of ‘mild anosognosia’ recalls

an insightful and perhaps insufficiently recognised
contribution to the field by Willanger, Danielsen and Ankerhus
(1981). In their study, 55 patients admitted to hospital
following right-hemisphere stroke were asked general
questions about their stay in hospital and were also explicitly
asked whether they could move their limbs. Patients who
consistently reported their motor impairments ‘were grouped
as having adequate understanding of these symptoms’ (p.
315). What is noteworthy is that patients who acknowledged
their motor impairments only when they were specifically
asked if they could move their limbs (fulfilling Bisiach’s
criterion for mild anosognosia) were not classified as having
anosognosia.
Patients who did not report their motor impairments in this

initial stage of questioning were asked to move their affected
limb, and immediately afterwards were asked to reflect on
their performance during their attempt to move the limb. Once
their impairments had been demonstrated, eleven patients
who ‘admitted either that they could not move or had certain
difficulties in moving the affected limb’ (p. 316) were classified
as having neglect of their motor impairments. They did not
acknowledge their impairments in the initial stage of
questioning, they acknowledged their impairments when they
were demonstrated, but usually the acknowledgement was not
lasting. These patients fulfilled Bisiach’s criterion for
moderate anosognosia. Fourteen patients who demonstrated
‘obstinate denial of paresis even when the defect was
concretely shown at least three times’ (p. 316) were classified
as having denial of their motor impairments. These patients
fulfilled Bisiach’s criterion for severe anosognosia. Thus, in
Page 10 of 60
total, 25 of 55 right-hemisphere stroke patients (45%) were

classified as having neglect or denial of motor impairments
(that is, moderate or severe anosognosia, a score of 2 or 3 on
Bisiach’s anosognosia scale).
3.2 Further assessment of motor impairments

The requirement of complete hemiplegia (score of 0 on the
MRC Scale; see Table 23.1) will exclude patients who, despite
retaining some movement of the affected limb (scores of 1 to 4
on the MRC Scale), overestimate their ability to move the limb
(claiming, for example, that the affected limb is just as strong
as the corresponding unaffected limb). In more inclusive
studies of anosognosia for motor impairments, rather than
only anosognosia for complete hemiplegia, a brief yet detailed
motor assessment such as the Motricity Index (or the abridged
version of the Medical Research Council Scale1) can be used
to assess the degree of impairment across different body parts
and movement types.
(p.442) The Motricity Index (MI) for Motor Impairment after

Stroke (Demeurisse, Demol and Robaye, 1980) takes about five
minutes to administer, and consists of six tests providing a
rapid overall assessment of motor impairment:
1 Pinch grip using a 2.5 cm cube between the thumb

and forefinger
2 Elbow flexion from 90° so that the arm touches the
shoulder
3 Shoulder abduction moving the flexed elbow from off
the chest
4 Ankle dorsiflexion with the foot in a plantar flexed
position
5 Knee extension with the foot unsupported and the
knee at 90°
6 Hip flexion with the hip bent at 90° moving the knee
towards the chin.
Medical Research Council grades MRC 0 to MRC 5 are used to

measure movement at each joint, and these six grades are
then converted into weighted scores ranging from 0 (no
movement) to 33 (normal power). Full guidelines for
administration and scoring the Motricity Index are provided by
Collin and Wade (1990, p. 57).2 Patients receive an overall
score from 0 (no motricity) to 100 (normal motricity) for the
upper limb (Tests 1–3) and lower limb (Tests 4–6). As with the
Page 11 of 60
MRC scoring, these grades ‘indicate strength on the basis of a

patient’s ability to activate a muscle group, to move a limb
segment through a range of motion, and to resist the force of
an examiner’ (Bohannon, 1999, p. 59).
The Motricity Index has been shown to have excellent validity

for both the upper and lower limb scales. Upper limb validity
is supported by correlations with grip strength (Sunderland,
Tinson, Bradley and Hewer, 1989), with dynamometer
measures of muscle strength (Bohannon, 1999) and with other
measures of arm function (e.g., Action Research Arm Test:
Hsieh, Hsueh, Chiang and Lin, 1998; Rivermead Motor
Assessment: Collin and Wade, 1990). Lower limb validity is
supported by correlations with dynamometer measures of
muscle strength (Cameron and Bohannon, 2000) and with
other measures of leg function (e.g., Rivermead Motor
Assessment: Collin and Wade, 1990).
(p.443) 3.3 Assessment of the consequences of motor

impairments for activities of daily living
For a more comprehensive profile of a patient’s motor
impairments, encompassing the impairments themselves and
their consequences, the examiner may wish to use a standard
assessment of motor function, such as the Motricity Index,
together with an assessment of fundamental mobility (e.g.,
Rivermead Mobility Index; Collen, Wade, Robb and Bradshaw,
1991) and a measure of functional independence (e.g., Barthel
Activities of Daily Living Index; Collin, Wade, Davies and
Horne, 1988; Mahoney and Barthel, 1965).3 While the
assessment of motor function provides quantitative
information about muscle activation, range of movement and
motor strength, the functional measures provide information
about the impact of motor impairments on mobility and
independence when the patient is engaged in activities of daily
living. Together, these measures provide the basis for
subsequent assessment of whether the patient acknowledges
the impairment itself and appreciates the consequences of the
impairment for activities of daily living.
The Rivermead Mobility Index (RMI) is a short, simple,

clinically relevant and widely used outcome measure, which
focuses on aspects of mobility that are fundamental ‘activities
that most people will undertake if they possibly can’ (Wade,
1992, p. 77). The RMI takes about five minutes to administer,
Page 12 of 60
and consists of one direct observation (Question 5, below) and

fourteen questions about the patient’s ability to perform
common daily movements:
1 Turning over in bed

2 From lying in bed to sitting on edge of bed
3 Sitting balance (on edge of bed without holding on for
10 seconds)
4 From sitting in chair to standing
5 Observe patient standing unsupported for 10 seconds
(no aid and no support)
6 Transfer (from bed to chair and back without help)
7 Walking 10 metres inside (with an aid if needed but
no standby help)
8 Flight of stairs (without help)
9 Walking outside (even ground, without help)
10 Walking 10 metres inside (with no aid or standby
help)
11 Picking items off floor (walking 5 metres to the
dropped item and back)
12 Walking outside (uneven ground, without help)
13 Bathing (in and out of bath or shower unsupervised)
14 Climbing up and down four steps (with no rail, but
with an aid if needed)
15 Running or fast walking (10 metres in 4 seconds).
(p.444) Patients receive a score from 0 to 15, with higher

scores indicating better mobility. The RMI has been shown to
be reliable and sensitive to change during hospital
rehabilitation and it is a valid measure of functional status,
both before and after rehabilitation programmes (Antonucci,
Aprile and Paolucci, 2002; Chen, Hsieh, Lo, Liaw, Chen and
Lin, 2007; Green, Forster and Young, 2001). Good validity has
been demonstrated in correlations with other validated
measures (e.g., Motricity Index for the Lower Limb, Trunk
Control Test and Functional Independence Measure:
Franchignoni, Tesio, Benevolo and Ottonello, 2003).
The Barthel Activities of Daily Living (ADL) Index (Collin et al.,

1988; Mahoney and Barthel, 1965) is probably the most widely
used instrument for measuring functional independence
following stroke, and for most patients the ten questions take
only five minutes to complete:
Page 13 of 60
1 Control bowels
2 Control bladder
3 Grooming (personal care with implement provided:
face, hair, teeth, shave)
4 Toilet use (reach toilet, handle clothes, clean self)
5 Feeding (food provided within reach but not cut up)
6 Transfer (from bed to chair and back)
7 Mobility (with aid e.g., stick; in wheelchair must
negotiate corners/doors unaided)
8 Dressing (selecting clothes and using buttons, zips,
laces)
9 Stairs (ascending and descending)
10 Bathing self (bath or shower, unsupervised and
unaided).
A scale ranging from 0 to 20 in one-point increments is

commonly used, as it has been argued that Mahoney and
Barthel’s original scoring (with a scale ranging from 0 to 100
in five-point increments) may give an exaggerated impression
of accuracy (Collin et al., 1988; Wade and Hewer, 1987). For
each item, the patient is rated as either independent (1, 2, or 3
points, depending on the item), able to perform the given task
with help (0, 1, or 2 points, depending on the item), or cannot
meet the criteria for a higher score (0 points). A maximum
score of 20 (or 100 in the original scoring system) means that
the patient is functionally independent (but not necessarily
that the patient has normal mobility). Full guidelines for
administration and scoring of the Barthel ADL Index, using the
20-point scale, are provided by Collin and colleagues (1988).
Reliability and validity of the Barthel ADL Index as a measure
of disability have been established in a number of studies
(Collin et al., 1988; Green et al., 2001; Wade and Collin, 1988;
Wade and Hewer, 1987).
3.4 Assessment of anosognosia for the consequences of motor

impairments
Collin and colleagues (1988) also investigated four methods of
obtaining information for the Barthel ADL Index:
(a) asking for information from:

— (1) the patient (or a relative) or
(p.445)
Page 14 of 60
— (2) a nurse who had worked with the patient

for at least one shift,
(b) direct observation of the patient, who was tested

either by:
— (3) a trained nurse or
— (4) an occupational therapist.
The findings obtained by the four methods were comparable,

and the authors state ‘the method of obtaining the information
does not appear to be important, but allowance needs to be
made for confused patients if self-reporting is used’ (p. 62).
They found that method (1) was slightly less reliable, in that
the patient’s (or relative’s) report was the most likely not to
agree with the other three methods.
These findings lead us to implement a dual scoring system

when administering the Barthel ADL Index (and also the
Rivermead Mobility Index). Specifically, the system separates
a score based on self-report (that is, by the patient) from a
score based on report by a nurse who had worked with the
patient for at least one shift. On this dual scoring system, the
nurse’s report provides a quick and reliable measure of the
patient’s mobility and independence, while comparison with
the patient’s self-report reveals the extent to which the patient
fails to appreciate the consequences of his or her motor
impairments for activities of daily living.
Summary: A simple assessment of motor impairments using

the MRC Scale, the NIH Stroke Scale, or the Bisiach Motor
Impairment Scale can be combined with a simple assessment
of anosognosia for motor impairments using Bisiach’s
Anosognosia Scale. A diagnosis of anosognosia would be based
on a score of 2 (moderate anosognosia) or 3 (severe
anosognosia) on Bisiach’s Anosognosia Scale. A more
comprehensive assessment of motor impairments and their
consequences (using, for example, the Motricity Index, the
Rivermead Mobility Index, and the Barthel ADL Index) invites
a more nuanced assessment of anosognosia for motor
impairments and, with a dual scoring system for the functional
measures, allows an initial assessment of anosognosia for the
consequences of motor impairments. A diagnosis of
anosognosia would be based on a substantial difference
Page 15 of 60
between the patient’s self-report and the report by a nurse

who had worked with the patient for at least one shift.
4 Assessment of anosognosia: structured interviews

A structured interview can provide important information
concerning the patient’s beliefs — whether the patient
acknowledges his or her motor impairments and whether the
patient appreciates the consequences of those impairments for
activities of daily living. Table 23.2 lists the questions used in
nine structured interviews for which the assessment protocol
has been published. The table reveals the overlap amongst
these interviews, and the manner in which later protocols have
built on earlier ones. For example, the interviews presented by
Nathanson and colleagues (1952), Cutting (1978) and
Starkstein and colleagues (1992) include five questions in
common, two general questions about the reasons for the
patient’s hospitalisation and three questions about the
patient’s motor impairments (see columns 1, 2, and 4 of Table
23.2A and 23.2B). (p.446)
Page 16 of 60
Table 23.2 Questions from Nine Structured Interviews for the Assessment of Anosognosia
Nathanson Cutting Anderson Starkstein Berti et al. Maeshima Feinberg et Marcel et Spinazzola
et al. (1952) (1978) and Tranel et al. (1992) (1996) et al. (1997) al. (2000) al. (2004) et al. (2008)
(1989)
A. General Questions:
Where are √ √
we?
Do you √
have any
trouble?
Why are √ √ √ √ √ √ √ √
you here?
or Why are
you in the
hospital? or
Why are
you now in
the
hospital?
What is the √ √ √ √ √
matter with
you? or
What is
Page 17 of 60
(1989)
wrong with
you?
Is there √
anything
wrong with
you?
If primary √
reason for
hospitalisati
on is not
explicitly
described,
Examiner
asks: Did
you have a
stroke?
B. Acknowledgement of Motor Impairments:
Are you √
paralysed?
How do √
your arms
(legs)
work? Can
Page 18 of 60
(1989)
you move
them
normally?
Both of
them?
Can you √
move your
arms or
legs?
Examiner √
indicates
paralysed
limb: Can
you move
this hand or
foot?
Is there √ √ √
anything
wrong with
it [limb]? or
Is there
anything
Page 19 of 60
(1989)
wrong with
your arm or
leg?
Examiner √
either
points to or
raises the
affected
limb: Is
there
anything
wrong with
it?
Can you √
move it
[limb]?
Raise it?
Is your limb √ √ √
weak,
paralysed,
or numb?
How does
Page 20 of 60
(1989)
your limb
feel?
Examiner √ √ √
holds up
affected
limb: What
is this?
Can you lift √ √

it [arm]?
You clearly
have some
problem
with this?
Examiner √ √
asks patient
to raise
both arms:
Can’t you
see that the
two arms
are not at
Page 21 of 60
(1989)
the same
level?
How well √
do your
arms and
legs work?
Can you √
move your
arms (legs)
normally?
Both of
them?
Is either of √
your arms
(legs)
weak? This
one, that
one?
Do you √
have
weakness
anywhere?
Page 22 of 60
(1989)
Is your arm √
causing you
any
problems?
Does it √
[arm] feel
normal?
Can you √
use it [arm]
as well as
you used
to?
Are you √
fearful
about
losing your
ability to
use your
arm?
The doctors √
tell me that
there is
some
Page 23 of 60
(1989)
paralysis of
your arm.
Do you
agree?
Examiner √
lifts and
drops
patient’s
affected
arm, first in
contralater
al
hemispace,
then in
ipsilateral
hemispace:
It seems
there is
some
weakness.
Do you
agree?
Page 24 of 60
(1989)
Take your √
right arm,
and use it
to lift your
left arm. Is
there any
weakness
of your left
arm?
How is your √ √
left arm
(leg)? Can
you move
it?
If patient √
says he/she
cannot
move arm,
Examiner
asks: Why
can you not
move your
left arm?
Page 25 of 60
(1989)
If patient √
verbally
denies left
upper limb
motor
impairment
, Examiner
asks:
Please,
touch my
hand with
your left
hand. Have
you done it?
Why have
you not
done it? Are
you sure? It
is very
strange
because I
have not
seen your
hand
Page 26 of 60
(1989)
touching
my hand.
C. Appreciation of the Consequences of Motor Impairments:
How do you √
think you
did on
these tests
today?
Based on √
how you
are doing
now, do you
think you
will be able
to return to
your
normal
activities in
the next
several
weeks?
Page 27 of 60
(1989)
In your √
current
state, do
you have
any
problems
with daily
activities
(e.g.,
eating,
dressing,
washing,
getting
about)?
Patient √
asked
whether he
or she can
perform a
range of
‘analytic’
movements
(e.g., put
left hand on
Page 28 of 60
(1989)
left
shoulder,
straighten
knee).
Patient √ √ √
asked to
estimate his
or her
capacity to
perform
unimanual,
bimanual
and bipedal
tasks.
Third- √ √
person
estimate:
Patient
asked to
estimate
examiner’s
capacity to
perform
unimanual,
Page 29 of 60
(1989)
bimanual
and bipedal
tasks if the
examiner
were in the
patient’s
present
state.
Can you √
walk
without any
problem?
Post- √
performanc
e estimate:
Patient
asked to re-
estimate
capacity to
perform
unimanual,
bimanual
and bipedal
tasks (after
Page 30 of 60
(1989)
attempt has
been made
to perform
these
tasks).
D. Anosognosic Phenomena:
Is it a √
nuisance?
How much
trouble
does it
cause you?
What
caused it?
Do you ever √
feel that it
doesn’t
belong? Do
you feel
that it
belongs to
Page 31 of 60
(1989)
someone
else?
Do you feel √
the arm is
strange or
odd?
Has your √
arm or leg
felt strange
in any way?
Have you √
had any
other
strange
sensations?
Do you √
dislike the
arm? Do
you hate it?
Do you √
have strong
Page 32 of 60
(1989)
feelings
about it?
Do you ever √
call it
names?
Do you ever √
feel it
moves
without
your
moving it
yourself?
How is the √
other arm?
Do you ever √
feel a
strange
arm lying
beside you
separate
from the
real arm?
Page 33 of 60
√ Researchers who used the question(s) indicated.
Page 34 of 60
(p.447) (p.448) (p.449) (p.450) It is important to notice that,

although most researchers ask patients whether they are able to
move or raise their limbs, the researcher may or may not ask the
patient actually to attempt the movement. Questions that do
involve a request for the patient to move an affected limb, and
consequently provide a demonstration of the patient’s impairment,
allow the examiner to distinguish moderate from severe
anosognosia (Bisiach et al., 1986) or, equivalently, mere neglect of
motor impairments from full denial of motor impairments
(Willanger et al., 1981).
Some structured interviews investigate the patient’s
appreciation of the consequences of motor impairments for
activities of daily living (see Table 23.2C). Patients who
correctly acknowledge their motor impairments may still fail
to appreciate the consequences of those motor impairments
and so they may overestimate their ability to carry out
everyday activities. In the structured interview of Marcel and
colleagues (2004), patients are specifically asked whether they
have problems with everyday activities of eating, dressing,
washing, and getting about. Since patients with motor
impairments may develop strategies for accomplishing these
tasks, denial of problems with these everyday activities does
not, by itself, amount to unequivocal evidence of anosognosia.
A more sensitive method of detecting anosognosia for the

consequences of motor impairments is to ask patients about
their capacity to perform bimanual and bipedal tasks (Nimmo-
Smith, Marcel and Tegnér, 2005), that is, tasks that involve
both sides of the body. This approach has been used by Berti
and colleagues (1996), Marcel and colleagues (2004) and
Spinazzola and colleagues (Spinazzola, Pia, Folegatti,
Marchetti and Berti, 2008).
However, the patient’s answers to questions about tasks that

are assumed to be bimanual or bipedal may still not provide an
accurate assessment of whether the patient appreciates his or
her limitations. It is strongly recommended that the examiner
should ask patients to demonstrate, or at least describe how
they would execute, any bimanual or bipedal tasks that they
claim to be able to perform. Recently, we assessed a
gentleman with complete right-side hemiplegia. When asked
whether he could attach a handkerchief to a ring by tying a
knot, he responded ‘yes’ and promptly carried out the task —
antecedently classified as bimanual — using his left hand only.
The patient’s affirmative answer to our initial question
Page 35 of 60
whether he could perform the task might have led us to

assume that he was overestimating his abilities and had
anosognosia for the consequences of his motor impairments.
(The ‘tie a knot’ question is a good predictor of consistent
overestimation of bimanual abilities; Nimmo-Smith et al.,
2005.) Only by asking the patient actually to perform the
action did we discover that, having acknowledged his
impairments and appreciated their consequences, he had
developed impressive skills for managing so-called bimanual
tasks with his unaffected left hand.
Patients who, in response to questions, overestimate their

abilities may nevertheless display some partial or implicit
knowledge of their limitations. For example, patients
may make an accurate estimate of the abilities of another
impaired person, even while acknowledging that the other
person’s condition is similar to their own (House and Hodges,
1988). (p.451) Marcel and colleagues (2004) investigated this
phenomenon by asking questions about bimanual and bipedal
tasks in two forms. For example: ‘In your present state, how
well can you tie a knot?’ (first-person form) versus ‘If I were in
your present state, how well would I be able to tie a
knot?’ (third-person form).4 Marcel and colleagues (2004)
found that some patients following right-hemisphere stroke
gave higher estimates in response to the first-person form of
questions than in response to the third-person form (for
discussion, see Vallar and Ronchi, 2006, p. 249). Using a
similar protocol, Berti and colleagues (1996) did not find
differences in patients’ responses to the two forms of the
questions.
The final section of the table (see Table 23.2D) lists questions
on anosognosic phenomena, defined as unusual beliefs or
experiences relating to the affected limbs. These questions are
for the most part taken from Cutting (1978), who assessed a
wide range of phenomena involving the contralesional arm,
such as beliefs about non-belonging of the arm, including
attribution of the arm to another person (somatoparaphrenia)
and experiences of a third arm protruding from the patient’s
own body (supernumerary phantom limb). The structured
interview of Marcel and colleagues (2004) also includes
questions along these lines.
4.1 Occurrence rates for anosognosia
Page 36 of 60
There are substantial differences in reported occurrence rates

for anosognosia (number of patients with anosognosia divided
by study population). Table 23.3 presents the occurrence rates
for those studies that did not use presence (or absence) of
anosognosia, or related pathologies such as unilateral neglect,
as a selection criterion. As can be seen from the table, the
method of assessment of anosognosia varies widely across the
studies (column 1). This variation may contribute to the
differences in reported occurrence rates. Some studies include
both left- and right-hemisphere stroke patients while other
studies include only left-hemisphere or only right-hemisphere
patients (column 3). These differences in study population may
impact on occurrence rates, as may time since stroke (column
4) and the level of motor impairment that is required for entry
to the study (column 5). In addition, as discussed in Section
3.1, reported occurrence rates may depend heavily on the
decision whether to classify patients with a score of 1 on
Bisiach’s Anosognosia Scale as having anosognosia (Baier and
Karnath, 2005). (p.452)
(p.453) (p.454) (p.455) (p.456) 5 A comprehensive

assessment of anosognosia for motor impairments
Page 37 of 60
Table 23.3 Occurrence Rates for Anosognosia in Patients with Left- or Right-Hemisphere Lesions
Method of Published Study Time since Level of motor Occurrence rates for anosognosia: % (number
assessment report population stroke impairment assessed)
Left Right Left and right

hemisphere hemisphere hemisphere
Nathanson et Nathanson et 100 (95 stroke) 1 day to Complete 23.08% (39) 51.35% (37) 36.84% (76)
al. (1952) al. (1952) consecutive several years. hemiplegia.
patients with
hemiplegia; 76
assessed for
anosognosia.
Cutting (1978) Cutting (1978) 100 (96 stroke) Within 8 days. 4-point scale: 13.64% (22) 58.33% (48) 44.29% (70)
patients with slight,
hemiplegia moderate,
over 2-year severe, total.
period in a
General
Hospital; 70
assessed for
anosognosia.
Stone et al. 171 2–3 days. Not selected 5.36% (56) 28.33% (60) 17.24% (116)
(1993) consecutive by motor
stroke impairment.
patients; 116
Page 38 of 60

assessed for
anosognosia.
Willanger et al. Willanger et al. 55 consecutive Not specified. Paresis graded 45.45% (55)*
(1981) (1981) RH-stroke as: slight-
patients over a moderate or
3-year period. marked-severe.
Hier et al. Hier et al. 41 RH-stroke Within 7 days. 6-point scale: 36.59% (41)
(1983) (1983) patients 0 (no
assessed movement) to
consecutively 5 (normal
by Stroke strength).
Service.
Bisiach et al. Bisiach et al. 97 RH Within 37 Severe motor 33.33% (36)*

(1986) (1986) patients; 36 days. impairment.
with complete
hemiplegia
assessed for
anosognosia.
Pederson et al. 566 Within first Not selected 9% 36% 20.85% (566)
(1996) consecutive week. by motor
unselected impairment.
Page 39 of 60

stroke
patients.
Azouvi et al. 206 Average 11.1 4-point scale: 17% (206)

(2002) consecutive weeks. 0 (no deficit) to
RH patients 3 (severe
with first-ever hemiplegia).
stroke.
Beis et al. 89 consecutive Average 10.8 3-point scale: 6.41% (78)

(2004) LH-stroke weeks. 0 (no deficit) to
patients from 2 (severe
19 Centres; 78 hemiplegia).
assessed for
anosognosia.
Baier and 128 Up to 15 days. 6-point scale: Total: 22.66%

Karnath (2005) consecutive 0 (no (128)
stroke patients movement) to Moderate or
with 5 (normal severe: 9.38%
hemiparesis or movement). (128)*
hemiplegia.
Page 40 of 60

Spalletta et al. 50 consecutive Within 3 Not selected 26% (50)*

(2007) RH-stroke months. by motor
inpatients. impairment.
Baier and 79 RH-stroke Within 10 6-point scale: 15.19% (79)*

Karnath (2008) patients with days. 0 (no
left movement) to
hemiparesis or 5 (normal
hemiplegia. movement).
Method of Published Study Time since Level of motor Occurrence rates for anosognosia:% (number

Anderson and Anderson and 32 stroke 3–25 days. Dense 27.77% (18)
Tranel (1989) Tranel (1989) patients hemiparesis.
referred for
neuropsycholo
gical
assessment; 18
with dense
hemiparesis
Page 41 of 60

assessed for
anosognosia.
Wagner and 108 Average 4.9 Not selected 18.1% (108)

Cushman consecutive weeks. by motor
(1994) stroke patients impairment.
from two acute
Neurorehabilit
ation Centres.
Hartman- 60 patients 4–8 weeks. Severe. 23.53% (17) 27.59% (29) 26.09% (46)
Maeir et al. with first-ever
(2001) stroke; 46 with
severe motor
deficit of arm
assessed for
anosognosia.
Starkstein et Starkstein et 80 stroke Approximately Not selected Total: 33.75%

al. (1992) al. (1992) patients 1 week. by motor (80) Moderate
selected from impairment. or severe:
96 consecutive 23.75% (80)*
admissions.
Page 42 of 60

Appelros et al. 377 stroke 1–4 days. Not selected Total: 17.39%
(2002) patients by motor (276)
recruited from impairment. Moderate or
Örebro, severe: 11.96%
Sweden over (276)*
12 months;
276 assessed
for
anosognosia.
Berti et al. Berti et al. 34 chronic Average 60 Complete 26.47% (34)

(1996) (1996) stoke patients days. hemiplegia.
from
Geriatrics,
selected by RH
damage and
complete
hemiplegia.
Maeshima et Maeshima et 50 patients Within 30 Severe or 24% (50)

al. (1997) al. (1997) with RH days. moderate-mild.
cerebral
haemorrhage.
Page 43 of 60

Marcel et al. Marcel et al. 64 stroke Average 79.1 Severe motor Arm: 0% (22) Arm: 28.57% Arm: 18.75%
(2004) (2004) patients days (LH) 55.7 deficit in at Leg: 9.09% (42) (64)
recruited from days (RH). least one limb. (22) Leg: 29.27% Leg: 22.22%
seven ADL: 13.64% (41) (63)
hospitals, (22) ADL: 52.38% ADL: 39.06%
selected by (42) (64)
hemiplegia.
Cocchini et al. Cocchini et al. 33 LH-stroke Average 73.8 4-point scale: 40% (30)
(2009) (2009) patients with days. 0 (normal
motor motor
impairments; performance)
30 patients to
selected as per 3 (complete
reliable hemiplegia).
responses on
the Visual
Analogue Test.
LH = Left Hemisphere; RH = Right Hemisphere; ADL = Activities of Daily Living.
* Moderate or severe anosognosia: The patient did not acknowledge his or her deficits until these were demonstrated (moderate) or
never acknowledged the deficits (severe).
Page 44 of 60
A new structured interview for the assessment of anosognosia

for motor impairments is presented at the end of this chapter.
The approach is theoretically motivated and relatively
comprehensive. The assessment incorporates items from the
interviews presented in Table 23.2 as well as items that build
on earlier protocols. Any assessment of anosognosia depends
on a prior assessment of the patient’s motor impairments and
their consequences and so the structured interview is to be
used alongside assessments of motor impairments and their
functional consequences, such as the Motricity Index, the
Rivermead Mobility Index, and the Barthel Activities of Daily
Living Index (Section 3). A full investigation of anosognosia
must also include assessments of factors that may play a role
in its aetiology such as unilateral neglect, ‘a notable suspect in
anosognosia’ (Vuilleumier, 2004, p. 10), and other factors that
may impact on recovery and rehabilitation.
The new structured interview is made up of four modules. The

first module does not involve any request for the patient
actually to perform tasks using the affected limbs. It includes
questions about the primary reason for hospitalisation (Q1),
about the patient’s acknowledgement of motor impairments
(Q2), and about the patient’s appreciation of the consequences
of his or her motor impairments for activities of daily living
(Q3). It also investigates anosognosic phenomena (Q4).
Although questions about these phenomena have not been
incorporated into most structured interviews, we believe that
they may prove useful for assessment and rehabilitation, since
patients are unlikely to mention these unusual beliefs and
experiences spontaneously.
Thereafter, the structure of the assessment is dictated by the

threefold distinction (explained in Section 2 of this chapter)
between concurrent unawareness of an impairment, failure to
acknowledge the impairment itself, and failure to appreciate
the consequences of the impairment for activities of daily
living. Thus, the second module investigates whether the
patient is concurrently aware of motoric failures of the
affected arm or leg. With vision precluded, the patient is
requested, for the first time, to move his or her limbs (Q5). If
the patient is seated, he or she is requested to raise each arm,
and then both arms, to shoulder level and to raise each leg by
extending it at the knee. If the patient is supine, he or she is
Page 45 of 60
requested to raise each arm, and then both arms, and each leg
from the bed surface, to a position indicated by the examiner.
It is not the primary purpose of this second module to

investigate the patient’s beliefs as to whether he or she is
really able to move the affected limbs. Still less is it intended
to challenge the patient’s beliefs by providing evidence of
failure. Instead, the purpose of the module is to provide
information about the patient’s proprioceptive experience as
he or she tries to move the affected limbs; that is, information
about the patient’s bodily awareness or unawareness of
motoric failures when they occur.5 This is theoretically
important because concurrent (p.457) unawareness of motor
impairments may be a factor in failure to acknowledge those
impairments. It is only at the end of the module, and only if the
patient has reported feeling as if he or she succeeded in
moving the affected limbs (illusory limb movements), that the
examiner asks whether the patient believes that the limbs
really moved. The patient’s beliefs about whether he or she
can move the affected limbs are the focus of the next module.
As we have seen, one of the key aspects of the assessments of

anosognosia by Willanger and colleagues (1981) and Bisiach
and colleagues (1986) is that the patient’s impairment is
demonstrated and the patient is given the opportunity to
reflect on this evidence of failure and to acknowledge his or
her motor impairments. This allows us to distinguish between
moderate and severe anosognosia. The third module
investigates whether the patient acknowledges his or her
motor impairments, both before (prior belief) and after
(posterior belief) an impairment is demonstrated (Q6, raise the
limb, and Q7, maintain the limb in a raised position). In order
that the evidence of failure should be maximally available to
the patient, vision is permitted. All questions are first asked
concerning the unaffected limb. This allows the examiner to
check that the patient understands the task and also provides
a control condition against which responses to questions about
the affected limb can be compared.
The fourth module investigates whether the patient

appreciates the consequences of motor impairments for
activities of daily living. One of the key points in Section 4 of
this chapter is that an investigation of anosognosia for the
consequences of motor impairments should include asking the
patient to perform, or at least describe how they would
Page 46 of 60
perform, various tasks. In this module, first-person and third-

person forms of questions about unimanual, bimanual, and
bipedal tasks are used (Q8) and the patient is asked to rate his
or her abilities both before (prior belief) and after (posterior
belief) actually trying to perform an action (Q9). Some of the
actions involve interaction with objects and so the subsequent
position of the objects provides clear evidence of success or
failure of the attempt.
By testing the patient’s belief revision, the third and fourth

modules assess whether the patient makes appropriate use of
available evidence of his or her limitations. Thus, the second,
third, and fourth modules together could, in principle, go
beyond detecting anosognosia for motor impairments and
provide the beginnings of an explanation of some cases of
anosognosia. The explanation would be of a familiar two-factor
kind in which impairment of immediate bodily experience of
motoric failure, and cognitive impairments that obstruct the
appropriate use of available evidence to update beliefs, would
(p.458) both play a role (Aimola Davies and Davies, 2009;
Aimola Davies et al., 2009; Davies, Aimola Davies and
Coltheart, 2005; Levine, 1990; Levine et al., 1991). As
Vuilleumier says (2004, p. 11): ‘any neurological dysfunction
susceptible to alter the phenomenal experience of a defect
might provide the ground out of which anosognosia can
develop when permissive cognitive factors are also present’.
Page 47 of 60
6 Conclusion
A theoretical framework for this chapter is provided by the
threefold distinction between concurrent unawareness of an
impairment, failure to acknowledge the impairment itself, and
failure to appreciate the consequences of the impairment for
activities of daily living (Section 2). A simple assessment of
anosognosia for motor impairments can be carried out at the
same time as a routine assessment of motor impairments. An
initial assessment of anosognosia for the consequences of
motor impairments can be obtained by using a dual scoring
system with functional measures of mobility and
independence. A more comprehensive assessment of motor
impairments and their consequences invites a correspondingly
more nuanced assessment of anosognosia (Section 3).
We began this chapter with the proposal that a comprehensive

and widely accepted procedure for assessing anosognosia for
motor impairments would contribute to a better understanding
of the many factors in anosognosia and might also lead to
improvement in the clinical management of patients. Building
on published structured interviews (Section 4) and other
protocols, we have presented a theoretically motivated and
relatively comprehensive instrument for assessing
anosognosia (Section 5). We hope that this new structured
interview will contribute to our understanding of the
occurrence, aetiology, time course, and treatment of
anosognosia and that this will lead, in turn, to improved
recovery and rehabilitation for patients.
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Table 23.4 Structured Interview: Anosognosia for

Motor Impairments
Page 54 of 60
Page 55 of 60
Page 56 of 60
Page 57 of 60
(p.463) (p.464) (p.465) (p.466) (p.467)
Notes:
2
Scoring for Test 1:
(0) No movement
(11) Beginnings of prehension (any movement of finger
or thumb)
(19) Able to grip the cube, but not hold it against
gravity (examiner may need to lift wrist)
(22) Able to grip and hold the cube against gravity, but
not against a weak pull
(26) Able to grip and hold the cube against a weak pull,
but weaker than the other side
(33) Normal pinch grip.
Scoring for Tests (2–6) :

(0) No movement
(9) Palpable contraction in muscle, but no movement
(14) Visible movement, but not full range and not
against gravity
(19) Full range of movement against gravity but not
against resistance
(25) Full movement against resistance, but weaker than
the other side
(33) Normal power.
3
Recommended versions of each measure – Motricity Index,
Rivermead Mobility Index and Barthel Activities of Daily Living
Index – can also be found in Measurement in neurological
rehabilitation (Wade, 1992 ).
Page 58 of 60
4
The questions actually used by Marcel and colleagues
(2004,p. 24) were rather more complicated than this. First-
person form:‘In your present state how well, compared with
your normal ability, can you tie a knot? If you can do it as well
as usual, say “ten”. If you cannot do it at all, say
“nought”.’Thirdperson form:‘If I were in your present state,
how well would I be able to tie a knot, compared with my usual
ability? If I could do it as well as usual, say “ten”. If I could not
do it at all, say “nought”.’
5
The second module builds on a protocol used by Marcel and
colleagues (2004 ). In their study, as part of an assessment of
motor function and separately from the main anosognosia
interview, patients were asked to raise each limb with vision
precluded and their performance was rated objectively using
the MRC scale (Table23.1). As soon as the assessment of
motor function was complete,‘patients were asked how much
they had been able to move each arm and each leg’ (p. 23). In
making this postperformance evaluation, patients had to rely
on ‘immediate episodic experience’ provided by
proprioception, since they were blindfolded and no other
feedback was given (p. 32). To the extent that patients gave an
unrealistically high evaluation of their performance in trying
to move their affected limbs, they were judged to be
concurrently unaware of their motoric failure.
(1) The sixteen commonly tested upper and lower limb

movements from the abridged version of the Medical Research
Council Scale are listed below (Guarantors of Brain, 2000, p.
62). Five of these sixteen movements are included in the
Motricity Index for Motor Impairment after Stroke.
(a)) Upper Limb Movements (shoulder abduction; elbow

flexion; elbow extension; radial wrist extension; finger
extension; finger flexion; finger abduction);
(b)) Lower Limb Movements (hip flexion; hip abduction;
hip extension; knee flexion; knee extension; ankle
dorsiflexion; ankle eversion; ankle plantar flexion; big
toe extension).
Page 59 of 60
Page 60 of 60


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Assessment of anosognosia for

motor impairments
Anne M. Aimola Davies
Rebekah C. White
Martin Davies (Contributor Webpage)
DOI:10.1093/acprof:oso/9780199234110.003.023

This chapter begins with a threefold distinction that organizes
the investigation of anosognosia: the distinction between
failure to experience a motor impairment (concurrent
unawareness); failure to acknowledge the impairment itself;
and failure to appreciate the consequences of the impairment.
It then reviews methods for the assessment of motor
impairments and anosognosia for motor impairments including
structured anosognosia interviews that have been published.
improvement in the clinical management of patients. The
chapter presents a structured interview that offers a
Page 1 of 60
theoretically motivated and relatively comprehensive approach

to the assessment of anosognosia for motor impairments.
Keywords: anosognosia, motor impairments, neuropsychological assessments,

structure interview
1 Introduction
Patients with anosognosia fail to acknowledge their motor
impairments. Anosognosia is usually assessed by means of a
structured interview, beginning with questions about general
health and moving to specific questions about the patient’s
motor impairment. A patient whose arm or leg is paralysed or
weak following a stroke may deny the weakness in response to
questions like ‘Is there anything wrong with your arm or leg?’
or ‘Is your limb weak, paralysed, or numb?’ (questions from
Cutting, 1978; Nathanson, Bergman and Gordon, 1952;
Starkstein, Federoff, Price, Leiguarda and Robinson, 1992),
and may continue to deny the impairment even when it has
been demonstrated. The examiner may ask the patient to raise
both arms and then demonstrate to the patient that one arm is
not raised as high as the other. Recognising that a patient has
anosognosia may be relatively straightforward, for example,
when the patient denies outright that there is anything the
matter. In many patients, however, a full assessment will
reveal a more complex profile.
In this chapter, we begin (Section 2) with a threefold

distinction that organises our investigation of anosognosia —
the distinction between failure to experience a motor
impairment (concurrent unawareness), failure to acknowledge
the impairment itself, and failure to appreciate the
consequences of the impairment (Aimola Davies, Davies,
Ogden, Smithson and White, 2009). Then, we review methods
for the assessment of motor impairments and anosognosia for
motor impairments (Section 3) including structured
anosognosia interviews that have been published (Section 4).
improvement in the clinical management of patients (Orfei,
Caltagirone and Spalletta, 2009). We present a structured
Page 2 of 60
interview (Section 5) that offers a theoretically motivated and

relatively comprehensive approach to the assessment of
anosognosia for motor impairments.
(p.437) 2 A threefold distinction

Two ideas figure in the Oxford English Dictionary definition of
anosognosia: ‘unawareness of or failure to acknowledge one’s
hemiplegia or other disability’. Unawareness suggests a failure
of experience (sensation and perception). Failure to
acknowledge suggests a failure of judgement (belief and
assertion). This important distinction is obscured if the term
‘unawareness’ is used interchangeably with ‘anosognosia’. We
regard anosognosia as a failure or pathology of belief: a
mismatch between the patient’s estimate of his or her abilities
and the reality of the impairment. The patient believes that he
or she does not have the impairment despite the fact that it is
clearly present. This incorrect belief will be manifested in the
patient’s failure to acknowledge the impairment verbally in
response to questions.
Consider a hypothetical case of a patient with hemiplegia

following right-hemisphere stroke. When the patient intends to
raise his left arm, proprioception and vision tell him that the
arm is still hanging by his side. When the patient tries to raise
his arm, a comparator within the motor control system detects
a mismatch between the expected movement of the arm and
what actually happens and the patient is alerted to his
paralysis. If the patient directs his attention to the left side of
his body, this only confirms that his left arm has not moved.
This hypothetical patient has immediate experiences —
concurrent awareness — of his motoric failure and these
experiences may lead him to abandon long-held beliefs about
his motor abilities. In contrast, patients with proprioceptive
loss (Levine, 1990), or unilateral neglect (Vuilleumier, 2004),
or with damage to the comparator in the motor control system
(Gold, Adair, Jacobs and Heilman, 1994; Heilman, 1991;
Heilman, Barrett and Adair, 1998), may not fully experience
their motoric failures. They may even seem to experience
motoric success — illusory limb movements (Frith, Blakemore
and Wolpert, 2000; Feinberg, Roane and Ali, 2000; Levine,
Calvanio and Rinn, 1991). Such patients, with concurrent
unawareness of motoric failure, may be more likely to
Page 3 of 60
maintain long-held beliefs that are now incorrect — beliefs

that overestimate their motor abilities.
It is plausible that concurrent unawareness often plays an

important role in the aetiology of anosognosia. But the
distinction between concurrent unawareness (a failure to
experience motoric failures when they occur) and anosognosia
(a failure of belief) is confirmed by thought experiments and
empirical findings (Marcel, Tegnér and Nimmo-Smith, 2004).
In principle, a patient with impaired proprioception might
have no immediate bodily experience of failure to move a
paralysed limb yet, on the basis of other evidence, the patient
might still reach the correct belief about his or her paralysis
(failure of experience without failure of belief). Conversely, a
patient with intact proprioception might have vivid bodily
experiences of failure to move a paralysed limb but, because
the information is not consolidated into more lasting
representations, the patient might fail to reach the correct
belief about his or her paralysis (failure of belief without
failure of experience).
Having an incorrect belief about the severity of an impairment

itself is also distinct from having an incorrect belief about the
seriousness of the consequences of the impairment for
activities of daily living. House and Hodges (1988) present an
example that is relevant to (p.438) this second distinction.
They describe an 89-year-old woman who suffered left-side
paralysis following a right-hemisphere stroke. When she was
examined six months after her stroke, she acknowledged that
her left arm was weak, and weaker than her left leg. When it
was demonstrated to her that her left arm was completely
paralysed and her left leg nearly completely paralysed, she
rated the strength of her left elbow and hand/wrist zero out of
ten and her left hip, knee and ankle/foot two out of ten. But
even while she acknowledged her motor impairments she
failed to appreciate their consequences, ‘she insisted that she
could walk upstairs unaided if she were allowed to’ (whereas,
in reality, she was restricted to a wheelchair) (House and
Hodges, 1988, p. 113). Marcel and colleagues (2004) also
report several patients who acknowledged that their left arm
was paralysed yet overestimated their ability to carry out
bimanual tasks such as tying a knot, clapping hands, or
shuffling cards. We might describe such patients as having
anosognosia for the consequences of their motor impairment
but not anosognosia for the impairment itself. They
Page 4 of 60
overestimate their ability to carry out activities of daily living

even if they do not, strictly speaking, overestimate their motor
abilities.
Thus, we reach the threefold distinction between concurrent

unawareness of an impairment, failure to acknowledge the
impairment itself, and failure to appreciate the consequences
of the impairment for activities of daily living. The first is a
failure of experience; the second and third are both failures of
belief.
In cases of mild motor impairment, where patients have

considerable residual movement in their impaired limbs, there
is less room for overestimation of motor abilities. It may be
difficult to classify such patients as having substantially
incorrect beliefs about their motor abilities. Even mild motor
impairments can, however, have serious consequences for
activities of daily living such as walking, washing, dressing,
grooming, and feeding. So patients who do not have complete
hemiplegia may still have dramatically incorrect beliefs about
their ability to carry out everyday activities. Assessment of
anosognosia, considered as a pathology of belief, should
investigate both failure to acknowledge the motor impairment
itself and failure to appreciate its consequences. Assessment
of the causes of anosognosia should extend to investigation of
concurrent unawareness of motoric failure.
3 Assessment of motor impairments and anosognosia

Before one can assess whether a patient has anosognosia for
motor impairments, it is necessary to establish that the patient
does have a motor impairment. In fact, some researchers (e.g.,
Berti, Spinazzola, Pia and Rabuffetti, 2007) have argued that
only patients with complete hemiplegia should be included in
studies of anosognosia because, otherwise, the patient’s belief
that he or she can move the affected limbs is at least partly
correct (see also Berti, Làdavas and Della Corte, 1996;
Bisiach, Vallar, Perani, Papagno and Berti, 1986; for
discussion, see Vallar and Ronchi, 2006, pp. 252–3).
3.1 Simple assessment of motor impairments and anosognosia

We now outline a procedure for establishing that the patient
has a motor impairment. If the primary purpose is to identify
patients with complete hemiplegia then a simple assessment
(p.439) of motor performance is sufficient. The examiner
might, for example, ask the patient to raise the affected limb,
Page 5 of 60
or to maintain a raised position following passive elevation by

the examiner. Three ordinal rating scales that can be used to
assess patient performance are presented in Table 23.1:
Medical Research Council (MRC) Scale (Guarantors of Brain,
2000), National Institute of Health (NIH) Stroke Scale (Brott,
Adams, Olinger, Marler, Barsan, Biller et al., 1989; Goldstein,
Bertels and Davis, 1989; Lyden, Lu, Levine, Brott and
Broderick, 2001), and the Bisiach Motor Impairment Scale
(Bisiach et al., 1986). Complete plegia corresponds to a score
of 0 on the MRC Scale, 4 on the NIH scale, and 3 on the
Bisiach scale. All three scales have been used in previous
studies of anosognosia.
Alongside the Bisiach Motor Impairment Scale (see Table

23.1), Bisiach and colleagues (Bisiach et al., 1986) introduced
the Bisiach Anosognosia Scale. A four-point scale is used for
assessment of anosognosia, ranging from 0 (no anosognosia)
to 3 (severe anosognosia):
0 The disorder is spontaneously reported or mentioned

by the patient following a general question about his
complaints (no anosognosia)
1 The disorder is reported only following a specific
question about the strength of the patient’s affected
limbs (mild anosognosia)
2 The disorder is acknowledged only after its
demonstration through routine techniques of
neurological examination (moderate anosognosia)
3 No acknowledgement of the disorder can be obtained
(severe anosognosia).
The distinction between moderate and severe anosognosia

depends on whether or not the patient acknowledges the
disorder ‘after its demonstration through routine techniques of
neurological examination’. This demonstration would be
provided by the assessment of motor impairments mentioned
in the previous paragraph. In the case of a patient with a score
of 3 for motor impairment of the left arm according to the
Bisiach Motor Impairment Scale, the demonstration would be
provided by the patient’s raised arm falling to the bed surface
within five seconds (see Table 23.1).
Many studies (including Bisiach et al., 1986; see also Baier and
Karnath, 2005; Berti, Bottini, Gandola, Pia, Smania, Stracciari
et al., 2005; Karnath, Baier and Nägele, 2005; Spalletta, Serra,
Page 6 of 60
Fadda, Ripa, Bria and Caltagirone, 2007) classify patients as

having anosognosia only if they receive a score of 2 (moderate
anosognosia) or 3 (severe anosognosia). In a recent study of
128 acute left- and right-hemisphere stroke patients, Baier and
Karnath (2005) found that twelve patients (9%) had a score of
2 or 3 (moderate or severe anosognosia). They also found that
sixteen of the seventeen patients with a score of 1 (mild
anosognosia) spontaneously mentioned other neurological
deficits or symptoms of stroke when asked a general question
and immediately acknowledged their motor impairments when
asked specifically about the strength of their limbs. Baier and
Karnath proposed that these patients had no problem
accepting their motor impairments but simply mentioned
‘subjectively more prominent’ symptoms (p. 361) in response
to a general question. The authors therefore argued that
patients with a score of 1 on Bisiach’s Anosognosia Scale
should not be classified as having anosognosia. (p.440)
Table 23.1 Assessment of Motor Impairments
Medical Upper limb: 5. Normal power

Research The patient 4. Active movement
Council abducts the against gravity and
(MRC) upper arm resistance:
Scale* against 4+ strong
resistance. resistance
(Guarantors of 4
Brain, 2000, moderate
Fig. 21). resistance
Lower limb: 4 - slight
The patient lies resistance
on his or her
back and flexes 3. Active movement
the thigh at the against gravity
hip against 2. Active movement
resistance with with gravity
the leg flexed at eliminated
the knee and 1. Flicker or trace of
hip (Guarantors contraction
of Brain, 2000, 0. No contraction
Fig. 70).
Page 7 of 60
National Upper limb: 0. No drift; arm holds

Institute of The arms are 90° (or 45°) for full
Health placed in the 10 seconds
(NIH) appropriate 1. Drift; arm holds
Stroke position: arms 90° (or 45°) but drifts
Scale outstretched down before full 10
(palms down) at seconds; does not hit
90° if sitting, or bed or other support
at 45° if supine. 2. Some effort
Full effort is against gravity; arm
requested for cannot get to or
10 seconds. If maintain (if cued) 90°
consciousness (or 45°), drifts down
or to bed but has some
comprehension effort against gravity
are abnormal, 3. No effort against
cue patient by gravity; arm falls
actively lifting 4. No movement of
arms into arm
position as
request for 0. No drift; leg holds
effort is orally 30° position for full 5
given. seconds
Lower limb: 1. Drift; leg falls by
The leg is the end of the 5-
placed in the second period but
appropriate does not hit bed
position: while 2. Some effort
supine, the against gravity; leg
patient is asked falls to bed by 5
to maintain seconds, but has
weaker leg at some effort against
30° for 5 gravity
seconds. If 3. No effort against
consciousness gravity; leg falls to
or bed immediately
comprehension 4. No movement of
are abnormal, leg
cue patient by
actively lifting
the leg into
position as
Page 8 of 60

request for
effort is orally
given.
Bisiach Upper limb: 0. No defects or

Motor The supine minimal defects not
Impairment patient is asked scorable as 1
Scale to hold the 1. Appearance of at
following least one of the
position for 30 following signs:
seconds: arm finger
flexed at 45°, abduction,
forearm pronation
extended and of the
supinated, forearm,
fingers lowering
abducted. of limb
Lower limb: without
The supine reaching
patient is asked bed
to hold the surface
following within 15
position for 30 seconds
seconds: thigh
flexed at 90°, 2. Limb lowers and
leg flexed at reaches bed surface
90°. within 15 seconds
3. Limb reaches bed
surface within 5
seconds
0. No defects or
minimal defects not
scorable as 1
1. Lowering of limb
without reaching bed
surface within 15
seconds
2. Limb lowers and
reaches bed surface
within 15 seconds
Page 9 of 60

3. Limb reaches bed
surface within 5
seconds
*Medical Research Council Scale is different in two ways

from the NIH Stroke Scale and the Bisiach Motor
Impairment Scale: the assessment is for raising the limb (as
opposed to maintaining a raised limb) and scoring is in the
opposite direction, so that higher scores indicate better
motor function.
(p.441) This recent discussion of ‘mild anosognosia’ recalls

an insightful and perhaps insufficiently recognised
contribution to the field by Willanger, Danielsen and Ankerhus
(1981). In their study, 55 patients admitted to hospital
following right-hemisphere stroke were asked general
questions about their stay in hospital and were also explicitly
asked whether they could move their limbs. Patients who
consistently reported their motor impairments ‘were grouped
as having adequate understanding of these symptoms’ (p.
315). What is noteworthy is that patients who acknowledged
their motor impairments only when they were specifically
asked if they could move their limbs (fulfilling Bisiach’s
criterion for mild anosognosia) were not classified as having
anosognosia.
Patients who did not report their motor impairments in this

initial stage of questioning were asked to move their affected
limb, and immediately afterwards were asked to reflect on
their performance during their attempt to move the limb. Once
their impairments had been demonstrated, eleven patients
who ‘admitted either that they could not move or had certain
difficulties in moving the affected limb’ (p. 316) were classified
as having neglect of their motor impairments. They did not
acknowledge their impairments in the initial stage of
questioning, they acknowledged their impairments when they
were demonstrated, but usually the acknowledgement was not
lasting. These patients fulfilled Bisiach’s criterion for
moderate anosognosia. Fourteen patients who demonstrated
‘obstinate denial of paresis even when the defect was
concretely shown at least three times’ (p. 316) were classified
as having denial of their motor impairments. These patients
fulfilled Bisiach’s criterion for severe anosognosia. Thus, in
Page 10 of 60
total, 25 of 55 right-hemisphere stroke patients (45%) were

classified as having neglect or denial of motor impairments
(that is, moderate or severe anosognosia, a score of 2 or 3 on
Bisiach’s anosognosia scale).
3.2 Further assessment of motor impairments

The requirement of complete hemiplegia (score of 0 on the
MRC Scale; see Table 23.1) will exclude patients who, despite
retaining some movement of the affected limb (scores of 1 to 4
on the MRC Scale), overestimate their ability to move the limb
(claiming, for example, that the affected limb is just as strong
as the corresponding unaffected limb). In more inclusive
studies of anosognosia for motor impairments, rather than
only anosognosia for complete hemiplegia, a brief yet detailed
motor assessment such as the Motricity Index (or the abridged
version of the Medical Research Council Scale1) can be used
to assess the degree of impairment across different body parts
and movement types.
(p.442) The Motricity Index (MI) for Motor Impairment after

Stroke (Demeurisse, Demol and Robaye, 1980) takes about five
minutes to administer, and consists of six tests providing a
rapid overall assessment of motor impairment:
1 Pinch grip using a 2.5 cm cube between the thumb

and forefinger
2 Elbow flexion from 90° so that the arm touches the
shoulder
3 Shoulder abduction moving the flexed elbow from off
the chest
4 Ankle dorsiflexion with the foot in a plantar flexed
position
5 Knee extension with the foot unsupported and the
knee at 90°
6 Hip flexion with the hip bent at 90° moving the knee
towards the chin.
Medical Research Council grades MRC 0 to MRC 5 are used to

measure movement at each joint, and these six grades are
then converted into weighted scores ranging from 0 (no
movement) to 33 (normal power). Full guidelines for
administration and scoring the Motricity Index are provided by
Collin and Wade (1990, p. 57).2 Patients receive an overall
score from 0 (no motricity) to 100 (normal motricity) for the
upper limb (Tests 1–3) and lower limb (Tests 4–6). As with the
Page 11 of 60
MRC scoring, these grades ‘indicate strength on the basis of a

patient’s ability to activate a muscle group, to move a limb
segment through a range of motion, and to resist the force of
an examiner’ (Bohannon, 1999, p. 59).
The Motricity Index has been shown to have excellent validity

for both the upper and lower limb scales. Upper limb validity
is supported by correlations with grip strength (Sunderland,
Tinson, Bradley and Hewer, 1989), with dynamometer
measures of muscle strength (Bohannon, 1999) and with other
measures of arm function (e.g., Action Research Arm Test:
Hsieh, Hsueh, Chiang and Lin, 1998; Rivermead Motor
Assessment: Collin and Wade, 1990). Lower limb validity is
supported by correlations with dynamometer measures of
muscle strength (Cameron and Bohannon, 2000) and with
other measures of leg function (e.g., Rivermead Motor
Assessment: Collin and Wade, 1990).
(p.443) 3.3 Assessment of the consequences of motor

impairments for activities of daily living
For a more comprehensive profile of a patient’s motor
impairments, encompassing the impairments themselves and
their consequences, the examiner may wish to use a standard
assessment of motor function, such as the Motricity Index,
together with an assessment of fundamental mobility (e.g.,
Rivermead Mobility Index; Collen, Wade, Robb and Bradshaw,
1991) and a measure of functional independence (e.g., Barthel
Activities of Daily Living Index; Collin, Wade, Davies and
Horne, 1988; Mahoney and Barthel, 1965).3 While the
assessment of motor function provides quantitative
information about muscle activation, range of movement and
motor strength, the functional measures provide information
about the impact of motor impairments on mobility and
independence when the patient is engaged in activities of daily
living. Together, these measures provide the basis for
subsequent assessment of whether the patient acknowledges
the impairment itself and appreciates the consequences of the
impairment for activities of daily living.
The Rivermead Mobility Index (RMI) is a short, simple,

clinically relevant and widely used outcome measure, which
focuses on aspects of mobility that are fundamental ‘activities
that most people will undertake if they possibly can’ (Wade,
1992, p. 77). The RMI takes about five minutes to administer,
Page 12 of 60
and consists of one direct observation (Question 5, below) and

fourteen questions about the patient’s ability to perform
common daily movements:
1 Turning over in bed

2 From lying in bed to sitting on edge of bed
3 Sitting balance (on edge of bed without holding on for
10 seconds)
4 From sitting in chair to standing
5 Observe patient standing unsupported for 10 seconds
(no aid and no support)
6 Transfer (from bed to chair and back without help)
7 Walking 10 metres inside (with an aid if needed but
no standby help)
8 Flight of stairs (without help)
9 Walking outside (even ground, without help)
10 Walking 10 metres inside (with no aid or standby
help)
11 Picking items off floor (walking 5 metres to the
dropped item and back)
12 Walking outside (uneven ground, without help)
13 Bathing (in and out of bath or shower unsupervised)
14 Climbing up and down four steps (with no rail, but
with an aid if needed)
15 Running or fast walking (10 metres in 4 seconds).
(p.444) Patients receive a score from 0 to 15, with higher

scores indicating better mobility. The RMI has been shown to
be reliable and sensitive to change during hospital
rehabilitation and it is a valid measure of functional status,
both before and after rehabilitation programmes (Antonucci,
Aprile and Paolucci, 2002; Chen, Hsieh, Lo, Liaw, Chen and
Lin, 2007; Green, Forster and Young, 2001). Good validity has
been demonstrated in correlations with other validated
measures (e.g., Motricity Index for the Lower Limb, Trunk
Control Test and Functional Independence Measure:
Franchignoni, Tesio, Benevolo and Ottonello, 2003).
The Barthel Activities of Daily Living (ADL) Index (Collin et al.,

1988; Mahoney and Barthel, 1965) is probably the most widely
used instrument for measuring functional independence
following stroke, and for most patients the ten questions take
only five minutes to complete:
Page 13 of 60
1 Control bowels
2 Control bladder
3 Grooming (personal care with implement provided:
face, hair, teeth, shave)
4 Toilet use (reach toilet, handle clothes, clean self)
5 Feeding (food provided within reach but not cut up)
6 Transfer (from bed to chair and back)
7 Mobility (with aid e.g., stick; in wheelchair must
negotiate corners/doors unaided)
8 Dressing (selecting clothes and using buttons, zips,
laces)
9 Stairs (ascending and descending)
10 Bathing self (bath or shower, unsupervised and
unaided).
A scale ranging from 0 to 20 in one-point increments is

commonly used, as it has been argued that Mahoney and
Barthel’s original scoring (with a scale ranging from 0 to 100
in five-point increments) may give an exaggerated impression
of accuracy (Collin et al., 1988; Wade and Hewer, 1987). For
each item, the patient is rated as either independent (1, 2, or 3
points, depending on the item), able to perform the given task
with help (0, 1, or 2 points, depending on the item), or cannot
meet the criteria for a higher score (0 points). A maximum
score of 20 (or 100 in the original scoring system) means that
the patient is functionally independent (but not necessarily
that the patient has normal mobility). Full guidelines for
administration and scoring of the Barthel ADL Index, using the
20-point scale, are provided by Collin and colleagues (1988).
Reliability and validity of the Barthel ADL Index as a measure
of disability have been established in a number of studies
(Collin et al., 1988; Green et al., 2001; Wade and Collin, 1988;
Wade and Hewer, 1987).
3.4 Assessment of anosognosia for the consequences of motor

impairments
Collin and colleagues (1988) also investigated four methods of
obtaining information for the Barthel ADL Index:
(a) asking for information from:

— (1) the patient (or a relative) or
(p.445)
Page 14 of 60
— (2) a nurse who had worked with the patient

for at least one shift,
(b) direct observation of the patient, who was tested

either by:
— (3) a trained nurse or
— (4) an occupational therapist.
The findings obtained by the four methods were comparable,

and the authors state ‘the method of obtaining the information
does not appear to be important, but allowance needs to be
made for confused patients if self-reporting is used’ (p. 62).
They found that method (1) was slightly less reliable, in that
the patient’s (or relative’s) report was the most likely not to
agree with the other three methods.
These findings lead us to implement a dual scoring system

when administering the Barthel ADL Index (and also the
Rivermead Mobility Index). Specifically, the system separates
a score based on self-report (that is, by the patient) from a
score based on report by a nurse who had worked with the
patient for at least one shift. On this dual scoring system, the
nurse’s report provides a quick and reliable measure of the
patient’s mobility and independence, while comparison with
the patient’s self-report reveals the extent to which the patient
fails to appreciate the consequences of his or her motor
impairments for activities of daily living.
Summary: A simple assessment of motor impairments using

the MRC Scale, the NIH Stroke Scale, or the Bisiach Motor
Impairment Scale can be combined with a simple assessment
of anosognosia for motor impairments using Bisiach’s
Anosognosia Scale. A diagnosis of anosognosia would be based
on a score of 2 (moderate anosognosia) or 3 (severe
anosognosia) on Bisiach’s Anosognosia Scale. A more
comprehensive assessment of motor impairments and their
consequences (using, for example, the Motricity Index, the
Rivermead Mobility Index, and the Barthel ADL Index) invites
a more nuanced assessment of anosognosia for motor
impairments and, with a dual scoring system for the functional
measures, allows an initial assessment of anosognosia for the
consequences of motor impairments. A diagnosis of
anosognosia would be based on a substantial difference
Page 15 of 60
between the patient’s self-report and the report by a nurse

who had worked with the patient for at least one shift.
4 Assessment of anosognosia: structured interviews

A structured interview can provide important information
concerning the patient’s beliefs — whether the patient
acknowledges his or her motor impairments and whether the
patient appreciates the consequences of those impairments for
activities of daily living. Table 23.2 lists the questions used in
nine structured interviews for which the assessment protocol
has been published. The table reveals the overlap amongst
these interviews, and the manner in which later protocols have
built on earlier ones. For example, the interviews presented by
Nathanson and colleagues (1952), Cutting (1978) and
Starkstein and colleagues (1992) include five questions in
common, two general questions about the reasons for the
patient’s hospitalisation and three questions about the
patient’s motor impairments (see columns 1, 2, and 4 of Table
23.2A and 23.2B). (p.446)
Page 16 of 60
Table 23.2 Questions from Nine Structured Interviews for the Assessment of Anosognosia
(1989)
A. General Questions:
Where are √ √
we?
Do you √
have any
trouble?
Why are √ √ √ √ √ √ √ √
you here?
or Why are
you in the
hospital? or
Why are
you now in
the
hospital?
What is the √ √ √ √ √
matter with
you? or
What is
Page 17 of 60
(1989)
wrong with
you?
Is there √
anything
wrong with
you?
If primary √
reason for
hospitalisati
on is not
explicitly
described,
Examiner
asks: Did
you have a
stroke?
B. Acknowledgement of Motor Impairments:
Are you √
paralysed?
How do √
your arms
(legs)
work? Can
Page 18 of 60
(1989)
you move
them
normally?
Both of
them?
Can you √
move your
arms or
legs?
Examiner √
indicates
paralysed
limb: Can
you move
this hand or
foot?
Is there √ √ √
anything
wrong with
it [limb]? or
Is there
anything
Page 19 of 60
(1989)
wrong with
your arm or
leg?
Examiner √
either
points to or
raises the
affected
limb: Is
there
anything
wrong with
it?
Can you √
move it
[limb]?
Raise it?
Is your limb √ √ √
weak,
paralysed,
or numb?
How does
Page 20 of 60
(1989)
your limb
feel?
Examiner √ √ √
holds up
affected
limb: What
is this?
Can you lift √ √

it [arm]?
You clearly
have some
problem
with this?
Examiner √ √
asks patient
to raise
both arms:
Can’t you
see that the
two arms
are not at
Page 21 of 60
(1989)
the same
level?
How well √
do your
arms and
legs work?
Can you √
move your
arms (legs)
normally?
Both of
them?
Is either of √
your arms
(legs)
weak? This
one, that
one?
Do you √
have
weakness
anywhere?
Page 22 of 60
(1989)
Is your arm √
causing you
any
problems?
Does it √
[arm] feel
normal?
Can you √
use it [arm]
as well as
you used
to?
Are you √
fearful
about
losing your
ability to
use your
arm?
The doctors √
tell me that
there is
some
Page 23 of 60
(1989)
paralysis of
your arm.
Do you
agree?
Examiner √
lifts and
drops
patient’s
affected
arm, first in
contralater
al
hemispace,
then in
ipsilateral
hemispace:
It seems
there is
some
weakness.
Do you
agree?
Page 24 of 60
(1989)
Take your √
right arm,
and use it
to lift your
left arm. Is
there any
weakness
of your left
arm?
How is your √ √
left arm
(leg)? Can
you move
it?
If patient √
says he/she
cannot
move arm,
Examiner
asks: Why
can you not
move your
left arm?
Page 25 of 60
(1989)
If patient √
verbally
denies left
upper limb
motor
impairment
, Examiner
asks:
Please,
touch my
hand with
your left
hand. Have
you done it?
Why have
you not
done it? Are
you sure? It
is very
strange
because I
have not
seen your
hand
Page 26 of 60
(1989)
touching
my hand.
C. Appreciation of the Consequences of Motor Impairments:
How do you √
think you
did on
these tests
today?
Based on √
how you
are doing
now, do you
think you
will be able
to return to
your
normal
activities in
the next
several
weeks?
Page 27 of 60
(1989)
In your √
current
state, do
you have
any
problems
with daily
activities
(e.g.,
eating,
dressing,
washing,
getting
about)?
Patient √
asked
whether he
or she can
perform a
range of
‘analytic’
movements
(e.g., put
left hand on
Page 28 of 60
(1989)
left
shoulder,
straighten
knee).
Patient √ √ √
asked to
estimate his
or her
capacity to
perform
unimanual,
bimanual
and bipedal
tasks.
Third- √ √
person
estimate:
Patient
asked to
estimate
examiner’s
capacity to
perform
unimanual,
Page 29 of 60
(1989)
bimanual
and bipedal
tasks if the
examiner
were in the
patient’s
present
state.
Can you √
walk
without any
problem?
Post- √
performanc
e estimate:
Patient
asked to re-
estimate
capacity to
perform
unimanual,
bimanual
and bipedal
tasks (after
Page 30 of 60
(1989)
attempt has
been made
to perform
these
tasks).
D. Anosognosic Phenomena:
Is it a √
nuisance?
How much
trouble
does it
cause you?
What
caused it?
Do you ever √
feel that it
doesn’t
belong? Do
you feel
that it
belongs to
Page 31 of 60
(1989)
someone
else?
Do you feel √
the arm is
strange or
odd?
Has your √
arm or leg
felt strange
in any way?
Have you √
had any
other
strange
sensations?
Do you √
dislike the
arm? Do
you hate it?
Do you √
have strong
Page 32 of 60
(1989)
feelings
about it?
Do you ever √
call it
names?
Do you ever √
feel it
moves
without
your
moving it
yourself?
How is the √
other arm?
Do you ever √
feel a
strange
arm lying
beside you
separate
from the
real arm?
Page 33 of 60
√ Researchers who used the question(s) indicated.
Page 34 of 60
(p.447) (p.448) (p.449) (p.450) It is important to notice that,

although most researchers ask patients whether they are able to
move or raise their limbs, the researcher may or may not ask the
patient actually to attempt the movement. Questions that do
involve a request for the patient to move an affected limb, and
consequently provide a demonstration of the patient’s impairment,
allow the examiner to distinguish moderate from severe
anosognosia (Bisiach et al., 1986) or, equivalently, mere neglect of
motor impairments from full denial of motor impairments
(Willanger et al., 1981).
Some structured interviews investigate the patient’s
appreciation of the consequences of motor impairments for
activities of daily living (see Table 23.2C). Patients who
correctly acknowledge their motor impairments may still fail
to appreciate the consequences of those motor impairments
and so they may overestimate their ability to carry out
everyday activities. In the structured interview of Marcel and
colleagues (2004), patients are specifically asked whether they
have problems with everyday activities of eating, dressing,
washing, and getting about. Since patients with motor
impairments may develop strategies for accomplishing these
tasks, denial of problems with these everyday activities does
not, by itself, amount to unequivocal evidence of anosognosia.
A more sensitive method of detecting anosognosia for the

consequences of motor impairments is to ask patients about
their capacity to perform bimanual and bipedal tasks (Nimmo-
Smith, Marcel and Tegnér, 2005), that is, tasks that involve
both sides of the body. This approach has been used by Berti
and colleagues (1996), Marcel and colleagues (2004) and
Spinazzola and colleagues (Spinazzola, Pia, Folegatti,
Marchetti and Berti, 2008).
However, the patient’s answers to questions about tasks that

are assumed to be bimanual or bipedal may still not provide an
accurate assessment of whether the patient appreciates his or
her limitations. It is strongly recommended that the examiner
should ask patients to demonstrate, or at least describe how
they would execute, any bimanual or bipedal tasks that they
claim to be able to perform. Recently, we assessed a
gentleman with complete right-side hemiplegia. When asked
whether he could attach a handkerchief to a ring by tying a
knot, he responded ‘yes’ and promptly carried out the task —
antecedently classified as bimanual — using his left hand only.
The patient’s affirmative answer to our initial question
Page 35 of 60
whether he could perform the task might have led us to

assume that he was overestimating his abilities and had
anosognosia for the consequences of his motor impairments.
(The ‘tie a knot’ question is a good predictor of consistent
overestimation of bimanual abilities; Nimmo-Smith et al.,
2005.) Only by asking the patient actually to perform the
action did we discover that, having acknowledged his
impairments and appreciated their consequences, he had
developed impressive skills for managing so-called bimanual
tasks with his unaffected left hand.
Patients who, in response to questions, overestimate their

abilities may nevertheless display some partial or implicit
knowledge of their limitations. For example, patients
may make an accurate estimate of the abilities of another
impaired person, even while acknowledging that the other
person’s condition is similar to their own (House and Hodges,
1988). (p.451) Marcel and colleagues (2004) investigated this
phenomenon by asking questions about bimanual and bipedal
tasks in two forms. For example: ‘In your present state, how
well can you tie a knot?’ (first-person form) versus ‘If I were in
your present state, how well would I be able to tie a
knot?’ (third-person form).4 Marcel and colleagues (2004)
found that some patients following right-hemisphere stroke
gave higher estimates in response to the first-person form of
questions than in response to the third-person form (for
discussion, see Vallar and Ronchi, 2006, p. 249). Using a
similar protocol, Berti and colleagues (1996) did not find
differences in patients’ responses to the two forms of the
questions.
The final section of the table (see Table 23.2D) lists questions
on anosognosic phenomena, defined as unusual beliefs or
experiences relating to the affected limbs. These questions are
for the most part taken from Cutting (1978), who assessed a
wide range of phenomena involving the contralesional arm,
such as beliefs about non-belonging of the arm, including
attribution of the arm to another person (somatoparaphrenia)
and experiences of a third arm protruding from the patient’s
own body (supernumerary phantom limb). The structured
interview of Marcel and colleagues (2004) also includes
questions along these lines.
4.1 Occurrence rates for anosognosia
Page 36 of 60
There are substantial differences in reported occurrence rates

for anosognosia (number of patients with anosognosia divided
by study population). Table 23.3 presents the occurrence rates
for those studies that did not use presence (or absence) of
anosognosia, or related pathologies such as unilateral neglect,
as a selection criterion. As can be seen from the table, the
method of assessment of anosognosia varies widely across the
studies (column 1). This variation may contribute to the
differences in reported occurrence rates. Some studies include
both left- and right-hemisphere stroke patients while other
studies include only left-hemisphere or only right-hemisphere
patients (column 3). These differences in study population may
impact on occurrence rates, as may time since stroke (column
4) and the level of motor impairment that is required for entry
to the study (column 5). In addition, as discussed in Section
3.1, reported occurrence rates may depend heavily on the
decision whether to classify patients with a score of 1 on
Bisiach’s Anosognosia Scale as having anosognosia (Baier and
Karnath, 2005). (p.452)
(p.453) (p.454) (p.455) (p.456) 5 A comprehensive

assessment of anosognosia for motor impairments
Page 37 of 60
Table 23.3 Occurrence Rates for Anosognosia in Patients with Left- or Right-Hemisphere Lesions

Nathanson et Nathanson et 100 (95 stroke) 1 day to Complete 23.08% (39) 51.35% (37) 36.84% (76)
al. (1952) al. (1952) consecutive several years. hemiplegia.
patients with
hemiplegia; 76
assessed for
anosognosia.
Cutting (1978) Cutting (1978) 100 (96 stroke) Within 8 days. 4-point scale: 13.64% (22) 58.33% (48) 44.29% (70)
patients with slight,
hemiplegia moderate,
over 2-year severe, total.
period in a
General
Hospital; 70
assessed for
anosognosia.
Stone et al. 171 2–3 days. Not selected 5.36% (56) 28.33% (60) 17.24% (116)
(1993) consecutive by motor
stroke impairment.
patients; 116
Page 38 of 60

assessed for
anosognosia.
Willanger et al. Willanger et al. 55 consecutive Not specified. Paresis graded 45.45% (55)*
(1981) (1981) RH-stroke as: slight-
patients over a moderate or
3-year period. marked-severe.
Hier et al. Hier et al. 41 RH-stroke Within 7 days. 6-point scale: 36.59% (41)
(1983) (1983) patients 0 (no
assessed movement) to
consecutively 5 (normal
by Stroke strength).
Service.
Bisiach et al. Bisiach et al. 97 RH Within 37 Severe motor 33.33% (36)*

(1986) (1986) patients; 36 days. impairment.
with complete
hemiplegia
assessed for
anosognosia.
Pederson et al. 566 Within first Not selected 9% 36% 20.85% (566)
(1996) consecutive week. by motor
unselected impairment.
Page 39 of 60

stroke
patients.
Azouvi et al. 206 Average 11.1 4-point scale: 17% (206)

(2002) consecutive weeks. 0 (no deficit) to
RH patients 3 (severe
with first-ever hemiplegia).
stroke.
Beis et al. 89 consecutive Average 10.8 3-point scale: 6.41% (78)

(2004) LH-stroke weeks. 0 (no deficit) to
patients from 2 (severe
19 Centres; 78 hemiplegia).
assessed for
anosognosia.
Baier and 128 Up to 15 days. 6-point scale: Total: 22.66%

Karnath (2005) consecutive 0 (no (128)
stroke patients movement) to Moderate or
with 5 (normal severe: 9.38%
hemiparesis or movement). (128)*
hemiplegia.
Page 40 of 60

Spalletta et al. 50 consecutive Within 3 Not selected 26% (50)*

(2007) RH-stroke months. by motor
inpatients. impairment.
Baier and 79 RH-stroke Within 10 6-point scale: 15.19% (79)*

Karnath (2008) patients with days. 0 (no
left movement) to
hemiparesis or 5 (normal
hemiplegia. movement).

Anderson and Anderson and 32 stroke 3–25 days. Dense 27.77% (18)
Tranel (1989) Tranel (1989) patients hemiparesis.
referred for
neuropsycholo
gical
assessment; 18
with dense
hemiparesis
Page 41 of 60

assessed for
anosognosia.
Wagner and 108 Average 4.9 Not selected 18.1% (108)

Cushman consecutive weeks. by motor
(1994) stroke patients impairment.
from two acute
Neurorehabilit
ation Centres.
Hartman- 60 patients 4–8 weeks. Severe. 23.53% (17) 27.59% (29) 26.09% (46)
Maeir et al. with first-ever
(2001) stroke; 46 with
severe motor
deficit of arm
assessed for
anosognosia.
Starkstein et Starkstein et 80 stroke Approximately Not selected Total: 33.75%

al. (1992) al. (1992) patients 1 week. by motor (80) Moderate
selected from impairment. or severe:
96 consecutive 23.75% (80)*
admissions.
Page 42 of 60

Appelros et al. 377 stroke 1–4 days. Not selected Total: 17.39%
(2002) patients by motor (276)
recruited from impairment. Moderate or
Örebro, severe: 11.96%
Sweden over (276)*
12 months;
276 assessed
for
anosognosia.
Berti et al. Berti et al. 34 chronic Average 60 Complete 26.47% (34)

(1996) (1996) stoke patients days. hemiplegia.
from
Geriatrics,
selected by RH
damage and
complete
hemiplegia.
Maeshima et Maeshima et 50 patients Within 30 Severe or 24% (50)

al. (1997) al. (1997) with RH days. moderate-mild.
cerebral
haemorrhage.
Page 43 of 60

Marcel et al. Marcel et al. 64 stroke Average 79.1 Severe motor Arm: 0% (22) Arm: 28.57% Arm: 18.75%
(2004) (2004) patients days (LH) 55.7 deficit in at Leg: 9.09% (42) (64)
recruited from days (RH). least one limb. (22) Leg: 29.27% Leg: 22.22%
seven ADL: 13.64% (41) (63)
hospitals, (22) ADL: 52.38% ADL: 39.06%
selected by (42) (64)
hemiplegia.
Cocchini et al. Cocchini et al. 33 LH-stroke Average 73.8 4-point scale: 40% (30)
(2009) (2009) patients with days. 0 (normal
motor motor
impairments; performance)
30 patients to
selected as per 3 (complete
reliable hemiplegia).
responses on
the Visual
Analogue Test.
LH = Left Hemisphere; RH = Right Hemisphere; ADL = Activities of Daily Living.
* Moderate or severe anosognosia: The patient did not acknowledge his or her deficits until these were demonstrated (moderate) or
never acknowledged the deficits (severe).
Page 44 of 60
A new structured interview for the assessment of anosognosia

for motor impairments is presented at the end of this chapter.
The approach is theoretically motivated and relatively
comprehensive. The assessment incorporates items from the
interviews presented in Table 23.2 as well as items that build
on earlier protocols. Any assessment of anosognosia depends
on a prior assessment of the patient’s motor impairments and
their consequences and so the structured interview is to be
used alongside assessments of motor impairments and their
functional consequences, such as the Motricity Index, the
Rivermead Mobility Index, and the Barthel Activities of Daily
Living Index (Section 3). A full investigation of anosognosia
must also include assessments of factors that may play a role
in its aetiology such as unilateral neglect, ‘a notable suspect in
anosognosia’ (Vuilleumier, 2004, p. 10), and other factors that
may impact on recovery and rehabilitation.
The new structured interview is made up of four modules. The

first module does not involve any request for the patient
actually to perform tasks using the affected limbs. It includes
questions about the primary reason for hospitalisation (Q1),
about the patient’s acknowledgement of motor impairments
(Q2), and about the patient’s appreciation of the consequences
of his or her motor impairments for activities of daily living
(Q3). It also investigates anosognosic phenomena (Q4).
Although questions about these phenomena have not been
incorporated into most structured interviews, we believe that
they may prove useful for assessment and rehabilitation, since
patients are unlikely to mention these unusual beliefs and
experiences spontaneously.
Thereafter, the structure of the assessment is dictated by the

threefold distinction (explained in Section 2 of this chapter)
between concurrent unawareness of an impairment, failure to
acknowledge the impairment itself, and failure to appreciate
the consequences of the impairment for activities of daily
living. Thus, the second module investigates whether the
patient is concurrently aware of motoric failures of the
affected arm or leg. With vision precluded, the patient is
requested, for the first time, to move his or her limbs (Q5). If
the patient is seated, he or she is requested to raise each arm,
and then both arms, to shoulder level and to raise each leg by
extending it at the knee. If the patient is supine, he or she is
Page 45 of 60
requested to raise each arm, and then both arms, and each leg
from the bed surface, to a position indicated by the examiner.
It is not the primary purpose of this second module to

investigate the patient’s beliefs as to whether he or she is
really able to move the affected limbs. Still less is it intended
to challenge the patient’s beliefs by providing evidence of
failure. Instead, the purpose of the module is to provide
information about the patient’s proprioceptive experience as
he or she tries to move the affected limbs; that is, information
about the patient’s bodily awareness or unawareness of
motoric failures when they occur.5 This is theoretically
important because concurrent (p.457) unawareness of motor
impairments may be a factor in failure to acknowledge those
impairments. It is only at the end of the module, and only if the
patient has reported feeling as if he or she succeeded in
moving the affected limbs (illusory limb movements), that the
examiner asks whether the patient believes that the limbs
really moved. The patient’s beliefs about whether he or she
can move the affected limbs are the focus of the next module.
As we have seen, one of the key aspects of the assessments of

anosognosia by Willanger and colleagues (1981) and Bisiach
and colleagues (1986) is that the patient’s impairment is
demonstrated and the patient is given the opportunity to
reflect on this evidence of failure and to acknowledge his or
her motor impairments. This allows us to distinguish between
moderate and severe anosognosia. The third module
investigates whether the patient acknowledges his or her
motor impairments, both before (prior belief) and after
(posterior belief) an impairment is demonstrated (Q6, raise the
limb, and Q7, maintain the limb in a raised position). In order
that the evidence of failure should be maximally available to
the patient, vision is permitted. All questions are first asked
concerning the unaffected limb. This allows the examiner to
check that the patient understands the task and also provides
a control condition against which responses to questions about
the affected limb can be compared.
The fourth module investigates whether the patient

appreciates the consequences of motor impairments for
activities of daily living. One of the key points in Section 4 of
this chapter is that an investigation of anosognosia for the
consequences of motor impairments should include asking the
patient to perform, or at least describe how they would
Page 46 of 60
perform, various tasks. In this module, first-person and third-

person forms of questions about unimanual, bimanual, and
bipedal tasks are used (Q8) and the patient is asked to rate his
or her abilities both before (prior belief) and after (posterior
belief) actually trying to perform an action (Q9). Some of the
actions involve interaction with objects and so the subsequent
position of the objects provides clear evidence of success or
failure of the attempt.
By testing the patient’s belief revision, the third and fourth

modules assess whether the patient makes appropriate use of
available evidence of his or her limitations. Thus, the second,
third, and fourth modules together could, in principle, go
beyond detecting anosognosia for motor impairments and
provide the beginnings of an explanation of some cases of
anosognosia. The explanation would be of a familiar two-factor
kind in which impairment of immediate bodily experience of
motoric failure, and cognitive impairments that obstruct the
appropriate use of available evidence to update beliefs, would
(p.458) both play a role (Aimola Davies and Davies, 2009;
Aimola Davies et al., 2009; Davies, Aimola Davies and
Coltheart, 2005; Levine, 1990; Levine et al., 1991). As
Vuilleumier says (2004, p. 11): ‘any neurological dysfunction
susceptible to alter the phenomenal experience of a defect
might provide the ground out of which anosognosia can
develop when permissive cognitive factors are also present’.
Page 47 of 60
6 Conclusion
A theoretical framework for this chapter is provided by the
threefold distinction between concurrent unawareness of an
impairment, failure to acknowledge the impairment itself, and
failure to appreciate the consequences of the impairment for
activities of daily living (Section 2). A simple assessment of
anosognosia for motor impairments can be carried out at the
same time as a routine assessment of motor impairments. An
initial assessment of anosognosia for the consequences of
motor impairments can be obtained by using a dual scoring
system with functional measures of mobility and
independence. A more comprehensive assessment of motor
impairments and their consequences invites a correspondingly
more nuanced assessment of anosognosia (Section 3).
We began this chapter with the proposal that a comprehensive

and widely accepted procedure for assessing anosognosia for
motor impairments would contribute to a better understanding
of the many factors in anosognosia and might also lead to
improvement in the clinical management of patients. Building
on published structured interviews (Section 4) and other
protocols, we have presented a theoretically motivated and
relatively comprehensive instrument for assessing
anosognosia (Section 5). We hope that this new structured
interview will contribute to our understanding of the
occurrence, aetiology, time course, and treatment of
anosognosia and that this will lead, in turn, to improved
recovery and rehabilitation for patients.
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Table 23.4 Structured Interview: Anosognosia for

Motor Impairments
Page 54 of 60
Page 55 of 60
Page 56 of 60
Page 57 of 60
(p.463) (p.464) (p.465) (p.466) (p.467)
Notes:
2
Scoring for Test 1:
(0) No movement
(11) Beginnings of prehension (any movement of finger
or thumb)
(19) Able to grip the cube, but not hold it against
gravity (examiner may need to lift wrist)
(22) Able to grip and hold the cube against gravity, but
not against a weak pull
(26) Able to grip and hold the cube against a weak pull,
but weaker than the other side
(33) Normal pinch grip.
Scoring for Tests (2–6) :

(0) No movement
(9) Palpable contraction in muscle, but no movement
(14) Visible movement, but not full range and not
against gravity
(19) Full range of movement against gravity but not
against resistance
(25) Full movement against resistance, but weaker than
the other side
(33) Normal power.
3
Recommended versions of each measure – Motricity Index,
Rivermead Mobility Index and Barthel Activities of Daily Living
Index – can also be found in Measurement in neurological
rehabilitation (Wade, 1992 ).
Page 58 of 60
4
The questions actually used by Marcel and colleagues
(2004,p. 24) were rather more complicated than this. First-
person form:‘In your present state how well, compared with
your normal ability, can you tie a knot? If you can do it as well
as usual, say “ten”. If you cannot do it at all, say
“nought”.’Thirdperson form:‘If I were in your present state,
how well would I be able to tie a knot, compared with my usual
ability? If I could do it as well as usual, say “ten”. If I could not
do it at all, say “nought”.’
5
The second module builds on a protocol used by Marcel and
colleagues (2004 ). In their study, as part of an assessment of
motor function and separately from the main anosognosia
interview, patients were asked to raise each limb with vision
precluded and their performance was rated objectively using
the MRC scale (Table23.1). As soon as the assessment of
motor function was complete,‘patients were asked how much
they had been able to move each arm and each leg’ (p. 23). In
making this postperformance evaluation, patients had to rely
on ‘immediate episodic experience’ provided by
proprioception, since they were blindfolded and no other
feedback was given (p. 32). To the extent that patients gave an
unrealistically high evaluation of their performance in trying
to move their affected limbs, they were judged to be
concurrently unaware of their motoric failure.
(1) The sixteen commonly tested upper and lower limb

movements from the abridged version of the Medical Research
Council Scale are listed below (Guarantors of Brain, 2000, p.
62). Five of these sixteen movements are included in the
Motricity Index for Motor Impairment after Stroke.
(a)) Upper Limb Movements (shoulder abduction; elbow

flexion; elbow extension; radial wrist extension; finger
extension; finger flexion; finger abduction);
(b)) Lower Limb Movements (hip flexion; hip abduction;
hip extension; knee flexion; knee extension; ankle
dorsiflexion; ankle eversion; ankle plantar flexion; big
toe extension).
Page 59 of 60
Page 60 of 60
Treatment and rehabilitation of paediatric/developmental neuropsychological
disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Treatment and rehabilitation of

paediatric/developmental
neuropsychological disorders
Stephen Whitfield
DOI:10.1093/acprof:oso/9780199234110.003.24

This chapter begins with a discussion of the role of the
paediatric neuropsychologist. It then discusses specific issues
in paediatric treatment and rehabilitation, neuropsychological
dysfunction, neuropathological disorders, and
neurodevelopmental disorders.
Keywords: paediatric neuropsychology, neuropsychological dysfunction,

neuropathological disorders, neurodevelopmental disorders
1 The role of the paediatric neuropsychologist

The role of the paediatric neuropsychologist differs from that
of clinical neuropsychologists working with adults both in
terms of: (1) the perspective adopted, i.e. that the child is a
growing individual so that a developmental view must be
adopted when considering the results of clinical assessment
and implementing treatment programmes, and (2) the context
within which treatment/rehabilitation takes place. In terms of
context, the paediatric neuropsychologist is generally much
more involved in multidisciplinary working with health, social
Page 1 of 25
disorders
services, and education personnel than would be the case

when working with adults. Treatment is also frequently
carried out by others and in non-health (particularly
educational) environments.
In the area of intervention/treatment the paediatric

neuropsychologist contributes in an advisory, monitoring, and/
or therapeutic role.
◆ The advisory role will include educating and informing

the child (where appropriate and practicable), parents,
therapists, teachers, and peers of the nature of the child’s
condition or injury and its likely impact upon his/her
development and future education/occupation.
◆ Monitoring will include the evaluation of any intellectual

or behavioural changes brought about by a disorder or
injury and its clinical (e.g. radiation treatment) or
pharmacological management (e.g. antiepileptic medication
side-effects).
◆ The therapeutic role will include the management/

treatment of behaviour disorders, memory complaints,
emotional and adjustment problems, etc.
The psychological approaches used will include

neurobehavioural and cognitive-behavioural methods;
application of psychometric, developmental, and observational
assessment techniques; rehabilitation methodology; and
counselling. Contexts for interventions will include all aspects
of the child’s environment including home, school/college (or
work), and leisure situations.
(p.472) 2 Specific issues in paediatric treatment and

rehabilitation
Page 2 of 25
disorders
2.1 Neuroplasticity
For children predictive factors would be the extent of damage
(the more localized the damage, the greater the chance of a
plastic response) and age at time of injury. Theoretically,
plastic reorganization should be more easily achieved in the
younger (under 2 years) brain where less development has
taken place. Animal studies have shown some evidence to
support this view, but it is not supported by research with
human infants. Consequently, the process is either not a
spontaneous one or it has critical periods during which injury
will not stimulate neuronal modification. If the latter is true,
the evidence so far suggests that the least favourable time for
a plastic response is probably the period from the end of
gestation to the first month of life, while the most favourable
period is the age band of 1 to 2 years. At present neural
transplantation has no role in childhood disorders.
2.2 Localization, lateralization, and modularity

Traditional approaches to adult neuropsychological
assessment have emphasized localization or lateralization of
cognitive functioning. This view has never been appropriate in
young children where abnormal cerebral development or
acquired injury could interrupt the establishment of localized
or lateralized functions.
The view of cognitive abilities that emphasizes ‘modularized’

skills is more appropriate to the mature brain of adults.
Cognitive—developmental views see a generalized and
interdependent progression in skills throughout childhood,
which explains the different patterns of deficit seen in adults
and children following similar insults (see Section 3). The most
important aspect of the paediatric neuropsychologist’s
approach is to relate neuropsychological observations to the
developmental stage of the child.
2.3 Recovery
In the earliest stages of recovery the regular monitoring of the
extent of postinjury confusion and disorientation is essential to
ensure that therapeutic interventions with cognitive
requirements are matched to orientation level.
◆ There is no UK-derived assessment for children. One can

modify the Children’s Orientation and Amnesia Test (Ewing-
Cobbs et al. 1990).
Page 3 of 25
disorders
◆ Questions relating to orientation to person, place, and

time are most commonly used, with return of orientation
usually occurring in this same order.
2.4 Rehabilitation
There is no evidence that rehabilitation efforts during the
early stages of recovery alter its course or that sensory
stimulation reduces the depth or duration of coma. However,
physical (p.473) health can deteriorate without appropriate
medical and nursing support during this time. Children are
also prone to the development of maladaptive behaviours
during this period, which require management to prevent
them entering the child’s behavioural repertoire. A hospital or
rehabilitation setting may prevent all the above.
Rehabilitation is distinct from recovery (the spontaneous

process of return of pre-injury skills) and habilitation (the
passive adaptation of environments to disabilities). The aim of
rehabilitation is to reduce the ‘mismatch between the skills a
person possesses and the actual demands of the
environment’ (Dixon and Bäckman 1999). Its methodology is to
use ‘restorative’ or ‘compensatory/adaptive’ strategies. This
distinction is of less value in children as early insult denies
many early learning experiences that the ‘restorative’
approach would utilize in rehabilitating adults. Consequently,
the ‘compensatory/adaptive’ approach has primacy in younger
children.
Restoration focuses upon reducing disability, whereas

compensation and adaptation focus upon the reduction of
handicap (World Health Organization 1980). The differences in
these approaches can be summarized as follows.
◆ Restorative approaches are based upon recovering a lost

skill.
◆ Compensation approaches aim to revive and/or modify a

latent skill or develop a new skill to substitute for the lost
one.
◆ Adaptation focuses upon modifying environments to

reduce the mismatch between skills and demands or on
altering the parents’, teachers’, and child’s expectations to
meet the changed circumstances.
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Restorative and compensatory approaches are appropriate to

higher levels of meta-awareness; adaptation to the lowest
levels. As orientation returns, the strategies used will need to
be adapted to incorporate the former as well as the latter.
2.5 Adjustment
2.5.1 Adjustment to a developmental disorder
A child with a developmental disorder may have little difficulty
in adjusting to the neuro-psychological consequences of the
disorder as he or she will have always lived with it and will not
have a model of ‘normality’. The difficulty lies in trying to alert
others to view the world from the child’s perspective. This may
not only yield empathic understanding of ‘oddities’ in the
child’s behaviour, but may also be useful in generating
creative behavioural management solutions.
2.5.2 Adjustment to an acquired brain injury

Conversely, a child with an acquired brain injury in the later
stages of recovery may feel a sense of loss for those things
that he or she was able to do prior to the injury, but cannot do
postinjury. This not infrequently leads to anxiety, frustration,
and depression that can manifest themselves as oppositionality
and aggression. Behavioural management will not be
successful without addressing the underlying emotional
adjustment issues involved.
(p.474) Sharing with older children and their parents the

rehabilitation team’s analysis of their predicament and
prognosis together with their full involvement in rehabilitation
programme goal-setting can, in appropriate cases, be highly
efficacious in reducing these feelings and moving forward the
process of adjustment. After a period in which the child and
parents have largely been recipients of medical treatment,
they can find this emphasis on involvement empowering.
However, such an approach is dependent upon an adequate
degree of self-awareness, which may not be present in the
early stages of recovery, in severe attentional or executive
disorders, or where the child has been left with significant
generalized learning difficulties. The same criteria would
apply to those children who might benefit from cognitive-
behavioural therapy.
2.5.3 Adjustment for parents and families
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Parental adjustment encompasses a whole range of emotions

including fear, detachment, helplessness, denial, anger,
anxiety, depression, and guilt. Information, though needed by
parents, may not be heard or may be rejected if given at the
wrong time. Anger directed at professional staff, or even the
child, is evidence of poor adjustment at that time, but not
necessarily of poor overall adjustment.
Families have resources that they have to allocate to deal with

life events with each member contributing their share to the
collective whole. Multiple demands on these resources
decrease that which can be devoted to any particular
situation. Continuous demands, as produced by the long-term
care of a family member, deplete the resources of the entire
family. The additional demands of poverty, divorce, work
pressures, young children, elderly parents, etc. draw even
further on these finite resources.
Parents do not experience their child as a collection of

cognitive abilities, but as a functioning individual within a
social and personal historical context. Adjustment will be
facilitated if the paediatric neuropsychologist does not
describe the child’s deficits, but integrates findings into an
explanation of the neurological disorder in the context of the
child’s world and his or her past and future.
3 Neuropsychological dysfunction
Disturbance to central nervous system (CNS) development in
the prenatal period primarily results in structural
abnormalities (e.g. dysplasias, spina bifida, agenesis of the
corpus callosum). Postnatal interruptions affect the
elaboration of connections within the brain, processes that
continue into early adolescence. The nature and severity of the
insult determine, as for adults, outcome in a dose-response
fashion. However, in children, the developmental stage
attained at the time of insult/onset interacts with the nature of
the insult to produce a complex pattern of deficits, unlike the
more proscribed impairments found in adults.
Childhood CNS disorders are more likely to have a generalized

effect (traumatic brain injury, infections, etc.). Focal disorders
(tumour, stroke) are relatively rare. Consequently, specific
impairments such as apraxias and aphasias are less common,
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while attention, memory, and executive disorders are most

prevalent (see box below). (p.475)
4 Neuropathological disorders
Functional impairments associated with specific

conditions
Perceptual and spatial disorders

◆ Turner’s syndrome
— Impairments in visual Gestalt perception and

integrative spatial construction
— Most significant in children with karyotype

45XO
◆ William’s syndrome
— Problems with drawing, copying, and block

design
— Attention to detail rather than overall picture
Memory disorders
◆ Epilepsy
— Memory problems primarily associated with

temporal lobe epilepsy (TLE) due to close
anatomical association with hippocampus
— Lateralized impairments to verbal and

nonverbal memory associated in some studies
with side of TLE focus
Language disorders
◆ Auditory agnosia in Landau–Kleffner syndrome
◆ Pragmatic disorders in autism and Asperger’s

syndrome
Executive disorders
◆ Autism
◆ Phenylketonuria
◆ Gilles de la Tourette’s syndrome
◆ Treatment of acute lymphoblastic leukaemia
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◆ Turner’s syndrome
4.1 Acquired brain injury

The types of acquired brain injuries are summarized in the box
below.
4.1.1 Prognosis
The extent of cognitive sequelae and subsequent prognosis for
intellectual recovery are dependent upon the nature and
severity of the injury and the age at time of injury.
Suitable indices of severity of injury are the depth and

duration of coma and length of posttraumatic amnesia (PTA).
(p.476)
◆ Depth of coma is most commonly assessed by the Glasgow

Coma Scale (Jennett and Teasdale, pp. 258–63) or the
paediatric version (Simpson et al. 1991). The lower the
score, the poorer the prognosis for recovery.
◆ Duration of coma. Less than 20 minutes, mild; 20 minutes

to 6 hours, moderate; 6–48 hours, severe; over 48 hours,
very severe.
◆ Length of PTA. Under 60 minutes, mild; 1–24 hours,

moderate; 1–7 days, severe; 1–4 weeks, very severe; over 4
weeks, extremely severe.
Types of acquired brain injury
Traumatic
◆ Road traffic accidents (RTA) result in a combination of
focal and diffuse injury
◆ Falls
◆ Non-accidental injury
— Cause of the majority of severe head injuries in

children under 1 year, 10% of injuries in the
under-fives. 50% will have permanent cognitive
sequelae
— High incidence of repeated assaults/damage
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— Higher incidence during teenage years

probably as a result of parent–child conflicts
◆ Projectile injury
Hypoxic–ischaemic
◆ Near drowning
◆ Neonatal hypoxia—most commonly problems with

labour and delivery.
◆ Anaesthetic accidents
◆ Prolonged status epilepticus
◆ Cerebrovascular accidents
Other medical
◆ CNS infections
◆ Tumours and their treatment
◆ Acute encephalopathies
◆ Metabolic disorders
PTA is more difficult to assess in children as they may become

confused between actual memories and information provided
by parents/visitors.
The ‘nature’ of the injury relates to primary brain damage

(whether focal, diffuse, or both) combined with results of any
secondary factors (oedema, raised intracranial pressure,
hypoxic/ischaemic injury, haematoma).
Contrary to the Kennard principle (commonly interpreted as ‘if

you are going to have brain damage, have it early’),
experimental and clinical work now indicates that injuries (p.
477) sustained at a young age, before the brain has had time
to mature, lead to greater cognitive sequelae than those
occurring in the adult years (Johnson and Rose 1996).
Functional deficits may not be obvious until the area of the
brain concerned begins to mature. For the prefrontal lobes
this happens between about 8 and 15 years. These delayed
effects are sometimes referred to as ‘sleeper’ phenomena.
4.1.2 Cognitive sequelae
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The most common cognitive sequelae to an acquired head

injury are impairments to orientation and attention, memory
(in children this includes access to long-term memory, which
will be less well developed than in adults), new learning, and
executive skills.
4.1.3 Behavioural sequelae

These are present in 30% of children with mild to severe
traumatic brain injury (TBI) and 73% of children with multiple
functional impairments. They occur most commonly after
frontal and temporal lobe damage. They arise in part from
cognitive impairments such as poor insight into their own
behaviour and poor application of environmental feedback.
Disinhibition presents severe problems of social acceptability,

which can be aided by a set of rules to apply in common
settings, e.g. do not shout out in class. This approach is only
successful if memory skills have returned to a level that
permits its retention. Behavioural contracts can be successful
with less severe cases.
4.1.4 The rehabilitation of neuropsychological functions

Cognitive rehabilitation
This consists of the application of strategies (largely

behavioural) to improve cognitive and affective functioning
following acquired brain injury. The methodology tends to be
split between direct training of cognitive processes and
functional skills training. The evidence is that functionally
based cognitive rehabilitation in everyday life settings is more
successful than rehabilitation exercises detached from the
child’s normal living environment. Success appears to be
independent of the particular method used.
Attention training
There is no solid research basis that proves the effectiveness

of retraining approaches.
Memory rehabilitation
The effectiveness of retraining has not been proven.

Compensatory aids are useful in improving function. The use
of external memory aids to assist recall is only successful if the
child remembers that they have a problem with their memory!
Without this they go unused. Thus, they are more useful for
those with mild rather than severe problems. The use of aids
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has to be built up with frequent reminders in ‘real-life’

situations. Similar considerations apply to the use of internal
(verbal mnemonics) aids.
As procedural memory is frequently retained when explicit

memory is impaired, this is often incorporated into
compensatory strategies, e.g. inclusion of pre-injury
procedural learning into new behaviours that are repeatedly
practised using errorless learning approaches.
Rehabilitation of executive functions
There has been some success in training for specific tasks, e.g.
self-organization skills. Compensatory aids, e.g. diaries,
electronic organizers, (p.478) copies of school timetables,
home–school books, picture sequences, etc., completed under
guidance can be useful in training these skills. However, only
limited generalization is seen in the training of problem-
solving skills.
4.1.5 Neurobehavioural management

On emergence from coma, restlessness, wandering, and
destructiveness occur. Acute phase problems with behaviour
usually resolve with reduction in PTA. However, environmental
control is important with avoidance of high-level stimulation,
minimalization of staff changes, uncluttered treatment areas,
acoustically quiet environments, etc.
In the early post-acute phase, whilst orientation is poor,

memory is thrown back upon procedural learning rather than
the more explicit systems. If not prevented, errors become
established that are not open to correction using cognitively
based interventions. In particular, this makes the child prone
to the development of maladaptive behaviours and requires
preventive management emphasizing errorless learning
approaches. This stage may continue for months if the child’s
recovery is slow.
While cognitive difficulties persist (orientation, attention, and

memory in particular), the use of contingency management
will prove less effective than antecedent control techniques in
the treatment of behavioural excess or deficit.
Focal impairments to the frontal lobes in the teenage years

generally lead to one of two behavioural phenotypes
manifesting as:
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◆ irritability, anxiety, obsessionality, false euphoria, over

sexualized behaviour, poor social responses, increased risk-
taking behaviour (though unimpaired social or moral
reasoning), and poor self-monitoring. The fundamental
problem appears to be one of failure to inhibit responses.
◆ apathy, poor initiation, failure to maintain activity, and

pseudo-depression.
Both groups benefit from a structured approach with a regular

timetable, clear rules, and contingencies. Behavioural
approaches are helpful. Management based upon reasoning,
dependent as it is upon the ability to self-reflect, is seldom
effective. It is preferable to create overlearned responses to
simple everyday situations that utilize the tendency towards
stimulus-driven behaviour. This approach is of proven
effectiveness. Such an approach will allow basic anger
management techniques to be trained with well-oriented
children.
The psychosocial environment of the child during recovery is

an important additional source of behavioural difficulties.
Parental reactions to the child’s injury may lead to
overprotection, overindulgence, loss of confidence, guilt,
anger, stress, anxiety or depression, all of which can have an
effect upon behaviour. Social factors of peer rejection, loss of
status (academic or sporting), and social isolation may add to
this.
Neuropsychiatric disorders appearing after TBI include the

following.
◆ Disorders of thought and perception. Their manifestations

are aggression, agitation, conduct disorders, or
disinhibition. Their neuropathology is still unclear.
Paediatric neuropsychiatric evaluation is required.
◆ Disorders of mood and affect. The head-injured child is

vulnerable to emotional and psychiatric disorders (double
the vulnerability of peers at 2 years post-injury) emerging
(p.479) as lowered self-esteem and depression linked to
poor adaptive skills. Daily variation is common and can be
investigated by a paediatric neuropsychologist through
standard behavioural recording. However, one should be
aware that problems might arise from cyclical
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neuropsychiatric disturbance as well as environmental

stimuli or contingencies.
4.1.6 Rehabilitation settings

The majority of children with an acquired brain injury will
have early post-acute rehabilitation provided within their local
community following discharge from hospital. A planning
conference to coordinate professional inputs and resources
will generally take place within 1 or 2 weeks of discharge. A
key worker is generally identified to act as a case manager,
though this should not be confused with head injury case
management services, usually appointed following the
settlement of a claim for compensation. Though postacute
head injury teams exist in some health authorities, they
seldom consist of staff dedicated to this role. In consequence,
the head-injured child has to compete for resources with other
children. Alternatively, some areas will use staff from adult
head injury services to provide services. This is problematic in
that staff may have little experience or knowledge of childhood
disorders, child development, or paediatric interventions.
A small number of children, usually with more severe and

complex needs, will be catered for within specialist paediatric
head injury facilities.
The role of the paediatric neuropsychologist in rehabilitation is

to provide a framework within which other therapeutic
interventions may take place. He or she should ensure that the
cognitive demands placed upon the child are within their
present level of cognitive functioning, while bearing in mind
that this will alter as the process of recovery takes place.
4.1.7 Education
Unlike adults who may become unemployed following head
injury, there is a statutory duty to educate all children
whatever their degree of disability. This means that the
educational system has a central role to play in the
rehabilitation of head-injured children, as schools will be the
principal environments to which the children will return.
Advice given to teachers should be precisely geared to the
individual child rather than general based upon a particular
syndrome or condition. The latter will reflect too great a
variability across children to allow the teacher to formulate
specific educational programmes for the child.
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Unfortunately, few local education authorities have specific

policies on providing for the educational needs of brain-injured
children. The situation in the UK has several disadvantages.
◆ The system established in England and Wales (with minor

variations in Scotland and Northern Ireland) for the
drawing up of statements of special educational needs
embodies a view of static educational needs. This model is
unsuited to the situation of head-injured children who have
(at least during the early postacute phase and not
uncommonly during later ‘spurts’ in recovery) frequently
changing needs. Though the review system for such
statements can be utilized to accommodate changes, the
time period for implementing changes can be protracted.
(p.480)
◆ There is a danger that the recovering child will have a
placement suited to their apparent level of cognitive
functioning at the time of assessment, but increasingly
inappropriate as recovery takes place.
◆ If physical needs are significant, placements may be

offered based on the location of resources such as physio-
and occupational therapy, nursing, etc., rather than based
upon the appropriateness of educational environment.
The paediatric neuropsychologist must have a role as an

advocate for the child in seeking appropriate provision.
4.1.8 Family needs

The early stages of postacute recovery are important ones in
beginning the process of adjustment to the changed
circumstances of the child. Adjustment is an essential step to
the success of rehabilitation.
◆ Parents may become ‘stuck’ and become focused upon

the physical aspects of recovery (will she be able to walk?)
when cognitive recovery may be the more important
determinant of successful rehabilitation.
◆ Information is critical to parental adjustment and the

paediatric neuropsychologist is best placed within a
multidisciplinary team to objectively outline (after
comprehensive assessment) what has happened to their
child’s brain and what the cognitive prognosis is likely to
be.
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◆ The paediatric neuropsychologist has an importance

similar to that of other key figures in the child’s world, e.g.
teachers, classmates, friends on the social side, social
workers, educational psychologists, and solicitors.
◆ Siblings frequently get left out whilst the focus is on the

injured child. They too will suffer shock and sometimes guilt
at their resentment of the attention being given to their
brother or sister. Embarrassment at the reaction of friends
can lead to anger and frustration. Counselling and play
therapy can assist adjustment.
4.2 Brain tumours
Sixty per cent are astrocytomas or gliomas; 20–25% primitive
neuroectodermal tumours. Neuropsychological sequelae
include problems with:
◆ fine-motor coordination;
◆ perceptual–motor skills;
◆ visual constructional abilities;
◆ memory.
In turn these lead to decrements in IQ. The functional

consequences are in academic and vocational skills. Memory
problems can affect daily living and self-care.
However, these sequelae seem principally to be a consequence

of radio- and, to a lesser degree, chemotherapy treatments,
not of surgery. Age at diagnosis and treatment and the type
and location of the tumour are also important factors in long-
term outcome. (p.481) Academic difficulties should be
anticipated and teachers informed in order to adjust
expectations in the classroom. Neuropsychologists have a role
as information providers and interpreters and in the
monitoring of post-treatment changes.
4.3 Epilepsy
The distribution of IQ in children with epilepsy is close to that
of the general population. However, some epilepsy syndromes
are associated with specific cognitive sequelae.
◆ Moderate to severe learning difficulties are observed in

the majority of children with Lennox–Gastaut and West’s
syndrome.
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◆ There are many other abnormalities of brain development

or acquired disorders that include epilepsy in their
symptomatology. These would include: developmental
disorders, e.g. tuberous sclerosis and Angelman syndrome;
CNS infections; acquired brain injuries; metabolic
disorders; Rett syndrome; and neurofibromatosis.
◆ Epilepsy is a co-symptom of severe learning difficulties

(9–31%), autism (11–35%), and cerebral palsy (18–35%).
Other factors associated with cognitive or functional problems

in epilepsy are the following.
◆ Intellectual decline in epilepsy (not associated with other

underlying conditions) is usually associated with
antiepileptic drug (AED) toxicity.
◆ A history of status epilepticus is associated with

decreased functioning.
◆ Children with early onset to their seizure disorder, poor

response to anticonvulsant medication, and mixed seizure
types tend to perform more poorly on IQ measures.
However, these factors could disguise a common factor in
the existence of pre-existing neurological impairments prior
to seizure onset.
◆ Specific impairments likely to be associated with epilepsy

are poor sustained attention and reduced short-term
memory performance. A confounding factor again is AED
toxicity.
◆ Subclinical electrical activity of even brief duration can

produce educational difficulties referred to as transitory
cognitive impairments (TCI). The mediating factor here is
most probably disruption to attention.
◆ Some studies suggest that left temporal lobe epilepsy is

associated with decreased performance on verbal memory
tasks and right temporal lobe epilepsy related to reduced
visual memory function. Others suggest bilateral memory
impairments.
◆ Hippocampal damage from frequent seizures is

associated with decreased new learning.
Despite a near-normal distribution in IQ, children with

epilepsy are more at risk of educational underachievement.
This is not yet understood, but is not associated with seizure
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type, duration, severity, or AED used in treatment. Self-esteem

and emotional variables such as locus of control appear
important.
Behavioural and psychiatric problems are also more prevalent

in children with epilepsy. There is no specific symptomatology.
Difficulties arise from a combination of neurological (brain
damage, seizure activity in areas of brain associated with
affective functioning, (p.482) variations in neurotransmitter
function) and psychosocial factors (lowered self-esteem,
externalized locus of control, stigmatization, lowered
expectations, reactions to parental overprotection, and lack of
independence). The degree of neuropsychological dysfunction
predicts behavioural and neuropsychiatric dysfunction, i.e.
brain dysfunction not epilepsy is causative. AED treatment is
also a factor with phenobarbitone associated with the most
difficulties and carbamazepine and sodium valproate with the
least, but dosage and multiple drug therapy are also important
factors. It is important to include assessment and treatment of
affective and behavioural functioning in management.
The paediatric neuropsychologist’s role is as part of a

multidisciplinary approach addressing medical treatment,
educational management, and emotional and social adjustment
—specifically, the monitoring of cognitive and behavioural
change and the provision of information and management
advice to the child, his/her parents, and teachers.
4.4 Hydrocephalus
Hydrocephalus is a secondary condition arising from a number
of primary disorders. It is the primary disorder that is the
dominant factor in outcome. It is associated in all aetiological
groups with:
◆ gross and fine motor problems and visuomotor and spatial

difficulties;
◆ greater impairment to language content than to structure

(particularly in children with shunts);
◆ list-learning problems—results in regard to other aspects

of memory are unclear other than that children with
shunted hydrocephalus perform more poorly than other
groups.
◆ problems with focused attention;
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◆ deficits in executive skills where children with shunted

hydrocephalus require an increased number of trials to
reach the correct answers in problem-solving tasks;
◆ behavioural difficulties—children with shunted

hydrocephalus have higher rates of behaviour disorder than
those without.
Functional difficulties are apparent in school work (associated

with visuospatial, executive, and learning problems) and
everyday living (language, attention, and behaviour) The
paediatric neuropsychologist’s role is in the interpretation of
cognitive and behavioural findings and in the provision of
information and management advice appropriate to the needs
of the referred child.
4.5 Meningitis
This is an infectious disease involving inflammation of the
meningeal membrane with either a viral or bacterial cause.
The latter is more likely to lead to disability. Of children with
early childhood bacterial meningitis, 40% suffer additional
acute neurological problems (sensory impairments,
hydrocephalus, seizures, etc.), but only 20% of those who
survive have persistent difficulties. In addition, many have
cognitive, behavioural, (p.483) and educational sequelae.
The pattern of these is diverse covering motor, perceptual,
language, attentional, and executive skills. Overall IQ is
probably little affected.
The pattern and extent of deficits is thought to be dependent

upon the age at the time of infection, time since insult, and
developmental stage at time of assessment.
◆ Age at the time of infection is significant in that that pre-

infection learning is retained, but new learning is
significantly impaired.
◆ During the time following the insult compensation may

have taken place, which will in turn influence the deficit
observed.
◆ The developmental stage at time of assessment

determines the expectations of the child’s abilities at that
stage and thus helps determine the extent of the deficits.
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Initially, gross motor problems dominate; subsequently fine

motor problems. Perceptual and language difficulties occur
during the primary years, while, in the secondary phase,
impairments to higher-order language and executive skills are
most frequently reported.
Once again, the picture is of a multifactorial process affecting

outcome with psychosocial and environmental issues
important contributory factors. This would suggest that
rehabilitative efforts could have significant benefits in this
condition. The paediatric neuropsychologist’s role is to inform
parents and educators of the implications of observed deficits
and to formulate suitable management approaches to
behaviour and adaptive learning. The changing pattern of
deficits suggests the need for neuropsychological oversight
throughout childhood.
4.6 Metabolic and neurodegenerative disorders

These disorders arise from built-in errors of metabolism
leading to a build-up of neurotoxins and consequent
neurodegeneration. Cognitive deterioration is often difficult to
detect in children due to the active interaction between
normal development and the degenerative process. The earlier
the onset, the more difficult this becomes with the lack of a
clear premorbid period of ‘normal’ development. Decline in IQ
can be misleading as it may represent a failure to maintain a
rate of intellectual growth in keeping with one’s peers, a
period of ‘plateaued development’, or a ‘real’ loss of skills.
Initial identification of any decline should be by developmental

history taking and educational reports (nursery, primary, and
secondary) combined with cognitive assessment. Monitoring
should be by periodic assessments combined with educational
reports specifically asking if the child is keeping up with peers
or has lost skills.
◆ Lost skills should be identified to ensure that their

absence is not solely situation-specific or that they have not
been subsumed into more complex behaviours.
◆ Educationalists may fear that a child is declining when

they may simply not be keeping up with their peers—thus
there is no absolute decline, only a relative one.
Comparison of raw scores rather than scaled scores on
normative tests will reveal the true state of affairs.
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The pattern of decline observed is dependent on the periods

between assessments. The shorter the period, the more
obvious the continuing development of the child alongside the
degenerative process. Longer periods give greater emphasis
to the decline.
(p.484) Childhood neurodegenerative diseases largely affect

white rather than grey matter and consequently are enhanced
by the factor of age at onset as it relates to the degree of both
myelination and intellectual development that has already
taken place. The specific neuropsychological and consequent
functional sequelae of these multitudinous disorders are
dependent upon the precise condition (see Shapiro and
Balthazor 2000).
The paediatric neuropsychologist has a central role in the

interpretation of this information, the provision of feedback to
medical colleagues, and the support of parents and teachers
coming to terms with a progressive intellectual decline in
childhood.
4.7 Neurofibromatosis
Type one neurofibromatosis has known cognitive and
behavioural sequelae; type two does not. The sequelae
associated with type one are as follows.
◆ Mean IQ is lowered and mild-to-moderate learning

difficulties are slightly more common than in the general
population. About half of patients have reduced academic
attainments.
◆ The range of neuropsychological impairments observed in

different individuals includes attention deficits, speech and
language difficulties, difficulties in visuospatial processing,
and motor coordination problems. There is no specific
neuropsychological profile.
◆ The increased presence of tumours (15–50% of cases) and

their treatment may lead to further cognitive sequelae.
Educational provision should be matched to the individual’s

difficulties. There are no specialist approaches specific to
neurofibromatosis type one or two. The extent of emotional
problems appears to be related to the degree of physical
disfigurement. Behavioural difficulties centre around attention
deficits, hyperactivity, impulsivity, and distractability.
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5 Neurodevelopmental disorders
5.1 Attention deficit hyperactivity disorders (ADHDs)
These are characterized by a triad of inattention, overactivity,
and impulsivity. They can occur with or without ‘hard’
neurological signs. Symptoms persist into adolescence in two
out of three cases. The problems associated with ADHD
include:
◆ poor educational attainments;
◆ peer/friendship difficulties;
◆ conflict with parents;
◆ (in adolescence) engagement in high-risk behaviours—

one in three has conduct disorder in adolescence.
These problems can result in reduced self-esteem and

sometimes depression. The prognosis is poorer in the presence
of a comorbid conduct disorder.
(p.485) In carefully selected children stimulant medication

can show significant benefits on attentional tasks and in
everyday functioning. A multiple treatment approach would
include:
◆ information provision;
◆ use of stimulant medication;
◆ family and school management advice;
◆ self-instructional training;
◆ (in some cases) dietary monitoring.
This approach improves long-term treatment efficacy.
The child clinical or paediatric neuropsychologist’s role is the

following.
◆ Diagnosis of children with the disorder. In particular,

diagnosis must be based on the persistence of symptoms
across settings. ADHDs are usually identified through use
of structured questionnaires such as the Achenbach Child
Behaviour Checklists (Achenbach 1991).
◆ On-going monitoring of cognitive and behavioural

changes using measures of focused and sustained attention
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and behavioural observation schedules such as those by

Conners (1996).
◆ Provision of information, behavioural management

advice, and self-control training to be used as adjunctive
therapy with medication.
5.2 Specific learning difficulties (SpLDs)
This term is applied by educators to a number of
‘disorders’ (reading, writing, arithmetic, and spelling) having
some similarities in symptomatology to conditions seen in
persons with an acquired brain injury. The nature of the
underlying pathologies and their relationships to observed
neuropsychological impairments continue to be investigated
(Hynd and Hiemenz 1997), but these are considered to be
‘necessary, but not sufficient’ elements for the manifestation of
the condition with significant contributions from
environmental and pedagogical factors.
There is a range of proven educational approaches in use by

specialist teachers working in this field selected according to a
child’s particular pattern of strengths and weaknesses. The
paediatric neuropsychologist would be best advised to seek
referral to such local services.
5.3 Nonverbal learning disability (NVLD)

NVLD is a postulated condition of multiple aetiology including
neuropathological disorders. Its characteristics are:
◆ bilateral tactile–perceptual difficulties particularly

affecting the left side;
◆ impaired visual recognition and discrimination;
◆ problems with visuospatial organization;
(p.486)
◆ bilateral psychomotor coordination difficulties, again
more marked on the left side;
◆ problems with managing novel information.
Auditory–verbal processing is preserved as are simple motor

skills, auditory perception, rote learning, selective and
sustained attention for auditory–verbal information, basic
expressive and receptive language, reading, and spelling.
Rourke (1989) outlines a wide range of secondary and tertiary
Page 22 of 25
disorders
neuropsychological, academic, and socioemotional deficits

arising from NVLD.
The model is specifically a cognitive–developmental one

linking neurological impairment to neuropsychological deficit
by way of the ‘white-matter hypothesis’ that emphasizes the
need for integrity of white matter function for normal child
development. Rourke reasons that in the right hemisphere
white matter is important for development and maintenance of
function; in the left hemisphere it is only important for
development. Consequently, the right hemisphere is seen as
particularly reliant upon cerebral integrity in order to continue
functioning effectively. As one would expect from a cognitive–
developmental model, the implication is that the degree of
white matter damage, the nature of the lesion, and the
developmental stage at the time of cerebral insult determine
symptom severity.
There is no proven treatment for the condition. Management is

through utilization of language-based strengths at home and in
school. Visually based information needs to be supported with
verbal description. Large tasks need to be broken down into
smaller, more easily assimilated steps. Abstract material
requires discussion and verbal labelling of concepts. There is
limited evaluation of the success of such interventions.
Achenbach, T. (1991). Integrative guide for the 1991 Child

Behaviour Checklist/4–18, YSR and TRF profiles. University of
Vermont Department of Psychiatry, Burlington, Vermont.
Anderson, V., Northam, E., Hendy, J., and Wrennall, J.

(2001). Developmental neuropsychology: a clinical approach.
Conners, C. (1996). Conners Abbreviated Symptom

Questionnaire. Psychological Assessment Resources, Odessa,
Florida.
Dixon, R.A. and Bäckman, L. (1999). Principles of

compensation in neurorehabilitation. In Cognitive
Page 23 of 25
disorders
rehabilitation (ed. D.T. Stuss, G. Winocur, and I.H. Robertson),

pp. 59–72. Cambridge University Press, Cambridge.
Ewing-Cobbs, L., Levin, H.S., Fletcher, J.M., Miner, M.E.,

and Eisenberg, H.M. (1990). The Children’s Orientation and
Amnesia Test: relationship to severity of acute head injury and
to recovery of memory. Neurosurgery 27, 683–91.
Hynd, G.W. and Hiemenz, J.R. (1997). Dyslexia and gyral

morphology variation. In Dyslexia: biology, cognition and
intervention (ed. C. Hulme and M. Snowling), pp. 38–58.
Whurr Publishers Ltd, London.
Jennett, B. and Teasdale, G. (1981). The management of

head injuries. F.A. Davis and Co., Philadelphia.
Johnson, D. and Rose, D. (1996). Brain injury in childhood—

is younger better?, Disability Awareness No. 13. Disability
Management Research Group, Astley Ainslie Hospital,
Edinburgh.
Rourke, B.P. (1989). Nonverbal learning disabilities. Guilford

Press, New York.
(p.487) Shapiro, E. and Balthazor, M. (2000). Metabolic

and neurodegenerative disorders. In Pediatric
neuropsychology: research, theory and practice (ed. K.O.
Yeates, M.D. Ris, and H.G. Taylor), pp. 171–205. Guilford
Press, New York.
Simpson, D.A., Cockington, R.A., Hanieh, A., Raftos, J.,

and Reilly, P.L. (1991). Head injuries in infants and young
children: the value of a paediatric coma scale. Child’s Nerv.
Syst. 7, 183–90.
Temple. C. (1997). Developmental Cognitive

Neuropsychology. Psychology Press, Hove, East Sussex.
World Health Organisation(WHO) (1980). International

classification of impairments, disabilities and handicaps. WHO,
Geneva.
Yeates, K.O., Ris, M.D., and Taylor H.G. (eds.) (2000).

Pediatric neuropsychology: research, theory and practice.
Guilford Press, New York. (p.488)
Page 24 of 25
disorders
Page 25 of 25
Neuropsychopharmacology


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Chris M. Bradshaw
DOI:10.1093/acprof:oso/9780199234110.003.025

An understanding of the principles of
neuropsychopharmacology is important for the practising
clinical neuropsychologist because a large proportion of
neurological and psychiatric patients receive medication that
can affect higher functions, both for good and for ill. Improved
understanding of the cellular mechanisms underlying the
therapeutic and adverse effects of psychoactive drugs has
shed considerable light on the neural bases of normal and
abnormal neuropsychological function. As yet, however, there
are no validated pharmacological treatments for specific
neuropsychological dysfunctions (dysmnesias, dysphasias,
etc.). This chapter discusses synaptic transmission in the
central nervous system, pharmacodynamic principles,
pharmacokinetic principles, therapeutic effects and side-
effects, and classes of centrally acting drugs.
Keywords: neuropsychopharmacology, synaptic transmission,

pharmacodynamic principles, pharmacokinetic principles, therapeutic effects
1 Introduction
Page 1 of 46
An understanding of the principles of

neuropsychopharmacology is important for the practising
clinical neuropsychologist because a large proportion of
neurological and psychiatric patients receive medication that
can affect higher functions, both for good and for ill.
Improved understanding of the cellular mechanisms

underlying the therapeutic and adverse effects of psychoactive
drugs has shed considerable light on the neural bases of
normal and abnormal neuropsychological function. As yet,
however, there are no validated pharmacological treatments
for specific neuropsychological dysfunctions (dysmnesias,
dysphasias, etc.). Rational pharmacotherapy (i.e treatment
based on the actions of drugs on known pathological
processes) exists for some neurological conditions (e.g.
Parkinson’s disease, some forms of epilepsy), but the utility of
nearly all the drugs that are currently used to treat ‘functional’
psychiatric disorders has been discovered by fortuitous clinical
observation.
Establishing the efficacy of drug treatment in psychiatry poses

significant problems due to the complex and variable
symptatology and time-courses of the disorders, imperfect
measuring instruments, and the frequently weak effects of the
drugs in question, which are often confounded by side effects
(see Section 5). A readable critique of the design of controlled
clinical trials, their advantages and pitfalls, is provided by
Harrison-Read and Tyrer (2004).
2 Synaptic transmission in the central nervous system

2.1 General principles
Chemical synaptic transmission involves the following steps:
◆ Precursor accumulation. Precursors of transmitters are

often amino-acids that are present in the circulating blood.
They are actively transported into neurones by a membrane
‘pump’.
◆ Transmitter synthesis. Precursor molecules are converted

into transmitter molecules by a sequence of enzyme-
catalysed reactions.
◆ Storage. Transmitter molecules may be retained within

vesicles in presynaptic terminals by a membrane ‘pump’.
(p.492)
Page 2 of 46
◆ Release. Ejection of transmitter molecules from the

synaptic terminal is triggerred by the passage of an action
potential along the axon, causing depolarization of the
terminal membrane. Channels in the terminal membrane
are opened, permitting influx of calcium ions, which cause
the vesicles to discharge their contents into the synaptic
cleft.
◆ Receptor stimulation. The binding of a transmitter

molecule to a receptor initiates a sequence of events
culmination in a change in the electrical excitability of the
postsynaptic cell (see Section 2.3).
◆ Inactivation. Transmitter molecules may be removed from

their site of action by the action of enzymes on the pre- and
postsynaptic membranes, or by transport into presynaptic
terminals (re-uptake). After re-uptake, transmitter
molecules may be re-stored in vesicles or destroyed by
enzymes.
2.2 Neurotransmitters and neuromodulators
2.2.1 Glutamate
Glutamate is an amino-acid that mediates excitatory
transmission in many central pathways. Corticofugal
glutamatergic neurones are believed to play a key role in
cognitive functions subserved by ‘cortico-striatal loops’.
Excessive release of glutamate may cause over-excitation of
postsynaptic neurones, which may die as a consequence
(excitotoxicity). This may account for neuronal loss in the area
surrounding a cerebral infarct, and for neuronal loss in
convulsive seizure disorders.
2.1.2 γ-Aminobutyric acid

γ-Aminobutyric acid (GABA) is the principal inhibitory amino-
acid transmitter in supraspinal pathways. The inhibitory
efferent pathways from the basal ganglia and the cerebellum
are GABAergic, and GABA also mediates the inhibitory effects
of intracortical neurones. Suppression of GABAergic
transmission can lead to convulsions.
2.2.3 Acetylcholine
Acetylcholine is the transmitter at skeletal neuromuscular
junctions, parasympathetic (and some sympathetic) effector
junctions, and all autonomic ganglia. It mediates both
excitatory and inhibitory effects in the central nervous system.
It is synthesised from choline by the enzyme choline
Page 3 of 46
acetyltransferase. Synaptically released acetylcholine is

metabolized by acetylcholinesterase located on pre-and
postsynaptic membranes. Cholinergic interneurones oppose
the influence of dopamine in the basal ganglia, and
manipulation of cholinergic function is an important strategy
in the management of Parkinson’s disease and drug-induced
parkinsonism (see below). Cholinergic neurones in the basal
forebrain project to the hippocampus and neocortex;
degeneration of these neurones is thought to underlie some of
the cognitive deficits of Alzheimer’s disease.
2.2.4 Dopamine
Dopamine is a catecholamine synthesised from the amino-acid
tyrosine. Tyrosine hydroxylase converts tyrosine to L-DOPA,
which is converted to dopamine by the action of aromatic
amino-acid decarboxylase. Synaptically released dopamine is
inactivated by (p.493) re-uptake into presynaptic terminals
followed by re-storage or degradation by monoamine oxidase
(MAO). The cell bodies of dopaminergic neurones reside in
circumscribed nuclei in the brainstem, their unmyelinated
fibres projecting to many parts of the neuraxis. The three
principal dopaminergic pathways are:
◆ the nigrostriatal pathway (substantia nigra → corpus

striatum), whose degeneration underlies the
pathophysiology of Parkinson’s disease;
◆ the mesolimbic/mesocortical pathway (midbrain ventral

tegmental area → limbic structures and cerebral cortex),
hyperfunction of which has been postulated to occur in
schizophrenia;
◆ the tuberoinfundibular pathway (hypothalamus →

pituitary stalk), which regulates the secretion of some
adenohypophyseal hormones.
2.2.5 Noradrenaline (norepinephrine)

Noradrenaline is a catecholamine that is synthesised from
tyrosine via the intermediate compounds L-DOPA and
dopamine. Synaptically released noradrenaline is inactivated
by re-uptake into terminals followed by re-storage or
degradation by MAO. Noradrenaline is the transmitter at most
sympathetic effector junctions. The cell bodies of central
noradrenergic neurones reside in nuclei in the pons and
Page 4 of 46
medulla, their axons projecting to most parts of the neuraxis.

Noradrenergic pathways include:
◆ the dorsal noradrenergic bundle (coeruleocortical

pathway: locus coeruleus → neocortex and hippocampus);
◆ the ventral noradrenergic bundle (tegmental nuclei →

hypothalamus);
◆ descending noradrenergic pathways (tegmental nuclei →

spinal cord and medullary autonomic nuclei).
Central noradrenergic transmission may contribute to the ‘fine

tuning’ of some higher functions (e.g. improving the signal/
noise ratio in some sensory pathways) and the maintenance of
arousal. Central noradrenergic dysfunction may be involved in
some anxiety states.
2.2.6 5-Hydroxytryptamine (5-HT, serotonin)

5-HT is an indolamine synthesised from tryptophan via the
intermediate precursor 5-hydroxytryptophan. Synaptically
released 5-HT is inactivated by re-uptake into terminals
followed by re-storage or degradation by MAO. The cell bodies
of 5-HTergic neurones reside in the raphe nuclei of the
brainstem, their axons projecting to most parts of the
neuraxis. 5-HTergic pathways include:
◆ ascending pathways from the dorsal and median raphe

nuclei;
◆ descending raphe-spinal pathways.
The projections from the dorsal and median raphe nuclei show
considerable overlap. However the median nucleus provides
most of the 5-HTergic afferents to the hippocampus, while the
dorsal nucleus provides most of the input to the striatum. 5-
HTergic dysfunction has been proposed as a
pathophysiological factor in depressive illness, (p.494)
obsessive-compulsive disorder and anxiety disorders. There is
evidence for 5-HTergic hypofunction in some impulse-control
disorders.
2.2.7 Histamine
Histamine is a monoamine. It plays an important role in the
control of acid secretion in the stomach. Its presence in the
brain has been known for some time, but its neurotransmitter
role has only recently been established. Histaminergic
Page 5 of 46
neurones in the tuberomammillary nucleus of the

hypothalamus project to the cerebral cortex. They are believed
to play an important role in the maintenance of wakefulness.
2.2.9 Neuropeptides
Neuropeptides are large molecules, made up of sequences of
amino-acids. Many ‘families’ of neuropeptides have been
identified (e.g. hypothalamic hormone-releasing and release-
inhibiting factors, tachykinins, opioid peptides). In some cases
they are co-localized with ‘classical’ neurotransmitters, and act
at specific receptors on pre- and postsynaptic membranes.
One of the postulated roles of neuropeptides is to modulate
the action of co-localized ‘classical’ transmitters.
Neuropeptites have been implicated in pain transmission
(substance P), anxiety (cholecystokinin) and the rewarding
effects of drugs of abuse (enkephalin) (Hökfelt et al. 2000;
Leonard 2004). The orexins, two peptides expressed by groups
of neurones in the lateral and dorsomedial hypothalamus, have
been implicated in arousal mechanisms and feeding.
Orexinergic neurones of the lateral hypothalamus, which
project to the ventral tegmental area (the origin of the
mesolimbic/mesocortical dopaminergic pathway), may help to
regulate the ‘reward value’ of both food and drug reinforcers
(Harris and Aston-Jones 2006).
2.3 Receptors
There are two main receptor ‘superfamilies’, distinguished by
the effector mechanisms to which they are coupled:
◆ ionotropic (ion-channel-coupled) receptors, in which the

transmitter (or drug) molecule binds directly to a site on an
ion channel and thereby regulates the movement of ions in
or out of the postsynaptic cell;
◆ metabotropic (G-protein-coupled) receptors, in which

binding of the transmitter or drug molecule initiates a
cascade of events within the postsynaptic cell, culminating
in a change in the permeability of the membrane to
particular ionic species.
Ionotropic receptors mediate rapid changes in electrical

excitability, whereas metabotropic receptors mediate slower
responses. In the case of metabotropic receptors, attachment
of the transmitter molecule to the binding site alters the state
of a protein in the postsynaptic membrane (‘G-protein’), which
Page 6 of 46
in turn alters the activity of an enzyme. Two principal enzymes

are associated with metabotropic receptors:
◆ adenylyl cyclase, which converts adenosine triphosphate

(ATP) to cyclic adenosine monophosphate (cyclic AMP);
◆ phospholipase-C, which converts phosphatidylinositol to

inositol trisphosphate and diacylglycerol.
(p.495) The products of these reactions are called second

messengers (in distinction from the neurotransmitter, the ‘first
messenger’); they activate a protein kinase that regulates ion
channel opening. A transmitter may act at many types of
receptor coupled to different effector mechanisms, giving
scope for a great variety of postsynaptic effects (Table 25.1).
2.4 Regulation of neurotransmitter function

Many neurones regulate their own function via autoreceptors
(receptors on the membrane of a neurone which respond to
that neurone’s own transmitters). Somatodendritic
autoreceptors reside on the cell bodies and dendrites, and
terminal autoreceptors on the
Page 7 of 46
Table 25.1 The major central nervous system transmitters and some of their receptors
Transmitter Receptor Typea Effectorb Function
Glutamate AMPA IR Na+/K+ channels postsynaptic excitation
Kainate IR Na+/K+ channels postsynaptic excitation
NMDA IR Ca2+/Na+/K+ channels postsynaptic excitation
mGlu group I MR PL (↑) postsynaptic excitation
mGlu groups II, III MR AC (↓) postsynaptic excitation
GABA GABAA IR Cl− channel postsynaptic inhibition
GABAB MR ? postsynaptic inhibition
Acetylcholine Nicotinic IR Ca2+/Na+/K+ channels postsynaptic excitation
muscarinic M1 MR PL (↑) postsynaptic excitation
muscarinic M2 MR AC (↓) postsynaptic excitation/

inhibition (?)
muscarinic M3 MR PL (↑) postsynaptic excitation
muscarinic M4 MR AC (↓) postsynaptic excitation/

inhibition (?)
Dopamine D1 MR AC (↑) postsynaptic inhibition

(?)
D2 MR AC (↓) postsynaptic excitation/

inhibition (?),
Page 8 of 46

somatodendritic
autoreceptor
D3 MR ? postsynaptic excitation/
inhibition (?),
somatodendritic
autoreceptor
D4 MR ? postsynaptic excitation/
inhibition (?)
Noradrenaline α1-adrenoceptor MR PL (↑) postsynaptic excitation
α2-adrenoceptor MR AC (↓), K+/Ca2+ somatodendritic

channels autoreceptors
β1-adrenoceptor MR AC (↑) postsynaptic inhibition
β2-adrenoceptor MR AC (↑) non-neuronal (glial,

vascular)
responses
5-HT 5-HT1A MR AC (↓) somatodendritic

autoreceptor,
postsynaptic inhibition
(?)
Page 9 of 46
5-HT1B/D MR AC (↓) terminal autoreceptor,

postsynaptic inhibition
(?)
5-HT2A MR PL (↑) postsynaptic excitation/

inhibition (?)
5-HT2C MR PL (↑) postsynaptic excitation/

inhibition (?)
5-HT3 IR Na+/K+ channels postsynaptic excitation
5-HT4 MR AC (↑) postsynaptic excitation/

inhibition (?)
5-HT5 MR AC (↓) ?
5-HT6 MR AC (↑) ?
5-HT7 MR AC (↑) ?
a
receptor types: IR, ionotropic receptor; MR, metabotropic receptor.
b
effectors: AC, adenylyl cyclase system; PL, phospholipase-C system.
↑and ↓ indicate stimulation or inhibition, respectively.
Note that the list is not exhaustive, and that the functions mediated by many of the receptors are poorly understood.
Page 10 of 46
(p.496) presynaptic terminals. Autoreceptors usually serve a

negative feedback role, receptor stimulation resulting in
suppression of neuronal activity.
Neurotransmitter function is also regulated by receptor
adaptation. Excessive receptor stimulation leads to a decrease
in the number of available receptors (down-regulation), with a
consequent loss of sensitivity to the transmitter and other
agonists (desensitization). Conversely, low levels of receptor
stimulation (e.g. following atrophy of afferent fibres) result in
homeostatic receptor proliferation (up-regulation), with
consequent enhancement of sensitivity.
3 Pharmacodynamic principles
The attachment of transmitters and other drugs to receptor
molecules is determined by the laws of reversible chemical
reactions. The affinity of a drug (D) for a receptor (R) is
defined by the ratio of the rate constants for the formation and
dissolution of a drug-receptor complex (DR). In the absence of
any complicating biological processes, the concentration of DR
is hyperbolically related to the drug concentration:
where Rt is the total number of receptors, and KD, the

equilibrium dissociation constant, is the reciprocal of the
affinity. This concentration-binding relation has a sigmoidal
form when concentration is plotted on a logarithmic scale (Fig.
25.1(a)). In a living system, the magnitude of the biological
response evoked by an agonist is related to concentration of
occupied receptors [DR]. However the nature of this
relationship can be (p.497) highly complex. In addition to the
affinity constant and the size of the receptor population,
empirical dose-response relations depend upon a host of other
factors, including limitations on the response capacity of the
effector (biological ‘ceiling’), limtations on the ability of the
agonist to elicit a full response (‘instrinsic activity’), and
factors unrelated to receptor, such as drug inactivation
mechanisms (e.g. uptake and enzymatic degradation) and
biological ‘barriers’ that impede access of the drug molecules
to the receptor sites.
Transmitters and drugs that stimulate receptors and evoke

physiological responses are referred to as agonists.
Antagonists evoke no response of their own but prevent the
action
Page 11 of 46
(p.498) of
agonists.
Different forms
of drug
antagonism are
possible. In
competitive
antagonism the
agonist and
antagonist
compete for
access to the
same receptor
site.
Competitive
antagonism is
surmountable, Fig. 25.1 Pharmacological concentration-
because response curves. (a) Relation between
increasing the response (expressed as a percentage of
concentration
the maximum response) and
of the agonist
concentration of an agonist (note
results in
displacement
logarithmic scale). The concentration
of antagonist corresponding to the half-maximal
molecules from response (EC50) is indicated by the arrow.
the receptors. (b) Effect of a competitive antagonist. The
The dose- concentration-response curve for the
response curve agonist alone is shown by the continuous
is displaced to line, and the curve for the agonist in the
the right
presence of a fixed concentration of the
without any
antagonist by the broken line. Note the
change in the
parallel displacement of the curve by the
maximum
response (Fig. antagonist. (c) Effect of a non-competitive
25.1(b)). In antagonist (conventions as in (b)). Note
non- that the antagonist depresses the
competitive maximum response without displacing
antagonism the the curve to the right. (See text for
antagonist details.)
impedes the
production of
the biological response but does not prevent the agonist from
binding to its receptor. In this case, the maximum of the dose-
response curve is reduced, but the curve is not displaced to the
right (Fig. 25.1(c)). Partial agonists are agonists with low intrinsic
activity.
4 Pharmacokinetic principles
Page 12 of 46
The magnitude of a drug’s effect is related to its concentration

at its site of action. For centrally acting drugs, this is not
directly measurable, and plasma concentration provides the
only practical index of tissue concentration. This is satisfactory
for drugs that gain easy access to the brain. However, many
drugs enter the brain with difficulty, because of the blood-
brain barrier (see Section 4.4).
4.1 Absorption, distribution and elimination

The single-dose kinetics of a drug describe the rise in plasma
concentration as the drug is absorbed into the circulation, and
the subsequent fall in concentration as the drug is distributed
to the tissues and eliminated by metabolism and/or excretion
(Fig. 25.2(a)). The rate of elimination of a drug relative to its
concentration in the plasma is known as clearance. The
clearance of most drugs is fairly constant over a wide range of
concentrations; i.e. a constant fraction of the total amount of
drug present in the plasma is eliminated per unit time ( first-
order kinetics). The plasma half-life (t½) is the time taken for
the plasma concentration to fall by 50%. Active metabolism of
a drug may result in a short t½. However this does not
necessarily imply a short duration of action; for example, the
benzodiazepine flurazepam has a t½ of about 2 hours, but its
effects are prolonged due to the production of an active
metabolite, desalkylflurazepam, whose t½ is about 30-100
hours.
The rate of absorption is influenced by the route of

administration. The most common routes are:
◆ intravenous (i.v.) infusion, which results in a very rapid

rise in concentration because the obstacles to absorption
posed by lipid membranes in the gut and the capillaries are
bypassed;
◆ intramuscular (i.m.) injection, which results in somewhat

slower absorption into the circulation;
◆ oral (per os, p.o.) administration, which results in the

slowest absorption, and is also less reliable than parenteral
routes because the rate of absorption may be affected by
such factors as the presence of food in the stomach. An
orally administered drug, having been absorbed into the
circulation, is first transported to the liver via the hepatic
portal vein. Liver enzymes may destroy a substantial
Page 13 of 46
proportion of the absorbed drug ( first-pass metabolism).

(p.499)
4.2 Multiple dosing and steady-state concentration
To produce a
sustained
effect, a drug
must be
continuously
present in the
body in an
adequate
Fig. 25.2 (a) Single-dose kinetics.

Ordinate, plasma concentration of the
drug; abscissa, time measured from the
time of administration. Note that plasma
concentration falls to half its peak level in
one half-life (t½). A further half-life
results in a further halving of plasma
concentration, and so on. (b) Change in
plasma concentration following repeated
dosing at intervals of approximately t½.
The therapeutic range is indicated by the
horizontal lines. Steady-state mean
plasma concentration is attained after
approximately 4 half-lives (indicated by
the arrow). Note that the peaks and
troughs of the steady-state concentration
may fall outside the therapeutic range.
(c) Administration of smaller doses more
frequently (indicated by the arrow)
results in smaller fluctuations in plasma
concentration. (See text for details.)
concentration. The purpose of repeated dosing is to maintain
Page 14 of 46
the concentration within the therapeutic range. If the drug

concentration is not allowed to fall to zero between doses,
mean plasma concentration rises progressively with repeated
dosing, eventually approaching a steady state (Fig. 25.2(b)).
However, in the case of a drug with a narrow therapeutic
range, the inter-dose fluctuations in concentration may result
in unacceptable side-effects soon after a dose and
therapeutically insufficient concentrations before the next
dose is administered. One solution to this problem is to give
smaller doses more frequently (Fig. 25.2(c)); however this may
place an unbearable burden of inconvenience (p.500) on the
patient. More satisfactory alternatives are available for some
drugs in the form of sustained-release or depot preparations.
4.3 Sustained-release and depot preparation

Sustained-release preparations provide a gradual release of
the drug from particles during their passage through the gut.
They allow once-daily dosing rather than the three or four
doses per day that may be needed with conventional oral
preparations. Depot preparations provide a slow release from
an oily vehicle administered by deep intramuscular injection;
injections given at 2- or 4-week intervals may be used in place
of multiple daily oral doses.
4.4 Blood-brain barrier (BBB)

This is a property of capillaries in the cerebral circulation that
prevents passage of fat-insoluble molecules into the brain
tissue.
4.5 Drug interactions

The presence of one drug in the body may alter the effect of
another drug. There are two main types of interaction:
◆ pharmacodynamic interactions, e.g. drugs A and B

competing for the same receptor site, as in competitive
antagonism (see Section 3);
◆ pharmacokinetic interactions, e.g. drug A altering the

activity of an enzyme that metabolizes drug B.
5 Therapeutic effects and side-effects

Most centrally acting drugs have multiple effects. However,
different concentrations of a drug may be needed to exert its
desired (therapeutic) effect and undesired effects (side-
effects). The therapeutic range is the concentration range in
which therapeutic effects are obtained without intolerable
Page 15 of 46
side-effects. The therapeutic index is the ratio of the maximum

tolerated concentration to the minimum effective
concentration.
5.1 Cognitive side-effects

Cognitive side-effects of psychoactive drugs are readily
quantifiable in placebo-controlled single-dose laboratory
experiments, but are difficult to pin down in clinical settings.
Many psychiatric and neurological conditions are associated
with cognitive dysfunction which may be mistaken for side-
effects of the drug. Side-effects seen in single-dose studies
may be poor predictors of side-effects in chronic treatment;
some side-effects dissipate during continuous treatment,
whereas other emerge only after months of regular treatment.
In most cases, cognitive side-effects of psychoactive drugs are

not specific to particular classes of drug, although strongly
sedative drugs and drugs that affect extrapyramidal functions
have especially pronounced effects on test performance that
requires fine movement or rapid responding. Memory test
performance tends to be more vulnerable than linguistic or
visuospatial performance. Although cognitive side-effects do
complicate the (p.501) interpretation of neuropsychometric
data, it should be remembered that psychiatric symptoms
(mood disturbance, psychosis) may distort test results to an
even greater degree than the drug used to treat them.
5.2 Drug withdrawal

Adverse effects are sometimes seen in drug withdrawal.
During continued use, tolerance may occur to the therapeutic
and/or side-effects of the drug. This may arise from:
◆ a change in tissue sensitivity(neuroadaptation,

pharmacodynamic tolerance); and/or
◆ a change in the rate of elimination of the

drug(pharmacokinetic tolerance).
After drug withdrawal there may be a rebound of physiological

processes that have been suppressed by the drug, and reversal
of tolerance that may have developed during chronic
treatment. An example of the former is the occurrence of
seizures on rapid withdrawal of a drug with anticonvulsant
properties. An example of the latter is the fatal overdose that
Page 16 of 46
may occur when an opiate addict takes his ‘usual’ dose after a
period of abstinence.
6 Classes of centrally acting drugs

6.1 Antipsychotics
Antipsychotics (neuroleptics) are currently classified as(i)
conventional or typical and(ii) atypical, on the basis of their
pharmacological profiles.
6.1.1 Conventional antipsychotics

These include the chemical classes:
◆ phenothiazines (e.g. chlorpromazine, trifluperazine,

thioridazine);
◆ thiaxanthines (e.g. flupenthixol, clopenthixol);
◆ butyrophenones (e.g. haloperidol, droperidol);
◆ diphenylbutylpiperidines (e.g. pimozide);
◆ substituted benzamides (e.g. sulpiride).
Mode of action
Conventional antipsychotics are D2 dopamine receptor

antagonists. This fact is one of the cornerstones of the
dopamine theory of schizophrenia (see Kapur et al. 2000). D2
receptors mediate postsynaptic effects of dopamine in the
three major dopaminergic pathways. Blockade of D2 receptors
in the neocortex and limbic structures (mesolimbic/
mesocortical projection) probably underlies the therapeutic
action of conventional antipsychotics, whereas blockade of D2
receptors in the striatum (nigrastriatal projection) and
pituitary stalk (tuberinfundibular pathway) is responsible for
many of their side-effects (see below). These drugs differ
widely in therapeutic potency. The average prescribed daily
dose correlates highly with affinity for D2 receptors (Seeman
et al. 1976).
Receptor cloning techniques have revealed a ‘family’ of D2-like

receptors (D2, D3, D4) with different regional distributions. D3
and D4 receptors are more abundant in the limbic system and
neocortex than in the striatum. Conventional antipsychotics
have (p.502) somewhat higher affinity for D2 than for D3 and
D4 receptors. At therapeutic doses, conventional
Page 17 of 46
antipsychotics occupy 65-80% of D2 receptors (Kapur et al.

2000).
Therapeutic uses
Conventional antipsychotics are effective in managing acute

psychotic episodes and as maintenance therapy for relapse
prevention in chronic schizophrenia. They are better able to
ameliorate positive psychotic symptoms (hallucinations,
delusions) than negative symptoms (avolition, anhedonia,
poverty of thought). They are also used to suppress manic
excitement, and (in combination with antidepressants) to treat
psychotic depression.
Pharmacokinetics
Conventional antipsychotics are well absorbed following oral

or parenteral administration, peak plasma concentration being
attained 1-4 hours after oral administration. The t½ of most
typical antipsychotics is between 10 and 30 hours. They
undergo first-pass metabolism. Hepatic metabolism of some
drugs (e.g. chlorpromazine) increases during chronic
treatment(enzyme induction), resulting in falling plasma
concentration. Treatment with depot preparations may require
months to attain steady-state plasma levels, and the drug may
be detected months after discontinuation.
Side-effects
Conventional antipsychotics, particularly high-potency

butyrophenones, are liable to induce extrapyramidal side-
effects (EPSs: akathisia, dystonia and ‘parkinsonian’ symptoms
– rigidity, bradykinesia and tremor). EPSs probably arise from
dopamine receptor blockade in the striatum. They are treated
by co-administration of centrally-acting anticholinergic drugs
(e.g. benztropine), which may correct the imbalance of
dopaminergic and cholinergic influences on striatal function
occasioned by D2 receptor blockade. Phenothiazines have
some anticholinergic action and are therefore less liable to
induce EPSs than butyrophenones. About 10% of patients
undergoing chronic treatment with conventional
antipsychotics experience a delayed side-effect, tardive
dyskinesia (involuntary orofacial movements and
choreoathetoid movements of the extremities). Patients
suffering from Lewy-body dementia show greatly enhanced
Page 18 of 46
sensitivity to the EPS-inducing effects of antipsychotics

(Ballard et al. 1998).
Single acute doses of conventional antipsychotics reduce

vigilance and impair psychomotor performance. In patients
undergoing chronic treatment, it is difficult to disentangle the
effects of the drug from the effects of the illness. Cognitive
performance may actually improve as a result of antipsychotic
medication, relative to the impairment seen in the
unmedicated state (King and Waddington, 2004).
These drugs increase prolactin secretion due to D2 receptor

antagonism in the tuberoinfundibular system. In sensitive
males this may cause impotence and galactorrhoea.
A rare, idiosyncratic, life-threatening side-effect is the

neuroleptic malignant syndrome, characterized by fever,
muscular rigidity, autonomic instability and coma.
6.1.2 Atypical antipsychotics

These include clozapine, risperidone, quetiapine, olanzapine,
amisulpiride, aripiprazole and sertindole.
Mode of action
These drugs have lower affinity for D2 receptors than

conventional antipsychotics. Clozapine has high affinity for
many receptors (D3 and D4 receptors, 5-HT2A, (p.503) 5-HT2C
and 5-HT1A receptors, muscarinic cholinoceptors, α1- and α2-
adrenoceptors, H1 histamine receptors), making it difficult to
attribute its therapeutic efficacy to any one mechanism. Most
other atypical antipsychotics share clozapine’s high affinity for
5-HT2 receptors. It has been suggested that dual antagonism
of dopamine and 5-HT receptors may underlie the therapeutic
effect of these drugs (Meltzer 1995). Some writers, however,
argue that since affinity for dopamine receptors is a common
feature of most, if not all, atypical antipsychotics, dopamine
receptor blockade offers the most parsimonious account of all
antipsychotic action (Kapur et al. 2000). One (controversial)
explanation for the low incidence of EPSs induced by atypical
antipsychotics (see below) is that these drugs may have a
higher affinity for dopamine receptors in limbic structures
than in the dorsal striatum (‘limbic selectivity’), resulting in
effective symptom control without concomitant disruption of
extrapyramidal motor control.
Page 19 of 46
Therapeutic uses
Atypical antipsychotics are generally as effective as the

conventional antipsychotics in treating positive psychotic
symptoms. Good symptom control may be achieved in some
patients whose illness is refractory to conventional
antipsychotics. There is a growing body of evidence that
negative schizophrenic symptoms respond more favourably to
atypical antipsychotics, which are notoriously refractory to
conventional antipsychotics (Burton, 2006).
Pharmacokinetics
Clozapine, olanzapine and quetipine are rapidly absorbed from

the gut and undergo first-pass metabolism. Their t½ values are
7 (quetiapine), 15 (clozapine) and 30 (olanzapine) hours.
Olanzapine can be given once daily, but twice-daily dosing is
recommended for the others. Risperidone is now available as a
depot injection preparation.
Side-effects
Atypical antipsychotics are less liable to induce EPSs than

conventional antipsychotics, possibly due to their relatively
low affinity for D2 receptors in the striatum (see above).
Clozapine produces a potentially life-threatening blood
disorder, agranulocytosis, in 1-2% of patients. Its use is
therefore restricted to patients whose symptoms do not
respond well to other antipsychotics, and regular blood counts
are implemented during treatment. Other adverse effects of
clozapine include sedation, nocturnal hypersalivation, and
anticholinergic effects (blurred vision, urinary retention,
constipation). Other atypical antipsychotics that have lower
affinity for muscarinic cholinoceptors are less liable to induce
anticholinergic side-effects. Olanzapine and risperidone have
been associated with increased risk of stroke in elderly
patients.
6.2 Antidepressants and mood-stabilizing drugs

Two major classes of antidepressants are:
◆ monoamine oxidase inhibitors (MAOIs);
◆ monoamine uptake inhibitors.
A few drugs with clinical antidepressant efficacy do not fit into

either category (see Szabadi and Bradshaw (2004). The most
Page 20 of 46
widely prescribed mood stabilizer is lithium. Carbamazepine,

valproate and lamotrigine also have mood-stabilizing
properties (see Section 6.4).
(p.504) 6.2.1 MAOIs

Mode of action
MAOIs block the enzyme MAO that normally destroys

monoamine transmitters within presynaptic terminals. This
increases the availability of the transmitter, and thus increases
postsynaptic receptor stimulation. MAO exists in two forms, A
and B. In the brain, noradrenaline and 5-HT are deaminated
mainly by MAO-A, and dopamine by MAO-B. The traditional
MAOIs, phenylzine, tranylcypromine and isocarboxasid, block
both forms irreversibly. Clorgyline is selective for MAO-A and
deprenyl for MAO-B. Deprenyl is not an effective
antidepressant, suggesting that dopaminergic mechanisms do
not play a major role in depressive illness. Unlike the
aforementioned MAOIs, moclobemide is a reversible inhibitor
of MAO-A (RIMA). Reversible MAO-A inhibition conveys some
advantage in terms of safety (see ‘Side-effects’, this section).
When administered chronically, MAOIs induce downregulation

of central 5-HT2 and 5-HT1A receptors and β-adrenoceptors.
The functional significance of this is controversial. The overall
effect of chronic MAOI treatment on monoaminergic
transmission is mainly facilitatory, as receptor downregulation
merely attenuates the increased postsynaptic receptor
stimulation caused by increased transmitter availability (Blier
et al. 1991).
Therapeutic uses
MAOIs are seldom the first choice of antidepressant due to

their potential for adverse effects (see below). They are useful
in some anxiety disorders (panic disorder, post-traumatic
disorder, social phobia) (Krishnan 1998).
Pharmacokinetics
MAOIs are rapidly absorbed. They undergo extensive first-pass

metabolism, and have short half-lives (Mallinger and Smith
1991).
Side-effects
Page 21 of 46
Orthostatic hypotension is a common-side effect. MAOIs

potentiate the effects of sympathomimetic amines, including
tyramine (a constituent of some foods, e.g. cheese) and
amphetamines, and may induce hypertensive crises. RIMAs
are safer in this respect, because high concentrations of
sympathomimetic amines are able to displace the RIMA from
the MAO molecule, allowing effective metabolism of the
amines. MAOIs are never combined with selective serotonin
reuptake inhibitors (SSRIs) as this can result in the potentially
lethal serotonin syndrome (agitation, autonomic instability,
progressing to convulsions and coma).
6.2.2 Monoamine uptake inhibitors

Mode of action
Re-uptake into presynaptic terminals is the principal

inactivation mechanism for monoamine transmitters. Uptake
blockade therefore potentiates monoaminergic transmission.
Chronic administration of uptake inhibitors results in
downregulation of β-adrenoceptors, α2-adrenoceptors, 5-HT2
receptors and presynaptic 5-HT1A receptors. These changes
may reflect homeostatic adaptation to increased postsynaptic
stimulation. Electrophysiological evidence indicates that
monoaminergic transmission continues to be enhanced during
chronic treatment with uptake inhibitors (Blier et al. 1991).
Monoamine uptake inhibitors are classified as:
◆ tricyclic antidepressants (TCAs) include imipramine,

desipramine, amitriptyline dosulepin [previously, dothiepin],
clomipramine, lofepramine, nortriptyline and (p.505)
trimipramine. They inhibit both noradrenaline and 5-HT
uptake, and block muscarinic cholinoceptors and α1-
adrenoceptors.
◆ selective serotonin re-uptake inhibitors (SSRIs) include

fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram
and escitalopram. These drugs specifically block 5-HT
uptake;
◆ selective noradrenaline re-uptake inhibitors (NARIs)

include maprotiline and reboxetine;
◆ serotonin-noradrenaline re-uptake inhibitors (SNRIs)

include venlafaxine and duloxetine. They block the uptake
Page 22 of 46
of both noradrenaline and 5-HT, but lack the anticholinergic

and adrenolytic effects of TCAs.
Therapeutic uses
TCAs are effective treatments for moderate/severe depressive

illness. However, SSRIs, and more recently NARIs and SNRIs,
have become more popular because they have fewer side-
effects and are safer in overdose than TCAs. It should be
recognised, however, that a favourable response to treatment
is not the same as complete remission of symptoms. In double-
blind trials, only about 40% of patients attain full remission of
depressive symptoms (Trivedi et al. 2006), and the remission
rate in general clinical practice may be even lower (Israel
2006). Augmentation treatment may be helpful in difficult
cases; the use of lithium and thyroid hormone is supported by
evidence from controlled clinical trials (DeBattista 2006).
TCAs and SSRIs are prescribed at low dose levels for chronic
pain. SSRIs are prescribed for panic disorder, obsessive-
compulsive disorder and impulse-control disorders (den Boer
et al. 2000).
Pharmacokinetics
TCAs are readily absorbed from the gut. They have relatively
long half-lives (8-36 hours), allowing once-daily dosing. SSRIs
are also eliminated slowly and are therefore suitable for once-
daily dosing. Fluoxetine has a particularly long t½ (85 hours)
and its active metabolite even longer; it is recommended that
5 weeks be allowed for effective ‘washout’ before replacement
with potentially interactive drugs (e.g. MAOIs). Venlafaxine
and its active metabolite have shorter half-lives (4-10 hours);
venlafaxine is usually given in divided doses or as an extended-
release preparation.
Side-effects
The affinity of TCAs for muscarinic cholinoceptors accounts

for the cluster of side-effects (anticholinergic side-effects)
brought about by suppression of parasympathetically mediated
functions: dry mouth, constipation, blurred vision, urinary
hesitancy/retention and erectile impotence. Tachycardia may
reflect both anticholinergic action and peripheral
noradrenaline uptake blockade, and postural hypotension may
reflect β-adrenoceptor blockade. Increased sweating probably
reflects central noradrenaline uptake blockade, as peripheral
Page 23 of 46
muscarinic receptor blockade would be expected to supress

sweating. TCAs are notoriously sedative, which may reflect
blockade of central α1-adrenoceptors and H1 histamine
receptors. TCAs may cause cognitive dysfunction, especially
memory impairment, which may reflect central cholinoceptor
blockade.
SSRIs have fewer side-effects and a wider therapeutic range

than SSRIs (Szabadi and Bradshaw 2004). In combination with
MAOIs they can cause the serotonin syndrome (see above).
Sexual dysfunction, a common complaint, is attributable to
central 5-HT potentiation. Nausea is common, but usually
disappears during continued use. Although (p.506) early
reports of increased risk of suicide in patients treated with
SSRIs have not been substantiated (Warshaw and Keller,
1996), close monitoring of suicidal or hostile ideation is
recommended, particularly at the beginning of treatment of
after a dosage change.
NARIs and SNRIs have the expected side-effect profile of

drugs that potentiate central and peripheral noradrenergic
transmission, including mild hypertension and increased
alertness.
6.2.3 Other antidepressant drugs

For a review of the pharmacology of the following compounds,
see Szabadi and Bradshaw (2004).
◆ Mirtazepine is a presynaptic α2-adrenoceptor antagonist.

Blockade of these receptors is proposed to enhance central
noradrenergic and 5-HTergic transmission. The drug has
some sedative effect but lacks the antimuscarinic effects of
TCAs.
◆ Trazodone is a weak 5-HT uptake inhibitor. It has

antagonistic action at α1- and α2-adrenoceptors.
◆ Mianserin has some noradrenaline uptake inhibiting

action and is a potent antagonist at α2-adrenoceptors.
◆ Tryptophan, the precursor of 5-HT, is occasionally used as

an adjunct to standard antidepressant therapy in refractory
depresion.
6.2.4 Lithium
Mode of action
Page 24 of 46
Lithium is administered as a salt (lithium carbonate or lithium

citrate), in which lithium exists as a monovalent cation. It can
replace other cations in ion transport systems, allowing it to
enter neurones and blood cells. It has numerous effects on
monoaminergic transmission, including facilitation of
tryptophan uptake, increased 5-HT and noradrenaline release,
prevention of postsynaptic dopamine receptor supersensitivity,
and inhibition of the cyclic AMP and phosphoinositol second
messenger systems. The relationship between these effects
and clinical mood stabilization is uncertain (Lenox and Manji
1998).
Therapeutic uses
Lithium is the first-line treatment for manic-depressive illness.

Because of the high relapse rate of this disorder, continued
treatment over a period of years is recommeded (see Goodwin
and Young 2003). Lithium can augment the effects of TCAs and
SSRIs in treating refractory depression. It has also been
advocated in the management of impulsive agression
(Kavoussi and Coccaro 1998).
Pharmacokinetics
Lithium is rapidly absorbed from the gut and has a t½ of about

20 hours. Because of its low therapeutic index (see below),
divided doses are recommended in the early stages of
treatment in order to avoid toxic side-effects.
Side-effects
Lithium has a low therapeutic index, and regular monitoring of

serum concentration is standard practice. Serum
concentrations of 0.4–1.0 mEq l−1 are cited as the therapeutic
range, but there is considerable variation between individuals.
The signs of lithium toxicity are vomiting, diarrhoea, coarse
tremor, ataxia, dysarthria, agitation or lassitude, and cognitive
impairment. Untreated, lithium toxicity can progress to
seizures and coma. Within the therapeutic range many
patients experience side-effects, including (p.507) memory
problems, thirst, polyuria and fine tremor. There are few
objective data about the cognitive side-effects of lithium,
although in this writer’s experience memory impairment and
general reduction of mental acuity are not uncommon in
patients treated with lithium.
6.3 Anxiolytics and hypnotics
Page 25 of 46
Barbiturates are no longer used as anxiolytics or sedatives.

Benzodiazepines, β-adrenoceptor antagonists and 5-HT1A
receptor agonists are considered here. Antidepressants are
also used to treat some anxiety disorders (see Section 6.2).
Pregabalin is finding increasing popularity as an anxiolytic for
medium- or long-term use (see Section 6.4).
6.3.1 Benzodiazepines
Mode of action
Benzodiazepines bind to specific sites on the GABAA receptor-

ionophore complex. GABA’s inhibitory action is mediated by
the opening of Cl− channels in postsynaptic membranes.
Benzodiazepines have no effect of their own on the Cl−
channel, but potentiate GABA’s channel-opening action. This
action of benzodiazepines differs from that of barbiturates
which act directly on the ionophore to promote Cl− influx
(Haefely 1990). The sites within the brain where
benzodiazepines’ GABA-potentiating action gives rise to their
anxiolytic, sedative and anticonvulsant actions remain elusive.
The GABAA receptor-ionophore complex comprises several
‘subunits’, different forms of which are differentially expressed
in different brain regions. This offers the hope of developing
benzodiazepine-like drugs that may target specific regions and
thereby exert more selective therapeutic effects.
Therapeutic uses
Benzodiazepines are effective in relieving the symptoms of

generalized anxiety disorder. Their popularity waned in the
1980s when problems of dependence were first recognized.
However more recent studies have generally failed to find
compelling evidence for addiction to benzodiazepines in
routine clinical use (Miller et al. 1995). In the UK they are
recommended for prescription for limited periods only (2-4
weeks) in severe anxiety. In longer-term treatment their
effectiveness is equalled by SSRIs, venlafaxine and pregabalin
(Hidalgo et al, 2007). Benzodiazepines are also used as night-
time sedatives, as anticonvulsants, in alcohol withdrawal (to
reduce distress and prevent seizures), and as intravenous
anaesthetics for minor surgery.
Page 26 of 46
Pharmacokinetics
A range of benzodiazepines is available with pharmacokinetic

profiles to suit their different uses. An ideal hypnotic has a
rapid onset of action, and should not produce a ‘hangover’ the
following day. Temazepam, which is rapidly absorbed and has
a t½ of about 8 hours, is appropriate for this purpose. Patients
with generalized anxiety disorder require sustained anxiolysis,
such as that afforded by the long t½ of diazepam. Diazepam’s
slow elimination is also advantageous in the management of
withdrawal from alcohol or other benzodiazepines.
Side-effects
Benzodiazepines are among the safest centrally acting drugs

when taken in overdose. Their principal side-effect is sedation,
resulting in impairment psychomotor performance and slow
information processing. Higher doses induce dysarthria and
ataxia. Antergrade amnesia may follow intravenous
administration (Cooper 2004).
(p.508) 6.3.2 β-adrenoceptor antagonists

Mode of action
These drugs (e.g. propranolol) block the effects of

noradrenaline mediated by β-adrenoceptors, including
tachycardia and tremor. By preventing these somatic
manifestations of anxiety they may break the ‘vicious cycle’ of
physiological and psychological responses that is postulated by
some theories of anxiety (Granville-Grossman and Turner,
1966).
Therapeutic uses
β-adrenoceptor antagonists suppress somatic anxiety

symptoms (excluding sweating and xerostomia, which are
cholinoceptor- and α-adrenoceptor-mediated). They are helpful
in managing situational anxiety, for example in performing
artists or public speakers. They are not useful for patients
whose subjective anxiety is not accompanied by β-
adrenoceptor-mediated somatic symptoms.
Pharmacokinetics
Propranolol’s t½ is about 4 hours. A slow-release preparation is

available.
Side-effects
Page 27 of 46
β-adrenoceptor blockade can induce hypotension and

dizziness, and may provoke asthma attacks in susceptible
individuals. Lethargy is the most common central side-effect.
6.3.3 5-HT1A receptor antagonists

Mode of action
Buspirone (the only drug of this class available for

prescription) is an antagonist at somatodendritic 5-HT1A
autoreceptors and a partial agonist at postsynaptic 5-HT1A
receptors; it also blocks dopamine receptors. Under conditions
of 5-HTergic hypofunction (which is postulated to occur in
anxiety states), buspirone’s net effect is to promote 5-HTergic
function.
Therapeutic uses
Buspirone is mainly used in generalized anxiety disorder,

although it may also have some antidepressant potential (den
Boer et al. 2000). Unlike the benzodiazepines, the onset of
buspirone’s anxiolytic action is usually delayed by about two
weeks.
Pharmacokinetics
Buspirone undergoes first-pass metabolism and has a short t½,

but its major metabolite, 1-PP, is eliminated more slowly from
the brain.
Side-effects
Buspirone is much less sedative than the benzodiazepines.

Adverse effects on cognition are seldom encountered. Nausea
is the most commonly reported side-effect.
6.4 Antiepileptic drugs (anticonvulsants)

Mode of action
The pathophysiological basis of all epileptic seizures is
assumed to be the abnormal synchronous discharge of
neurones. All antiepileptic drugs share the ability to suppress
neuronal excitability, either by enhancing inhibitory
neurotransmission or by suppressing excitatory transmission
(see Table 25.2). For reviews of current developments in
antiepileptic medication, see Löscher and Schmidt (2006) and
Rogawski (2006). (p.509)
Therapeutic uses
Page 28 of 46
Table 25.2 Commonly prescribed antiepileptic

drugs and their putative mechanisms of action
Drug Indication Neuronal Probable

effect mechanism
First-line treatments
carbamazepine all seizures reduces inhibition of

except excitation voltage-/use-
absences dependent
Na+ channels
phenytoin all seizures reduces inhibition of

excitation voltage-/use-
dependent
Na+ channels
valproate all seizures reduces inhibition of

dependent
Na+ channels
ethosuximide absence reduces inhibition of

seizures excitation voltage-
dependent
Ca2+ channels
lamotrigine all seizures reduces inhibition of

dependent
Na+ channels
topiramate mainly partial reduces blockade of

seizures excitation AMPA
glutamate
receptors,
inhibition of
Na+ channels
oxcarbazepine complex reduces inhibition of

partial excitation voltage-/use-
seizures with dependent
or without Na+ channels
generalization
Adjunctive treatments
Page 29 of 46
Drug Indication Neuronal Probable

effect mechanism
gabapentin partial reduces reduction of

seizures with excitation vesicular
or without transmitter
generalization release
pregabalin partial reduces reduction of

levetiracetam partial reduces reduction of

phenobarbitone, generalized increase facilitation of

primidone seizures inhibition Cl− channel
opening
tiagabine complex increases inhibits GABA

partial inhibition uptake
seizures
vigabatrin complex increases blockade of

partial inhibition GABA
seizures catabolism by
GABA
transaminase
zonisamide complex reduces inhibition of

partial excitation voltage-/use-
seizures dependent
Na+ channels
and Ca2+
channels
clobazam, all seizures, increase potentiation

clonazepam, status inhibition of GABA-
midazolam epilepticus induced Cl−
channel
opening
Although monotherapy is always desirable, combination

therapy is often necessary to produce adequate seizure
control. The main first-line options are as follows:
Page 30 of 46
◆ carbamazepine is effective in primary convulsive

generalized seizures (tonic-clonic seizures – grand mal) and
complex partial seizures, but not in primary absence
seizures (petit mal).
(p.510)
◆ phenytoin, although effective in both convulsive and
complex partial seizures, is seldom used as a first-line
treatment because of its unfortunate pharmacokinetics and
side-effect profile (see below);
◆ valproate is effective in most forms of epilepsy, and is

widely prescribed for complex partial seizures (with and
without secondary generalization) and absence epilepsy;
◆ ethosuximide is especially effective in absence seizures;
◆ lamotrigine and topiramate are used to treat generalized

and complex partial seizures;
◆ oxcarbazepine is prescribed for complex partial seizures

with or without secondary generalization.
The following drugs are more commonly prescribed as

adjuncts to first-line drugs, or as alternative monotherapies
when first-line treatments have failed to produce adequate
seizure control:
◆ gabapentin and pregabalin are used in complex partial

seizures with or without secondary generalization;
◆ levetiracetam is also used for treating complex partial

seizures, occasionally as a monotherapy;
◆ the barbiturates phenobarbitone and primidone are rarely

used except in highly refractory epilepsy, because of their
cognitive side effects;
◆ tiagabine, vigabatrin and zonisamide are used as an

adjunctive treatments in complex partial seizures;
◆ the benzodiazepines clobazam and clonazepam are

sometimes used as adjunctive treatments in refractory
epilepsy. Diazepam, administered intravenously or per
rectum, is used to arrest status epilepticus; midazolam is
available as a buccal preparation for this purpose.
In addition to their use in the treatment of epilepsy,

carbamazepine and valproate are used as mood stabilizers and
in the management of impulsive aggression. Pregabalin is
Page 31 of 46
used in the management of neuropathic pain, and as an

anxiolytic. According to a recent meta-analysis, pregabalin
may be more effective than benzodiazepines and SSRIs in
generalized anxiety disorder (Hidalgo et al., 2007).
Pharmacokinetics
◆ Phenytoin Unlike other antiepileptics, phenytoin’s

pharmacokinetics are non-linear (zero-order kinetics); i.e.
metabolism of phenytoin is saturable at therapeutic
concentrations, resulting in a decline in clearance and a
rise in t½ with increasing doses. Since small changes in
dose can produce large changes in plasma concentration of
phenytoin, regular monitoring of plasma concentration is
essential;
◆ Carbamazepine is slowly absorbed following oral

administration, and has a t½ of about 10 hours;
◆ Valproate is rapidly absorbed and has a t½ of about 15

hours;
◆ Ethosuximide’s absorption is also rapid, but its t½ is >30

hours;
(p.511) With the exception of tiagabine, pregabalin and

gabapentin, which have short half-lives (6 hours), most of the
newer antiepileptics have t½s >8 hours, and are suitable for
twice-daily administration.
A major problem in prescribing anitepileptics is

pharmacokinetic interaction (e.g. one drug altering the
metabolism of another):
◆ Carbamazepine enhances the metabolism of (and

therefore reduces plasma levels of) phenytoin and
valproate;
◆ Valproate inhibits the metabolism of phenobarbitone and

lamotrigine;
◆ Vigabatrin, levetiracetam and gabapentin are relatively

free of pharmacokinetic interactions (Elwes and Binnie,
1996).
Side-effects
Page 32 of 46
◆ Phenytoin has a low therapeutic index. Acute toxic effects

include cerebellar and vestibular dysfunction (ataxia,
intention tremor, nystagmus, imbalance). Hirsutism and
thickening of the gums are troublesome long-term side-
effects.
◆ Carbamazepine and valproate can induce liver

dysfunction, which necessitates immediate discontinuation
of treatment.
All antiepileptics can induce sedation and cognitive

impairment. Barbiturates, benzodiazepines, phenytoin and
topiramate are especially culpable. However, valproate and
carbamazepine may also adversely affect cognition at
therapeutic plasma concentrations (Kalvainen et al. 1996).
Lamotrigine, gabapentin and vigabatrin may be less sedative
than other antiepileptics. There have been reports of
confusion, aggression and psychosis with lamotrigine and
vigabatrin; levetiracetam may also induce irritability and
aggression. Visual field defects have been associated with
vigabatrin. Skin reactions are troublesome side-effects of
carbamazepine and lamotrigine.
6.5 Antiparkinsonian drugs

The main symptoms of Parkinson’s disease (PD), rigidity,
bradykinesia and tremor, arise from atrophy of the brainstem
catecholaminergic nuclei. Atrophy of the dopaminergic
nigrostriatal pathway results in >90% loss of dopamine from
the striatum in advanced PD. Conventional antipsychotics,
which block D2 dopamine receptors, induce EPSs which
include some features of PD (drug-induced parkinsonism).
Drug treatment of PD aims to:
1 restore dopaminergic function, or

2 restore the balance of dopaminergic/cholinergic
function in the basal ganglia.
Treatment of drug-induced parkinsonism is discussed in

Section 6.1.
6.5.1 L-DOPA and other ‘dopamine-enhancing’ drugs
Page 33 of 46
Mode of action
L-DOPA is converted into dopamine by L-aromatic amino-acid

decarbolylase, an enzyme that is present in both 5-HTergic
and catecholaminergic neurones. Amantadine releases
dopamine and blocks dopamine uptake. Bromocriptine,
cabergoline, lisuride, pergolide, pramipexole, ropinirole and
rotigotine are postsynaptic D2 receptor agonists. (p.512)
Selegiline is an MAO-B inhibitor. All these drugs are assumed
to promote dopaminergic function in the striatum.
Therapeutic uses
L-DOPA is the most effective treatment for PD. Other

‘dopamine-enhancing’ drugs may be used as monotherapies in
the early stages of the disease, and are often prescribed as
adjuncts to L-DOPA therapy in more advanced disease.
Dopamine-enhancing therapy is generally unsuccessful in
counteracting drug-induced parkinsonism, presumably
because high concentrations are needed to displace the
antagonist from receptor sites. Bromocriptine is useful in
treating hyperprolactinaemia (e.g. due to pituitary tumours),
because prolactin secretion is regulated by the dopaminergic
tuberoinfundibular pathway.
Pharmacokinetics
L-DOPA is rapidly absorbed from the gut. However, more than

90% of the administered dose is metabolized by peripheral L-
aromatic amino-acid decarboxylase. This problem is overcome
by administering an inhibitor of this enzyme (e.g. carbidopa)
together with L-DOPA. This prevents the conversion of L-DOPA
to dopamine in the periphery, but, as carbidopa cannot cross
the BBB, the therapeutically useful metabolism of L-DOPA in
the brain is not affected.
Most of the dopamine receptor agonists have relatively short

half-lives, and twice- or thrice-daily dosing is needed.
Rotigotine is available as a slow-release skin patch
preparation.
Page 34 of 46
Side-effects
Nausea is troublesome early in L-DOPA therapy. Dyskinesias

constitute a more serious problem for about 50% of patients
during prolonged treatment. Behavioural side-effects include
mood disturbance (depression or mania), insomnia, delirium
and, occasionally, psychosis. Hypersexuality may result from
limbic/hypothalamic dopaminergic hyperfunction. The on/off
effect refers to episodes of relapse into akinesia and rigidity
which occur with increasing frequency during prolonged L-
DOPA therapy. D2 receptor agonists are useful in managing
‘off’ periods.
6.5.2 Anticholinergic drugs

Mode of action
Procyclidine, benztropine and related drugs block muscarinic

cholinoceptors. By suppressing cholinergic function in the
striatum they may restore the dopaminergic/cholinergic
balance that is disturbed by dopamine insufficiency in PD.
Therapeutic uses
They are used in the initial stages of PD, and in cases where
dopamine-enhancing treatments produce intolerable side-
effects. They are routinely used to treat drug-induced
parkinsonism and other EPSs (see Section 6.1).
Pharmacokinetics
They are well absorbed following oral administration.

Treatment is usually by divided doses; intramuscular injection
is used for rapid relief of dystonias.
Side-effects
Peripheral anticholinergic effects are common. Sedation may

occur. In view of the putative role of the central cholinergic
pathways in cognition, cognitive impairment might be
expected; however, there do not appear to be any data on the
long-term neuropsychological effects of these drugs.
Dependence/abuse is a problem in some patients.
(p.513) 6.6 Psychostimulants

Mode of action
Cocaine and amphetamine enhance catecholaminergic

neurotransmission: cocaine inhibits uptake, whereas
amphetamine releases catecholamines (it also has some
Page 35 of 46
uptake-blocking and MAO-inhibiting actions). Dopamine

potentiation in the mesolimbic pathway probably underlies the
euphoriant/reinforcing effects. Noradrenaline potentiation in
the periphery accounts for many of the adverse effects. The
precise mode of action of methylphenidate, atomoxetine and
modafinil remains controversial, although potentiation of
catecholaminergic function is probably involved. It has been
proposed that modafinil enhances central noradrenergic
function by facilitating transmission in the ‘mesocoerulear’
dopaminergic pathway from the ventral tegmental area to the
locus coeruleus (Hou et al. 2005; Szabadi 2006).
Therapeutic uses
Historically, amphetamine was used as an antidepressant and

anorectic. Its alerting effect, exploited by pilots and radar
operators in World War II, is the basis of its use in narcolepsy.
This application has been largely supplanted by modafinil,
which lacks amphetamine’s propensity for abuse. Modafinil is
also used to counteract fatigue in various conditions including
PD, multiple sclerosis and fibromyalgia (US Modafinil in
Narcolepsy Multicentre Study Group 2000). Amphetamine’s
use in attention-deficit hyperactivy disorder has been largely
usurped by the less dependence-prone methylphenidate and
atomoxetine.
Pharmacokinetics
Amphetamine is rapidly absorbed from the gut, and has a t½ of

about 10 hours. Intravenous infusion produces a very rapid
onset of action (‘rush’). Cocaine is well absorbed via the nasal
mucosa (‘snorting’) and alveolar surface (smoking). Inhalation
of the aesosol of particles produced by heating cocaine base
(‘crack’) produces a very rapid rise to peak plasma
concentration, resulting in an intense subjective effect. The t½
of cocaine is about one hour. Modafinil is readily absorbed
from the gut, reaching a peak plasma concentration after
about 2-4 hours. It is metabolized in the liver and its
elimination half-life is about 15 hours.
Page 36 of 46
Side effects
The vigilance-enhancing effects of small doses of amphetamine

represent the peak of a Yerkes-Dodson ‘inverted-U’ function;
higher doses produce disorganization of cognitive
performance and a disadvantageous speed/accuracy tradeoff.
Psychotoxic effects of psychostimulants include anorexia,
anxiety, hallucinations, paranoid ideation and behavioural
stereotypies. Peripheral adverse effects, reflecting
noradrenergic potentiation, include tachycardia, hypertension,
tremor and pupil dilatation (mydriasis). Tolerance to the
psychostimulants may be partly pharmacokinetic (facilitated
elimination). Sensitization (‘reverse tolerance’) to repeated
doses occurs in some users, possibly reflecting enhanced
dopaminergic function. The withdrawal syndrome includes
fatigue, somnolence, dysphoria, anhedonia and hyperphagia.
The side-effects of modafinil, methylphenidate and
atomoxetine are qualitatively similar to those of amphetamine,
but are much less severe. In general, these drugs are
relatively well tolerated in therapeutically useful doses.
(p.514) 6.7 Opiates

Mode of action
Morphine, diamorphine (heroin) and related drugs are

agonists at opioid receptors (μ-, δ- and κ-receptors). Their
action is blocked by opioid antagonists (e.g. naloxone).
Stimulation of μ-receptors in the brain and κ-receptors in the
spinal cord mediates their analgesic effects. Stimulation of μ-
receptors in the mesolimbic dopaminergic pathway probably
underlies their euphoriant/reinforcing effects.
Therapeutic uses
Opiates are the most effective treatment available for acute

pain due to tissue damage and the pain of cancer. They are
less effective in relieving neuropathic pain and ‘chronic pain’.
Opiates are occasionally used to suppress cough and to
produce a firmer stool following ileostomy or colostomy.
Pharmacokinetics
Opiates are well absorbed from the gut, but undergo extensive
first-pass metabolism, Parenteral administration is commonly
used both therapeutically and illicitly. Morphine’s t½ is about 2
hours. As its therapeutic index is quite low, continuous
infusion is sometimes employed in order to maintain a stable
Page 37 of 46
plasma concentration in the management of intolerable pain.

Methadone, which is used in replacement therapy for opiate
addiction, has a t½ of 12-16 hours.
Side-effects
Respiratory depression, nausea, vomiting and constipation are

significant adverse effects during therapeutic use. Central
side-effects include euphoria, sedation and pupil constriction
(miosis). Delirium/hallucinosis occurs occasionally; this has
been attributed to σ-receptor stimulation. Pharmacodynamic
tolerance develops to the eurphoriant and analgesic effects.
The withdrawal syndrome includes restlessness, craving,
anxiety, mydriasis, lacrimation and piloerection (‘gooseflesh’).
6.8 Hallucinogens and other drugs affecting perception

These drugs include:
◆ ‘indoleamine-like’ hallucinogens (e.g. lysergic acid

diethylamide [LSD], psilocybin);
◆ ‘catecholamine-like’ hallucinogens (e.g. mescaline,

methylenedioxy-methamphetamine [MDMA, ‘ecstasy’]);
◆ dissociative anaesthetics (e.g. ketamine, phencyclidine

[PCP]);
◆ cannabinoids (e.g. Δ9-tetrahydrocannabinol [THC] – the

principal active ingredient of cannabis resin).
Mode of action
LSD and related drugs have both agonist and antagonist

actions at 5-HT receptors; their principal action is thought to
be stimulation of somatodendritic 5-HT1A autoreceptors.
Mescaline and related drugs combine sympathomimetic
(‘amphetamine-like’) action with LSD-like effects; facilitation
of dopaminergic/noradrenergic mechanisms contribute to their
mode of action. MDMA releases 5-HT and has a selective
neurotoxic effect on 5-HTergic neurones. PCP binds to specific
sites(sigma receptors) within the ionophore linked to
glutamate (N-methyl-D-aspartate, NMDA) receptors; it thus
interferes with glutamatergic transmission mediated by these
receptors. THC binds (p.515) to specific metabotropic
receptors ( cannabinoid receptors). The relationship between
these actions and the perceptual and cognitive effects of these
drugs is unknown.
Page 38 of 46
Therapeutic uses
Mescaline- and LSD-like drugs have no legitimate therapeutic

use. Ketamine is used as an analgesic/anaesthetic. THC (in the
form of cannabis) is used illegally not only for recreational
purposes, but also as an anxiolytic and, notably by some
multiple sclerosis sufferers, as an alalgesic. THC has anti-
nauseant and anti-emetic effects which have been used to
counteract the side-effects of cancer chemotherapy.
Pharmacokinetics
Mescaline- and LSD-like drugs are well absorbed from the gut.
Their half-lives are in the range of 3-6 hours. However,
depending on the dose, the psychological effects may last for
24 hours or more. PCP’s t½ can be as long as 3 days, but in
treating overdose victims, excretion can be facilitated by
acidification of the urine. Ketamine is administered
intravenously as an anaesthetic; its t½ is about 3 hours. THC,
which is usually self-administered by inhaling the smoke of
cannabis resin, has an elimination t½ of about 30 hours;
however, its metabolites are eliminated much more slowly, and
can be detected in the plasma and urine weeks after cannabis
use.
Page 39 of 46
Psychological and somatic effects
These drugs alter perception in all modalities. Enhanced

subjective sensory acuity, perceptual distortion and illusions
are more common than frank hallucinosis. LSD- and
mescaline-like drugs have little effect on arousal, whereas PCP
and ketamine induce drowsiness. THC in modest recreational
doses impairs attention and information-processing
performance. Mood is affected somewhat unpredictably by all
drugs in this class; europhoria may give way to dysphoria and
outright panic within a single ‘trip’.
Mescaline and related drugs induce emesis, probably by an

action on the chemosensitive ‘trigger-zone’ in the brainstem.
Tachycardia and mydriasis reflect the sympathomimetic
effects of these drugs (see above).
Long-term effects of habitual use of hallucinogens are

controversial. Delayed ‘flashbacks’ are sometimes reported by
LSD users; these may reflect persistent, rather than episodic,
perceptual disturbance (Abraham et al. 1996). MDMA’s
neurotoxic effects may be irreversible. Regular use of THC
may lead to an ‘amotivational syndrome’ and sexual
dysfunction. However there is little evidence that this is not
fully reversible following discontinuation (Leonard 2004). PCP,
administered chronically to animals, produces a range of
cognitive and motivational deficits that has been proposed as a
veridical model of the negative symptom profile of
schizophrenia.
The tar from cannabis resin is more carcinogenic than that

from tobacco.
6.9 Drug treatment of Alzheimer’s-type dementia

6.9.1 Cholinergic enhancement treatments
Page 40 of 46
The major neuropathological features of Alzheimer’s disease

(AD) are:
◆ extracellular plaques containing β-amyloid protein;
◆ intraneuronal neurofibrillary tangles;
◆ neuronal loss.
(p.516) Among the most severely affected pathways are the

cholinergic projections from the basal forebrain to the
hippocampus and neoocortex, atrophy of which has been held
responsible for the cognitive decline in AD (Whitehouse 1998).
A number of treatments have been developed with the aim of
boosting cholinergic function and thereby slowing down or
reversing the dementing process. It is fair to say that the
outcome of this endeavour has, so far, been somewhat
disappointing. There are currently three drugs of this class
licenced in the UK for the treatment of ‘moderate’ AD:
donepezil, rivastigmine and gallantamine.
Mode of action
Donepezil and gallantamine are reversible competitive

inhibitors of acetylcholinesterase, the enzyme that curtails the
postsynaptic action of acetylcholine. Gallamantine is also an
allosteric modulator of nicotinic cholinoceptors. Rivastigmine
is a reversible non-competitive acetylcholinesterase inhibitor.
Therapeutic uses
Anticholinesterases are used to treat mild-to-moderate AD.

There have been some reports that patients suffering from
Lewy-body dementia respond well to these drugs, perhaps
better than patients with AD. Anticholinesterases may also be
useful in vascular dementia (Roman 2004). However, they are
not generally regarded as useful in frontotemporal lobar
degeneration. The evidence for the clinical efficacy of these
drugs has been controversial, and has been the source of
heated public debate (Pelosi et al. 2006). Recent reviews and
commentaries generally give them credit for producing
modest clinical benefit in terms of slowing the progression of
cognitive decline and deterioration of activities of daily living
(Hogan et al. 2007; Lemstra et al. 2007).
Pharmacokinetics
Page 41 of 46
Donepezil has a t½ of 70-100 hours, allowing once-daily dosing.

Gallantamine’s t½ is about 10 hours; it is usually given twice
daily. Rivastigmine has a very short t½ (1 hour), but
acetylcholinesterase inhibition lasts for about 10 hours,
making it suitable for twice-daily dosing. All three drugs
undergo metabolism in the liver.
Side-effects
All three drugs are prone to inducing nausea, vomiting,

diarrhoea, anorexia and fatigue. Gradually increasing doses
are recommended.
6.9.2 Memantine
Mode of action
Memantine is a non-competitive blocker of NMDA glutamate

receptor-regulated ion channels. It is assumed that, by
reducing glutamate-induced excitation, memantine exerts a
‘neuroprotective’ effect – preventing neuronal death due to
excitotoxicity (Johnson and Kotermanski 2006)
Therapeutic uses
Memantine is used to treat ‘moderate-to-severe’ AD.
Pharmacokinetics
The elimination half-life of memantine is about 60 hours.

Nevertheless, twice-daily treatment is usual.
Side-effects
Memantine is generally well tolerated, constipation,

drowsiness, dizziness and headache being the most commonly
reported adverse effects.
(p.517) Acknowledgement
I am grateful to my colleague Professor E. Szabadi for helpful
discussions and practical suggestions for improving an earlier
version of this chapter.
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The neuropsychology of vascular disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The neuropsychology of vascular

disorders
Clive Skilbeck
DOI:10.1093/acprof:oso/9780199234110.003.26

The term ‘vascular disorders’ covers a range of conditions,
including cerebrovascular disease (e.g., stroke, vascular
dementia) and specific blood vessel problems, such as
aneurysm with associated sub-arachnoid haemorrhage or
arteriovenous malformation. An apparently discrete event,
such as stroke, is often associated with a prior history of
transient ischaemic attacks and pre-existing risk factors (e.g.,
hypertension). Due to the wide range of conditions subsumed
under ‘vascular disorders’, there are a number of roles for the
clinical neuropsychologist. These range from early screening
to identify possible cognitive changes from pre-stroke vascular
problems in people apparently functioning ‘normally’ (e.g.,
SVD: small vessel disease), through an involvement at the
acute, diagnostic, stage (for example, in evaluating cognitive
functioning early in the course of a vascular dementia), to an
extended participation in the rehabilitation process following
stroke. This chapter discusses pre-stroke conditions;
definition, diagnosis, assessment, and treatment of stroke;
Page 1 of 33
vascular dementia, subarachnoid haemorrhage, and vascular

surgery.
Keywords: vascular disorders, stroke, vascular dementia, subarachnoid

haemorrhage, vascular surgery
1 Introduction
The term ‘vascular disorders’ covers a range of conditions,
including cerebrovascular disease (e.g., stroke, vascular
dementia) and specific blood vessel problems, such as
aneurysm with associated sub-arachnoid haemorrhage (SAH),
or arteriovenous malformation (AVM). An apparently discrete
event, such as stroke, is often associated with a prior history
of transient ischaemic attacks (TIAs) and pre-existing risk
factors (eg, hypertension). There have been recent major
advances in the characterisation of vascular disorders,
including development of the concept of mild cognitive
impairment (MCI) from cerebrovascular disease and a greater
understanding of precursor/risk conditions for stroke or
vascular dementia.
Due to the wide range of conditions subsumed under ‘vascular

disorders’, there are a number of roles for the clinical
neuropsychologist. These range from early screening to
identify possible cognitive changes from pre-stroke vascular
problems in people apparently functioning “normally” (e.g.,
SVD – small vessel disease), through an involvement at the
acute, diagnostic, stage (for example, in evaluating cognitive
functioning early in the course of a vascular dementia), to an
extended participation in the rehabilitation process following
stroke. In assessment terms, the clinical neuropsychologist
may be monitoring the cognitive abilities of a patient with
hypertension, or SVD, over a prolonged period, be charting the
process of recovery after neurosurgery in SAH, or be
providing data on the rate and extent of cognitive decline in
vascular dementia. Increasingly, clinical neuropsychologists
are active in the rehabilitation process, offering interventions
both for the cognitive deficits they have documented and for
psychological problems such as anxiety and depression that
accompany vascular disorders.
2 Pre-stroke conditions
2.1 Hypertension
2.1.1 Definition
Page 2 of 33
Raised blood pressure: high systolic pressure is a major risk

factor for stroke (hypertension has been estimated as the
cause of intracerebral haemorrhages in 25%-94% of cases;
Allen et al. 1988).
(p.522) 2.1.2 Diagnosis

Unfortunately, hypertension often appears virtually symptom-
free for a considerable period of time and so the most efficient
method for its detection is routine screening. In recent years
there has been research interest in investigating the cognitive
functioning of those who are non-symptomatic, or pre-
symptomatic, as indicated below.
2.1.3 Neuropsychological presentation

People aged 70 years or older who are hypertensive (but have
not suffered stroke) will show a wide range of cognitive
difficulties, including a variety of memory and learning
deficits, compared with people of the same age who have
normal blood pressure. Similarly, high blood pressure in
patients at age 50 years has been shown to correlate with the
cognitive deficits noted (using the neuropsychological tasks of
digit span, trail making, and verbal fluency) in these same
patients when they were tested approximately 20 years later
(Kilander et al. 2000). There is evidence that the longer the
period of uncontrolled hypertension, the more marked is the
resulting cognitive impairment (eg, Dufouil et al. 2001). Very
strong evidence of the link between hypertension and
cognitive impairment was provided by Li et al. (2007) in their
very large (n=2,356) prospective community study of
hypertension. These authors noted a highly significant
relationship between high systolic blood pressure or
borderline-high diastolic blood pressure and the subsequent
development of dementia, compared with participants showing
normal systolic and diastolic blood pressure. These findings
held for those aged 65–74 years, but not for older people.
Recent research interest has included the examination of

vascular indicators in ‘normal’ (i.e., non-symptomatic, or pre-
symptomatic) people. For example, Waldstein et al.(2005)
tested 101 older adults (aged 53–84 years), reporting that the
subgroup with undiagnosed high blood pressure showed
cognitive deficits involving visuo-spatial memory (Wechsler
Memory Scale), motor speed, and manual dexterity (Grooved
Pegboard). As was expected, the subgroup with diagnosed and
Page 3 of 33
poorly controlled blood pressure displayed more severe

deficits, including visuomotor speed (Trails A).
2.1.4 Psychosocial aspects

These are minor in the absence of significant adverse physical
effects upon the patient. Similarly, patient compliance with the
medication regimen and recommended lifestyle changes can
be problematic when no short-term threat to health is obvious.
2.1.5 Treatment & outcome

If blood pressure is raised during mid-life, then there is a
greater risk of cognitive impairment in late-life (Kivipelto et al.
2001). A significant reduction in the probability of subsequent
stroke or vascular dementia is achieved when hypertension
has been successfully treated and blood pressure is reduced
and controlled. However, blood pressure reduction in
hypertensive patients needs to be at a controlled rate: if the
reduction is too rapid, patients risk white matter damage with
associated attentional deficits. There is evidence that
providing biofeedback training to control heart rate variability
is effective in reducing hypertension, and that it can be used
to reduce anti-hypertensive medication dosage. (p.523) Given
the increasing aged profile of the population in many
countries, coupled with increasing longevity, there is great
interest in the possible beneficial effects of treating
hypertension in elderly patients: one current study involves 16
countries and patients aged at least 80 years, in a randomised,
double-blind, placebo-controlled trial (Peters et al. 2006).
There is also a role for the clinical neuropsychologist in
providing advice to hypertensive patients who wish to reduce
their risk of stroke by stopping smoking and adopting a
healthier diet and lifestyle. The identification of early/mild
cognitive impairment may help to persuade patients to better
adhere to medical advice. Issues of cognitive rehabilitation are
dealt with under the ‘Stroke’ section, below.
2.2 Hypotension
2.2.1 Definition
Low blood pressure.
2.2.2 Diagnosis
Patients often complain of light headedness, dizziness, or
weakness accompanying sudden postural change. The
Page 4 of 33
diagnosis can usually be confirmed by noting a significant

drop in blood pressure on moving from sitting to standing.

Low blood pressure is associated with cognitive impairment in
those aged 80 years and above (Nilsson et al. 2007), although
Wharton et al. (2006) also demonstrated such a significant
association, involving poorer visuospatial ability, in healthy
young adults. There is very recent evidence that the adverse
effects of chronic hypotension upon cognitive functioning can
be treated pharmacologically: Duschek et al. (2007a,b) noted
gains in visual processing using Vernum.
2.3 Cerebral Small Vessel Disease (SVD)

2.3.1 Definition
A narrowing of penetrating arterioles which supply the deep
white matter of the brain, leading to gradual ischaemic
damage. It is a major cause of Vascular Dementia (VaD; see
below).
2.3.2 Diagnosis
Lesions in the white matter identified using MRI. McManus
and Stott (2005) provided a comprehensive review.

If detected and assessed early, then mild general cognitive
difficulties are expected similar to those observed with TIAs. A
number of studies suggest that executive dysfunction is the
early, prominent cognitive feature of the disease. If initial
assessment is undertaken only after a first stroke, then
greater cognitive deficit is observed, the pattern being
determined by the site of the stroke. A stepwise progression of
the disease usually occurs, (p.524) resulting in dementia for
approximately 50% of patients. Given the importance of SVD,
O’Sullivan et al. (2005) investigated possible cognitive
screening instruments for its identification. Although Mini-
Mental State Examination (MMSE) total scores were
significantly lower in SVD patients compared with normal age-
matched controls, the authors noted that a brief (< 20
minutes) executive test battery, comprising Trails A & B, letter
fluency (FAS), WAIS-R Digits Backwards, and WAIS-R Digit
Symbol was superior to the MMSE in correctly assigning
participants to ‘Normal’ or ‘SVD’ groups. Such identification
should aid early identification and intervention of patients at
risk of subsequent VaD or stroke. The importance of the
Page 5 of 33
executive function findings were supported by Prins et al.

(2005), in a large prospective Dutch study involving repeat
testing of over 800 participants prior to the development of
SVD. These authors also noted a significant reduction in
information processing speed in those patients who developed
SVD.
Patients showing Mild Cognitive Impairment (MCI) with

vascular disease show greater impairments than MCI patients
without vascular disease on tests of speed and attention,
visuospatial function, and executive function. As might be
predicted, those MCI patients with a pre-existing stroke or
multiple cognitive deficits are significantly more likely to
progress to VaD.

Mood problems are noted in 20% of SVD patients.

As knowledge of SVD increases, the indications for early
treatment with acetyl cholinesterase inhibitors to slow the
progression of cognitive deficits strengthen.
2.4 SVD: CADASIL (Cerebral Autosomal Dominant Arteriopathy

with Subcortical Infarcts and Leuoencephalopathy)
2.4.1 Definition
This rare genetic variant of SVD produces cerebrovascular
problems in early adulthood or middle age (Vikelis et al. 2006).
2.4.2 Diagnosis
In approximately 75% of cases, the disease presents as TIAs or
young stroke, with migraine also being a frequent (40%)
presenting symptom. MRI examination reveals subcortical
white matter lesions, with cerebral hypointense (lacunar)
lesions and microhaemorrhages. The number and size of the
lacunar lesions relates significantly to the severity of the
cognitive impairment observed (MMSE), and to the level of
physical disability as assessed using the modified Rankin Scale
and the Barthel Index (Viswanathan et al. 2007).

The cognitive natural history of CADASIL is that of VaD,
although progression begins at an earlier age. A very rare
study (Harris and Filley 2001) involved case studies across
three (p.525) generations of one family, noting a range of
Page 6 of 33
cognitive deficits with relatively well preserved language

functions.

Depression is a presenting symptom in approximately 10% of
patients and with a prevalence of mood disorder of about 30%.
Frequent coping problems are to be expected, given the
disease’s relatively early onset, its predictable progression,
and the lack of any effective treatment.

Currently, there is no proven effective treatment for CADASIL,
although anti-hypertensive medication may slow the rate of
progression. Disease progression is faster in men, although
the reasons for this are not clear (a role for sex hormones has
been suggested). For most patients the picture is one of
deteriorating cognitive and physical functions. For example,
more than 50% will be unable to walk unaided after the age of
60 years. The prognosis is poorer for men, in terms of
psychological intervention. In addition to addressing any mood
disorder in the patient, which should include family support,
given the genetic basis of CADASIL any intervention may need
to be episodic over a prolonged period.
2.5 Transient Ischaemic Attacks (TIAs)

2.5.1 Definition
As the name suggests, TIAs are temporary (lasting less than
24 hours) neurological deficits arising from an ischaemic
episode.
2.5.2 Diagnosis
This is made on clinical grounds and in the light of the
patient’s history.

Given that TIAs usually occur against a history of a generally
deteriorating cerebrovascular supply, a wide range of
cognitive deficits may be observed. There is evidence that
severity of cognitive impairment correlates significantly with
the patient’s longest TIA episode. Early adverse cognitive
effects from TIA include a slowed speed of information
processing (e.g., reduced WAIS-III Digit Symbol age-scale
score) and new learning (e.g., relatively poor Rey Auditory
Verbal Learning Test scores).
Page 7 of 33
These are usually relatively minor, but expressed anxiety by

the patient can be utilised to reinforce adherence to medical
advice. If TIAs persist they are likely to acquire occupational
relevance, as job performance suffers with developing
cognitive impairment.

One of the reasons why TIAs are important is because they
carry an annual 10% risk of subsequent stroke for the patient.
Hart et al. (2001) found that a simple four-item (p.526)
questionnaire on TIA was an excellent predictor of subsequent
stroke in a study involving over 15,000 participants and a 20-
year follow-up. For the large majority of patients aspirin or
short-term anticoagulation therapy is recommended. In a
national UK five-year study (Gibbs et al. 2001) results
indicated that the prescription of antiplatelet and
anticoagulant agents significantly reduced the subsequent
occurrence of stroke. Pharmacological treatment of TIA may
also reduce the probability of developing vascular dementia
(Bos et al. 2007). In cases where major stenosis (narrowing) of
the carotid artery is noted, referral for carotid endarterectomy
surgery may be appropriate although an uncertain cognitive
prognosis may be the result (Lunn et al. 1999). The issue of
cognitive rehabilitation is dealt with under the ‘Stroke’
section, below.
3 Stroke
3.1 Definition
Stroke is a disruption of the vascular supply to the brain, of
rapid onset with neurological symptoms persisting longer than
24 hours, caused by haemorrhage from an artery or from its
occlusion through progressive narrowing of the vessel
(athetosclerosis) or a blockage (embolism). Haemorrhage
accounts for only about 10%-15% of strokes and is particularly
associated with coma, neck stiffness and vomiting.
3.2 Risk factors

These include age, cardiac disease, TIAs (see above),
hypertension (see above), and Diabetes Melitus (Allen et al.
1989). For example, from age 60 years the risk of suffering a
stroke doubles each decade. Smoking is a risk factor for those
under 65 years old, as is gender (30% higher risk in men).
3.3 Diagnosis
Page 8 of 33
Initially, the diagnosis of stroke is usually a clinical decision,

based upon medical examination and symptoms, although it
may be confirmed by a subsequent CT or MRI scan.
3.4 Neuropsychological presentation

This is extremely variable – impairment in any cognitive ability
can be observed, depending upon the site of the stroke and its
severity. The length of the period of cerebrovascular disease
pre-stroke will also influence the cognitive picture. Motor
deficits in the limbs contralateral to the side of stroke may be
acquired, in severe cases constituting hemiplegia. When the
stroke involves the hemisphere in which the patient’s primary
language centres are located, aphasic problems often result.
The ‘classic’ cognitive disturbance in right hemisphere stroke
is perceptual deficit, particularly left-sided neglect: the patient
behaves as if the left side of visual space does not exist. They
are unaware of it and so neglect in-coming information from
this side. For example, this lack of awareness can lead to the
patient bumping into/falling over furniture on their left side
and (in severe cases) ignoring food on the left-hand side of
their plate during meals. Although most of the early reports of
this disorder stressed the right hemisphere-left visual space
(p.527) relationship, right side neglect following left
hemisphere stroke is now well recognised (although occurring
less frequently, and less severely). The visual impairment
demonstrated is perceptual - the deficit occurs at the cortical
level, in the presence of adequate primary sensory and motor
input from peripheral receptors (it is not merely the
consequence of a visual field defect).
3.5 Neuropsychological examination

Again, the specific content of this will depend partly upon the
site of stroke, although given the likelihood of significant pre-
existing cerebrovascular disease a wide range of cognitive
functions should be assessed. Skilbeck (1992) provided a
general review of the assessment of cognitive functions in
stroke. There are a number of reasons for carrying out a
neuropsychological assessment, including the provision of
prognostically useful information and the obtaining of a
baseline against which to judge spontaneous recovery or the
effectiveness of cognitive rehabilitation. It may also make a
contribution towards the decision relating to the most
appropriate post-acute care setting for the patient.
Page 9 of 33
In the last few years the validity of reading tests traditionally

used in estimating premorbid IQ has received much attention.
In the absence of significant oral and/or written language
impairment, the National Adult reading Test (NART; Nelson
1982) probably still offers the best estimation of premorbid
intellectual level. However, recent research indicates that
reading test estimators of pre-morbid IQ may be affected by
cognitive impairment. Skilbeck et al. (2005), using the NART,
concluded that mod/severe cognitive impairment led to too-low
estimates of premorbid IQ. In a comparison study of the NART
and WTAR (Wechsler Test of Adult Reading) in healthy
Australians, Mathias et al. (2007a), noted that the NART was
more accurate in its estimations of IQ. In another study,
(Mathias et al. (2007b) she also found that the WTAR
underestimated premorbid IQ in severe TBI. Similar findings
of prediction underestimates have been noted with the WTAR
in mild Alzheimer’s Disease. (McFarlane et al. 2006).
The Wechsler Adult Intelligence Scale-III (WAIS-III; Wechsler

1997) is the most often used instrument to assess IQ, although
obtaining a meaningful verbal IQ may be impossible if the
stroke involves the language-dominant hemisphere and
produces significant dysphasia. Similarly, marked manual
motor deficit as a consequence of stroke often renders the
WAIS-III inappropriate for the assessment of performance IQ.
When either marked language or motor impairment is
apparent post-stroke, then Raven’s Matrices can be
particularly useful in assessing intellectual level, as it only
requires either a simple pointing, or a minimal verbal,
response and time to respond is not included in scoring the
test. A number of versions of this test are available, to cover a
wide age range (Raven 1977).
Examination of perceptual functions may employ a number of

instruments. The most appropriate include assessment for
unilateral visual neglect, given that the reported rate of this
disorder after right hemisphere stroke is very high (up to 85%
immediately and approximately 40% at least one week after
stroke). Examples are the Rivermead Perceptual Assessment
Battery (RPAB; Whiting et al. 1985) and the Behavioural
Inattention Test (BIT; Wilson et al. 1987). The RPAB has been
shown to be useful in predicting patients’ functional outcome
at discharge from rehabilitation (Donnelly, 2002). Star
Cancellation (p.528) tasks, such as that offered by the BIT
have been shown to be amongst the best predictors of
Page 10 of 33
functional outcome after stroke, and the BIT is often used as

an outcome measure by which to judge the efficacy of a
treatment intervention (e.g., Shindo et al., 2007). The BIT was
specifically devised to test for visual neglect, as was the
Balloons Test (Edgeworth et al. 1998). The latter not only
assesses unilateral visual neglect, but also allows computation
of an index of general visual inattention. It comprises two
subtests. Subtest A incorporates the phenomenon of
perceptual ‘Pop-out’, providing a measure in which the
attentional processing demands for serial search are minimal.
Subtest B requires effortful serial search, thereby requiring a
much greater attentional resource. Patients showing unilateral
visual neglect are significantly more impaired on subtest B
than subtest A. Whilst subtest A scores do not differ in healthy
older adults and dementia, the latter show subtest B scores
which are significantly lower (Lincoln et al. 2006).
Even very simple, brief testing, such as asking the patient to

draw a clock face or a daisy, can also elicit contralateral visual
neglect. When attempting to write in the numbers around the
clock face, the right hemisphere stroke patient with neglect
tends to ignore its left side, resulting in all of the numbers
being crammed into the right-hand side (between positions
‘12’ and ‘6’). When drawing a daisy the same patient will
usually omit the petals on the left side of the flower or produce
only rudimentary versions of them. An excellent and
comprehensive consideration of the clinical and theoretical
aspects of unilateral neglect phenomena was provided by
Robertson and Marshall (1993).
3.6 Assessing memory

Assessment of memory functioning after stroke can involve a
number of approaches, from brief screening instruments
through to test batteries. While memory screening tests often
show a number of disadvantages, including poor/no data on
their reliability and validity, some provide useful clinical
information.
◆ The Mini-Mental State Examination (MMSE; Folstein et

al. 1975) remains amongst the most useful. The MMSE
offers only a brief screen, with scores <24/30 usually being
interpreted as indicating cognitive impairment.
Page 11 of 33
◆ The Rivermead Behavioural Memory Test (Wilson et al.

1989) is a particularly appropriate test of everyday memory
functioning, often used in assessing stroke patients and
their progress through rehabilitation.
◆ Examples of batteries for memory examination are the

BIRT Memory and Information Processing Battery (BMIPB;
Oddy et al. 2007), a revision and extension of the Adult
memory and Information Processing Battery (AMIPB;
Coughlan & Hollows 1985), and the Wechsler Memory
Scale-III (WMS-III; Wechsler 1998). The BMIPB has a
number of advantages, including its inclusion of three
parallel forms which allows repeat testing to assess the
progression of cerebrovascular disease over time or
recovery from stroke.
Studies suggest that approximately 20% of patients will be

dysphasic at one month post-stroke, reducing slightly to about
15% by the six months follow-up. Information on disordered
language is obtained from intellectual assessment, though
specialised and (p.529) comprehensive instruments such as
the Boston Diagnostic Aphasia Examination and the Western
Aphasia Battery may be employed by speech therapists or
neuropsychologists working with stroke patients. Walker
(1992) provided a very good overview of language dysfunction
and its assessment.
3.7 Importance of cognitive deficits

Continuing cognitive impairment post-stroke has implications
for a person’s daily living activities. For example, someone
with significant persisting memory difficulties may not
remember to switch the cooker off after preparing food, may
forget to buy needed food items when shopping, and may not
recall ‘phone messages. Post-stroke perceptual problems will
often preclude the person from taking responsibility for
personal self-care such as shaving, food preparation, or
leaving the house unaccompanied. The assessment methods
outlined above will help to form a judgement of the person’s
abilities and functional competence after stroke. A recent
example study by Jehkonen et al. (2000) noted that the
presence of visual neglect following right hemisphere stroke,
identified using the BIT, was associated with poor real-life
activities at follow-up 12 months post-stroke. A number of
studies have shown significant correlations between scores on
the RPAB and ADL performance, with some RPAB scores on
Page 12 of 33
admission to rehabilitation being good predictors of discharge

home. Admission scores from memory tests and Raven’s
Coloured Matrices have also proved useful in predicting
discharge from hospital and ADL competence. Even the brief
cognitive screen offered by the MMSE, administered soon
after stroke has been shown to predict later functional
independence (Hama et al. 2007). In addition, the findings
from cognitive assessment after stroke provide good
predictors of subsequent driving ability (eg, Klavora, et al.
2000), which is an important finding given that older adults
are at greater risk of causing a road traffic accident after
stroke.
In addition, post-stroke cognitive problems can help in coming

to an opinion regarding physical prognosis. Wang et al. (2000)
found that cognitive impairment was a significant independent
factor in predicting survival for at least two years post-stroke,
and in a major review of relevant studies Anstey et al. (2006)
noted a large number of studies reporting an association
between post-stroke cognitive functioning and subsequent
death.
Page 13 of 33
3.8 Psychosocial aspects

A limited range of mood and quality of life instruments has
been used with stroke patients and their relatives, including
Hospital Anxiety and Depression Scales, Frenchay Activities
Index, Beck Scales, Nottingham Health Profile and the
Sickness Impact Profile (Skilbeck 1996; Ellis-Hill and Horn
2000). However, many studies have investigated depression
following stroke, usually concluding that it is a frequent
problem. In a rare population study, involving 850 patients,
Wade et al. (1985) noted a 20% depression rate in both
patients and their carers six months post-stroke, and there is
evidence that the frequency of patient depression may rise as
high as 33% by one year after stroke. In addition to its direct
negative effects upon the individual stroke patient’s well
being, depression also has adverse effects upon cognitive
functioning, producing ‘dementia of depression’. (p.530) The
question of the cause of this depression is unresolved, there
being conflicting evidence to implicate the site and size of the
stroke and the occurrence of cognitive sequelae. Recent
research findings (Hama et al. 2007) suggest that affective
aspects of depression are associated with left frontal stroke,
whereas apathy is more often a result of bilateral stroke in the
basal ganglia. Depression at three months post-stroke shows a
similar prevalence and hemisphere link, and is associated with
slower information processing, poor verbal memory, and a
younger age group (Barker 2007). By three years post-stroke
approximately 20% of patients are still depressed, their mood
disorder being associated with poor functional independence.
A high level of depression in carers is not surprising given the
major physical, functional and cognitive impairments that
many stroke patients are left with. The position of spouses as
carers is made more difficult given that they are likely to be of
similar age to their patient partner. Spouses of stroke patients
provided with group CBT report improvements in their level of
depression (Beck Depression Inventory) and quality of life
(Wilz and Barskova 2007). Such early interventions are
important, as improvements in psychological health and the
prevention of medical problems in spouse caregivers are very
important in enabling stroke patients with disabilities to live at
home.
3.9 Treatment & outcome
Page 14 of 33
One of the best predictors of death or long-term disability

following stroke is urinary incontinence (Wang et al. 2001). In
addition, Baird et al. (2001) found that recovery could be
predicted from the extent of the ischaemic damage noted on
MRI and a stroke scale score, these measures being obtained
within 36 hours of the stroke. Medical treatment for stroke is
limited. Vascular surgery to remove the blockage is not
supported by research studies, and endarterectomy to prevent
stroke may raise the mortality rate. However, recent research
(Hillis et al. 2000) has demonstrated the role of hypoperfusion
in determining acquired cognitive deficits in acute stroke.
Reducing hypertension has also been shown to reduce the
probability of recurrent stroke, and secondary prevention can
also be assisted through the use of Aspirin and antiplatelet
medication generally. Although the possible treatment of
stroke using transplanted neuronal tissue has yet to
investigated adequately, there are studies (for example, using
basal ganglia stroke patients) reporting relevant research and
arguing for the feasibility of this approach. In addition, there
is now good evidence that a significant element in the
spontaneous recovery of functioning post-stroke is associated
with a complex pattern of brain reorganisation (Cramer and
Bastings 2000). Research using Transcranial Magnetic
Stimulation (TMS; Tropetto et al. 2000), in which magnetic
pulses are delivered to the motor cortex and adjacent areas via
the scalp surface, suggests that reorganisation of motor tissue
post-stroke and functional gains can be enhanced using TMS.
Rehabilitation after stroke is still primarily directed towards
physical, rather than cognitive, functioning. In a major review
of the relevant studies, Majid et al. (2000) concluded that
there was insufficient evidence to decide whether or not
cognitive rehabilitation of memory deficits following stroke is
effective, although there is strong support from meta-analysis
studies for rehabilitation (p.531) effectiveness with a range of
language and perceptual deficits. With regard to the latter,
work by Robertson has demonstrated the therapeutic value of
ipsilateral motor stimulation in treating unilateral visual
neglect. Research has also demonstrated the successful,
stable, transfer (generalisation) from rehabilitation unit to
home of apraxia rehabilitation. Skilbeck (2000) provided a
review of the range of strategies available to treat cognitive
deficits in people suffering stroke, dividing them into internal
and external approaches. The former aim to directly reduce
the level of cognitive deficit using remedial training on the
Page 15 of 33
affected function (examples being the use of mnemonics with

memory impairments and scanning training in visual neglect).
External approaches concentrate upon the use of aids to
ameliorate the effects of cognitive deficits, such as the
employment of electronic diaries and ‘reminder’ systems.
Older adults have been shown to cope surprisingly well with
the involvement of PC and electronic aids in the re-training of,
or compensation for, their cognitive impairments.
Mood disorder following stroke represents a major challenge

for services. It is important in itself, although there is evidence
that its successful resolution also carries the bonus of
enhanced ADL gains (Chemerinski et al. 2001). Psychological
intervention for post-stroke depression is under-researched,
though the evidence suggests that CBT is the current
treatment of choice. Recent examination of pharmacological
approaches to treatment of depression after stroke, using
double-blind studies, have supported the use of Nortryptyline
and Fluoxetine, with some evidence that the former may be
more effective in improving both cognitive abilities and ADL
functioning as measured by the Functional Independence
Measure (Robinson et al. 2000).
4 Vascular Dementia (VaD)

4.1 Definition
A generalised, significant reduction in cognitive functioning
that is cerebrovascular in origin. The term ‘vascular’ dementia
has tended to replace the traditional and more specific
characterisation of ‘multi-infarct’ dementia.
4.2 Diagnosis
As with other dementias, the most frequent identification is
carried out using the WAIS-III, comparing the IQ figures
obtained with the predicted pre-morbid IQs for the patient
generated using the NART. Significant discrepancies between
the two methods of IQ estimation, favouring the pre-morbid
figures, can lead to the label ‘dementia’. In addition other
neuropsychological test data, such as evidence that memory/
learning abilities are significantly poorer than would be
predicted from estimated premorbid cognitive level may also
be used in the decision.
Page 16 of 33
In the most frequently observed dementia, namely Alzheimer’s

Disease, neuropsychological examination early in the condition
frequently produces a characteristic profile of (p.532) subtest
results in which the age-scale scores for Vocabulary and
Information within the Verbal scale will be higher than for
Similarities and Digit Span. Similarly, within the Performance
scale, the Picture Completion age-scale score is usually higher
than the scores observed for Block Design and for Digit
Symbol/Coding. Of course, the timing of the emergence of this
pattern of subtest scores, and how marked it is, depends upon
the stage of dementia when testing is undertaken and upon its
speed of progression.
Whilst the above pattern of IQ subtest scores is also noted in

VaD, its appearance is much more variable. This is because the
development of vascular dementia is more idiosyncratic, the
particular cognitive deficits emerging according to the
location and number of infarcts of a significant size at the time
of assessment. It may be worth distinguishing two versions of
VaD, the first being this less predictable pattern of cognitive
deficits that is dependent upon infarct location and number.
The second is more generalised, producing an IQ subtest
profile that is more predictable and similar to that noted in
Alzheimer’s Disease. Its basis is prolonged cerebrovascular
disease, without major stroke, in which the gradual reduction
of the blood supply to the cerebral cortex, principally through
the narrowing of vessels, produces cognitive loss.
Interestingly, one of the significant differences between
Alzheimer’s and VaD patients is the greater sleep disturbance
seen in the latter.
Page 17 of 33

Whilst in some ways the psychosocial issues raised in VaD are
the same as those in Alzheimer’s Disease, there are some
differences. The principal amongst these is the question of
insight. Frequently (and sometimes mercifully) in Alzheimer’s
Disease quite early in the progression of the illness patients
lose insight into their condition and their failing cognitive and
ADL abilities. This loss of insight occurs less often for patients
with a vascular dementia, unless there is significant ischaemic
damage to frontal areas. An understandably higher level of
distress usually accompanies preservation of insight for the
patient, and sometimes for relatives. As with Alzheimer’s
Disease, the general picture is one of progressive cognitive
decline, which requires much of the coping responses of both
patient and relatives. Commensurate with the preservation of
insight, depression in VaD has been found to be resistant to
treatment (Li et al. 2001). A comprehensive review of
depression in vascular disorders has been provided by
McDougall and Brayne 2007).

The rate of cognitive decline is dependent upon perfusion
decline. Risk factors that accelerate the latter include TIAs
and hypertension, so the use of aspirin and/or anti-
hypertensive agents is recommended. The effectiveness of
antithrombotic/antiplatelet drugs in preventing VaD remains to
be proved. Cognitive rehabilitation efforts are modelled on
those referred to in stroke (above), although the realistic
successful outcome may be one of slowing down, or
temporarily ameliorating, the process of cognitive impairment,
rather than arresting or reversing its effects. There is some
evidence that (p.533) recreational rehabilitation (e.g.,
dancing, board games) arrests cognitive decline in VaD
patients, possibly by improving cortical blood flow.
5 Subarachnoid Haemorrhage (SAH)
Page 18 of 33
5.1 Definition
The term ‘haemorrhagic Stroke’ is usually applied to bleeding
into the substance of the brain, whereas SAH refers to a blood
vessel rupturing and bleeding into the subarachnoid space.
However, the separation of these two causes of
cerebrovascular haemorrhage is not always clear cut. About
80% of SAHs arise from the rupture of an aneurysm (sac
extruded from the wall of an artery). Aneurysms can vary
widely in their shape and size, although the majority are small
(‘berry’). In approximately 15% of SAH no cause is found, with
the remaining 5% of cases involving blood vessel
malformations (arteriovenous malformations; AVM) or other
causes.
Most aneurysms arise sporadically, although a familial link is

identified in a minority of cases, and it is worth noting that
SAH affects a younger population (average age 50–55 years)
than ‘stroke’ and has a higher incidence in women (60%). The
overall incidence in the general population is 1–2 per 10,000
per year (Deane et al. 1996).
5.2 Diagnosis
Patients often present to the Accident and Emergency
Department of their local hospital complaining of severe
headache of sudden onset, although in a minority of cases
initial loss of consciousness occurs. Diagnosis of SAH is
confirmed via CT scan and angiography.

This varies widely, according to site of SAH and severity of the
haemorrhage. 85% of aneurysms are found on the anterior
cerebral artery distribution (Adams and Biller 1992). The next
most common are middle cerebral artery aneurysms, with the
posterior cerebral circulation having the lowest occurrence. As
might be predicted, those patients with an SAH involving an
anterior artery often show some changes in personality, with
increased irritability. Research studies in the past have
provided inconsistent evidence of severe memory deficits
following anterior communicating artery (ACA) SAH and it
may be that at one time the neurosurgical intervention to clip
the aneurysm itself used to produce some additional damage
(to small perforator blood vessels).
Page 19 of 33
The pattern of neuropsychological impairments observed

generally follows that expected from cerebral functional
geography with, for example, left hemisphere aneurysms of
the anterior or middle cerebral arterial supply producing
deficits in verbal expression and verbal memory.

SAH often produces a very poor psychological (as opposed to
cognitive) response. Depression of mood is frequently seen,
with a minority seeking pharmacological treatment. (p.534) A
key factor in post-SAH mood problems appears to be the
unexpected nature of the event – for nearly all patients there
are no warning signs of the impending haemorrhage, as far as
they were aware they were healthy, and many are young or
middle-aged. The psychological shock of the SAH, with its
serious health implications and probable ‘brain surgery’, also
results in marked anxiety in patients. In a number of ways, the
picture presented by some patients is similar to that noted in
Post-Traumatic Stress Disorder (Sheldrick et al. 2006).
Page 20 of 33

Except in the cases where the SAH is of unknown origin,
specific treatment for the aneurysm will be undertaken. Most
often this requires neurosurgical intervention to clip the
aneurysm, thereby ablating it, sometimes with the additional
procedure of wrapping the vessel for extra security. Successful
surgically treatment provides a permanent solution. It is also
sometimes possible to avoid surgical intervention completely
by using a coil. In this procedure a coil is passed, via the
cerebrovascular arterial supply, to the site of the aneurysm
and into it. This results in clotting, which seals off the
aneurysm. This procedure is only suitable for a minority of
aneurysms (generally, small and narrow-necked). A coil
intervention is associated with a better neuropsychological
presentation and recovery, probably because neurosurgical
intervention is not required and because coiling can only be
used only with smaller (ie, less destructive) aneurysms.
Cognitive recovery at six months post-SAH provides a good

guide to the final outcome although, unlike stroke, significant
cognitive gains can be noted to at least the 12-month follow-up
point. The occurrence of vasospasm or hydrocephalus
following SAH are poor prognostic signs for the final cognitive
recovery achieved by the patient. Whilst there are few longer-
term outcome studies, the available research suggests that a
majority of patients show some permanent cognitive
impairment as a consequence of SAH (eg, Tidswell et al. 1995).
One of the most difficult cognitive deficits to rehabilitate is
apraxia. There is some evidence to suggest improvements are
possible: in a recent small study involving four SAH
participants (all being at least 10 months post-haemorrhage),
Geusgens et al. (2007) noted significant gains in ADL skills
which generalised to patients’ homes and were stable over
time.
Despite reassurances from neurosurgeon and

neuropsychologist, a sizeable minority of patients harbour the
belief that an SAH may happen again (which is only realistic in
cases where a person has multiple aneurysms). This can result
in patients post-SAH being very reluctant to leave their house
at all, or only doing so if accompanied. An almost phobic
anxiety about being away from their house or being in public
places may result. Symptoms of depression and anxiety tend to
remit over the first few months after the haemorrhage,
although a significant mood disturbance may persist for 6–12
Page 21 of 33
months post-SAH. For these patients, intervention by a clinical

neuropsychologist is recommended. Longer-term
psychological difficulties tend to result from either marked
persisting cognitive deficit (usually involving memory and/or
language functions) or from permanent personality change.
(p.535) 6 Vascular surgery

6.1 Cardiovascular disease
Cardiovscular disease is frequently associated with cognitive
impairment. Whilst this cognitive impairment has often been
shown to be a consequence of cardiovascular dysfunction, the
value of cognitive deficits in predicting the subsequent
development of cardiovascular disease in asymptomatic
patients has only recently been investigated. In a very large
prospective study involving more than 12,000 middle-aged
people, none of whom had any history or evidence of heart
disease at the time of assessment, Elkins et al. (2007) found
that cognitive test scores (WAIS-R Digit Symbol, Benton FAS)
predicted the subsequent development of cardiovascular
disease (median follow-up time of 6.4 years).
6.2 Cardiopulmonary bypass surgery

Whilst the evidence is that cognitive impairments affecting
attention and both verbal & visual memory occurs post-
operatively, the use of a neuro-protective agent, such as
Trasylol, during surgery, limits the subsequent observed
cognitive deficits.
6.3 Carotid revascularisation

There have been mixed findings from the few studies which
have specifically investigated the association between carotid
stenosis (narrowing) and cognitive dysfunction. However, in a
large Norwegian study (Mathiesen et al. 2004) cognitive
impairment was noted in a group of 189 asymptomatic patients
showing carotid stenosis. Early studies on revascularisation,
focussing upon Carotid Endarterectomy, tended to find
cognitive impairments following neurosurgery (or, at best,
equivocal outcomes). However, a recent review of the field
(Berman et al. 2007), involving 18 studies on carotid
revascularisation, noted significant gains in most of the
studies, with only 3 studies noting cognitive impairment after
surgery. One of the studies in the latter category focussed on
older patients (mean age: 72 years), and using the MMSE and
Clock Tests and found a cognitive decline only in those
patients with pre-surgical symptomatic Left Internal Carotid
Page 22 of 33
Artery (LICA) stenosis; asymptomatic LICA patients and those

with Right Internal Carotid disease showed few post-operative
cognitive problems (Bo, et al., 2006). Research in this field is
becoming increasingly specific, including into genetic factors,
and it is now clear that the APOE-ε4 allele is a good predictor
of cognitive impairment after Carotid Endarterectomy surgery.
6.4 Coronary Bypass Graft Surgery (CABG)

Research in this area usually finds a significant percentage of
patients (50%–60%) showing post-operative cognitive
impairment. Some studies have only noted cognitive decline
long after the surgery. In terms of psychosocial outcome, poor
pre-operative psychological functioning is the major
psychological risk factor for poor psychological functioning,
including mood, six months post-operatively (Oxlad et al.
(2008). A recent study of women (>= 65 years) undergoing
CABG surgery demonstrated the value of an intervention (p.
536) to manage post-operative symptoms, both in terms of
physical activities and psychological well-being (Zimmermann
et al. 2007). Preoperative psycho-education to help patients for
surgery and its aftermath is highly recommended.
Page 23 of 33
7 Summary
From the neuropsychological point of view, vascular disorders
are best regarded as specific features of the general process
of cerebrovascular disease. Early signs of this process are
represented by persisting hypertension and TIA, which are
associated with usually mild, though developing cognitive
impairment, and Small Vessel Disease. Strokes are major
events, involving physical, cognitive and psychosocial
sequelae. The pattern of deficits noted is dependant upon the
site and size of the lesion caused by the stroke. Significant
coping and adjustment problems are caused for patient and
carers by stroke, which are somewhat different for those
presented to people suffering SAH. The latter often occurs in
middle-aged, rather than older, adults and for these patients
there is a need to judge their recovery against additional
criteria, including those linked to employment. The term
Vascular Dementia encompasses both the step-wise
deterioration in functioning arising out of multi-infarct
dementia and the more general progression of cognitive
impairment produced by cerebrovascular disease. The role of
the neuropsychologist continues to develop. The well-
established contributions in the diagnostic process and the
assessment of change include both the measurement of
recovery (e.g., following stroke or vascular surgery) and the
charting of disease progression (e.g., in vascular dementia). In
addition, recent research findings point to an important role in
the assessment/screening of pre-symptomatic/sub-clinical
populations to identify important risk factors such
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Neuropsychology of cardiovascular disease. LEA, New Jersey.
Page 32 of 33
Page 33 of 33
Neuropsychological presentation and treatment of traumatic brain injury


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Neuropsychological presentation
and treatment of traumatic brain
injury
Nigel S. King
Andy Tyerman
DOI:10.1093/acprof:oso/9780199234110.003.027

Clinical neuropsychologists play a vital role in assessment and
treatment after head injury across acute, rehabilitation, and
community settings, drawing upon both specialist
neuropsychological knowledge and general clinical training.
The British Psychological Society identified a number of key
functions for clinical neuropsychologists: carrying out detailed
assessments of cognition, emotion, behaviour, and social
competence; devising and implementing training programmes;
liaising with educational agencies/employers to advise on the
resumption of educational/vocational life; providing and
advising about long-term care; and facilitating personal,
family, and social adjustment. This chapter discusses the
epidemiology of head injuries, mild and moderate head injury,
and severe and very severe head injuries.
Keywords: head injuries, clinical neuropsychology, cognitive rehabilitation,

social competence, training programmes, long-term care
Page 1 of 31
1 Introduction
1.1 Clinical neuropsychology and head injury
Clinical neuropsychologists play a vital role in assessment and
treatment after head injury across acute, rehabilitation and
community settings, drawing upon both specialist
neuropsychological knowledge and general clinical training.
The British Psychological Society (1989) identified a number of
key functions for clinical neuropsychologists: carrying out
detailed assessments of cognition, emotion, behaviour and
social competence; devising and implementing training
programmes; liaising with educational agencies/employers to
advise on the resumption of educational/vocational life;
providing and advising about long-term care; and facilitating
personal, family and social adjustment (British Psychological
Society, 1989). In a further report (British Psychological
Society, 2005) key recommendations included the need for: a
brain injury service network/care pathways; early assessment
and treatment by specialist staff; specialist facilities for people
with high physical dependence, severe challenging behaviour
and for those who are minimally responsive; post-acute
community rehabilitation service; and integration of brain
injury and vocational rehabilitation services.
In the acute setting clinical neuropsychologists are usually

based in regional neurosciences centres, working closely with
neurosurgical and nursing staff during the acute admission.
They will often see patients for more detailed assessment as
out-patients at a ‘post-acute’ stage when the attention has
shifted more towards cognitive and other psychological
changes. Clinical neuropsychologists working in rehabilitation
in the U.K. were based originally primarily within regional in-
patient neurological rehabilitation centres or specialist units in
the independent sector for the management of severe
behavioural difficulties. However, they are now commonly
based in generic physical disability teams, specialist
community brain injury rehabilitation services and specialist
centres for cognitive and vocational rehabilitation after brain
injury.
Page 2 of 31
1.2 Epidemiology
The annual incidence of hospital admission after head injury is
estimated to be 229 per 100,000 in England: 356 per 100,000
for children (aged 0–15); 178 per 100,000 for adults (p.542)
(aged 16–75); and 384 per 100,000 for older adults (aged 75
and over) (Tennett, 2005). Whilst 75–85% of such injuries are
mild in nature (Miller & Jones, 1985; Kraus & Nourjah, 1988),
the incidence of moderate or severe TBI is estimated to be 25
per 100,000 (RCP/BSRM, 2003). The range of outcomes is
huge, from complete recovery to persistent coma or death.
Serious disability from head injury occurs in an estimated 150

per 100,000 of the population in England and Wales (British
Society of Rehabilitation Medicine, 1998), with an estimated
210 totally disabled and 1500 severely or profoundly disabled
every year. One family in 300 is thought to have a member
with persisting disability following a head injury (Lancet,
1983). A large proportion of head injury involves young males
aged 18-25. Whilst rates vary with severity and geography, the
most common causes of injury are road traffic accidents
(RTAs), assaults, falls, occupational accidents and recreational
accidents.
The disabilities associated with severe and very severe head

injuries are extremely varied encompassing both physical
disability (i.e. motor and sensory deficits) and psychological
changes (e.g. cognitive impairment, altered emotional
response and loss of behavioural control). These often impact
not only on the injured person but also on the family and wider
psychosocial networks. The vast majority of rehabilitation
services are therefore targeted on the more severely injured.
1.3 Severity of head injury

The severity of a head injury is usually measured by: i) depth
of unconsciousness -usually measured immediately after
resuscitation, using the Glasgow Coma Scale (GCS) (Appendix
1); ii) length of post traumatic amnesia (PTA) - the period of
time between receiving a head injury and regaining
continuous day-to-day memory for events; iii). length of
unconsciousness (i.e. GCS <9); and/or iv) presence of
neurological signs (e.g. paresis, damage revealed by neuro-
imaging techniques).
A widely accepted classification of severity is detailed in Table

27.1. (p.543)
Page 3 of 31
2 Mild and moderate head injury

Table 27.1 Severity of head injury
Severity Glasgow Length of Post-

coma scale unconsciousness traumatic
amnesia
Mild 13–15 <15 mins. <1 hour
Moderate 9–12 15 mins.–6 hrs. 1–24 hours
Severe 3–8 >6 hrs.* 1–7 days
Very N/a * 1–4 weeks

severe
Extremely N/a * >4 weeks

severe
*N.B. As many patients in extended coma are sedated and
electively ventilated, it is often not possible to determine
the duration of unconsciousness.
2.1 Pathophysiology
For the majority of mild and moderately head injured patients
there are no measurable pathophysiological changes. In some
cases however temporary EEG abnormalities, reduced
cerebral blood flow or temporary macroscopic lesions
(revealed by CT or MRI) are present. These predominate in the
frontal or temporal cortical areas and usually resolve within 3
months. Where apparently minor injuries are associated with
neurological signs or complications, it is usually not
appropriate to make a classification of ‘mild’ head injury. Such
injuries should be classified according to the extent of
neurological signs and/or complications.
2.2 Clinical presentations and natural course

Many with mild or moderate injuries experience few or no
symptoms and make a full recovery within a few days.
Approximately 50% will, however, experience post concussion
symptoms (PCS)-headaches, dizziness, fatigue, irritability, poor
concentration, nausea, sensitivity to light, sensitivity to noise,
poor memory, sleep disturbance, tinnitus, slowed thinking,
blurred/double vision, anxiety, depression, or frustration.
These are caused by organic and/or psychological factors. For
the majority, full recovery from PCS occurs within a few days
to three months. However 6–8% have persisting PCS at and
beyond 1 year post injury. Slow and/or incomplete recovery is
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associated with the following: >40 years old; pre-morbid

psychopathology; previous head injury; pre-morbid alcohol/
substance misuse; and female gender. When PCS do persist
major psychosocial disabilities can result (King, 2003).
2.3 Neuropsychological deficits

The most common neuropsychological impairments following
mild and moderate head injuries involve speed of information
processing and divided attention (as measured by tests such
as the Paced Auditory Serial Addition Task (PASAT) and Stroop
Test). These types of impairments correlate well with severity
of PCS and tend to mirror symptomatic recovery (i.e. recovery
within three months of injury). Impairments in reaction time,
verbal short term and long term memory (as measured by
paragraph recall tests) and visuo-spatial short term and long
term memory (as measured by figure recall tests) can also be
present. These correlate less well with severity of PCS but also
usually resolve within three months.
2.4 Related emotional disorders

The events which cause head injury are often precisely those
where psychological trauma might also be expected. Post
traumatic stress symptoms (PTS) are therefore quite common
and these often include phobic avoidance of situations where
the injury occurred (e.g. driving). Whilst organic amnesia
following head injury is thought to offer some (p.544)
protection against PTS the incidence of post traumatic stress
disorder (PTSD) following RTA and mild head injury is similar
to the equivalent non head injured population (20%).
Frustration, depression and anxiety due to the psychosocial
disabilities caused by persisting PCS are also common. A
vicious cycle can easily develop where anxiety, depression or
frustration exacerbates PCS and leads to reduced coping. This
causes further distress and further exacerbation of PCS. They
may also be exacerbated by uncertainty over the relative
contribution of psychological and organic factors, particularly
when symptoms persist and are of a chronic nature.
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2.5 Treatment/Rehabilitation
Early assessment within 1–4 weeks of discharge is optimal and
should include the following: assessment of the severity of
head injury (e.g. by assessing the length of PTA); investigation
of the extent and nature of PCS (e.g. using the Rivermead Post
Concussion Symptoms Questionnaire); assessment of relevant
premorbid factors (eg. neurological and psychological/
psychiatric history); assessment of anxiety and depression
symptoms (e.g. using the Hospital Anxiety & Depression Scale
– HADS, Beck Depression Inventory – BDI; the Beck Anxiety
Inventory - BAI); investigation of the extent and nature of any
post traumatic stress symptoms (e.g. using the Revised Impact
of Event Scale - IES); assessment of any co-morbid factors
which might contribute to disabilities (eg. pain, orthopaedic
injuries).
Intervention would normally focus on the provision of

information, reassurance, education, support and regular
monitoring of progress. The information should address: the
normality of PCS; good prognosis; regulating and pacing
activities in line with the severity of PCS (e.g. taking short
breaks when PCS feel worse rather than trying to push on
through until longer breaks become unavoidable); graduated
return to work and pre-morbid activities; and education about
the potential for developing the vicious cycle where stress and
PCS becoming mutually exacerbating. The overall aim is to
minimise the effects of anxiety, worry and stress on PCS by
preventing the development of the vicious cycle. One single,
hour long assessment and intervention session can be an
effective intervention for the majority of cases (Wade et al.,
1998). Specialist psychological and medical interventions are
appropriate for persisting problems with post-traumatic stress,
headaches, dizziness, anxiety, depression, return to work
difficulties, irritability, tinnitus or neuropsychological
impairment.
When assessing and treating patients at later stages after

their injury it is also important to investigate in some detail
how their symptoms have developed over time (e.g., when
symptoms were first noticed); whether any symptoms were
present premorbidly; whether symptoms have improved,
deteriorated, plateaued or remained constant over time. This
will help in judging the relative contribution of organic and
psychological factors in the sequelae presented. Interventions
for those presenting with persisting post concussion symptoms
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should be preceded by the development of an individualised

collaborative formulation of the patients’ problems (King,
2003). This should focus on; i) helping the patient make sense
of their symptoms, ii) aiding their understanding of the
contributory (p.545) factors involved in their problems and
the interactions between them, and iii) the means by which
their problems can be maximally ameliorated or managed.
For example a diagrammatic representation might be shared

demonstrating how post concussion symptoms, post traumatic
stress symptoms and orthopaedic pain symptoms may have
become mutually exacerbating over time and led to reduced
day to day coping, impoverished sleep, fatigue, increased
anxieties/worries and the development of maladaptive
cognitions like ‘I’m going mad’ or ‘something wrong in my
brain has been overlooked’. Component parts of the
formulation might then be addressed in turn within the shared
understanding of an agreed formulation.
2.6 Effectiveness
Studies evaluating the effectiveness of interventions for
patients with mild and moderate head injuries are sparse.
Randomised control trials in this area however have
demonstrated that early intervention involving education,
reassurance, support and monitoring of progress can reduce
the incidence and severity of persisting post concussion
symptoms. There is little hard evidence however to inform
management guidelines when symptoms persist and become
chronic. Later interventions are therefore mainly informed by
experienced clinicians in the field rather than by empirical
data.
3 Severe and very severe head injuries

There are two main types of severe injury - open head injury
and closed head injury. Open head injury occurs when the skull
and protective linings of the brain are damaged so that brain
is exposed. Closed injury occurs when the skull and protective
linings of the brain are not penetrated. The latter is by far the
most common form of head injury in peace time.
3.1 Pathophysiology
There are two kinds of damage to the brain following severe
forms of head injury-primary damage and secondary damage.
3.1.1 Primary damage
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This includes diffuse white matter damage, contusion

(bruising) and haemorrhage.
◆ Diffuse white matter damage is due to the widespread

rupturing of axons caused mainly by the brain impacting
against itself as it moves within the skull. This is usually the
most prevalent form of damage.
◆ Contusion is usually most pronounced in the

undersurfaces of the frontal and temporal poles where the
shearing forces of the brain impacting upon the sharpest
and most confined parts of skull are maximal. Contusion
can also occur both under the direct point of impact of the
injury and directly opposite it (contrecoup injury).
◆ Haemorrhage occurs when the blood vessels supplying

oxygen to the brain are ruptured.
(p.546) 3.1.2 Secondary damage

This includes damage due to haematoma (collections of blood),
cerebral haemorrhage leading to anoxic damage or death, sub-
arachnoid haemorrhage, swelling, infection, hydrocephalus
(build up of cerebro-spinal fluid) and hypoxic neural damage
due to breathing difficulties or low blood pressure.
3.2 Clinical presentation and natural course

For the majority of severely injured patients improvement
takes place slowly over months and years. It is usually best to
use the word ‘improvement’ rather that ‘recovery’ after more
severe injuries, as recovery implies complete restoration of
function which may well not occur. Permanent cognitive
impairments are probable with severe injuries, although for
some they will be quite subtle and only evident under stress,
in busy environments or on formal testing. Cognitive
impairments are rarely absent after very severe injuries.
The rate and extent of recovery is impossible to predict early

on and the process is not fully understood. It may involve the
following: i) resolution of brain swelling and contusion, leading
to restoration of neuronal efficiency; ii) disrupted
neurotransmitters regaining some of their original efficiency;
iii) damaged neurones repairing themselves/axonal sprouting;
and possibly iv) some degree of neural plasticity for very
widely distributed functions (e.g. language).
Page 8 of 31
Typically the majority of recovery occurs in the first two years

after injury such that significant difficulties evident at two
years rarely resolve completely thereafter. However, further
small amounts of natural recovery can occur up to and beyond
five years for the more severe injuries. Adaptation to long-
term disability is therefore an ongoing process and can result
in improved function many years post-injury, especially when
early rehabilitation has been limited.
3.3 Neuropsychological impairments

When physical disabilities (such as paresis, ataxia, dysarthria,
dyspraxia or reduced motor speed) are present, they are often
the main concern for the patient during the first months after
injury. Cognitive impairments, however, tend to have greater
impact on long term disability and handicap. These occur
predominantly in the areas of attention, speed of information
processing, explicit memory and executive functioning. They
reflect the most common areas of damage in the frontal and
temporal cortical areas and with diffuse axonal shearing.
3.3.1 Attention
Impairments in speed of information processing are one of the
most common deficits following severe head injury. These are
often evident on tests like the PASAT, BIRT Memory &
Information Processing Battery (BMIPB), Stroop Test or
Wechsler Adult Intelligence Scale III (WAIS-III) Digit Symbol
Coding sub-test. They may also be evident on tests requiring
speed (e.g. WAIS-III Performance sub-tests or Trail Making
Test).
(p.547) Specific deficits in divided, selective or sustained

attention may be evident on tests like the Test of Everyday
Attention, WAIS-III Picture Completion sub-test and Trail
Making Test. Verbal active attention span is often impaired as
evidenced by backward digit span deficits. Visuo-spatial
attention span deficits may also be evident on tests like the
Corsi Block Tapping Test. These deficits can cause reported
problems with concentration, distractibility, tasks requiring
more effort, memory, fatigue, irritability, reduced speed of
thinking and increased error rates.
3.3.2 Memory
Short term and long term memory deficits are common for
both verbal and visuo-spatial material. Verbal memory deficits
are often indicated by impaired performance on paragraph
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recall tests and list learning tests (e.g. Wechsler Memory Scale
III (WMS III) Paragraphs, WMS III Paired Associate Learning
Test, BMIPB Story Recall and List Learning Tests). Visuo-
spatial memory deficits are commonly indicated on measures
like Figure Recall Tests (e.g. Rey Complex Figure, BMIPB
Figure Recall). Remote memory and procedural/implicit
memory functions are usually spared. Memory difficulties are
therefore usually for new, explicit learning rather than from
previously learned material, overlearned procedures and
autobiographical memory. Some of the most commonly
reported memory difficulties include not being able to
remember conversations, appointments, reading material,
peoples’ names, new routes or where things have been put.
The patient may also have been told that they repeat
themselves a lot.
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3.3.3 Executive
Executive impairment following severe head injury is common.
It is not unusual however for there to be little such evidence
on formal testing - neuropsychological assessment is by its
very nature highly structured and is conducted in a
distraction-free setting. Therefore, judgements on executive
impairments must often be inferred from behavioural
observations, qualitative aspects of test performance and
reported observations by those close to the patient or other
health care professionals. The patient’s own reports are of the
utmost importance but difficulties with insight can often mean
that they, themselves are unaware of such deficits.
Psychological denial of problems is a natural coping
mechanism but can be mistaken for dysexecutive problems in
some cases. Similarly, reports from those close to the patient
may minimise difficulties due to their own psychological
denial, in addition to the natural tendency to underplay the
significance of difficulties early post-injury in the aftermath of
major trauma.
Deficits in cognitive flexibility, mental set shifting and

perseveration may be indicated on tests such as the Trail
Making Test, Wisconsin Card Sorting Test, Stroop Test, Verbal
Fluency Test or Card Sorting sub-test of the Behavioural
Assessment of Dysexecutive Syndrome (BADS).
Verbal concept formation and verbal abstract thinking deficits

may be evident on tests like the WAIS-III Similarities sub test
and on proverbs tasks (e.g. from the WAIS-III Comprehension
sub test). Planning and problem solving deficits may be
evident on tests (p.548) like the Six Elements, Zoo Search
and Motor Action Program sub tests of the BADS and by the
quality of performance on tests like the WAIS-III Block Design
sub test and the copy task of figure recall tests.
Insight difficulties may be highlighted through large

discrepancies between patient and others’ reports of
problems. Assessment of insight may be aided by separate
administration of standard problem schedules with patients
and family members as part of routine assessment. Specific
questionnaires may also highlight cognitive, behavioural and
emotional problems associated with executive impairments
(e.g. Dex questionnaire from the BADS).
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Observed problems in executive functioning might include

difficulties with social regulation, fragmented speech, reduced
abstract reasoning, fixed and concrete thinking, poor
initiation, egocentricity, reduced creativity, tangential speech,
reduced insight or difficulties with organising thoughts,
decision-making, problem solving and in adapting to new
situations.
3.3.4 Language
Pure language and dysphasic impairments following
uncomplicated head injury are less common than attentional,
memory and executive impairments. Indeed some language
based tests are used as ‘hold’ measures to help estimate pre-
morbid levels of intellectual functioning, due to their
resistance to the effects of brain injury of a generalised nature
(e.g. National Adult Reading Test, WAIS-III Vocabulary sub
test). Problems with word finding, sentence construction
paraphasias however are common language based
impairments.
3.3.5 Visual perception

Visual perceptual impairments following uncomplicated head
injury are rare. A small but significant proportion may have
visuo-constructional difficulties but visual agnosias are not
often seen. However patients may be slow in their processing
of visual material.
A wide range of cognitive impairments are therefore seen after

severe head injury. It can often be difficult to predict their
specific impact upon an individual’s life after head injury as
such deficits typically form part of a complex interaction of
cognitive and other disabilities. Management and resultant
long-term impact of cognitive impairment is also mediated by
level of insight, the use of compensatory strategies and the
extent of concomitant behavioural and emotional difficulties.
3.3.6 Neuro-behavioural problems

An extensive array of behavioural change is often reported
after severe head injury including increased irritability,
disinhibition, impulsivity, emotional lability, mood swings and
aggressive outbursts. Deficits in executive functioning (leading
to lack of insight, egocentricity, poor social regulation and low
initiation) often mean that a head injured patient’s personality
are seen as significantly changed, by both themselves and by
others. In addition, problems arising from other impairments
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such as fatigue, low drive, frustration, (p.549) irritability,

reduced emotional and behavioural control, may lead to a very
significant sense of changed personality. The wide range of
behavioural changes observed, reflect the interaction of
primary neurological damage and secondary psychological
reactions to head injury and its effects.
3.4 Related emotional disorders

Short and long term emotional sequelae of severe head injury
include the following:
i) post traumatic stress reactions (PTS) relating to the

events which caused or followed the head injury (e.g.
road traffic accidents, assaults etc). While
unconsciousness and organic amnesia from severe
injury can protect against PTS, this is not always the
case. The prevalence of PTSD (3–6%), however, is
almost certainly much less than in mild or moderate
head injury.
ii) anger, frustration, depression and anxiety are
common emotional responses to the disabilities that
patients confront. For some this may be an early
reaction to the trauma of neurological illness/injury, the
loss of skills, roles and control over one’s life, the slow
pace of progress and the uncertain extent of future
recovery. Reduced impulse control may also exacerbate
the control of anger, irritability and aggression.
However, early in rehabilitation, many may appear
unconcerned about their predicament due to limited
insight into the extent of cognitive and emotional/
behavioural changes, together with unrealistic
expectations of a full recovery.
iii) major distress in adjusting to and coming to terms
with the losses and changes arising as a result of a
head injury e.g. break up of relationships, inability to
return to work, shattered aspirations and ambitions,
changes in personality and sense of identity. These
responses often develop over many years as changes
and disabilities become emotionally ‘accepted’ by the
patients as being permanent.
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3.5 Social and family consequences

The complex array of disability after head injury often has far-
reaching social consequences. Those with the most severe
injuries may require assistance in daily living. This may
include practical assistance in personal and domestic care for
those with severe physical disability and guidance or
supervision for those with marked cognitive or personality
changes. Others may be independent in daily care but unable
to travel independently, or need help from the family in
making decisions or managing their financial affairs. Leisure
pursuits are often compromised by motor, sensory and
cognitive difficulties. Friendships and social opportunities
often decline progressively over subsequent years. This may
be due to a combination of loss of confidence, low mood,
intolerance to noise or difficulty in contributing to
conversations on the part of the patient, and embarrassment
and unease on the part of others in response to unpredictable
behaviour and loss of refinement in social skills.
Many people with severe head injury are unable to return to

previous occupation due to a wide range of difficulties (BSRM/
JCP/RCP, 2004). Reduced speed, poor concentration, (p.550)
unreliable memory, headaches and/or fatigue combine to
render many uncompetitive in their work. Specific physical,
sensory and/or cognitive difficulties (e.g. seizures, visual field
loss, executive or communication difficulties) may restrict or
preclude a return to occupations where such skills are vital.
Executive difficulties may also limit awareness of restrictions
and the effective use of coping strategies in the workplace.
Emotional difficulties may reduce the capacity to cope with
pressure or responsibility, irritability or frustration may cause
difficulties in work relationships. Disinhibited or aggressive
behaviour is rarely tolerated in the workplace. Difficulties may
arise gradually after a seemingly successful initial return to
work or later on moving to a new job.
The social impact for the patient is often paralleled by major

impact upon the family. High levels of stress and distress for
primary carers are common, tending to increase rather than
decrease over time after very severe injuries. Couple
relationships often become strained with increased discord
and high rates of breakdown after more severe injuries. For
couples who remain together, there is often a reduction in
emotional intimacy and a lower frequency and satisfaction in
sexual relations. Spouses may struggle to cope with competing
Page 14 of 31
needs of work, home, partner and children, whilst parents may

find themselves locked into a long-term caring role for their
adult children, with major concerns about the future. The
impact on children and siblings can also be marked but tends
to be more variable. Many families face far-reaching changes
in roles and relationships and disruption to overall family
functioning. As life revolves around the needs of the patient,
so the occupational, leisure and social lives of family members
often falters (cf. Oddy & Herbert, 2008).
3.6 Treatment/Rehabilitation
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The focus of neuropsychological rehabilitation varies

according to the nature and severity of injury, the patients’
psychosocial context, the clinical setting (e.g. acute, post-
acute or community) and time since injury. It is essentially a
process by which creative and practical solutions are found to
minimise the unique neuropsychological, emotional, social and
vocational difficulties faced by the patient. The process
emanates from, and is constantly informed by a thorough
understanding of clinical neuropsychology in general and the
specific cognitive strengths and weaknesses of the patient in
particular. Neuropsychological understanding therefore
provides both the bedrock and the framework for this
approach. Early rehabilitation optimises outcome, but late
rehabilitation can also improve function significantly. Two key
principles underpin rehabilitation and these centre around the
formation of effective therapeutic relationships and the
development of insight and understanding: i) engaging and
maintaining patient (and family) involvement with
rehabilitation services by the provision of an emotionally
supportive environment and relationships within which
empathic expert help can be easily accessed and ii) increasing
patients’ (and their family’s) understanding of head injury,
their strengths and weaknesses and the means by which
impairments may be best managed.
These principles become increasingly important as the patient

moves beyond acute settings to post-acute and community
settings where engagement with services may be (p.551)
impeded by poor insight, lack of understanding, psychological
denial, emotional disorder or challenging behaviour.
There are at least four important aspects of the process of

rehabilitation: i) engaging the patient (and their family) in the
rehabilitation process; ii) facilitating the setting of realistic
rehabilitation targets and goals; iii) facilitating the
achievement of targets and goals via co-ordinated
interventions; and iv) evaluating, reviewing and modifying
targets and goals over time.
Successful engagement of a patient (and their family) is often

linked intrinsically to the collaborative development of
realistic targets and goals. It is common for the patient (and
their family), initially, to have unrealistic expectations about
the extent and pace of targets that are achievable (e.g.
complete cognitive recovery or return to full time work within
Page 16 of 31
weeks of injury). These commonly need to be negotiated to

allow for more time, a greater number of intervening targets
or the inclusion of additional forms of support. Formal goal
planning procedures may help this process, although there is
no consistent evidence as yet that they affect outcomes
(Levack et al., 2005).
The principles which should guide the setting of goals and

targets should include the following: i) the maintenance and
development of appropriate levels of cognitive stimulation
while avoiding cognitive overloading; ii) education and
minimisation of the vicious cycle of cognitive impairments
leading to reduced coping, leading to distress, leading to
exacerbated cognitive impairments etc.; iii). the emphasis of
cognitive rehabilitation through compensatory strategies and
prostheses rather than through cognitive restoration and
‘brain function therapy’(i.e. de-emphasising the analogy that
the brain operates like a muscle and discouraging
inappropriate attempts to train unaffected brain areas to take
over damaged areas); iv) the provision of emotional support
and specific psychological interventions for the emotional
sequelae associated with head injuries for both the patient and
their family; v) facilitating patients and families adjustment to
changes in personality, identity and psychosocial functioning;
and vi) liaison with education and vocational systems to advise
on and plan return to previous work or education.
Co-ordination and review of interventions is essential so that

there is continuous feedback between professionals, patient
and family. This helps interventions to remain focused on
mutually agreed goals and targets and goals to be refined and
modified as the patient progresses and circumstances change.
The use of groups for cognitive rehabilitation, education and

emotional support should not be underestimated. These allow
peer support, sharing of cognitive and emotional coping
responses and an opportunity to provide formal education in
an efficient way. They can be a very powerful and supportive
means for developing insight into impairments and for
exploring ways of minimising disability.
Cognitive rehabilitation strategies which benefit patients with

severe head injury are usually pragmatic in nature.
Neuropsychological assessment, however, provides vital
information for knowing what strategies should be attempted,
Page 17 of 31
what modifications might be beneficial, what might cause

strategies to be unsuccessful, how to develop new strategies
and what kind of advice and education is appropriate. The
following list highlights (p.552) frequent examples of
management strategies for common areas of difficulty: general
cognitive function; memory; executive function; behaviour
difficulties; social skills. There is of course significant overlap
between these areas.
3.6.1 General cognitive strategies

◆ Developing habits, routines and over-learnt procedures
to:
i) maximise the use of implicit and procedural
memory functions;
ii) provide structure; and
iii) minimise cognitive load.
◆ Developing a tidy living and working environment where

belongings are kept in the same, intuitively obvious, places
and can easily be found. This helps to minimise demand on
memory and problem solving skills and make maximum use
of spared implicit memory.
◆ Taking many small breaks when impairments become

apparent rather than ‘pushing on’ until forced to take a
break due to ‘cognitive overload’.
◆ Rearranging working environments to minimise

background noise, ‘busyness’, unexpected events and time
pressures. This helps to reduce restrictions arising from
attentional deficits, slow speed of information processing
and cognitive inflexibility.
◆ Graduated return to premorbid activities and

minimisation of non-essential activity to reduce cognitive
overload and fatigue. This maximises the chances of
successful completion of activities.
◆ Identifying specific times, or specific types of activity

where fatigue, irritability, anxiety or frustration occur and
facilitating appropriate changes in these areas.
◆ Training the patient to allow extra time for tasks where

temporal judgement or speed of information processing is
reduced.
Page 18 of 31
◆ Using a diary systematically as

i) an aide-memoire,
ii) a means of structuring time,
iii) an orientation ‘anchor’,
iv) an aid to overcoming initiation difficulties or
v) a reminder of key messages, conclusions and

‘self statements’ from therapy.
3.6.2 Strategies for managing memory

◆ Using a dictaphone/tape recorder to record meetings,
lectures, etc (i.e. as an aide-memoire).
◆ Using a watch with an alarm or a paging device as a cue

to look in a diary, or perform particular tasks. (This may
also increase immediate arousal levels sufficiently to
overcome initiation impairments).
(p.553)
◆ Systematically using written or photo journals for
episodic memory deficits (i.e. memory for events).
◆ Using notes, calendars and lists as external cues and

reminders. These may also help with initiation difficulties.
◆ Introduce a noticeboard or white board in a prominent

place in the home to prompt patients about specific actions,
as well as daily/weekly schedules.
◆ Systematising storage of household items with explicit

labelling (e.g. colour coding) (such strategies are especially
important for safety of toxic substances for patients with
visual agnosia).
◆ Using errorless learning when teaching new skills to

minimise the need to ‘unlearn’ mistakes (i.e. prompting and
cueing in such a way that no errors are made during a
training process).
◆ Developing internal memory strategies via repetition,

association, chunking, visualisation of verbal material,
verbalisation of visual material; and/or maximising the
relevance and depth of understanding (of material). It
should be noted however that the degree of cognitive effort
required for such ‘internal’ memory strategies often
exceeds their utility for patients with memory and executive
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impairments. They can, however, be useful for specific tasks

like remembering names of people or studying for an exam
where external strategies are inappropriate.
◆ Using principles from behavioural psychology such as

shaping, modelling, chaining, and contingent
reinforcement, to maximise learning of new skills.
3.6.3 Strategies for executive difficulties

◆ Providing problem solving skills training to help develop
an explicit and systematic approach to solving difficulties
e.g.:
i) defining the problem to be overcome;
ii) generating different strategies to overcome

problem;
iii) highlighting the pros and cons of each

strategy;
iv) deciding the best strategy based on the pros

and cons;
v) implementing the strategy; and
vi) evaluating the outcome.
◆ Using an alarmed stopwatch to help patients monitor the

amount of time taken on given tasks to help planning and
temporal judgement impairments.
◆ Using self talk and self instruction (verbal mediation) to

help overcome initiation problems and to remind the patient
of self statements for aiding social regulation.
◆ Breaking tasks down into their component steps with

written instructions to reduce disabilities from planning
deficits.
◆ Introduce repeating routine/cycles to reduce unnecessary

decision-making (e.g. weekly menus; shopping lists, set
times for visiting the gym etc.).
(p.554) 3.6.4 Strategies for behavioural management

◆ Identifying a small range of people to provide behavioural
feedback to help modify inappropriate social behaviours.
This should be done with careful and sensitive collaboration
between the patient and those providing the feedback. (It is
important to stress that the feedback should be immediate,
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concrete, supportive and constructive and aimed at very

specific behaviours only).
◆ Using a hand held counter to aid the self monitoring of

specified inappropriate social behaviours.
◆ Using video feedback to improve insight into specific

inappropriate behaviours. As patients may be surprised or
upset by being confronted visibly with inappropriate
behaviours this should always:
i) be discussed and negotiated carefully with the
patient;
ii) be undertaken in a controlled and supportive

atmosphere; and
iii) be conducted with sufficient time allocated for

debriefing immediately afterwards.
◆ Using principles from behavioural psychology to help

shape, model and increase the frequency of appropriate
social behaviours.
3.6.5 Strategies for social skills

◆ Teaching conversation skills for slowing, pacing and
allowing ‘thinking time’ during interactions to help
minimise word finding, sentence construction and
concentration difficulties in conversation.
◆ Teaching social skills so that the patient is comfortable

asking for things to be repeated during conversation when
attention, memory or language deficits have caused them to
lose track.
◆ Encouraging others to use short sentences and high

frequency words and to allow enough time for the patient to
reply to questions when word finding, attentional, receptive
language or expressive language impairments are present.
◆ Encouraging those close to patient to use closed, multiple

choice type questions rather than open ended questions
where decision making and initiation of ideas is impaired.
3.6.6 Intervention for related emotional disorders

Psychological interventions for emotional disorders following
head injury have largely been developed from the adult mental
health field of clinical psychology and adapted to the specific
challenges of this population. The most common forms of
intervention include both individual and group therapies in the
Page 21 of 31
following areas: i) cognitive behavioural psychotherapy (CBT)

with exposure and/or cognitive restructuring for post
traumatic stress symptoms (with the possible adjunct of
Serotonin Specific Re-uptake Inhibitor (SSRI) antidepressant
medication following medical review); ii) CBT for anger
management (with the possible adjunct of Carbamazepine or
other mood (p.555) stabilising medication); iii) CBT for
anxiety and depression (with the possible adjunct of
antidepressant medication); iv) anxiety management training
and CBT for control of anxiety symptoms.
In utilising such interventions it is vital that the

neuropsychological context and constraints are accommodated
in the therapeutic process.
Alongside these types of interventions, there is a need for

specialist ‘neurorehabilitation counselling’ to assist clients in
their understanding and coping with the effects of head injury
during the course of recovery. This is likely to involve provision
of the following:
◆ general information and explanation about head injury;

feedback about specific impairments; explanation of
treatment rationale; negotiation of treatment goals; general
advice and emotional support; promotion of insight,
awareness and coping strategies; and progress review.
While the above list outlines some of the most commonly used
interventions, it is in no way exhaustive. Also, it is essential
that emotional disorders after head injury are addressed
within the overall context of the head injury and patients’
aspirations, hopes, social network and overall psychosocial
circumstances. ‘Atomising’ their emotional experiences to a
series of disorders or symptoms will not adequately address
the complexity of emotional needs. Indeed, this principle must
underpin all forms of rehabilitation for head injured patients.
Page 22 of 31
3.6.7 Facilitating personal, vocational and family adjustment

Many persons with severe head injury face major challenges of
adjustment as they are unable to resume their former work,
family and social roles. The process of psychological
adjustment is compounded by executive difficulties, especially
lack of insight and reduced capacity for self-appraisal and
problem solving, often combined with lack of emotional and
behavioural control. Without specialist help many struggle to
make the necessary adjustments to their residual disability
and continue to strive for an unrealistic degree of recovery.
Others make decisions which do not take due account of
restrictions arising from head injury, leading to repeated
failure, loss of confidence and self belief.
The need to support people with neurological conditions in

making long-term psychological adjustments to altered
personal, family and social circumstances is recognised in
Quality Requirement 5 on ‘Community Rehabilitation and
Support’ in the National Service Framework for Long-term
Conditions (UK Department of Health, 2005). The National
Clinical Guidelines on Rehabilitation following Acquired Brain
Injury (RCP/BSRM, 2003) include specific guidelines on
individual and/or group neuropsychotherapeutic interventions
to facilitate long-term psychological, family and social
adjustment, including sexual relationships.
The provision of specialist ‘neuropsychotherapy’ requires the

adaptation of standard psychotherapeutic techniques to take
into account neuropsychological constraints of the person (cf.
Tyerman & King, 2004). Our experience is that it is often
possible to assist the person in moving from a position of
denying, feeling controlled by (or of a sense of (p.556)
battling constantly with) one’s disability and oneself, to a
position of understanding and accommodation to disability and
resultant personal and life changes sufficiently to deal
constructively with their altered circumstances and move
forward in their lives.
Return to education or employment represents for many a

major decision, which can either facilitate positive adjustment
or provoke a downward spiral of failure.
The National Service Framework for Long-term Conditions

(UK Department of Health, 2005) includes a specific Quality
Page 23 of 31
Requirement on ‘Vocational Rehabilitation’. This requires

provision of:
◆ a coordinated multi-agency approach; routine

identification of needs and vocational goals within local
rehabilitation services; availability of specialist vocational
rehabilitation programmes; and routine monitoring of
vocational outcomes.
This is supported by guidelines on a co-ordinated inter-agency

approach to vocational assessment and rehabilitation after
brain injury (BSRM/JCP/RCP, 2004).
Those able to return to previous employment or training need

a carefully managed process of return with advice and support
in the workplace, close liaison with the employer (or tutor) and
other agencies (e.g. Jobcentre Plus, Occupational Health),
ongoing support and proactive review/follow-up (BSRM/JCP/
RCP, 2004). For those unable to return to previous
employment, a programme of specialist vocational
rehabilitation may be required: to highlight vocational
strengths and weaknesses; provided a graded return to
alternative occupation; voluntary work trials to test out the
viability of alternative occupations and refine coping
strategies; assistance with job search/application and set up;
and long-term supported placements with job coaching input
as required (Tyerman et al. 2008).
It is vital to include the family as fully as possible in the

process of rehabilitation. Close liaison with the family is
essential both to obtain feedback about difficulties and
progress in the home and to explain rehabilitation strategies,
which can then be reinforced by family members. However, as
set out in the National Service Framework for Long-term
Conditions (UK Department of Health, 2005) family members
need access to support both in their role as carer and in their
own right. Family members may themselves need specialist
advice and support in understanding and coping with the
impact of severe head injury both upon themselves and the
family as a whole. Kreutzer et al. (2002) for example, describe
a brain injury family intervention commonly delivered through
family, marital, individual or group therapy in combination
with bibliotherapy. A wide range of family services is required
to facilitate family adjustment including family education;
Page 24 of 31
individual and group family support; and specialist couple and

family counselling.
3.6.8 Effectiveness
Studies evaluating the effectiveness of cognitive rehabilitation
for patients with severe head injury are relatively sparse and
frequently suffer from significant methodological constraints.
There is some modest evidence that restorative techniques
involving repeated practice of specific tasks in laboratory
settings can be effective for improving some specific attention
and language based functions. There is insufficient evidence,
however, that (p.557) any gains are generalised to everyday
activities. Restorative strategies for other impairments have
virtually no empirical support. In contrast, the current
evidence suggests that compensatory strategies are effective
in reducing everyday memory failures, minimising anxiety and
increasing self-concept and quality of interpersonal
relationships (Halligan and Wade, 2005). Behavioural
approaches aimed at maximising skill acquisition and
monitoring, including performance feedback and
reinforcement, have also demonstrated their efficacy. It is
these types of rehabilitation that generalise best to everyday
life situations.
Cognitive rehabilitation programmes which have the strongest

outcomes tend to be those combining early intervention,
compensatory strategies and supported employment (Carney
and Coudray, 2005). Our clinical experience is that
neuropsychological interventions (including educational,
cognitive, behavioural, psychotherapeutic and family
components) are most effective when delivered as part of
specialist inter-disciplinary brain injury rehabilitation
programmes. There is evidence that multi-faceted post-acute
rehabilitation programmes can significantly improve psycho-
social outcome after severe head injury.
4 Summary and conclusions

Patients with head injury present with a complex interaction of
cognitive, behavioural and emotional changes, which often
exert a major impact upon their lives and the lives of their
family.
After mild and moderate head injury cognitive impairments

are usually of mild severity and temporary. Speed of
information processing is most frequently affected but
Page 25 of 31
reaction time, short-term and long-term memory deficits are

also common. Post-traumatic stress reactions are at least as
prevalent as for those without head injury. Where post-
concussion symptoms persist anxiety and depression are
common reactions to the disabilities caused by these. Anxiety
can also result from uncertainty over the relative contribution
of psychological and organic factors to problems and the
uncertainty of ultimate prognosis.
After severe head injury cognitive impairments are often wide

spread, significant and permanent. They are most often in
some or more of the following domains:
◆ speed of information processing; divided, selective and

sustained attention; short-term and long-term memory;
executive function; and expressive language (in terms of
word finding and sentence construction).
Depression, anger, anxiety and frustration often result from

the disabilities caused by severe head injury, while post-
traumatic stress reactions are less prevalent than in mild/
moderate injuries. Irritability, anger and aggression can be
exacerbated by reduced impulse control. Difficulties in long-
term adjustment are common, as are difficulties in marital,
family and social relationships.
Specialist neuropsychological interventions are required

across acute, post-acute and community settings if patients
are to make and sustain their optimal recovery. For those (p.
558) with mild and moderate injury early brief assessment
and intervention can help reduce further complications but
individualised formulations are required when post concussion
symptoms persist. Whilst patients with severe head injury
often respond positively to rehabilitation and make marked
improvement over a period of years, many are left with
substantial psychological disability and associated social
restrictions. Patients often struggle to maintain the full
benefits of rehabilitation once active therapeutic involvement
has been phased out, particularly those with executive
difficulties. Even after long periods when patients have
appeared settled, they may struggle to adapt to changes in
work, family and social circumstances. As such, further
intervention may be required from time to time throughout the
whole of their life. Open door access to specialist
Page 26 of 31
rehabilitation and support is vital if patients and their families

are to maintain optimal adjustment to the long-term effects of
their injury.
British Psychological Society (1989). Services for adults

patients with acquired brain injury. Leicester: British
Psychological Society.
British Psychological Society (2005). Clinical

Neuropsychology and Rehabilitation Services for Adults with
Acquired Brain Injury. Leicester: British Psychological Society
- Division of Neuropsychology.
BSRM/JCP/RCP (2004). Vocational Assessment and

Rehabilitation after Acquired Brain Injury. Inter-Agency
Guidelines. (Edited by A Tyerman & MJ Meehan). Inter-Agency
Advisory Group on Vocational Rehabilitation after Brain Injury.
London: British Society of Rehabilitation Medicine, Jobcentre
Plus and Royal College of Physicians.
British Society of Rehabilitation Medicine (1998).

Rehabilitation after traumatic brain injury. A Working Party
Report. London: British Society of Rehabilitation Medicine.
Carney N and Coudray H (2005). Cognitive rehabilitation

outcomes for traumatic brain injury. In Halligan PW & Wade
DT (eds). Effectiveness of rehabilitation for cognitive deficits.
Oxford. Oxford University Press.
Department of Health (2005). The National Service

Framework for Long-term Conditions. London: Department of
Health. www.dh.gov.uk/longtermnsf.
Halligan P.W and Wade D.T (2005). Effectiveness of

rehabilitation for cognitive deficits. Oxford. Oxford University
Press.
King N.S (2003). The post concussion syndrome: clarity amid

the controversy? British Journal of Psychiatry , 183, 276–278.
Kraus J.F and Nourjah P (1988). The epidemiology of mild

uncomplicated brain injury. Trauma , 28, 1637–1643.
Page 27 of 31
Kreutzer J.S., Kolakowsky-Hayner S.A., Demm S.R., and

Meade M.A (2002). A structured approach to family
intervention after brain injury. Journal of Head Trauma
Lancet (1983). Caring for the disabled after head injury. The
Lancet , II, 948–949.
Miller, J.D and Jones, P.A (1985). The work of a Regional

Head Injury Service. The Lancet, May 18, 1141–1141.
Levack W.M.M., Taylor K., Siegert RJ., Dean S.G.,

McPherson K.M and Weatherall M (2005). Is goal planning
in rehabilitation effective? A systematic review. Clinical
Oddy M and Herbert C (2008). Brain injury and the family: A

review. In A Tyerman & NS King (eds.). Psychological
approaches to rehabilitation after traumatic brain injury.
Oxford: BPS Blackwell.
(p.559) RCP/BSRM (2003). Rehabilitation following

acquired brain injury: national clinical guidelines (Turner-
Stokes L, ed.). London: Royal College of Physicians/British
Society of Rehabilitation Medicine
Tennett A (2005). Admission to hospital following head injury

in England: Incidence and socio-economic determinants.
BioMedCentral Public Health (March 2005), 5, 21.
Tyerman A and King N.S (2004). Interventions for

psychological problems after brain injury. In LH. Goldstein & J.
McNeil (eds.). Clinical Neuropsychology. A Practical Guide to
Assessment & Management for Clinicians. Chichester: Wiley.
Tyerman A., Tyerman R., and Viney P (2008). Vocational

rehabilitation programmes. In A. Tyerman & NS. King. (eds.).
Psychological approaches to rehabilitation after traumatic
brain injury. Oxford: BPS Blackwell.
Wade D.T., King, N.S., Wenden, F.S., Crawford, S., and

Caldwell, F.E (1998). Routine follow-up after head injury: a
second randomised controlled trial. Journal of Neurology,
Neurosurgery & Psychiatry , 65, 177–183.
Further reading
Page 28 of 31
British Psychological Society (2005). Clinical

Neuropsychology and Rehabilitation Services for Adults with
Acquired Brain Injury. Leicester: British Psychological Society
- Division of Neuropsychology.
BSRM/JCP/RCP (2004). Vocational Assessment and

Rehabilitation after Acquired Brain Injury. Inter-Agency
Guidelines. (Edited by A Tyerman & MJ Meehan). Inter-Agency
Advisory Group on Vocational Rehabilitation after Brain Injury.
London: British Society of Rehabilitation Medicine, Jobcentre
Plus and Royal College of Physicians.
Halligan P.W and Wade D.T (eds) (2005). Effectiveness of

Rehabilitation for Cognitive Deficits. Oxford. Oxford University
Press.
King N.S (2003). The post concussion syndrome: clarity amid

the controversy? British Journal of Psychiatry , 183, 276–278.
Ponsford J., Sloan S., and Snow P (1995). Traumatic brain

injury: Rehabilitation for everyday adaptive living. Hove:
Lawrence Erlbaum Associates.
RCP/BSRM (2003). Rehabilitation following acquired brain

injury: national clinical guidelines (Turner-Stokes L., ed.).
London: Royal College of Physicans/British Society of
Rehabilitation Medicine.
Rose, F.D and Johnson, D.A (1996). Brain injury and after.
Towards improved outcome. John Wiley & Son, Chichester.
Tyerman A and King N.S (eds.). (2008) Psychological

approaches to rehabilitation after traumatic brain injury.
Oxford: BPS Blackwell.
Wade D.T., King N.S., Wenden F.S., Crawford S., and

Caldwell F.E (1998). Routinefollow-up after head injury: a
second randomised controlled trial. Journal of Neurology,
Neurosurgery & Psychiatry , 65, 177–183.
Wood R.L and McMillan T.M (2001). Neurobehavioural

disability and social handicap following traumatic brain injury.
Hove: Psychology Press. (p.560)
Page 29 of 31
APPENDIX 1 Glasgow coma scale
Sub-scale Response Score
Eye opening Opens eyes on his/her own 4

(score 0–4)
Opens eyes when asked to do so in a 3
loud voice
Opens eyes to pain 2
Does not open eyes 1
Verbal Carries on a conversation correctly 5

response and tells examiner where he is, the
(score 0–5) year and month.
Seems confused or disoriented 4
Talks so the examiner can 3

understand him/her but makes no
sense
Makes sounds that the examiner 2

cannot understand
Makes no noise 1
Motor Follows simple commands 6

response
Pulls examiner’s hand away on 5
(score 0–6)
painful stimuli
Pulls a part of his body away on 4

painful stimuli
Flexes body appropriately to pain 3
Decerebrate posture 2
Has no motor response to pain 1
TOTAL SCORE 3–15
Page 30 of 31
Page 31 of 31
The neuropsychological presentation of Alzheimer’s disease and other
neurodegenerative disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The neuropsychological
presentation of Alzheimer’s disease
and other neurodegenerative
disorders
Julie Snowden
DOI:10.1093/acprof:oso/9780199234110.003.028

Alzheimer's disease and other neurodegenerative diseases that
lead to progressive cognitive impairment are conventionally
classified as ‘the dementias’. Dementia is traditionally defined
as a generalized impairment of intellect, the implication being
that all aspects of mental function are uniformly impaired. A
logical corollary is that the dementia associated with different
disorders should be indistinguishable. This is far from the
case. Degenerative diseases do not affect the brain in an
undifferentiated manner. Rather, they have predilections for
certain brain regions and show relative of sparing of others. In
consequence, they are associated with distinct profiles of
cognitive and behavioural change that can be identified with a
high degree of accuracy. This chapter describes the
neuropsychological presentations of the most common
neurodegenerative disorders associated with cognitive
change: Alzheimer's disease, frontotemporal lobar
Page 1 of 39
degeneration, dementia with Lewy bodies, Huntington's

disease, motor neurone disease, progressive supranuclear
palsy, and corticobasal degeneration.
Keywords: neurodegenerative disorders, dementias, cognitive change,

Alzheimer's disease, Huntington's disease, motor neurone disease, progressive
supranuclear palsy, corticobasal degeneration
1 Introduction
Alzheimer’s disease and other neurodegenerative diseases
that lead to progressive cognitive impairment are
conventionally classified as ‘the dementias’. Dementia is
traditionally defined as a generalised impairment of intellect,
the implication being that all aspects of mental function are
uniformly impaired. A logical corollary is that the dementia
associated with different disorders should be
indistinguishable. This is far from the case. Degenerative
diseases do not affect the brain in an undifferentiated manner.
Rather, they have predilections for certain brain regions and
show relative of sparing of others. In consequence, they are
associated with distinct profiles of cognitive and behavioural
change that can be identified with a high degree of accuracy.
This chapter describes the neuropsychological presentations
of the most common neurodegenerative disorders associated
with cognitive change.
The disorders under consideration can be classed broadly in

terms of the predominant topographical emphasis of
pathological change (Table 28.1). Alzheimer’s disease (AD),
frontotemporal dementia (FTD) and its associated syndromes
of semantic dementia and progressive aphasia result from
degeneration principally of the neocortex. The salient
presenting characteristic is alteration in mental function.
Physical symptoms and signs are minimal or absent initially
and typically emerge only late in the disease course.
By contrast, in conditions that fall within the category of

‘movement disorders’ the primary site of pathology is the
basal ganglia. Physical symptoms and signs predominate and
mental changes may be subsidiary or emerge later in the
disease. Some disorders (e.g. dementia with Lewy bodies and
corticobasal degeneration) may be characterised from the
outset by a combination of cortical and subcortical features.
Neuropsychological evaluation can aid recognition of each
condition, but is particularly crucial in the cases of neocortical
Page 2 of 39
disorders, for which neurological examination provides few

clues.
In the past, a common view was that accuracy of dementia

diagnosis was unimportant. As there is no effective treatment -
the argument went - provision of a precise diagnostic label has
little value. This nihilistic view is beginning to change. The
advent of novel therapies for disorders such as AD means that
correct diagnosis is essential. Only then can (p.562) therapies
be targeted appropriately and their effects meaningfully
evaluated. Basic science research, addressing causation and
risk factors for disease, is critically dependent on accurate
classification of patients’ clinical phenotype. In clinical
practice, the nature of patients’ disorder can have profound
implications for patients’ management and for the advice
offered to carers. Neuropsychologists have a vital role.
2 Alzheimer’s disease (AD)

AD is the most common form of dementia. Its prevalence
increases with age, although onset may occur in middle age
and occasionally as early as the fourth decade of life. It is
more common in women. The longer normal life span of
women contributes to the higher female prevalence, although
does not fully account for it. The course is insidiously
progressive over about eight years. People with AD are
typically physically well in the early stages, feature important
in differential diagnosis. With progression parkinsonian signs
of slowing and limb rigidity emerge and myoclonic jerking
movements of the limbs. Nevertheless, physical problems are
overshadowed by the momentous cognitive disturbance.
Table 28.1 Overview of neurodegenerative

disorders associated with cognitive change
Disorder Dominant site of Dominant Neuropsychological

pathology impairment presentation
Alzheimer’s Medial temporal Cognitive Cognitive

disease lobes impairment,
Temporoparietal especially memory
neocortex
Frontotemporal Frontal and Behavioural Personality and

dementia anterior behavioural
temporal lobes
Page 3 of 39
Disorder Dominant site of Dominant Neuropsychological

pathology impairment presentation
change, executive
impairment
Semantic Temporal Cognitive Loss of ‘memory’

dementia neocortex, for words and
especially concepts. Impaired
inferior and naming and word
middle gyri comprehension.
Progressive Left perisylvian Cognitive Expressive

(non-fluent) cortex language disorder
aphasia
Dementia with Basal ganglia + Mental + Fluctuating mental

Lewy bodies/ neocortex physical state. Memory,
Parkinson’s perceptuospatial
disease and executive
dementia impairments
Huntington’s Basal ganglia Mental + Psychomotor

disease (striatum) Physical slowing, executive
impairments
Motor neuron Brain stem and Physical Executive

disease motor cortex impairment
Progressive Basal ganglia Physical Psychomotor

supranuclear slowing, executive
palsy impairments
Corticobasal Basal ganglia + Physical Ideomotor apraxia,

degeneration frontoparietal executive
cortex impairments
Page 4 of 39
(p.563) There is not a single causal factor. In a minority of cases,

AD is familial and shows an autosomal dominant mode of
inheritance. Genes responsible for familial cases have been found
on chromosomes 1,14 and 21. The presence of an e4 allele in the
Apolipoprotein (APOE) gene is a known risk factor for AD. There
are likely to be other genetic influences that increase susceptibility.
The earliest pathological changes in AD are in medial temporal
structures, and structural MR imaging shows atrophy of the
hippocampi (Jack et al. 1999). On functional imaging (Jagust et al.
1988; Talbot et al. 1995) early changes are seen in temporoparietal
cortex. Over the course of the disease structural and functional
changes become more widespread. The characteristic histological
appearances are of β-A4 amyloid deposition, senile plaques
consisting of degenerating neuronal processes and intra-neuronal
neurofibrillary tangles, leading to the death of large cortical
neurones. Detailed background information about AD can be found
in Burns et al. (2005).
2.1 Cognition in AD
2.1.1 Memory
The earliest presenting symptom is typically of problems in
memory (Welsh et al. 1991; Perry and Hodges 2000).
Symptoms may include difficulty remembering appointments,
impaired recall of recent events, repetitiveness in conversation
and an increased tendency to mislay objects. Memory for the
more remote past may appear to be better preserved, and
patients ‘live in the past’. Patients may themselves
acknowledge memory problems although predictably (since
they forget that they have asked the same question
repeatedly), they often underplay the magnitude of the
impairment. The disparity between relatives’ and patients’
account is of value in distinguishing AD from the memory
complaints of the ‘worried well’.
The history of memory problems is supported by findings of

impaired performance on standard tests of episodic memory,
such as list learning, story recall, face and object memory.
Although performance may show some benefit from cueing
and recognition memory procedures, performance is not
typically restored to normal levels. Moreover, if memory is re-
tested following a delay there is typically evidence of loss of
information over time, suggesting that the problem is not
simply one of initial attention/registration of information.
Impairments are frequently demonstrable on both visual and
verbal memory tasks. Nevertheless, impairment may be more
marked in one modality, the visual-verbal disparity reflecting
Page 5 of 39
the greater emphasis of atrophy in the right or left medial

temporal lobe.
2.1.2 Working memory and attention

Deficient immediate or ‘working’ memory may contribute to
patients’ impaired memory functioning. This is frequently
manifest clinically by patients’ tendency to lose train of
thought. On testing patients may show a reduced digit span
and require constant repetition of test instructions. The
precise basis for ‘working memory’ deficits remains a subject
of debate. Working memory deficits in early-stage AD have
most commonly been attributed to a ‘central executive’
impairment (Baddeley et al. 1991) or to problems in divided (p.
564) attention (see Perry and Hodges 1999 for excellent
review), by virtue of the fact that patients have difficulty
coping with multiple tasks. The inference is that such
executive/attentional deficits reflect impaired frontal lobe
function. Yet, at odds with this assumption is the characteristic
finding on functional neuroimaging in early AD of changes in
temporoparietal and not frontal regions. Moreover, an
association has been demonstrated between working memory
impairment and problems on posterior hemisphere (language
and visuospatial) tasks (Stopford et al. 2007), suggesting that
reduced storage capacity for phonological and spatial
information may contribute substantially to patients’ working
memory difficulties. Recognition of the presence of problems
in working memory is important. In some patients they occur
in the absence of a severe classical amnesia. Such patients
may have profound difficulty holding information in the
immediate present, yet what information is assimilated is
retained reasonably well over a delay.
2.1.3 Language
The most common language symptom in AD is a problem in
word finding, which is often most pronounced for Proper
nouns, such as recall of people’s names. Conversational
speech may become halting because of word retrieval
difficulty, and sentences may be unfinished because of loss of
train of thought. Occasional paraphasic errors may be noted,
although phonological and semantic errors are rarely a
prominent feature. Speech may develop a stuttering, festinant
quality (logoclonia). Difficulties are not confined to spoken
language. Patients frequently have difficulty in spelling,
Page 6 of 39
reading and writing as well as in calculation. Relatives may be

dismayed to discover that patients can no longer produce their
signature.
Word finding difficulties in AD are commonly ascribed to

impaired semantic memory (Hodges et al. 1992a; Salmon et al.
1999). However, there is a need for caution in assuming that
this is invariably the case. AD patients are frequently
frustrated by their difficulty in word retrieval, suggesting that
they have in mind words that they cannot retrieve. Moreover,
in a factor analytic study of cognitive test performance in AD
(Stopford et al. 2008) naming scores loaded on to a general
language factor, which included measures of repetition and
spelling that make no semantic demands, and not on to a
factor comprising tasks ostensibly tapping semantic memory.
Understanding of language is typically relatively well

preserved at a single word level. However, AD patients may
have difficulty comprehending complex syntax and
conversations involving multiple participants, a factor that
may lead to a reticence to socialise. Appreciation that patients
may become easily ‘overloaded’ is important in ensuring
optimal communication.
2.1.4 Perception and spatial skills

A variety of symptoms may be indicators of perceptuospatial
impairment, reflecting pathological involvement of parietal
cortex. There may be reports of minor driving accidents,
resulting from spatial misjudgement (e.g. driving too close to
parked cars; veering across lanes, driving round a roundabout
the wrong way). Patients may become lost, initially in
unfamiliar and later familiar surroundings. Patients may have
difficulty (p.565) orienting clothing when dressing, and may
put on garments back-to-front or inside out. They may have
difficulty aligning cutlery when laying a table and folding
clothes. They may be hesitant going up and down stairs,
because of difficulty judging spatial depth. Severe spatial
problems are manifest by disorientation within the home and a
difficulty locating objects within the patients’ visual fields.
Frank perceptual impairments are usually relatively late
features, and may include problems in recognising faces,
including their own reflection in a mirror, and
misidentification of objects.
Page 7 of 39
Constructional tasks such as clock drawing and copying of

simple line drawings are highly sensitive to spatial difficulties.
The salient qualitative feature of performance is a breakdown
in overall configuration and spatial relationship between
elements. The Visual Object and Space Perception battery
(VOSP) (Warrington and James 1991) is a valuable instrument
in eliciting perceptual and spatial deficits. It makes minimal
motor demands so allows spatial deficits to be identified
independently of deficits in praxis, which may also contribute
to patients’ constructional problems. When shown an array of
dots spatially impaired patients omit some dots while re-
counting others. They have difficulty appreciating the three-
dimensional nature of cubes and tend to count edges. They
have difficulty identifying degraded perceptual stimuli and
tend to respond on the basis of local features rather than
global configuration.
2.1.5 Praxis
Manual skills such as symbolic gesture (e.g. waving) and
manipulation of objects (e.g. folding clothes) may be
compromised by spatial deficits. However, in some patients
impairments in praxis far outweigh the degree of spatial
impairment, and occasionally may be the dominant presenting
feature of the disease (Green et al. 1995).
2.1.6 Executive Functions

AD patients commonly perform poorly on executive tasks, even
when structural and functional imaging shows no evidence of
frontal lobe pathology and patients’ preserved social skills
suggest an absence of “frontal” behaviour. It is important to
keep in mind that executive tasks make multiple cognitive
demands, so that performance failure might arise secondary to
patients’ problems in memory, language, perception, spatial
appreciation or praxis (Thompson et al. 2005). Consideration
of the qualitative nature of errors (perseverations, concrete
responses, failures of mental set shifting) is crucial in
interpreting the basis for executive test failures.
Page 8 of 39
2.2 Behaviour and affect in AD

A striking feature of AD patients presenting to a diagnostic
clinic is their preserved social façade. Patients’ emotional
warmth, social manner and facility in use of social platitudes
in conversation frequently mask the magnitude of the
underlying cognitive disorder. That is not to say that
behavioural changes are totally absent. Relatives frequently
report an increase in irritability, which is usually directed
towards family members and may reflect frustration at failing
cognitive powers and loss of functional independence. Patients
may also be noted to be more anxious, low in mood, lacking in
confidence and less (p.566) gregarious than formerly,
features that can also reasonably be interpreted as secondary
to their emerging cognitive problems. Notwithstanding such
alterations, gross character change is not a hallmark of early
and middle-stage AD and patients are regarded as the ‘same
person’ as before, albeit with acquired difficulties.
2.3 Phenotypic variation in AD

The prototypical picture of AD is of a constellation of cognitive
difficulties, with memory impairment being a central feature.
However, patients are not identical. Whereas some patients
are densely amnesic, others show only mild inefficiencies in
memory, despite more pervasive impairments in other
cognitive domains. The prominence of language or visuospatial
symptoms may differ. Aside from these general differences in
weighting of symptoms there are some more striking
phenotypic variations (Galton et al. 2000; Snowden et al.
2007a). Some patients present, not with symptoms of memory
loss, but with a circumscribed disorder of language associated
with asymmetric atrophy of the left hemisphere (aphasic
presentation). Others may present with problems in ‘vision’,
which may reflect impaired spatial skills (biparietal
syndrome), or impaired visual perception (posterior cortical
atrophy). Such patients have often consulted opticians and
ophthamologists on the assumption that the problem is ocular.
Occasionally, the dominant presenting feature is of difficulty in
carrying out skilled actions (praxic presentation). These ‘focal’
presentations of AD are likely to represent extreme examples
of the normal variation seen within the AD population
(Snowden et al. 2007a; Stopford et al. 2008).
2.3.1 Factors influencing clinical phenotype
Page 9 of 39
Age of onset influences presentation. Amnestic presentations,

reflecting dominant medial temporal pathology, are most
common in the elderly. Elderly patients are also more likely to
exhibit ‘frontal lobe’ characteristics, although in many
instances this is due to coincidental small vessel vascular
disease affecting subcortical-frontal pathways. The presence
of perceptuospatial impairment in the early stages of disease,
reflecting involvement of temporoparietal cortex, is
characteristic in patients presenting in their 50s and 60s. The
APOE ε4 allele, an established risk factor for AD, appears
specifically to influence the degree of amnesia (Snowden et al.
2007a).
Page 10 of 39
2.4 Diagnostic criteria for AD

The most frequently used diagnostic criteria for AD in
research studies remains the NINCDS-ADRDA criteria
(McKhann et al. 1984). A diagnosis of probable AD requires
the presence of impairments in memory and at least one other
cognitive domain. Despite their continued use the criteria
were intended, at their inception, to be provisional. They are
limited for two main reasons. First, they lack specificity. They
are sufficiently broad that many patients with disorders other
than AD would fulfil AD criteria (Varma et al. 1999). Second,
they are insensitive to early-stage disease. People with
significant, yet relatively circumscribed memory deficits would
be excluded, even though such patients might be expected to
benefit most from anti-cholinesterase therapies.
(p.567) Recognition of these limitations has prompted the

development of a new set of AD criteria (Dubois et al. 2007),
which focus exclusively on memory, reflecting the perceived
importance of memory loss in AD. A diagnosis of probable AD
is determined by historical reports of a gradual and
progressive change in memory function together with
demonstrations of significantly impaired episodic memory
(encompassing recognition and cued recall as well as free
recall) on neuropsychological testing. The memory loss should
be supported by evidence of medial temporal lobe atrophy on
structural imaging, a cerebrospinal fluid biomarker, functional
imaging abnormalities or proven genetic mutation in the
family.
These new criteria have the advantage of reducing the number

of false positive diagnoses, so increasing specificity. Also, by
acknowledging that the memory disorder may be an isolated
symptom, the criteria are likely to be sensitive to earlier stage
of disease. Their chief drawback is that they make the
assumption that memory impairment is an invariable feature
of AD and do not encompass other focal presentations of AD. It
is important to keep in mind the fact that AD can present as a
disorder of language, spatial function or “vision”.
3 Frontotemporal lobar degeneration: frontotemporal

dementia, progressive aphasia and semantic dementia
Frontotemporal lobar degeneration (FTLD) is an umbrella
term for a collection of pathologically-linked clinical
syndromes that result from circumscribed atrophy of the
anterior hemispheres. These include frontotemporal dementia
Page 11 of 39
(FTD), a disorder of behaviour and executive function

associated with bilateral atrophy of the frontal and anterior
temporal lobes, progressive non-fluent aphasia (PNFA), a
disorder of expressive language associated with left
perisylvian atrophy, and semantic dementia (SD), a disorder of
conceptual understanding associated with bilateral atrophy of
the inferior and middle temporal cortices. Because of the
psychological and anatomical specificity of these disorders
they are frequently described under the rubric of ‘focal
dementias’. It is worth emphasising, however, that ‘focal’ does
not necessarily imply ‘less severe’: the extent of tissue loss in
the affected regions is typically greater in FTLD than in AD
and overall brain weight at death is typically lower.
Unlike AD which increases in prevalence with advancing age

the syndromes of FTLD present most commonly in the 50s and
60s and can present even earlier. Men and women are affected
equally. A positive family history is present in approximately
40% of cases.
The disorders are insidiously progressive, and have an average

total duration of about 8 years. There is, however, wide
variation in time course, reflecting patients’ physical state.
Many patients remain physically well, parkinsonian signs
emerging only late in the course. Such patients may survive
for 10 or 15 years. By contrast, a minority of patients develop
physical signs of motor neurone disease, leading to an
attenuated course of 2-3 years.
The pathological changes underlying FTLD are not uniform,

and can broadly be classified into two types. Some brains
show transcortical gliosis with tau-reactive intraneuronal
inclusions (Pick bodies) and sometimes swollen neurons (Pick
cells). These cases would fulfil (p.568) traditional
pathological criteria for ‘Pick’s disease’ and are now referred
to as ‘tau-positive’ or ‘Pick-type’. Other brains show
microvacuolation, with intraneuronal inclusions that stain for
ubiquitin, and are referred to as ‘tau-negative, ubiquitin-
positive’ or FTLD-ubiquitinated (FTLD-U) type. FTD and PNFA
can be associated with both histopathological types, whereas
SD is typically associated with FTLD-U (Snowden et al. 2007b).
Just as the pathology underlying FTLD is not uniform, so too

there appear to be different molecular substrates. Causal
genetic defects have been identified on chromosome 17, in the
Page 12 of 39
tau gene in some familial cases of FTD and in the progranulin

gene in cases of FTD and PNFA. These account collectively for
less than half of all familial cases indicating that other faulty
genes are yet to be discovered.
Page 13 of 39
3.1 Behaviour in FTD

The dominant presenting feature of FTD is altered behaviour
(Neary et al. 1988). Formerly responsible and conscientious
individuals become disinhibited and socially inappropriate,
they neglect self-care and personal responsibilities, and show
a total lack of insight or concern into their altered mental
state. Relatives report the patient to be radically altered in
character and not the same person as before. Socially
inappropriate behaviour may include infringements of social
etiquette, such as ignoring visitors to the home or drinking
wine from the bottle in a restaurant as well as more major
violations of social norms, such as wandering naked,
shoplifting and incontinence without concern.
There are three broad domains of behaviour that are

particularly important in differentiating FTD from other
common dementias (Bathgate et al. 2001): affect, repetitive
behaviours/stereotypies and eating/oral behaviours. FTD
patients no longer show the normal range of basic and social
emotions. They are typically fatuous and puerile, or else
emotionally blunted. They show a lack of sympathy, empathy
or compassion towards others, and exhibit no signs of
embarrassment at their socially inappropriate behaviour. An
emotional response to a situation that is out-of-character may
be the first signal that something is wrong: for example, an
absence of grief reaction at the death of a loved one.
Repetitive behaviours in FTD range from simple motor

mannerisms (e.g. repetitive humming, grunting, hand rubbing,
clapping, foot tapping) to complex behavioural routines (e.g.
wandering the same route, doing the same activity at the same
time each day). There may be verbal stereotypies, such as
saying a favoured word or phrase repeatedly. Some repetitive
behaviours are environmentally driven. For example, patients
may persistently read aloud notices or street signs, or hoard
objects. Utilisation behaviour, which is occasionally seen, is an
extreme form of environmental dependency: the patient
carries out the action associated with an object (e.g. drinking
from a cup; putting on glasses) even when that action is
contextually inappropriate (e.g. the patient repeatedly picks
up and drinks from a cup even though it is empty; the patient
puts on the pair of glasses in front of him/her even though the
glasses belong to the examiner).
Page 14 of 39
FTD patients may eat excessively and cram food, leading to

weight gain. Relatives may report that the patient would carry
on eating if food was continually available, suggesting that
excessive eating may in part be stimulus-driven. Often patients
acquire a preference for (p.569) sweet foods, and seek out
sweets, chocolates and biscuits. Some patients show food fads,
showing a preference for a particular brand of chocolate bar
or biscuit. Hyperorality may include excessive drinking and
smoking. An increase in alcohol consumption may raise the
diagnostic question of an alcohol-related aetiology, although in
the case of FTD the increase in alcohol intake is a symptom of
the patient’s disorder and not the cause. Attempts to eat
inedible objects (Klüver-Bucy syndrome) may be present in
late stage disease.
3.2 Cognition in FTD

3.2.1 Executive functions
FTD is predominantly a ‘frontal’ lobe disorder. In keeping with
the distribution of atrophy, patients exhibit impairments in a
range of frontal executive skills: abstraction, planning,
organisation, attention and mental set switching. Performance
is typically markedly impaired on standard rule-based tasks
such as the Wisconsin card sorting, Weigls and Brixton spatial
anticipation tests. Patients commonly show striking
perseveration of one response pattern, and make no attempt
to alter this pattern in the face of feedback that it is no longer
correct. On verbal and design fluency tests they generate a
paucity of items, and performance is characterised by
response perseverations, concrete responses (e.g. naming
their own dog instead of animal species) and rule violations
(e.g. giving proper names when instructed not to do so). On
picture sequencing tasks they may make minimal effort to
alter the original ordering of items, and fail to notice logical
anomalies. They typically perform poorly on tests of sustained
and selective attention and response inhibition.
The prevailing qualitative characteristics of patients’ cognitive

performance are economy of mental effort, impulsivity of
responding without checking, poor persistence, distractibility,
concreteness of thought, perseveration of responses, and a
general lack of concern for performance accuracy. These
features colour patients’ performance on tasks that extend
well beyond the realm of executive function.
3.2.2 Language, perceptuospatial and constructional skills
Page 15 of 39
In language, patients typically show reduced speech output,

echolalia, perseveration, verbal stereotypies and ultimately
mutism. On a standard confrontation naming test, although
frank semantic errors may sometimes be present, low naming
scores commonly reflect a high prevalence of perseverations
or ‘don’t know’ responses. On constructional tasks drawings
may be poorly organised and show perseveration of strokes.
On a simple spatial test such as counting an array of dots
performance may be inaccurate because of patients’ impulsive
responding: if patients are asked to point to the dots they have
no difficulty doing so (in contrast to spatially impaired AD
patients), indicating that the low accuracy scores are not the
result of primary problems in spatial localisation. The key
message here is that it is important to take account of the
qualitative characteristics of patients’ performance in
interpreting the nature of patients’ deficits. There is not a one-
to-one correspondence between a test and a function, and
failure on ‘posterior’ hemisphere tests may arise for ‘anterior’
hemisphere reasons (Thompson et al. 2005).
(p.570) 3.2.3 Memory

FTD patients typically exhibit a characteristic “frontal” type of
memory impairment. Performance is severely impaired on
open-ended recall tests, yet improves on more constrained
cued recall and multiple-choice recognition tests. Moreover,
what information is assimilated is relatively well retained over
a standard 20 or 30-minute delay, suggesting that the problem
is one of registration rather than retention per se. Patients do
not show the topographical memory loss that is so common in
AD, evidenced by the fact that patients who wander often
follow the same route without becoming lost. Qualitative
characteristics of patients’ memory performance are
informative. Severely defective scores on a multiple-choice
recognition test, when they occur, are typically associated with
impulsive responding, overt distractibility, a high incidence of
response perseverations (e.g. repeated selection of the right-
hand item), or lack of adherence to goal (e.g. the patient
selects the item he/she prefers rather than the one presented
previously).
3.2.4 Social cognition and emotion recognition

Deficits can commonly be elicited on tests of social cognition
(Lough et al. 2001; Snowden et al. 2003) and recognition of
Page 16 of 39
emotion (Keane et al. 2002). This domain is important because

deficits may be elicited early in the disease course, at a time
when performance on standard executive tests is relatively
well preserved.
3.3 Phenotypic variation in FTD

In the initial stages of disease many FTD patients are fatuous
and socially disinhibited and this gradually gives way to
emotional blunting, apathy and inertia, reflecting spread of
pathological change from orbitofrontal into dorsolateral
frontal cortex. However, in some patients the presentation is,
from the outset, of apathy and inertia, which may be mistaken
for depression. Recognition of behavioural variation in FTD is
important because it has a bearing on patients’ cognition.
Executive impairments on neuropsychological testing are most
severe in patients with widespread frontal lobe pathology
associated with an apathetic behavioural profile. Disinhibited
patients in whom atrophy is more circumscribed may, at least
in the early stages of disease, perform surprisingly well on
standard tests of executive function, contrasting with the
severe breakdown in social, interpersonal conduct.
3.4 Cognition in semantic dementia

3.4.1 Word meaning
Semantic dementia (Snowden et al. 1989; 1996; Hodges et al.
1992b) refers to a multi-modal loss of conceptual knowledge.
The initial presentation is most commonly of problems in word
meaning. Patients have problems in naming and may make
semantic category errors (e.g. “dog” for horse). They also have
difficulty understanding words and may ask what individual
words mean (e.g. Qu: “Would you like a banana?” Patient:
“Banana. What’s banana?”), a feature that is not notable in AD
or any other neurodegenerative disorder. Non-semantic
aspects of language are well preserved. Patients speak fluently
and effortlessly, in grammatical sentences without
phonological error. They do not struggle (p.571) to retrieve
words, since those words are no longer available to be
retrieved, and indeed they may be frankly garrulous. Rather,
there is simply a progressive reduction in the patient’s range
of vocabulary and repertoire of conversational topics. Patients
use words over-inclusively (e.g. ‘dog’ to refer to all types of
animal), and utterances have an increasingly stereotyped
quality. In the later stages only a few stereotyped phrases
Page 17 of 39
remain and ultimately patients become mute. At no time does

speech output have a non-fluent, effortful quality.
3.4.2 Non-verbal concepts

The semantic impairment is not confined to words. Patients
develop difficulty recognising faces, objects, nonverbal
environmental sounds, smells, tastes and tactile stimuli. It
should be emphasised that the problem is not one of
elementary perception. Patients have no difficulty carrying out
perceptual matching and discrimination tasks in all modalities,
and they can reproduce drawings of objects accurately
indicating that they perceive them normally. The problem lies
in attribution of meaning to sensory stimuli that are perceived
normally.
3.4.3 Memory
The semantic impairment is frequently construed by both
patients and their relatives as a problem in memory, and their
presenting complaint is often that they ‘do not remember
things’. Not surprisingly, a misdiagnosis of AD is common.
Important features in the history are, however, telling. If
informants are asked to clarify the kind of things the patient
cannot remember they describe problems specifically in
semantic memory, such as difficulty remembering names of
people and objects, difficulty recognising acquaintances. By
contrast, patients’ day-to-day event memory is well preserved.
They find their way around without becoming lost, remember
daily activities and keep track of time. They retain a degree of
functional independence that would be unthinkable in a
patient with a classical amnesia.
Page 18 of 39
3.4.4 Cognitive assessment in semantic dementia

Patients’ preserved speech fluency may convey the notion of a
facility with language, which, at least in the early stages,
masks the emerging semantic impairment. Neuropsychological
assessment has a vital role to play. Whereas the semantic
deficits may be barely apparent at clinical interview,
performance on formal naming tests is typically dramatically
impaired. Floor level scores on the demanding Graded Naming
test are common. Assessment needs to include tests of word
comprehension, which ideally should encompass biological
categories (animals, fruits, vegetables) as well as inanimate
objects. Forced choice word-picture tests are valuable because
they can provide clear evidence of semantic breakdown (e.g.
selection of a picture of a rhinoceros in response to the
stimulus word ‘duck’). Famous face and name recognition tests
are also useful because of their sensitivity to disease. Whereas
most patients in the early stages of AD recognise names such
as Margaret Thatcher, Elvis Presley and Marilyn Monroe most
semantic dementia patients do not. Patients with semantic
dementia recognise names and faces of personal
acquaintances better than those of famous people, whereas AD
patients show no such disparity.
(p.572) Formal memory tests may elicit impaired

performance by virtue of their semantic demands. However,
performance on picture recognition memory tests is typically
well preserved. Moreover, although they may lose marks on
place orientation questions because of a difficulty in naming,
patients are typically very well oriented in time.
The Visual Object and Space Perception battery (Warrington

and James 1991) is a valuable instrument in the identification
of semantic dementia because it elicits a characteristic profile.
Patients perform normally on spatial tests, contrasting with
the spatial impairment typical of early onset AD. SD patients
also perform generally well on perceptual subtests, except
where these require recognition of identity. Failure is most
pronounced on the Silhouettes subtest. Calculation
performance can also help to differentiate SD from AD.
Arithmetical skills are typically relatively preserved in SD,
whereas they are impaired early in the course of AD.
3.5 Behaviour in semantic dementia
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The semantic impairment is the defining feature of the

disorder and the aspect that is most striking to the
neuropsychologist. However, SD is also associated with
alterations in behaviour and it is these changes that are often
most troublesome to families. Patients become egocentric,
reflecting their narrowed world view. They typically adhere to
a rigid daily routine and show preoccupation with a narrowed
range of interests which they pursue to excess. They may
become time-bound and clockwatch constantly. They may
restrict their diet to a narrow range of foods. There is some
overlap with the behavioural changes of FTD. However, SD
behaviours have a more compulsive quality (Snowden et al.
2001). Moreover, whereas FTD patients are typically
inattentive and show a lack of engagement and persistence in
activities, SD patients show a remarkable degree of focused
attention and dogged persistence in their favoured pursuits.
3.6 Phenotypic variation in semantic dementia

Semantic dementia is perhaps the most homogeneous of all
neurodegenerative disorders. Patients show predictable
profiles of cognitive impairment and strikingly similar patterns
of behavioural change. One identifiable difference between
patients relates to hemispheric asymmetries. Patients with
more left-sided temporal atrophy typically present with
problems in naming and word comprehension whereas those
with more right sided atrophy may present with problems in
face recognition.
In ‘pure’ semantic dementia cases the atrophy is relatively

confined to the temporal lobes. However, there are some
patients in whom the atrophy encroaches into the frontal
lobes. These patients show a mixed behavioural picture of
FTD, combined with the semantic disturbance of SD. Such
patients are more behaviourally disturbed than pure SD cases
and show more obvious executive impairments.
3.7 Neuropsychological presentation of progressive non-fluent

aphasia
Reports of primary progressive aphasia (Mesulam 1982, 2001;
Tyrrell et al. 1990; Snowden et al. 1992) typically distinguish a
fluent form, characterised by effortless output and problems in
naming and word comprehension and a non-fluent form,
characterised by (p.573) marked problems in expressive
language in the context of well preserved word
comprehension. The former is likely to represent the precursor
Page 20 of 39
to semantic dementia: careful examination typically shows that

the semantic impairment extends beyond the verbal domain.
The non-fluent form (PNFA), by contrast, remains clinically
and anatomically distinct from semantic dementia throughout
the disease course.
3.7.1 Language
A prominent feature of most PNFA patients is anomia, which is
characterised by a difficulty accessing words that remain
within the patient’s vocabulary. Unlike patients with semantic
dementia, PNFA patients may exhibit a tip-of-the-tongue effect
and show immense frustration, reflecting their awareness of
the existence of the word that they cannot bring to mind.
PNFA may be associated with effortful speech, agrammatism
and phonological disturbances, and bear resemblance to
Broca’s aphasia. However, there is considerable heterogeneity
within PNFA. Whereas phonological production errors are
marked in some patients they are notable for their absence in
others. Production is agrammatic in some patients but not in
others. In some patients there are parallel difficulties in
spoken and written language, whereas in other patients
performance dissociates across modalities. In some patients
‘non-fluency’ reflects effortful production associated with
speech apraxia, whereas in others there is no effort and the
non-fluent quality of patients’ speech output is a consequence
of the magnitude of anomia. The latter distinction has
anatomical and apparently also aetiological significance. The
apraxic form of PNFA has been associated with neuroimaging
changes predominantly in the left frontal regions, whereas the
anomic form has been linked to extensive left perisylvian
atrophy. The presence of speech apraxia is a strong predictor
of tau histopathology, whereas its absence is a predictor of
tau-negative, ubiquitin-positive histology.
3.7.2 Gesture
Even in patients without obvious speech apraxia, a difficulty in
use of symbolic gesture may accompany patients’ problems in
spoken and written communication, preventing patients from
compensating for their expressive language difficulties
through nonverbal means. Effectively, patients become mute
and all mediums of communication become lost. This
predicament might intuitively be expected to lead to an
increase in the patient’s level of frustration. In reality,
Page 21 of 39
frustration and distress tend to diminish over the course of the

disease, reflecting reduced insight due to spread of frontal
lobe pathology.
3.7.3 Distinction from AD

PNFA is not always easy to distinguish from focal language
presentations of AD, so that pathological series of patients
with a clinical diagnosis of PNFA frequently include cases with
AD pathology. Important features that typify non-Alzheimer
PNFA include striking hemispheric asymmetry of atrophy and
specificity in the nature of linguistic breakdown.
3.8 Diagnostic criteria for FTLD

Clinical and pathological diagnostic criteria published by the
Lund and Manchester groups (1994) focused on the
behavioural disorder of FTD. Subsequently published (p.574)
clinical criteria (Neary et al. 1998) extended to PNFA and SD,
and provided more precise operational definitions of
symptoms. They have been shown to have good sensitivity and
specificity (Knopman et al. 2005). A simplified set of guidelines
(McKhann et al. 2001) has also been introduced, aimed at the
general physician, which subsumes PNFA, SD and FTD under
the general umbrella of ‘FTD’ and refers to the overarching
presenting feature as ‘an early and progressive change in
personality or language’. This definition inevitably excludes SD
patients whose conceptual loss manifests as a disorder of face
or object recognition, while including AD patients presenting
with a circumscribed language disorder. Histopathological
differences associated with FTD, PNFA and SD (Snowden et al.
2007), together with the very striking clinical differences and
differing management needs of patients suggest that clinical
distinctions should be maintained.
4 Dementia with Lewy bodies

The form of dementia most akin to AD, is dementia with Lewy
bodies (DLB). This is a disorder principally (although not
exclusively) of the elderly (McKeith et al. 2004), which shares
clinical and pathological features with both Parkinson’s
disease and AD. The core defining features are cognitive
impairment, together with mental fluctuations, visual
hallucinations and parkinsonism. Recognition of the disorder
is crucial for patients’ optimal management. DLB patients
frequently show sensitivity to traditional neuroleptic agents,
which need to be avoided. On the other hand, DLB patients
show greater benefit than AD patients from cholinesterase
Page 22 of 39
inhibitors, despite the fact that these therapies were originally

designed for AD. Neuropsychological assessment can
contribute substantially to the diagnosis.
4.1 Cognition in DLB

DLB patients, like those with AD, exhibit impairments in
memory, language, visual perception, spatial, attention and
executive functions. Comparative studies of the two disorders
show that in DLB attentional deficits are particularly
pronounced (e.g. Calderon et al. 2001). Perceptuospatial
deficits are more marked in DLB than in AD whereas memory
deficits are less severe (cf. Metzler-Baddeley 2007). Such
relative quantitative differences are important and informative
at a group level, but inevitably present ambiguities in the
interpretation of data from individual patients. Qualitative
features of patients’ performance can provide valuable
additional information that can improve accuracy of diagnosis
(Doubleday et al. 2002). Qualitative differences between DLB
and AD are summarised in Table 28.2, and described in more
detail below.
4.2 Qualitative characteristics of DLB
Page 23 of 39
4.2.1 Fluctuations and interference

A salient and striking characteristic of DLB patients is
fluctuation in their mental state. The fluctuations are typically
apparent to relatives who may describe the patient as having
‘good days and bad days’ and within a single day, periods of
lucidity in which the patient appears ‘back to his/her normal
self’ and periods of confusion during which the (p.575)
patient behaves and speaks irrationally. These fluctuations are
reflected by variable performance on neuropsychological
testing. Responses to questions may at one moment be entirely
lucid and appropriate and at another moment incoherent and
off the point. Sometimes a tenuous link can be detected
between the wording of the question and the patient’s
response. For example, when requested to “point to the source
of illumination in this room” the patient might respond by
talking about Blackpool. There may also be interference from
extraneous visual environmental stimuli. The patient might,
for example, produce the entirely irrelevant response ‘fire
exit’, because his/her gaze happens to fall on the Fire Exit
notice in the room. Patients may be distracted too by
irrelevant auditory stimuli, and ascribe personal relevance to
extraneous sounds (e.g. a telephone ringing in a distant office:
‘my daughter is calling me’; a noise outside the hospital
consulting room: ‘the cat’s trying to get out’). In addition to
intrusions arising from association of ideas and from
environmental stimuli there is also characteristically evidence
of interference within and across tests. Thus, elements of one
short story may intrude into the recall of a second story; items
from a picture arrangement test may intrude into the recall of
a word list. Open-ended tasks such as story recall are of
particular diagnostic value in the assessment of DLB because
they provide the scope to elicit features that distinguish DLB
from AD: confabulation (introduction of information not in the
original story), misconstruction (incorrect juxtaposition and
integration of story elements) and interference effects (within-
task, across-task, induced from external environment or
semantic association). Perseverations of verbal and motor
responses are also more prominent in DLB than AD.
4.2.2 Hallucinations and perception

The core behavioural characteristic of DLB, other than mental
fluctuation, is visual hallucinations. These are formed and
most commonly consist of people or animals. The patient can
Page 24 of 39
typically provide a detailed vivid description of their

appearance, including the colour and style of their clothing,
and the activities in which they are engaged. They may
Table 28.2 Qualitative performance

characteristics in DLB and AD
DLB AD
Performance May fluctuate over Consistent over

consistency test session test session
Rate of Slowed Unremarkable

performance
Conversational Incoherent line of Coherent, despite

speech thought expressive
difficulties
Distractibility Distracted by Not overtly

irrelevant stimuli distractible
Interference Within and Minimal

between-test interference
interference:
intrusion errors
Confabulation Story recall may be Story recall poor

confabulatory and but not
misconstrued confabulatory
Perseveration Verbal and motor Minimal

perseveration perseveration
present
(p.576) be linked to a particular location (e.g. ‘an old woman and

little girl who sit on the sofa in the living room’), although they are
not always static. Characteristically, the hallucinations are silent
and non-threatening, so the patient accepts them with equanimity.
Some apparent hallucinatory phenomena are more accurately
classified as illusions since they have an identifiable perceptual
substrate. For example, the patient might report seeing ‘a monkey’
in the pattern of a curtain, or ‘a burglar trying to get in’ in the
swaying branches of the trees outside the window. It is of interest
in this regard that patients often perform particularly poorly on
perceptual sub-tests of the Visual Object and Space Perception
battery and may over-interpret visual stimuli (e.g. a fragmented
letter ‘F’: “a man riding a bicycle”).
Page 25 of 39
It is worthy of note, in relation to these misperceptions, that

Capgras syndrome has also been reported in association with
DLB (Baldwin et al. 1995). This is a form of delusion in which
the patient believes a person, usually a close family member,
to be an imposter. The patient concedes that the ‘imposter’
looks like the ‘real’ person (i.e. the patient’s spouse), although
may sometimes report subtle differences (e.g. ‘he/she is about
an inch taller’). Because of their entrenched belief, the patient
may refer to their spouse in the third person when talking
directly to him/her (e.g. ‘he likes to play golf at weekends’).
4.3 Phenotypic variation in DLB

The initial presentation and evolution of symptoms of DLB may
vary. In some patients cognitive change is the earliest
symptom and physical signs of parkinsonism emerge later. In
other patients parkinsonism signs emerge first. The
neuropsychological profile is identical in both types of patients
(Doubleday et al. 2002).
4.4 Parkinson’s disease dementia and DLB

Parkinson’s disease is predominantly a movement disorder,
characterised by tremor, physical slowing and rigidity.
However, it is recognised that people with Parkinson’s disease
may develop cognitive problems during the disease course. In
their mild form these may constitute mild inefficiencies in
memory, reduced generation on fluency tasks and subtle
difficulties on complex executive tests. However, cognitive
changes may be of sufficient magnitude to acquire the label of
Parkinson’s disease dementia. This raises the important
question of the relationship between DLB and the cognitive
impairment of Parkinson’s disease.
Early consensus criteria for DLB (McKeith et al. 1996)

specified that for a diagnosis of DLB cognitive impairment
should emerge prior to or within 12 months of the onset of
extrapyramidal neurological signs. In cases where the clinical
history of parkinsonism is longer than 12 months then a
diagnosis of Parkinson’s disease with dementia would be more
appropriate. In reality, the 12 month cut-off is arbitrary, and
the cognitive phenotype is identical regardless of whether the
cognitive impairment emerges a few months or many years
after the onset of parkinsonism. It is now generally accepted
that DLB and Parkinson’s disease dementia are the same
disease.
Page 26 of 39
(p.577) 4.5 Diagnostic criteria for DLB

Early consensus guidelines (McKeith et al. 1996) required for
the diagnosis of DLB the presence of cognitive impairment,
with prominent deficits in attention, frontal-subcortical skills
and visuospatial ability, together with two of the following core
features: fluctuating cognition, visual hallucinations and
parkinsonism. These criteria yield acceptable specificity but
suboptimal sensitivity, because at least two core features may
not be present early in the course. A revised set of guidelines
(McKeith et al. 2005) has attempted to improve sensitivity by
introducing additional suggestive features, commonly present
in DLB: a) REM sleep disorder, b) neuroleptic sensitivity and c)
low dopamine transporter uptake in basal ganglia
demonstrated on functional neuroimaging. It is suggested that
a diagnosis of probable DLB can be made when at least one
core feature and one additional feature is present. In
neuropsychological practice, a diagnosis of DLB may be
suspected, by virtue of the features of incoherence,
misconstructions, perseverations and interference effects,
prior to the frank development of all core symptoms.
5 Huntington’s disease
Page 27 of 39
Huntington’s disease (HD) is a genetic disorder caused by a

trinucleotide (CAG) repeat mutation in the huntingtin gene on
chromosome 4. It is associated with autosomal dominant
inheritance, each child of an affected parent having a 50% risk
of inheriting the HD mutation and developing the disease.
Onset of symptoms is typically around 40 years, although it
may occur, rarely, both in childhood and in old age. The
duration of illness to death is about 15 years, although there is
a wide range. The cardinal features are involuntary (choreic
and dystonic) movements, cognitive impairment and mood/
behavioural changes (cf Bates et al. 2002 for comprehensive
background to HD).
The writhing, involuntary movements of HD patients are the

most visible sign of disease and their emergence typically
provides the principle basis for making a clinical diagnosis and
defining clinical onset. A genetic test is available that can be
used to confirm the clinical diagnosis in patients showing
symptoms and to offer pre-symptomatic testing for at-risk
individuals. It might be presumed therefore that
neuropsychology has little role. However, in HD it is the
mental rather than physical changes that are often the most
troublesome aspect of the disease and place greatest burden
on families. Recognition of the nature of those changes is
crucial for effective clinical management, as well as for
providing appropriate cognitive and behavioural markers to
assess efficacy of novel therapies.
Page 28 of 39
5.1 Cognition in HD
The salient characteristics are psychomotor slowing, and
impaired executive skills and memory (cf Craufurd and
Snowden 2002). Patients show impoverished generation in
verbal and design fluency tasks, poor sequencing, divided
attention and mental set shifting. They typically make a high
percentage of perseverative responses. Patients’ behaviour in
daily life is characterised by mental inefficiency and poor
organisation. Despite the ubiquitous report of poor (p.578)
memory, patients do not exhibit a classical amnesia, as found
in AD: HD patients are typically well oriented and can give an
account of autobiographical events. Rather they show poor
concentration and forgetfulness (e.g. forgetting to pick the
children up from school, forgetting a boiling pan on the stove).
On formal memory testing they show poor performance on
open-ended recall tests, but benefit greatly when performance
is assessed by cued recall and recognition techniques. The
pattern of memory performance suggests failure in
organisational aspects of memory, secondary to striato-frontal
dysfunction. If information is structured for the patient then
performance improves.
5.2 Mood and behaviour in HD

Common behavioural characteristics in HD include loss of
initiative and drive, poor self care, emotional blunting, self-
centredness, mental inflexibility, irritability, poor temper
control and depressed mood (Craufurd and Snowden 2002).
Apathy, like cognitive change, increases systematically over
the course of the disease. Patients, if left to their own devices
may stay in bed all day or watch television. Irritability tends to
peak in the middle stages of the illness and then wanes.
Depression has an increased prevalence in HD compared to
the normal population but is unrelated to stage of disease.
5.3 Phenotypic variation in HD

An akinetic-rigid form of HD, as distinct from the typical
choreic form, has been associated with juvenile onset of
disease. In typical cases, there is some variation in the extent
and characteristics of the movement disorder. Patients may
vary too with respect to the degree of cognitive impairment.
Typically, patients who have a late onset of disease exhibit
milder cognitive impairment than those with early onset and
show fewer behavioural problems.
6 Motor neurone disease
Page 29 of 39
Motor neurone disease (MND) has traditionally been

construed as a disease of the motor system, in which higher
mental function is spared. This prevailing view has been
challenged from two sources. First, a proportion of patients
with established FTD develop, during the course of their
illness, the physical signs of MND, suggesting a link between
the two disorders (Neary et al. 1990). Second, close
examination of patients attending MND clinics shows that a
proportion develops cognitive impairment of varying degree.
Deficits have been identified most commonly in the realm of
executive functions, particularly on verbal fluency tasks
(Abrahams et al. 2000). Some MND patients develop
behavioural changes akin to those seen in FTD (Gibbons et al.
2008). In keeping with the cognitive and behavioural profiles,
structural and functional imaging demonstrates abnormalities
in the frontal lobes.
Current data point to a spectrum of change: at one extreme

patients show no cognitive or behavioural impairment,
whereas at the other extreme they fulfil criteria for FTD. The
precise factors that determine patients’ susceptibility to
cognitive impairment remain to be determined.
(p.579) 7 Progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a basal ganglia
disorder, the hallmark of which is a progressive reduction in
voluntary eye movements, culminating in total
ophthalmoplegia. Whereas patients with Parkinson’s disease
have a flexed posture those with PSP tend to hold their head in
extension, and are prone to falling backwards. The
pathological changes in PSP fall within the rubric of
‘tauopathy’, thus sharing a pathological link with FTD.
7.1 Cognition in PSP

PSP patients commonly show mental slowing, which may be
most marked in the initiation of responses. They exhibit
particular difficulties in open-ended tasks, requiring the active
generation of information (e.g. verbal fluency; recall of story).
By contrast, they perform relatively well when responses are
constrained (e.g. confrontation naming, forced-choice
recognition of story). They may also show impairments in
sequencing and other executive tasks, The characteristic
features of mental slowing and inefficiency, in the absence of
frank ‘cortical’ features of aphasia, agnosia, spatial
Page 30 of 39
disorientation or apraxia has been referred to as a ‘subcortical

dementia’ (Albert et al. 1976).
The cognitive profile in PSP shares commonalities with that of

FTD, in keeping with disruption of striatal-frontal pathways.
However, PSP patients do not typically show the gross
character change, breakdown in social behaviour and lack of
insight that is pathognomonic of FTD. Moreover, FTD patients
are typically impulsive rather than slowed in their responses.
7.2 Phenotypic variation in PSP

Patients vary in the severity of cognitive impairment. In some
patients cognitive change is mild and limited to slight slowing
and inefficiencies, whereas in others there are very marked
executive deficits, comparable to those found in FTD.
8 Corticobasal degeneration
Corticobasal degeneration (CBD), like PSP, falls within the
rubric of ‘Parkinson-plus’ disorders. Patients show
parkinsonian signs of akinesia and rigidity, resulting from
pathological change in the basal ganglia, together with
asymmetric limb apraxia, resulting from pathology in
frontoparietal cortex. The pathological changes in CBD fall
within the classification of ‘tauopathy’, providing a
pathological link between CBD and both PSP and FTD.
8.1 Neuropsychological presentation of CBD

The striking abnormality in CBD is limb apraxia of the
ideomotor type: the patient has the idea of the required action
but cannot implement it effectively. Typically, both upper and
lower limbs are affected, albeit to differential degree.
Involvement is typically asymmetric, one side being affected
more than the other. Buccofacial apraxia develops with
progression of disease causing difficulty with speech. Patients
are often insightful and (p.580) initially frustrated by their
profoundly disabling disorder. However, with disease
progression patients develop increasing executive
impairments associated with functional impairment of the
frontal lobes, and insight and distress gradually diminish.
8.2 Phenotypic variation in CBD

The principle variation across patients is in the relative
proportion of ‘basal’ and ‘cortical’ features. In the former,
there is substantial limb rigidity and actions are slowed and
Page 31 of 39
reduced in amplitude but relatively accurate in terms of their

spatial configuration, whereas in the latter configuration is
impairment.
9 Management issues
The primary aim of this chapter has been to describe the
neuropsychological characteristics of different
neurodegenerative disorders, allowing those disorders to be
recognised and differentiated from other disorders. An in-
depth evaluation of management implications is beyond the
scope of the chapter. Nevertheless, it is worth re-emphasising
that provision of a correct diagnostic label is not merely an
academic exercise. It can have considerable importance for
patients and their families. Recognition that a specific
‘disease’ is the cause of patients’ altered cognition or
behaviour can aid considerably the process of adjustment. It
can assuage relatives’ feelings of guilt that they are to blame
and eliminate beliefs that the patient’s behaviour is wilful and
therefore under his/her control.
Moreover, the particular characteristics of a patient’s

problems may reasonably lead to different and indeed even
opposing forms of advice. For example, the family of an AD
patient with a reduced immediate span might sensibly be
advised to ‘keep sentences short and simple’ when conversing
with the patient. Conversely, the family of a semantic dementia
patient would be advised to ‘provide a lot of context’ in order
to compensate for the patient’s failure to understand
individual nouns.
In the cases of neurological disorders that are associated with

severe physical disability, the presence of alterations in
cognition and/or behaviour may sometimes be ignored. Yet,
recognition and acknowledgement of patients’ mental status is
crucial: to optimise patients’ cooperation in physical and
speech therapy; to involve patients and their relatives
appropriately in clinical management decisions, and to provide
support and advice to families who may have difficulty coping
with patients’ altered behaviour.
10 Theoretical considerations
The notion of dementia as a global, undifferentiated
impairment of intellect is entrenched in the literature. Yet, the
evidence against such a notion is overwhelming. Different
neurodegenerative disorders lead to distinct and highly
Page 32 of 39
characteristic patterns of cognitive impairment and disorders

can be differentiated with a high degree of accuracy on
neuropsychological grounds. If dementia were ‘global’ then
such differentiation should not be possible. Differences
between patients are apparent not merely on sophisticated
neuropsychological analysis, but are well recognised by
nursing home carers and (p.581) family members. For
example, relatives of patients with frontotemporal or semantic
dementia who attend an Alzheimer support group rapidly
recognise that their relative ‘is different’ from the rest, even
when they have not yet been formally diagnosed so are
without preconceptions.
The development of neuropsychology, with its well validated

assessment instruments, has undoubtedly contributed to
improved recognition and understanding of the ‘dementias’.
Yet, it may unwittingly too have contributed to the notion of
global impairment. If ‘global’ is defined as ‘failure on tests that
tap different areas of cognition’ then most patients would fulfil
those criteria. Yet, there is not a one-to-one correspondence
between a test and a function, and patients may fail diverse
tests for very circumscribed reasons, such as an impairment of
attention due to frontal lobe damage. Clinical
neuropsychologists need to bear in mind that ‘posterior’
hemisphere tests may be performed poorly for ‘frontal’
reasons and vice versa. Evaluation of patients’ performance
requires the analysis not only of overall test scores but also
qualitative characteristics of performance failure.
The term ‘focal’ dementia has, in recent years, been adopted

to refer to disorders such as FTD, in which there is very clear
demarcation between areas that are atrophied and those that
are not. It is worth re-iterating that the distinction between
‘focal’ and ‘generalised’ disorders is relative rather than
absolute, since all disorders have some degree of anatomical
selectivity. Moreover, ‘focal’ does not necessarily mean less
severe. Atrophy in patients with forms of frontotemporal lobar
degeneration is typically more profound than that found in AD
patients, albeit more topographically circumscribed.
Page 33 of 39
11 Conclusions
The notion of dementia as a global, undifferentiated
impairment of intellect needs to be abandoned. It is more
appropriate to regard the ‘dementias’ as representing
constellations of deficits, which form distinct performance
profiles, corresponding to the topographical distribution of
degenerative change within the brain. Neuropsychological
assessment can play a crucial role in characterising those
distinct profiles, leading to improved clinical diagnosis and
more person-centred management and care of patients and
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Page 39 of 39
The neuropsychological presentation and treatment of demyelinating disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The neuropsychological
presentation and treatment of
demyelinating disorders
Peter A. Arnett
Amanda R. Rabinowitz
DOI:10.1093/acprof:oso/9780199234110.003.029

Clinical neuropsychologists play a pivotal role in assessment
and treatment of multiple sclerosis (MS) patients.
Neuropsychologists can first evaluate the extent to which
tested difficulties displayed by patients may map onto real-
world problems, then help patients make modifications to daily
routines that allow them to circumvent cognitive difficulties
they display. Neuropsychologists can also help identify and
treat the depression that is so common, but often overlooked,
in MS patients. This chapter discusses the pathophysiology of
MS, neuropsychological deficits in MS, related emotional
disorders, neuropsychological/cognitive rehabilitation in MS,
and other demyelinating diseases.
Keywords: multiple sclerosis, clinical neuropsychology, demyelinating diseases,

emotional disorders, depression
1 Introduction
Page 1 of 34
By far the most commonly seen and studied demyelinating

disorder in clinical neuropsychology is multiple sclerosis (MS).
As such, most of this section will focus on MS. Other
demyelinating disorders on which some neuropsychological
data are available will be reviewed in a brief section at the
end.
Clinical neuropsychologists play a pivotal role in assessment

and treatment of MS patients. Prior to the advent of sensitive
neuropsychological tests, when cognitive evaluations involving
brief mental state examinations were primarily used, cognitive
difficulties were thought to affect less than 5% of patients
(Rao, 1986). Prevalence estimates with use of
neuropsychological tests now range from 40-60% (see below).
Because cognitive deficits in MS are associated with real-
world functioning, neuropsychologists can first evaluate the
extent to which tested difficulties displayed by patients may
map onto real-world problems, then help patients make
modifications to daily routines that allow them to circumvent
cognitive difficulties they display. Neuropsychologists can also
help identify and treat the depression that is so common, but
often overlooked, in MS patients.
2 Pathophysiology of MS
Page 2 of 34
MS is a demyelinating disease of the central nervous system

whose cause is not yet fully explained, although it is thought to
be related to an autoimmune process, a slow-acting virus or a
delayed reaction to a common virus, or epigenetic factors
interacting with the environment (ie. lack of vitamin D). One
specific autoimmune process identified involves antibodies
against antigens located on the myelin sheath that may
infiltrate the blood-brain barrier and directly cause
demyelination. Various pathophysiological processes may be
involved in disease progression. Also, there is considerable
variability among patients with regards to structural and
immunologic disease features. These observations suggest
that MS may be a series of syndromes, rather than a uniform
disorder with a singular etiology and disease process
(Noseworthy, Lucchinetti, Rodriguez, & Weinshenker, 2000).
(p.586) The defining pathological feature of the disease is

the demyelinated plaque - a lesion characterized by the loss of
myelin, the relative preservation of axons, and the presence of
astrocytic scars. Myelin is fatty tissue comprised of
oligodendrocytic glial cells. Oligodendrocytes surround the
neuronal axon and facilitate the propagation of action
potentials. Multiple discrete plaques that are found at
demyelinated sites are formed, in part, by proliferating
astrocytes. Myelin sheaths within plaques are either destroyed
or swollen and fragmented. Neural conduction facilitated by
myelin because an intact nerve is enclosed in myelin sheaths
separated by gaps from which the nerve impulse jumps.
Affected areas thus interfere with or block neural transmission
by limiting this process known as saltatory conduction. Axons
and cell bodies of neurons often remain intact until late stage
disease. Early symptoms of disease believed to be a result of
the demyelination process. Remission of symptoms attributed
to reduction of inflammatory edema and partial remyelination.
As disease progresses, however, irreversible axonal injury may
occur. Furthermore, oligodendrocyte progenitor pool
exhaustion can inhibit remyelination. Remyelination much
more likely to occur during acute phases and early in the
disease process; minimal remyelination occurs with chronic
lesions. These fluctuating disease processes may be
responsible for chronic and progressive decline in functioning
observed in many patients.
Page 3 of 34
Size of plaques varies from about 1.0mm to several cm.

Resulting symptoms typically reflect functions associated with
affected areas. Plaques can occur in the brain or spinal cord.
Location of plaques is highly variable between patients: Within
the cerebrum, plaques near the lateral and 3rd ventricles are
most common. Frontal lobes are the next most commonly
affected, even when size of frontal lobes relative to rest of
brain considered. Plaques in other major lobes of the brain are
also frequently observed; additionally, plaques commonly seen
in the optic nerves, chiasm, or tracts, as well as the corpus
callosum, brain stem, and cerebellum. Majority of plaques
(about 75%) are observed in white matter, but some occur in
gray matter and in the juncture between gray and white
matter. Some remyelination occurs with acute MS plaques.
2.1 Clinical presentation and natural course of MS

Likely acquired before puberty, but actual disease onset
occurs in most (2/3rds) patients between ages 20 and 40.
Onset before age 15 rare; late onset after age 40 is commonly
characterized by quicker progression and greater morbidity.
Average life expectancy following onset estimated at 30+
years, but variability is great.
Environmental contribution suggested by generally higher

prevalence in temperate zones away from equator with
prevalence decreasing near tropics towards equator. Highest
prevalence rates (greater than 30 in 100,000) are in Northern
Europe, Southern Australia, and middle latitude zones of
North America. The 30-40% concordance in identical twins but
only 1-13% in fraternal, suggests a genetic and/or epigenetic
contribution. Risk in first-degree offspring of MS patients is
only 5%, but 20-40 times greater than in general population.
No increased risk in adopted children of patients with MS.
Presence of HLA-DR2 allele significantly increases risk for MS;
populations with greater incidence (p.587) of this allele (such
as Scotland) have greater risk of MS (Noseworthy, Lucchinetti,
Rodriguez, & Weinshenker, 2000).
Page 4 of 34
2.1.1 Symptoms
Common symptoms: Muscle weakness, urinary disturbance,
and visual anomalies like diplopia, loss of visual acuity, blurry
vision, and visual field defects. Fatigue, problems with
balance, and paresthesias (usually numbness and tingling in
the limbs, trunk, or face) are also common. Significant
cognitive difficulties and problems with depression constitute
very common symptoms as well. Most common symptoms at
MS onset are muscle weakness, paresthesias, visual
disturbances, and gait/balance problems. About 50% of
patients require assistance walking within 15 years of disease
onset (Noseworthy, Lucchinetti, Rodriguez, & Weinshenker,
2000). Mode of symptom onset is typically acute or subacute.
Many MS symptoms are transient and unpredictable. For
example, visual disturbances and paresthesias may last for
seconds or hours. Because of the short-lived and sometimes
bizarre nature of symptoms, it is not uncommon for patients in
early stages before formal diagnosis to be labeled with
hysteric/somatization disorders.
2.1.2 Diagnosis
Diagnosis of MS is clinical and laboratory based. Latest
criteria involve various combinations of clinical and laboratory
based evidence (McDonald et al., 2001). Patients can get MS
diagnosis from either discrete episodes or insidious
progression. Regarding a diagnosis from discrete episodes,
patients must have had at least one disease attack. If patients
have had two or more attacks lasting at least 24 hours and
separated in time (at least 30 days), combined with objective
clinical evidence of two or more lesions, then that is sufficient
for diagnosis. One attack can also lead to diagnosis if there is
clinical evidence of at least two lesions, combined with the
lesions being disseminated in time as demonstrated by MRI.
Other combinations of attacks are also possible. MRI data are
considered preferable to other paraclinical tests; however,
additional tests can be used when clear-cut MRI findings are
not present or atypical clinical presentations occur.
Specifically, the presence of oligoclonal IgG bands in the
cerebrospinal fluid (CSF) different from those in the serum, or
elevated IgG, can be used. Additionally, Visual Evoked
Potentials (VEPs) can be used to supplement the clinical
examination to reveal evidence of additional lesions. Attacks,
relapses, or exacerbations that imply new disease activity are
common. Regarding insidious onset where discrete disease
Page 5 of 34
attacks are not present, positive CSF results involving

presence of oligoclonal bands or raised IgG levels are
necessary, combined with both abnormal VEP and various
combinations of lesions disseminated in space. Furthermore,
there must be MRI or abnormal VEP evidence that lesions are
separated in space. Lastly, separation in time should be
evident, as reflected by the onset of new MRI lesions or
increased level of disability over the course of at least one
year. McDonald and colleagues also lay out specific criteria for
defining lesions detected on MRI as abnormal and
characteristic of MS.
Several course types have been identified (Lublin & Reingold,

1996):
1 Relapsing-remitting (RR) - Most common and

characterized by clearly defined disease relapses.
Recovery can be full or with sequelae and residual
deficit. Complete (p.588) remission following the
initial episode of symptoms is common. Subsequent
episodes are unpredictable, occurring weeks to years
later. Symptoms associated with them remit less
completely or not at all. Relapses are highly variable,
lasting days to weeks, and more rarely, hours and
months. No progression of disease between relapses.
About 80% of MS patients have this type or secondary-
progressive type. The RR and secondary-progressive
types are more common in females than males by about
a 2:1 ratio.
2 Secondary-progressive (SP) - Next most common
type: First characterized by RR course then
progression. Relapses and remissions may or may not
occur. Approximately 70% of RR proress into SP.
3 Primary-progressive - Next most common type:
Unremitting disease progression from onset for most
patients, but occasional stabilization and even
improvement in functioning for others. No clear
relapses. Prevalence is equivalent in males and
females.
4 Progressive-relapsing - Least common type: Disease
progression from onset. Acute relapses also occur from
which patients may or may not fully recover. The term
Page 6 of 34
“chronic-progressive” formerly encompassed all

progressive types.
Two severity outcome definitions also identified:
1 Benign - Patient remains fully functional 20 years post

disease onset. This occurs in about 10% of patients.
2 Malignant - Rapidly progressing course leading to
significant disability or death relatively soon after
disease onset. Most patients fall in between these two
extremes.
Several factors predict poor outcome including frequent

relapses within first two years of onset, early motor and
cerebellar findings, and male sex. Predictors of better outcome
include female sex, predominantly sensory symptoms, and
optic neuritis.
3 Neuropsychological deficits in MS
3.1 Prevalence of neuropsychological deficits
On average, about 45% of community based samples have
been shown to have cognitive impairment (Jonsson et al., 2006;
Rao, et al., 1991). Prevalence rates shown to be higher among
clinic based samples, typically falling between 55% and 65%
(Amato, Zipoli, & Portaccio, 2006). Most (about 80%) patients
with deficits are relatively mildly affected. Global cognitive
deficits uncommon, occurring in about 5-10% of patients
(Longley, 2007). However, even mild cognitive problems in MS
have been shown to relate to everyday activities (e.g., work,
homemaking, personal care activities, social activities)
(Higginson, Arnett, & Voss, 2000), including driving
(Schultheis, Garay, & DeLuca, 2001), and even employment
status (Benedict et al., 2005; Rao et al., 1991).
3.2 Nature of neuropsychological deficits

3.2.1 Intellectual functioning
This is affected significantly in about 20% of patients. Most
patients score within a broad normal range.
(p.589) 3.2.2 Academic Skills

Little systematic research conducted on these in MS, but
assumed to be intact in most patients.
3.2.3 Memory
Page 7 of 34
One of the most commonly affected cognitive domains in MS.

Problems encoding and/or retrieving both verbal and visual
information are most common. It is typically manifested as
immediate and delayed recall memory deficits on
neuropsychological testing. About 30% of patients have
substantial problems, another 30% have moderate problems,
and the remaining 40% have mild or no problems with this
type of memory (Brassington & Marsh, 1998). Working
memory, the ability to maintain and manipulate information
“on-line,” also commonly impaired. Delayed recall deficits
usually a function of deficient immediate recall, not forgetting.
Learning curve across repeated trials is similar in slope to
controls, but lower in magnitude. Percent retention,
recognition, and incidental memory following a delay, and
remote memory are usually intact. Clinically, memory
problems often manifested as complaints of difficulty
remembering conversations, appointments, work tasks, etc.
3.2.4 Attention & concentration/speeded information processing

One of the most commonly affected cognitive domains in MS.
Difficult to separate speeded information processing from
attentional functioning because the latter is necessary for
performing any speeded cognitive task. Attention necessary in
clinical evaluations to the possibility that memory problems in
MS may, in part, be a function of deficits in these domains. MS
patients show greatest difficulty on tasks requiring rapid and
complex information processing, such as those requiring swift
application of working memory operations, attentional
switching, or rapid visual scanning. About 20-50% of MS
patients have substantial difficulty with this cognitive domain,
depending on the task used, with tasks like Oral Symbol Digit
revealing more impairment than the PASAT (Benedict,
Cookfair et al., 2006). Such increased sensitivity may be due to
the visual demands of the Symbol Digit, something that recent
research has shown can compromise performance on the task
in even MS patients with mild visual acuity problems (Bruce,
Bruce, & Arnett, 2007). Simple attention span usually intact,
but mild impairments sometimes found. Clinically, attention/
speeded processing problems commonly manifested as
difficulty tracking and keeping up with and focusing on details
of conversations, work tasks, television programs, etc.
3.2.5 Verbal/linguistic deficits
Page 8 of 34
Aphasias are rare in MS, but mild confrontation naming

difficulties are sometimes seen. Deficits in verbal fluency are
common. Important in clinical evaluations to determine if the
latter deficits are associated with memory retrieval difficulties
common to MS (Fischer et al., 1994). Also, there is some
evidence that the later parts of verbal fluency tasks are most
sensitive to the fluency deficits in MS (Smith & Arnett, 2007).
Because fluency tasks require rapid production of information,
patients’ poor performance on them may also be related (p.
590) to their speeded processing deficits. Additionally, slowed
speech common to MS should be considered as possible
contributor to patients’ verbal fluency, as well as speeded
attentional, deficits. 20-25% of patients have substantial
problems on verbal fluency tasks (Rao, Leo, Bernardin, &
Unverzagt, 1991), though some studies have reported
impairment frequencies lower than 15% (Benedict, Cookfair et
al., 2006). Fluency problems may manifest clinically as word-
finding problems impairing the flow of patients’ conversations.
3.2.6 Visual-spatial deficits

About 10-20% of individuals with MS show substantial
difficulty with higher-order visual-spatial skills involving angle
matching or face recognition. Unclear whether higher order
visual deficits are a function of primary visual disturbances
involving blurred vision and diplopia (Bruce, Bruce, & Arnett,
2007; Rao, Leo, Bernardin, & Unverzagt, 1991). Clinical
manifestations may involve accounts of running into things
frequently while walking (e.g., doorways) or driving (e.g.,
curbs) because of visual miscalculations.
3.2.7 Executive skills

Executive skills are commonly affected in MS. Deficits in
cognitive flexibility, concept-formation, verbal abstraction,
problem-solving, and planning are found. 15-25% of
individuals with MS show substantial difficulties in this
cognitive domain. May manifest clinically as difficulty planning
day-to-day activities (e.g., job tasks, meals, grocery shopping),
verbal disinhibition and tangential speech, as well as problems
organizing ideas and shifting appropriately from one topic to
another in conversation.
3.3 Measurement of neuropsychological deficits

3.3.1 Brief screening batteries/repeatable batteries
Page 9 of 34
An efficient way of approaching neuropsychological testing in

MS is to conduct a brief screening evaluation to determine if
further testing is warranted. MS patients impaired in one
domain of cognitive functioning are not necessarily impaired
in others (Rao et al., 1991). Thus, neuropsychological
assessments that evaluate major areas of cognitive functioning
typically impaired in MS is critical because performance on a
test in one domain provides little information about the
likelihood of deficits in other domains.
Brief Repeatable Battery (BRB)
Rao and colleagues have developed the Brief Repeatable

Battery of Neuropsychological Tests in Multiple Sclerosis (Rao,
and the Cognitive Function Study Group of the National
Multiple Sclerosis Society, 1990) comprised of tests most
sensitive to cognitive impairments typically seen in MS; most
tests also include 15 alternate forms to allow for repeat
testing. Battery includes six-trial version of the Verbal
Selective Reminding Test, 10/36 Spatial Recall, Oral Symbol
Digit Modalities Test, 2s and 3s Paced Auditory Serial Addition
Test (PASAT), and Word List Generation (verbal fluency).
Comprehensive norms for BRB can be found in Boringa et al.
(2001). BRB takes 20-30 minutes to administer. Wechsler Test
of Adult Reading (WTAR) (Psychological Corporation, 2001)
also recommended and takes 5 minutes. Provides reliable and
valid estimate of Full Scale WAIS-III IQ and has excellent
norms. Adding the Chicago Multiscale Depression Inventory
(CMDI) (Nyenhuis et al., 1995), and Fatigue Severity Scale
(FSS) (p.591) (Krupp et al., 1988) also suggested. Together,
the latter two measures take about 10 minutes and are self-
administered, so could be completed in a waiting room before
actual testing. Thus, in only 35-45 minutes of actual patient
contact time, a reasonably comprehensive neuropsychological
screen can be obtained and more extensive testing conducted
if deficits are detected.
3.3.2 Minimal Assessment of Cognitive Functioning in MS

(MACFIMS)
Developed by consensus from the meeting of a group of
experts on neuropsychological functioning in MS (Benedict et
al., 2002). Somewhat longer than the BRB, taking
approximately 90 minutes. The MACFIMS consists of the
following five cognitive domains with tests measuring those
domains listed in parentheses: Processing speed/working
Page 10 of 34
memory (Oral Symbol Digit Modalities Test, 2s and 3s PASAT),

learning and memory (California Verbal Learning Test - 2nd
Edition (CVLT-II) and Brief Visuospatial Memory Test – Revised
(BVMT-R)), executive function (D-KEFS Sorting Test), visual-
spatial processing (Judgment of Line Orientation), and word
retrieval (Controlled Oral Word Association Test (COWAT)). In
validation study, Benedict and colleagues (2006) found that
nearly 60% of MS patients were impaired on at least two of
these subtests. Caution required for PASAT use in lower
functioning patients; can damage rapport because of their
great difficulty performing. Poor performance on Arithmetic
subtest of WRAT-4 (see below) may suggest that primary
arithmetic calculation difficulties contribute to PASAT deficits.
The authors of MACFIMS also suggest including a number of

additional measures to assess potential confounds. First, they
recommended employing a culturally appropriate measure of
premorbid ability on the first occasion a patient is seen.
Several suggestions provided, with the North American Adult
Reading Test (NAART) favored by most panel members.
Second, panel recommended that a measure of depression be

routinely administered. The CMDI, a depression measure that
includes mood, evaluative, and vegetative scales, was
recommended as a screen for depression. Because of the
overlap of MS disease symptoms and vegetative depression
symptoms (e.g., fatigue, sleep disturbance, concentration
difficulties, sexual dysfunction), CMDI allows clinician to
evaluate whether total depression score is artificially elevated
due to differential contribution of vegetative scale. The panel
also suggested the possibility that the Beck Depression
Inventory - Fast Screen (BDI – FS) be used, though this was
recommended with caution since, at the time of this
publication, the BDI – FS had not been validated on an MS
sample, but since then it has (Benedict et al., 2003). Consists
of only 7 items and does not include any vegetative symptoms,
thus it circumvents the potential vegetative depression
symptom/MS disease symptom confound. Raw scores greater
than 3 suggest further evaluation of depression is needed.
A third confound that the consensus authors suggested needed

to be addressed were potential problems with vision. They
recommended that a measure like the Rosenbaum Pocket
Vision Screener could be used, and that a 20/50-70 threshold
Page 11 of 34
at 14 inches from the corrected eye was necessary because

that was similar to the small print characters presented during
neuropsychological testing.
(p.592) Fourth, although most tests chosen involved a

spoken response to circumvent fine motor writing deficits
common to MS, the authors suggested that motor confounds
that could potentially interfere with performance on the
BVMT-R be addressed. They suggested using the copy portion
of the BVMT-R administration, in addition to the 9-Hole Peg
Test.
Related to motor functioning, the authors of the MACFIMS

paper also suggested that a measure of rudimentary oral
motor speed be included given that many of the recommended
tests required a rapid spoken response. The task they
recommended, the Maximum Repetition Rate of Syllables and
Multisyllabic Combinations (MRRSMC), requires examinees to
repeat the phonemes “pa” “ta” or “ka” as quickly as possible
in one good breath lasting at least six seconds. A fourth trial
requiring the repetition of the “pa-ta-ka” sequence is also
administered. Number of syllables per second is the main
scoring index. Given the frequency of dysarthria in MS, it was
suggested that slowed speech might impair patients’
performance on such tasks. At the time of the MACFIMS
publication, no data were available on the MRRSMC. A recent
publication examined this test in MS and controls and found
that MS patients performed significantly slower on the task
compared with controls (Arnett et al., 2008). These authors
also found that consideration of the MRRSMC task before
comparing group differences on several standard
neuropsychological tasks requiring a rapid oral motor
response (e.g., COWAT, Animal Naming, Oral Symbol Digit, &
PASAT) significantly reduced group differences with controls.
Thus, the data suggested that a significant proportion of the
variance in group differences between MS patients and
controls on these standard neuropsychological tasks was due
to the relatively slower speech of MS patients.
Finally, the authors suggested that fatigue be screened using

the Fatigue Impact Scale. Although the authors acknowledged
that the literature on the influence of fatigue on cognitive
functioning in MS was mixed, they noted that fatigue may
influence performance in some patients and also was known to
influence other domains of quality of life in MS patients. A
Page 12 of 34
recent study has shown that the MACFIMS has excellent

validity in detecting cognitive impairment in MS (Benedict et
al., 2006).
3.3.3 Comprehensive batteries

The MACFIMS provides a core battery from which a more
comprehensive battery can be developed. In addition to this
minimal battery, the following tests can be added if a more
comprehensive evaluation is deemed clinical necessary.
Intellectual functioning
Best measured using four-subtest (Vocabulary, Similarities,

Matrix Reasoning, Block Design) form of WASI, which allows
for derivation of reliable and valid Full Scale, Verbal, and
Performance IQ estimates. Entire Wechsler Adult Intelligence
Scale, 3rd Edition (WAIS-III) is not necessary in most cases.
However, individual subtests are useful for measurement of
specific functional areas and are highlighted below. Interpret
Block Design cautiously because motor manipulation and
visual demands required for it and many other WAIS-III
Performance subtests make it difficult to use reliably and
validly in MS patients with sensorimotor disturbance. Consider
performance on 9-Hole Peg test mentioned above for
assistance with interpretation. (p.593)
Table 29.1 Recommended brief and

comprehensive neuropsychological batteries for
assessing Multiple Sclerosis patients
Brief Screening Battery (About 30 minutes)
Premorbid Intellectual Functioning

Wechsler Test of Adult Reading (WTAR)
Memory
Verbal Selective Reminding Test (6-Trial Version) with
delayed recall and recognition
10/36 Spatial Recall with delayed recall and copy
Attention & Concentration/Speeded Information

Processing
Symbol Digit Modalities Test (SDMT), Oral Version
Paced Auditory Serial Addition Test (PASAT), 2s and 3s
versions
Verbal-Linguistic
Page 13 of 34
Controlled Oral Word Association test (COWAT)
Affective/Emotional, Fatigue
Chicago Multiscale Depression Inventory (CMDI)
Fatigue Severity Scale
Mid-Length Battery (about 90 minutes)
Premorbid Intellectual Functioning

North American Adult Reading Test (NAART)
Memory
California Verbal Learning Test - 2nd Edition (CVLT-II)
Brief Visuospatial Memory Test – Revised (BVMT-R)

Processing
versions
Verbal-Linguistic
Executive
D-KEFS Sorting Test
Visuospatial
Judgment of Line Orientation (JLO)
Chicago Multiscale Depression Inventory (CMDI) or BDI –
Fast Screen
Fatigue Impact Scale (FIS)
Sensorimotor
9-Hole Peg Test
Maximum Repetition Rate of Syllables and Multisyllabic
Combinations (MRRSMC)
Rosenbaum Pocket Vision Screener
Standard Comprehensive Battery (About 3 hours)
Orientation
Information and Orientation subtest from Wechsler
Memory Scale, 3rd Edition (WMS-III)
Intellectual Functioning
Four- subtest form of the Wechsler Abbreviated Scale of
Intelligence (WASI)
Page 14 of 34
Academic Functioning
Wide Range Achievement Test, 4th Edition (WRAT-4)
Memory
California Verbal Learning Test - 2nd Edition (CVLT-II)
Brief Visuospatial Memory Test – Revised (BVMT-R)
10/36 Spatial Recall with delayed recall and copy
Logical Memory subtests from WMS-III
Information subtest from Wechsler Adult Intelligence
Scale, 3rd Edition (WAIS-III)

Processing
versions
Digit Span subtest from WMS-III
Spatial Span subtest from WMS-III
Letter-Number Sequencing subtest from WMS-III
Verbal-Linguistic
Boston Naming Test
Executive
Tower subtest from Delis-Kaplan Executive Function
System (D-KEFS)
Card Sorting subtest from D-KEFS, free-sorting condition
only
Similarities subtest from WAIS-III
Visuospatial
Judgment of Line Orientation (JLO)
Chicago Multiscale Depression Inventory (CMDI) or BDI –
Fast Screen
Hospital Anxiety and Depression Scale (HADS)
Fatigue Impact Scale (FIS)
Sensorimotor
9-Hole Peg Test
Maximum Repetition Rate of Syllables and Multisyllabic
Combinations (MRRSMC)
Rosenbaum Pocket Vision Screener
Disability
Page 15 of 34
Multiple Sclerosis Functional Composite
(p.594) Academic functioning
Best evaluated using the Wide Range Achievement Test

(WRAT-4), a battery that takes approximately 30-45 minutes to
administer, and assesses reading, writing, and arithmetic
skills. Significantly worse performance on subtests compared
with Full Scale IQ can suggest possibility of a developmental
learning disability contributing to pattern of cognitive test
performance observed. Such a possibility should be explored
in interview, as well, when discussing developmental history.
Memory
The Logical Memory subtests (I & II) from the Wechsler

Memory Scale - 3rd Edition (WMS-III) are a useful supplement
to the memory tests suggested for the MACFIMS. The 10/36
Spatial Recall is also useful, as many patients have significant
motor-writing difficulties and 10/36 tests visual memory
without any drawing component. Remote memory screened by
Information subtest of WAIS-III, orientation by Information
and Orientation subtest from WMS-III.
(p.595) Attention & concentration/speeded information

processing
In addition to PASAT and Oral Symbol Digit to assess this

cognitive domain, Digit Span forward and Spatial Span
forward from WMS-III most useful as measures of simple
attention span. Letter-Number Sequencing, Spatial Span –
Backward, and Digit Span – Backward subtests from WMS-III
are recommended as measures of working memory relatively
independent of speed.
Verbal/linguistic
Confrontation naming may be assessed by Boston Naming

Test, 2nd Edition, which is useful only as a screen for verbal
function. In addition to the COWAT, semantic fluency (e.g.,
animal naming) can be useful. Significantly better animal
naming than letter-word fluency can suggest that letter-word
fluency problems are, in part, a function of semantic memory
retrieval difficulties. Comprehensive review has suggested
that semantic fluency is just as sensitive as letter-word fluency
to verbal fluency problems in MS (Henry & Beatty, 2006), and
can be more easily interpreted in non-English speakers (but
Page 16 of 34
base-line speaking rate needs to be measured, to rule out

artifacts due to slowed articulation).
Executive
Wisconsin Card Sorting Test (WCST) has traditionally been

used to measure cognitive flexibility and concept formation in
MS. However, a study by Beatty and colleagues (1996)
suggested that the California Card Sorting Test (CCST) may be
better because it allows for differentiation of perseverative
responding and concept formation, unlike the WCST. It is
important to note that MS patients tended to show impaired
concept formation but not perseverative responding. The
Delis-Kaplan Executive System battery (D-KEFS; (Delis et al.,
2001)) now includes a subtest analogous to CCST called the
Card-Sorting Test that can be used and has excellent norms.
Because of lengthy administration time, however, only
administration of the free-sorting condition is recommended.
The Tower Test from D-KEFS is recommended for measuring
planning ability, and the Similarities subtest from WAIS-III is a
good index of verbal abstraction.
3.4 Possible causes of cognitive deficits

Primary causes of cognitive deficits emanate from a direct
consequence of location and extent of brain damage. Thus,
cognitive problems caused by primary influences are generally
not reversible. There is clear evidence that overall cognitive
impairment is associated with total lesion damage in the brain
(Rao et al., 1989), gray matter hypointensities (Brass et al.,
2006), and especially atrophy (Benedict et al., 2006). There is
some evidence that frontal lobe lesions are associated with
deficits on executive tasks like Wisconsin Card-Sorting Test
(WCST). The association of lesions in other brain areas and
specific cognitive deficits is less clear.
Secondary causes of cognitive impairment are a consequence

of something associated with a disease such as depression,
anxiety, or fatigue. Cognitive problems caused by these
secondary influences are potentially reversible if the
secondary influence is successfully treated. Relative to
primary causes, less attention has been paid in the MS
literature to these possible causes of cognitive dysfunction.
Recent work shows that depression is associated with
impairments in speeded attentional functioning, working
memory, and (p.596) executive functions, but this link is still
Page 17 of 34
controversial (Arnett, 2005; Landro et al., 2004). There is little

evidence that self-reported fatigue or anxiety are significantly
associated with cognitive deficits in MS, but these associations
are relatively infrequently examined to date. However, one
study suggests that MS patients show greater decline in
performance on cognitively demanding tasks over the course
of an evaluation with other demanding cognitive tasks. This
suggests the possiblity that there is greater susceptibility to
cognitive fatigue during testing in MS (Krupp & Elkins, 2000),
something that should be taken into consideration when
ordering tests in a battery.
3.5 Relationship between cognitive deficits and illness variables

Kurtzke’s Expanded Disability Status Scale (EDSS; (Kurtzke,
1983)) has been the most commonly used measure of disability
in MS. Occasional studies have reported a relationship
between EDSS scores and cognitive impairment, but the
majority of studies have not found this. Because of problems
with EDSS as a measure of disability, the Multiple Sclerosis
Functional Composite (MSFC; (Fischer et al. 1999)) was
developed. It assesses three clinical dimensions: Leg function/
ambulation, arm/hand function, and cognitive function, and is
now recommended for use in standard clinical evaluations.
Recent longitudinal work on cognitive decline in MS paints a

variable picture. Most studies show relative stability over
about a 3-4 year period (Longley, 2007). However, patients
identified as cognitively impaired are the most likely to show
cognitive decline (Kujala, Portin, & Ruutiainen, 1997), even
over a relatively short period of time (e.g., three years). The
most extensive longitudinal study to date (10 years) has shown
that nearly 50% of MS patients unimpaired initially, remained
so 10 years later (Amato et al., 2001). These investigators also
found, however, that whereas 26% of patients were mild/
moderately impaired at baseline, 56% were impaired at the
10-year follow-up. Visual and verbal recall memory, verbal
fluency, visuospatial function, processing speed, and verbal
intelligence may be most susceptible to decline over an 8-10
year period (Achiron et al., 2005; Bobholz & Rao, 2003; Piras
et al., 2003). Compared with relapsing-remitting patients,
progressive patients show greater cognitive dysfunction; one
study estimated that secondary-progressive patients had seven
times greater risk of cognitive impairment than relapsing-
Page 18 of 34
remitting patients (Chelune et al., 2004). Nonetheless,

relapsing-remitting patients shown to be cognitively impaired
relative to healthy matched controls even when they are in
remission.
4 Related emotional disorders

4.1 Depression
Very common in MS with lifetime prevalence around 50% for
major depression. Point prevalence rates vary between about
15-50%, depending on diagnostic approach. Studies using
clinical interviews and diagnostic criteria report lower
prevalence; those using cutoffs from self-report measures
report higher. Accurate screening and diagnosis of depression
is extremely important, given the increased risk of suicide in
MS; the latter may be the cause of death in up to 15% of MS
clinic patients (Chwastiak & Ehde, 2007).
(p.597) Depression has been shown to be treatable through

brief and even telephone-based cognitive-behavioral therapy
(Mohr et al., 2000), as well as group therapy. Also, cognitive-
behavioral stress management training shown to reduce
emotional distress in MS (Fischer et al., 1994). Nonetheless,
depression/distress historically undertreated in MS. Successful
treatment of depression associated with greater adherence to
immunotherapy.
There has been no consensus regarding the nature of

depression in the MS literature. Some investigators have
presented evidence that neurovegetative symptoms of
depression are not valid indicators of depression because of
their overlap with MS symptoms (e.g., sleep disturbance,
fatigue, sexual dysfunction), while others have provided
evidence to the contrary. This debate suggests caution is
warranted in interpreting neurovegetative symptoms of
depression as depression symptoms in any individual MS
patient.
The cause of depression in MS unknown, but high levels of

perceived stress, low levels of social support, and disease
exacerbation/pharmacological treatment of shown to be
associated with increased emotional distress. Depression is
associated with reduced quality of life and employment of
generally less effective (emotion-focused, avoidant) coping
strategies in MS. Negative cognitive schema associated with
depression, and these also may moderate the impact of pain
Page 19 of 34
(Bruce et al., 2007) and stress (Beeney & Arnett, 2008) on

depression in MS. Lesion burden, especially in temporal brain
regions, associated with depression in MS, and may represent
a neural substrate (Feinstein, 2004). Premorbid history of
depression is no greater than in non-MS. However, patients
with history of depression, before or after MS onset, may be at
increased risk for future depressive and manic states.
4.2 Anxiety
Possibly more common than depression, but infrequently
studied in MS. Data are limited, but point prevalence of
clinically significant anxiety thought to be about 25% with
lifetime prevalence estimates around 35% (Korostil &
Feinstein, 2007). Lifetime prevalence of specific anxiety
disorders has only been minimally studied, but most frequent
include generalized anxiety disorder, followed by panic
disorder, and then obsessive compulsive disorder. Cause of
anxiety in MS unknown, but prominent in early stages of
disease when diagnosis and prognosis most uncertain. Decline
in distress associated with more definitive diagnostic
statements by treatment professionals. Best predictors of
anxiety disorders include being female, a co-morbid diagnosis
of depression, and limited social support. Drinking to excess,
higher social stress, and contemplation of suicide also
associated with anxiety (Korostil & Feinstein, 2007).
Comorbidity of anxiety and depression more associated with
thoughts of self-harm, social dysfunction, and somatic
complaints than either alone (Feinstein et al., 1999). Limited
existing research suggests that anxiety disorders are
undetected and untreated in the majority of patients.
4.3 Other emotional disorders

Only other emotional disorder occurring with any significant
frequency in MS is bipolar disorder. Point prevalence
estimated at 0-2% and lifetime prevalence 13-16%. No
published treatment studies of bipolar disorder in MS. Cause
unknown. Pseudobulbar affect, a condition where patients
laugh or cry out of proportion to any underlying emotion, (p.
598) occurs in some patients and is sometimes referred to as
pathological laughing or crying (Chwastiak & Ehde, 2007). The
cause is not well understood, but thought to represent some
type of disconnection syndrome where there is a loss of
Page 20 of 34
brainstem inhibition of laughing and crying. It occurs in about

10% of patients.
4.4 Measurement of emotional disorders

There is no consensus on how depression is best measured in
MS because of neurovegetative symptoms debate outlined
above. However, CMDI recommended because it has been
validated in MS and allows for breakdown of depression into
mood, evaluative, and neurovegetative symptoms of
depression in separate scales. Mood and evaluative scales are
more likely to reflect depression in MS because they are not
confounded with MS symptoms like neurovegetative scale.
Nonetheless, neurovegetative symptoms may reflect
depression in some patients, so should not be dismissed, just
interpreted with caution. BDI – Fast Screen is also a useful
screening tool that has been validated in MS. Clinical
interview can be used to follow-up initial screening with
CMDI, if necessary.
There is no consensus on how anxiety is best measured in MS,

but the Hospital Anxiety and Depression Scale been shown to
be useful (Feinstein et al., 1999); a measure that takes only
about 5 minutes to complete and can be followed up with
clinical interview, if necessary. It is unclear how bipolar
disorder is best measured in MS. Diagnostic interviews are the
only reliable method reported to date.
5 Neuropsychological/cognitive rehabilitation in MS
Approaches to cognitive rehabilitation in MS have been
suggested, but few have convincing empirical validation. Many
early empirical studies of cognitive retraining interventions
were characterized by small sample sizes, absence of control
groups, and disappointing results in terms of their effect on
cognitive functioning (Brassington & Marsh, 1998). However,
more recent and well-designed studies have demonstrated
positive initial results for some interventions. Given that many
patients remain relatively stable cognitively over long periods
of time, they may be more likely than patients with other
neurological conditions to benefit from cognitive rehabilitation
(Longley, 2007).
The story memory technique (SMT) is designed to train

individuals to make use of imagery and context in order to
improve learning. This intervention was investigated in a
randomized clinical trial as a treatment for memory
Page 21 of 34
impairment in a group of MS patients with memory deficits.

MS patients with moderate to severe impairments showed a
significant improvement on the Selective Reminding Test
compared with patients in the control condition. The treatment
group also reported significant self-reported improvement in
memory, suggesting that improved performance on the
neuropsychological measure may be reflective of meaningful
improvements in real life cognitive functioning (Chiaravalloti
et al., 2005; Krupp et al., 2004).
Recent research on self-generated learning in MS patients has

yielded promising results as well. Items generated by an
individual are better remembered than items that are simply
presented; this phenomenon is robust within the general
population, and has been labeled the generation effect
(Slamecka & Graf, 1978). Chiaravalloti and DeLuca (2002) (p.
599) demonstrated the generation effect in a sample of MS
patients with mild to moderate memory impairment, reporting
significantly better recall and recognition of self-generated
stimuli compared with presented stimuli. These results were
replicated and extended in a study by Basso and colleagues
(2006). This study examined self-generated encoding for
information related to activities of daily living - specifically
names, appointments, and object locations. In a sample of MS
patients with moderate to severe memory impairment, the
investigators found significantly better memory for self-
generated, compared with didactically presented, stimuli. The
results of these two studies suggest that cognitive
rehabilitation interventions based on self-generated learning
could improve memory performance in MS patients. The
findings reported by Basso and colleagues (2006) indicate that
such an intervention may promote memory improvements that
are relevant to real-life functioning.
Other interventions have focused on improving attentional

functioning in MS patients. One study examined the efficacy of
computer-aided retraining of memory and attention in a
randomized, double-blind, controlled trial. The study
treatment - a computer-assisted memory and attention
retraining intervention - was compared with a control
intervention - a visuo-constructional and visuo-motor
coordination computer-assisted intervention. Although the
results did not support superiority of the study treatment, in
both groups about 45% of patients demonstrated significant
improvement on measures of neuropsychological functioning
Page 22 of 34
(Solari et al., 2004). These results may suggest that computer-

assisted cognitive intervention is helpful in MS patients,
irrespective of specificity (Penner et al., 2006); however, as the
authors acknowledge, improvements by all study participants
could simply have been a function of practice effects.
Failure of some large well-designed studies to detect

significant treatment effects of cognitive retraining
interventions has suggested that cognitive rehabilitation may
not be viable for MS patients. However, some have argued that
certain methodological limitations are in part responsible for
the disappointing findings to date. Chiaravalloti and
colleagues (2005) suggest that future studies should focus on
including only those patients who are selectively impaired in
the cognitive domain targeted by the experimental
intervention. This methodological consideration, in
conjunction with some recent promising findings, suggests
that cognitive retraining may be effective in some MS patients.
However future work is needed to continue to develop
effective treatments, and better identify patients who will
respond to specific interventions.
The inconsistent findings in the literature regarding cognitive

retraining have led some to suggest that pursuing
compensatory strategies for MS patients may be more
promising; however, cognitive retraining has not been
sufficiently studied to rule out the possibility that it may work
for some patients. Nonetheless, because compensatory
strategies have been studied more extensively in other
neurologic populations (e.g., traumatic brain injury) and been
shown to be beneficial, it may be useful to apply them to MS
patients (Fischer et al., 1994). These include strategies such
as:
1 Using external aids (e.g., date books, wristwatches

with alarms, electronic planners) for tracking and
prompting for important information such as
appointments, to-do lists, and medication times;
(p.600)
2 keeping things that must be remembered in one
place; and
3 putting calendars in prominent locations and having
family members use them so that the affected
Page 23 of 34
individual can track family and her/his own activities

better.
Although also not systematically studied to date, making

workplace modifications that involve things such as reducing
distractions and minimizing requirements for speed in the
work area might be especially beneficial to persons with MS
who suffer from attentional and speeded processing
difficulties. Also, because even MS patients with memory
difficulties typically show learning with repetition, providing
opportunities for recording important meetings, lectures, etc.
for later review/rehearsal may be helpful to some patients.
Given how common speeded processing difficulties are in MS,
making changes in patients’ day-to-day environments that
allow for adequate time to process information may improve
their accuracy in performing day-to-day cognitive tasks
(Demaree et al., 1999).
Some recent studies suggest that medications are a promising

option for treating MS related cognitive impairment. An
acetylcholinesterase inhibitor (donepezil) has been used to
treat cognitive impairment in Alzheimer’s disease. A recent
study found that donepezil is also effective in improving
memory performance on the Selective Reminding Test (SRT) in
MS patients compared with placebo matched controls. This
effect remained significant when controlling for physical
disability, MS subtype, β-interferon use, gender, baseline SRT
score, and other covariates (Christodoulou et al., 2006).
Another study by Fischer and colleagues (2000) examined the

efficacy of a β-interferon medication for improving cognitive
functioning. 166 persons with relapsing forms of MS from the
original double-blind, placebo-controlled trial of IFNβ-1a were
compared at baseline then after two-year follow-up on a
variety of neuropsychological tests. Compared with the
placebo group, the IFNβ-1a group improved significantly more
on the CVLT (trials 1-5 total), Tower of London, and Ruff
Figural Fluency Test. Additionally, significantly fewer IFNβ-1a
group patients showed sustained PASAT decline by treatment
end. Because study sample restricted to patients with
relapsing MS between ages 18-55 and very restricted range of
EDSS scores (1-3.5), however, caution warranted in applying
results to patients not meeting such criteria. Effect of
depression treatment on neuropsychological functioning in MS
has been studied systematically in only one study (Rodgers et
Page 24 of 34
al., 1996). Significant improvement in performance on tests of

word-list learning and verbal abstraction corresponded to
significant reduction in depression in a cognitive therapy
treatment group. Although characterized by non-random
assignment of patients to treatment groups, non-clinically
depressed patients, and relatively small n, results were
promising and suggest that depression treatment (even in
subclinical patients) could have beneficial cognitive effects in
MS. Therefore, beyond improving the well being of individuals
with MS and making them more likely to adhere to important
disease-modifying medication regimens (see above), successful
treatment of depression may improve patients’ cognitive
functioning in some domains.
6 Other considerations for MS

Sleep problems are common in MS, but poorly understood.
High and debilitating levels of fatigue reported by MS patients
appear likely to be related to sleep problems, disease (p.601)
severity, and depression (Strober & Arnett, 2005).
Recommended that fatigue be briefly screened using FSS or
examined in more detail using Fatigue Impact Scale (FIS)
(Fisk et al., 1994). The latter allows for evaluation of physical,
social, and cognitive fatigue in separate scales. Cutoff score of
75 for total score recommended to identify those with
significant functional limitations relating to fatigue. Providing
breaks throughout testing day may help minimize possible
impact of fatigue on test performance.
7 Other demyelinating diseases

Demyelinating diseases other than MS are comparatively rare,
have been only minimally studied neuropsychologically, and
are infrequently seen by clinical neuropsychologists. What
follows is a brief discussion of two other demyelinating
diseases.
7.1 Marchiafava-Bignami disease

This is characterized by focal demyelination in the medial zone
of corpus callosum and most commonly associated with
chronic alcoholism. Rare but well-documented cases have
been reported in nonalcoholics. Degeneration of anterior and
posterior commissures, centrum semiovale, middle cerebellar
peduncles, subcortical white matter, and long association
bundles also sometimes seen. Symptom onset is usually
insidious and nonspecific with both focal and diffuse
manifestations of cerebral disease common; acute
Page 25 of 34
presentations involving deteriorating speech, gait, orientation,

and consciousness also seen. Psychiatric symptoms are
frequently present including delusional states, paranoia,
mania, and depression. Psychomotor slowing, apathy, and
dysarthria also seen. Neuropsychologically, nonspecific
dementia is most common. Callosal signs also characteristic.
For example, patients may be able to name objects placed in
one hand or presented to one visual field, but not in the other
hand or field. Hemispheric disconnection signs also include
unilateral apraxias and agraphias in the absence of aphasia, in
addition to unilateral sensory (i.e., auditory, tactile, visual)
simultaneous extinction. Alien hand syndrome is sometimes
seen, most often on the left side or bilaterally.
7.2 Central Pontine Myelinolysis (CPM)

This involves destruction of the myelin sheaths in the central
portion of the basis pontis, and is most often found in young to
middle-aged adults. Myelinolytic lesions are not restricted to
the brain stem and are observed in the cerebral cortex,
thalamus, basal ganglia, subcortical white matter, amygdala,
centrum semiovale, internal capsule, cerebellum, and corpus
callosum. It is associated with chronic alcoholism and/or
malnutrition in most cases, but also with liver, kidney, and
brain disease and organ transplants. More recently it has been
seen with AIDS, chemotherapy, and viral infections. Definitive
causes are unknown, but rapid correction of hyponatremia is
suspected. Acute symptoms include altered levels of
consciousness, seizures, lethargy, mutism, pseudobulbar palsy,
and quadriparesis. Course of disease can be rapid, with death
ensuing within days or weeks of symptom onset, but more
patients have survived acute phase of illness in recent years.
Neuropsychological data to date are limited to case reports
that indicate persistence (p.602) of deficits beyond the acute
stage involving global intelligence and reasoning, learning and
memory, visual- and fine-motor speed, and attention and
concentration. Confusional states most likely associated with
underlying metabolic problem that causes CPM are not
uncommon. Neuropsychiatric features including pressured
and tangential speech, restlessness and agitation, and
impaired insight and judgment have been reported as initial
presenting symptoms of CPM.
Acknowledgements
Page 26 of 34
Special thanks to our colleagues in the field Drs. Stephen Rao,

Michael Basso, William Beatty, John DeLuca, Lauren Krupp,
and David Mohr for their thoughts regarding the optimal
battery of tests to be used for neuropsychological assessment
of MS patients. We also express our gratitude to the MS
participants and their significant others who have contributed
their time in our studies to helping us to better understand the
nature of multiple sclerosis.
Correspondence concerning this article should be addressed

to: Peter Arnett, Psychology Department, Penn State
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Page 34 of 34
The neuropsychology of endocrine disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The neuropsychology of endocrine

disorders
David M. Erlanger
Geoffrey Tremont
Jennifer Duncan Davis
DOI:10.1093/acprof:oso/9780199234110.003.30

A basic understanding of how endocrine dysfunction affects
the central nervous system is important for a majority of cases
referred for assessment by clinical neuropsychologists. Beyond
playing a role in assessment and management in more obvious
scenarios, such as pituitary adenoma and Graves' disease,
increasing attention is being paid to the role of
neuropsychology in assessment and management of cognitive
dysfunction due to illnesses with direct or indirect effects on
the endocrine system and, secondarily, the central nervous
system. This chapter discusses principal syndromes of the
neuroendocrine system, disorders involving the thyroid
hormones, diabetes mellitus, disorders involving the
reproductive hormones, disorders involving the adrenal
hormones, and melatonin.
Keywords: endocrine dysfunction, neuropsychological assessment,

neuroendocrine system, hormones, melatonin
Page 1 of 53
1 Introduction
A basic understanding of how endocrine dysfunction affects
the central nervous system is important for a majority of cases
referred for assessment by clinical neuropsychologists. Beyond
playing a role in assessment and management in more obvious
scenarios, such as pituitary adenoma and Graves’ disease,
increasing attention is being paid to the role of
neuropsychology in assessment and management of cognitive
dysfunction due to illnesses with direct or indirect effects on
the endocrine system and, secondarily, the central nervous
system. Alternatively endocrine dysfunction can result from a
primary neurologic insult or condition. In addition, patients
referred for routine assessment of traumatic brain injury,
attention deficit/hyperactivity disorder, or neurodegenerative
disorder may have significant histories of thyroid dysfunction,
diabetes, and other common endocrine conditions with known
effects on the brain and cognitive function. In all such cases,
neuropsychologists should be prepared to integrate their
understanding of these factors into their clinical interview and
the interpretation of their objective neuropsychological test
findings.
Regardless of the referral question, clinical

neuropsychologists have expertise in understanding how
cognitive problems play out in real life situations at work and
at home. Problems with the endocrine system can have
discrete, often remediable, effects on motor function, learning,
or even emotional functions. Monitoring and intervention in
such cases by means of periodic assessment has the potential
to lead to more cost-effective healthcare and improved quality
of life (Ryan and Hendrickson, 1998).
1.1 Guidelines for assessment of metabolic history

Critical issues to keep in mind:
◆ Because patients may not be aware of the relevance of

information, they may neglect to mention an illness with no
obvious association with cognition. Therefore,
neuropsychologists should carefully review medical records
or ask detailed questions about medical history.
◆ Even though many treatments for some chronic clinical

syndromes are provided in an outpatient setting, clinicians
should be careful to include a thorough inpatient and
outpatient medical history in their interview.
Page 2 of 53
(p.607)
◆ Because chronic syndromes can be stable and well-
controlled for years, history should extend to the initial
onset of symptoms, regardless of how remote.
◆ Age may be an important consideration. Generally,

perinatal and/or early childhood onset increases the
possible relevance of such history to current cognitive
dysfunction. Older adult onset of endocrine disorders may
involve atypical symptoms. Also, because of the associated
reductions in levels of metabolic and endocrine function, an
aging brain may be more vulnerable and may be less
responsive to intervention.
◆ Psychiatric and emotional disturbances can be associated,

either directly or indirectly, with endocrine dysregulation.
By obtaining a detailed history of psychiatric symptom
onset, clinicians can examine these relationships.
Obtaining an accurate history of metabolic imbalance may be

a complex undertaking. Determining the date of onset is
frequently ambiguous. Because the endocrine system and
metabolism in general is subject to degeneration due to age,
subclinical syndromes may exist for years before being
identified, which may be associated with poorer response to
therapeutic intervention. Also, because multiple systems may
be affected, presenting symptoms may be physiological,
psychiatric, cognitive, or a combination. As a result,
misdiagnosis is common, even in overt disease. Psychiatric
symptoms, in particular, frequently accompany the insidious
onset of symptoms in most syndromes entailing dysregulation
of the endocrine system. Physiological symptoms secondary to
autonomic system dysfunction such as weight gain or sexual
dysfunction, similarly, may be useful indicators of the onset of
illness retrospectively.
Once diagnosed, stabilization may entail ongoing consultation

because (not infrequently), treatment of a hypofunctional
system may result in hyperfunction of that same system (or
vice-versa), resulting in an ongoing process of adjustment.
Therefore in addition to noting the duration of the illness,
severity should be ascertained according to the patient’s
individual history of metabolic control. Adolescent males with
Type I diabetes, for example, typically have more difficulty
maintaining stable glucose levels due to lifestyle factors. Even
remote periods of poor control may be worthy of
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consideration. Of even greater importance, episodes

associated with extreme hormonal imbalance and acute
metabolic crises such as hypoglycemic shock are particularly
relevant. A single such event may produce persistent
symptoms, including cognitive sequelae.
Finally, metabolic control for the several days preceding

neuropsychological assessment as well as on the day of the
evaluation may affect neuropsychological test performance.
This may be due to a direct effect of a hypometabolic condition
on performance, or to a secondary effect of a psychiatric
symptom such as anxiety or depression on the patient’s
interaction with the examiner and the test materials.
1.2 Guidelines for assessment

◆ With few exceptions, neuroendocrine dysregulation
results in worsening of cognitive functions due to
disruptions in neurochemical messages in a manner both
generalized and focal. The cognitive domains of attention,
memory, and psychomotor speed are most commonly
affected, although the effects are often subtle. As such, it is
(p.608) important to use very sensitive measures of
cognitive efficiency and working memory.
◆ Even in the context of minimal or no objective cognitive

deficits, subjective cognitive and health complaints
associated with endocrine dysfunction are common and can
impact daily functioning and quality of life. Thus, it is
important to include self-report measures of these domains
in assessments.
◆ Because relatively subtle differences may be clinically

meaningful, IQ data will be useful to determine relative
decreases from an individual’s expected level of
performance.
◆ Because follow-up may be of interest for individuals

receiving a treatment intervention such as hormone
replacement therapy, neuropsychological instruments may
be chosen based on the availability of alternate forms for
repeat assessment.
◆ Because of the frequent comorbidity of psychiatric

symptoms, the use of mood inventories and mental status
evaluations will facilitate assessment and allow for recovery
to be monitored multidimensionally (Erlanger et al., 1999).
Page 4 of 53
1.3 Principles of endocrine system operation

The endocrine system produces its effects on bodily and
mental functions by means of various hormones secreted by
specific endocrine glands and transmitted via the bloodstream
to proximate or remote sites. Table 30.1 lists the endocrine
glands and hormones with particular relevance to cognitive
functioning. Metabolic control of hormone levels is maintained
by feedback loops or axes of related hormones. For example,
the hypothalamic-pituitary-thyroid axis, or HPT axis, is
comprised of Thyrotropic Releasing Hormone (TRH), a
hormone manufactured in the hypothalamus that induces the
pituitary gland to produce Thyroid Stimulating Hormone
(TSH), which stimulates the Thyroid gland to produce
Triiodothyronine (T3) and Thyroxine (T4), the principle Thyroid
hormones. These in turn provide feedback both directly and
indirectly to the hypothalamus, thus regulating stable thyroid
hormone levels. Disruption can occur at any location along the
axis. It is in this way, for instance, that a pituitary tumor can
affect thyroid functioning.
Individual hormones may perform a number of roles and have

multiple types of receptors located throughout the body,
including the brain. Two general categories of actions have
been described. Those that affect the developing brain are
known as organizational effects. For instance, congenital
hypothyroidism can produce permanent functional and
structural changes by altering the pattern of thyroid receptors
present in the brain substrate. Activational effects on the other
hand, are the result of a chemical being present at any given
moment. Like any chemical substance, a given hormone’s
activational effects on behavior are due not only to the
identity, dose, and duration of the hormone, but also to the
brain substrate upon which it acts.
1.3.1 The hypothalamus

The hypothalamus is the principal autonomic center of the
brain, acting on the sympathetic and parasympathetic nervous
systems to maintain homeostasis and to prepare the (p.609)
Table 30.1 Principal endocrine glands and

hormones
Anterior pituitary gland
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Growth Hormone causes growth of most bodily

tissues and cells.
Prolactin promotes breast development and milk

secretion.
Follicle-Stimulating Hormone is involved in

reproductive and gonadal functioning.
Luteinizing Hormone causes ovulation in females

and stimulates the gonads in both sexes.
Adrenocorticotropin stimulates the adrenal

cortex to secrete adrenocortical hormones.
Thyroid Stimulating Hormone causes the release

of thyroid hormones by the thyroid gland.
Posterior pituitary gland
Vasopressin causes the kidneys to retain water

and regulates blood vessels.
Oxytocin facilitates childbirth and lactation.
Thyroid gland
Thyroxine and Triiodothyronine regulate the

chemical processes in cells.
Calcitonin causes the deposit of calcium in

bones.
Adrenal cortex
Cortisol contributes to the control of proteins,

carbohydrates and fats.
Aldosterone regulates levels of sodium and

potassium.
Pancreas
Insulin promotes the storage of glucose into

cells.
Glucagon promotes the release of glucose into

the bloodstream.
Testes
Page 6 of 53
Testosterone causes growth of male sex organs

and secondary sex characteristics.
Ovaries
Estrogen causes growth of female sex organs and

secondary sex characteristics.
Progesterone nurtures the developing fetus and

causes development of milk apparatus.
Pineal gland
Melatonin regulates circadian rhythms and

aspects of sexual behavior.
Parathyroid gland
Parathormone controls calcium ion

concentrations in extracellular fluid.
body to deal with emergencies. In addition, the hypothalamus is an

integral component of the limbic system, mediating drives for
hunger and thirst, sexual activity, and aggression. Finally, the
hypothalamus directly regulates the vast majority of endocrine
functions, largely by means of its regulatory effect on the pituitary
gland.
1.3.2 The pituitary gland
Immediately juxtaposed to the hypothalamus is the pituitary
gland, or hypophysis. Known as the master endocrine gland,
the pituitary affects the body’s overall metabolism, the
nervous system, and many aspects of behavior both through
the direct effect of its hormones and secondarily through its
effects on other endocrine glands. Pituitary hormones are
secreted primarily under stimulation by hormones generated
in the hypothalamus, and are modulated by means of feedback
loops and various neurotransmitter mechanisms. (p.610) The
anterior pituitary secretes a number of hormones vital to the
body’s metabolic function and capacity to deal with stress.
Known as trophic hormones, these substances act to stimulate
their target organs at distances from the pituitary. Chief
among these are Growth Hormone (GH), Adrenocorticotropin
Hormone (ACTH), Thyroid Stimulating Hormone (TSH), the
gonadotropins known as Follicle Stimulating Hormone (FSH)
and Luteinizing Hormone (LH), and Prolactin.
2 Principal syndromes of the neuroendocrine system

Cognition and Generalized Dysfunction of the Neuroendocrine
System
Page 7 of 53
Cognitive dysfunction secondary to irregular hypothalamic or

pituitary operation may be due to a number of causes
including trauma, vascular disease, and neoplasm. As would
be expected given their role as the principal mediators of the
autonomic nervous system, the resulting symptoms can
produce an array of autonomic dysregulation. Symptoms may
include temperature dysregulation, obesity, aphagia,
hypersomnia and sexual dystrophy. Affective symptoms of fear
and rage may also ensue.
Commonly, hypothalamic dysfunction may result from

compression secondary to a pituitary adenoma or
craniopharyngioma. Macroadenomas (>10 mm) frequently
come to medical attention due to their prominent mass effect,
producing symptoms such as headache and visual
abnormalities. Symptoms may result from either
hypersecretion of a hormone as a result of the tumor and/or
hyposecretion of other hormones secondary to the tumor’s
mass effect on the pituitary gland and hypothalamus.
Hormonal declines due to mass effect follow a pattern:
Hyposecretion of Growth Hormone (GH) precedes that of
Lutenizing Hormone (LH) and Follicle Stimulating Hormone
(FSH), which precedes Thyroid Stimulating Hormone (TSH),
which precedes Adrenocorticotropin Hormone (ACTH).
Cognitive deficits including amnesia and executive dysfunction
have been noted following surgery and hormone replacement
therapy (Grattan-Smith et al., 1992; Peace et al., 1997).
However, these cognitive symptoms appear to be due to
multiple factors such as surgical sequelae, pre- and
postsurgical hormonal imbalance, tumor size, secondary
hydrocephalus and radiotherapy. Indeed, some patients with
craniopharyngiomas manifest physiological changes such as
extreme weight gain and visual disturbance to such an extent
neuropsychological test data may be difficult to interpret
clearly.
The primary empty sella syndrome refers to a flattening or

shrinkage of the sella turcica, which is the bony structure that
houses the pituitary gland. As a result, the gland is
compressed and difficult to view on neuroimaging. The
syndrome is most common in women who are overweight or
have high blood pressure and is typically an incidental finding
on neuroimaging. In most cases, the pituitary gland is normal
in function. When symptomatic, patients may complain of low
libido, impotence, lack of menstruation, and visual changes. A
Page 8 of 53
secondary empty sella syndrome describes compression or

shrinkage of the pituitary gland secondary to injury, tumor, or
radiation and is associated with hypopituitarism.
In adults, a generalized hypopituitarism syndrome may result

from prounounced age-related changes in multiple hormone
systems including the gonadal, thyroid, pancreatic, (p.611)
and adrenal axes (Lamberts et al., 1997). Patients experience a
range of symptoms such as decreased energy, loss of libido
and depressed mood and/or increased irritability. Women may
experience irregular menses or amenorrhea and men may
experience impotence and fertility problems.
3 Disorders involving the thyroid hormones

The thyroid hormones T3 and T4 result from iodine processed
in the presence of thyroid stimulating hormone (TSH), a
product of the anterior pituitary gland. Although the primary
action of thyroid hormones is typically described as the
stimulation of heat production, their influence on metabolic
processes throughout the organs and tissues is significant.
Dysregulation of thyroid functioning is therefore a frequent
concomitant of systemic illness. The hormones and their
receptors are widely distributed throughout the brain,
affecting adrenergic function, striatal dopaminergic activity,
and levels of substance P and serotonin.
3.1 Thyrotoxicosis and Graves’ disease

An excessive presence of thyroid hormone is referred to as
thyrotoxicosis (low TSH, elevated T4). When associated with
diffuse goiter, ophthalmopathy, and dermopathy due to an
autoimmune disorder, hyperthyroidism is referred to as
Graves’ disease.
◆ Patients with Graves’ disease, the most common cause of

thyrotoxicosis/hyperthyroidism, typically present with
symptoms similar to a generalized anxiety disorder:
nervousness, poor concentration, apprehension,
restlessness, and emotional lability.
◆ Other symptoms include heat intolerance, increased

sweating, weight loss, muscle weakness, fatigue with
dysomnia, and—in women—changes in menstrual flow.
Increased metabolic rates may produce tachycardia
autonomic tremor.
Page 9 of 53
◆ Incidence is approximately 0.3 per 1,000 in the United

States. The condition peaks during the third and fourth
decades of life and is seven to ten times more common in
women than in men. The explanation for this gender
difference and for the underlying cause of the disease is
unknown.
◆ Delayed diagnosis and misdiagnosis as a psychiatric

condition is common.
3.1.1 Psychiatric symptoms

Although prominent psychiatric symptoms have been noted
since the earliest descriptions by Parry (1825) and Graves
(1835), researchers have generally found that psychiatric
symptom presentations are understated. Whybrow et al.
(1969), for instance, found MMPI profiles in thyrotoxic
patients to be somewhat elevated, but inconsistent with
hypomania. MacCrimmon et al. (1979) similarly found
nonsignificant elevations on a number of MMPI scales
(hypochondriasis, depression, hysteria, psychasthenia, and
schizophrenia). Although a number of researchers have found
that psychiatric symptoms largely resolve when patients are
treated with beta-adrenergic antagonists (Trzepacz et al.,
1988) and/or are returned to a euthyroid state (e.g., Vogel et
al., 2007), in Stern et al.’s (p.612) (1996) survey, 33.1% of
respondents reported being prescribed psychotropic
medication following diagnosis and treatment of Graves’
disease even though only 7.7% of the sample reported any
premorbid history of psychotropic medication. In addition to
any direct effects of altered thyroid hormones on mood,
individuals with Graves’ disease also report reductions in
health-related quality of life and can experience psychiatric
conditions related to coping with their illness (Watt et al.,
2007).
3.1.2 Neuropsychological symptoms

In the thyrotoxic state, many studies have found that patients
manifest worsened performances on tests of attention,
concentration, memory and fine motor speed (e.g., Tremont et
al., 2003; Trzepacz et al., 1988). However, there are some
conflicting findings revealing little impact of thyrotoxicosis on
cognitive skills (e.g., Vogel et al., 2007). Methodological and
sampling factors may account for the differences. Many of the
findings are consistent the presence of thyroid hormones
acting on the noradregenergic system to affect attention with
Page 10 of 53
dose correlating as an inverted U-shaped curve. Thus, Schlote

et al. (1992) also found impaired psychomotor speed in overt
but not subclinical cases. However, it is plausible that the
effects are due to a more general disruption of the brain’s
thyroid economy as well. Such would help account for reports
of poor performances on tests of conceptual thinking and
organization. In contrast to generally improved psychiatric
symptoms, there are a number of reports of ongoing worsened
performance on neuropsychological tests of attention, fine
motor speed, and memory long after a euthyroid state has
been established (Perrild et al., 1986; Trzepacz et al., 1988;
Bommer et al., 1990). One possible explanation of persisting
cognitive changes may be that an autoimmune component of
the disease is directed at the brain.
Although relatively rare in older adults, hyperthyroidism in

elderly individuals often presents with fewer overt symptoms
or with apathy and decreased motivation as the prominent
symptoms (Trivalle et al., 1996). There is also evidence of
dementia associated with hyperthyroidism that reverses
following achievement of euthyroidism (Fukui, 2001).
Hyperthyroidism in children is quite rare, but can have a
significant impact on growth and behavior.
Page 11 of 53
3.2 Congenital hypothyroidism

Children born with congenital hypothyroidism (CH) are
typically identified at birth. In the USA, whites are affected at
a substantially higher rate than African-Americans (1:5,000 vs.
1:32,000). Due to the infant brain’s vulnerability to the
organizational effects of a lack of thyroid hormone, those who
do not receive replacement therapy are at high risk for
developing severe motor and sensory impairments, as well as
mental retardation. Even in children receiving early
intervention, however, meta-analysis demonstrates a relatively
small but significant trend toward lower IQ (≈ 6.3 points) and
poorer motor skills in treated CH children (Derksen-Lubsen,
1996). Lower intellectual function is even seen when
comparing children with CH treated early after newborn
screening to their siblings (Rovet, 2005). Earlier and optimal
treatment, appear to be two important variables for (p.613)
long-term outcome of intellectual and motor functioning. The
earlier the treatment, the better outcome for overall
intellectual functioning 7 years following birth, even when
comparing groups receiving treatment at less than 15 days
compared to greater than 3 weeks after birth (Boileau et al.,
2004). Similarly, the more rapidly serum thyroid hormones
normalize following treatment, the better the outcome in
overall intellectual functioning several years later (Oerbeck et
al., 2003; Salerno et al., 2002). Untreated congenital
hypothyroidism leads to a syndrome known as Cretinism,
characterized by mental retardation, deaf mutism, short
stature, and myxedema—a puffiness in the face, hands and
feet due to the infiltration of the tissues with
mucopolyscacharides. In geographic areas with iodine
deficient diets, the severity of deficits correlates with the
extent of the deficiency (Aghini-Lombardi et al., 1995; Sankar
et al., 1994).
3.3 Adult hypothyroidism

Primary hypothyroidism (elevated TSH, low T4) in adults has
an incidence approximately one-eighth that of
hyperthyroidism. Hypothyroidism may also result from
Hashimoto’s thyroiditis, a condition similar to Graves’ disease,
in which the thyroid gland at first enlarges and subsequently
atrophies. Autoimmunity is the underlying etiology of thyroid
disease in Hashimoto’s thyroiditis. Another frequent cause is
secondary to thyroid replacement therapy for Graves’ disease.
Page 12 of 53
◆ Clinical symptoms of hypothyroidism include intolerance

to cold, puffy face, coarse, dry skin and hair, fatigue and
somnolence, muscular sluggishness, bradycardia and
reduced cardiac output, weight gain, development of a
husky voice, constipation, ematous body tissue and
arteriosclerosis.
◆ There is a significant gender bias, being four to seven

times more common in females than males.
◆ The prevalence of hypothyroidism steadily increases with

age, with subclinical hypothyroidism manifesting as
lethargy and dysphoria, although these symptoms appear to
resolve with treatment.
◆ Myopathies and delayed tendon reflexes may be evident

on neurologic exam.
◆ Depression is frequently a presenting symptom, and

misdiagnosis as a psychiatric condition is common.
3.3.1 Psychiatric symptoms

The most typical presenting picture is that of a depressed
patient: dysphoria, apathy, fatigue, diminished libido, motor
and psychomotor retardation, and even suicidal ideation.
MMPI profiles of individuals are characteristic of other
depressed populations, with elevated Depressed and reduced
Mania scales. With thyroid replacement therapy, remission of
psychiatric symptoms is common.
3.3.2 Neuropsychological symptoms

Classically, severe hypothyroidism or ‘Myxedema Madness’ is
considered a ‘reversible dementia’ with treatment by thyroid
replacement therapy. However, variables mediating (p.614)
the extent of recovery following treatment are still being
investigated. In extreme cases, coma can result from severe,
prolonged hypothyroidism. Impairment in cognition has been
noted in hypothyroidal patients since Gull’s (1874) initial
description.
Bradyphrenia, increased response latencies, poor

concentration and memory are typical presenting symptoms
(Burmeister et al., 2001; Hall, 1983; Denicoff et al., 1990;
Whybrow et al., 1969). There is a surprising lack of
investigations into severe hypothyroidism despite its relative
prevalence. A number of studies have identified cognitive
deficits on tests of mental status, psychomotor speed, memory,
Page 13 of 53
semantic fluency, concentration, and design fluency during the

acute stage. Treatment studies are equivocal with regard to
reversibility of cognitive symptoms (cf. Davis and Tremont,
2006). Serum thyroid levels may take up to three months to
normalize, and there is no consistent pattern of recovery of
cognitive symptoms following treatment, nor prospective,
objective research studies to clearly address reversibility of
cognitive and/or psychiatric symptoms in overt
hypothyroidism. Also, two published case studies (Menemeier
et al., 1993; Leentjens and Kappers, 1995) found that
replacement therapy did not reverse cognitive deficits, but
may have prevented further deterioration. These and other
studies suggest that duration of thyroid dysfunction is an
important factor, although such duration would have to be
extreme because healthy individuals have up to a 100-day
reserve available.
Controlled and uncontrolled treatment studies have focused

on mild, or subclinical, hypothyroidism and generally show
modest improvements in cognition and mood (Cooper et al.,
1984; Nyström et al., 1988; Osterweil et al., 1992; Monzani et
al., 1993; Jaeschke et al., 1996; Baldini et al., 1997; del Ser
Quijano et al., 2000; Meier et al., 2001; Bono et al., 2004;
Gulseren et al., 2006; Miller et al., 2006). A few studies,
however, have produced negative treatment results or lack of
significant improvement on a number of cognitive tests
following stabilization of thyroid levels (Osterweil et al., 1992;
Jorde et al., 2006), suggesting deficits in effortful attention
may persist.
3.4 Hypothyroidism in the older adult

There is evidence that age may increase vulnerability to the
effects of hypothyroidism on cognitive functioning. The
mechanism for this is unclear, though it is likely that the brain
relies to a greater extent on hormone levels during aging and
is more sensitive to changes in thyroid function (cf. Davis et
al., 2003; Loosen, 1992). In an analysis of 2781 cases of
hypothyroidism, only one case of reversible dementia
secondary to hypothyroidism was identified (Clarnette and
Patterson, 1994). Despite the lack of complete reversibility, it
appears that aspects of cognition respond to treatment (Haupt
and Kurtz, 1993) across the lifespan. More recent data also
indicates that mild thyroid failure may place an individual at
Page 14 of 53
greater risk for future dementia (Ganguli et al., 1996; Volpato

et al., 2002).
4 Diabetes mellitus
Diabetes Mellitus is a term applied to certain disorders that
result in chronic elevations in blood glucose levels or
hyperglycemia.
(p.615)
◆ Type I Diabetes: In the United Sates, approximately
500,000 persons have been diagnosed with juvenile-onset
insulin-dependent diabetes mellitus (IDDM), also known as
Type I diabetes with most children diagnosed in their early
teens. In these individuals, beta cells within the pancreas
are destroyed, curtailing the body’s supply of insulin.
Treatment is by means of intramuscular injection of insulin,
with the primary goal of therapy being the maintenance of
metabolic control by avoiding both hyperglycemic and
hypoglycemic states.
◆ Type II Diabetes: Non-insulin-dependent diabetes

(NIDDM), or Type II diabetes, is characterized by an
insidious onset of symptoms due to hyposecretion of insulin
and/or insulin resistance. Type II diabetes typically occurs
in adulthood with the prevalence increasing with age so
that approximately 20% of the population over 65 years of
age is affected (Winograd, 1990). Of recent concern is the
emergence of childhood type II diabetes associated with the
increasing rates of obesity in childhood. For a majority of
adults and children diagnosed with NIDDM, metabolic
control is frequently achieved through a combination of diet
and/or oral hypoglycemic agents.
4.1 Psychiatric symptoms
Both Type I and Type II diabetes may be accompanied by
symptoms of depression, anxiety, and, infrequently, mania.
More severe psychiatric symptoms are correlated with poorer
compliance to therapeutic regimes and more severe course,
although no clear cause-effect model has been established.
Stressors include factors associated with living with chronic
disease such as stress and concern with dietary regimen.
Chronic pain associated with neuropathy is also present for a
sizable subset of diabetics. Importantly, depression may
exacerbate current cognitive deficits associated with the
disease (Watari et al., 2006).
Page 15 of 53
4.2 Neuropsychological symptoms

4.2.1 Type I diabetes
Cognitive deficits due to diabetes have been the subject of
many investigations. For Type I patients, age of onset has been
shown to be related to cognitive deficits with impairments in
visuospatial tasks in patients afflicted before the age of four.
This is likely due to higher rates of hypoglycemic seizures and
the increased vulnerability of the developing brain,
particularly the process of myelination (Ryan, 1988). Cognitive
outcome also appears to be related to presence and duration
of hypoglycemia as well as hyperglycemic episodes around the
time of puberty (Desrocher and Rovet, 2004). Cognitive
problems have been identified in motor strength, visuospatial
functioning, attention, memory, and aspects of executive
functioning, but the pattern of cognitive deficits and prognosis
are complex and closely associated with disease variables.
There is limited evidence for any long-term, significant
declines in cognitive function in patients with type I diabetes,
even in those with recurrent hypoglycemia (Jacobson et al.,
2007).
In adult Type I diabetics, medical complications due to macro-

and microvascular damage are common, increasing diabetics’
risk for stroke, heart attack, retinopathy and (p.616) end-
stage renal disease. Peripheral neuropathies with the potential
to affect ADLs and IADLs are common as are paresthesias and/
or painful sensations in the distal limbs. Cognitively, this
increased risk of stroke results in increased rates of vascular
dementia in diabetics (McCall, 1992). Long histories of poorly
controlled glucose levels are associated with the vascular
complications noted above, the peripheral neuropathies being
most immediately pertinent to performance on
neuropsychological tests entailing a psychomotor speed
component. Poorly controlled glucose levels have also been
associated with reduced mental flexibility, poor conceptual
reasoning, and inefficient information processing.
Page 16 of 53
4.2.2 Type II diabetes

Ironically, neurocognitive deficits in Type II diabetics may be
somewhat more pronounced—particularly in regard to
memory function—despite these patients’ shorter histories.
Ryan and Williams (1993) hypothesized an age by
hyperglycemia interaction to account for these findings, noting
that the aging brain has been found to be increasingly
vulnerable to mnestic dysfunction in other patient groups
(e.g., alcoholics). This notion is supported by neuroimaging
findings in which type II diabetics have been shown to have
greater deep white matter disease and cortical atrophy than
type I diabetics with a longer history of illness (Brands et al.,
2007). Cognitive deficits are typically mild and likely in the
domains of verbal memory, processing speed, and executive
functioning (Awad et al., 2004). Moreover as with Type I
diabetes, history of metabolic control has been found to be key
to understanding who is most vulnerable (Assisi et al., 1996).
Research has shown that improved metabolic control may
improve cognitive functions in both Type I and Type II
diabetics.
Type II diabetes is also a risk factor for Alzheimer’s disease

(Ott et al., 1999). The mechanism underlying this risk is
unclear, but may be related to the effects of peripheral
insulinemia on amyloid clearance from the brain (Selkoe,
2000). Recent attention is being paid to the role of insulin in
Alzheimer’s disease, and the possibility of neuronal insulin
resistance reflecting a type III diabetes (de la Monte and
Wands, 2005). As such, obtaining a history of blood glucose
control and/or type II diabetes in the clinical interview is
important and may be a possible prognostic indicator for
conversion in patients with mild cognitive impairment
(Luchsinger et al., 2007; Williamson et al., 2007).
5 Disorders involving the reproductive hormones
Page 17 of 53
In concert with chromosomal factors, the reproductive

hormones are responsible for sexually dimorphic
characteristics in behavior, affect, and cognition. Through
their influence on sexual differentiation during key
developmental phases, the reproductive hormones play an
important organizational role in neuronal development, with
women’s brains having, on average, a larger corpus callosum
and planum temporale. These differences correlate with
women generally out-performing men on certain verbal tasks
and having lower rates of language disorders such as dyslexia.
In contrast, men display relative strengths in quantitative and
visuospatial skills, particularly mental rotation (Maccoby (p.
617) and Jacklin, 1974; Halpern, 1992). Importantly,
differences between groups of men and women on such
cognitive tests are far smaller than the variability within each
gender group. Nevertheless, individuals affected by disorders
marked by excessive or diminished levels of reproductive
hormones during key developmental periods manifest
behaviors and characteristics determined by permanent
structural changes in brain morphology. Due to the effects of
physiological differences on an individual’s self-concept,
resultant syndromes may require some period of social and
emotional adjustment in adolescence or later. Reproductive
hormones may also play an activational role in producing
transient changes in cognitive function in both healthy and
afflicted individuals. However, these changes appear to be
relatively minor and may depend to an extent on pre-existing
organizational pathways for their effects.
5.1 Genetic, perinatal, and environmental abnormalities

5.1.1 Klinefelter’s syndrome
Klinefelter’s syndrome results from the presence of an
additional X chromosome in the male. The syndrome is
characterized by delayed maturation, hypogonadism and
infertility, gynecomastia, and androgen deficiency. Individuals
manifest relative strengths in visuospatial abilities, and may
rely more on the right hemisphere for processing both verbal
and nonverbal information. Although lowered IQ has been
found in a number of studies, this does not always appear to
be the case (Netley and Rovet, 1984). Recent findings in adults
provide evidence of three cognitive subtypes: 1) individuals
with left hemisphere dysfunction, including VIQ<PIQ and
language impairment; 2) individuals with right hemisphere
dysfunction, including PIQ<VIQ, visuospatial deficits, and left-
Page 18 of 53
sided manual dexterity problems; 3) mild bilateral dysfunction,

including VIQ=PIQ and executive dysfunction (Boone et al.,
2001). Interestingly, age is associated with lower PIQ scores
suggesting an older age of onset in right hemisphere
dysfunction in the PIQ<VIQ subtype. Mechanisms for subtypes
are complex, but likely reflect varying responses to low levels
of androgens and/or corresponding increases in estradiols.
5.1.2 Turner’s syndrome

Turner’s syndrome is due to a single X chromosome in
females, resulting in short stature, webbing of the neck, and
sexual infantilism. A number of deficiencies in brain structure
have been identified, including decreased hippocampal,
thalamic, caudate and lenticular nuclei volumes, and
decreased right temporal evoked potentials. Cognitively,
individuals with Turner’s syndrome manifest relative
weaknesses in visuospatial ability and nonverbal memory,
consistent with right hemisphere dysfunction (Schucard et al.,
1994; cf Rovet, 2004). Although most verbal skills are intact,
individuals with Turner’s syndrome can show reduced fluency,
poor articulation, and difficulties with language syntax
(Temple, 2002). Motor clumsiness, attentional problems and
executive dysfunction are also commonly associated with the
syndrome. Many of the visuospatial and constructional deficits
continue into adulthood, although improvements can be seen
in motor planning and perceptual judgment (Romans et al.,
1998). Psychosocial (p.618) problems can include low self
esteem, social awkwardness, and face processing deficits
(Rovet, 2004).
5.1.3 Congenital adrenal hyperplasia

Excessive levels of androgens are associated with congenital
adrenal hyperplasia (CAH), an endocrine disorder beginning in
the early prenatal environment. The condition is typically
detected at birth and androgen levels are normalized.
Clinically, CAH females manifest masculinization of the
genitalia and clitoral hypertrophy. In males, an enlarged
phallus typically results. CAH can be further divided into two
subtypes:
1 salt wasters who experience high level prenatal

androgen exposure and severe episodes of
hyponatremia and hypotension; and
Page 19 of 53
2 simple virilizers who only experience high level

prenatal androgen exposure.
In understanding the effects of androgens on the developing

brain, researchers have focused on CAH females since
identifying the effects of excessive androgens in CAH males is
by definition a difficult proposition. It has been hypothesized
that overexposure to androgen also has masculinizing effects
on brain development, resulting in enhanced spatial skills and
increased incidence of left-handedness.
Research by Resnick et al. (1986) utilizing a sample of

adolescent CAH females revealed selectively better
performance on tests of mental rotation and hidden figures,
compared to unaffected siblings. Similarly, Hampson et al.
(1998) found an advantage in spatial capacity among pre-
adolescent CAH females on a mental rotation test. Curiously,
the researchers found that CAH boys scored significantly
lower than control boys on a test of spatial relations,
suggesting that overexposure to androgens may have a
demasculinizing effect on males. Kelso et al. (2000) found a
higher incidence of left-handers among CAH individuals and
more frequent pattern of PIQ>VIQ. Other studies have not
found these masculinizing effects in females for either spatial
skills or handedness (Malouf et al., 2006). Reasons for these
contradictory findings may reflect methodological variability
or sample bias or could be a result of mixing subgroups or
males and females. Johannsen et al. (2006) found that
individuals who were found to be salt wasters had lower IQs
than simple virilizers. Despite higher IQ among simple
virilizers, there is evidence of increased likelihood of
language-based disorders (i.e., learning disabilities) in this
group compared to salt wasters (Nass and Baker, 1991).
5.1.4 Androgen insensitivity

Patients with Androgen Insensitivity (AI) are genetic males
who produce androgens but manifest partial to total
insensitivity of androgen receptors. Depending on the degree
of insensitivity they are born either with external female
genitalia (and no female reproductive organs)–total AI–and are
raised as girls, or ambiguous genitalia–partial AI–and are
raised as either girls or boys. AI patients typically demonstrate
a VIQ-PIQ discrepancy with decreased PIQ (Imperato-
McGinley et al., 1991). However, lower PIQ subtest scores in
Page 20 of 53
these individuals may be due to either visuospatial deficits or

attentional factors on speeded tests.
(p.619) 5.1.5 Idiopathic hypogonadodtropic hypogonadism

At puberty, some males manifest a deficiency of gonadropic
releasing factor (GnRF), resulting in smaller testes and
decreased levels of androgens. Consistent with the
organizational effects of androgens on the brain, IHH males
have impaired visuospatial abilities and intact verbal skills
(Hier and Crowley, 1982).
5.2 Gonadal hormones influence on adult behavior

5.2.1 Androgens
Behaviorally, androgens have been associated with sexual
drive and increased aggression in both genders. However,
because aggressive encounters alter testosterone levels, no
clear cause/effect relationship between the two variables has
been established. Males receiving testosterone replacement
therapy report enhanced well-being and increased energy.
However, testosterone in males is converted or aromatized into
estrogens, obscuring the interpretation of these phenomena.
Optimal levels of androgens in both genders are necessary for

normal visuospatial functioning. Moreover, androgens appear
to have an activational effect on spatial abilities in females.
However, high levels of testosterone in males have been
associated with decreased spatial ability, suggesting a sex by
hormone interaction (Gouchie and Kimura, 1991). These
capacities are best measured by means of route learning tasks
and mental rotation tasks, although gross PIQ-VIQ
discrepancies may also be evident. There is support from the
animal literature for enhanced spatial ability in males. In a
number of non-human species, spatial-navigational ability is
sexually differentiated, with males learning to utilize routes
more efficiently (Beatty, 1984). Further, male mice castrated at
birth exhibit reduced spatial efficiency in adulthood relative to
controls (Williams et al., 1990).
Aging is generally associated with progressive decline in

testosterone in males, although it may vary based on physical
health and other lifestyle factors. Consistent relationships
have been found between testosterone levels (especially free
testosterone) and cognitive functioning in older men,
suggesting that lower levels of testosterone could lead to
dementia or Alzheimer’s disease (e.g., Yeap et al., 2007). In
Page 21 of 53
fact, men with Alzheimer’s disease have lower testosterone

levels than age-matched controls (Hogervost et al., 2004).
Whether higher levels of testosterone are associated with a
lower risk for Alzheimer’s disease remains unclear given
conflicting findings (Moffat et al., 2004; Geerlings et al., 2006).
There also appears to be an interaction between testosterone
levels and apoliproprotein ε4 allele, in which high levels of
testosterone are associated with poor cognitive peformance in
ε4-positive individuals and good cognitive functioning in non-
carriers (Burkardt et al., 2006). Finally, it remains uncertain
whether testosterone supplementation can improve cognitive
abilities, again because of several conflicting findings
(Cherrier et al., 2005; Lu et al., 2006).
Page 22 of 53
5.2.2 Estrogens and progesterone

Emotional changes have been associated with normal variation
in ovarian hormones as well as with pre-menstrual syndrome
(PMS), a cyclical disorder with depressive/mood-related (p.
620) and somatic symptoms occurring during the luteal phase
of the menstrual cycle (Schmidt et al., 1998). Cognitively,
increased verbal ability and decreased spatial ability have
been identified during the high estrogen phases, suggesting
that estrogen may differentially affect hemispheric
functioning. Despite clinical reports, there has been little
empirical support for variation in memory functioning
according to the menstrual cycle that cannot be accounted for
by the co-occurrence of mood symptoms. Furthermore, there
is no clear association between endogenous estrogen levels
and cognition prior to, during, or after menopause (Herlitz et
al., 2007), despite the fact that women experiencing
menopause often have memory complaints.
In post-menopausal women, hormone replacement therapy

(HRT) has been utilized for many years due to its association
with reduced risk of stroke, heart disease, vascular dementia,
and osteoporosis. ERT may be contraindicated for some
women, however, especially those with a family history of
breast cancer (cf. Colditz et al., 1995). The Women’s Health
Initiative, a very large longitudinal study to objectively address
the risks and benefits for hormone replacement therapy on
women’s health, was stopped in 2002 due to increased
incidence of breast cancer and cardiovascular disease (Writing
Group for the Women’s Health Initiative Investigators, 2002).
As such, the utility of HRT for reducing health risks remains
somewhat controversial and may be age dependent. Risk for
coronary artery disease seems far less in women under the
age of 60 who begin HRT closer to the onset of menopause
(Rossouw et al., 2007).
The effects of HRT on cognition have yielded conflicting

results. Some reports have shown that HRT and ERT have a
beneficial effect on verbal and nonverbal memory in younger
women. Short-term, cognitive advantages in ERT may be due
to enhanced activation of frontal lobe functioning, which could
account for improved performance on cognitive measures in
general, as well as on memory specifically via associated
executive functions (Berman et al., 1997; Joffe et al., 2006).
Interestingly, the effects of HRT on cognition may be age
dependent with early initiation of HRT around the time of
Page 23 of 53
menopause being beneficial and later initiation could have a

detrimental effect on cognition (MacLennan et al., 2006; Rapp
et al., 2003). A review of randomized placebo-controlled trials
concluded that there is minimal evidence to support cognitive
enhancement with HRT or estrogen replacement therapy
(ERT) in postmenopausal women (Hogervost et al., 2002), but
clearly other factors need to be considered, such as the timing
of when HRT was initiated and for how long.
Page 24 of 53
5.2.3 Estrogen and Alzheimer’s disease

A potential role for female reproductive hormones in
Alzheimer’s Disease (AD) is suggested by the disease’s greater
prevalence among women than men, even after adjusting for
differences in life expectancy (Jorm et al., 1987). Likewise,
several studies have found that women with AD perform worse
than men with AD on various verbal tasks (Henderson and
Buckwalter, 1994; Ripich et al., 1995), despite a premorbid
advantage on such tasks favoring women. A number of other
clinical and experimental findings including body weight,
neurophysiological processes and genetic mechanisms further
support the relevance of estrogen to AD (cf. Henderson, 1997).
Historically, ERT has been utilized in the (p.621) treatment
of women with Alzheimer’s Disease for many years. However,
trials of ERT to improve cognition and slow cognitive decline
in women with Alzheimer’s disease have been negative with
only modest, positive short-term effects on memory
(Hogervorst et al., 2002).
The possible role of ERT in reducing an individual’s risk for

developing AD has also been investigated. Several
retrospective studies found a reduced risk factor for dementia
in women receiving ERT (Birge, 1994; Henderson et al., 1994;
Mortel and Meyer, 1995). Similarly, prospective
epidemiological studies have also suggested a significant
reduction—more than 50% in some studies—in risk for AD in
women receiving ERT (Henderson et al., 1994; Paganini-Hill
and Henderson, 1994; Morrison et al., 1996; Kawas et al., 1997;
Tang et al., 1996; Yaffe et al., 1998). However, very large
controlled studies have failed to support the results seen in
clinical observation or smaller cross-sectional studies. There is
even recent evidence that women 65 years of age and older
taking combination hormone therapy had twice the rate of
dementia, including Alzheimer’s disease, compared to placebo,
and combined therapy did not protect against mild cognitive
impairment (Shumaker et al., 2003). Taken together, the
beneficial effect for the use of hormone replacement therapy
in treating the cognitive effects of Alzheimer’s disease and
reducing the risk of developing Alzheimer’s disease appear
minimal.
6 Disorders involving the adrenal hormones

The adrenal glands are located at the superior poles of the
kidneys. Each gland is divided into two distinct portions:
Page 25 of 53
◆ the adrenal medulla, which secretes the hormones

epinephrine and norepinephrine and is functionally related
to the sympathetic nervous system, and the adrenal cortex,
which secretes the hormones known as corticosteroids, of
which cortisol is of principle interest in regard to cognitive
functions.
Another adrenal hormone, dehydroepiandrosterone (DHEA),

has recently been studied for its possible effects on mood and
memory and is discussed below. The adrenal glands also
produce small amounts of certain androgens.
6.1 Cortisol
The hypothalamic-pituitary-adrenal axis is an integral
component of the body’s reactions to physiologic stressors.
Cortisol acts to increase blood glucose concentrations, which
in turn mobilizes available energy stores, and helps the body
to maintain homeostasis through its regulatory effects on
protein, carbohydrate, and lipid metabolism. The axis is
controlled by a feedback loop as follows: Corticotropin
releasing hormone (CRH) is produced by hypothalamic
neurons both according to a circadian pattern and in response
to physiologic stress. CRH regulates the release of
adrenocorticotropin hormone (ACTH) from the pituitary. ACTH
stimulates the adrenal glands, which in turn produce cortisol.
Cortisol completes the feedback loop by its effect on the
hypothalamus and other structures.
(p.622) In normal subjects, administration of exogenous

glucocorticoids may produce euphoria, hyperactivity, and
increased appetite, leading to dependence and abuse. Short-
and long-term administration of corticosteroids has been
shown to produce mild impairments in verbal memory,
although it is unclear if the dysfunction is due to disruption of
attentional factors, memory processes or both. However, mild
increases in psychomotor speed and verbal fluency have also
been reported, possibly due to a hyperactivation effect (Naber
et al., 1996). Elevated cortisol levels are also seen in
individuals diagnosed with major depression, in whom memory
and attention problems are frequently observed. However,
elevations in serum cortisol cannot solely account for these
cognitive problems.
6.1.1 Hypercortisolism
Page 26 of 53
Cushing’s syndrome refers to the clinical manifestation of

increased concentrations of cortisol due to any number of
disorders.
◆ Cushing’s syndrome may be the result of a pituitary

adenoma, a primary adrenal tumor, ectopic production of
ACTH by a carcinoma of the lung or, frequently, the long-
term treatment of a variety of diseases with exogenous
cortisol such as cortisone or prednisone.
◆ When cortisol evelations are secondary to a pituitary

adenoma, the condition is known as Cushing’s disease.
Onset typically occurs between the ages of 20–40, but has
also been reported in infants and elderly patients. Unlike
Cushing’s syndrome, females are eight times more likely
than males to develop Cushing’s disease.
◆ Typical features associated with hypercortisolism include

truncal obesity, plethoric (full) facies, hirsutism and
baldness, osteoporosis, impotence or amenorrhea,
hypertension, and generalized muscular weakness.
Psychiatric symptoms
Psychiatric symptoms are present in more than half of all

cases of hypercortisolism and may include depression, anxiety,
irritability, affective lability, decreased libido, and psychosis
(i.e., ‘steroid psychosis’). Because psychiatric symptoms may
be the initial indications of Cushing’s syndrome,
dexamethasone-suppression testing is frequently used as a
screening tool. However, as noted above, patients with major
depression may have elevated cortisol levels with no evidence
of endocrinopathy.
Neuropsychological symptoms
A wide array of cognitive functions may be affected in more

than two-thirds of all patients with Cushing’s syndrome,
including deficits in attention, memory, and executive
functions (Starkman et al., 1999, 2003). Both medial prefrontal
cortex and hippocampus have been implicated as
dysfunctional in Cushing’s syndrome/disease because of their
high concentrations of glucocorticoid receptors. In fact,
hippocampal volumes decrease during the active phase of the
illness and increase following stabilization of cortisol levels
and show a relationship to memory performance (Starkman et
al., 2003; Hook et al., 2007). Normalization of ACTH and
Page 27 of 53
cortisol levels is accompanied by a significant cognitive

recovery for these patients, although there may be a delayed
recovery in older individuals (Hook et al., 2007).
(p.623) Chronic elevations in cortisol in the elderly have

been associated with deficits in explicit memory and selective
attention (Lupien et al., 1994). Hippocampal atrophy has been
associated with both chronic and short-term elevations in
cortisol in patients with Alzheimer’s disease, depression, post
traumatic stress disorder (Davis et al., 1986; Bremner et al.,
1995), consistent with the presence of concentrations of
corticosterone receptors in the hippocampus (Ruel and
DeKloet, 1985 ; Campbell et al., 2004).
6.1.2 Hypocortisolism
Addison’s disease, a rare autoimmune disorder, accounts for
approximately 75% of all cases of primary adrenocortical
insufficiency. Insufficient production of cortisol results in
increased levels of ACTH due to decreased feedback to the
hypothalamus and anterior pituitary. Etiology is typically an
autoimmune adrenalitis due to tuberculosis, malignancy,
sarcoidosis, or infection but may also result from bilateral
adrenal hemorrhage after sepsis, trauma, surgery, or burns.
Hypocortisolism may also result secondary to pituitary or
hypothalamic dysfunction, resulting in diminished CRH and/or
ACTH. Clinical features of hypocortisolism include
pigmentation of the skin and mucous membranes, nausea,
vomiting, weight loss, muscle weakness, fatigue, and
dizziness. Psychiatric symptoms include depression, confusion,
apathy, anhedonia, psychosis, paranoia, schizophrenic
behaviors, and self-mutilation.
Neuropsychological sequelae of Addison’s disease have been

the subject of few studies. Reports document confusion and
severe problems with short-term memory and attention in the
acute stage, with improved cognition following treatment with
adrenal replacement therapy. At present, it is unclear whether
the psychiatric and cognitive symptoms are due to diminished
cortisol, or increased CRH and ACTH acting on the central
nervous system.
6.2 Dehydroepiandrosterone
The biological role of dehydroepiandrosterone (DHEA) and its
sulfate (DHEA-S) have recently been the subject of numerous
investigations due to their decrease with normal aging and
Page 28 of 53
correlation with age-related immune system decline (Thoman

and Weigle, 1989). Epidemiological data has demonstrated an
association between low circulating DHEA and cardiovascular
morbidity in males (Barrett-Connor et al., 1986) and breast
cancer in females (Helzlsouer et al., 1992). DHEA and DHEA-S
are also thought to affect behavior and cognition by mediating
GABA receptors and by acting as a GABA antagonist,
respectively.
In healthy subjects, DHEA appears to enhance general well-

being, manifested as increased energy, deeper sleep, improved
mood, greater relaxation and better stress-handling capacity.
Although some benefit in mnestic functions has been shown in
depressed patients receiving DHEA, this has not been
demonstrated in healthy populations, including age-related
cognitive impairment in the elderly (Grimley Evans et al.,
2006). Despite reduced DHEA levels in Alzheimer’s disease,
DHEA-S levels do not correlate with cognitive impairment (Bo
et al., 2006), and placebo-controlled trials of DHEA (p.624) in
patients with Alzheimer’s disease have not significantly
improved cognitive performance or overall ratings of change
severity (Wolkowitz et al., 2003).
7 Melatonin
The pineal gland is known by many as Descartes’ hypothetical
‘seat of the soul’ and for its phyloanatomical history as a
remnant of a ‘third eye’ in the posterior portion of the head in
lower animals. In addition to its possible role in the seasonal
regulation of human sexual behavior and its role in regulating
body temperature, the pineal gland has received scrutiny
because of its synthesis of the hormone melatonin.
Melatonin is secreted cyclically, with low levels associated

with daylight, and increases peaking toward midnight and
then gradually returning to baseline by morning. Exogenous
melatonin is currently sold as a treatment for jet lag, due to its
ability to re-set the body’s circadian rhythms, and to induce
sleepiness. Several studies have found significant variation in
cognitive functioning, particularly in reaction time tasks.
However, there is no evidence that circulating melatonin has a
direct effect on cognitive functioning. Instead, cognitive
weaknesses appear to be due to reduced speed of information
processing secondary to melatonin’s hypothermic properties.
Trials of melatonin for sleep disturbance (Singer et al., 2003)
Page 29 of 53
and cognitive impairment in Alzheimer’s disease (cf. Jansen et

al., 2006) have been negative.
7.1 Growth hormone

There has been recent interest in the use of human growth
hormone (GH) to potentially stave off the effects of aging on
the body and on cognition. For individuals with GH deficiency,
GH replacement significantly improves cognition, especially in
attention and memory (Falletti et al., 2006). Similarly, children
with GH deficiency have notable cognitive deficits that
improve with replacement therapy (Vander Reijden-Lakeman
et al., 1997). The use of GH in healthy individuals is quite
controversial and is associated with negative physical effects,
including soft tissue edema, arthralgias, carpal tunnel
syndrome, and gynecomastia. There are also concerns about
negative effects on glucose tolerance and possible increased
risk of cancer. Despite these effects, most studies have shown
improved cognition in healthy older adults after a trial of GH
or GH-releasing hormone (e.g., Deijen et al., 1998; Vitiello et
al., 2006). Whether GH is a safe and effective anti-aging
therapy or a treatment for geriatric cognitive disorders,
remains to be seen.
Page 30 of 53
8 Summary
Hormones act on the brain and nervous system in general to
produce an array of physiological, psychiatric, affective, and
cognitive sequelae. In many instances, the resulting symptoms
may be mild, but they can have a pronounced impact on daily
functioning, quality of life, and perception of cognitive ability.
Neuropsychologists are well prepared to assess and interpret
these multidimensional findings, given the comprehensive and
detailed nature of the exams. Neuropsychological assessment
of neuroendocrine dysfunction is a relatively new area of
research. Consequently, no ‘gold standards’ have (p.625)
been established regarding which instruments should be used
in research and clinical applications. It is recommended that
exams are comprehensive, including a broad range of
cognitive measures, psychiatric instruments, and self report
measures of cognitive complaints and daily functioning. The
purpose of neuropsychological evaluation in endocrine
disorders may vary somewhat based on age at presentation.
For children, the evaluation may be geared toward
developmental issues and establish overall intellectual and
academic functioning. The evaluation will also focus on
generating recommendations for school and related academic
activities. For adults, differential diagnosis may be more
salient, and the emphasis placed on establishing the
contribution of psychiatric and other factors on cognitive
abilities. For older adults, differential diagnosis is also
important, particularly as it related to degenerative
dementias. Table 30.2 presents cognitive domains and areas of
emphasis for the different age groups. Examples of tests are
provided as a guide, although clinicians may opt for different
measures of the same domains. For ready reference, Table
30.3 summarizes the principal characteristics and cognitive
findings relevant to neuropsychological assessment and the
neuroendocrine system. Where known, response to
intervention is indicated.
Table 30.2 Proposed areas to assess during

neuropsychological evaluation based on different
ages
Page 31 of 53
Child/ Adult Older adult

Developmental
Primary
cognitive
domains
to assess
Intellectual Full IQ testing Abbreviated IQ Abbreviated IQ

(note verbal- (Wechsler WASI
performance Abbreviated
differences; Scale of
Wechsler Intelligence)
Intelligence
Scale for
Children – IV)
Academic Comprehensive N/A N/A

(Woodcock-
Johnson-III,
Wechsler
Individual
Achievement
Test II)
Attention Sustained, Information Information

Speed of Processing and Processing and
Processing, Psychomotor Psychomotor
multiple Speed (Paced Speed (Digit
measures Auditory Serial Symbol, Trail
(Continuous Addition Test, Making Test B)
Performance Trail Making
Test, Trail Test A)
Making Test)
Executive Abstract Abstract Abstract

Functions Reasoning, Reasoning, Reasoning,
Problem- Problem- Problem-
Solving, Set Solving, Set Solving, Set
Shifting, Shifting, Shifting,
Inhibition Inhibition Inhibition
(Dellis-Kaplan (Wisconsin (Similarities,
Executive Card Sorting Trail Making
Function Test, Trail Test -B)
System
Page 32 of 53

Developmental
Wisconsin Making Test-B,
Card Sorting Stroop)
Test)
Language Fluency, Screen Fluency,

articulation (Controlled Naming
(Controlled Oral Word (Controlled
Oral Word Association) Oral Word
Association; Association,
Clinical Boston Naming
Evaluation of Test)
Language
Fundamentals
–IV)
Visuospatial Perceptual, Construction Construction

construction, (Rey-Osterrieth (Rey-Osterrieth
visuomotor Complex Complex
integration Figure, Block Figure, Block
(Beery- Design) Design, Clock
Buktenica Drawing Test)
Developmental
Test of Visual-
Motor
Integration)
Motor/ Handedness Fine Motor Fine Motor

Sensory Skills (Grooved Skills
Pegboard) (Grooved
Pegboard)
Learning Comprehensive Comprehensive Comprehensive

and assessment of assessment of assessment of
Memory memory memory memory
processes processes processes
(encoding, (encoding, (encoding,
retrieval, retrieval, retrieval,
verbal, visual) verbal, visual) verbal, visual)
(Wide Range (Wechsler (Wechsler
Assessment of Memory Scale- Memory Scale-
Memory and III, California III, Hopkins
Learning, Verbal Verbal
Page 33 of 53

Developmental
Children’s Learning Test - Learning Test -
Memory Scale) II) Revised)
Personality/ Behavior Personality Mood

Behavior checklists, testing and questionnaires
parent and mood (Beck
teacher report questionnaires Depression
(Connors (Minnesota Inventory-II,
Behavior Multiphasic State-Trait
Checklist, Personality Anxiety
Behavior Inventory – II, Inventory,
Assessment Beck Cornell Scale
System for Depression for Depression
Children-2) Inventory-II, in Dementia)
State Trait
Anxiety
Inventory)
Daily Adaptive Quality of Life Activities of

Functioning functioning Daily Living,
(Vineland Quality of Life
Adaptive (Lawton Brody
Behavior ADLs)
Scales – II)
(p.626) (p.627)
Page 34 of 53
Table 30.3 Reference summary of neuroendocrine effects on behavior and cognition
Hormone/ Primary Primary Axial Aging Effects? Psychological Principal Permanency of

Condition Hormonal Axis Hormones Features Cognitive Deficits?
Findings
Androgens Hypothalamic- GnRH, LH, FSH, Gradual Decline Libido, Inverted U- Improvement
(Congenital Pituitary-Gonadal T, E2, in Males Aggression Shaped Curve with
Adrenal Progesterone with Replacement
Hyperplasia, Visuospatial in Therapy
Androgen Males;
Insufficiency) Improved
Visuospatial in
Females
Ovarian Hypothalamic- GnRH, LH, FSH, Rapid Decline in Depression, E2 with Verbal Equivocal – Both
Hormones Pituitary-Gonadal T, E2, Females Anxiety Fluency; Verbal Improvement and
Progesterone Memory; Declines
Attention; Visual Depending on
Memory; Age of Initiation
Executive of Replacement
Functions Therapy
Hyperthyroidsi Hypothalamic- TRH, TSH, T3, T4 Decline Anxiety, Fine Motor; Improvement
m (Graves’ Pituitary-Thyroid Hypomania Attention; with Beta-
Disease) Memory Adrenrergic
Blockers and
Suppression
Therapy
Page 35 of 53

Findings
Hypothyroidism Hypothalamic- TRH, TSH, T3, T4 Decline Depressive General Improvement in

(Congenital Pituitary-Thyroid Symptoms Cognition; Depression;
Hypothyroidism) Attention; Limited
Learning; Improvement in
Psychomotor Cognition,
Speed Especially of
Attention
Hypercortisolis Hypothalamic- CRH, ACTH, Possible Increase Anxiety, Memory; Limited

m (Cushing’s Pituitary-Adrenal Cortisol Psychosis, Attention Improvement,
Disease/ Hypomania Especially of
Syndrome) Memory
Hypocortisolis Hypothalamic- CRH, ACTH, Possible Increase Depression, Poor General Improvement
m (Addison’s Pituitary-Adrenal Cortisol Motivation Attention and with Suppression
Disease) Motivation Therapy

Findings
DHEA NA DHEA, DHEAS Decline DHEA: General Improvement

Depression Cognition; with
DHEA-S: Anxiety Memory Replacement
Therapy
Page 36 of 53

Findings
Type I Diabetes NA Insulin, Decline in Insulin Anxiety Psychomotor Improvement

(IDDM) Glucagon, Speed; with
Somatostatin Inefficient Replacement
Processing; Therapy
Visuospatial;
Executive
Functions;
Memory
Type II Diabetes NA Insulin, Decline in Insulin Anxiety Psychomotor Improvement

(NIDDM) Glucagon, Speed; except for
Somatostatin Inefficient Memory
Processing;
Memory
Melatonin NA Melatonin None NA Reduced Speed NA

of Information
Processing
Growth Somatrotrophic GH, GHRH Decline Depression, Memory, Improvement

Hormone Anxiety Attention with
Replacement
Therapy
*Normal Type indicates Inconsistent or Unreplicated Findings
**Bold Type indicates Strong Findings
Page 37 of 53
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Assisi, A., Alimenti, M., Maceli, F., Di Pietro, S., Lalloni,

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Vander Reijden-Lakeman, I.E., de Sonneville, L.M.,

Swaab-Barneveld, H.J., Slijper, F.M., and Verhulst, F.C.
(1997). Evaluation of attention before and after 2 years of
growth hormone treatment in intrauterine growth retarded
children. Journal of Clinical and Experimental
Vitiello, M. V., Moe, K.E., Merriam, G.R., Mazzoni, G.,

Bucjner, D.H., and Schwartz, R.S. (2006). Growth hormone
releasing hormone improves the cognition of healthy older
adults. Neurobiology of Aging, 27, 318–323.
Vogel, A., Elberling, T.V., Hording, M., Dock, J.,

Rasmussen, A.K., Feldt-Ramussen, U., Perrild, H., and
Waldemar, G. (2007). Affective symptoms and cognitive
functions in the acute phase of Graves’ thyrotoxicosis.
Psychoneuroendocrinology, 32, 36–43.
Volpato S., Guralnik J.M., Fried L.P., Remaley, A.T.,

Cappola, A.R., and Launer, L. J. (2002). Serum thyroxine
level and cognitive decline in euthyroid older women.
Neurology, 58, 1055–1061.
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Haroon, E., Miller, J., Darwin, C., and Kumar, A. (2006).
Cognitive function in adults with type 2 diabetes and major
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Watt, T., Hegedus, L., Rasmussen, A.K., Groenvold, M.,

Bonnema, S.J., Bjorner, J.B., and Feldt-Rasmussen, U.
(2007). Which domains of thyroid-related quality of life are
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Mental changes accompanying thyroid gland dysfunction. A
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Organizational effects of early gonadal secretions on sexual
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104, 84–97.
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L.H., Johnson, J., Cukierman, T., Horowitz, K.R., Murray,
A., Launer, L.J. for the ACCORD Study Group. (2007). The
Action to Control Cardiovascular Risk in Diabetes Memory in
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McPhillips, T.B. (1990). Community-based study on the
prevalence of NIDDM in older adults. Diabetes Care, 13 (Suppl
2), 3–8.
Writing Group for the Women’s Health Initiative

Investigators. 2002. Risks and benefits of estrogen plus
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333.
(p.636) Wolkowitz, O.M., Kramer, J.H., Reus, V.I., Costa,

M.M., Yaffe, K., Walton, P., Raskind, M., Peskind, E.,
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Further reading
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neurohypophysis: A window on brain function. The New York
Academy of Sciences, New York.
Tartar, R.E., Butters, M., and Beers, S.R. (2001). Medical

neuropsychology, Second Edition. Kluwer Academic/Plenum
Publishers, New York.
Snyder, P.J., Nussbaum, P.D., and Robins, D.L. (2006).

Clinical Neuropsychology: A pocket handbook for assessment.
American Psychological Association, Washington, DC.
Page 53 of 53
The epilepsies


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The epilepsies
Pamela J. Thompson
DOI:10.1093/acprof:oso/9780199234110.003.31

Clinical neuropsychology is able to make a unique contribution
to the management of epilepsy. Neuropsychological deficits
are hidden and are often overlooked as most attention is
focused on seizures and the need for control. Undetected
cognitive deficits will have far reaching negative
consequences that extend beyond academic concerns. The
longer cognitive problems go unrecognized the worse the
outcome and the more difficult it can be to redress the effects.
A neuropsychological assessment provides a systematic and
standardized record of cognitive strengths and weaknesses
and can be vital in the management of the epilepsies. This
chapter begins with a general description of epilepsy. It then
discusses investigations for epilepsy, treatment,
neuropsychological deficits, chronic cognitive disturbance,
neuropsychological impact of treatment, psychological
disorders associated with epilepsy, and neuropsychological
assessment and rehabilitation.
Keywords: neuropsychological assessment, epilepsy management, cognitive

deficit, epilepsy, treatment for epilepsy
1 Introduction
Page 1 of 37
The epilepsies
Clinical neuropsychology can make a unique contribution to

the management of epilepsy a role identified in the UK
National Institute of Clinical Excellence guidelines of 2004
(Stokes et al., 2004).
Neuropsychological deficits are commonly associated

with epilepsy and its treatment. Awareness of these
problems may facilitate education, social integration and
employment.
Neuropsychological deficits are hidden and are often

overlooked as most attention is focused on seizures and the
need for control. Undetected cognitive deficits will have far
reaching negative consequences that extend beyond academic
concerns. The longer cognitive problems go unrecognised the
worse the outcome and the more difficult to redress the
effects. A neuropsychological assessment provides a
systematic and standardised record of cognitive strengths and
weaknesses and can be vital in the management of the
epilepsies.
A verbal learning deficit may present in focal epilepsy arising

from left temporal lobe structures. This may cause a child to
fall behind at school and fail examinations. Frequent academic
knock backs result in loss of confidence. A failing child may
also be the butt of jokes at school and a cause of distress
within the family. Low self-esteem, social withdrawal and
bullying may ensue.
Neuropsychological assessment may assist diagnosis and

treatment. It is a major tool in detecting dementia and
monitoring its course. It may be important in identifying
certain epilepsy syndromes. Neuropsychological test profiles
may help differentiate between a focal and a generalised
epilepsy and this in turn may result in more effective drug
management. Possible adverse drug side effects can be
measured with cognitive tests and drug changes can be more
promptly implemented if difficulties are demonstrated.
The neuropsychologist has a well-established role in the

surgical multidisciplinary team. Cognitive test profiles often
yield vital cerebral lateralising and localising information. Pre-
operative test scores provide evidence regarding probable
post-operative cognitive complications. These can be
Page 2 of 37
The epilepsies
discussed with the patient and their family and result in better
informed surgical decision making.
There is an increasing emphasis on cognitive rehabilitation

and this can positively influence epilepsy management.
Undetected memory impairments will result in poor
compliance. Forgotten tablets will result in an increase in
seizures. Teaching and training (p.638) memory support
strategies will improve compliance and may reduce the need
for medication increases and in turn improve memory
efficiency.
2 Epilepsy - general description

Epilepsy is the most serious, common chronic neurological
condition, with a lifetime incidence of 2–5%. The usual
prevalence figure given is 5–10 cases per 1000. Rates are
higher in those with a learning disability, increasing with the
severity of the cognitive impairment (Sander and Shorvon
1996).
Epilepsy refers to a group of conditions that have recurrent

seizures as a symptom and consequently the epilepsies is the
term recommended in the NICE guidelines (Stokes et al.,
2004). An epileptic seizure is a transient, abnormal electrical
discharge from a set of neurons in the brain; the region
involved will shape the behavioural manifestation of the
attack. Seizures may involve motor, sensory, psychic or
autonomic disturbances, alone or in combination. Epileptic
seizures are stereotyped and often have a sudden onset and a
brief duration, lasting minutes. Seizure occurrence is
generally unpredictable.
There are a number of voluntary organisations that offer

information and support to patients, families and health
professionals (See Table 31.1 for UK details).
2.1 Classification
The classification of epilepsy is complex and a multi-axial
diagnostic system has recently been proposed so that a variety
of approaches are possible (Engel, 2001). Seizure type is
Page 3 of 37
The epilepsies
Table 31.1 Additional sources of information/support
Organisation Website Address Helpline Services offered
Epilepsy action www.epilepsy.org.uk New Anstey House, Gate 0808 800 Local support groups,
Way Drive, Yeadon, 5050 accredited volunteers,
Leeds LS19 7XY fundraising events,
regional conferences for
people with epilepsy and
their families, epilepsy
awareness training,
magazines and
publications
Epilepsy Scotland www.epilepsyscotland.or 48 Govan Road, Glasgow 0808 Training, fundraising,

g.uk G51 IJL 800 2200 community support
services for one to one
service within the
community
Epilepsy bereaved www.sudep.org.uk PO Box 112, Wantage 01235 Support services to the
OX12 8XT 772850 bereaved. Free
information in relation to
epilepsy deaths. Raise
awareness of SUDEP.
Provide opportunities for
bereaved families to
meet
Page 4 of 37
The epilepsies
Organisation Website Address Helpline Services offered
National society for www.epilepsysociety.org. Chalfont Centre, 01494 Helpline, forum, leaflets,
epilepsy uk Chalfont St Peter, Bucks 601400 books and videos,
SL9 ORJ trained volunteers,
membership scheme,
epilepsy awareness
training, medical,
assessment and
residential services.
Page 5 of 37
The epilepsies
(p.639) one axis and this is likely to remain the main categorizing
tool. The major and long-standing distinction drawn is between
partial and generalised seizures. In the newly proposed
classification of seizures the term focal is recommended in
preference to partial. It is likely this change in terminology will
take time to come into common clinical usage and in this chapter
partial will continue to be used.
Most seizure types can be classified as partial or generalised
although it is recognised some seizures are not adequately
encompassed by this dichotomy including multi-focal seizures.
2.1.1 Partial seizures

Partial seizures begin with epileptic activity in a localised
brain region. Any area of the cortex can be the epileptogenic
zone but the temporal lobes are the most susceptible. 60–70%
of partial epilepsies involve onset in the temporal lobes.
Simple partial seizures are brief in duration and awareness is
retained. Common presentations include a strange taste or
smell, usually unpleasant in nature; an epigastric rising
sensation; flushing and changes in heart rate; memory
disturbances such as déjà vu and jamais vu; affective
disturbances of which fear is the most common and which can
be intense.
Complex partial seizures of temporal lobe origin are relatively

long, in the order of 2–3 minutes. Awareness and
responsiveness are altered and there is memory loss for the
event. Common presentations include automatisms such as lip
smacking, chewing, fiddling and rubbing movements. A person
may wander around. The attack may be followed by confusion
of 5–10 minutes or longer. Post-ictal dysphasia frequently
follows seizures arising from the language dominant
hemisphere.
The frontal lobes are the next most common site of partial
epilepsy. Simple partial seizures include a strange sensation
like a ‘wave’ going through the head, stiffness or jerking on
the face or in a limb. Complex partial seizures of frontal origin
are characteristically short, lasting less than a minute and in
contrast to temporal lobe seizures recovery is generally quick.
During seizures limbs may raise, there may be tonic or clonic
deviation of the head and eyes to one side, unilateral limb
jerking or posturing or sudden speech arrest.
Page 6 of 37
The epilepsies
Seizures arising in parietal regions may present with tingling,

numbness and burning sensations; illusions of size (macropsia,
micropsia), shape and sound. Seizures from occipital regions
may present with visual perceptual phenomenon (flashing
lights, coloured shapes) often restricted to a hemi-field.
Partial seizure activity may spread to involve the whole brain

and progress into a generalised seizure.
2.1.2 Generalised seizures

In generalised seizures the epileptogenic activity involves the
whole cortex from the outset. Consciousness is lost and
accordingly there is no awareness for the event. Absence
seizures involve only a brief arrest of consciousness in the
order of a few seconds. Absences are a common seizure type
in children with epilepsy. Atypical absences refers to attacks of
longer duration that may involve some body jerking.
(p.640) Generalised tonic clonic seizures can last several

minutes and are biphasic. The attack begins with muscle
contraction and stiffness. The person will fall if standing and
muscle tightening around the chest may result in a
vocalisation as air is expelled from the lungs (tonic phase).
Limb jerking follows (clonic phase). Often breathing is affected
with grunting and snorting and the patient may be
incontinent. Seizures last a few minutes although exhaustion is
common and a period of sleep may be needed.
Tonic seizures are brief. Suddenly all muscles stiffen, the

person becomes rigid and will fall if standing. Injuries are
common. Recovery of consciousness is rapid. Atonic seizures
involve a sudden loss of body tone. If standing the person will
fall, more usually forwards. As for tonic seizures injuries are
common and recovery is quick. Myoclonic seizures are the
briefest attacks and involve sudden muscle jerks lasting only
seconds, most usually affecting the arms.
Most seizures are short-lived and stop spontaneously. Status

epilepticus refers to prolonged episodes lasting more than 30
minutes or serial seizures with inadequate recovery between
attacks. It can occur for any seizure type but is most
dangerous for tonic-clonic seizures and is a medical
emergency.
2.1.3 Reflex seizures
Page 7 of 37
The epilepsies
Reflex seizures have a specific trigger. Seizures are classified

according to the precipitating stimuli. The most common
precipitants are visual stimuli (flickering lights and patterns)
and the most frequent environmental triggers are watching
television, computer games and other computer graphics.
Other documented precipitants are hot water, startle and
higher mental activity, including reading, writing, arithmetic,
memorising, chess and card playing. Seizures can be
precipitated by other special circumstances such as fever or
alcohol withdrawal but these are not reflex seizures.
2.2 Prognosis
70–80% of people with epilepsy will become seizure free and
about 50% will be able to discontinue their antiepileptic
medication. The remainder will present with difficult to control
epilepsy and it is this group who are at greater risk of
cognitive impairments.
At one time epilepsy was considered a benign condition but

recent studies have indicated an elevated mortality rate. Death
in newly diagnosed epilepsy is invariably due to the underlying
aetiology. In more longstanding epilepsy the main cause of
death is the seizures and is classified as sudden unexpected
death in epilepsy (SUDEP). This accounts for an estimated 500
deaths a year in the UK (Hanna et al. 2002; Tomson et al.
2005).
Seizure type is of limited utility in assessing prognosis. The

underlying cause and any identified syndrome are better
indicators.
2.3 Causes
The causes of epilepsy are varied.
◆ Epilepsy may be genetically determined. Idiopathic

generalised epilepsies include childhood absence epilepsy.
Of these 80% remit by adulthood. The mode of inheritance
is unclear and is likely to be multigenetic. There are a large
number of rare inherited (p.641) disorders with seizures
as a common feature including tuberous sclerosis and
neurofibromatosis both autosomal dominant. and
Unverricht Lundborgs Disease autosomal recessive.
◆ Congenital malformations of the brain may cause

epilepsy. Cortical dysgenesis refers to brain abnormalities
that have developed as the result of faulty neuronal
Page 8 of 37
The epilepsies
migration during embryo-genesis. The most severe cases

involve gyral abnormalities such as lissencephaly, where
there is an absence of gyri over the whole brain. Invariably
such individuals have severe learning disabilities. Prognosis
is usually poor. At the other end of the spectrum there may
be more localised small areas of dysgenesis (i.e.
dysembryoplastic neuroepithemial tumours (DNETs)).
Causes of cortical dysgenesis are thought to include
intrauterine infection and illness.
◆ Hippocampal sclerosis is the most common lesion

identified in resected tissue following temporal lobe
resections. It is strongly associated with a prolonged
childhood febrile convulsion(s). Habitual epilepsy may not
develop for several years. It remains controversial whether
hippocampal sclerosis results from epileptic activity or
whether it precedes and is the cause of the epilepsy.
◆ The incidence of epilepsy is high following cerebral

infections and often seizures are difficult to control. Rates
for herpes simplex encephalitis are 25%; for bacterial
meningitis 10% and for human immune deficiency virus
(HIV) related cerebral toxoplasmosis 25%.
◆ Epilepsy may be caused by head injuries. The risk is high

when the post-traumatic amnesia exceeds 24hrs.
Intracranial haematomas and open head injuries increase
the risk.
◆ Seizures can develop de novo following neurosurgery:

The occurrence of seizures will be influenced by the site
(increased frontal and temporal), the extent of resection
(increased with larger volumes) and the condition for which
the craniotomy is performed (e.g. higher for arteriovenous
formations than for intracranial aneurysms).
◆ Cerebro-vascular disease may cause epilepsy. It depends

on the extent and site of the infarction. The rates are low
for transient ischaemic attacks and high for haemorrahagic
stroke.
◆ Neoplasms increase the risk of epilepsy and the risk

varies with type (oligodenrogliomas 90%; meningiomas and
astrocytomas 70%; malignant tumours 35%).
◆ Seizures may be a symptom of dementias and

neurodegenerative conditions. Approximately 25% of cases
Page 9 of 37
The epilepsies
with Alzheimer’s Disease develop seizures. The response to

AED treatment in this group is good.
◆ Metabolic disorders may underlie epilepsy. Changes in

blood concentrations of sodium, potassium, calcium,
magnesium and glucose are implicated.
◆ There are reports of epilepsy following drug ingestion.

Drugs that have been implicated include antibiotics,
antimalarials, antidepressants and antipsychotic agents.
Illicit drug use and heavy alcohol consumption can cause
epilepsy.
(p.642) 3 Investigations for epilepsy

A diagnosis of epilepsy is commonly made on the basis of a
behavioural description of the seizure that is generally
provided by the family. Rarely do physicians witness an attack.
3.1 Electroencephalography (EEG)

EEG recordings are used to support a diagnosis of epilepsy in
patients with a history that suggests an event was epileptic
(Stokes et al., 2004). An EEG trace represents the summation
of synchronised excitatory or inhibitory postsynaptic
potentials. An EEG should never be used in isolation to make a
diagnosis of epilepsy. Neither should an EEG be used to
exclude a diagnosis of epilepsy. About 10% of patients with
epilepsy will have normal EEGs. In about 30% of cases
epileptic abnormalities are seen on routine recordings (20–30
minutes). This increases to 95% if a recording captures a
seizure; unfortunately the chances of recording a seizure
during a routine recording are low.
EEGs may provide useful information about epilepsy type.

Generalised spike and wave discharges typically occur during
absences and indicate a generalised epilepsy. Evolving
temporal slow wave activity may be seen in temporal lobe
seizures supporting a diagnosis of a focal seizure disorder.
More prolonged EEG recordings increase the chances of

seizure detection. Small portable EEG machines allow longer
recordings (ambulatory EEG monitoring). These may be worn
for several days in the home environment until an attack
occurs. More prolonged EEG recordings can also be
undertaken as an inpatient and this also allows for
simultaneous video recordings (video-telemetry). During
Page 10 of 37
The epilepsies
inpatient assessment AEDs can be reduced or withdrawn or

the patient can be sleep deprived, conditions that increase the
chances of seizures occurring.
3.1.1 Intracranial EEG recordings

These are undertaken on selected surgical candidates usually
when epileptic sites are suspected but the precise origin is
unclear. Depth electrodes with multi-contact wires are
inserted stereotactically under MRI guidance into the
region(s) of interest.
Subdural grids and strips consist of larger arrays of

electrodes. These are placed directly onto the brain intra-
operatively. These are used when the suspected epileptogenic
area is extensive and may involve eloquent cortex. Brain
stimulation via the electrodes enables mapping of the
epileptogenic region. Stimulation when a patient is awake is
undertaken to map language and the motor cortex.
Intracranial EEG recordings are invasive and carry an
increased risk of morbidity.
3.2 Brain imaging

Magnetic Resonance Imaging (MRI) and Computerised
Tomography (CT) cannot be used to diagnose epilepsy. Brain
imaging plays a vital role in epilepsy in establishing aetiology
and in pre-surgical investigations. MRI is the imaging tool of
choice and it is recommended best practise to obtain a scan in
the majority of patients with epilepsy (Stokes, 2004). The most
common abnormalities identified in epilepsy are hippocampal
sclerosis, malformations of cortical development vascular
malformations, tumours and acquired cortical damage.
(p.643) Diffusion tensor imaging (DTI) is a method derived

from MRI technology that looks at the flow of water within the
brain that highlights how different areas of the brain are
connected. Trachtography utilises DTI to delineate white
matter tracts and demonstrate the connectivity between
regions. Recent research has used this technique to delineate
language pathways in TLE patients (Powell et al. 2007a).
MRI Spectroscopy is an imaging technique that measures

neurotransmitter levels and it has been used to explore how
the activity of the brain is affected by seizures. This remains
largely a research tool.
Page 11 of 37
The epilepsies
3.2.1 Functional MRI (fMRI)

fMRI has been a valuable research technique and increasingly
is being developed as a clinical tool. In epilepsy, paradigms are
being developed to identify the locus of seizure onset. In
epilepsy surgery programmes, fMRI paradigms are being
developed to assess brain regions involved in critical cognitive
functions such as language and memory and to generate data
that contributes to surgical decision making. Consensus is
growing regarding the utility of such procedures to lateralise
language functions but more controversial to date is the use of
fMRI data for memory assessment as an alternative to the
intracarotid amytal procedure (Powell et al. 2004).
3.3 The Intracarotid Amytal Procedure (IAP)

This test used to be carried out prior to all anterior temporal
lobe resections and many other surgical procedures. It was
originally developed to assess language dominance.
Subsequently it was used to screen for the risk of post-
operative amnesia in candidates undergoing a temporal lobe
resection. Each cerebral hemisphere in turn is temporarily
anaesthetised by injecting sodium amobarbital into a single
carotid artery via a catheter placed in the femoral artery. The
drug effects are variable but last approximately ten minutes. A
transient hemiplegia and EEG changes indicate a lateralized
effect. The patient is shown stimuli before and after the
injection. Speech arrest and dysphasic responses indicate
language dominance in the injected hemisphere. Intact
memory performance when the ‘to be resected’ hemisphere is
injected indicates no risk of post-operative amnesia. The IAP is
an invasive procedure and although complications are rare
they can be severe and have included cerebral infarction. The
application of this test in many surgical centres has been
reduced in recent years due to concerns about such risks
together with doubts regarding its reliability and validity (see
later).
4 Treatment
4.1 Acute management
Convulsive seizures are usually short-lived and do not
require immediate medical treatment. Nothing can be done to
influence the course of the seizure.
Page 12 of 37
The epilepsies
1 The patient should be made as comfortable as

possible, preferably lying down, or eased to the floor if
seated.
2 The head should be protected and any tight clothing
should be released.
(p.644)
3 Clear a space around the person in order to avoid
injury.
4 Do not attempt to open the mouth and do not force
anything between the teeth.
5 After the convulsive movements have stopped, roll the
person on to their side.
6 Check the airway is not obstructed.
7 Patients may take a variable time to recover and may
wish to sleep or rest.
8 Emergency treatment will only be needed if the
person sustains an injury, the convulsive stage lasts
longer than ten minutes, the patient takes a long time
to regain consciousness following the episode, or a
second convulsive attack follows on shortly.
Non-convulsive seizures require minimal management.
1 Many attacks are very brief and have little impact on

a patient’s behaviour.
2 In complex partial seizures the patient may wander
and fiddle with items. An attempt should be made to
guide the person out of danger if necessary.
3 No attempt should be made to restrain them.
Attempts at doing so can make a patient become quite
agitated and at times aggressive.
4.2 Medication
Antiepileptic drugs (AEDs) form the mainstay of treatment.
The range of drugs available is given in Table 31.2 and the
most common side effects in Table 31.3. About 70% of patients
developing epilepsy may expect to become seizure free with
AED therapy. The majority will achieve control with a single
drug and 10–15% with two drugs.
Table 31.2 Antiepileptic drugs
Page 13 of 37
The epilepsies
Generic name Brand Abbreviation Dose range

name (mgs)
Carbamazepine Tegretol CBZ 400–1600
Clobazam Frisium CLB 10–30
Clonazepam Rivotril CZP 0.5–4
Ethosuximide Zarontin ESM 500–1500
Gabapentin Neurontin GBP 900–3600
Lamotrigine Lamictal LTG 100–400
Levetiracetam Kepra LT 750–3000
Phenobarbitone Luminal PB 60–180
Phenytoin Epanutin DPH 200–400
Pregabalin Lyrica PGB 150–600
Oxcarbazepine Trileptal OXC 600–2400
Sodium Epilim VPA 500–2500

valproate
Tiagabine Gabitril TGB 30–45
Topiramate Topamax TPM 75–400
Zonisimide Zonegram ZNS 150–600
(p.645)
4.3 Surgical treatment
Table 31.3 Common AED side effects
Anti-epileptic Common side effects

drug
Carbamazepine Diplopia, dizziness, headache, nausea
Clobazam Fatigue, drowsiness
Clonazepam Fatigue, drowsiness, sedation
Ethosuximide Nausea
Gabapentin Somnolence, ataxia, dizziness, diplopia
Lamotrigine Drowsiness, headache, diplopia, tremor
Levetiracetam Headache, irritability
Page 14 of 37
The epilepsies
Anti-epileptic Common side effects

drug
Phenobarbitone Fatigue, depression, insomnia

(children), distractibility (children),
irritability (children)
Phenytoin Nystagmus, ataxia
Pregabalin Dizziness, drowsiness
Oxcarbazepine Fatigue, diplopia, dizziness
Sodium Tremor, weight gain, hair loss

valproate
Tiagabine Dizziness, headache, tremor,

concentration difficulties
Topiramate Weight loss, impaired concentration and

speech, paraesthesia
Zonisamide Drowsiness, dizziness
There are two major types of surgery for epilepsy, resective

and functional. Resective surgery aims to remove the
epileptogenic brain region in order to stop seizures (Duncan
2007). Advances in MRI technology have increased the yield of
abnormalities that are amenable to this approach. The most
commonly performed operation is an anterior temporal lobe
resection and the most common pathology hippocampal
sclerosis. In such cases up to two thirds can be expected to
achieve complete seizure control post-operatively.
A lesionectomy may be performed if there is a small

circumscribed area of abnormality. Such lesions include
cavernomas, focal cortical dysplasias and indolent tumours
such as dysembryoplastic neuroepithelial tumours. A seizure
free outcome is highest for extratemporal lesions and is lower
when the lesion is within the temporal lobe.
A hemispherectomy represents the most radical procedure;

resection of the temporal lobe and central cortex is followed
by disconnection of frontal and occipital neocortices from the
subcortical structures and corpus callosum. It is most
commonly carried out with children when there is evidence of
major structural abnormalities and limited functional capacity
in the epileptogenic hemisphere.
Page 15 of 37
The epilepsies
The aim of functional surgery is palliative. It is only considered

when resective surgery has been ruled out. The surgical plan
is to disconnect the epileptogenic region or to prevent the
spread of epileptic discharges to other regions.
Corpus callosotomy involves disconnecting the callosal fibres

between the cerebral hemispheres; most operations involve a
partial disconnection of the anterior fibres. The procedure is
most commonly used in patients with disabling drop attacks.
(p.646) Multiple subpial transection, also known as Morrel’s

Procedure, involves multiple cuts being made vertically in the
assessed epileptogenic cortical region in an effort to reduce
seizure generation while maintaining anatomical function. It is
undertaken when seizures arise from language areas or motor
cortex.
Vagal nerve stimulation (VNS) is a recently developed

procedure. A small device, akin to a cardiac pacemaker, is
placed subcutaneously and connected surgically to the left
vagus nerve. This generator sends regular mild electrical
impulses via this nerve to the brain. The rate of pulse
generation is programmed at outpatient hospital visits
beginning a few weeks after implantation. The patient also has
a magnet which can be used to produce extra impulses
following seizure warnings. There are reports of reduced
seizure frequency and also reductions in seizure duration and
recovery time. A VNS may take several months to have an
effect. Side effects include discomfort in the throat, a cough
and a hoarse voice. Once implanted, VNS is a contra-indication
to higher resolution MRI scanning (even if the VNS has for
some reason been disabled).
4.4 Psychological treatment

A number of treatments have been proposed as seizure
reducing techniques (Whitmarsh, 2004). From a behavioural
viewpoint, a seizure is part of a sequence of events and by
interrupting the behavioural chain at some stage, the
likelihood of seizure is reduced. Avoidance is a behavioural
technique that has been successfully employed in reflex
epilepsies. Individuals with photosensitive epilepsy can reduce
the likelihood of a seizure by viewing the television at a
distance, covering one eye, viewing in good, ambient lighting
and by using polarised glasses. Anxiety reduction techniques
have been employed with varying success. Recent studies have
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shown substantial seizure reduction using biofeedback

although such approaches require intense input and high
levels of motivation. Studies of the efficacy of CBT are few and
the support for improving seizure control is limited (Goldstein
et al. 2003).
4.5 Diet and lifestyle changes

The Ketogenic Diet is the most established dietary control for
epilepsy. It is high in fat but low in carbohydrate and protein.
It is used almost invariably with children. The diet can be
continued for months, or even years, if necessary but many
children find it unpalatable and accordingly compliance can be
a problem.
In some generalised epilepsies, changes in lifestyle have been

associated with improved seizure control and complete seizure
freedom. Routines including regularising sleep together with
abstinence from alcohol are the most commonly advocated.
5 Neuropsychological deficits
5.1 Intelligence
In the past epilepsy has been associated with limited
intelligence. This misperception was a consequence of biased
sampling with over-representation of institutionalised and (p.
647) intractable cases. More representative sampling
indicates people with epilepsy span the spectrum of
intellectual ability.
A few epilepsy syndromes are characterised by failed or

arrested cognitive and intellectual development.
◆ Early infantile epileptic encephalopathy has an onset in

early infancy. The MRI shows extensive abnormalities and
atrophy. Many infants die and survivors have severe and
profound learning disabilities, often with sensory and motor
abnormalities.
◆ In West’s Syndrome and Lennox Gastaut Syndrome:

There is developmental delay but with plateauing. Sufferers
invariably have lifelong, frequent and severe seizures.
◆ In some other conditions there is co-morbidity and the

onset of seizures may not develop until later childhood,
adolescence or in adulthood. The estimated risk of epilepsy
in Down’s Syndrome is 10%; in Autism 30% in Cerebral
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Palsy 50%, in Tuberous Sclerosis 60%, and in Angelman’s

Syndrome 80%.
The likelihood of epilepsy increases with the severity of a

learning disability. Both the seizures and the cognitive
impairment are a consequence of extensive brain damage and
immature cerebral development.
5.2 Intellectual deterioration

Longitudinal studies over substantial time periods are few but
indicate that intellectual level can remain stable even when
seizures are poorly controlled (Thompson and Duncan 2005).
Intellectual decline however is a symptom of some rarer
syndromes.
Rasmussen’s Encephalitis presents with constant partial motor

seizures, usually in one limb, with gradual progression to
involve the ipsilateral limb, causing a hemiplegia. It is
associated with progressive focal brain atrophy. In left
hemisphere cases there is a fall in VIQ and language skills and
in right hemisphere cases a fall in PIQ and visuo-spatial
abilities.
Electrical status epilepticus during slow-wave sleep (ESES)

develops in childhood often following several years of normal
development. Cognitive decline can be dramatic. EEG studies
demonstrate almost continuous periods of abnormal EEG
patterns of generalised spike and wave predominant during
sleep. EEG abnormalities and seizures remit in the majority in
adolescence, but intellectual gains thereafter are small.
Landau Kleffner Syndrome involves ESES but in addition with
left hemisphere temporo-parietal spike wave discharges while
awake and aphasia (see later).
There are a few progressive myoclonic syndromes. Unverricht

Lundborg’s Syndrome (Baltic myoclonous) is one. The onset is
usually between the ages of 5–15. Progressive motor and
cognitive deterioration can be dramatic.
5.3 Ictally related cognitive disturbance

Transient cognitive deficits may be temporally related to the
seizures. Deficits will vary in severity and type depending on
the duration and site of the epileptic discharge. Transient
cognitive impairment is a term used to describe fleeting
cognitive lapses associated with brief epileptic discharges.
These may only become apparent during continuous (p.648)
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cognitive activity. When such discharges are frequent

cognitive disturbance is marked. Any cognitive activity may be
disrupted but cases have been reported of localised discharges
having a selective effect (e.g. left temporal discharges
impairing verbal but not spatial memory tasks) (Holmes and
Lenck-Santini, 2006).
Overt seizures may present as more obvious intermittent

cognitive disturbances. For example, word finding difficulties
may be the manifestation of partial seizures arising from
dominant lateral temporal regions or brief episodes of
topographical disorientation may reflect seizures in the non-
dominant temporal lobe.
Non-convulsive absence and partial status epilepticus can

present as severe cognitive impairment that mimics dementia.
Misdiagnosis can occur, most frequently in the elderly and
individuals with learning disabilities. EEG recordings confirm
this diagnosis and AED treatment can bring about rapid
control and reversal of the cognitive disturbance.
There may be post-ictal cognitive changes which persist. For

instance verbal memory deficits can persist several days
following a cluster of left temporal lobe seizures when other
cognitive functions have recovered.
6 Chronic cognitive disturbance

There is no cognitive deficit or neuropsychological test profile
that characterises epilepsy. The majority of individuals who
are well controlled by drug treatment will not experience
problems and accordingly do not come to the attention of a
clinical neuropsychologist. Those with intractable epilepsy,
however, will be at risk of persisting cognitive difficulties. The
most potent factor influencing the nature and severity of a
deficit is the presence and location of brain pathology and the
epileptic focus. Given the increased risk of epilepsy with
temporal and frontal pathology, cognitive deficits associated
with these regions are the most frequently encountered in
clinical practice.
6.1 Memory
Deficits of new learning have been the subject of most
investigations and are the most common cognitive impairment
in temporal lobe epilepsy (Thompson, 1997). Memory
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impairment is most extensive in cases with known bilateral

temporal lobe damage, with the amnesic syndrome being the
most severe case scenario. Amnesia is most often encountered
in adult onset post-encephalitic cases.
Unilateral temporal lobe epilepsy has been associated with

material specific memory disorders. Assuming left hemisphere
language dominance, left temporal lobe disturbance is
reported to be associated with verbal memory difficulties and
right temporal lobe disturbance with spatial and other non-
verbal memory deficits (Baxendale et al. 1998; Baxendale et
al., 1998b). Such material specific memory disorders are more
likely to be encountered post surgically. In unilateral temporal
lobe cases, material specific memory problems may not be
found and are less likely in early onset epilepsy, particularly
where the underlying pathology is a cortical dysplasia.
Patients’ accounts suggest that memory decline may occur

several hours or days following successful registration.
Research studies have provided some support for this
demonstrating (p.649) that patients with temporal lobe
epilepsy can perform adequately when recall is tested with
delays up to one hour, but that abnormally accelerated
forgetting can occur at longer delays (Blake et al. 2000).
Routine clinical assessments will miss such memory
disturbance.
6.2 Language
Language problems arise most frequently in partial epilepsy
emanating from the language dominant hemisphere
particularly in the presence of a structural lesion. A seizure
focus in fronto-temporal regions will interfere with expressive
functions and more posterior temporal lesions with receptive
functions. Dominant parietal foci may underlie reading and
spelling problems.
6.2.1 Language dominance

Atypical language dominance (i.e. language functions
predominantly lateralised to the right hemisphere or
bilaterally represented), is not uncommon in epilepsy.
Predisposing factors include early cerebral insult to the left
hemisphere, early onset of recurrent seizures, left
(pathological) handedness or weak right handedness.
Language laterality in epilepsy is a clinically relevant variable
in individuals being considered for surgery and may influence
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the decision to proceed to surgery, the extent of a resection,

the need for an awake craniotomy and the content of pre-
operative counselling outlining post-operative cognitive risks.
6.2.2 Landau Kleffner’s syndrome

This is also known as acquired epileptic aphasia and is a rare
disorder. Linguistic regression develops in association with
severe focal EEG abnormalities. It usually presents between
the ages of four to eleven with generally normal language
development prior to the onset. Receptive language difficulties
may be the first symptom. The majority of cases go on to
develop generalised and partial seizures. Language
deterioration occurs over time and total mutism can result.
EEG recordings show multi-focal spike and wave discharges
predominately in temporal and parietal regions. Language
functions may improve as seizures become less frequent or
stop although many individuals are left with significant
language problems (Holmes and Lenck-Santini 2006).
6.3 Executive Functions

Partial epilepsy of frontal lobe origin is associated with an
increased risk of executive skills deficits (Upton and
Thompson, 1996; Upton and Thompson, 1999; Risse, 2006)
Research studies have reported impaired programming and
co-ordination of motor sequences, impaired working memory
and reduced attention and response inhibition. Executive
function deficits are more evident in individuals with bilateral
and more extensive pathology. For some, the cognitive burden
is very handicapping. A characteristic of frontal lobe epilepsy
is rapid seizure propagation, especially to the contralateral
lobe and to mesial temporal regions. As a consequence, frontal
lateralising and localising cognitive deficits may not be found
and, when seizure activity spreads to temporal regions,
patients may present with memory deficits more characteristic
of temporal lobe epilepsy cases.
(p.650) Juvenile Myoclonic Epilepsy is a generalised epilepsy

syndrome. Neuropsychological studies are few but subgroups
with this diagnosis do exhibit working memory and decision
making deficits (Pascalicchio et al. 2007). Negative social
behaviours attributed to dysexecutive syndromes have been
described by some authors. Recent imaging studies have
raised the possibility of abnormalities in frontal brain regions.
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Executive skills deficits have also been described in patients

with temporal lobe epilepsy. There are rich connections
between frontal and temporal regions, and executive
dysfunction in TLE may arise as a result of the propagation of
epileptic activity to frontal regions. Executive skills
impairments have been reported as more likely when seizures
have secondary generalisation (Martin et al. 2000).
7 Neuropsychological impact of treatment

7.1 AEDs
There is no evidence that AEDs have any independent
cognitive-enhancing properties. Improvements in cognition
can occur as a consequence of better seizure control. For
individuals with multiple daily absences effective drug
treatment will result in improved attention and information
processing. For those at risk of status epilepticus effective
drug treatment may prevent damage in hippocampal
structures and subsequent memory decline. Where seizures
take the form of transient cognitive deficits, effective
treatment will improve cognition by eliminating such episodes.
Control of seizures does not always result in cognitive
improvement. AEDs are developed to suppress the symptoms
of epilepsy and not the underlying cause. Patients with
epilepsy arising from structural brain pathology will tend to
experience persisting cognitive problems despite good seizure
control.
AEDs should always be considered a possible factor in patients

referred with cognitive complaints. AEDs are given to
suppress neuronal over-excitability in the brain and they are
not selective in their action. Drugs will also affect normally
behaving neurons. When a single drug controls seizures at
small doses, adverse cognitive effects may be negligible.
Where seizures are more difficult to control, the risk of
adverse cognitive effects is higher. The aim of drug treatment
is to achieve the best seizure control with minimal side effects.
This balance can be difficult to achieve. Any drug can exert an
effect when blood concentrations are too high. Cognitive
disturbance usually presents with other symptoms of
intoxication such as ataxia and diplopia. Cognitive blunting
however may be the only sign.
Conflicting results predominate in the research literature.

Randomized controlled trials tend to report minimal cognitive
side effects. Such studies may miss adverse drug effects if the
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response is not uniform across patients. The pharmaceutical

industry sponsors most research which can influence the
reporting of results. Case studies and less rigorously designed
studies tend to report more negative drug effects. These
designs however have their own biases (Ortinski and Meador
2004).
The cognitive profile of individual drugs is far from clear and

accordingly, generalisations are difficult. A drug can have an
adverse effect in one patient but not another. Genetic factors
may underlie side effect susceptibility. A drug effect may
manifest as reduced efficiency on a range of tests. Mental
slowness and impairments of working (p.651) memory are
more common indicators of a drug effect. However, some
patients do experience an exacerbation of pre-existing
cognitive problems.
Among the more established AEDs phenobarbitone has been

most frequently associated with adverse cognitive effects.
Phenytoin is a drug with peculiar pharmacokinetics. A minimal
increase in dose can result in a dramatic increase in blood
concentrations and in turn impaired concentration and
information processing deficits. There have been reports of
pseudodementia on this drug. Cases of sodium valproate
induced dementia have also been documented often associated
with raised ammonia levels (hyperammonaemia). Marked
cognitive slowing can arise when phenobarbitone is co-
prescribed. Carbamazepine has been associated with fewer
cognitive side effects.
The evidence is limited for most of the more recently

introduced AEDs with the exception of topiramate. Patients’
complaints on this drug highlight effortful thinking and
reduced verbal fluency, and this has been confirmed by
research studies (Thompson et al. 2000). For some, the
cognitive loss is marked with VIQ falls of more than ten points
recorded, and accompanied by poor academic and work
performance. Reports of cognitive decline in young people
with epilepsy on TPM should be taken seriously and
thoroughly investigated as examination failure can have major
social and psychological ramifications.
The risk of cognitive impairment increases with polypharmacy.

Unfortunately those with poorly controlled seizures will
invariably be prescribed two or more different agents. The
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cognitive impact of AED combinations has received scant

attention and no study has looked at the cognitive risks of co-
medications such as antidepressants and antipsychotic agents.
The lack of clear research findings means that objective

cognitive monitoring is all the more important. In all patients
reporting cognitive decline or deficits, drug treatment should
be considered a possible factor. Questions should be asked
regarding the onset of cognitive difficulties and changes in
drug type or dosage. To assess for drug effects requires
assessment before and following changes. Several months
should elapse between assessments.
7.2 Surgery
7.2.1 Temporal lobe resections
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Neuropsychological assessment has a long established role in

the pre-surgical evaluation of candidates for temporal lobe
surgery. In the 1950s, the profound amnesia recorded
following bilateral hippocampal ablation was instrumental in
the discontinuation of this surgical approach. A few cases of
post-operative amnesia were recorded following unilateral
temporal lobe resections however retrospective analysis in all
cases indicated pathological changes in the unresected
temporal lobe (Baxendale et al. 2003). Impaired memory
function in the hemisphere contra-lateral to the proposed
surgery highlights the possibility of structural abnormalities
and underscores the vital role of pre-operative memory
assessment. A good surgical candidate will have a material
specific memory deficit which is concordant with MRI
identified pathology and with lateralised EEG disturbance (p.
652) (e.g. a verbal memory deficit in a person with left
hippocampal sclerosis and ictal epileptic discharges from the
left mesial temporal region). However, as described earlier,
material specific memory deficits are more likely to be
encountered post-operatively. In pre-operative cases, the
presence and severity of material specific disorders will be
influenced by the underlying pathology, the age of onset and
other characteristics of the seizure disorder.
The development of post-operative memory deficits will

depend upon the functional adequacy of the tissue removed
and the cognitive reserve of the remaining structures. Some
plasticity and the development of compensatory strategies
post-operatively may also influence the nature and extent of
post-operative neuropsychological deficits. Pre-operative
neuropsychological scores in conjunction with MRI and other
clinical data can be utilised to predict post-operative
neuropsychological change. Patients at risk of significant
memory decline are older (>40) with higher pre-operative
memory scores, and have neuropsychological signs of
impaired processing in the contralateral temporal lobe
(Baxendale et al. 2006). Left temporal lobe resections are
associated with memory decline that is more readily apparent
to the patient and their family.
Left hemisphere resections are associated with an increased

risk of language problems post-operatively. Such deficits are
most prominent in the early post-operative period and tend to
resolve over time. About one third of cases are left with a mild,
persisting nominal dysphasia. A small subgroup of patients, in
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the order of 10%, do well cognitively view post-operatively and

such individuals warrant earlier identification as such
cognitive improvements are likely to have a lasting impact on
academic, occupational and social functioning.
Intra-carotid Amytal Procedure (IAP)
In recent years the reliability and validity of the IAP as a

screen for amnesia have been questioned. A systematic review
of the literature on post-operative amnesia revealed that all
reported cases to date would have had MRI evidence of
contra-lateral temporal lobe pathology, had the technology
been available. Currently there is an active debate between
surgical centres around the world concerning its use and a
recent survey indicates several centres have stopped using the
procedure or have reduced the number of procedures
undertaken (Baxendale et al., 2008). Other centres no longer
use the test to screen for amnesic risk but now employ the
measure to predict post-operative memory decline and to
provide additional data regarding the laterality of the seizure
focus. The added value of using the IAP for these reasons,
above data derived from other sources remains unproven.
At the National Hospital for Neurology and Neurosurgery in

London, the use of the IAP has decreased over time, and we
have not undertaken an IAP for four years. Our follow up data
in almost 300 cases provides no evidence that this decision
has adversely affected surgical outcome, resulted in any
unforeseen debilitating cognitive sequelae or has had an
adverse impact on patient care. Noteworthy, several patients
who had previously had surgery deferred due to a previous
IAP ‘failure’, have since undergone surgery, become seizure
free, and are leading fulfilling lives. Currently our assessment
of amnesic risk is based primarily on MRI and baseline
neuropsychological test findings. Our ongoing (p.653)
research studies are exploring the value of fMRI memory
paradigms to predict post-operative memory outcome (Powell
et al. 2007b).
Reducing the IAP has enabled patients to proceed to surgery

more quickly; an important consequence, as this group has an
increased risk for epilepsy related death. In addition, the
physical and psychological risks accompanying this procedure
are avoided and the financial savings are not insignificant (as
a 2–3 day hospital admission, and the attendant professional
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time is no longer required). As important, it has freed up

neuropsychology time for patient counselling, follow up and
memory rehabilitation work.
7.2.2 Frontal lobe surgery

There are few post-operative cognitive outcome studies. Some
cases show exacerbation of existing deficits. Cognitive
outcome is poorest in those with continuing seizures who were
cognitively intact pre-operatively. Resection involving the pre-
motor and sensory motor area increases risk of impaired
response inhibition. Marked language disturbance has been
reported with dominant hemisphere operations (Helmstaedter
et al. 1998).
7.2.3 Hemispherectomy
This procedure is most often performed in paediatric cases
with evidence of significant hemi-atrophy. Children often have
a hemiparesis and cognitive and adaptive abilities are often
limited with further decline anticipated (e.g. Rasmussens
encephalitis, Sturge-Weber Syndrome). In a recent study with
follow up data on 71 children at least five years after surgery,
seizure outcome was good with 50% rendered seizure free and
half of these off medication (Pulsifer et al. 2004). Intelligence
and other cognitive functions including language abilities were
impaired but had generally not worsened as a consequence of
the operation. This must be considered a positive outcome for
the cases with Rasmussens Encephalitis as progressive
cognitive decline is a feature of this syndrome. Cognitive
outcome was poorer in children with hemimegalencephaly and
other larger dysplasias particularly in those who continued to
have frequent seizures.
7.2.4 Corpus callosotomy

The group undergoing this procedure tend to have severe life
threatening seizures including drop attacks. Cognitive data on
corpus callosotomy cases indicates a trend towards improved
functioning with anterior resections. Outcome is generally less
favourable for complete resections. Better cognitive outcome
is reported with an early age of surgery. Transient deficits
such as alien hand syndrome and mutism are rare and tend to
occur earlier in the post-operative period and following total
resections (Jenssen et al. 2006; Lassonde and Sauerwein
1997).
8 Psychological disorders associated with epilepsy
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8.1 Mood disturbance

Mood disturbance can be a direct manifestation of a seizure or
it may present as a pre-ictal or post-ictal phenomenon. Pre-
ictal mood disturbance may last hours and sometimes days but
will resolve following a seizure. Post-ictal mood disturbance
often (p.654) follows seizure clusters and can persist for
days. Depression is most commonly encountered and may be
severe and involve suicidal ideation. Improving seizure control
will reduce ictally related mood disturbance. Helping patients
recognise the seizure related cause can help manage these
psychologically disturbing episodes.
AEDs can cause mood disturbance. Phenobarbitone,

primidone, tiagabine and topiramate have been associated
with depression. In such cases the onset of mood disturbance
will coincide with the introduction of the drug.
Transient mood disturbance develops following temporal lobe

resections in up to 1 in 4 cases, typically 2 to 3 months post-
operatively and in a few patients may persist and require
treatment.
Research studies have demonstrated high rates of inter-ictal

depression in epilepsy. Anxiety has been less frequently
studied although it is commonly encountered in clinical
neuropsychological practice. Many factors exist which
contribute to adverse mood change in epilepsy:
◆ unpredictability of ongoing seizures.
◆ intrusive and embarrassing aspects of seizures, such as

bizarre behaviours and incontinence.
◆ risk of injury, particularly for those with drop attacks.

Others may be placed in danger, such as small children if a
parent has epilepsy.
◆ fear of death; 20–40 year olds have an eight-fold

increased risk of death.
◆ need to adhere to a restrictive drug regime (especially

with side effects such as weight gain, facial hair, acne and
cognitive difficulties).
◆ experience of successive treatment failures in intractable

epilepsy. Hopes are raised following the introduction of a
new drug, only to be dashed when seizures recur.
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◆ failure of surgical treatment which may occur in

approximately a third of cases, particularly when this
follows years of freedom from seizures.
◆ teasing and bullying at school
◆ employment and financial difficulties
◆ for potential parents, anxieties may be raised regarding

the pregnancy, the birth and subsequent development of the
child.
◆ epilepsy still carries a sizeable social stigma or prejudice

and imbues varying degrees of fear and suspicion.
Professionals working in the field need to be aware of possible

negative emotional reactions and the potential causes.
Allowing time to talk about the experience of having epilepsy
and to raise ongoing concerns can be beneficial. Mood rating
scales are useful clinical screening tools.
8.2 Psychosis
Post-ictal psychosis is a well recognised phenomenon that
generally occurs after seizure clusters but which may develop
after several hours or days of recovery. Symptoms include (p.
655) delusions, hallucinations, thought disorder and mania
that can last several weeks. Short-term use of benzodiazepines
or antipsychotic medication may be helpful and may curtail the
episode. Controlling seizures will lessen the occurrence.
Psychosis can develop between seizures and become a chronic
problem. The onset is usually after several years of seizures
and it is more commonly encountered in early onset temporal
lobe epilepsy. Psychosis is a rare complication of AED
treatment (topiramate, ethosuximide) and temporal lobe
surgery.
8.3 Aggression
Aggression is an infrequent complication of epilepsy. Ictal
aggressive episodes are rare but will be stereotyped in nature
and will occur in the absence of environmental precipitants
and be undirected. Aggressive behaviour more commonly
occurs in the post-ictal phase often as a result of attempts to
restrain before a person has sufficiently recovered. Interictal
aggression in epilepsy is more likely to arise in the presence of
widespread underlying cerebral damage particularly involving
the frontal lobes. Drug treatment may have a role. Irritability
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has been identified as a side effect of levetiracetam in adults

and of phenobarbitone in children.
8.4 Non-epileptic attack disorder (NEAD)

NEAD is a term used to describe transient episodes of altered
movement, sensation or experience resembling epilepsy but
caused by a psychological process, and not associated with
any abnormal activity in the brain (Reuber and Elger 2003).
NEAD was previously known as pseudoseizures, a term
discouraged due to pejorative connotations. NEAD is
recognised as a heterogeneous grouping that may be a
manifestation of an anxiety disorder or a dissociative disorder.
In the latter group there may be a history of past emotional
trauma including physical violence and/or sexual abuse and
ongoing psychosocial stressors. Occasionally NEAD may
reflect a more conscious process with some obvious secondary
financial gain (malingering) or a pathological need (as in
Munchausens Disorder). In tertiary referral centres NEAD is
diagnosed in up to 25% of cases with a previous diagnosis of
epilepsy, and in up to 50% of patients presenting with status
epilepticus at A&E departments.
Differentiating between epileptic and non-epileptic seizures is

difficult. No characteristics are exclusive to epilepsy and no
features occur only in non-epileptic attacks. Incontinence and
injury do not reliably distinguish epileptic from non-epileptic
seizures. Features suggestive of NEAD include gradual onset,
long duration (>5 mins), asynchronous limb flailing, directed
actions especially aggression, reactivity to external stimulation
and identifiable environmental/psychological triggers.
Treatment begins with a positive presentation of the diagnosis

which should be extended to the immediate family. The
diagnosis does not mean attacks are consciously put on, but
may be the brain’s way of dealing with past and/or ongoing
stresses. The attacks will not respond to AED drugs and these
can be withdrawn, which is likely to have cognitively beneficial
effects. CBT is the treatment of choice advocated although the
evidence base is limited (Goldstein et al. 2004).
(p.656) Follow up studies of NEAD indicate that in about a

third of cases seizures stop, following a change of diagnosis
and minimal psychological input. For others, more long-term
psychotherapy is beneficial. A favourable prognosis is
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associated with a shorter duration of seizures and acceptance

of a psychological mechanism (Carton et al., 2003).
9 Neuropsychological assessment
9.1 General
◆ Have a description of seizure(s): In partial epilepsy this
may provide pointers to area of cerebral disturbance (e.g. if
patient described to have post-ictal dysphasia, suggests
language areas implicated and assessment may need to
focus on this). Will enable prompt recognition of an attack
occurring during the assessment.
◆ Measurement of mood is recommended; high rates of

anxiety and depression will influence the interpretation of
the test results.
◆ Test selection usually influenced by the referral question

(although some centres have a standard battery of tests).
◆ Test selection may also be shaped by the results of

investigations (e.g. EEG and MRI findings may indicate
localised cerebral disturbance).
◆ Documentation of drugs taken including dosages.

9.2 Patient complains of memory impairment and/or decline
The most common referral for neuropsychological assessment
in patients with epilepsy are:
◆ Memory tests should include measures of recall, learning,

and recognition of both verbal and non-verbal material.
◆ Immediate and delayed retention: The time available and

test standardisation does not permit retention at intervals
greater than forty-five minutes, but a longer interval may be
helpful for some individuals.
◆ Measures of general intellectual capacity: WAIS-R, WAIS-

III provide an indication of ability level (which provide
context for interpretation of memory test scores).
◆ Measures of other skills, especially language and

executive function, as memory declines, may reflect
problems in these areas rather than memory per se.
◆ Subjective rating of memory by patient and ideally an

observer provide valuable information as to the nature of
memory problems encountered in everyday situations.
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◆ Where negative findings, may need a broader and/or

more experimental approach (e.g. remote and
autobiographical memory measures; delayed recall > one
hour).
9.3 Assessing negative impact of drugs
◆ Unlikely a single assessment will provide the answer.
Ideally, testing should be undertaken before and after a
drug change. Recommend two to three months between
assessments.
(p.657)
◆ Require tests available in parallel forms or minimally
sensitive to practice effects.
◆ Include some speeded tests, as drugs seem to impact on

speed of processing more than accuracy. Computerised
tests enable accurate measure of speed.
◆ Useful tests include digit span, timed cancellation tasks,

verbal fluency and verbal learning.
9.4 Evaluation of candidate for resective surgery
◆ Assess for cognitive disturbance concordant with known
lesion and electrophysiological disturbance. With temporal
cases, attention will be on memory skills; with frontal cases,
attention to executive functioning.
◆ Assess for cognitive competency in other areas; a good

surgical candidate will be the individual who functions well
on other tests.
◆ Pre-operative counselling: High pre-operative functioning,

older age at operation, and discordant neuropsychological
deficits, place individuals at risk of cognitive decline post-
operatively and this needs to be discussed with patient.
◆ Arrange post-operative re-assessments to monitor change

and to provide rehabilitation if necessary.
10 Neuropsychological rehabilitation
Research evidence of effectiveness is limited, although clinical
experience suggests memory training can be useful and have a
significant impact on the management of the condition.
Patients have to remember appointments, to take tablets, to
document seizure frequency. An unreliable memory will result
in the physician being presented with a less than accurate
picture of seizure control. In a recent unpublished survey of
Page 32 of 37
The epilepsies
people with epilepsy, 18% indicated that they forget their

medication at least on a weekly basis.
People with epilepsy are a good target for memory training.

Memory problems are usually less devastating than for other
neurological cases and insight is generally retained. Many
people with epilepsy live independently and are less likely to
have a “carer” on hand to act as an external support for a
weak memory.
◆ Feedback the test results. Individuals may be relieved by

the confirmation that a memory difficulty exists and in
many cases it is possible to reassure that it is not going to
get progressively worse. This would be the case for an
individual with well controlled seizures but with known left
hippocampal sclerosis.
◆ If a young person is struggling to achieve academic

standards comparable to siblings or parents expectations,
confirmation of a memory deficit may result in a reappraisal
and redirection to courses with less reliance on written
examinations.
◆ Sessions can be offered to focus on memory support

strategies; use techniques employed with other
neurological groups. Clinical experience indicates that
external memory aids are generally the most valuable (e.g.
box organisers, wall planners). Computerised diaries and
personal organisers are also useful.
(p.658)
◆ One of the most valuable external memory aids is the
drug wallet. Many people find this device helps them to
remember to take their tablets, and also not to take too
many. Drug wallets usually consist of seven small
containers, one for each day of the week. Compartments
can be filled once a week at set times. The seven individual
containers are removable. Drug wallets can be obtained
from local chemists and are generally not very expensive
(less than £10).
◆ Internal memory aids involving mental strategies may

have a use, although generally for small amounts of
information which is a, less easily committed to diary or
other external memory aids.
Page 33 of 37
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“Neuropsychological profile of patients with juvenile
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2007b, “Preoperative fMRI predicts memory decline following
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Page 37 of 37
Clinical presentation of neuropsychiatric disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Clinical presentation of
neuropsychiatric disorders
Ronan O’Carroll
DOI:10.1093/acprof:oso/9780199234110.003.032

Clinical neuropsychology plays a crucial role in the assessment
of cognitive impairment in clinical practice and in research in
psychiatry. Recent advances in knowledge have allowed for
more fine-grained cognitive analysis of specific impairments.
This in turn can lead to a greater understanding of the neural
basis of abnormal behaviour. The development of
neuropsychological measures allows for the valid and reliable
assessment of treatment efficacy. This is particularly important
as ‘negative features’ (including cognitive impairment) have
become increasingly recognized as key targets for
pharmacological treatment in psychiatry. This chapter reviews
the clinical presentation and common neuropsychological
features of some of the major psychiatric disorders. These
include anorexia nervosa, Asperger's syndrome, autism,
bulimia nervosa, Capgras syndrome, conversion disorder
(hysteria), Cotard syndrome, and De Clerambault's syndrome.
Keywords: neuropsychological assessment, psychiatric disorders, anorexia

nervosa, Asperger's syndrome, autism, bulimia nervosa, Capgras syndrome,
conversion disorder, Cotard syndrome, De Clerambault's syndrome
Page 1 of 49
1 Introduction
Neuropsychology is the study of brain-behaviour relationships,
and has traditionally utilised the classical lesion-based
approach; relating focal brain damage to patterns of preserved
and impaired cognitive functioning. In the majority of
psychiatric disorders however, focal brain lesions are rare, and
the challenge of the discipline of cognitive neuropsychiatry is
to try to understand abnormal behaviour in terms of
dysfunctional processing of information (Halligan and David,
2001; Frith, 2008). This is more likely to be related to
cognitive processes reflecting abnormalities of brain systems
than localised brain damage.
The determination of brain-cognition relationships represents

a formidable undertaking in psychopathalogical states. Many
neuropsychological studies in major psychiatric disorder are
conducted on patients who are taking psychotropic
medication, and such drugs may well have confounding effects
on measures of cognitive functioning. Most psychiatric
disorders disturb affective status, and mood and motivation
critically impact on neuropsychological test performance. How
does one distinguish between a ‘core deficit’ and a lack of
motivation or effort due to the effects of depression? To take a
specific example, imagine you were invited to participate in a
neuropsychological research project on PTSD. You fulfilled
DSM-IV criteria for PTSD and comorbid major depressive
disorder. If your sleep had been disrupted for the previous
month, if you were exhausted, felt worthless, a total failure,
hopeless and useless and totally lacking in motivation, how
well do you think you would perform on a two-hour
neuropsychological test battery? Would the test results be a
valid representation of your true abilities? One must also
address the issue of diagnosis (i.e. how psychiatric disorders
are traditionally classified).
The conventional approach is to adopt the medical model and

describe ‘illness’ states that allegedly share common features.
However, many critics have challenged the validity and
reliability of standard psychiatric diagnoses, such as
schizophrenia, arguing that they represent such
heterogeneous groupings that effectively ‘apples are being
mixed with oranges’, and classified as the same fruit (Bentall,
1992). In recent years greater attention has been placed on
exploring specific syndromes or symptoms rather than
‘illnesses’. For example, rather than trying to explain
Page 2 of 49
schizophrenia, attempts have been made to explain (p.664)

specific features (e.g. paranoid delusions) in
neuropsychological terms (e.g. tendencies to jump to
conclusions on limited evidence). Recent work suggests that
many people with delusions accept the most salient current
hypothesis. They do not reflect on past learning to consider
whether the information fits with previous knowledge, with
the result that the possibility that one might be mistaken is not
considered (Garety et al. 2005). Studies are ongoing to test
whether these information processing styles are amenable to
change.
Clinical neuropsychology also has a crucial role to play in the

assessment of cognitive impairment in clinical practice and in
research in psychiatry. Recent advances in knowledge have
allowed for more fine-grained cognitive analysis of specific
impairments. This in turn can lead to a greater understanding
of the neural basis of abnormal behaviour. The development of
neuropsychological measures allows for the valid and reliable
assessment of treatment efficacy. This is particularly important
as ‘negative features’ (including cognitive impairment) have
become increasingly recognised as key targets for
pharmacological treatment in psychiatry (Kraus and Keefe,
2007; O’Halloran et al. 2007). Furthermore, ecologically valid
neuropsychological outcome measures are essential in the
rapidly developing field of cognitive rehabilitation.
In the following sections, the clinical presentation and

common neuropsychological features of some of the major
psychiatric disorders will be briefly reviewed.
2 Anorexia nervosa
The essential features of anorexia nervosa are: body weight
15% below the standard weight (i.e. a body mass index below
17.5) and an intense fear of gaining weight or becoming fat,
even though the individual is clearly under weight. There is an
associated perceptual disturbance in the way the person’s
body shape is seen (e.g. in the mirror), and in women, the
presence of amenorrhea (i.e. the absence of at least three
consecutive menstrual cycles). Patients generally eat very
little and set themselves very restrictive daily calorie limits
(e.g. 500 calories per day). Additional strategies to achieve
weight loss include laxative abuse, vomiting and excessive
exercise. Anorexia nervosa is approximately ten to twenty
Page 3 of 49
times more frequent in women than in men and occurs in

approximately 1% of young women. Six to 10% of female
siblings of patients with anorexia suffer from the condition,
compared to 1–2% found in the general population of the same
age. This increase may be due to family environment or to
genetic influences.
Page 4 of 49
2.2 Neuropsychological features

A variety of biological, psychological and environmental
factors have been implicated in the aetiology of anorexia
nervosa. Hypothalamic dysfunction has been proposed in
anorexia as there is a profound disturbance of weight
regulation. However, the endocrine and metabolic
abnormalities may be a consequence of low weight and
disturbed eating habits, rather than the cause. Brain imaging
abnormalities have also been reported (e.g. enlarged
ventricles and decreased hippocampal volume in anorexia
nervosa). However, these (p.665) brain changes are often
reversed by weight gain, suggesting again that they may
represent a consequence rather than a cause. Connan et al.
(2006) recently reported that after adjustment for total
cerebral volume, there was significant bilateral reduction in
hippocampal volume in anorexic patients. However there was
no evidence of impaired hippocampus-dependent cognitive
function and no evidence of a relationship between
hippocampal volume and clinical features of anorexia or with
changes in cognitive function. They propose that it is
important to integrate endocrine, neuropsychological and
neuroimaging studies in order to understand the cause and
consequence of hippocampal size and function in anorexia
nervosa.
Several studies have documented neuropsychological

impairments in anorexia, affecting a variety of cognitive
domains (memory, attention, set shifting and problem solving).
Fowler et al. (2006) recently reported that patients with

anorexia nervosa demonstrate subtle neuropsychological
impairments, however in those patients with more severe
degrees of impairment, these may have important adverse
effects on more complex tasks of social and occupational
functioning. The authors caution that further work is required
to determine the nature of relevant causal mechanisms,
including the effects of potential confounders. Cognitive
improvements following weight gain suggest again that these
impairments are reversible, not primary, and may be related to
nutritional status. A recent systematic review and meta-
analysis in eating disorders concluded that problems in set
shifting as measured by a variety of neuropsychological tasks
Page 5 of 49
are common in people with eating disorders (Roberts et al.

2007).
3 Asperger’s syndrome
Asperger’s syndrome is a pervasive developmental disorder,
first described by Asperger in 1944. The condition is
characterised by marked impairment in social interaction (e.g.
avoidance of eye-to-eye gaze and failure to develop
relationships, restricted, repetitive and stereotyped patterns of
behaviour, with clinically significant impairment in social
functioning). Asperger’s syndrome differs from autism because
in the former there is no general delay or retardation of
cognitive development or language. Non-verbal
communication problems and clumsiness are common.
Asperger’s syndrome is well reviewed by Frith (1991).

There is relatively little known about neuropsychological
functioning in Asperger’s syndrome, though theory of mind
deficits are commonly observed (see section on Autism,
below). It has been suggested that right hemisphere
impairments may contribute to the behavioural abnormalities
seen in Asperger’s syndrome (e.g. face processing problems
and poor gaze perception (Ellis and Leafhead, 1996). Autism
and Asperger’s syndrome have been considered as part of the
same spectrum of disorders. Miller and Ozonoff (p.666)
(2000) proposed that Asperger’s may simply reflect high-IQ
autism, and that separate categories for the disorders may not
be warranted. Thede and Coolidge (2007) recently conducted
a comparison of Aspergers children versus high functioning
autistic children. Both groups demonstrated marked executive
deficits and evidence of Attention Deficit Hyperactivity
Disorder compared to healthy controls. The authors concluded
that there were more similarities than differences between the
Asperger and high functioning autistic children, however the
Asperger’s children exhibited significantly greater anxiety.
4 Autism
4.1 Clinical Presentation
Autistic children show deficits in social interaction; in
particular they fail to show the usual intimate relationship
with people close to them, including parents and sibs. Many
autistic individuals lack a social smile and do not display an
anticipatory posture for being picked up (e.g. when a parent
Page 6 of 49
approaches), and abnormal eye contact is frequently observed.

Disturbances of communication and language delay are also
common. When autistic individuals do learn to converse, they
often lack social competence and their conversations do not
exhibit the normal reciprocal responsive interchanges. Autistic
children often demonstrate abnormalities in play (e.g.
engaging in rituals and frequently insisting on ‘sameness’ and
being resistant to change). Autistic children may also be over-
responsive or under-responsive to sensory stimuli.
Hyperkinesis is also a common behaviour problem in young
autistic children.

Autism is often associated with developmental conditions that
have associated neurological lesions (e.g. rubella and in
untreated or uncontrolled phenyl ketonuria). EEG
abnormalities are common, although no EEG findings are
specific to autism. Approximately 40% of children with
infantile autism have IQ scores below 50-55. Some autistic
children however, demonstrate precocious talents (e.g. in
cognitive and visuo-motor abilities). Examples include ‘idiots
savants’, individuals who have exceptional memory, artistic,
musical or calculating abilities. Some previous studies have
reported working memory deficits in autism, but findings have
been inconsistent. Steele et al. (2007) claimed that deficits in
this domain are present only when working memory load
exceeds some limited capacity.
A major current theory proposes that autistic children lack a

‘theory of mind’ (i.e. the ability to see the world from the
perspective of another). This is commonly assessed using tests
such as the ‘Sally-Anne problem’, where two dolls, Sally and
Anne, act out a scene: Sally puts a marble in a basket before
leaving the room and Anne then moves it to a box. The
question is where will Sally look for it when she returns?
Autistic children commonly respond ‘In the box’ (Frith, 1991).
Happe and Frith (1996) proposed that it is useful to consider
three main neuropsychological areas when attempting to
understand autism; mentalizing impairment, executive
dysfunction and weak central coherence (p.667) (a
characteristic of normal information-processing, the tendency
to draw together diverse information to construct higher-level
meaning in context). It is notable that in autism, weak central
Page 7 of 49
coherence can result in superior performance to healthy

controls on tasks such as the embedded figures test, where
one has to try and detect a target hidden in a complex
background.
In a recent review, Tonn and Obrzut (2005) concluded that

there is overwhelming evidence that individuals with autism
have neuropsychological impairments across a number of
domains. They conclude that while central coherence,
executive function and theory of mind hypotheses are helpful
in conceptualising the disorder, it is unlikely that any of them
represent ‘mutually exclusive’ abnormalities. Baron-Cohen
(2005) has recently proposed a provocative “extreme male
brain” theory to explain autistic behaviour. An important
assumption of the model is that all individuals fall on a
continuum as regards male and female brain types. His model
proposes that autism (and Asperger Syndrome) represents an
extreme form of the male brain. Further work is needed to test
this model. The interested reader is also referred to a recent
special issue of the Quarterly Journal of Experimental
Psychology, Vol. 61, January 2008, entitled “Neurocognitive
approaches to developmental disorders: a Festschrift for Uta
Frith.
5 Bulimia nervosa
Bulimia nervosa is characterised by recurrent episodes of
binge eating associated with a lack of control over eating
during the binge episode. The binge is usually followed by
recurrent eliminatory behaviours aimed at preventing weight
gain (e.g. vomiting and laxative abuse). The binge eating and
eliminatory behaviours occur, on average, at least twice a
week for three months. As in anorexia nervosa, bulimia is
much more common in women than in men. Bingeing tends to
precede vomiting by about one year in the development of the
disorder. Sticking fingers down the throat commonly produces
vomiting, though some bulimic patients can vomit at will.
Vomiting acts to decrease the abdominal pain and feeling of
being bloated. Depressed mood often follows the episode and
has been called “post binge anguish”.

Attempts have been made in the past to associate cycles of
bingeing and purging with various neurotransmitter
abnormalities. Treatment with antidepressants, particularly
Page 8 of 49
selective serotonin re-uptake inhibitors have achieved some

success, leading to the hypothesis that serotonin is implicated
in the aetiology of the disorder. Marked impulsivity, problem-
solving and decision making deficits are commonly observed in
patients with bulimia (Ferraro et al. 1997). Brand et al. (2007)
reported that, in bulimic patients, decision making
abnormalities and executive reductions can be demonstrated
and may represent neuropsychological correlates of the
patent’s dysfunctional everyday life decision making
behaviour. They proposed that these neurocognitive functions
must be (p.668) taken into consideration in the treatment of
bulimia nervosa. A recent systematic review and meta-analysis
of neuropsychological studies in eating disorders is provided
by Roberts et al. (2007), who identified set shifting as a
common problem in eating disorders.
6 Capgras Syndrome
The Capgras syndrome involves the belief that impostors have
replaced people who the sufferer is emotionally close to (e.g.
loved ones or relative). It is believed that the impostors have
assumed the roles of the persons they impersonate and behave
like them. Some patients who suffer from Capgras syndrome
may threaten, harm or even kill the supposed impostor.
Page 9 of 49

Up to 40% of cases are associated with organic disorders, e.g.
head injury and dementia. Right cerebral hemisphere
dysfunction has also frequently been reported in patients
suffering from Capgras syndrome. Ellis and Young (1990)
presented a cognitive account of Capgras syndrome. They
proposed two distinct routes to facial recognition, one for the
actual identification of the face, and the other to give it
emotional significance. They proposed that prosopagnosia
results from a disruption of the first route, whereas Capgras
syndrome is “a mirror image” of prosopagnosia. Thus, Ellis
and Young (1990) propose that Capgras patients have an
intact primary route to face recognition but have a
disconnection or damage within the route that gives the face
its emotional significance. Ellis et al. (1997) demonstrated that
people with the Capgras delusion fail to show autonomic
discrimination between familiar and unfamiliar faces. Their
model proposes that to the person with Capgras syndrome, the
impostor’s face looks identical but the emotional feelings
associated with their face are abnormal. Put another way, they
receive a veridical image of the person they are looking at,
which stimulates the appropriate semantic data about the
person, but the patient lacks another set of confirmatory
information which may carry the appropriate affective tone for
a loved one. The patient then adopts a rationalisation strategy
(i.e. the person looks the same but somehow does not feel the
same, and therefore the person must be an impostor). The
Capgras patient mistakes a change in themselves, for a change
in others (i.e. ‘they must be impostors’). This area is well
reviewed by Ellis and Lewis (2001).
Coltheart (2007) proposes a general two deficit cognitive-

neuropsychiatric account of delusional belief that attempts to
account for delusions such as Capgras, Fregoli, Cotard etc. He
proposes that (a) the patient has a neuropsychological deficit
of a kind that could plausibly be related to the content of a
patient’s delusion, that is a deficit that could plausibly be
viewed as having prompted the initial thought that turned into
a delusional belief and (b) the patient has right-hemisphere
damage (i.e. damage to the putative belief evaluation system
located in that hemisphere). He concludes that further studies
should focus on the right hemisphere (particularly right frontal
Page 10 of 49
lobe) for the brain circuits underlying the fixation and

mutation of human beliefs (Coltheart, 2007).
(p.669) 7 Conversion disorder (hysteria)

Hysteria was described by the ancient Greeks to account for a
condition where physical and mental symptoms occurred in
the absence of the organic pathology which was thought to
cause the clinical features. Hysteria has been largely replaced
by the terms conversion and dissociative disorders, which
distinguish conditions with physical and mental symptoms
respectively. Freud proposed that hysteria was caused by
emotionally charged ideas that have become lodged in the
unconscious of the patient. Classic examples include paralysis
of the arm or ‘glove anaesthesia’ in the absence of organic
pathology to account for the paralysis or anaesthesia.
Diagnostic features include: (a) symptoms that suggest a
neurological or medical condition, (b) psychological features
are judged to be associated with the symptom, (c) the
symptom is not intentionally produced or feigned, (d) the
symptom or deficit cannot be fully explained by a medical
condition, (e) the symptom or deficit causes clinically
significant distress or impairment, and (f) the symptom is not
limited to pain or sexual dysfunction.
Classically, these disorders are said to produce secondary gain

(e.g. arm paralysis leading to the sufferer not having to go to
work). In addition, patients are said to display ‘la belle
indifference’ (i.e. that the patients show less distress than
would be expected of someone with these symptoms). It is
often difficult to distinguish between hysteria and malingering.

It is important to note that diagnostic criteria for conversion
disorder state that the symptom or deficit, after appropriate
investigation, cannot be fully explained by a general medical
condition. However, in a significant study Slater and Glithero
(1965) followed up a series of patients who had been referred
to a neurological hospital after having been diagnosed as
having hysteria. Approximately one third of those patients
developed a definite organic illness within 10 years of the
original diagnosis and a further third developed depression or
schizophrenia. This study has proved very influential, leading
to the fear that the diagnosis of hysteria was a fertile source of
Page 11 of 49
clinical error, with significant neurological or psychiatric

disease often being missed.
However, Crimlisk et al. (1998) followed up 64 patients who

had medically unexplained motor symptoms for 6 years. Only
three patients were subsequently diagnosed with a
neurological disorder that could explain their initial
presentation, leading to the conclusion that following up to
date thorough evaluation, the chance of a missing a
neurological condition that could account for the initial
complaint is small.
It has also been proposed that conversion disorders have a

neuropsychological basis in that it is possible that excess
cortical arousal results in inhibition of afferent sensory motor
impulses, thus diminishing the awareness of bodily sensations
that in some conversion disorders could explain the observed
sensory deficits (e.g. glove anaesthesia). Spence (1999)
proposed an interesting avenue to pursue in the study of
hysterical paralysis, using functional neuroimaging to test the
extent that the pathophysiology of hysteria resembles (p.670)
either (a) the normal functional anatomy of willed action
(exercising an intent to deceive) or (b) a failure of the will
(through a demonstrable dysfunction of ‘higher’ centres).
Recent work in this area is reviewed by Vuilleumier (2005),

who concludes that the data do not support previous proposals
that hysteria might involve an exclusion of sensorimotor
representations from awareness through attentional
processes. Rather, the data seem to point to a modulation of
such representations by primary affective or stress related
factors. Vuilleumier (2005) proposes that this may involve
primitive reflexive mechanisms of protection and alertness
that are partly independent of conscious control, and mediated
by dynamic modulatory interactions between limbic and
sensorimotor networks. A useful overview of anatomical/
neuropsychological mechanisms in hysteria is provided by
Halligan et al. (2001).
8 Cotard syndrome
Cotard syndrome is essentially the delusion of nihilism. This
condition was described by the 19th Century French
psychiatrist, Jules Cotard who gave an account of several
patients who suffered from a syndrome he referred to as
Page 12 of 49
‘délire de négation’. Patients exhibiting this syndrome may

complain of having lost possessions, status and strength, and
also internal organs such as the heart and lungs. Patients may
not only claim that they are dead, but that corpses have
replaced their bodies. They may state that they have no
feelings, and it is important to note that many are severely
depressed.

Non-specific neurological lesions have been reported in many
patients with Cotard’s syndrome (e.g. neoplastic, vascular, and
encephalopathic lesions). Young and Leafhead (1996)
proposed a right hemisphere dysfunction, as evidenced by the
observation of face processing impairments in patients with
Cotard delusions. In this model, the delusion of being dead is
viewed as a misinterpretation of abnormal perceptual
experiences in which things seem strange and unfamiliar.
There is a lack of emotional responsiveness, together with
feelings of emptiness and derealisation. The depressed mood
of the patient leads them to exaggerate the negative effects of
the perceptual changes while correctly attributing the changes
to themselves. In sum, this model proposes that the Cotard
delusion represents a depressed person’s attempt to account
for abnormal perceptual experience.
Recent experimental support for this model is provided by

McKay and Cipolotti (2007). Berrios and Luque (1995) have
suggested that it is useful to distinguish between patients
presenting with Cotard’s syndrome in the presence or absence
of clinical depression, arguing that the former may be best
understood in terms of affective disorder, the latter in terms of
delusional disorder. Kudlur et al. (2007), provide an overview
of the neurological correlates of Cotard syndrome. In a review
of over 100 papers on the Cotard syndrome, they report that
the most commonly reported neurological abnormalities in
these patients include structural brain changes (bilateral
cerebral atrophy, dilated lateral ventricles), funcional brain
changes (p.671) (hypoperfusion in the frontal and parietal
cortices) and neuropsychological abnormalities, (particularly
impaired face recognition). They conclude that, from a clinical
perspective, it is important to maintain a low threshold for
suspicion for neurological cause in cases of Cotard’s and to
therefore consider appropriate neurological investigations. A
Page 13 of 49
recent review of Cotard’s delusion is provided by Edelstyn and

Oyebode (2006).
9 De Clerambault’s syndrome
De Clerambault’s syndrome is one of erotomania. It is
currently classified in DSM-IV as a delusional disorder of the
erotomanic type. It is exceedingly rare and more commonly a
disorder of women. The subject, usually a single woman,
believes that a ‘higher status’ person is in love with her. The
target is usually inaccessible as he may be married, or be a
famous personality or public figure. The sufferer is convinced
that the object of her affection cannot be a happy or complete
person without her. People suffering from this syndrome can
become extremely difficult for the target of the affection to
deal with, and in many cases, police and court involvement
may be required in order to protect the target from the
sufferer. A proportion of ‘stalkers’ who threaten celebrities
suffer from delusional erotomania (Kamphuis and
Emmelkamp, 2000). Many patients suffering from De
Clerambault syndrome also suffer from paranoid
schizophrenia (Litman, 2004), and it has been suggested that
the syndrome may not exist as a separate nosological entity,
but rather is a variant of schizophrenia or affective disorder
(Ellis and Mellsop, 1985).

Little is known about neurological or neuropsychological
abnormalities in this condition, although the emergence of
erotomania has been reported following brain injury. As stated
above, the syndrome often presents in the context of
schizophrenia, with associated impairments in memory and
executive functioning. Kopelman et al. (1995) utilised the case-
study approach, and tested the hypothesis that executive
dysfunction may underlie delusional memories in erotomania.
However, they found executive functioning to be intact, but
reported an impairment in retrograde memory for the period
around the onset of the patient’s psychosis. Kopelman et al.
(1995) propose that delusional memories may result from
slippage in the relationship between memory schemata,
leading to a predisposition to interpret the world in particular
ways, contingent upon underlying affective or cognitive
factors.
10 Depression
Page 14 of 49

Depression has been recorded since ancient times. Episodes of
major depression are characterised by a period of at last two
weeks, which represents a change from previous functioning
associated with either depressed mood or loss of interest or
pleasure.
(p.672) DSM-IV criteria for a major depressive episode

requires five out of the following nine features:
1. Depressed mood most of the day, nearly every day.

2. Markedly diminished interest or pleasure in
activities.
3. Significant weight loss or weight gain.
4. Insomnia or hypersomnia nearly every day.
5. Psychomotor agitation and retardation nearly every
day.
6. Fatigue or loss of energy nearly every day.
7. Feelings of worthlessness or excessive or
inappropriate guilt.
8. Diminished ability to think or concentrate or
indecisiveness nearly every day.
9. Recurrent thoughts of death.
Importantly, in addition, the symptoms must not meet criteria

for a Mixed Episode, they must cause clinically significant
distress and/or impairment, are not attributable to a medical
condition or drug effects and the symptoms are not better
accounted for by bereavement.
Unipolar depression (i.e. depression with no episodes of

mania) is among the most common of psychiatric disorders of
adults. In many countries surveyed, at any given moment one
person in twenty is significantly depressed, with a life-time
prevalence rate of approximately 15%, (twice as prevalent in
women as in men). There appears to be a genetic loading for
depression in that children of severely depressed patients
have a morbid risk of 20% for mood disorder as against about
7% in the relatives of controls. Major depression can be a fatal
disorder, approximately two thirds of depressed patients
contemplate suicide and 10–15% go on to commit suicide. An
excellent overview of depression is provided by Hammen and
Watkins (2007).
Page 15 of 49
Noradrenaline and serotonin abnormalities have been

implicated in the pathophysiology of depression. In addition,
abnormalities of the limbic hypothalamic pituitary adrenal axis
have been the most consistent reported neuroendocrine
abnormalities. The dexamethasone suppression test (DST) has
been extensively researched in depression. Dexamethasone is
a steroid that suppresses the blood level of cortisol and the
DST is abnormal in approximately half the depressed patients.
However, the DST has been shown not to be specific for
depression and may be abnormal in patients with other
disorders such as OCD, eating disorders etc. Brain imaging
studies have used CT, MRI and PET to investigate possible
brain abnormalities in major depression. The results of these
studies have not been consistent. However, several have
reported decreased blood flow and metabolism in the dorso-
lateral prefrontal cortex, the cingulate cortex and in some
cases, the basal ganglia. A recent consensus paper on
biological markers in depression concluded that no biological
markers for major depression are currently available for
inclusion in the next set of diagnostic criteria, namely DSM-V
and ICD-11 (Moner et al. 2007).
(p.673) Neuropsychological studies have consistently found

psychomotor slowing and impairments in memory and
executive functioning (Veiel, 1997). Many studies using
affectively-toned stimuli have shown that depressed patients
have a memory bias towards negative material, which is
thought to help maintain or exacerbate the depressed mood
(e.g. Ridout et al. 2003).
In bipolar disorder (episodes of depression and mania), the

evidence suggests that while neuropsychological functioning is
clearly impaired during illness episodes, some residual
impairments can be observed in the euthymic state (Ferrier et
al. 1999). In a recent meta-analysis of neuropsychological
functioning in euthymic bipolar disorder, medium to large
performance effect size differences were consistently observed
between patients and controls, particularly in the domains of
attention/processing speed, episodic memory and executive
functioning (Torres et al. 2007). There is therefore evidence of
a trait related neuropsychological deficit in bipolar disorder.
A more severe course of illness and a greater number of illness

episodes are often associated with more impaired
neuropsychological functioning, suggesting that repeated
Page 16 of 49
manic episodes may be neurotoxic. The pathophysiological

mechanisms are not fully understood, though
hypercortisolaemia may be implicated and may result in
impaired neuropsychological functioning (McAllister-Williams
et al. 1998). Relatively few neuropsychological studies have
been conducted on manic patients. Preliminary work suggests
that both manic and depressed patients are impaired on tests
of memory and planning, but differences have been noted in
attentional shifting, with manic patients having difficulty with
inhibition of behavioural response and attentional focus, with
depressed patients impaired in their ability to shift the focus of
their attentional bias (Murphy et al. 1999). The same authors
confirmed the affective bias for negative material in
depression, but also demonstrated the opposite affective bias
for positive stimuli in mania.
Taylor Tavares et al. (2007) reported a comparison of

unmedicated, depressed patients with major depressive
disorder and bipolar depression. Both groups were depressed
at the time of assessment. The major depression group were
impaired on tests of spatial working memory and attentional
shifting and were over-sensitive to loss trials on a decision
making task, and these deficits were not attributable to
current medication status. In contrast, the bipolar depressed
group were generally cognitively intact and did not differ
significantly from control subjects on the test. Steele et al.
(2007) also found a blunted response to feedback information
in depression. Stoddart et al. (2007) recently claim to have
described a dissociation between unipolar and bipolar
affective illness. They reported that bipolar individuals
demonstrate a specific executive deficit that is independent of
attention impairment on the Hayling Sentence Completion
Test (HSCT).
11 Dissociative Fugue (formally Psychogenic Fugue)

Fugue state is one of the dissociative disorders. DSM-IV
diagnostic criteria include:
1. The predominant disturbance is sudden, unexpected

travel away from home or one’s customary place of
work, with an inability to recall one’s past.
(p.674)
Page 17 of 49
2. Confusion about personal identity or assumption of a

new identity (partial or complete).
3. The disturbance does not occur exclusively during
the course of dissociative identity disorder and is not
due to the direct physiological affects of a substance
(e.g. drug of abuse) or a general medical condition (e.g.
temporal lobe epilepsy).
4. The symptoms cause:
— clinically significant distress
— impairment in social, occupational or
other important areas of functioning.
Dissociative Fugue can be mistaken for Malingering, because

both conditions occur under circumstances that a person
might understandably wish to evade. Critically however,
Dissociative Fugue occurs spontaneously and is not faked
whereas in Malingering the person feigns illness because it
removes them from accountability for their actions. The focus
of treatment is helping the person restore lost memories as
soon as possible.
Page 18 of 49
11.2 Neuropsychological Features

Fugue state seems to appear more often in Hollywood movies
than in the scientific literature, however there are a number of
notable case-studies where neuropsychological examination
has attempted to explain the mechanisms underlying fugue
state. Kapur (1991) reported the case of an individual who had
memory loss for five days during which he wandered
extensively. However, he did not have selective amnesia for the
public events which had occurred during the five days for
which he claimed memory loss. Kapur (1991) argued that this
finding was incompatible with the case having a neurologically
based global memory disorder during the fugue state and that
this data supports a distinction between personal and public
episodic memory. In a later paper, Kapur (1996) argued that
most cases of functional retrograde amnesia may represent a
combination of conscious simulation and unconscious
processes.
Kopelman et al. (1994) reported the case-study of a patient

who experienced a seven day fugue episode. The patient was
assessed soon after admission to hospital and at regular
intervals thereafter. Intervention with a sodium amytal
abreaction produced substantial recovery of memory.
Kopelman et al. (1994) proposed a hierarchical model of
awareness in memory suggesting that patients with
psychogenic amnesia manifest different levels of awareness
for differing memories.
Glisky et al. (2004), described a case study of psychogenic

fugue where the individual lost access, not only to his
autobiographical memories, but also to his native German
language. A series of laboratory tasks were conducted and led
to the conclusion that the individual suffered an episode of
psychogenic fugue during which he lost explicit knowledge of
his personal past and his native language. However, at the
same time, he appeared to retain implicit knowledge of
autobiographical facts and semantic or associative structure of
the German language. Stracciari et al. (2005) proposed that, in
Fugue state, the episodes appear as examples of ‘functional’
memory inhibition, possibly triggered by (p.675) different
conditions, including psychological trauma. The memory
profile in fugue state may therefore be explained by a lost
access to abstract autobiographical knowledge.
Page 19 of 49
A useful recent review of the dissociative disorders including

fugue states is provided Kihlstrom (2005), who concludes that
while these disorders have been attributed to trauma and
other psychological stress, the existing evidence favouring this
hypothesis is plagued by poor methodology. Prospective
studies of traumatized individuals reveal no convincing cases
of genuine amnesia that could not be attributed to brain insult,
injury, or disease.
12 Factitious Disorder
Factitious disorder is a condition where the person acts as if
he or she has an illness by deliberately feigning or
exaggerating symptoms. The DSM-IV essential diagnostic
criteria are:
1. Intentional production or feigning of physical or

psychological signs or symptoms.
2. The motivation for the behaviour is to assume the
sick role.
3. External incentives for the behaviour (such as
economic gain, avoiding legal responsibility or
improved physical wellbeing (as in malingering) are
absent.
Factitious disorder differs from malingering in that the

motivation for the symptom production in malingering is an
external incentive, whereas in factitious disorder, external
incentives are absent. Evidence of an internal need to
maintain the sick role suggests Factitious disorder. Motivation
for the behaviour in factitious disorder must be to assume the
‘sick role’ and the individual does not ‘act sick’ for personal
gain, as in the case of malingering. When the individual
applies the pretended sickness to a dependent (e.g. a child)
this is referred to as ‘Factitious disorder by proxy’.
Munchausen syndrome is a Factitious disorder (see separate
entry for Munchausen syndrome).

As with Munchausen syndrome, Factitious disorders are poorly
understood with no consistent neuropsychological features or
widely accepted explanatory neuropsychological models.
13 Frégoli delusion
Page 20 of 49
The essence of the Frégoli delusion is that the patient believes

that other people are able to disguise themselves to look like
anyone they wish in order to achieve some influence - usually,
a sinister one. The patient will identify a familiar person
(usually someone who is believed to be his or her persecutor),
and insist that this person takes the form of a variety of others
he or she comes into contact with. The patient will maintain
that although there is no physical resemblance between the
familiar person and the others, nevertheless they are the same
person. The syndrome is often associated with schizophrenia.
(p.676) 13.2 Neuropsychological features

Neurological abnormalities are common in Frégoli delusion
(e.g. brain atrophy is often reported (Joseph and O’Leary
1987)). However, transient forms of the delusion have also
been described (e.g. following toxic psychoses induced by
cannabis). Ellis and Young (1990) offered a cognitive
neuropsychiatric explanation for the Frégoli delusion. They
employed an information processing model of face recognition
which deconstructs into three essential stages:(a) an initial
structural encoding (b) the excitation of units sensitive to the
unique characteristic of each known phase and (c) the link to
other multi-modal nodes that access biographical/episodic
information about people.
Ellis and Young (1990) proposed that it is a malfunction in

stage (c) that results in the Frégoli delusion. This area is well
reviewed by Ellis (2004).
14 Ganser’s syndrome
This syndrome was first reported by Ganser in 1898, in which
three prisoners showed an unusual clinical picture. The
condition has four main features: (a) giving approximate
answers; (b) psychogenic physical symptoms; (c)
hallucinations; and (d) apparent clouding of consciousness.
The term ‘approximate answers’ indicates that although the

answer is plainly wrong, it is clearly related to the correct
answer in a way which suggests that the correct response is
known (e.g. when asked to multiply four times four, the patient
answers ‘seventeen’). A distinction has been made between
the Ganser symptom (approximate answers) and the Ganser
syndrome, with the symptom common and the syndrome
extremely rare. Ganser’s syndrome has variously been
Page 21 of 49
regarded as akin to hysterical conversion reactions,

malingering, organic confusion and psychotic thought
disorder. Ganser’s syndrome is often thought to represent the
voluntary production of psychiatric symptoms (e.g. in an
attempt to avoid imprisonment, and in fact, has been termed
‘prison psychosis’). It may be difficult to distinguish whether
the condition is genuine or whether the patient is malingering.
However, it should be noted that a number of cases have been
reported following head injury, indeed of Ganser’s original
three cases, two had suffered head injury and the third was
recovering from typhus fever (Lishman 1998). The syndrome
may also occur in people with other disorders such as
schizophrenia and depression.

Ganser’s syndrome is a poorly understood phenomenon.
Originally, Ganser proposed that the condition represented an
unusual hysterical confusional state.
Merckelbach et al. (2006) described a case study of detecting

malingering in an individual who presented with Ganser-like
symptoms. The middle aged man had been involved in a car
crash and was seeking disability insurance benefits.
Malingering tests (p.677) revealed that he performed below
chance on simple memory tests. The authors then collected
collateral information which showed the patient was involved
in high level sports activities that were difficult to reconcile
with the severe cognitive impairment that he claimed to suffer
from. The authors conclude that their case highlights that
Ganser like symptoms deserve close scrutiny, preferably with
tests of malingering.
There are no clear and consistent neuropsychological features

that provide an adequate explanation for this disorder. As
Lishman (1998) concluded, exactly one hundred years after
the syndrome was first described, “Uncertainty surrounds its
nosological status and the mechanisms behind its
appearance” (p.480).
15 Kluver-Bucy Syndrome
Kluver-Bucy syndrome is a behavioural disorder that occurs
following damage to right and left medial temporal lobes of
the brain. The amygdala has been particularly implicated in
the pathogenesis of this syndrome. This syndrome is a rare
Page 22 of 49
neurological disorder that causes individuals to engage in a

number of inappropriate behaviours (e.g. putting objects in
their mouth and engaging in inappropriate sexual behaviour).
Other symptoms can include visual agnosia, loss or normal
fear and anger responses, memory loss, distractibility, seizures
and dementia. The syndrome is named after Kluver and Bucy,
who removed the temporal lobe bi-laterally in a Rhesus
monkey in an attempt to determine its function. The operated
monkey developed marked problems including emotional
changes, altered sexual behaviour, visual agnosia and oral
tendencies. It became notably less fearful of things that would
have previously caused marked anxiety (e.g. humans or
snakes).

There is a relatively limited neuropsychological literature on
the Kluver-Bucy syndrome. In a historical review of the Kluver-
Bucy syndrome, Nahm (1997) proposed that Kluver’s work
helped to unify both neuropsychological and neuroanotomical
theories regarding the visual and emotive functions of the non-
human primate temporal lobe. Approximately 20% of
individuals presenting with neuropsychiatric features,
characteristic of frontal temporal dementia, went on to
develop the Kluver-Bucy syndrome on two year follow-up
(Mendez and Perryman 2002). Pestana and Gupta (2007)
recently described an interesting case of an 11 year old boy
with epilepsy who has fluctuating Kluver-Bucy symptoms. He
had three or four daily complex partial seizures over two to
three days per month followed by a seizure free interval of
approximately three to four weeks. During the seizure free
period, he exhibited marked hyper orality, sniffing, irritability,
unsolicited sexual gestures etc. The Kluver-Bucy features
escalated up to the onset of the seizure cluster and then
remitted after the seizures. The authors claim this is the first
reported case of Kluver-Bucy syndrome due to congenital bi-
temporal malformations.
(p.678) 16 Malingering
According to DSM-IV, the essential feature of Malingering is
the intentional production of false or grossly exaggerated
physical or psychological symptoms, motivated by external
incentives such as avoiding military duty, avoiding work,
obtaining financial compensation, evading criminal
Page 23 of 49
prosecution or obtaining drugs. Malingering should be

strongly suspected in the following situations:
1. Medical legal context of presentation.

2. Marked discrepancy between the person’s claimed
stress or disability and objective findings.
3. Lack of co-operation during diagnostic evaluation
and in complying with prescribed treatment.
4. The presence of anti-social personality disorder.
As stated previously, Malingering differs from Factitious

disorder in that the motivation for the symptom production in
Malingering is an external incentive. Malingering differs also
from Conversion disorder, and other somatoform disorders, by
the intentional production of symptoms and the obvious
external incentives associated with it.

There is a vast literature on attempts to detect Malingering
using neuropsychological measures and a detailed review of
this area is clearly beyond the scope of this brief section. Many
authorities now propose that it is good practice to include both
a measure of mood and a measure of malingering in all
medico-legal neuropsychological assessments (e.g. The
National Academy of Neuropsychology Policy and Planning
Committee recently proposed that “the assessment of
response validity as a component of medically necessary
evaluation is medically necessary” (Bush et al. 2005)).
Currently, the Test of Memory Malingering (TOMM) appears to

be the most frequently used symptom validity test and appears
to be relatively robust. The TOMM is a very simple forced
choice visual recognition memory test where even patients
with significant cognitive impairment perform well. A low
score therefore is suspicious. Both clinical participants and
community dwelling adults have been shown to achieve
exceptionally high scores.
TOMM scores do not appear to be significantly influenced by

self reported symptoms of depression and anxiety (Rees et al.
2001; O’Bryant et al. 2007). Similarly, Iverson et al. (2007)
reported that TOMM scores were not affected by chronic pain
or depression. A very useful overview of Malingering in
Page 24 of 49
relation to illness deception is provided by Halligan et al.

(2003).
(p.679) 17 Munchhausen’s syndrome

Munchhausen’s syndrome is a factitious disorder (i.e. a
condition characterised by physical or psychological symptoms
that are intentionally produced or feigned). Physical or mental
illness is simulated with the objective of assuming the ‘sick
role’ of a patient. Essential features include intentional
production of symptoms, the motivation for the behaviour to
assume a sick role and external incentives for the behaviour
such as financial gain. Munchhausen patients are often
admitted to hospital with an apparently serious and acute
illness that is often supported by a plausible or dramatic
history. However, the history is not true and the patient is
often found to have attended hospital and deceived doctors on
many previous occasions. Discharge often occurs after hospital
staff confront the patient with evidence regarding similar
fraudulent presentations. The condition is most often seen in
young men. Patients are often resistant to contact with
psychologists or psychiatrists and treatment is often refused.
Munchhausen syndrome by proxy describes a condition where
parents give a false history to explain their child’s signs and
symptoms (e.g. history suggestive of appendicitis, when in
reality, the parent has been poisoning the child). This is clearly
child abuse.

Munchhausen is a poorly understood phenomenon, with no
consistent neuropsychological features or widely accepted
explanatory neuropsychological models.
18 Obsessive Compulsive Disorder (OCD)

Obsessive/Compulsive Disorder (OCD) is characterised by the
presence of obsessions or compulsions. Obsessions are
persistent and recurrent thoughts and impulses that cause
anxiety and distress that the person tries to suppress,
neutralise or ignore and that the person recognises as being
the product of his or her own mind. Compulsions are repetitive
behaviours or mental acts that the person feels driven to
perform, and the behaviour or mental acts are aimed at
preventing or reducing distress, or preventing a dreaded event
or situation. Common examples include obsessional cleaning
Page 25 of 49
and checking. However, the compulsive behaviours or acts are

not connected in a realistic way with what they are designed
to neutralise or prevent (e.g. removing all hairs from clothing
and carpets in the house in order to prevent a loved one dying
in a road traffic accident). The obsessions or compulsions are
recognised by the individual as being unreasonable and
frequently cause marked distress. While OCD is classified as
an anxiety disorder, obsessional patients are often depressed.
Page 26 of 49
(p.680) 18.2 Neuropsychological features

Brain imaging findings have suggested that abnormalities in
the orbito-frontal cortex and caudate nucleus may be common
in OCD (Insel and Winslow, 1992). Cognitive abnormalities
often include executive, non-verbal and praxic deficits in OCD,
consistent with theories of fronto-striatal functioning which
may represent the cognitive substrate of doubt-related
phenomena such as checking (Tallis et al. 1999).
OCD is a heterogeneous condition. Lawrence et al. (2006)

showed that OCD patients with prominent hoarding symptoms
showed impaired decision making as well as reduced skin
conductance responses. Symmetry/ordering symptoms were
negatively associated with set shifting. Lawrence et al. (2006)
claim that this result helps explain previously inconsistent
neuropsychological research on OCD and that dissociable
neural mechanisms are involved in mediating the different
OCD symptom dimensions. On a related theme, Mataix-Cols et
al. (2004) reported distinct fMRI correlates of washing,
checking, and hoarding symptom dimensions in obsessive-
compulsive disorder. They concluded that that different
obsessive-compulsive symptom dimensions are mediated by
relatively distinct components of fronto-striato-thalamic
circuits implicated in cognitive and emotion processing. OCD
may therefore better be conceptualized as a spectrum of
multiple, potentially overlapping syndromes rather than a
unitary diagnostic category.
Menzies et al. (2007) studied neurocognitive endophenotypes

of OCD. They assessed OCD patients, unaffected first degree
relatives and matched controls. Interestingly both patients and
relatives had delayed response inhibition on a stop-signal task
compared to healthy controls. They then used magnetic
resonance imaging and identified that behavioural impairment
on the stop-signal task was significantly associated with the
reduced grey matter in orbitofrontal and right inferior frontal
regions, and increased grey matter in cingulate, parietal and
striatal regions. A structural variation in large scale brain
systems related to motor inhibitory control may thus mediate
the genetic risk for OCD.
In a recent selective review of memory and executive

functioning in obsessive compulsive disorder, Olley et al.
(2007) concluded that the neuropsychological profile of OCD
appeared to be primarily one of executive dysfunction. While
Page 27 of 49
memory function is often compromised, they argue that these

memory deficits are secondary to a primary executive failure
of organisational strategies during encoding. They also note
that, given the prominence of chronic doubt and indecision in
clinical settings, it is surprising that decision making as
related to OCD has not received greater attention in the
neuropsychological literature.
19 Othello syndrome
The Othello syndrome is one of delusional jealousy where the
person is convinced (without due cause) that his or her spouse
or partner is unfaithful. Pathological jealousy is not an
uncommon presentation in psychiatric practice, and is more
common in men than in women and in some cases, the
individual may be highly dangerous. The syndrome often (p.
681) is associated, or may be part of other conditions such as
paranoid schizophrenia, depression or alcoholism.

Organic disorders (e.g. head injury) have been suggested as
being present in up to 20% of such cases, often involving right
hemisphere damage. In addition, drug abuse (e.g.
amphetamine and cocaine) can often precipitate delusional
jealousy, as can a wide range of brain disorders, including
metabolic and endocrine disorders, degenerative conditions
e.g., dementia, infections and neoplasms.
Malloy and Richardson (1994), in a review of the frontal lobes

and content specific delusions, concluded that a high
proportion of such delusions have a neurological basis and the
lesions of the frontal lobes and right hemisphere are often
critical to the development and persistence of many content
specific delusions. We await convincing and testable
neuropsychological models of delusional jealousy.
20 Post-traumatic Stress Disorder (PTSD)
Page 28 of 49

PTSD is a condition where exposure to an intense frightening
emotional experience leads to lasting changes in behaviour,
affect and cognition. Typically after a life threatening incident
(e.g. a violent assault, rape or wartime experience), the
individual displays re-experiencing of the event(s) (e.g. via
intrusive, distressing thoughts, images, ‘flashbacks’ or
nightmares). The individual may exhibit phobic avoidance and/
or physiological reactivity to reminders of the trauma.
Increased arousal in terms of sleep disturbance, irritability,
and exaggerated startle response are common. In addition, the
individual may exhibit a restricted range of affect, sense of a
foreshortened future, and may lose interest in previously
rewarding hobbies or activities.

As stated above, PTSD is characterised by intrusive distressing
memories of the traumatic event. Paradoxically, it is also often
associated with marked impairments in learning and memory
for new material. Patients often complain that they remember
what they do not want to, yet cannot remember what they now
wish to. Heightened arousal at the time of encoding may result
in modulation (strengthening) of the memory trace, possibly
via noradrenaline release in the amygdala (Cahill 2000).
Subsequent anterograde memory impairment may be due to
the deleterious effects of stress hormones (e.g. long term
hypercortisolaemia) on hippocampal function. Several MRI
studies have now shown that PTSD is associated with
reduction in volume of the hippocampus, a brain area critically
involved in new learning and memory (Bremner 1999).
However, this finding was not replicated in Nazi holocaust
survivors who had PTSD (Golier et al. 2005).
Brewin et al. (1996) developed a dual representation theory of

PTSD. They propose that two memory systems are implicated
in the disorder, one that is verbally accessible (p.682) and
one that is automatically accessed via situational cues. They
also propose that clinical features may correspond to chronic
or premature inhibition of emotional processing of trauma.
Recent neuropsychological studies have suggested that some
of the differences in cognitive performance observed between
PTSD patients and controls may reflect pre-existing individual
differences (Crowell et al. 2002). The neuropsychology of
Page 29 of 49
PTSD has been well reviewed recently in a book edited by

Vasterling and Brewin (2005).
21 Reduplicative paramnesia
Reduplicative paramnesia is a clinical condition where a
patient states that there are two or more places with almost
identical attributes, although only one exists in reality. Luzzatti
and Verga (1996) describe the clinical presentation of several
patients presenting with reduplicative paramnesia. For
example, a man who had suffered a head injury, stated that he
was in Grimsby, when in fact he was in hospital outside
Edinburgh and accounted for this state of affairs by saying “I
call it Grimsby, you call it Scotland”.

The majority of cases described in the literature suffer from a
bilateral frontal lesion associated with lesions in other brain
areas. The condition has been proposed as being an
orientation problem, a memory problem, a perceptual problem
or a mixture of all three. Luzzatti and Verga (1996) proposed
that the disorder might be considered as an adaptive rather
than a reduplicative phenomenon. In particular, they suggest a
difficulty in integrating the actual perceived reality with one’s
own internal belief. They propose that this is an exaggeration
of normal experience, for example waking up in a strange
room where the internal belief is compared to the information
acquired sensorially from the external world and thus the
internal belief adapts to the perceived reality. This integration
may be reduced or lost in patients with reduplicative
paramnesia and the incapacity to shift from a believed to the
perceived reality might be considered a set-shifting or
perseverative behaviour. Moser et al. (1998) proposed that
reduplicative paramnesia is secondary to temporal-limbic-
frontal dysfunction giving rise to a distorted sense of
familiarity and impaired ability to resolve the delusion via
logical reasoning. A recent case report of an elderly patient
with Alzheimer’s disease who had reduplicative paramnesia
confirmed the presence of high neurofibrillary tangle densities
in frontal and temporal association cortex (von Gunten et al.
2005).
23 Schizophrenia
Page 30 of 49
Schizophrenia has been described as perhaps the most

devastating illness known to man, because it appears in early
adolescence and can drastically impair the subsequent life of
the sufferer and his or her family. A variety of diagnostic
systems have been used over the (p.683) past 100 years,
leading to much confusion. Currently, the DSM-IV system
requires two or more of the following symptoms: delusions,
hallucinations, disorganised speech, disorganised or catatonic
behaviour or negative symptoms. These must be accompanied
by social/occupational dysfunction, continuous signs of
disturbance which persists for at least six months and also
that other disorders have been excluded. The life-time risk of
developing schizophrenia is about 1%, a figure which varies
very little around the world. There appears to be a strong
genetic component to schizophrenia. For example, if there is a
1% prevalence of schizophrenia in the general population, the
probability of developing schizophrenia in a monozygotic twin
of a schizophrenic patient is 47% versus 12% in a dizygotic
twin of a schizophrenic patient. Many of the syndromes
reviewed in this chapter (De Clerambault, Capgras, Othello
etc.) are considered by many to fall within the broad spectrum
of schizophrenia.

A key finding in schizophrenia research was the report by Eve
Johnstone and colleagues in 1976 that confirmed ventricular
enlargement in CT scans in patients with schizophrenia versus
controls (Johnstone et al. 1976). In the 1960s, there was a wide
spread view that schizophrenia was a socially created disorder
and family dynamics, and in particular the ‘schizophrenogenic
mother’ was often blamed. The finding of CT abnormalities
shifted the balance back to viewing schizophrenia as a brain/
neuropsychological disorder. However, while several studies
have found ventricular enlargement in schizophrenia, only
about 30% of patients have an increase of one standard
deviation greater than the healthy control mean. Furthermore,
MRI studies have also confirmed reductions in temporal lobe
volume (Nelson et al. 1998). Functional brain imaging studies
using PET and fMRI have tended to report decreases in frontal
lobe blood flow (hypofrontality). This is most readily
demonstrated during cognitive challenge tasks where patients
have to perform a task, such as the Wisconsin Card Sort Test,
and patients typically fail to show the same level of frontal
lobe metabolic activity as healthy controls. However, it should
Page 31 of 49
be borne in mind that the patients often have difficulty

performing the cognitive task, so the finding may tell us more
about neural substrate of the cognitive task performance
rather than schizophrenia.
Gur et al. (2007) recently reviewed brain imaging studies in

schizophrenia. They concluded that replicated findings include
reduced whole brain and hippocampal volume as potential
vulnerability markers with further progression at onset and
that these are not attributable to medication effects.
The dopamine hypothesis has been central in attempting to

explain schizophrenia, mainly supported by the fact that
virtually all effective antipsychotic drugs are dopamine
receptor antagonists, particularly D2 receptors. There are at
least two problems with the dopamine hypothesis. First,
dopamine antagonists are effective in treating virtually all
psychotic and agitated patients regardless of diagnosis (i.e.
response is not unique to schizophrenia and secondly, there is
evidence that dopaminergic neurones may, in fact, increase
their firing rate in response to chronic exposure to
antipsychotic drugs, rather (p.684) than reduce them).
Second, many patients who have been resistant to treatment
with dopamine antagonists have responded to the atypical
antipsychotics such as clozapine and resperidone which target
other neurotransmitter systems.
There is a huge neuropsychological literature on

schizophrenia. However, as stated in the introduction, this may
not have been a particularly fruitful research endeavour given
that it may be more profitable from a neuropsychological
perspective to try and explain particular signs or symptoms
(e.g. auditory hallucinations, passivity or paranoid delusions).
Neuropsychological abnormalities are, however, consistently
reported in patients diagnosed with schizophrenia. Cognitive
deficits are now being increasingly recognised as core
features of schizophrenia. These deficits are not secondary to
medication or symptoms and have a huge negative impact on
everyday functioning (Kraus and Keefe, 2007). The most
consistent findings are of impairments in learning, memory
and executive functioning (Heinrichs and Zakzanis, 1998).
Importantly, these abnormalities can be observed in patients
who are drug-free.
Page 32 of 49
The natural history of cognitive impairment in schizophrenia

has been much debated. Low intelligence and poor
educational achievement precede early onset schizophrenic
psychosis (Jones et al. 1994). These findings support the view
of schizophrenia as a neurodevelopmental disorder. Well
designed longitudinal studies have produced some conflicting
results with some supporting the notion of progressive decline
and other refuting it. Morrison et al. (2006) published a long
term follow-up study where patients with schizophrenia were
assessed 33 years after baseline assessment on admission to
hospital. At follow-up there was a significant decline in non-
verbal intelligence over time (Raven’s Progressive Matrices) in
patients with schizophrenia but this was not observed in
matched controls. No decline was observed in verbal
intelligence. Thus there appears to be convincing evidence
that some patients with a diagnosis of schizophrenia have
detectable cognitive impairments which precede illness onset,
and following development of the disorder, continued cognitive
decline occurs in some patients.
Attempts to explain schizophrenia per se in neuropsychological

terms have had limited success, possibly because of the
heterogeneity of the disorder. However, certain features (e.g.
specific delusions have been explained via recent testable
neuropsychological models; see entries for Capgras, Cotard
and Frégoli). Frith (1992) has been particularly influential in
this area, by developing a model where internal stimuli (e.g.
thoughts or intentions) are thought to be misclassified and
misattributed to an external source. For example, Frith (1992)
proposed that auditory hallucinations in schizophrenia arise
from a failure in the self-monitoring of speech processing. In
this model, hallucinations are experienced as a result of a
failure of the internal registration of the intention to generate
inner speech (i.e. the hallucinating person’s inner speech is
perceived as alien, attributable to an external source). Frith
has extended his model to account for a variety of features of
schizophrenia including thought broadcasting, insertion and
withdrawal. Frith’s model has been subjected to several
empirical tests with generally supportive results (e.g. Mlakar
et al. 1994; Stirling et al. 1998; Torres et al. 2004). A pivotal
feature of Frith’s theory is that some key features of
schizophrenia are due to an inability to monitor the beliefs and
intentions of others.
Page 33 of 49
(p.685) This is similar to the theory of mind deficit in autism,

with one key difference: “The autistic person has never known
that other people have minds. The schizophrenic knows that
other people have minds, but has lost the ability to infer the
contents of these minds: their beliefs and intentions. They may
even lose the ability to reflect on the contents of their own
mind. However, they will still have available ritual and
behavioural routines for interacting with people, which do not
require inferences about mental states.” (Frith, 1992, p.121).
Pickup and Frith (2001) reported that TOM impairments in
schizophrenia are less severe than in autism, but are specific
and not a reflection of general cognitive deficits.
In recent years there has been increasing research on

relatives of affected individuals aimed at determining if similar
cognitive deficits and brain abnormalities are also found in
those with increased genetic vulnerability to schizophrenia.
Young adult relatives who are at high genetic risk of
developing schizophrenia exhibit memory and executive
impairments (Byrne et al. 1999) together with reductions in
hippocampal/amygdala complex volume (Lawrie et al. 1999).
In general, findings suggest that deficits are apparent in
unaffected relatives and are similar to those observed in
schizophrenia (eg memory and executive impairments) but are
less marked (Whalley et al. 2007).
In a recent review, Reichenberg and Harvey (2007) concluded

that the most severe impairments in schizophrenia are
apparent in episodic memory and executive control processes,
over a background of generalised cognitive deficit. They go on
to propose that these neuropsychological impairments may
represent genetic liability to the disorder, as similar, milder
impairments are evident in schizophrenia patients even before
the onset of psychotic symptoms as well as in the non-
psychotic relative is schizophrenia patients. The cognitive
neuroimaging literature during executive function, episodic
memory and working memory tasks in schizophrenia generally
report abnormalities in frontal and medial temporal lobe
systems (Reichenberg and Harvey, 2007).
24 Somatoform disorders
Somatoform disorders share the common feature of the
presence of a physical symptom that suggests an underlying
general medical condition, but the symptom is not fully
Page 34 of 49
explained by a general medical condition, and the symptoms

cause clinically significant distress or impairment. Unlike
factitious disorders and malingering, the physical symptoms
arenot thought to be intentional. Gelder (1996) pointed out
that there are several problems with the whole concept of
somatoform disorder; (a) the lack of clear operational
definitions for the overall category and unsatisfactory
description of sub-categories, (b) some of the disorders such
as hypochondriasis are so enduring that they could be
classified as personality disorders rather than mental
disorders, and (c) many patients have clinical features which
fit the criteria for more than one diagnostic category.
Somatoform disorders include somatisation disorder
(historically referred to as hysteria or Briquette’s syndrome),
undifferentiated somatoform disorder, conversion disorder,
pain disorder, hypochondriasis, body dysmorphic disorder or
somatoform disorder not (p.686) otherwise specified. It is
important to note that patients with chronic somatoform
disorder can become grossly disabled, e.g. wheelchair bound
(Bass et al. 2001).

Some recent studies have investigated processing of emotional
material in somatoform disorder. Lim and Kim (2005) utilised
the emotional Stroop paradigm and demonstrated that
somatoform patients showed supraliminal interference for
physical threat words and showed bias for physical threat
words on an explicit memory task. This profile differentiates
them from patients with major depression, panic disorder and
healthy participants.
There is little consistent evidence regarding

neuropsychological abnormalities in the somatoform disorders
and, in fact, as indicated above, this may reflect the lack of
clear operational definitions for the overall category and the
unsatisfactory descriptions of some of the sub-categories (see
section on conversion disorder). Recent debates have focused
on whether functional somatic syndromes should be defined as
separate entities or as one overall syndrome (Moss-Morris and
Spence 2006).
25 Tourette syndrome
Page 35 of 49
Tourette syndrome involves multiple motor and one or more

vocal tics e.g. shouting profanities, and was first described by
Gilles de la Tourette in 1885. The tics can occur many times a
day and the disturbance causes marked distress or significant
impairment in social and/or occupational functioning. The
onset is before age 18 and the condition is not due to drugs or
a general medical condition such as Huntingdon’s disease. The
prevalence of Tourette syndrome is approximately 1 per 2000
and the condition has a high genetic loading with a
concordance rate of approximately 50% in monozygotic twins
versus 8% in dizygotic twins. Obsessive, compulsive symptoms
occur frequently in patients with Tourette’s syndrome.
Page 36 of 49

Visuo-motor difficulties are common in Tourette’s disorder and
abnormal, non-specific EEG findings are also common
(Robertson 1989). CT brain scan studies suggest that
approximately 10% of those with Tourette’s have non-specific
abnormality, with the cingulate gyrus and basal ganglia often
suggested as possible candidate sites for the disorder. The
central dopaminergic system is thought to malfunction in
Tourette’s as dopaminergic stimulants exacerbate the disorder
and dopamine blockers such as chlorpromazine often improve
the condition.
Attentional dysfunction may be central to the disorder as

attention difficulties and poor frustration tolerance often pre-
date the tics. Indeed, approximately 25% of people with
Tourette’s have been prescribed stimulants for a diagnosis of
attention deficit hyperactivity disorder (ADHD)before
receiving a diagnosis of Tourette’s disorder. Recent work has
suggested the presence of executive dysfunction, particularly
problems with (p.687) inhibitory control in patients with the
Tourette syndrome (Margolis et al. 2006). However, Channon
et al. (2006) reported that uncomplicated TS is associated with
only mild, circumscribed cognitive impairment.
Research has also shown that individuals with Tourettes can

suppress their ticks for brief periods of time, and suppression
is enhanced when programmed reinforcement is provided for
tick free intervals and short periods of suppression do not
result in a paradoxical rebound in tick frequency when active
suppression has ceased. The ability to suppress tics appears to
be correlated with omission but not commission errors on the
Continuous Performance Task (Woods et al. 2008). Recent
neuroimaging research has shown robust activation of
cerebellum, insula, thalamus and putamen during tick release.
The involvement of cerebellum and insula suggests their
involvement in tick initiation and execution (Lerner et al.
2007).
26 Conclusion
The neuropsychological study of psychiatric disorders is still in
its infancy, but the infant appears to be thriving. As Frith
stated in a commentary on a paper on a neuropsychological
model of schizophrenia: “A few years ago articles of this sort
would have been unthinkable. For most psychologists,
schizophrenia either did not exist or was a social disorder of
Page 37 of 49
no interest to hard-headed experimental psychologists. Today,

schizophrenia is unquestionably a disorder of the brain
(however caused) and, as such, it provides one of the most
exciting challenges for linking brain and cognition” (Frith
1991).
Exciting novel attempts to explain abnormal behaviour in

terms of dysfunctional information processing are rapidly
being developed. However, it is critical that such models are
explicitly amenable to experimental testing and refutation.
Only then will significant advances be made in our scientific
understanding of abnormal experience. We must be wary of
replacing neurotransmitter or structural lesion based
explanations of psychopathology with seductive, glossy PET or
fMRI illustrations, or simplistic ‘black-box’ cognitive models.
Demonstrating that a particular patient or patient group has
abnormal regional brain metabolism, or a specific cognitive
deficit is of interest, but it does not provide a causal
explanation of abnormal behaviour or experience.
Bentall et al. (2007) have recently commented that while there

is an increasing recognition of a neuro-developmental
approach to psychiatric disorder, this has generally failed to
take into account recent advances in the understanding of the
psychology of unusual experiences such as hallucinations and
delusions. They propose that developmental psychology offers
important clues about cognitive and socio-cognitive
abnormalities that might be involved in hallucinations and
delusions and that an integration of these findings with
existing knowledge on the neuro-development of psychosis
could offer profitable new avenues of research for
investigators working at both biological and psychological
levels of explanation.
Furthermore, Garety et al. (2007) propose a series of

implications for neurobiological research of cognitive models
of psychosis. They argue that the evidence increasingly
supports hypotheses proposed by cognitive models (i.e. that
psychosis is on a continuum; (p.688) specific cognitive
processes are risk factors for the transition from sub-clinical
experiences to clinical disorder, social adversity and trauma
are associated with psychosis and with negative emotional
processes, and these emotional processes contribute to the
occurrence and persistence of psychotic symptoms). They also
argue that reasoning biases contribute to the occurrence of
Page 38 of 49
delusions. They argue convincingly that the benefits for

incorporating cognitive processes into neurobiological
research include more sophisticated, bi-directional and
interactive causal models. They conclude that cognitive
models and their derived phenotypes constitute the missing
link in the chain between genetic or acquired biological
vulnerability, the social environment and the expression of
individual positive symptoms.
I ended the previous edition of this chapter with the following

conclusion, which I believe still largely holds true. While
significant progress has been made, in most instances we still
await truly convincing neuropsychological explanations of
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The clinical assessment of neuropsychiatric disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The clinical assessment of

Mervi Pitkanen
Eli J. Jaldow
Michael D. Kopelman
DOI:10.1093/acprof:oso/9780199234110.003.33

The primary objective of the neuropsychiatric clinical
assessment is to make a comprehensive and accurate
diagnosis and to set up a plan of management or care. It may
be necessary to identify what additional information, if any, is
required to substantiate the diagnosis. This unambiguous
objective is nevertheless difficult to achieve and misdiagnoses
are common. In general in neuropsychiatry, the greater the
care taken in the clinical assessment, the greater the
probability of obtaining the correct diagnosis. However, over-
investigating can be expensive and stressful for the patient.
This chapter focuses on the principles of what a
neuropsychiatrist attempts to do, and the particular
contributions of the neuropsychologist in assessment and
management of neuropsychiatric conditions.
Keywords: neuropsychological assessment, neuropsychiatric disorders, clinical

neuropsychology, over-investigating, plan of management
Page 1 of 20
1 Introduction
The primary objective of the neuropsychiatric clinical
assessment is to make a comprehensive and accurate
diagnosis and to set up a plan of management or care. It may
be necessary to identify what additional information, if any, is
required to substantiate the diagnosis (see Chapter 32). This
unambiguous objective is nevertheless difficult to achieve and
misdiagnoses are common (e.g. Taggard et al. 2006; Kishi et al.
2007; Voon et al. 2007). It can be intellectually unsatisfying to
have to depend upon a range of tests and investigations to
determine the correct diagnosis. In general in neuropsychiatry,
the greater the care taken in the clinical assessment, the
greater the probability of obtaining the correct diagnosis.
However, over-investigating can be expensive and stressful for
the patient. This chapter will focus on the principles of what a
neuropsychiatrist attempts to do, and the particular
contributions of the neuropsychologist in assessment and
management of neuropsychiatric conditions (see Chapter 32).
2 The clinical interview
Page 2 of 20
Neuropsychiatrists should be self-aware and realize that his or

her own general appearance, body language, eye contact and
posture will elicit a reaction from the patient and may
critically affect the patient’s responses. He or she should know
how to listen, to be generally perceptive, to take notes and
think simultaneously, to deal inconspicuously with
interruptions and to give the impression that there is no hurry
even when time may be very limited. At the very least, the
patient will receive respect and begin to build a therapeutic
relationship. It is usually necessary to have at least one follow-
up appointment, to review the results of tests and
investigations and/or to assess progress after the initial
therapeutic intervention. Findings should be reviewed if
follow-up appointments are not attended.
Many patients who are referred to a neuropsychiatrist have

complex medical histories. It is important that all collected
background information is considered carefully before the
initial interview. Referral letters often contain essential
information. It is often helpful, particularly in complex cases,
to begin by clarifying with the patient the reasons for (p.694)
the referral; by reviewing the referral letter with the patient
and identifying variations, if there are any, between the
referrer’s appraisal at the time of writing and the patient’s
current version of his problems. This should be done carefully
and avoid confrontation. In this context, the referrer may be
functioning as a collateral historian (see Section 2.1) and in
some cases, this may be the only collateral history available. A
review of the reason for referral at the beginning of the
clinical interview will focus the neuropsychiatrist and the
patient on the objectives of the consultation and identify the
major topics to be covered in the interview. Also one shouldn’t
forget that a careful medication review, including prescription
and over the counter medication, is required. Discontinuation
of all unnecessary medications is important, as medications
are an under-appreciated cause of cognitive complaints.
Neurologists and neuropsychiatrists deal with different

aspects of both acute and chronic organic reactions. Ideally
their approaches are complementary and neurological input
may be useful during the neuropsychiatric assessment.
Generally the neurologist is primarily concerned with the
diagnosis and treatment of specific lesions and diseases. The
neuropsychiatrist is concerned with the psychiatric
manifestations and complications of known neurological
Page 3 of 20
disorders, as well as with the diagnosis and management of

disorders evidenced by psychological/psychiatric signs and
symptoms. These include delirium and dementia, the
management of secondary disorders (e.g. depression after
head injury or stroke, psychosis in epilepsy or dementia), the
prevention of secondary complications and support for
relatives and carers. He/she has responsibility for the
coordination of care in the hospital and transfer of care at the
time of discharge. Sometimes the neuropsychiatrist will assess
an organic contribution to functional disorders, consider
detention under the Mental Health Act (if in the UK), or assess
issues of compensation or competence. Effective
communication skills and the exercise of tact are essential.
In many branches of medicine it is considered good practice to

strive to make a single diagnosis that best accounts for all the
symptoms (Occam’s razor). However, in neuropsychiatric
practice there are often several concomitant problems that
tend to cluster in familiar patterns. This has an impact on the
scope of the neuropsychiatric assessment and will be
considered further in Section 6.
The patient’s complaints should be asked about early in the

interview and should be considered thoroughly. Throughout
the clinical interview, the neuropsychiatrist will be collecting
information that will either support or reject certain possible
diagnoses. He/she will systematically ask questions to help
confirm or eliminate the differential diagnosis. Table 33.1
shows the common causes of dementia that a
neuropsychiatrist may consider. Patients presenting with
amnesia are most likely to have Wernicke-Korsakoff Syndrome,
but herpes encephalitis, vascular episode(s), anoxia, head
injury, subarachnoid haemorrhage, space-occupying lesion,
pituitary excision, radiotherapy, and transient global amnesia
are also possible diagnoses. Mild/moderate memory
impairment is frequently the result of a vascular episode,
epilepsy, alcohol, hypoxia or head injury; whilst non-
progressive generalized cognitive impairment is most often
due to anoxia or head injury (Kopelman and Crawford, 1996).
Tables 33.2 and 33.3 give some examples of aspects of the
presenting complaint and the past psychiatric history that may
be diagnostically (p.695)
Page 4 of 20
Table 33.1 Prevalence of different causes of

dementia in adults referred for evaluation of
progressive intellectual deterioration*
Cause Prevalence
(%)
Alzheimer’s disease (presumed) 39
Multi-infarct dementia 13
Dementia associated with psychiatric 9

disorder (pseudodementia)
Alcoholic 8
Metabolic disorders 4
Hydrocephalus 4
Cerebral neoplasms 3
Huntington’s disease 2
Not demented 2
Miscellaneous 15
*Data based on 708 patients from eight world-wide series
(Marsden 1985). Note that Lewy body dementia has
subsequently been shown to account for up to 20% of
patients with dementia at autopsy. AIDS dementia is not
included in this series.
helpful and should be enquired about. If there are a number of

complaints or symptoms, it is useful to list them numerically at the
outset, and then investigate them one by one.
2.1 Collateral clinical history
A detailed history from close relatives or friends is required to
establish the mode of onset of the disorder, the nature and
duration of symptoms and their subsequent course. The
patient’s own account may be distorted by confusion, memory
lapses, denial or lack of insight. If possible, it is often
advisable to have the collateral history taken by a second
interviewer in a separate room, or at least conduct a telephone
interview.
Table 33.2 The initial complaint and its

diagnostic significance
Page 5 of 20
Examples and comments
Description Diagnostically this is the most useful

aspect of the history and great care should
be taken to obtain detailed and precise
information about each complaint or
symptom
Mode of onset
Sudden Vascular episode, psychiatric disorder
Progressive Alzheimer’s disease, psychiatric disorder
Stepwise Multi-infarct dementia, multiple sclerosis
Circumstances Injury/accident (Did the illness cause the

of onset accident? Compensation?)
Course An episodic course is characteristic of

epilepsy, Kleine–Levin syndrome, and
mental illness
(p.696)
2.2 Mental state examination
Table 33.3 The past psychiatric history and its

diagnostic significance
Page 6 of 20
Type of Examples and comments

history
Family Genetic predisposition?

history
Personal
history
Childhood Brain damage, febrile convulsions, and

head injuries all increase the risk of
epilepsy
Occupations Educational attainment and peak

occupational level are better indicators of
premorbid IQ than end-of-bed evaluations.
Periods of unemployment may identify past
episodes of illness
Habits The impact of alcohol and other drugs is

related to doses consumed and precise
daily intake should be determined if
possible. Have there been epileptic
seizures, amnesic episodes, and/or
withdrawal phenomena? Drug injection
exposes the body to infections, emboli, and
thromboses
Forensic There may be genetic predisposition to
criminal behaviour, e.g. XYY syndrome,
Tourette’s syndrome
Psychosexual Unusual behaviour may be diagnostically

helpful, e.g. increased libido and sexual
disinhibition in mania and Kleine–Levin
syndrome. Having multiple partners
increases the risk of sexually transmitted
diseases. Pregnancy and breastfeeding may
effect some investigations and treatments
Sleep The timing of insomnia may help

distinguish between the type and severity
of mood disorder. Insomnia is also a feature
of delirium. Excessive daytime sleepiness
may be primary or secondary (e.g. drugs/
toxins, head injury, sleep apnoea)
Page 7 of 20
Type of Examples and comments

history
Family Genetic predisposition?

history
Past Previous symptoms, diagnoses, course of

psychiatric illness, and responses to previous
history treatments are characteristic of some
illnesses and this information is often
helpful diagnostically.
Old brain scans may be very useful for
identifying new pathology
Past medical Neurological (e.g. head injuries, epilepsy,

history meningitis/encephalitis, stroke) and
endocrinological (e.g. diabetes, thyroid
disease) histories are most often relevant
Personality A collateral history is important if a

and social personality change is suspected
history
The mental state examination begins with appearance and

general behaviour.
◆ Pallor, weight loss, disorders of facial expression, posture

and movement and standards of self-care draw attention to
the possibility of an organic disorder.
◆ Is the patient impulsive, disinhibited, or insensitive?
◆ Or are they slow, hesitant or unable to understand?
◆ Speech may be impaired in production, perception or

comprehension. The patient may be dysarthric, dysphonic,
wander off the point or be incoherent. Thought may be
impoverished, restricted to certain themes, concrete or
impaired in reasoning (Weismer, 2006).
(p.697)
◆ Mood may be severely disturbed in neuropsychiatric
patients (i.e. delirious patient’s mood may rapidly change
between periods of mild disinhibition or euphoria and
hostile agitation whereas in early dementia anxiety or
depression may characteristically prevail).
Page 8 of 20
◆ An empty, shallow quality to emotional expression is quite

common, as well as a catastrophic reaction, in which failure
at a previously accomplished task elicits an intense
emotional reaction with crying, negativity, withdrawal and
hostility.
Intelligence has a major modifying effect on the presentation

of thought content. A highly intelligent patient may appear
less severely impaired by virtue of cognitive compensations for
his or her deficits. Doctors should avoid making a glib
assessment of IQ based on a conversation - this is a common
trap that the medical profession falls into. It is quite possible
to have a “normal” conversation with a person who has
considerable intellectual impairment. Far more information
can be derived from a few ‘bedside’ clinical screening such as
having to copy a few simple shapes (Kopelman, 1986, 1994;
Mioshi et al. 2006). The tendency to report the experience of
unfamiliar abstract phenomena in simple, concrete terms may
be due to an inability to appreciate the different modalities of
perception and/or a lack of the vocabulary required to
accurately describe them. A result may be that delusions or
auditory hallucinations are reported as if they were visual
phenomena. Ideas of reference and delusions of persecution
are common, but often poorly elaborated, vague, shallow,
transient or inconsistently related. Anxious, depressive or
hypochondriacal ideas may co-occur with perceptual
distortions, illusions and hallucinations.
2.3 Assessment of cognitive state

The neuropsychiatrist’s assessment of cognitive state is
essentially a screening procedure. If abnormalities are found
they, combined with the clinical history, should help to focus
the referral for neuropsychological assessment by a
psychologist (see Section 4). However, it is paramount to
remember that when there is a significant psychiatric
presentation such as depression, anxiety or psychosis, the
importance of cognitive assessment becomes less and one
should take extreme caution prior to interpreting anything
significant from these tests.
◆ In acute psychotic or neurotic patients without apparent

organic pathology, it may be of importance to assess
orientation in time, place and person, as well as recent
Page 9 of 20
events (e.g. how they came to the clinic, how long they have
been an inpatient).
◆ In patients with suspected organic disorders, a brief

assessment of orientation, attention/concentration, memory
(including general information, remote and recent personal
memories and current learning), language (including
naming, comprehension, expression, repetition, reading and
writing, disorders of form and content), mental calculation,
drawing and copying, other agnosic or apraxic deficits and
frontal function is likely to provide relevant insights and
direct further assessments.
The scope for this type of assessment is described in Kopelman

(1994).
(p.698) 3 Physical examination

A thorough physical examination is required. Twelve per cent
of admissions to psychiatric hospitals have physical signs of
illness directly contributing to their mental disorders (Lishman
1998). The elderly are particularly vulnerable, with over one
third of hospitalised elderly having features of delirium
(Marcantonio et al. 2003; Kishi et al. 2007). Also it should be
noted that systemic infections and inflammation can cause
acute exacerbation of symptoms and drive the progression of
the neurodegenerative disease (Perry et al. 2007).
◆ It is important to examine the patient’s face as ‘there’s no

art to find the mind’s construction in the face’. A great deal
of information can be obtained about mood, perplexity, trust
and an impression of character from the face, although
beware not to over-interpret. Is there a suspicion that the
patient is experiencing hallucinations? This may be obvious
or quite subtle. There may be signs of liver disease: spider
naevi, jaundice and parotid enlargement in an alcoholic.
◆ The head should be examined for signs: scars, unusual

head shape, size or asymmetry, hair distribution and
texture.
◆ The eyes, windows of the mind, should be examined

carefully. Abnormal pupil size may be affected by drugs.
Pupillary accommodation and reaction to a light must be
checked if there is a suspicion of syphilis; the Argyll-
Robinson ‘prostitutes’ pupil accommodates but does not
react.
Page 10 of 20
◆ The hands may also reveal useful information about the

patient’s health and lifestyle. Is there a tremor, palmar
erythema and leuconychia, nicotine staining, clubbing or
calluses? Are the nails long, broken, bitten or unclean?
◆ The blood pressure must always be measured and the

pulse should be taken. Is there an arrhythmia? Is the pulse
fast because the patient is anxious or for some other reason
(e.g. thyroid disease)?
The traditional neurological examination is often not that

abnormal in patients with brain disease. If abnormalities are
present they may only be witnessed as ‘subtle signs’, for
example clumsiness, minor Parkinsonism or gait
abnormalities. Also “neurological soft signs” should not be
ignored (Cuesta et al. 2002).
4 Neuropsychological assessment
Within the context of a neuropsychiatric clinic,
neuropsychological assessment has three main purposes.
◆ The first is to help with diagnosis in the context of other

observations and findings from the background history,
clinical and mental state examination and the results of
physical investigations. Where all the indexes point in the
same direction, the assessment is easy. Where they differ, it
is more challenging, but particularly important to find an
explanation for the discrepancy. A patient may be found, on
formal testing, to be either more or less severely impaired
than expected. If more severely impaired, (p.699) it could
be that the clinician had under-estimated the degree of
decrement or that the patient is exaggerating or simulating
his/her handicap.
◆ The second main purpose is to identify and quantify the

pattern and severity of cognitive impairments. The details
of how this is done are discussed elsewhere in this volume.
◆ The third main purpose of assessment is to plan

strategies of cognitive rehabilitation and/or cognitive
behaviour therapy: mood disorders and post-traumatic
stress disorder being common correlates of cognitive
deficits (Kopelman and Crawford, 1996; Jacova et al. 2007).
Cognitive rehabilitation is carried out according to
principles developed elsewhere (Wilson, 1999; Stuss et al.
1999).
Page 11 of 20
The actual tests employed in neuropsychiatric settings vary

somewhat from clinic to clinic, but do not differ in essence
from those considered in relation to specific disorders
elsewhere in this volume. Within our own clinic, we commonly
employ as initial procedures the National Adult Reading Test–
revised (NART-R; Nelson and Willison 1991), or the Wechsler
Test of Adult Reading (WTAR; Wechsler, 2001a) for estimating
premorbid IQ, the Wechsler Abbreviated Scale of Intelligence
(WASI; Wechsler, 1999) as a brief assessment of current
intelligence, and the Wechsler Adult Intelligence Scale–III
(WAIS–III; Wechsler, 2001b) for more detailed assessment.
Measures of anterograde memory, employed in accordance
with clinical need and time availability, include the Wechsler
Memory Scale-III (WMS–III; Wechsler, 2001c), Wechsler
Memory Scale–revised (WMS–R; Wechsler, 1987), the Doors
and People test (Baddeley et al. 1994), the Recognition
Memory Test (Warrington, 1984), the Camden Memory Tests
(Warrington, 1996) and the Kendrick Object Learning test
(Kendrick, 1985). For naming, we commonly employ the
Graded Naming test (McKenna and Warrington, 1983), and for
executive function, tests such as verbal fluency (Benton, 1968),
Modified Card Sorting (Nelson, 1976), Trail Making (Reitan,
1958), and the Brixton-Hayling tests (Burgess and Shallice,
1996). Autobiographical memory is assessed using the
Autobiographical Memory Interview (Kopelman et al. 1990).
All patients are given the Beck Depression Scale-II (BDI-II;
Beck et al. 1996) and subjective evaluations of memory are
also used occasionally (Sunderland et al. 1983).
5 Investigations
Investigations are primarily directed towards excluding or
establishing and quantifying organic pathology.
5.1 Blood Tests

A biochemical screen is justified in all cases, even if the
diagnosis is known, as any problems in these can often easily
be corrected and electrolyte imbalances may complicate and
exacerbate other conditions (Rockwood, 2008). Biochemical
tests are essential to confirm many suspected diagnosis, for
example thyroid disease, parathyroid disease, Cushing’s
disease, diabetes, uraemia, liver failure and syphilis.
(p.700) 5.2 Electroencephalogram (EEG)
Page 12 of 20
The electroencephalogram is still widely used when organic

disorders are suspected, confirming abnormalities of brain
structure and function in about 60% of cases. In normal
subjects the EEG is symmetrical and classified into four
characteristic waveforms depending on frequency: delta,
theta, alpha and beta. There are rather specific findings in
EEG in certain neuropsychiatric disorders, however the
findings always need to be interpreted in the clinical context
and they are hardly ever diagnostic. Do note though that the
EEG is becoming an increasingly popular tool when combined
with advanced imaging techniques (cf. Jeong 2004; Oishi et al.
2007; Pomonavera et al. in press).
Page 13 of 20
5.3 Structural imaging

Brain structural imaging is considered a crucial component
when evaluating neuropsychiatric patients. Magnetic
Resonance Imaging (MRI) has a number of advantages over
Computerized Tomography (CT) and currently is the
examination of choice. However, a CT scan can still be very
informative and useful in acute situations.
In a setting of an acute cognitive decline or other acute

neuropsychiatric symptoms a CT scan is generally enough to
rule out surgically treatable disorders. However, problems
easily emerge when interpreting a CT scan due to its poor
ability to show subtle lesions particularly in the areas that are
difficult to image, but it does remain useful for patients with
claustrophobia, pacemaker or other metallic implants (van
Straaten et al. 2004).
The MRI shows high sensitivity in detecting macroscopic

abnormalities occurring in several neuropsychiatric conditions
(i.e. Neuropsychiatric SLE related cerebrovascular disease),
thus providing a substantial contribution in both diagnosis and
management. However, in clinical practice the conventional
MRI is typically obtained mainly to exclude the presence of a
potentially reversible cause (i.e. brain tumors, subdural
hematoma, normal-pressure hydrocephalus) but does not
provide any specific support to discriminate among different
forms of neurodegenerative disease. In clinical research and
more commonly in practice, interest is increasing to measure
regional or global brain atrophy and voxel-based morphometry
(VBM) is becoming popular (Bozzali et al. 2006). However, the
information that VBM provides is again related to brain
atrophy, which represents the final stage of the
pathophysiological processes occurring in neurodegenerative
disorders. Recently, more advanced MR techniques (i.e., 1H-
MR spectroscopy; diffusion-weighted MRI (DW-MRI),
magnetization transfer imaging) have been introduced with
the ability to detect subtle changes in brain tissue. Typically
these techniques are able to reflect more microscopic aspects
of the tissue damage (demyelination, microtubule breakdown,
axonal loss), which are supposed to precede the final stage of
tissue loss. Even though these techniques are not as yet in
common clinical use they do show promising results,
improving insight of the brain’s microstructural characteristics
Page 14 of 20
in neuropsychiatric disorders (Bozzali and Cherubini, 2007; cf.

Geuze et al. 2005; Farias and Jagust, 2004).
(p.701) 5.4 Functional imaging

Functional imaging, such as Single Photon Emission
Computerized (SPECT) and Positron Emission Tomography
(PET), provides the means for detecting in vivo metabolic and
neurochemical changes in neuropsychiatric disorders. PET
and SPECT are nuclear medicine techniques in which
temporal changes in the concentrations of radioactive tracers
are recorded in brain and other target organs. SPECT assesses
brain function by measuring the photon emission from
radiotracers which cross the blood brain barrier and distribute
in proportion to regional cerebral blood flow shortly after
intravenous injection. This provides an indirect measure of
cerebral metabolic function. The radioactivity involved is a
limiting factor and is an ethical issue. SPECT is cheaper and
more widely available than PET, which also permits evaluation
of brain metabolism. Transmitter and receptor studies can be
done with both SPECT and PET. Overall, PET has become
more prevalent in clinical practise but SPECT is being
reinvented with new applications (Janssen and Vanderheyden,
2007; cf. Minoshima, 2002; Thobois et al. 2001).
6 Concluding the neuropsychiatric assessment

Ideally the clinical history and examination as well as the
psychometric testing and the investigations all point to the
same diagnosis. However, they often do not, and in those cases
all the information should be reappraised carefully.
◆ Was part of the history missed?
◆ Is there any reason to suspect that the patient may be

malingering or embellishing symptoms?
◆ Is the patient depressed or suffering from excessive

daytime sleepiness (pseudodementia)?
A neuropsychiatrist, having made one probable diagnosis,

should then consider other disorders that sometimes cluster
with that diagnosis.
◆ Head injury may result in neurological signs, cognitive

deficits, personality change and/or emotional problems (i.e.
depression and PTSD).
Page 15 of 20
◆ Alcohol causes a range of problems including withdrawal

syndrome, acute hallucinosis or paranoia, hepatic
encephalopathy, the Wernicke-Korsakoff syndrome, or more
global cognitive deficits as well as a range of psychological
problems (i.e. depression, anxiety, and mood lability).
Finding evidence for the presence of the familiar clustering

disorders may increase the likelihood that the primary
diagnosis was accurate. Using a structured approach to
organizing the clinical material, and relying on overall clinical
judgement at both the initial and concluding stages will
usually furnish the neuropsychiatrist with sufficient
information to make a reliable diagnosis and to proceed to set
up a plan of management (cf. Cummings and Zhong, 2006).
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Burgess, P.W. and Shallice, T. (1996). Response

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Page 20 of 20
Neuropsychological rehabilitation of schizophrenia


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Neuropsychological rehabilitation of
schizophrenia
Bjørn Rishovd Rund
DOI:10.1093/acprof:oso/9780199234110.003.034

This chapter begins with a discussion of cognitive dysfunction
in schizophrenia. It describes the two distinctly different
approaches in cognitive therapy with schizophrenic patients.
One focuses on cognitive content, while the other is process-
oriented, emphasizing the correction of basic cognitive
deficits. The chapter then discusses the Oslo Cognitive
Training Programme.
Keywords: schizophrenia, cognitive dysfunction, cognitive therapy, Oslo

Cognitive Training Programme
1 Introduction
Schizophrenia is a disturbance, or a spectrum of disorders,
that is diagnostically defined ( Diagnostic and statistical
manual of mental disorders, 4th edn (DSM-IV); American
Psychiatric Association 1994) by a duration of at least 6
months, with at least 1 month of an active psychotic phase.
Two or more of the following symptoms should be present
during the active phase:
Page 1 of 20
◆ delusions;
◆ hallucinations;
◆ disorganized speech;
◆ grossly disorganized or catatonic behaviour;
◆ negative symptoms (i.e. affective flattening, alogia, or

avolition).
Even though modern antipsychotics and psychosocial

treatment programmes are effective in moderating symptoms
and reducing the rate of relapses, most patients with
schizophrenia do not function well outside structured, routine
settings, such as hospital wards. Outcomes other than
symptom improvement and relapse prevention have not been
well documented (Lehman et al. 1995; Hogarty and Flesher
1999). A majority of patients with schizophrenia interact in
ordinary social settings in a conspicuous way and also do not
manage an ordinary work or school situation very well. On
average, only 10–30% of patients with schizophrenia are
employed at any time, and few of these are able to maintain
their vocational gains (Attkisson et al. 1992; Hogarty and
Flesher 1999). What is the reason for this?
1.1 Cognitive dysfunction and outcome in schizophrenia

Many clinicians now claim that the reason is the serious
cognitive disturbances of these patients. Several prominent
researchers and clinicians have pointed out that cognitive
dysfunction is the enduring core feature of schizophrenia.
Some have called schizophrenia a thought disorder. Evidence
from neuropsychological, neuropathological, and
neuroimaging studies has documented schizophrenia as a
neuropsychiatric disease. Most cognitive dysfunctions seem to
some degree to remain impaired even when symptoms (p.705)
improve. Andreasen (1999) argues that the definition of
schizophrenia should be based on basic cognitive disturbances
rather than on phenomenology.
The fundamental importance of cognitive deficits in

schizophrenia is also substantiated by the fact that cognitive
functions have proven to be of much greater significance in
the prediction of prognosis and outcome than the symptoms of
the illness. Patients with the most serious cognitive
Page 2 of 20
dysfunctions appear to have the poorest outcome. Different

dysfunctions seem to relate to different functional outcomes.
◆ Verbal memory is related to all types of functional

outcomes.
◆ Vigilance predicts social problem-solving and the

acquisition of social skills.
◆ Executive functioning predicts the ability to function in

the community (Sharma 1999).
◆ Impairment in cognitive processing seems to mediate the

acquisition of behavioural competencies in schizophrenia.
We still have limited knowledge however, about the underlying

mechanisms through which cognitive dysfunctions operate on
behaviour and social functions.
1.2 The importance of cognitive prodromal symptoms for early

diagnosis
What Hogarty and Flesher (1999) term social cognition (i.e.
the ability to act wisely in social interactions), is an important
determinant of social and vocational recovery. Klosterkøtter
and Schultze-Lutter (2000) have shown that cognitive
prodromal symptoms are the only ones with a high diagnostic
efficiency. These symptoms have high specificity and positive
predictive powers as well as satisfactory percentages of false-
positive predictions and a good classification rate.
Klosterkøtter and Schultze-Lutter (2000) claim that because of
the high predictive value of these cognitive symptoms, a
diagnosis in the initial schizophrenic prodrome seems
possible. They conclude that in the future an early intervention
related thereto might enable prevention of early psychotic
episodes.
Page 3 of 20
1.3 Cognitive dysfunction as a target for treatment and

rehabilitation
The fact that deviance in cognitive functions is a core deficit in
schizophrenia makes them an appropriate target for treatment
and rehabilitation. The obvious area to address is the one that
is most impaired and most damaging for the person’s psycho-
social functioning. However, the targeting of cognitive and
neuropsychological deficits in schizophrenia for therapeutic
interventions has so far been greatly neglected. Attempts at
cognitive remediation have been relatively sparse. Effective
techniques for normalizing or neutralizing cognitive
impairments would be a decisive addition to the treatment
armamentarium for patients with a psychotic illness in general
and patients with schizophrenia in particular.
Neuropsychologists have contributed strongly to the
development of the few cognitive remediation programmes for
patients with schizophrenia that exist today, primarily the
process-oriented approach (see Section 3). This treatment
strategy originated in the areas (p.706) of experimental
psychopathology and the neuropsychology of schizophrenia. In
this approach, specific cognitive impairments detected in the
laboratory are targeted for change, first in the laboratory and
later in increasingly realistic situations (Spaulding et al. 1999).
As such, this treatment approach has much in common with
the models for rehabilitation of head traumas.
There are two distinctly different approaches in cognitive

therapy with schizophrenic patients. One focuses on cognitive
content, while the other is process-oriented, emphasizing the
correction of basic cognitive deficits.
2 The content-oriented approach to therapy

This is carried out according to the principles of cognitive
therapy (e.g. as described by Beck et al. 1979) for the
treatment of depression and other emotional disorders.
However, some modifications that are necessary for severely
disturbed patients are included. Outstanding advocates for
this approach in schizophrenia treatment are Perris (1989),
Fowler and Morley (1989), Bentall and collaborators (1994),
and Kingdon and Turkington (1994).
◆ Perris’s metacognitive approach has been developed in

small, community-based and family-style treatment centres
Page 4 of 20
in Sweden. Most of the treatment takes place in small

groups.
◆ Bentall et al. (1994) have developed a more behaviourally

oriented treatment package that directly targets persistent
auditory hallucinations. Their therapeutic programme
consists of procedures for fostering attribution of
hallucinations to the self rather than to external sources,
and for diminishing distress provoked by hearing voices.
◆ Kingdon and Turkington (1994) contend that people with

schizophrenia are not inherently irrational, but instead
suffer from a circumscribed set of irrational beliefs. Their
therapeutic approach attempts to help patients to alleviate
the impact of these beliefs.
◆ The treatment programme of Fowler and colleagues

(Garety et al. 1994) focuses on techniques aimed at
modifying psychotic thoughts.
3 The process-oriented approach to cognitive therapy

This approach focuses on remediation of deficits in cognitive
processes rather than changing distorted thoughts, attitudes,
beliefs, or hallucinations (Adams et al. 1981). This chapter will
be limited to this approach and the empirical studies
examining the effects of such therapeutic programmes.
There were a few clinical studies in the late 1960s and 1970s
reporting encouraging results. After this promising beginning,
research lay dormant for more than a decade. Interest in
cognitive training programmes based on empirical research
was to some extent rekindled in the 1990s. Some few
comprehensive training programmes have been developed,
and the effects of certain of these have been examined (Fowler
1992; Brenner et al. 1995; Spaulding et al. 1999). In addition
to these well-founded treatment (p.707) programmes, there
have also been several attempts to remediate more specific
elementary attentional and conceptual functions.
3.1 The integrated psychological therapy (IPT) programme

Brenner et al. (1992, 1995) developed the most complete
therapeutic programme, the so-called Integrated Psychological
Therapy (IPT). This is a multi-element hierarchical programme
in which there is an attempt to enhance basic cognitive
capacities before problem-solving and motor skills training is
Page 5 of 20
implemented. IPT is a step-by-step procedure devised for

groups of 5–7 patients. It is comprised of five subprogrammes:
◆ cognitive differentiation;
◆ social perception;
◆ communication skills;
◆ interpersonal problem-solving;
◆ social skills training.
The rationale behind the IPT is that remediation of cognitive

deficits will facilitate acquisition and maintenance of more
complex skills. A series of studies of IPT has demonstrated
significant treatment effects on cognitive functions and
reduction of symptomatology (Hodel and Brenner 1994).
However, it has not been documented that remediation of
cognitive functions has a pervasive effect on social behaviour.
In the USA, Will Spaulding has adapted and elaborated

Brenner’s IPT programme. Spaulding et al. (1999) published
the results from a study in which 90 subjects with severe and
disabling psychiatric conditions, predominantly schizophrenia,
participated in a controlled-outcome trial. Patients receiving
the cognitive training programme, consisting of the three
cognitive modules in Brenner’s IPT, were compared to control
subjects who received supportive group therapy. Patients
receiving cognitive training showed incrementally greater
gains compared with controls on the primary outcome
measures. There was equivocal evidence for greater
improvement in the cognitive training group on a
disorganization factor for psychiatric symptoms (the Brief
Psychiatric Rating Scale), and strong evidence for greater
improvement on a laboratory measure of attention processing.
Significant improvement was also found on two measures of
attention, memory, and executive functioning.
3.2 A trial of individual neurocognitive therapy

Wykes et al. (1998) reported the preliminary results of a
controlled trial of individual neurocognitive therapy. The
effects of cognitive remediation were compared to those of a
control therapy that consisted of intensive occupational
therapy to control for non-specific effects of treatment. In a
randomized control trial of 33 patients with schizophrenia,
results suggested a differential effect in favour of cognitive
Page 6 of 20
rehabilitation for tests in the cognitive flexibility and memory

subgroups, as well as for self-esteem, but not on symptoms or
social functioning. However, generalized improvements in
cognitive flexibility were related to improvements in social
functioning.
(p.708) 3.3 Remediation of conceptual and attentional skills and

memory
The attempts to remediate more specific cognitive dysfunction
have mainly concentrated on two areas: conceptual skills and
attentional skills.
3.3.1 Remediation of conceptual skills

Conceptual skills have been trained primarily by means of the
Wisconsin Card Sorting Test (WCST). These studies all show
some positive effects of training. The greatest gains have been
attained by providing positive reinforcement for correct
solutions. It has not been possible to demonstrate any
evidence of generalization for improved executive functions.
Bellack and co-workers (1996) showed that schizophrenic
patients trained on one of two problem-solving tasks similar to
the WCST exhibited a marked improvement on the trained
task. However, subjects trained on one test performed no
better on the other instrument than subjects who received
practice only.
3.3.2 Remediation of attentional skills

Regarding attentional skills (cf. Silverstein et al. 2001; Suslow
et al. 2001), two of the most common measures are the
Continuous Performance Test (CPT) and the Span Task.
Benedict and associates (1994) used six training tasks that all
required sustained vigilance and a high degree of mental
effort. Results showed improved performance on the training
tasks for the experimental group. However, no significant
changes on the outcome measures were observed. Benedict
and associates (1994) therefore conclude that the rather
substantial practice effect demonstrated did not denote an
improved fundamental cognitive skill.
The conclusion of Benedict and associates (1994) is in

accordance with the view of Bellack et al. (1996). They are
sceptical as to whether cognitive rehabilitation of
schizophrenic patients is an achievable goal. They admit that
practice on tasks can improve performance on that specific
Page 7 of 20
task, but state that there is little evidence for the

generalizability of such training. Thus, they claim that the task
for schizophrenia researchers is to develop real-world training
programmes.
Several more positive attempts to train attentional deficits in

patients with schizophrenia have been carried out recently.
◆ Kern and associates (1995) compared four groups of

schizophrenic patients in regard to improved performance
on a Span task. The findings revealed that the combination
of monetary reinforcement and instructional cues was
superior to other interventions. In the Oslo Cognitive
Training Programme that will be outlined in Section 4, we
have included an intensive Span training with
reinforcement, similar to that used by Kern and associates.
◆ Hermanutz and Gestrich (1991) showed that it was

possible to reduce the distraction of schizophrenic patients
on reaction-time tasks.
◆ Olbrich et al. (1993) found clearly positive effects of a

training module that addresses a combination of
attentional, mnemonic, and conceptual skills.
(p.709)
◆ Van der Gaag (1992) employed a clinical rehabilitation
programme and showed that, although the training
programme was effective in some processing domains, it
did not affect tasks that rely on fast processing of
information.
◆ Medalia et al. (1998) assessed the impact of attention

training with chronic schizophrenia patients. They found
that it is feasible to use practice and behavioural learning
to remediate core attention deficits in this patient group.
3.3.3 Remediation of memory

In addition several attempts have also been made to improve
memory in schizophrenic patients. For instance, Koh et al.
(1976) showed that patients were able to increase recall on a
memory task to levels close to that of normal control subjects
when their encoding was aided by rating stimuli (words) in
terms of pleasantness.
3.4 Other views on cognitive remediation in schizophrenia
Page 8 of 20
In an issue of Schizophrenia Bulletin (no. 1, 1999), the theme

was interventions for neurocognitive deficits in schizophrenia.
Here several outstanding therapists and researchers ask
pertinent questions about the results and designs of cognitive
remediation research. Bellack et al. (1999) point out that the
critical question in selecting neuro-cognitive targets is one of
generalizability. They question how far-reaching the effects of
training in any basic information-processing domain are.
Bellack and collaborators propose an alternative to the
cognitive rehabilitation programmes mentioned above. They
claim that a compensatory model is much more appropriate.
Their emphasis is not on eliminating impairment so much as
on minimizing the resulting disability. Bellack and associates
are critical of the belief that the neurodevelopmental nature of
impairments defies simple solution. Further, they don’t find
that rehabilitation strategies depending primarily on repeated
practice of neuropsychological tasks yield much improvement
in the underlying cognitive operations, or have much benefit
for community functioning.
Green and Nuechterlein (1999) point out another important

issue. Some neurocognitive deficits in schizophrenia are
rather stable over time and thus it would be unreasonable to
expect longstanding deficits to improve permanently after a
short-term treatment. They also point out that the key
question is whether changes in neurocognition translate into
changes in functional outcome.
Studies using the process-oriented approach are summarized

in Table 34.1.
4 The oslo cognitive training programme

The cognitive training programme developed at the Sogn
Centre for Child and Adolescent Psychiatry (SCCAP) in Oslo
aims to improve cognitive functioning and to develop and
strengthen cognitive skills. It takes into account the specific
psychopathological characteristics of schizophrenia. The
development of the Oslo Cognitive Training Programme is
based on research demonstrating that the most significant
dysfunctions in schizophrenia can be related to the areas of
attention, memory, and executive functions. Using the ‘Oslo
approach’, we have attempted to develop a programme that
covers all these areas of dysfunction. (p.710)
Page 9 of 20
Table 34.1 The process-oriented approach.

Characteristics of outcome studies
Study* Outcome of cognitive training
Koh et al. 1976 Increased recall on memory

task
Hermanutz and Gastrich Reduced distraction

1991
Van der Gaag 1992 No sign of improvement
Benedict et al. 1994 Improvement on attention task
Hodel and Brenner 1994 Reduction of symptoms
Kern et al. 1995 Improved span of apprehension
Bellack et al. 1996 Marked improvement on WCST
Medalia et al. 1998† Positive effect on attention
Spaulding et al. 1999‡ Improvement on cognitive

function
Wykes et al. 1999 Improvement in cognitive

flexibility/memory
*The groups studied are schizophrenic patients unless
otherwise indicated.
†This was a study comprising chronic schizophrenic

patients.
‡This was a study comprising chronic psychotic patients.
The treatment programme is, however, also based on the

presumption that cognitive impairment is a key characteristic in
other psychotic disorders. A broad spectrum of psychotic patients
is thus included in the study (Rund and Borg 1999).
The controlled treatment study at SCCAP aims to investigate
to what extent this cognitive training programme can be a
positive clinical supplement to a previously documented
psychoeducational training programme that has proven quite
effective (Rund et al. 1994). The psychoeducational
programme was carried out at SCCAP in the late 1980s and
early 1990s. The outcome of this programme was compared
with that of a standard reference treatment. Clinical outcome
was assessed by relapses during the 2-year treatment period
and by changes in psychosocial functioning as measured by
Page 10 of 20
the Global Assessment Scale (GAS). The results indicated that

the most effective programme as measured by relapse was
also the cheapest—namely, the psychoeducational programme.
Psychosocial functioning improved more, close to significance,
in the psychoeducational group. Patients with poor premorbid
psychosocial functioning benefit most from this treatment.
In the controlled treatment study now taking place at SCCAP,

the question of whether a cognitive training programme can
add anything to the effects of a psychoeducational programme
alone, will be assessed by comparing two groups at baseline,
post-treatment, and at a 1 year follow-up.
◆ Group A receives a psycho-educational programme alone.
◆ Group B receives the same psychoeducational treatment

package as group A plus the cognitive training programme.
We have chosen a battery of outcome measures for evaluating

treatment effects on cognition as well as psychiatric symptoms
(Brief Psychiatric Rating Scale (BPRS)) and psychosocial
functioning (GAS).
(p.711) 4.1 The training programme

The programme is arranged in four modules: cognitive
differentiation; attention; memory; and social perception.
◆ The cognitive differentiation module is based on the

supposition of a generalized impairment in verbal
intelligence, abstraction–flexibility, and auditory processing
that is congruent with a left-hemispheric dysfunction
hypothesis. Much of Brenner et al.’s (1995) original
methodology is adapted for these tasks.
◆ The attention module considers impairment of attention

as a central feature of schizophrenia. With the assumption
that deficits in attention are part of an underlying
mechanism of other cognitive dysfunctions, tasks aim to
strengthen sustained attention over time, as well as train
selective attention and scanning abilities.
◆ The memory module is based on studies involving both

verbal and visual memory. Tasks that primarily involve
short-term recall aim to improve the patient’s ability to
recall an increasing number of items.
Page 11 of 20
◆ The social perception module involves the cognitive

processes that allow the patient to respond and adapt
appropriately to his or her environment.
Training in verbal communication, attention, memory, and

social perception is conducted by administering systematic
training procedures.
◆ During the cognitive differentiation module patients learn

to discriminate among stimulus categories by participating
in a card-sorting task. After demonstrating competence on
this task, patients are introduced to a concept formation
task in which they are instructed to match antonyms and
synonyms, distinguish concepts with different definitions,
and establish a hierarchy of related concepts (Brenner et al.
1992).
◆ Attention and memory modules are presented

simultaneously with the concept formation task.
◆ Following these modules, patients participate in the social

perception module where they are trained to encode social
stimuli by viewing a series of slides showing actors in
different social activities and demonstrating emotions of
varied intensity.
In the social perception module the focus is on improving the

patient’s ability to attend to the statements of others and to
understand accurately what was said, as well as to encourage
association between the patients’ thoughts and the statements
of those with whom they interact. This training attempts to
address the lack of integration between strategies that target
information processing and social learning dysfunction.
Page 12 of 20
4.2 Programme structure

The four modules are systematically introduced to the patient
over a period of 8–10 weeks. The training consists of 30–35
hours of individual training with 15-minute work sessions. The
programme is designed so that the patient begins with
elementary tasks and progresses to more difficult ones. The
rate of progression is determined by the individual’s
functioning, though a standard protocol provides the structure
for progression.
(p.712) In addition to the cognitive training programme

outlined in Section 4.1, all patients in Group B participate in
an intensive span of apprehension training. Patients are
administered the same computerized version of the Span of
Apprehension task (Asarnow and Nuechterlein, version 1987)
in six different sessions:
◆ session 1, baseline;
◆ sessions 2–4, 3 consecutive days of intervention;
◆ session 5, immediate post-test;
◆ session 6, at the 10-day follow-up.
The Span task is run on an IBM computer. There are 128 test
trials, consisting of 3- and 12-letter arrays. Patients are
instructed to identify which of two target letters (T or F)
appear on the screen by pressing one of two buttons (marked
T or F, respectively) on a control pad as quickly as possible.
During interventions 2, 3, and 4, patients receive both
monetary reinforcement and enhanced instructions. The
reward (50 øre) is given immediately following a correct
response by dropping the coin into a metal container placed to
the patient’s right.
4.3 Initiation of the programme

Following completion of baseline measures of the patient’s
current level of functioning, he/she is given a standard
introduction to the training programme and develops a
training schedule together with the therapist. We have chosen
to implement our programme individually instead of in a
group.
Page 13 of 20
◆ Early on in the development of the training, it became

clear that the patients themselves preferred individual
sessions.
◆ In addition, these allow the therapist to take into

consideration patients’ tremendous variation in cognitive
functioning, and thus progress at an appropriate rate while
adhering to the standard protocol.
The cognitive training for the most part takes place in the
school at the clinic. A teacher is responsible for this part of the
programme. A few tasks, such as the visual scanning task
‘Where is Willy’, take place in the ward.
4.4 Some preliminary results from the Oslo study

The primary question asked in the present study is whether
the Cognitive Training Programme adds anything to the
psychosocial (psychoeducative) programme. We have
examined two central WCST measures at baseline, at post-test
(after 5 months of treatment), and at follow-up 1 year later.
The results show an improvement in both groups’
performance, but no difference in degree of performance
between those who have received cognitive training and those
who have not. The same pattern is evident for the Backward
Masking task as well as the CPT. (Backward masking is a
measure of early information processing.) The conclusion that
can be drawn from these preliminary results is that the
treatment (or the natural course of the illness) contributes to
an improvement in patients’ cognitive functioning. However, it
is uncertain whether the cognitive training programme
contributes specifically to the improvement.
(p.713) The second question that can be asked at the present

stage of the study is, ‘Is it possible to improve patients’
attentional performance (concentration) by intensive training
over a week, and with monetary reinforcement and enhanced
instructions added to the intervention?’ Results indicate that
span of apprehension can be improved by cognitive training
(Ueland et al. 2003).
5 Conclusions
Considering the results from the studies of Hans Brenner, Will
Spaulding, and Til Wykes, as well as the preliminary findings
in our project, the following answers to the questions asked in
this study emerge.
Page 14 of 20
1 Can basic cognitive functions be remediated?

Yes, cognitive remediation works in the sense that it is
possible to remediate cognitive dysfunctions in
psychotic patients. What works is uncertain, however.
Our preliminary results provide no basis for assuming
that the cognitive training programme is more effective
than the psychoeducational programme alone. This
stands in a certain contrast to the findings of Will
Spaulding and Til Wykes. It might be, however, that our
psychoeducational therapy includes elements that are
more effective in improving cognitive skills than the
treatment given to the comparison groups in the two
other studies. It is also possible that the number of
training hours in The Oslo Cognitive Training
Programme is not sufficient and needs to be increased
in order to obtain significant results.
2 Is it possible to generalize training effects to
other functions, and register this by use of
appropriate (cognitive and clinical) follow-up
instruments?
There is little evidence in the studies mentioned above
for a generalizability of cognitive training.
3 Is it possible to improve attentional skills by
intensive Span training?
Yes, more intensive training sessions, combined with
reinforcement, are effective in improving concentration
(continuous focusing of attention). This has been shown
in the present study, as well as in several previous
studies (Koh et al. 1976; Hermanutz and Gestrich 1991;
Kern et al. 1995). The challenge is to determine how to
obtain lasting results which have an impact on the
patient’s daily functioning.
We have learned that it is difficult to carry out a systematic

and consistent cognitive training programme in a clinical
setting.
◆ It is difficult to be totally sure that the treatment provided

to the two patient groups is in accordance with the therapy
manuals.
◆ It is also very difficult to determine the effects of

neuroleptics. It would be impossible, for ethical reasons,
either to withdraw all patients from antipsychotic
Page 15 of 20
medication or to give all patients a standard dosage of

medicines.
◆ Further, the researcher cannot require that all patients be

on the same drug and the same dosage over a treatment
period that lasts for at least 18 months.
(p.714) Should the ‘experiment’ of cognitive remediation of

psychotic patients continue? In my opinion, the answer is yes.
We have sufficient positive results to support this conclusion.
We have not received any reports of negative results or
negative consequences of cognitive training. More data and
new analyses of which variables are related to each other
might throw light on which factors are influencing cognitive
functions. Most probably, the improvement found in our study
cannot be attributed to the inherent process of the illness
alone (spontaneous remission), independent of the treatment
received. We have sufficient empirical evidence that the
typical course of schizophrenia is one with many relapses, in
which the level of patients’ social and cognitive functioning
goes up and down. With a longitudinal design such as ours,
with patient assessment at intervals of 5 and 18 months, there
is reason to assume that no improvement would have been
found on the average for the group if no treatment factors had
been influencing cognitive functioning.
It is important to remediate cognitive dysfunctions in patients

with schizophrenia. Treatment programmes that do not take
cognitive functions into consideration are of limited interest
and value. From this point of view, there are no alternatives to
cognitive training programmes at the present time. Therefore,
it is necessary to further develop useful therapeutic
interventions. The only way to do this is to gather empirical
evidence for what works in this connection and what does not
work. From a clinical perspective, it is warranted to
individualize the cognitive training programmes for each
patient according to the deficits disclosed through baseline
assessments. A related challenge is to find out which patients
benefit from cognitive training and which do not.
In order to answer these and related questions it may be

necessary to undertake case studies. However, research based
on individualized therapeutic interventions continues to be
problematic. Thus, a first step in creating evidence-based
Page 16 of 20
therapy for patients with schizophrenia—to assess what works

and what does not work—seems to be controlled-effect studies
in which the effects of therapeutic programmes/manuals are
studied at a group level.
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Brenner, H., Roder, W., Hodel, B., et al. (1995). Integrated

psychological therapy for schizophrenic patients. Hogrefe and
Huber, Bern.
Fowler, D. (1992). Cognitive behaviour therapy in

management of patients with schizophrenia. Preliminary
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treatment of hallucinations and delusions: a preliminary study.
Behav. Psychother. 17, 267–82.
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behavioural therapy for drug resistant psychosis. Br. J. Med.
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perspective. Probing the impenetrable darkness. Allyn and
Bacon, Boston.
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schizophrenia be treated as a neurocognitive disorder?
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attention training in schizophrenics. A comparative study. Eur.
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schizophrenic patients: conceptual basis, present state, future
directions. Acta Psychiatrica Scand. 90, (suppl. 384), 108–15.
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encoding and consequent remembering in schizophrenic
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(1995). Treatment outcomes in schizophrenia: implication for
practice, policy and research. Schizophren. Bull. 21, 669–74.
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time budget approach for the assessment of cognitive and
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schizophrenia. Cassel, New York.
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cognitive training in schizophrenic patients: a review. Acta
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Page 20 of 20
Treatment and rehabilitation of neuropsychiatric disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Treatment and rehabilitation of

Laura H. Goldstein
DOI:10.1093/acprof:oso/9780199234110.003.035

This chapter considers some of the issues and provides a
number of guidelines when considering the psychological
treatments of neuropsychiatric disorders. Topics discussed
include neuropsychological assessment, applying
psychological interventions to neuropsychiatric disorders, and
application of cognitive behavioural therapy to
neuropsychiatric disorders.
Keywords: psychological treatments, neuropsychiatric disorders,

neuropsychological assessment, cognitive behavioural therapy
Page 1 of 36
1 Introduction
This chapter will consider some of the issues and provide a
number of guidelines when considering the psychological
treatments of neuropsychiatric disorders. Neuropsychiatry
itself has been defined in a number of ways (Seli and Shapiro
1997) but for present purposes is best conceptualized as ‘an
aspect of psychiatry that seeks to advance the understanding
of clinical problems through increased knowledge of brain
function and structure’ (Lishman 1992) and, as indicated by
Lishman (1992), neuropsychiatry has greater applicability to
some forms of mental illness than others. In practice,
neuropsychiatry services tend to see three broad categories of
patients:
◆ those whose psychiatric disorders result from clearly

identifiable brain dysfunction;
◆ patients with psychiatric problems with neurological

comorbidity;
◆ patients who present with neurological symptoms in the

absence of underlying neurological disease (Lishman 1992).
It is towards the third of these groups of patients that

psychological interventions are most likely to be targeted and
therefore most attention will be given to these conditions
within this chapter. However, since neurological and
psychiatric disorders are clearly not mutually exclusive, issues
relevant to the treatment of one class of disorders may be
applicable to the other.
2 Assessment
Previous chapters have described some of the
neuropsychiatric conditions and investigations necessary to
enable the clinician to arrive at a neuropsychiatric diagnosis.
However, when commencing treatment, further assessment by
the clinical psychologist will inevitably be necessary in order
to document the nature of the thought pattern that may be
problematic (e.g. in depression, where the patient will be
required, in a cognitive behavioural therapy framework, to
record negative automatic thoughts as well as activity
schedules), the patient’s psychophysiological disturbance, or
the frequency or pattern of occurrence of the behaviour that is
to be changed (e.g. challenging behaviour after head (p.718)
injury or tics in Tourette’s syndrome). Even pharmacological
treatments of disorders will require good baseline recording of
Page 2 of 36
the behaviour or thought pattern to be changed so that clinical

psychologists’ skills in this area can also contribute to the
careful evaluation of treatment efficacy.
2.1 The antecedents–behaviour–consequences (A–B–C) model

In terms of behavioural assessments, the classical approaches
to functional analysis remain valuable (cf Goldstein 2003). The
simplest of these is the A–B–C model, which assesses the
antecedents and setting events of the behaviour, the behaviour
itself, and the consequences of the behaviour. This can be
applied to challenging behaviour (e.g. aggression following
closed head injury) or brief dissociative events such as non-
epileptic seizures (see Section 4.2.4), although it would be less
commonly applied to the assessment of psychiatric symptoms
such as might be present in delusional disorders. However, the
A–B link might be worthy of consideration in attempting to
examine any potential relationship between psychotic
phenomena (the ‘behaviour’ in this example) and the
occurrence of epileptic activity (the ‘antecendent’ in this
example) in individuals being investigated with respect to the
possible diagnosis of a post-ictal psychosis.
2.2 Other models of functional analysis

◆ Other models of functional analysis (e.g. Gardner 1971)
extend the area of enquiry to the interrelationship between
problem behaviours, and the therapist will need to become
aware of the broader environment in which the patient
exists and identify the resources available to the person to
assist in treatment as well as the factors that might exert
aversive control over them and their behaviour.
◆ Motivational analysis can also be used to increase the

likelihood of treatment success (Kanfer and Saslow 1969),
and to identify behavioural strengths as well as weaknesses
that can help maximize the opportunities for facilitating
progress in therapy (Yule 1987).
◆ The therapist should also consider developmental factors

(relevant biological, sociological, and behavioural changes
that have occurred in the person’s life) since these may also
impact on therapy and its likely outcome, as may the
interrelationship between the social, cultural, and physical
aspects of the person’s life.
Page 3 of 36
◆ It has also become common to consider the predisposing,

precipitating, and perpetuating factors that account for a
patient’s problems (e.g. Mayou et al. 1995; Sharpe et al.
1995a).
◆ Further insight into the nature of the behaviour and the

pattern of its occurrence can be gained through the use of
analogue conditions where the possible A–B–C relationships
can be manipulated (e.g. Iwata et al. 1982).
◆ During treatment using cognitive behavioural therapy, the

use of behavioural experiments, where the validity of
patients’ automatic thoughts can be challenged, may be
used to test out the content of their beliefs and then
disconfirm them.
(p.719) How behaviour is measured will to some extent

depend on the behaviour itself and the resources available.
For thought patterns, self-report is necessary. Within the
context of cognitive-behavioural interventions self-
observations and self-monitoring are important for the person
to be able to understand the nature of the target behaviour or
thought to be changed (Tazaki and Landlaw 2006). More
generally for overt behaviours a variety of techniques exists,
each with their advantages and disadvantages (Murphy 1987).
Wherever possible the clinician should use measures with
proven validity and reliability so that the extent of change can
be estimated accurately.
3 Applying psychological interventions to neuropsychiatric

disorders
3.1 The importance of awareness and insight
As discussed by Manchester and Wood (2000), cognitive
behavioural therapy has been applied to a range of psychiatric
disorders in which the awareness of, or insight into, the
inappropriate behaviour or thoughts might be sufficient to
facilitate change in the person’s thoughts and behaviour, via
therapy. With respect to psychiatric disorders, insight might
be conceived as awareness by the person that they are
suffering from a mental disturbance that may constitute an
illness and acceptance of the resulting medical implications
and of the need for treatment (Surguladze and David 1999). As
Surguladze and David (1999) indicate, insight is not
considered as an ‘all-or-none’ phenomenon but rather a
dimensional one, with individuals having varying levels of
awareness of their condition. Understanding cultural
Page 4 of 36
variations in insight and belief systems is likely to be

important when attempting to facilitate patients’ engagement
in mental health services (Saravanan et al. 2007).
As Manchester and Wood (2000) note, impaired awareness is

an important characteristic of many neuropsychiatric
disorders, and as such has implications for the access to and
continued contact with services, relapse rates, and morbidity
(Kent and Yellowlees 1994; Kemp and David 1995). Husted
(1999), defining insight in terms of awareness of having an
illness, attributing one’s symptoms to the illness, and
acknowledging the need for treatment, observes that one of
the difficulties in delivering continuous voluntary treatment
for people with severe mental illnesses is that these disorders
reflect disrupted brain function and in turn affect the person’s
reasoning ability so that they often do not believe that they are
ill or that their illness will respond to pharmacological (or
other) treatments.
Impaired insight is frequently found in schizophrenia and is

also of importance in bipolar disorder (Husted 1999). It is
worth noting that insight in bipolar disorder has been shown
to be more severely affected than has insight in affective
disorders (Michalakeas et al. 1994; Ghaemi et al. 1995).
Importantly, insight may not recover with treatment (Peralta
and Cuesta 1998). The clinician should be aware that insight
may be impaired in other neuropsychiatric disorders such as
obsessive–compulsive disorder (Eisen et al. 1994) and anorexia
nervosa (Feighner et al. 1972) and thus the concept is relevant
to (p.720) those undertaking therapy with a wide range of
patients. Indeed, data have indicated that patients with Body
Dysmorphic Disorder show greater impairment of insight than
do patients with Obsessive Compulsive Disorder (Eisen et al.
2004).
The clinician should recognize that insight, or lack of it, cannot

be simply related to neuropsychological test performance, as
the results from a number of studies across different disorders
are contradictory (Surguladze and David 1999). Data have
suggested that cognitive abilities, whether one is focusing on
executive function or more general abilities, may nonetheless
be related to measures of insight and to specific activities that
require the person to undertake cognitively demanding
introspection into particular aspects of their own mental life
(Surguladze and David 1999). More recently, Lysaker et al.
Page 5 of 36
(2006) reported that when considering different domains of

insight, awareness of symptoms and treatment need were
associated with scores on measures of executive function that
particularly involved alternating attention, planning and the
ability to derive meaning on the basis of contextual cues. As
noted by Surguladze and David (1999), a number of
approaches to the assessment of insight in psychiatric
disorders have been developed (e.g. McEvoy et al. 1989;
Amador and Strauss 1990; David 1990; Markova and Berrios
1992; Birchwood et al. 1994; Kemp and David 1997) and this
may make the elucidation of consistent relationships more
difficult. It is widely accepted that lack of awareness or insight
is a common feature of people who have sustained brain
damage, whether of a traumatic or of a neurodegenerative
nature (Migliorelli et al. 1995; Zanetti et al. 1999). The
integrity of insight or awareness has been shown to relate to
the success of neurorehabilitation (Ben-Yishay and Gold 1990;
Prigatano 1991) although some inconsistencies have been
noted, possibly relating to differences in measuring or defining
insight and outcome (Malia 1997). Of clinical relevance also
are recent observations that individuals may be unaware of
some deficits but not others (Dalla Barba et al. 1999).
The presence or otherwise of insight may also be relevant to

the development of depression in patients with brain damage.
Pewter et al. (2007) review literature indicating that
depression may occur once patients become aware of their
impairments and of their inability to function at their
premorbid level. They also raise an alternative possibility, (cf.
Prigatano 1997, cited Fleminger et al. 2003) namely that
increased levels of insight permit the brain-damaged
individual to deal with their problems more effectively and
therefore protect against depression. In a group of
encephalitis patients of mixed aetiology, Pewter et al. (2007)
found that the accuracy of patients’ appraisal of their everyday
difficulties was important in determining whether or not they
were depressed, with more accurate appraisals being
associated with lower levels of depression. Their data suggest
that once the process involved in changing awareness of
deficits has occurred, the development of an accurate
appraisal of difficulties may be beneficial in the longer term.
Page 6 of 36
Manchester and Wood (2000) suggest that whilst most

therapeutic interventions can be modified to accommodate
poor memory, attention, and concentration, it is the need to
overcome poor awareness, and also poor motivation that may
often be the crucial factor in bringing about treatment
success. Issues relating to motivation will be considered next.
(p.721) 3.2 Motivation to change

Manchester and Wood (2000) have suggested a pivotal role for
the establishment of a good therapeutic relationship as a
means of increasing both the awareness of people with brain
damage concerning their problems and their motivation to
change. They stress the importance of therapist variables such
as warmth, support, empathy, non-judgemental attitude, and
the expectation that change will occur (Leber and Jenkins
1996). They also emphasize the need for therapists to
understand their patients’ thinking patterns and to engage in a
collaborative rather than confrontational approach to therapy.
Although there is no supportive empirical evidence to date,
they favour the use of motivational interviewing as a means of
raising questions about the viability of the person’s thinking
and behaviour. They also note that it may be useful, in line
with Miller and Rolnick (1991), to consider motivation for
change in people with brain damage as something that
fluctuates over time and across situations. The potential use of
a motivational approach for people with cognitive impairment
has also obtained some support from its, albeit limited,
application in the field of learning disabilities (Rose and
Walker 2000).
3.2.1 A six-stage model of change

Manchester and Wood (2000) outline and recommend the use
of Prochaska and DiClemente’s (1982) six-stage model of
change in providing a useful guide to therapy, both from the
point of developing awareness of problems, and increasing
motivation to change. These stages are:
◆ the pre-contemplation stage where others are aware that

there is a problems but the patient has not yet considered
the possibility of changing;
◆ the contemplation stage where the patient is aware of the

need to change but may feel ambivalence over this;
Page 7 of 36
◆ the determination stage where the patient decides to take

action;
◆ the action stage where the patient undertakes activities to

achieve change;
◆ the maintenance stage where additional skills are learned

to prevent relapse;
◆ the relapse stage where the patient learns to cope with

relapse.
Manchester and Wood (2000) illustrate the use of this model

with two patients with very different behavioural problems
following acquired brain injury.
With respect to one of these cases, the individual had

sustained severe cognitive impairment and therapy was
designed to increase his motivation to stop absconding from
the treatment unit in response to negative feedback from staff
about his sexually inappropriate behaviour.
◆ The pre-contemplation and contemplation stages involved

first asking the patient why he absconded and what the
consequences (positive and negative) of this were, with
respect both to the short and longer term. Where negative
consequences could not be identified explicitly, the patient
was asked to describe how the events following his
absconding made him feel.
(p.722)
◆ The determination and action stages of treatment involved
facilitating the generation of longer-term goals by the
patient and his commitment to attempt alternative
behaviour in order to achieve these. In this case the longer-
term goal was to achieve discharge from the unit and
alternative behaviours included more appropriate ways of
responding to criticism by unit staff. The process was then
reviewed by the therapist and by the patient; the patient
was asked to state the behavioural trigger, the old response
and its negative consequences, and the new response and
its positive consequences. The patient’s commitment to
change was praised, the difficulty involved in changing
behaviour was acknowledged, and the need for practice to
achieve the consistent establishment of the new responses
was emphasized.
Page 8 of 36
◆ The maintenance stage involved the development of a

verbal script for the patient to employ and role-play
exercises.
◆ Finally instances of relapse were used to identify

difficulties the patient experienced in applying the new
behaviours and these were incorporated into role-play
exercises.
Other approaches to increasing awareness do exist, however

(cf. Malia 1997), and formal evaluation of such approaches will
ultimately guide the therapist’s choice of techniques. It may
also be necessary to bear in mind that it is sometimes difficult
to distinguish between the lack of awareness of deficits due to
clear evidence of brain damage and the use of denial as a
defence mechanism (Malia 1997; Manchester and Wood 2000).
Both Malia (1997), and Manchester and Wood (2000) highlight
the need for clinicians to consider that both psychological
factors and the direct impact of brain damage may interact to
produce the level of awareness that is apparent in an
individual patient.
4 The application of cognitive behavioural therapy to

4.1 Disorders with an identifiable organic basis
Relatively little attention has been paid to the application of
cognitive behavioural techniques to neuropsychiatric disorders
in which the associated cognitive impairment might itself
necessitate modification of the techniques in use, (but see
Chapter 34). Manchester and Wood (2000) suggest that where
there is cognitive impairment:
◆ The clinician may need to make therapy sessions more

highly structured;
◆ The sessions may need to occur with greater frequency.
◆ The sessions might need to deal with more specific

behaviours, possibly in a more concrete way.
In addition:
◆ It may be necessary to adapt therapy techniques and

materials to overcome a person’s memory or reading
impairments (e.g. Newsom-Davis et al. 1998), and the
clinician should take note of findings from
Page 9 of 36
neuropsychological assessments that have been

undertaken.
(p.723)
◆ Where an assessment of cognitive functions has not been
done, such an assessment may be of value in order for
therapy to be delivered most effectively.
◆ Behavioural experiments may provide concrete feedback

to an individual that may lead to balanced appraisals and
may also highlight the impact of neuropsychological deficits
on everyday function (Dewar and Gracey 2007)
However, in general, there is little to guide the clinician as to

when cognitive and neurological signs might predict poor
response to treatment. For example, neuropsychological
abnormalities and neurological soft signs in adults with
obsessive–compulsive disorder did not predict a poor response
to behavioural treatment (Bolton et al. 2000). Similarly, no
data yet exist to indicate whether cerebral activation
abnormalities detected in a patient with conversion disorder
(Marshall et al. 1997) might have any implications for
treatment.
In the field of adult mental health, cognitive behaviour therapy

(CBT) has been widely applied to people with depression and
various anxiety disorders (e.g. Hawton et al. 1989) and is also
now being applied to disorders such as schizophrenia and
bipolar disorder where insight or awareness of difficulties may
be an issue (e.g. Kuipers et al. 1998; Lam et al. 2003).
◆ Kuipers et al. (1998) reported that 9 months of CBT,

directed at medication-resistant symptoms of psychosis, led
to a reduction in the distress caused by delusions and in the
frequency of hallucinations, with the improvement
persisting at an 18-month follow-up. They reported clinical
improvements in 65% of the CBT group and in only 17% of
the standard care group.
◆ More generally, family interventions (especially those

aimed at a single family) appear effective in preventing
psychotic relapses and hospital readmissions, as well as
improving medication compliance; CBT has been shown to
produce greater ‘important improvement’ in mental state
than other treatments, and appears to be associated with
low drop-out rates (Pilling et al. 2002).
Page 10 of 36
◆ With respect to bipolar affective disorder, Lam et al.

(2003) demonstrated the effectiveness of CBT which
incorporated:
— a psychoeducational model, emphasising the need

for combined medical and psychological therapy;
— using CBT skills to monitor mood and enable

people to cope with prodromes and change their
behaviour to prevent prodromal symptoms from
developing into full-blown episodes;
— emphasizing the importance of routine and sleep,

and
— the monitoring of behaviours that compensated for

lost time due to previous episodes of illness.
In comparison to patients undergoing standard care, patients

who were allocated to CBT (undertaken during 12–18 sessions
over the first six months and two booster sessions in the
second six-month period) had fewer bipolar episodes, days in a
bipolar (p.724) episode and number of admissions for this
type of episode. They also had higher social functioning than
the standard care group.
◆ From a broader perspective, successful applications of

psychological treatments for bipolar disorder are those that
appear to contain psychoeducational components that focus
on enhancing compliance and early identification of
prodromal signs (Colom and Lam 2005).
However, there are few formal evaluations of the use of CBT to

treat affective disorders in patient groups where there is clear
evidence of acquired organic pathology such as might be
present in disorders more typically presenting with
neurological sequelae.
◆ Davis et al. (1984) applied CBT in a group format to a

small number of patients with epilepsy, who showed a
subsequent reduction in depression scores on various
measures.
◆ Larcombe and Wilson (1984), in an early study,

demonstrated the effectiveness of brief, group-based,
weekly CBT sessions in reducing depression in a sample of
Page 11 of 36
patients with multiple sclerosis (MS) for whom depression

was the major problem, and at least of moderate severity.
◆ While not focusing specifically on depression, Benedict et

al. (2000) demonstrated that 12 weeks of
‘Neuropsychological Compensatory Training’ (which set out
to use psychoeducational and cognitive-behavioural
methods to increase MS patients’ and carers’
understanding of cognitive, behavioural and personality
change) was superior to 12 weeks of non-specific
supportive psychotherapy in reducing scores on a measure
of social aggression (and in particular excessive egocentric
speech); a non-significant reduction in depression scores
was found.
◆ In their Cochrane review, Thomas et al. (2006) concluded

that existing evidence supports the potential benefit of
cognitive-behavioural interventions in the treatment of
depression or to generally facilitate coping in people with
MS, despite a lack of good randomized controlled trials and
manualised treatments.
In neither Davies et al.’s (1984) nor Larcome and Wilson’s

(1984) studies was it reported that the CBT required
modification in response to any cognitive difficulties of the
participants. When designing cognitive behavioural
interventions to treat mood disorders in patients with organic
disorders, it will be important however, to consider whether
the nature of depressive symptomatology might differ between
diseases. Thus, for example, in MS where depression may be
under-recognised and under-treated (Ghaffar and Feinstein
2007), irritability, frustration and discouragement are more
typical than feelings of guilt and low-self esteem (Minden et al.
1987). Similarly, in Parkinson’s disease, Cole and Vaughan
(2005) have suggested that the presence or otherwise of
cognitive symptoms of depression will have implications for
the cognitive model of depression applied (in the case of the
individual patient), and the focus of therapy.
The mechanisms potentially underlying the development of

depression in Parkinson’s disease have been summarized by
Cole and Vaughan (2005). Using an A-B design with a one-
month follow-up, they report a brief, home-based application
of CBT with five (p.725) people with Parkinson’s disease; four
patients showed a clinically meaningful reduction of
depressive symptoms, with the greatest reduction seen in the
Page 12 of 36
two people who had been most severely depressed prior to

therapy. In their study, in which therapy was based around a
structured self-help therapy booklet for people with
Parkinson’s disease (Beck 2000), they raise a number of
issues:
◆ the slowness of processing speed that is characteristic of

Parkinson’s disease may affect a person’s ability to process
information during therapy;
◆ it is important to hold therapy sessions when anti-

Parkinsonian medication is having its maximum effect; so
that “off” periods should be avoided;
◆ it may be necessary to modify therapy to take account of

patients’ cognitive deficits although there is little evidence
on how best to do this;
◆ medically ill people with less severe depression may show

less benefit from CBT in comparison to those who are more
severely depressed, and may not maintain therapeutic
benefits;
◆ in conditions such as Parkinson’s disease where physical

activity may be limited by the severity of the illness, more
research is needed to indicate the relevance of physical
activity for therapy to achieve a reduction in depressed
mood.
Focusing on other neurologically-impaired adults, Lincoln et

al. (1997) reported a number of A–B single-case designs
employing CBT with depressed stroke patients, comparing the
results of no more than 10 sessions of treatment within a 3-
month period, with baseline. Of the 19 patients treated, only
eight were noted to show definite (although modest)
improvement. Lincoln et al.’s (1997) findings would appear to
indicate that:
◆ stroke patients with intercurrent illness and further

stroke might not benefit from treatment;
◆ patients with impaired memory and reasoning abilities

might be less able to understand the concepts underpinning
the treatment and therefore might have difficulty applying
them independently.
Page 13 of 36
Thus clinicians should bear these difficulties in mind when

planning the use of effective CBT for stroke patients. However,
clinicians should remember the benefits of facilitating
increased leisure activities in improving psychological well-
being after stroke if formal CBT proves difficult to implement
(Drummond and Walker 1996).
4.2 Medically unexplained disorders

4.2.1 The nature of the problem
Neuropsychiatry services may deal with a range of patients
presenting with physical or cognitive disorders for which no
medical basis can ultimately be detected, or that are in excess
of what is known about the person’s medical disorder. These
medically unexplained disorders would not include recognized
psychiatric symptoms such as delusions and hallucinations.
(p.726) Within the Diagnostic and statistical manual of

mental disorders, 4th edition (DSM-IV; American Psychiatric
Association 1994) such disorders come within the
classifications of somatoform disorders (e.g. somatization
disorder, conversion disorder, hypochondriasis), factitious
disorders, and dissociative disorders. The clinician should be
aware that there is ongoing debate about the extent to which
such classifications are adequate (Rief and Hiller 1999). In
addition, the terminology itself has been questioned (Sharpe et
al. 1995b). Within ICD-10 (World Health Organisation 1992)
disorders of interest here, such as dissociative non-epileptic
seizures, are classified within the category of dissociative
(conversion) disorders.
It is well recognized that medically unexplained disorders pose

a sizeable problem for medical services (e.g. Mayou et al.
1995; Bass et al. 2001; Nimnuan et al. 2001). It is estimated
that approximately one third of somatic symptoms seen in
primary care, population studies and in neurological clinics
are ‘medically unexplained’ (cf. Kroenke 2003; Stone et al.
2005). It is worth remembering that patients referred to
specialist tertiary services with somatoform or conversion
disorders may experience very severe levels of disability in the
absence of any underlying organic disorder (Davison et al.
1999) or present with symptoms, only some of which will have
a clear medical explanation. Here treatment can be useful in
enabling the patient to distinguish between those symptoms
that are disease-based and those that have a psychological
Page 14 of 36
basis (Sharpe et al. 1992). However, it is likely that specialist

services will see only a fraction of patients with such
presentations (Mayou et al. 1995).
4.2.2 Expanatory mechanisms

Tazaki and Landlaw (2006) have outlined how somatoform
disorders may be explained in terms of the processes
underpinning classical (respondent) and operant conditioning,
which may in turn inform the design of therapeutic
interventions. Within classical (respondent) conditioning, they
suggest that
◆ in the context of a traumatic experience that gives rise to

a negative emotional state such as anger or fear, and which
is accompanied by physiological changes, the trauma is an
unconditional stimulus (UCS), and the emotional and
physiological responses are the unconditional response
(UCR);
◆ repeated presentation of any situation that is similar to

the UCS, or that represents part of it, becomes a
conditional stimulus (CS), produces a similar emotional
state and physiological responses, and gives rise to what
become conditional responses (CRs);
◆ these emotional and physiological responses include a

range of symptoms of autonomic arousal.
Within the context of operant conditioning, Tazaki and

Landlaw (2006) remind the reader that:
◆ behaviours are likely to increase in terms of frequency of

occurrence if they are followed by what the person views as
a positive outcome (i.e. the behaviour is positively
reinforced);
(p.727)
◆ behaviours that allow the person to avoid an undesirable
situation will increase in frequency (negative
reinforcement);
◆ this will lead to the occurrence of avoidance behaviour

(or, when the fear of the situation is not quite so severe that
the person avoids it completely), in the performance of
‘safety behaviours’.
Page 15 of 36
Tazaki and Landlaw (2006) indicate how a combination of

classical and operant conditioning processes may serve not
only to allow a condition to develop, but also to be maintained.
4.2.3 Approaches to treatment

Although not always based on explicit learning theory models
(as described above), there is increasing evidence that
cognitive behavioural approaches may be of considerable
value in treating a number of such disorders (Kroenke and
Swindle 2000); however there has been relatively little
systematic evaluation of the benefits of psychodynamic
psychotherapy (Sharpe et al. 1995a). Nonetheless, Guthrie
(1995) has outlined treatment considerations of relevance to
psychodynamic psychotherapists working with patients with
functional somatic disorders. Other therapeutic approaches
for somatization disorder have included behaviour therapy,
exploratory psychotherapy, and group psychotherapy (cf.
Wilkinson and Mynors-Wallis 1994). With respect to conversion
disorders, where patients present with symptoms that appear
to be neurological in nature (e.g. weakness, paralysis,
dysphonia, sensory impairment, or memory deficits), the
treatment emphasis (within relatively limited studies), appears
to be predominantly behavioural (Silver 1996), and the
consideration of psychosocial factors also seems crucial. It is
likely however, that cognitive behavioural therapy will also be
applicable to this group of patients (Halligan et al. 2000).
Sharpe et al. (1992) described the psychological treatment of

what they call functional somatic symptoms, and Speckens et
al. (1995) described the additional and successful use of CBT
in treating what has more recently been termed ‘medically
unexplained symptoms’ (which appear to include somatization
disorder).
Cognitive behavioural treatments for these different disorders

vary somewhat, but also share common features. It is likely
that the aims considered by the clinician will be:
◆ reducing the patient’s stress and disability;
◆ decreasing the patient’s symptoms;
◆ limiting inappropriate use of medical and other care

(Sharpe et al. 1992).
4.2.4 Issues to consider when implementing treatment
Page 16 of 36
Prior to treatment by a clinical psychologist or other

psychotherapist such patients are likely to have undergone
medical investigations for their symptoms. Bass and Benjamin
(1993) have suggested that maintenance of symptoms for
longer than 6 months would justify describing the person’s
disorder as chronic, and given the time that many medical
investigations may take to organize, clinicians may well find
that they are indeed being asked to treat patients whose
symptoms appear to fall in this category.
(p.728) The task facing the clinician embarking on

psychological interventions with such patients will depend in
part on the prior medical approach the patient has
experienced. Bass and Benjamin (1993) suggest that patients
require unambiguous information about the results of their
medical investigations, and there should be a limit set for the
range of investigations which may be appropriate (if possible
negotiated and agreed between doctor and patient). They
highlight the difficulty posed by doctors worrying about failing
to find a treatable medical disorder, but not about missing a
treatable psychological problem.
◆ Patients should come for psychological treatment having

been told clearly what illness(es) they do and do not have,
and the symptoms and disability that will and will not be
attributable to any such illnesses.
◆ They should come for treatment already knowing that

they are to see someone who will be treating their disorder
from a psychological perspective, not from a medical one
(Bass and Benjamin 1993).
◆ This should be preceded by a clear account given to the

patient to indicate that all necessary investigations have
been undertaken. It would be unwise to embark upon a
psychological intervention whilst medical investigations are
continuing, as it is important that a certainty about
diagnosis can be reached, and that the patient can be given
an unambiguous account of the aetiology of their disorder,
prior to the commencement of treatment.
Despite these recommendations, it is often unclear to the

clinician undertaking the psychological intervention exactly
what patients have previously been told about the medical
basis or otherwise of their condition. Indeed, some patients
will perceive that they have been incorrectly referred for
Page 17 of 36
psychological treatment, believing that their problems

continue to have a physical basis (Salkovskis 1989). They may
also be concerned about the stigma attached to having a
psychiatric or psychological as opposed to medical diagnosis
(House 1995).
◆ The clinician should seek early clarification from the

referring doctor as to what the patient was told prior to
referral. It will be important for the treating clinician to
understand the basis on which the patient’s diagnosis was
made so that a consistent explanation can be given to the
patient during therapy and any persisting erroneous beliefs
can be corrected (Sharpe et al. 1995a).
◆ It may be appropriate for one person to coordinate all the

different aspects of the patient’s care (medical and
psychological) (Sharpe et al. 1992; Bass and Benjamin
1993) so that throughout the patient receives consistent
explanations about their disorder as well as consistent
approaches to treatment. This may be particularly relevant
for patients with multiple somatic symptoms (e.g. Smith
1995).
◆ In addition, there ultimately needs to be a clear

communication to the patient’s general practitioner about
the diagnosis and management (Davison et al. 1999) so that
treatment is not undermined at this level of care provision.
In all cases, close liaison between the treating and referring

teams is extremely important.
(p.729) Where possible other, parallel treatments for the

same symptoms should be terminated or at the very least
suspended while the psychological intervention is underway
(Sharpe et al. 1992). Withdrawal of medication, which in some
instances may actually be having a detrimental effect on the
person’s condition, should be undertaken in consultation with
the prescribing doctor (Salkovskis 1989). However, a role
remains for antidepressant medication (Bass and Benjamin
1993).
In terms of treatment success, Bass and Benjamin (1993)

review evidence which suggests that sociodemographic, pain-
related, and psychological factors can predict treatment
success. Thus age, employment, pain-related financial
compensation, pain nature and history, and the extent of
Page 18 of 36
dysfunctional illness beliefs and beliefs about illness aetiology

as well as mode of referral may all be relevant. However, it is
also of considerable importance that the patient:
◆ engages in treatment;
◆ accepts that psychological/psychosocial factors are

important in maintaining the problem;
◆ is willing and able to negotiate treatment goals.
4.2.5 The use of CBT with somatoform, factitious, and dissociative

conversion disorders
A CBT approach to the treatment of these disorders will
essentially be a collaborative one but, depending on the
disorder, may require differing numbers of sessions. The
essence will be to formulate the person’s problems in
psychological terms even when their occurrence is
complicated by the presence of an existing medical condition
(Salkovskis 1989). The clinician needs to remember that the
patient may have been used to a more passive role,
undergoing medical tests and taking medication (Sharpe et al.
1992), and thus may need time to adjust to playing a more
active role in their own treatment. As with any
psychotherapeutic intervention it will be important for the
clinician to establish a good working relationship with the
patient, provide a plausible treatment rationale, offer hope for
improvement (as a cure may not be a realistic goal; Salkovskis
1989), and be sympathetic to the patient’s worries (Sharpe et
al. 1992).
In the case of dissociative, somatization, or conversion

disorder, it will be important to:
◆ reassure the patient that they are not thought to be

‘putting it on’ but that their symptoms are real, especially if
previous contacts with services have been characterized as
dismissive of the patient’s symptoms;
◆ determine whether the patient is misinterpreting bodily

signs or symptoms as evidence of illness or whether they
have misunderstood or misinterpreted what they have been
told by doctors or others so that they perceive slight
deviations from the norm as representing serious
impairment (Salkovskis 1989).
Page 19 of 36
In the case of factitious disorder, where there is deliberate

production or feigning of physical or psychological symptoms,
this being motivated by the adoption of the sick (p.730) role,
then therapy needs to assist patients to understand why they
are acting in that way, in a non-judgemental manner (Kinsella
2001).
An important aspect of treatment will be for the clinician to

involve the family members/carers, and to provide them with
the same treatment rationale. This will allow for the
involvement of a co-therapist, who can facilitate generalization
of treatment strategies beyond the treatment session.
Somatization disorders
The successful application of a CBT approach to the treatment

of somatic symptoms has largely involved the identification
and modification of dysfunctional automatic thoughts and the
use of behavioural experiments to break the vicious cycle of
the symptoms and their consequences (Speckens et al. 1995),
with this treatment often taking place in specialist services
and in-patient units (Bleichhardt et al. 2004). Such an
approach is often more sophisticated in terms of its
components than the previously described, more limited
therapeutic approaches designed for use in primary care
settings, involving reattribution and problem-solving
(Goldberg et al. 1989; Wilkinson and Mynors-Wallis 1994). This
latter treatment approach seemed to be most beneficial for
those people:
◆ whose somatization had lasted for less than a year;
◆ who acknowledged prior to treatment that they had

psychosocial problems;
◆ who suffered from anxiety disorders.
In the case of a more traditional CBT approach, clinicians

might expect that patients with a high level of illness
behaviour might have a relatively poor prognosis (Speckens et
al. 1997).
Page 20 of 36
Hypochondriasis (i.e. severe and persistent health anxiety)
Whereas the clinician treating somatization disorders may be

faced with the patient who needs to be reassured that the
results of their medical investigations have proved negative,
the effective use of CBT with a patient with hypochondriasis
will need to enable the patient to identify clear evidence that
their problem was health anxiety itself (Warwick et al. 1996).
This may be important in preventing patients from becoming
preoccupied with a new disease once they have successfully
overcome their fears about the original illness (Warwick et al.
1996). Wattar et al. (2005) indicate that treatment requires the
patient-specific development of a plausible explanation of how
health anxiety and the processes that are maintaining it
underpin the patient’s problems and the testing out of this less
threatening formulation of their disorder, using behavioural
experiments. CBT for severe and persistent health anxiety can
be effective when implemented in a routine clinical setting and
not just in academic research centres (Wattar et al. 2005).
Page 21 of 36
Factitious disorder
Little guidance is available for the treatment of factitious

disorder (used also to describe patients with what has also
been termed ‘pseudologia fantastica’: e.g. Newmark et al.
1999, and Munchausen’s syndrome, e.g. Fink and Jensen 1989).
Certainly it is important to remember that factitious disorder
can occur in the context of organic brain damage (e.g. Lawrie
et al. 1993).
(p.731) Within DSM-IV, factitious disorder is defined as

involving the intentional production or feigning of physical or
psychological signs or symptoms, the motivation for which is
the assumption of the sick role and there are no external
incentives (such as financial gain, avoiding legal responsibility,
or improving physical well-being). This is in contrast to
malingering, where the person again deliberately produces
false or exaggerated physical or psychological symptoms but
where the motivation is financial (including compensation for
injury), evading legal responsibility, avoiding military duty or
other forms of work, or obtaining drugs. It is worth pointing
out that factitious disorder and malingering are usually
considered to be mutually exclusive. However, there is
increasing recognition that the engagement in deceptive
behaviour could occur not only for financial benefit but also to
maintain the sick role (Bass and Halligan, 2007). Both
diagnoses (malingering and factitious disorder) are pejorative
and incorrect diagnosis may carry severe financial and social
consequences; nonetheless the accurate identification of what
is purely conscious deception as opposed to entirely
involuntary symptom production (as in conversion disorders)
or behaviour that lies somewhere in between these two
extremes, may pose a significant challenge for clinicians (Bass
and Halligan 2007).
Indeed, a cognitive–behavioural perspective on factitious

disorder suggests that, in such patients, the clinician may find
the coexistence of symptoms of somatization, factitious
disorder, and even malingering (Kinsella 2001). Kinsella (2001)
discusses the use of nonpunitive confrontation in cases of
factitious disorder. However, nonconfrontational (possibly
‘face-saving’) approaches may also be of use but require very
consistent application by a multidisciplinary team. The
clinician should be aware that confrontation may meet with
different responses from patients, and Kinsella provides most
Page 22 of 36
guidance on the use of CBT with those factitious disorder

patients who recognize that they need to stop their pattern of
behaviour, are able to admit their need to stop this pattern,
and seek help. He suggests that therapy should:
◆ help the person understand their behaviour;
◆ address face-saving issues and the benefits and

disadvantages of revealing the true picture to family and
other professionals;
◆ identify triggers for the behaviour;
◆ stress the disadvantages of repeated, often dangerous

medical investigations.
In addition, Kinsella recommends that activity scheduling

should be used to provide the person with a more pleasurable
way of meeting their needs, and the patient’s unhelpful
cognitive schemas should be addressed. However, as yet there
is no formal evaluation of such treatment to guide the clinician
as to its effectiveness.
Dissociative conversion disorders
In terms of the treatment of dissociative conversion disorders

some preliminary evidence, drawn from an open trial of CBT in
patients with dissociative non-epileptic seizures (Goldstein et
al. 2004) indicates that CBT may offer a useful therapeutic
model for these patients. Thus approaches similar to those
described above for somatization disorders may be effective in
reducing the occurrence of events that superficially resemble
epileptic seizures but that do not have an organic basis, (p.
732) although at present there is a lack of published
adequately-designed randomized controlled trials to
demonstrate the use of psychological therapy for dissociative
(non-epileptic) seizures (Brooks et al. 2007) and the field in
general is viewed as one in which treatment development is
needed (LaFrance and Barry 2005; LaFrance et al. 2006).
Mellers (2005) has provided a helpful overview of how to
manage such patients, emphasising that these patients can be
difficult to engage, having probably had multiple prior
contacts with medical services. Inherent in Mellers’ (2005)
approach are the following points:
◆ Patients with dissociative seizures will require a clear

message that their attacks do not have an epileptic basis,
Page 23 of 36
and must have the reasons for this explained to them and to
their carers/families. This explanation may require
repeating on subsequent occasions.
◆ It is essential, however, that these patients are not made

to feel that are ‘mad’ or that they have necessarily been
fabricating their seizures; it should be acknowledged that
they are real events, in that they are significant episodes of
disturbed behaviour that are disruptive to the person’s life
and represent the expression of psychological distress (i.e.
one should describe what they do have and a description of
dissociation may be helpfully provided). At the point at
which the diagnosis is presented (or treatment commenced)
the underlying psychological triggers may not be/have been
apparent, but if these and/or maintaining factors are
identified these should be raised with the person.
◆ If the person has no history of actual epilepsy yet has

previously been (incorrectly) prescribed anti-epileptic drugs
(AEDs), then they should start a process of medically-
supervised AED withdrawal; otherwise persistence with
AEDs may, for the patient, represent a ‘safety behaviour’ in
CBT terms and may continue to convey the message that
the person has an organic disorder (i.e. epilepsy), as well as
exposing them (and in the case of women of childbearing
age, their offspring) to unnecessary potentially adverse
(including teratogenic) effects from the medication.
While a percentage of patients with dissociative seizures will

become seizure-free following diagnosis, engaging those
patients who continue to have seizures in psychological
treatment may require the therapist to adapt treatments for a
range of psychological disorders, given the often complex
histories and comorbid problems seen in this patient group. A
detailed review of the potential application of different
psychological treatment approaches to this patient group is
provided by Reuber et al. (2005). More generally, however,
from a CBT perspective (and see Goldstein et al. 2004):
◆ The treatment of this group of patients is collaborative in

nature and will benefit from the involvement of other key
people in the person’s life to facilitate appropriate changes
to behaviour outside of the treatment session, and to assist
with exposure to situations and activities that the person
had avoided through fear of having a seizure.
Page 24 of 36
◆ Specific techniques may be used to distract the person

from symptoms warning them that they might be about to
experience a seizure and to encourage relaxation, thereby
reducing symptoms of anxiety that might precede a seizure.
◆ Treatment would also involve the use of problem-solving

techniques and the challenging of negative automatic
thoughts.
(p.733)
◆ Additional problems that might lead to low mood or act as
seizure triggers (including reminders of earlier trauma)
require attention.
◆ As with all the other disorders discussed here the

therapist needs to consider strategies to enable the patient
to prevent relapse of their symptoms.
4.2.6 Treatment of somatic symptoms in older adults

Specific attention has also been paid to the treatment of
somatic symptoms in older adults (Pearce and Morris 1995). In
this area of work, clinicians will need to consider the many
age-related changes that may influence symptoms found in the
elderly. Thus, in an older age group, in particular, somatic
symptoms may be wholly organic in origin, partially explained
by disease, or completely functionally determined. In practice,
it is more likely for older adults to present with a mixture of
organically and functionally based symptoms than younger
adults (Pearce and Morris 1995). Thus there will be an
emphasis on determining whether the physical condition is a
sufficient explanation for the level of disability experienced. In
addition, it will be necessary to remember that physical
failings can give rise to emotional distress, and early
dementias can be accompanied by mood change and concerns
over health. Pearce and Morris (1995) suggest that many of
the treatment approaches used for somatoform disorders in
younger adults may be appropriately modified for use with
older adults.
Page 25 of 36
5 Conclusions
Whether treating psychological disorders that have a purely
organic basis, that are determined by organic and
psychological factors, or that are purely psychological in their
aetiology, the clinical psychologist working with a
neuropsychiatric population has a number of treatment
approaches to employ that require similarly good skills of
problem assessment and formulation as well as engagement of
what can be very difficult to treat patients. However, the
refinement of treatment approaches will be ongoing and the
clinician is advised to keep abreast of the rapidly accumulating
literature relating to developments that continue to occur in
this challenging area of clinical work.
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Page 36 of 36
Forensic issues in neuropsychology


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001

William W. McKinlay
Michaela McGowan
Jane V. Russell
DOI:10.1093/acprof:oso/9780199234110.003.36

This chapter discusses the role of neuropsychology in civil and
criminal cases. Neuropsychologists may be called on to assist
in civil cases (e.g., in personal injury claims after traumatic
brain injury) and other brain injury including medical
negligence (e.g., anaesthetic accident). Cases in which there is
severe brain injury are amongst the largest personal injury
claims coming before the Courts. The large amounts at stake
reflect that the costs of providing specialized care to someone
with significant disability for the rest of their life are very
substantial, together with the fact that there may be
substantial loss of earnings. Neuropsychologists sometimes
also assist in criminal cases where issues regarding fitness to
plead and fitness to present evidence arise in individuals who
may be neuropsychologically impaired. In addition, retrograde
amnesia and post traumatic amnesia associated with traumatic
brain injury may limit recall of key events, such as an accident
or assault, and this can raise important issues so that the
Page 1 of 33
Court may require information about the nature and extent of

these periods of amnesia.
Keywords: neuropsychologists, neuropsychological assessments, civil cases,

criminal cases, post traumatic amnesia, retrograde amnesia
1 Introduction
Neuropsychologists may be called on to assist in civil cases
(e.g. in personal injury claims after traumatic brain injury
(TBI)) and other brain injury including medical negligence
(e.g. anaesthetic accident). Cases in which there is severe
brain injury are amongst the largest personal injury claims
coming before the Courts. The large amounts at stake reflect
that the costs of providing specialised care to someone with
significant disability for the rest of their life are very
substantial, together with the fact that there may be
substantial loss of earnings.
Neuropsychologists sometimes also assist in criminal cases

where issues regarding fitness to plead and fitness to present
evidence arise in individuals who may be neuropsychologically
impaired. In addition, retrograde amnesia (RA) and post
traumatic amnesia (PTA) associated with traumatic brain
injury may limit recall of key events, such as an accident or
assault, and this can raise important issues so that the Court
may require information about the nature and extent of these
periods of amnesia.
2 Civil cases
2.1 Why is a neuropsychologist’s opinion required?
Serious brain injury typically results in:
◆ physical/sensory sequelae;
◆ cognitive sequelae;
◆ emotional/behavioural sequelae
Psychological factors (cognitive and emotional/behavioural

sequelae) are the most important determinants of disability
(Jennett et al., 1981) – including reduced ability to work and
need for care/supervision. The sequelae of brain injury,
especially emotional/behavioural changes, cause stress on
family members and sometimes family breakdown, making
issues of care more pressing (cf. McKinlay and Watkiss 1999).
Loss of earnings and costs of care are often the two main
drivers of quantum of damages in these cases. The
Page 2 of 33
neuropsychological assessment is often a key assessment in

identifying the factors which may impede return to work and
give rise to the need for care and supervision.
(p.742) 2.2 What information do the lawyers and the court need?
In order to decide what, if any, compensation is due, the court
must decide on two broad areas:
◆ liability: did the defending party cause “loss, injury and

damage” to the plaintiff (England) or pursuer (Scotland) or
claimant/petitioner (some other jurisdictions)?
◆ quantum (amount) of damages, which depends on the

extent and implications of the loss, injury and damage
suffered.
In cases brought before the courts in the UK damages are

awarded under two broad headings. (In America, punitive
damages may also arise, and in other jurisdictions the basis of
calculation may differ.)
◆ There is a sum for‘general damages’ (England)

or‘solatium’ (Scotland). The extent of pain and suffering is
relevant here, as is the extent of the injured person’s
awareness: the more the injured person is aware of his/her
predicament, the greater this element of the damages,
other things being equal. At the time of writing this sum is
always less than £250,000 in the UK.
◆ There is a sum for‘special damages’, often by far the

larger part of the damages awarded in cases of serious
injury. Key factors in calculating quantum of special
damages include extent of loss of earnings and extra costs
arising from disability. This element of the damages may
take the total award to several million pounds after severe
disabling brain injury in the UK.
It follows that key information lawyers seek to take from

neuropsychologists’ reports (and, in their respective fields,
from other clinicians) is:
◆ the nature and extent of any impairment, disorder, or

other effect of injury;
◆ causality: did the injury cause or substantially contribute

to the difficulties suffered?
Page 3 of 33
◆ the prognosis (with and without treatment), including

timescale;
◆ the functional implications, especially for work and care

needs.
The neuropsychologist should therefore consider:
◆ What is the nature/extent of neuropsychological

impairment and emotional/ behavioural change? What
abilities remain intact? It is important to look for intact as
well as impaired abilities as these are relevant to
rehabilitation and work prospects, and prognosis.
◆ Are the impairments/disorders/etc more likely to be due

to the injury than to any other cause? Failing this, has the
injury made a significant contribution to these impairments/
disorders/etc?
◆ Is further treatment/rehabilitation indicated (and, if so,

what kind, with what aims)? What is the prognosis? Is it too
soon to estimate long-term outcome? (The likely long-term
prognosis will seldom be clear until at least 2-3 years after
serious brain injury.)
◆ What implications – in broad terms – do the impairments

and other changes have for functional outcome, including
ability to work and lead a social life, and need for care/
supervision?
(p.743) Civil cases are decided on the balance of probability.

The question is, for example, whether it is more likely than not
that the injury (rather than some other factor) caused – or
materially contributed to – the problems found. It is also
important to remember that the court will usually make a
once-for-all decision, based on the best evidence available at
the time. Damages in the UK and many other countries are not
punitive, but reflect loss of earnings, care costs, etc. In the
UK, an exception to this general rule is that the damages
awarded to the victims of criminal assault in the UK via the
Criminal Injuries Compensation Authority (CICA) are strictly
limited – the maximum total damages for any CICA case in
2008 is £0.5 million, unchanged for several years.
2.3 How should the assessment be conducted?

2.3.1 Stage 1 – Accepting instructions
Page 4 of 33
(i) Before accepting instructions, ensure that you can

do what is asked (i.e. can you comment on all of the
questions raised?). Amongst the questions there may be
some – such as life expectancy and risk of epilepsy –
that are matters for other experts. You should point this
out at the outset.
(ii) Experts are often asked by potential referring
sources about the percentage of instructions they
receive from Plaintiff side, Defender side, or on a joint
basis. That is information that experts should have to
hand, and on which they should reflect if they find that
a preponderance of instructions tends to come from
one side rather than the other. One has to bear in mind
an overriding duty to be fair and impartial.
(iii) A further point about expertise is that there is a
good argument that experts should have a current non-
litigating practice with the kinds of patients that they
are assessing for medico-legal purposes. That this is
desirable is generally agreed, at least in public
discussion, by both experts and lawyers although it is
not a standard which all experts are in fact able to
meet.
(iv) There may be strict time requirements, especially in
England under the Civil Procedure Rules (CPR) but
increasingly also in other jurisdictions. You should only
accept instructions if you can meet these time
requirements. If you cannot, there may be room for
negotiation but you should do this at the outset.
(v) There is no harm in agreeing at the outset, at least
broadly, the level of fee and when it will be paid and
further comment on this is made below in considering
the need to avoid having any financial interest in the
outcome.
Page 5 of 33
(vi) It is important to avoid conflict of interest. Obvious

conflict of interest may arise where an expert works for,
or is affiliated with, a provider of services (e.g.
rehabilitation services) and may end up recommending
such services. It is important to declare any such
conflict or potential conflict of interest. However, it
need not be a reason to reject such work so long as
conflict of interest is declared. At least those experts
who are also rehabilitation providers have current
experience in the field – some “experts” (p.744)
commenting on rehabilitation have not practised
rehabilitation for many years (or at all). It is always
possible for the instructing solicitors/insurers to
commission a commentary from a disinterested party if
it is felt that a conflict of interest may become active.
(vii) Lawyers will sometimes instruct the treating
clinician, will sometimes go to an independent expert,
and will sometimes use a mixture of both in an
individual case. The advantage of instructing a treating
clinician is that he or she is very well acquainted with
the case and will have known the injured individual
over a period. The potential disadvantages are firstly
that they may be (or may be perceived as being) overly
sympathetic to the individual because of their personal
involvement in the case; and a somewhat contrary
concern that they may overstate the degree of recovery
without necessarily intending to do so because they are
reviewing their own “handiwork”. Treating doctors
have a place in medico-legal work but very often
independent practitioners are preferred and provide
the main reports. A potential conflict would arise where
a treating clinician was asked by the Defenders to
provide a report. In one sense this might not seem to
lead to insuperable difficulties, as whatever the source
of instructions the report should be impartial.
Nevertheless the perception could be that, because of
instruction by the Defenders, the treating relationship
would be compromised.
Page 6 of 33
(viii) The Civil Procedure Rules in England and Wales

which can be found on the website www.dca.gov.uk are
particularly helpful in setting out the various matters
which an expert should consider before, during and
after the assessment. These do not apply in Scotland
although the broad principle that experts should be
impartial and not partisan certainly does apply. (It
would be helpful if the Scottish Courts produced a
website setting out what the Courts expect of experts.)
An important requirement under the Civil Procedure
Rules is that experts should enter the following
statement into reports: “I confirm that I have not
entered into any arrangement where the amount or
payment of my fees is in any way dependent on the
outcome of the case”. Notwithstanding this
requirement the first author has encountered the
situation where a legal firm seeks to make
arrangements for payment which could run contrary to
the CPR requirements. Specifically, a legal firm setting
up a panel of experts asked that experts “agree a price
structure … under which, if we are unable to recover
your fee from the third party insurers … you would
write your fee off”. Legal advice is that this would give
the expert a direct financial interest (e.g. where a case
was abandoned and the fee not recovered the expert
would not be paid). It is important to be sure that
arrangements for payment are transparent, with no
strings attached which could in effect give the expert a
financial interest in the outcome.
2.3.2 Stage 2 – Reviewing records

It is good practice to have all the records you need prior to
assessment, so that you are properly briefed, and also so that
issues arising can be clarified with patient/ relative. Lack of
records can be a reason for assessments being wrong. On the
other hand, there is an increasing tendency in UK cases for an
extremely large volume of records to be sent to experts and it
is worth making plain to those instructing you just which
records would be (p.745) helpful – it will not be helpful for a
neuropsychologist to see large volumes of results of blood
tests, x-rays films, etc. (Some experts charge an administrative
fee for sorting records which arrive poorly ordered.)
The following records are often useful:
Page 7 of 33
◆ GP medical records should make evident any significant

pre-injury disorders or handicaps and other factors or
conditions (e.g. poorly controlled diabetes, alcohol/drug
abuse, previous injuries, etc) which may impact
significantly on neuropsychological function.
◆ Educational records (especially for younger people

recently in education) or employment records (where
available) may help confirm test-based estimates of
premorbid ability. Sometimes due to young age at injury or
acquired language deficits, the usual methods for assessing
premorbid ability (e.g. Wechsler Test of Adult Reading –
WTAR) cannot be used, and these records will be even more
important. It should also be borne in mind that severe brain
injury has been found to compromise performance on the
WTAR (Mathias et al., 2007), so that exclusive reliance on
this test (and probably similar tests) is best avoided,
although such tests remain very useful indeed.
◆ Acute hospital records relating to the admission after

injury should be reviewed to confirm that there was indeed
a significant injury. Information on Glasgow Coma Scale,
scan results, and any clinical evidence of focal neurological
signs is important. Duration of post traumatic amnesia
(PTA) is often not explicitly recorded, but orientation may
be. The return of orientation and the ending of PTA cannot
be assumed to occur at exactly the same time, but the
ending of PTA is seldom long delayed after the return of
orientation. Information about orientation is often in the
notes – if not in the reports, then in the handwritten clinical
notes of the psychologist, speech and language therapist,
and other therapists and nurses.
Injury severity is a key consideration if seeming deficits are to

be reconciled with the injury. If you do not know from a source
independent of the patient/relative how severe the injury was,
there is a danger of incorrect assessment/diagnosis. In
particular, patients with post-concussion symptoms (PCS)
following mild-moderate injury (a condition which is
considered to be at least partially maintained by anxiety) may
show superficial similarities to patients with more severe brain
injury. There is also the risk of malingering: it is not entirely
unknown for long coma, long PTA, and great disability to be
Page 8 of 33
claimed falsely after what proves from actual records to have

been mild or moderate injury.
◆ Later hospital/rehabilitation records should also alert the

assessor to behavioural problems. These may not emerge in
the calm, contained environment of the neuropsychological
examination, but may be a problem in day-to-day
interactions with others, and must not be overlooked.
2.3.3 Stage 3 – The examination

It will be apparent from the comments above that the
instructing lawyers and the injured party and their family are
entitled to expect that expert witnesses will indeed have
expertise in the relevant area and that they will be impartial.
There are other expectations, however, that may potentially be
more problematic.
(p.746) The instructing solicitors may have ‘sold’ the expert

as a prominent practitioner who will be able to ‘help’ with the
case and there may be a perception on the part of some
injured persons and families that you are there to help them
win the most damages possible. It is of course not the job of
the expert either to maximise damages if instructed by the
Plaintiff or to minimise damages if instructed by the
Defenders. The expert may explore possible support or
rehabilitation, but should be cautious about holding out a firm
prospect of such help – the injured person may lose the case or
there may be significant contributory negligence (limiting the
damages awarded). To the extent that the expert can ‘help’, it
is that a comprehensive and clear report should help to
narrow the issues between the parties and help to move the
case towards the point of settlement.
A further expectation which has to be treated with caution is

to do with confidentiality. There are always limits to
confidentiality between psychologists/clinicians and patients.
(There are BPS guidelines which set out how to resolve such
issues – see www.bps.org.uk.) Injured persons and their
families should of course have been made aware by their
lawyers that there are further constraints on confidentiality in
the medico-legal process. However, one has the impression
that they are not always as aware as one might hope of the
limitations on confidentiality. It is therefore particularly
important to be alert to questions like, “Can I tell you this in
confidence?” and to ensure that the limits of confidentiality
Page 9 of 33
are explained. A relevant consideration is that when a case is

decided it may well enter the public arena. For example,
judgements in all cases decided by the Courts in Scotland (as
opposed to those settled out of Court) are published on the
Internet, and these reports may include considerable detail
about the medical and social history of the injured party, the
nature and extent of injuries, the effects of injury, and their
social circumstances. Further comment on the risk of
inadvertent breach of confidentiality is made below.
The assessment should usually include a joint interview

between the patient and a significant other; an interview and
assessment of the patient; and a separate interview with a
significant other. A further possible element in the assessment
is a further testing session with a psychological technician or
assistant psychologist on which further comment is made
below. It is very hard to do a satisfactory assessment without
also speaking to a relative or close friend given that the
patient may very well have memory gaps and limited insight.
In practice it is very rare indeed for patient/relative not to
agree to separate interviews (if the need is well explained). It
is however not unknown for follow-ups (not
neuropsychological follow-ups) to be based on a cursory
interview with the patient alone, and therefore to be
potentially misleading.
Joint interview
Since the patient may well have retrograde amnesia and post
traumatic amnesia, information about events around the time
of injury is often best collected with a relative also present.
Further information which may best be collected with both
present – in cases of memory or communication problems – is
social and health background.
Separate interviews
Due to the problem of lack of insight on the part of the injured

person, there is a danger of under-reporting. It is useful to
think of insight using the four stages suggested by Fleming et
al., (1996):
1 Lack of awareness (or admission) of deficit.

2 Awareness of deficit.
(p.747)
Page 10 of 33
3 Awareness of functional implications of deficit.

4 Ability to set realistic goals.
These stages typically are worked through first in relation to

physical limitations, and then cognitive limitations, and lastly
emotional/behavioural limitations. However, by no means
every injured person completes the process.
It is therefore essential for an interview with a relative or

‘significant other’ to be carried out – if at all possible,
separately. While the relative’s view cannot be assumed to be
the ‘gold standard’, there is evidence which suggests it is
more likely to be accurate. For example, Sunderland et al.,
(1983a) found relatives’ accounts had greater validity as
regards memory failure than those of patients. The separate
interviews with patient and relative should each cover the
main possible sequelae of injury (see McKinlay and Watkiss
1999). Deficits of functional significance may arise in the
following areas:
◆ The physical/sensory changes (including epilepsy) are of

course primarily matters for others, but nevertheless a
broad view of them should be kept in mind in considering
the psychological picture.
◆ There may be symptoms such as headaches, dizziness,

poor balance, intolerance of noise, tiredness, changes in
sleep/wake pattern, loss of libido. Some of these, especially
tiredness, are very common and can be very disabling
(Ziino and Ponsford 2005). Tiredness can exacerbate
behavioural disturbances, and can ‘bring out’ otherwise
silent residual deficits. It can also impact upon an
individual’s ability to participate in rehabilitation.
◆ The cognitive changes should be reviewed, and an

attempt made to identify how they affect daily life.
◆ The emotional/behavioural changes should likewise be

reviewed. Some patients will deny all such problems while
other evidence (relative’s account, records) suggests
otherwise.
◆ Progress in returning to education or employment should

of course be considered. Careful questions about how they
spend their time (‘an average day’) should be asked. Family
and social life, and maintenance of friendships, should be
Page 11 of 33
explored. Social isolation is the major long-term danger for

many patients and their families (Morton and Wehman
1995).
The above list is not exhaustive. Questions about other life

events and about such factors as alcohol/drug abuse are
relevant. Distinctions which are relevant to good clinical
practice in any event are even more important in medico-legal
reporting, and it is important to be clear about the following
points:
◆ The distinction between spontaneous and elicited

complaints
◆ The source of information should be clear (patient,

relative, test scores, or records?)
◆ The distinction between what is reported and observed

and inferred should be made clear.
Neuropsychological examination
There are several areas which it is important to assess. It is

probably not productive in a chapter such as this to debate the
merits and demerits (p.748) of particular tests. Perfectly
sound neuropsychological examinations may be based on
varying selections of tests, so long as the tests are suitable for
the purpose and the proper range of abilities is sampled. The
key areas which should be covered are as follows.
◆ A language screen should include consideration of

spontaneous speech and brief tests of repetition, naming,
obeying commands, reading and writing, as Lezak et al.,
(2004) have described.
◆ Intellectual level – premorbid and current. A caution

should be entered against using an “overall” IQ score in this
context. Scores which average subtests vulnerable to the
effects of brain injury with subtests which are not
vulnerable will mask the nature and extent of impairment.
Separate consideration of subtests or indices is therefore
better in this context than overall IQ scores.
◆ Both verbal and visuospatial memory should be assessed.

It is worth bearing in mind that verbal memory (especially
as assessed by Logical Memory from the Wechsler scale) is
one of the tests best related to ‘everyday’ memory failures
Page 12 of 33
(Sunderland et al., 1983b) and failure to return to work

(Brooks et al., 1987).
◆ Another key area to consider is attention/concentration.

Difficulties in ‘divided attention’ are especially common.
◆ Executive functions, impairment of which is associated

with frontal lobe damage, are also common and can be very
disabling even where other aspects of cognitive function
are not grossly impaired.
◆ ‘Focal’ problems (e.g. dyspraxia/agnosia/etc) should not

be overlooked, although they are not especially common in
marked form after TBI.
◆ Some clinicians include questionnaire measures of

emotional adjustment. However, it should be borne in mind
that – in a medico-legal context – these are often essentially
a series of leading questions. The manuals of many such
measures caution against their use in a medico-legal
context. They need to be interpreted with great care.
There has always been a certain divergence between those

who adopt a ‘battery’ approach to neuropsychological
assessment and those who use a hypothesis testing approach,
with the latter being much more parsimonious in the extent of
their testing, and not necessarily using the same set of tests
with each patient. There have been developments in testing
whereby for example more sophisticated tests of frontal lobe
or executive function have become available and where effort
tests have become almost de rigueur in neuropsychological
assessment. Some UK clinicians are increasingly adopting the
practice of using a test technician to complete a further
session of tests after their initial assessment. The argument
can be made that with the improved range of tests and
increasingly good norms now available, one should utilise
these fully. On the other hand, the argument can also be made
that test scores are best interpreted in the context of
information from interviews, records, and qualitative
observations, and best done by neuropsychologists rather than
by test administrators. Moreover there is room for debate
about the extent to which the increased demands made of the
patient in lengthy testing (which at least some find stressful) is
justified by the additional information obtained.
Page 13 of 33
(p.749) It is increasingly common to incorporate tests of

effort. In the American Academy of Clinical Neuropsychology
(AACN) Practice Guidelines (2007), it is noted that there is a
‘growing literature’ which suggests that ‘the assessment of
motivation and effort is critical when conducting a
neuropsychological evaluation’. This document incorporates
the following advice: “Clinicians utilize multiple indicators of
effort, including tasks and paradigms validated for this
purpose, to ensure that decisions regarding adequacy of effort
are based on converging evidence from several sources, rather
that depending on a single measure or method”. I understand
that the Division of Clinical Neuropsychology of the British
Psychological Society is currently considering the question of
offering guidance to neuropsychologists on the need to
incorporate measures of effort into their assessments
(McMillan, Personal Communication).
The assessment of effort is linked with the issue of

malingering although it is a link which has to be made with
some caution. Malingering is defined in DSM-IV as the
intentional production of false or grossly exaggerated
(symptoms or deficits) motivated by external incentives. On
the other hand, there has been a view that malingering is
more of an accusation than a diagnosis, and that clinical
assessments should stop short of reaching the conclusion that
there is actual malingering and should be limited to
considering whether the symptoms presented are credible.
Boone (2007a) notes that non-credible symptoms may be part
of somatoform disorders and also conversion disorders and
indeed observed that forced-choice methodology (a mainstay
of many effort tests) was originally used to help identify
conversion.
However, plainly in a personal injury litigation situation there

is a potential incentive to ‘fake bad’. In some studies subjects,
including psychology students, have been asked to simulate
(‘fake’) deficits. Such fakers tend to do badly across the board
– as if reluctant to do well even on easy items. TBI patients
usually still find some tasks quite easy and typically, although
not invariably, show:
◆ little deficit on measures of personal information, basic

language function, verbal IQ, and forwards digit span;
Page 14 of 33
◆ a degree of difficulty on measures of performance IQ;
◆ major difficulty on tests of memory and attention/

concentration (the latter including backwards digit span,
Digit Symbol, and PASAT).
◆ Some also have great difficulty with ‘frontal’ (executive

function) tests. A ‘flat’ profile, doing badly across the board,
is suspicious. Overall, key areas to look for are:
- A typical test performance, with seemingly great

difficulty on simple tests.
- Marked inconsistencies in what is expected from

the nature of injury and the patient’s presentation
and self-reports.
◆ It is also worth bearing in mind:
- Did the claimant consult a lawyer before seeking

full clinical assessment and/or help with ‘post-injury’
problems?
- Have symptoms shown typical progression over

time?
- Is the claimant’s account at interview consistent

with the records?
(p.750) There is a wide array of effort tests now available

and this is a topic which has been receiving increasing
attention (e.g. Millis 2008, Boone 2007b; Larrabee 2007). It is
important to keep in mind that effort testing is not a
straightforward matter of detecting malingerers but a matter
of detecting suboptimal effort or non-credible cognitive
performance. It is arguable that assessment of effort should
become a more prominent part of neuropsychological
assessment, not just in forensic (civil or criminal) settings, but
also more generally. The simulation of deficit may not only be
for external gain (compensation, evading punishment,
receiving benefits, or receiving sympathy) but could also
relate to internal conflicts – for example Boone (2007a)
discusses pseudo-seizures (‘several minutes of thrashing and
jerking’) which are usually accepted as non-conscious
behaviour with possibly complex motivations. It is possible
that sometimes suboptimal performance could perhaps be
analogous to this.
Page 15 of 33
Assessment of effort is in a sense not new. It has always been

integral to the neuropsychological assessment (as to a clinical
psychological or medical assessment) to form a view about the
nature and cause of the symptoms, and that includes forming a
view as to whether symptoms/deficits presented are credible
or not. The phenomenon of ‘answering past the point’ (How
many legs has a cow? 3; How many weeks in a year? 53) has
long been recognised as an indicator of non-credible ‘deficit’.
Neuropsychologists have long had an array of tests (e.g. the
Andre Rey 15-Item test and Dot Counting Test described by
Lezak et al., 2004) and also various indices which may be
derived from standard IQ/memory tests (Rawling and Brooks
1990; Gudjonnson and Shackleton 1986) to detect simulation.
To that extent, the introduction of effort test does not mark a
step change in the nature of neuropsychological assessment,
but rather an increased level of sophistication in the analysis
of the responses that patients give. Boone (2007a) notes some
debate about giving ‘warning’ to patients before using some of
these tests but rightly (in the present authors’ view) concludes
that specific warnings would be inappropriate. They may
render the administration of tests non-standard, and not as
intended by the test developers. Moreover, as Boone notes,
there is an understood social contract that presenting
fraudulent data is wrong and indeed may be punishable. In
any event the whole neuropsychological assessment, like other
medical/psychological assessments, must – if it is to be of any
value at all – include the formation of a view about the
credibility of the symptoms presented. That said however, it is
prudent and reasonable to encourage best efforts on testing.
There are specific tests which have become widely used

including the Test of Memory Malingering (TOMM, Tombaugh
1996) and the Word Memory Test (WMT, see Green et al.,
1999). Both of these are two-alternative forced-choice tests.
Consideration has to be given to the sensitivity of the tests.
Green (2007) discusses the relative failure rates on TOMM
and WMT effort subtests amongst others, noting that a much
higher percentage of the sample studied (32%) failed the
effort subtests on the WMT than on the TOMM (11%). An
analysis of the evidence is argued to suggest that the
difference is mainly due to false negatives on the TOMM. One
could debate the relative merits of these tests and that is
outside the scope of this chapter but it is important to
remember that tests are of varying degrees of sensitivity. It is
Page 16 of 33
wise to bear in mind through the whole assessment the (p.

751) need to form a view about the credibility of the
symptoms and not to rely only on a single measure.
It is important to remember too that these tests can provide

reassurance to the examiner that the deficits being seen are
probably real. One case seen by the first author was a young
man of 20 with a poor educational record and limited
employment history who had sustained a severe head injury.
Had he performed poorly on testing, a possible interpretation
would have been that this was contributed to by his being
unaccustomed to test taking. That concern on the part of the
assessor was allayed by a good performance on effort testing,
which gave confidence that the poor performance on other
aspects of memory testing was likely to represent real deficit.
Modern effort tests, however, do have significant advantages
over some of the more traditional tests in that they are more
likely to detect suboptimal effort in relatively sophisticated
test takers. Another case seen by the first author – an
academic in middle years – was able to give an intensely
detailed account of various aspects of the case, and was
running a household including driving a fairly large mileage.
On the WMT, performance on the effort tests was close to
chance and worse even than the ‘hospitalised elderly dements’
quoted amongst the norms. This was plainly not credible as a
reflection of true memory capacity. Indeed even without the
effort test, the very poor memory performance would have
been implausible, but the WMT provided detailed evidence
and normative comparisons which made that conclusion all the
more cogent.
It is important to remember that there may be some rare

exceptions, for example Broca’s aphasics are routinely misled
by aspects of sentence structure and this can lead to below
chance performance which is not malingered or representative
of a lack of effort (Grodzinsky 1995). There is also a more
general caveat that surprising and hard-to-understand
behaviour should not too readily be taken to suggest
malingering, as there may be an underpinning organic
explanation. For example, the first author has come across a
case of ‘foreign accent syndrome’ in which the subject spoke
(after a mild stroke allegedly due to medical negligence) with
a ‘mid-European’ sounding accent, despite no connection with
that part of the world. The question of malingering had been
raised. However, although rare, this condition has been
Page 17 of 33
reported to arise sometimes with and sometimes without

aphasia and to be related to anterior left (dominant)
hemisphere lesions, generally of the frontal and precentral
gyri (Kurowski et al., 1996; Moonis et al., 1996; Takayama et
al., 1993), as was the case with the subject.
2.3.4 Stage 4 – Reporting and giving evidence

The next stage is to write the neuropsychological report. As
the great majority of cases are settled before reaching an
actual court hearing, the report will often be the only means
by which the neuropsychologist’s opinion will be
communicated to the court.
What should be included in a medico-legal

neuropsychological report?
The report (like other medico-legal reports) should set out the
instructions given, state where and when the patient and
relative were assessed/interviewed, and describe the
documentation studied. The nature and severity of injury
should be considered, drawing on patient/relative (p.752)
interview and evidence from the records. As always, the social
and health background should be described. The information
from patient/relative interviews and from the
neuropsychological examination should be presented.
Neuropsychologists differ in whether they include scores,
centiles, etc in their reports or use terms like ‘moderate’ or
‘very severe’ impairment. Some argue that actual scores may
be misinterpreted by non-psychologists, but without scores
one is left only with vague and non-operational terms like
‘severe impairment’. Centile scores have the advantage that
they can be calculated for most tests and provide a basis for
comparison. One solution for those unwilling to include actual
scores in the body of the report is to provide a technical
summary as an appendix in which scores, test versions used,
etc are listed. This facilitates later assessment by other
neuropsychologists.
The report should set out conclusions on the key areas of

relevance to the court, as set out more fully above (i.e. nature/
extent of impairment and change; cause and effect; treatment
and prognosis; and functional implications).
What areas should be addressed with caution?
Page 18 of 33
There are also areas which it is not appropriate to cover as

they are primarily a matter for related reports. To stray into
these areas may confuse the issues and give rise to
unnecessary contradictions in the evidence. It may be quite
appropriate for a neuropsychologist to say that someone has
such severe deficits that they are likely to be incapable of open
market employment, or would be capable only of restricted/
simple work. However, to speculate as to what jobs may be
available in more detail may be unwise. Normally such
questions are for an employment expert with knowledge of
availability of employment in the appropriate travel-to-work
area; knowledge of factors which might militate against
employment in the relevant field; knowledge of competition for
such jobs; and so on.
There will often also be a report on future care which will

include costs. It is unhelpful for clinicians to be too specific on
care needs: the details are a matter for a care specialist who
knows the practicalities of care provision, and can seek to
match what is practicable with the patient’s needs. It would,
however, be appropriate and helpful in a neuropsychological
report to offer a view as to the broad level of care/supervision
needed.
However, a particular aspect of future care - rehabilitation -

may well merit fuller discussion. After brain injury, many
patients, at least in the UK, will not receive an adequate (or
indeed any) programme of specialised rehabilitation (e.g.
Thornhill et al 2000). One cannot consider prognosis without
considering what services may be available, and it will often
be appropriate to make recommendations for rehabilitation,
which may require funding. It is important to remember:
◆ You should not hold out to patient/family the definite

prospect of rehabilitation or other treatment until and
unless funding is in place.
◆ If there is a case for such rehabilitation, you should do no

more than discuss it with patient/family as a possibility (to
gauge their receptiveness), then raise the matter with your
instructing lawyers.
Page 19 of 33
◆ The lawyers acting for the injured person may be able to

obtain funding for this purpose, either by means of an
interim award of damages, or through negotiation with (p.
753) the defenders. However, that is a matter for them to
pursue where possible and the clinician’s role is to provide
them with any evidence that such rehabilitation may be of
benefit.
◆ The lawyers acting for the defenders may also be able to

arrange funding for this purpose, and the idea of doing so
may be attractive to defenders on the grounds that such an
investment now may reduce disability (and therefore
damages) later. Again the clinician’s role is to explain any
grounds to believe that such rehabilitation may be of
benefit.
◆ It will sometimes be possible for privately-funded

rehabilitation/treatment to be provided by a service with
which you (the person who recommended it) have no
connection. If the service may be provided by a unit with
which you do have a connection, you should declare a
possible conflict of interest.
If called to present evidence in court, it is well worth reading

some relevant material about the court in advance, or seeking
to speak to a colleague with court experience. Carson (1990),
a lawyer who describes the methods Barristers or Advocates
use to ‘test’ witnesses, provides a view from the ‘other side’
which is very helpful for prospective witnesses. Other useful
UK publications are: Psychologists as Expert Witnesses in
Scotland and Psychologists and the New Rules in Civil
Procedure published by the British Psychological Society.
What happens after an assessment is not always simply a

matter of the reports being prepared for negotiations and for
Court Hearings, but sometimes rehabilitation decisions follow.
In the UK the Association of Personal Injury Lawyers (APIL)
and the Forum of Insurance Lawyers (FOIL) have a
Rehabilitation Code under which they agree to consider the
advantages of rehabilitation, which can produce a potential
win-win situation whereby the injured party achieves a better
outcome as a result of investment by the insurers and the final
cost to the insurers is thereby reduced.
Page 20 of 33
It is clear that some lawyers have a degree of difficulty with

this – it is easier to measure one’s achievement in winning
damages by the size of an award and some more subtlety is
required to gauge success in terms of the outcomes achieved
by the injured persons. However, it is clear that the leading
practitioners in the field do have the welfare of their clients
more to the front of their minds than the size of the final
award attained.
The use of the Rehabilitation Code should normally lead to an

Immediate Needs Assessment prepared by an independent
practitioner who is not a compellable witness at Court and to
that extent is ‘outside’ the medico-legal process. It is however
important to be careful and disciplined about where
instructions come from and who one has permission to report
to when this process is in play. The first author has, for
example, been instructed to provide a neuropsychological
report by an ‘independent’ rehabilitation provider later to
receive a follow-up letter from the defending solicitors asking
for further comments. If however, one’s report was originally
for an independent rehabilitation provider, you cannot assume
that you have the consent of the injured party to divulge
information in this way – permission should be obtained from
their solicitors. It is also sometimes the case that instruction
from one party is then followed by agreed joint instruction and
it is essential to be clear as to the basis on which one is
instructed and to (p.754) ensure that there is no conflict.
Obviously one cannot accept instructions from the defender at
one point then (unless the parties agree) go on to accept
instructions from the plaintiff/pursuer side or vice versa.
2.4 Further issues

2.4.1 Premature ageing
An increased risk of dementia after brain injury has been
suggested by some. The idea that the injured brain may be
less able to resist the effects of ageing and/or dementia has
some plausibility. Bell (1992) was an emphatic proponent of
such a link. Lawyers, naturally, may raise the issue: if there
was an increased risk of dementia it would have implications
for long-term care and therefore costs, and it would only be
right that the diligent lawyer pursue the issue. There is a
growing literature on this topic.
Page 21 of 33
There are many retrospective studies reporting an association

between previous head injury and onset of Alzheimer’s
Disease. These are of limited interest as the relatives (whose
accounts have generally been the basis of these studies) may
be making an effort to ‘explain’ the dementia. Fleminger
(2003) provided a systematic review of case control studies
and sought to replicate the findings of an earlier meta-analysis
by other researchers. He was able to obviate some of the more
pressing objections to some of the individual earlier studies.
He reported an odds ratio of 2.26 for males (i.e. that males
with a head injury were over twice as likely to develop
Alzheimer’s Disease), although the relative risk for females
was slightly below parity. The author comments that, due to
the inherent complications in conducting case control studies,
other forms of research should be used in the future.
Two other studies which are of particular interest were by

Plassman et al., (2000) and Nemetz et al., (1999). The
Plassman study was of World War II US Navy or Marine
Veterans who were hospitalised during military service with
either head injury or with some other condition. Although this
was in the era prior to the use of GCS or PTA as markers of
injury severity, they nevertheless used satisfactory definitions
and a clear and staged procedure to follow up patients to see
if they had developed Alzheimer’s or other dementias. The
hazard ratio for those with moderate head injury was 2.32 and
for severe head injury 4.51. This is a study in which the
contaminating effects of the expectations of relatives and
experimenters are obviated. On the other hand, one has to
bear in mind that these patients were injured a long time ago
when the nature and extent of rehabilitation, treatment, and
support for people with brain injury was significantly different
from that which applies nowadays, and so some caution would
have to be applied in interpreting these findings.
There is also a study by Nemetz et al., (1999) which is a

population-based study of patients injured between 1935 and
1984 in one county in Minnesota. This too provides a good test
of the hypothesis insofar as the methodology is not susceptible
to expectations or selective recall by relatives. They found no
evidence that traumatic brain injury was a significant
independent risk factor for Alzheimer’s Disease. There were
some limitations of the study insofar as the diagnosis of
dementia and classification were based on retrospective
record (p.755) review not on current DSM assessments as in
Page 22 of 33
the Plassman study. One again would note that some of the
patients were injured many years ago, when standards of
treatment and care were different. Nevertheless, there was no
evidence here of a link.
Two editorials, both of which appeared in the Journal of

Neurology, Neurosurgery and Psychiatry in 2003 made
comment in this issue. Wilson (2003) provided an editorial
which accompanied the Fleminger paper noted above. Wilson
hoped that the Fleminger review would stimulate the follow up
of cohorts of patients with well-documented head injuries. In
the same year, Brooks (2003) commented on a paper by Millar
et al., (2003). Brooks noted the possibility of late decline after
TBI, although any decline was ‘clearly not major’. Brooks also
observed that “coming up with good data in this area is going
to take dedicated research teams with very long term
perspective”.
From a medico-legal point of view, therefore, the link between

brain injury and increased risk of dementia in later years
remains very hard to specify and particularly to specify what it
may mean in an individual case. However, it is plainly an area
which is potentially relevant in a medico-legal context.
2.4.2 Assessment of capacity

The question of Capacity is one which is often raised with
neuropsychologists in civil cases. This is a topic which has
been particularly to the fore following the case of Masterman-
Lister –v– Brutton & Co in 2002. Lush, Master of the Court of
Protection in England and Wales, has provided a summary in
which he notes that the decision in this case would be
expected to make the assessment of capacity “more arduous
for doctors, who have traditionally been gatekeepers of an
individual’s status as a patient”. He notes that they will need
to “consider a broader range of social, domestic and economic
factors” and he notes the judges’ observation that while “the
opinions of skilled and experienced medical practitioners are a
very important element in the evidence to be considered by
the court” that is done in conjunction with other evidence.
The Masterman-Lister judgement (2002, EWCA Civ 1889)

included that English law requires a person must have the
necessary mental capacity to make legally effective decisions,
to make testamentary dispositions, to enter into marriage,
consent to divorce and so on. Mental capacity required by law
Page 23 of 33
is a capacity “in relation to the transaction which is to be

effected” and that what is required therefore is the capacity to
understand the nature of “that transaction when it is
explained”. Capacity is therefore specific and, commonly in
personal injury cases, experts are asked to consider whether
the individual has capacity to ‘compromise’ their claim (to
reach a settlement of their claim for damages); and whether
they have the capacity for ‘fund management’ (to look after
their monies in time to come).
It would not be sufficient to say that someone lacks capacity

merely because they might behave unwisely. The Mental
Capacity Act of 2005 for England and Wales states that a
person is unable to make a decision for him or herself if
unable: (a) to understand the information relevant to the
decision, (b) to retain that information, (c) to use or weigh that
information as part of the process of making the decision, and
(d) to communicate the decision (by talking, using sign
language, or any other means).
(p.756) The requirements go on to state that a person is not

to be regarded as unable to understand the information
relevant to a decision if that person is able to understand an
explanation given to him in a way that is appropriate to his
circumstances – for example by use of simple language, visual
aids or by other means. The fact that the person is able to
retain the information for only a short period is considered not
to prevent him from being regarded as able to make the
decision. The first author has an impression that there is
currently a tendency amongst judges to seek to protect
individuals who have been injured from what they see as over-
zealous professionals wanting to remove capacity.
It is not sufficient to show that memory falls outside a normal

range and is grossly defective but it is also relevant to adduce
examples of how this affects the ability to make decisions –
perhaps by reference to difficulties with decision-making
which have arisen already, for example by looking at
rehabilitation or case management or social work records. The
criteria emphasise communication, retention, and so on. The
executive difficulties which are common after head injury do
not fall neatly under the rubric in the Act. The fact that
making an unwise decision would not mean that one lacked
Capacity is something which one has to consider carefully
alongside any tendency to be impulsive as a consequence of
Page 24 of 33
dysexecutive or frontal lobe problems. It is therefore

important to delineate these problems very clearly and to
consider whether the extent of these problems means that the
person has lost the Capacity to use or weigh information
perhaps due to extreme impulsiveness or difficulty in
sequencing thoughts. In short it is important to have careful
regard to the statements in the Act, to consider the
neuropsychological test findings, and also to consider wider
examples in order to arrive at a recommendation regarding
Capacity. One has to bear in mind too, of course, that the
Court will decide at the end of the day, and that lack of
Capacity need not be permanent but in some cases is able to
be revisited.
There are other very difficult issues, for example, the capacity
to consent to sexual relations. There is a judgement (and I am
grateful to Helen Dolan of Potter Rees for bringing this to my
attention) from a 2007 case (Re: MM [an adult] EWHC 2003
[Fam]). In this judgement it is stated that the law is set out
that an adult is presumed to have capacity until the contrary is
established, that capacity is issue-specific, and a person may
have capacity for one purpose but lack capacity for another.
The judgement states: “that is why in cases of this kind it has
now become the practice to grant separate declarations (for
example) as to a vulnerable adult’s capacity: (1) to litigate, (2)
to decide where she should reside, (3) to decide who she has
contact with, (4) to decide on issues concerning her care, (5)
to consent to sexual relations, (6) to consent to marriage and
(7) to manage her financial affairs.
The judgement goes on to say that capacity is not merely issue

specific in relation to different types of transaction but
capacity is also issue specific in relation to different
transactions of the same type – “thus a vulnerable adult may
have capacity to consent to a simple medical procedure but
lack capacity to consent to a more complex medical
procedure”. It follows therefore that in assessment one has to
consider not only the overall findings and level of function, but
to apply careful thought to the implications for the specific
issues or transactions which are under consideration.
(p.757) 3 Criminal cases
Page 25 of 33
The evidence of a neuropsychologist (as opposed to a forensic

psychologist) may also be required in criminal cases. There
are certain circumstances in which neuropsychological issues
bear on criminal proceedings and it may be that in the future
the range of neuropsychological issues arising in this setting
will increase, especially given the high reported incidence of
neuro-cognitive impairment in criminals (see Denney 2007).
3.1 Peri-traumatic loss of memory in TBI

Possible loss of memory at the time of an accident or assault is
a particular issue which sometimes involves
neuropsychologists in criminal cases. A period of amnesia
(comprising retrograde amnesia – RA; and post-traumatic
amnesia – PTA) is the signature of a significant concussional
head injury. The individual recalls nothing from sometime
before injury until sometime after it. This obviously may lead
to difficulty in criminal cases. The victim of an assault may be
unable to recall events just prior to assault due to RA, or the
immediate aftermath due to PTA, and this can lead to
problems in bringing the perpetrators to justice. Another
instance is after road traffic accidents when the injured person
may have been the victim or may have been a driver suspected
of an offence. RA/PTA may mean the injured person has no
recall of the event. In all cases where RA/PTA is an issue,
study of the contemporaneous records is a key step in trying to
clarify how extensive RA and PTA are likely to have been, as
the injured person may have a motive for claiming to
remember or forget what happened.
It is worth bearing in mind that although RA and PTA are

always found with significant concussional head injury, not all
assaults are of this sort. In assaults, depressed fractures or
penetrating wounds are not uncommon. Where concussion is
not the main mechanism of brain injury, the injured person
may recall the actual incident, and may have succumbed to
unconsciousness later. It should also be borne in mind that
many people who commit murder/violent acts claim to have no
memory of the act. It is thought that this commonly occurs as
a result of emotional shock/psychological trauma (Kopelman
1987). Obviously, this should not be confused with RA/PTA: it
is hard to conceive of a concussed person being able to carry
out such an act.
3.2 Neuropsychological deficits
Page 26 of 33
The lasting neuropsychological deficits in cognition and

emotional adjustment which may follow TBI or other brain
insult/disorder are also of potential relevance.
Neuropsychologists may be asked to comment on
vulnerabilities which affect the competency of a person with
brain injury to stand trial, or give evidence as victim or
witness. In the context of the police interview and testifying in
court, the term ‘psychological vulnerabilities’ refers to
psychological characteristics or mental states which render a
witness prone to providing information which is inaccurate,
unreliable, or misleading (Gudjonsson 1999).
3.2.1 Cognitive deficits

As well as RA/PTA, people who have had TBI or other brain
insult/disorder may have ongoing memory and other cognitive
impairments. The issue may arise as to whether (p.758) such
impairments undermine the ability to follow questions and
marshal facts in giving evidence. Obviously the bar should not
be set too high. In ordinary cases, where there is no
neuropsychological deficit, some accused or witnesses may be
of well below average ability. It would be wrong and arguably
would undermine the aims of justice to say that merely
because a witness has some loss of sharpness they could not
give evidence, because that might well mean that no charges
would be brought and justice would be defeated. However,
where there are substantial difficulties (e.g. dysexecutive
syndrome, word-finding difficulties, or memory problems)
there may be very specific difficulties in giving evidence. Some
individuals after severe TBI may be at such a disadvantage in
the dock or witness box that attempts at examination and
cross-examination would be in serious danger of ending in
farce. In this context, the fact that some neuropsychologically
compromised individuals may be subject to extreme emotional
responses (e.g. ‘catastrophic reaction’) is also relevant.
There is, however, a lack of hard indicators (such as test

cutting scores), and clinical judgement is required. As regards
thedefendant, a trial cannot be fair if the individual is unable
to understand the court proceedings, instruct their lawyer, and
participate in the court proceedings. The exact criteria set
down in the law to ensure a fair trial vary to some extent from
jurisdiction to jurisdiction.
Page 27 of 33
Where issues of intellectual and related impairment may arise

(e.g. due to head injury, neurological disorder, etc), a
neuropsychological assessment is necessary to define the
nature and extent of the limitations. However, competency
cannot be measured by just evaluating mental capacity and
there is a need to assess the functional ability of a defendant
matched to the contextual demands of the case (Grisso 1986).
As regardswitnesses, similar considerations apply. A witness

may be unable to give evidence if deemed not to have the
cognitive capacity to understand questions, articulate
answers, and understand the implications of their answers.
3.2.2 Suggestibility
Suggestibility is the tendency to yield to leading questions and
submit to interrogative pressure (Gudjonsson 1999).
Suggestibility can be assessed by the use of behavioural tests,
such as Gudjonsson Suggestibility Scales, which assess an
individual’s response to ‘leading questions’ and ‘negative
feedback’. Many neuropsychologists will have no experience of
such measures and may wish to cross-refer to forensic
psychologists.
3.2.3 Other variables

A neuropsychologist might also be asked to comment on
various further (criminal) forensic issues to the extent that
neuropsychological impairments interfere, or may interfere,
with the ability of the accused, or of a witness, to recall or
describe events. The more general factors which may affect
the witness’ ability to recall details of a crime at later date are
primarily of interest to forensic psychologists rather than
neuropsychologists. These factors include ‘estimator variables’
which may affect witness’ recall (such witness age, weapon
focus, duration of exposure to the crime, effects of stress/
arousal), and duration, which occur at the time of the event,
and ‘system variables’ which occur during the (p.759)
investigation process (impact of misleading questions,
exposure to ‘mug shots’/photographs leading to false
memories). Neuropsychological impairments may impact on
ability to recall information about crime and perpetrators
reliably. However, this is not a mainstream neuropsychological
concern and detailed discussion is outwith the scope of this
chapter.
3.3 Disposal
Page 28 of 33
An issue which occasionally arises, in the authors’ experience,

is that of ‘disposal’, or sentencing. A neuropsychologist may be
called upon to comment on whether there is treatment or
rehabilitation available which may help, which might be as an
alternative to fines or imprisonment.
Acknowledgements
We are grateful to the following for their helpful comments on
specific issues:Robert Swanney, Partner, Digby Brown,
Solicitors, Glasgow; Hugh Potter and Helen Dolan, Partners,
Potter Rees, Serious Injury Solicitors, Manchester; Richard
Crabtree, Partner, Pannone, Solicitors, Manchester
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Page 33 of 33
Functional neuroanatomy of spatial perception, spatial processes and attention


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Functional neuroanatomy of spatial

perception, spatial processes and
attention
Gabriella Bottini
Eraldo Paulesu
Martina Gandola
Paola Invernizzi
DOI:10.1093/acprof:oso/9780199234110.003.037

Empirical data from experimental psychology, primate
neurophysiology, and neuropsychological observations of brain
damaged patients are the primary generators of experimental
hypotheses for functional neuroimaging experiments in spatial
neurocognition: the way in which space is mapped from early
sensory codes (e.g., retinotopic maps, somatotopic maps)
through transformation to higher-order coordinates. This
chapter discusses the multicomponent nature of space
representation and the existence of several spatial frames
(e.g., far as opposed to near space); the distinction between
object- and space-based visual cognition; the relationship
between space and motion cognition; and the modulation of
spatial representation and perception through attentional
mechanisms.
Page 1 of 44
Keywords: spatial neural representation, space representation, visual cognition,

space cognition, motor cognition, attentional mechanisms
1 Introduction
Functional neuroimaging measures hemodynamic changes (of
blood flow in the case of positron emission tomography (PET);
Raichle 1987), and blood oxygenation in the case of functional
magnetic resonance imaging (fMRI); Turner 1997; Ogawa et
al. 1998; Logothetis et al. 2001). These indices are used as
indirect measures of synaptic activity and neural firing. PET
and fMRI have rapidly become the major sources of
neurophysiological information in humans. Since their early
inception, they have been extensively used to characterise the
neural bases of spatial cognition. The quantity of empirical
information now available is sufficiently large to allow for the
formulation of a summary which may prove useful to the
clinical and experimental neuropsychologist.
Empirical data from experimental psychology, primate

neurophysiology, and neuropsychological observations of brain
damaged patients, are the primary generators of experimental
hypotheses for functional neuroimaging experiments in spatial
neurocognition: the way in which space is mapped from early
sensory codes (e.g. retinotopic maps, somatotopic maps)
through transformation to higher-order coordinates;
◆ the multicomponent nature of space representation and

the existence of several spatial frames (e.g. far as opposed
to near space);
◆ the distinction between object- and space-based visual

cognition;
◆ the relationship between space and motion cognition;
◆ the modulation of spatial representation and perception

through attentional mechanisms.
In this review we will discuss the above areas of enquiry.

These themes will be introduced by a brief summary of the
relevant comparative information drawn from the primate
physiology literature and neuropsychology. As the reader will
notice, there is no complete agreement between lesion data
and functional imaging data of spatial processing and
attention; this we regard as a source of major interest for
further research.
Page 2 of 44
(p.766) 2 Building spatial neural representation from

earlier sensory codes
2.1 The higher-order nature of spatial representation
Space, perceived as unitary, is in fact mapped by several
systems all of which provide a representation relevant for a
given set of actions and for different parts of space itself,
including body space (Fig. 37.1) (Andersen et al., 1997; Colby
& Goldberg 1999; Rizzolatti et al., 2000).
Evidence for dissociation between spatial representations and

individual sensory codes in perception and directional coding
of movement is provided by case studies of brain damaged
patients:
◆ with relatively spared elementary perceptual (e.g. visual,

tactile) or motor skills and an impaired ability to report,
respond to, or orient towards stimuli presented in different
portions of space (spatial unilateral neglect: cf. Bisiach &
Vallar 2000);
◆ with altered visuomotor integration in reaching tasks (cf.

Jeannerod 1997).
Studies in spatial neglect have allowed us to dissociate

elementary somatotopic and retinotopic codes from body-
centered coordinate frames (cf. Bisiach & Vallar 2000; Vallar
1998). A third source of evidence for the role of sensory
afferents in the building of spatial
Page 3 of 44
(p.767) Fig. 37.1 Classification of spatial

frames.
The body, the space within reaching
distance and far space. Neuropsychology
and neurophysiology provide evidence
that the brain has separate
representations for these different spatial
frames. Personal space is somatosensory
space mapped as a body schema
independently from visual space.
Extrapersonal space also involves visual
space: This can be based on egocentric
coordinates (within reaching distance);
visual space is organized with reference
to head, trunk and limbs. Extrapersonal
space can be mapped in allocentric
(object-based) coordinates (See also
‘Plates’ section).
representations comes from the effects of lateralized or direction-

specific stimulations of peripheral sensory systems, with methods
such as caloric vestibular stimulation (CVS), posterior neck muscle
mechanical vibration (NV), and optokinetic stimulation (OKS) (cf.
Vallar et al., 1997). In healthy subjects these stimulations can
induce a distortion of egocentric coordinates (causing e.g. a
deviation of the subjective straight ahead (an index of spatial
representation) in pointing tasks (cf. Bottini et al., 2001)).
Therefore, the internal representation of space may involve the
integration of different sensory inputs - visual, somatosensory-
proprioceptive, vestibular, auditory - yielding reference frames that
are not based on individual peripheral sensory codes, organised, as
they are, in egocentric (e.g., head, trunk, arm), and object- or
environment-centered coordinates (Andersen et al., 1997; Rizzolatti
et al., 2000; Graziano & Gross 1994). To illustrate the integrative
nature of the neural representation of space, we first need to
briefly consider the individual sensory modalities. We have
constrained our review to visual and somatosensory space. We will
discuss how these individual modalities are combined into
multimodal representations, and the extent to which functional
imaging has contributed to describing the anatomical bases of
these representations in humans.
2.2 Visual space
Visual space is mapped primarily by the geniculostriate
pathway where magnocellular, parvocellular and koniocellular
information arrives segregated to different layers of primary
Page 4 of 44
visual cortex (area V1) (Livingstone & Hubel 1988; Zeki 1993;
Hendry & Reid 2000). Area V1 information is then conveyed to
extrastriate visual cortex through divergent pathways, usually
referred to as the ventral (object-centred or ‘what’) stream
and the dorsal (space-related or ‘where’) stream (Mishkin et
al., 1983). Neurons of the visual cortices have receptive fields
(RFs) of increasing complexity and size from area V1 to
extrastriate visual cortex. The farther from V1, the more
complex the receptive fields of the neurons; with neurons
having a RF nearly as large as the whole visual field. Cortical
visual areas may show retinotopic organization in that a single
neuron responds to visual events arising from the same part of
the retina. The part of the visual world mapped by these
neurons varies with the position of the eyes in the orbit. There
is now clear evidence that the brain makes extensive use of
both retinotopic and non-retinotopic representations of visual
space (cf. Rizzolatti et al., 2000; Graziano & Gross 1994;
Andersen 1994; Galletti & Fattori 2002). Even from an intuitive
point of view, this appears to be an efficient computational
strategy to enable stable phenomenological perception (e.g.
when the eyes move, the perceived world remains stable
despite the movements of the retinal images). Actions such as
reaching and grasping benefit from visual descriptions centred
on moving body segments (peripersonal space), or centred on
objects in space (allocentric space).
2.2.1 Where are the visual cells with increasingly complex RF

properties located?
In the primary visual cortex (area V1), visual space is mapped
in purely retinotopic space. Each neuron has a receptive field,
a sort of small window which captures a portion of the (p.
768)
Page 5 of 44
visual field.
Suppose we
observe a
basket full of
red apples and
fixate on one of
the apples. A
given single
visual cell in
V1 will provide
the same
information
when the eyes Fig. 37.2 Left cerebral hemisphere of
are fixating on
the macaque brain.
the closest
apple at the IPS, intraparietal sulcus; MT, motion
left end as on temporal area (V5); S1, primary
the farthest somatosensory area; S2, second
apple at the somatosensory area; CS, central sulcus;
right end of LS, lateral sulcus; STS, superior temporal
the basket. sulcus; AS, arcuate sulcus; PS, principal
That is to say,
sulcus. The nomenclature of motor areas
single neurons
follows Matelli et al. (1985,1991). Some
in V1 do not
discriminate
of the visual areas (V3, V6) cannot be
between seen on the lateral surface of the brain
spatial (See also ‘Plates’ section).
locations.
A first
departure from a purely retinotopic mapping of the visual field
is observed in the so-called gaze-dependent cells (Andersen
1994). In these cells the firing frequency depends not only on
what strikes their receptive field, but also on the position of
the eyes in the orbit or the dynamic component of gaze.
Initially found in the posterior parietal cortex (PPC),
particularly in area 7a, and in the lateral intraparietal sulcus
(LIP), they have been found in extrastriate visual areas V3,
V3A, V5/MT, MST, and V6 (see Figs 37.2 and 37.3) (Galletti &
Fattori 2002; Galletti et al., 1993). These neurons have
retinotopically organized RFs and therefore do not encode
visual space in a manner that is independent of eye position.
2.2.2 How does the brain build an eye-position-independent

coding of visual space?
There are two competitive hypotheses on this issue.
Page 6 of 44
◆ One maintains that this further level of visual space

representation may arise by the temporal integration of an
extensive system of gaze-dependent visual cells (Andersen
et al., 1997).
◆ A second theory postulates the existence of real-position

cells, in which visual stimuli given to the same part of space
cause similar neuronal responses in spite of the actual
direction of gaze and position of the eyes in the orbits. Cells
of this kind have been described in the PPC (area V6a or
PO; Galletti et al., 1993), in the ventral intra-parietal cortex
(Duhamel et al., 1992), and in the pre-motor cortex (area
F4) (p.769) (Graziano & Gross 1994; Fogassi et al., 1996).
Their property may arise from convergent input from a set
of gaze-dependent cells. The space coded by such cells, can
be called extrapersonal space. Evidence from patients with
unilateral neglect and neurophysiological evidence in the
monkey show that extrapersonal space can be further
divided into peripersonal space (the space within reaching
distance) and far space (cf. Rizzolatti et al., 2000).
2.3 Somatosensory and personal space
Cortical somatosensory representation of the body surface,
joints, and muscles includes areas of the postcentral gyrus
(areas of the S1 complex, Brodmann areas (BAs) 3, 1, 2), areas
of the dorsal posterior parietal region (BA 5 of the monkey and
human BAs 5 and 7), the secondary somatosensory area (area
S2, BA 43) which is located in the ventral bank of the parietal
operculum, the granular insula, the retroinsular cortex, and
the more rostral part of the inferior parietal lobule (area 7b of
the monkey and human area 40) (cf. Kaas 1990; Paulesu et al.,
1997). Much as for the visual areas, the RFs of individual
neurons of the various somatosensory areas and the overall
grain of the resulting maps change from area S1 to area S2,
granular insula, retroinsular cortex, and supramarginal gyrus.
◆ S1 has the finest grained somatotopy with strictly

contralateral receptive fields and limited callosal
connections.
◆ S2 has a large proportion of neurons with bilateral or

even ipsilateral receptive fields.
The same applies to the other somatosensory cortices (cf.

Paulesu et al., 1997).
Page 7 of 44
◆ Input to these cortices is purely somatosensory only in

area S1 proper (area 3b), and in area 1.
◆ The retroinsular cortex, part of area 3a, area S2, the

cortex at the tip of the intraparietal sulcus, and area 7b
receive vestibular input as well.
◆ Area 7b has approximately 20% of neurons which respond

to visual stimuli.
◆ Signals from the neck muscles reach the retroinsular

cortex, the insula, and area S2 (Guldin and Grüsser 1998).
◆ In keeping with the functional properties of these

cortices, the afferent thalamic inputs to these areas are
strictly from the specific ventroposterior somatosensory
nucleus for area 3b and 1, and from multiple thalamic
nuclei for the remaining areas.
Polymodal neurons with tactile and visual properties have also

been found in the lateral premotor cortex (cf. Rizzolatti et al.,
2000), which also receives vestibular signals (Guldin &
Grüsser 1998).
The integrative nature of body schema representation goes

well beyond a body map of the skin such as that represented in
area 3b. The body schema is probably based on a number of
body-centred spatial frames, including knowledge of the
spatial relationship of body segments. The midsagittal plane of
the body appears to be a robust neural/mental construct: its
representation is easily tested with tasks involving the
appreciation of the straight ahead coordinate on pointing or
visual detection tasks, and may arise from (p.770) the neural
operations of the brain regions receiving joint input from
tactile, muscle/joint receptors and vestibular receptors.
Orientation of the midsagittal plane can be pathologically
rotated towards the side of brain damage in patients with
spatial neglect, or physiologically rotated in normal subjects
by asymmetric input from the vestibular or neck-muscle
receptors (Karnath 1994; Karnath et al., 1994). The space
coded by this neural system is called personal space.
2.4 Merging visual, somatosensory, and motoric spatial

representations
Recently, the important discovery was made of a class of
bimodal neurons which respond to visual stimuli and to tactile
stimuli. These bimodal neurons have been found in:
Page 8 of 44
◆ the premotor cortex (area 6 or F4);
◆ the inferior parietal cortex (area 7b);
◆ the putamen (Graziano & Gross 1994).
In these regions, a hand bimodal neuron responds to both

tactile stimuli (delivered to the hand while the animal’s eyes
are closed) and to a visual stimulus (delivered in the space
surrounding the hand, about 20 to 100 cm away).
Interestingly, the visual field of these bimodal neurons moves
with the position of the limb and is independent of the position
of the eyes. The space coded by these neurons is peripersonal
space.
The aforementioned evidence of visual neurons in premotor

area 6 contributes to the now overwhelming demonstration
that space (visual, somatosensory, and even auditory) is not
only represented in posterior sensory regions but also in
frontal-lobe regions (including the agranular and dysgranular
premotor cortex, which have motor-like functions) (cf.
Rizzolatti et al., 2000). The premotor cortex (areas 6 and 8)
has neurons which enter in descending motor tracts, or are
connected to primary motor cortex. In the same regions, there
are visual neurons with clear visual or visuomotor properties,
and a recognizable visual receptive field. In the frontal eye-
fields (FEFs), the region which triggers saccadic eye
movements (to reach spatial location with gaze), there are
visual as well as visuomotor neurons whose firing is enhanced
by visual stimuli when the stimulus represents a target for an
ocular movement (Goldberg & Bushnell 1981). The visual
receptive field of these neurons is based on retinotopic
coordinates. On the other hand, in the ventral premotor cortex
(particularly in area F4), in addition to the motoric neurons
involved in reaching and grasping, there are also visual
neurons, or bimodal visuotactile neurons (whose visual
receptive fields are anchored to body segments and move with
them). The response of these neurons does not depend on
retinotopic coordinates. Rather, it contributes to egocentric/
peripersonal space representation. These premotor cortices
are selectively connected to posterior parietal regions of the
inferior parietal lobule, of the intraparietal sulcus, and of the
superior parietal lobule, sharing some functional properties
related to the space mapped. Area F4 is functionally related to
the inferior parietal lobule (BA 7b) and to the anterior
intraparietal area, which both predominantly encode
Page 9 of 44
peripersonal space within reaching distance. The FEFs are

functionally connected (p.771) to the lateral intraparietal
cortex and the posterior part of the inferior parietal lobule
(BA7a). Their function is concerned with eye movements and
visual space, coded in retinotopic and craniocentric
coordinates.
Another interesting description of neuronal properties of the

premotor and parietal network is based on task-dependent
classification of motor behaviour within space which is within
reaching distance (Jeannerod et al., 1995; Wise et al., 1997).
The dorsal stream is proposed as being a modular visuomotor
transformation network.
◆ There is now abundant evidence that the most dorsal part

of the parietofrontal network (superior parietal cortex and
dorsal premotor cortex) is primarily concerned with
reaching tasks and contributes to computing distance
between target and limb, as well as spatial location of
targets.
◆ The more ventral premotor and parietal network is more

concerned with grasping, and the relevant dynamic hand-
shaping processes.
Objects are therefore represented at multiple levels.
◆ In the ventral stream, objects are represented in

allocentric coordinates related to object semantics (i.e.
features such as shape, texture, colour).
◆ In the dorsal stream objects are coded for their spatial

position in an egocentric/peripersonal spatial frame used
for the generation of reaching and grasping behaviour.
Dissociation of these spatial frames has been indicated by

human neuropsychological evidence: object discrimination can
be severely impaired by ventral visual-cortex lesions, while
accurate reaching and grasping may still be possible. The
opposite anatomo-behavioural dissociation is also on record
(Goodale & Milner 1992).
3 Space representation in humans: evidence from lesion

studies
A major source of evidence comes from studies of unilateral
neglect and from studies of patients with reaching disorders
not associated with neglect. The evidence is somewhat limited
Page 10 of 44
by the nature of the acquired brain lesions, which are by

default, vast and not constrained to discrete cytoarchitectural
areas. Acquired lesions also usually involve sub-cortical white
matter, making the interpretation of the anatomoclinical
associations more challenging.
3.1 Anatomical basis of spatial neglect (see Chapter 5)

Reviews on the anatomical bases of spatial neglect can be
found in Bisiach & Vallar (2000), Mesulam (1990), and
Heilman et al., (1994). The distribution of cortical lesions
observed in neglect according to Vallar (1998), are presented
in Fig. 37.3 (shaded areas). Unilateral neglect, which is
characterized by the inability to represent and explore the side
of space contralateral to the brain lesion, is usually observed
after damage to the inferior parietal lobule: lesions are
typically centred on the supramarginal gyrus, with
involvement of the neighbouring inferior parietal and superior
temporal areas. Lesion of the (p.772)
premotor
cortices (BA 6,
44) can bring
about neglect
dominated by
motor
symptoms
rather than by
perceptual
symptoms (a
dichotomy
which remains
open to debate,
cf. Mattingley
et al., 1998).
Neglect has also been observed after thalamic lesions or
subcortical white matter lesions. It is much more frequent
after right- rather than left-hemisphere lesions. Damage
restricted to primary motor or sensory areas does lead to
neglect. This supports the higher level nature of the spatial
disorder observed in patients with spatial neglect.
It has recently been suggested that parietal neglect may be

confounded by visual field deficits. It has been proposed that
lesion of the superior temporal cortex (STG) might be a purer
anatomical correlate of space exploration deficit (Karnath et
al., 2001; Samuelsson et al., 1997). The role of STG (BA 22 and
Page 11 of 44
42) in causing Fig. 37.3 Brain areas associated with

neglect has spatial neglect (shaded areas) and
been further meta-analysis of three functional
confirmed by neuroimaging experiments in healthy
Karnath and individuals using line bisection.
co-workers
Circles represent the location of
(Karnath et
activation peaks expressed in stereotactic
al., 2004a)
space from three different imaging
using a large
studies (Fink et al. 2000a; Weiss et al.
sample of
2000; Galati et al. 2000). Only the
patients (140
activations on the lateral surface of the
right brain
right hemisphere are reported. The
damaged
horizontal line represents the plane
patients)
passing through the two commissures.
which were
The two vertical lines represent the
not selected
coronal planes passing through each of
on the basis
the two commissures. Mesial ventral
of a
occipital activations are not shown. (See
neurological/
also ‘Plates’ section).
symptom
based
constraint (absence of visual field defects) (Karnath et al.
2001).
This evidence is in contrast with the classical literature on

neglect anatomy (cf. Heilman et al. 1994; Bisiach (Karnath et
al., 2001; Karnath et al., 2004a) and Vallar 2000) and the
respective role of STG and PPC in the pathogenesis of neglect
is unresolved (Karnath et al., 2001; Karnath & Himmelbach
2002; Marshall et al., 2002; Mort et al., 2003; Karnath et al.,
2004b; Karnath et al., 2004a). Some authors have suggested
that the discrepancies (p.773) could be due to different tests
used to classify patients in the diagnostic phase. In fact, a
dissociation between cancellation and bisection tasks has been
reported not only in the behavioural domain (Halligan &
Marshall 1992; Marshall & Halligan 1995; McGlinchey-Berroth
et al., 1996; Ferber & Karnath 2001), but also anatomically
(Binder et al., 1992; Rorden et al., 2006). Binder and co-
workers observed an association between posterior lesions
and impairment in line bisection while more anterior lesions
were associated with deficits on cancellation tasks (Binder et
al. 1992).
Page 12 of 44
More recently, Rorden and colleagues, using modern lesions

mapping methods, compared brain lesions of patients with
impaired performance in bisection, to those from patients with
pathological performance on the cancellation task only. They
confirmed an association between deficits in bisection, and
temporo-occipital lesions (Rorden et al., 2006). The possibility
that the divergences observed in the anatomical-correlation
studies of neglect depend on the test used (for the patients’
selection) has also been investigated using transcranial
magnetic stimulation (TMS) (Ellison et al., 2004). They found
that while stimulation of the posterior parietal cortex (PPC)
induced a deficit on the landmark task of line bisection
judgment, and on hard conjunction visual search, stimulation
of the superior temporal cortex, did not impair the landmark
performance. Conversely, a stimulation of STG caused a deficit
on a hard feature visual task. Furthermore, some authors
suggested a correlation between neglect evaluated in the
chronic phase, and subcortical white matter lesions
connecting the parietal and frontal cortex. In particular, a
lesion at different levels of the superior longitudinal fasciculus
(SLF) could explain the complex and variegate symptoms
associated with hemineglect (Doricchi & Tomaiuolo 2003;
Doricchi et al., 2008).
Taken together, the anatomical localization of spatial neglect

suggests a distributed neural architecture for spatial
representation with a functional specialization in the right
hemisphere.
One area in which lesion data have not been informative (as
yet) is that of the dissociation between symptoms within the
neglect syndrome. Patients may present with neglect
symptoms only in one spatial frame (e.g. near space but not
far space; Halligan & Marshall 1991) or in the same
peripersonal space on one task (e.g. line bisection) but not
another (e.g. target cancellation tasks; Halligan & Marshall
1992). These dissociations have not yet been corroborated by
clear anatomical differences in lesion locations (cf. Vallar
2001), although different studies have tried to investigate the
neural correlates of specific neglect symptoms: the neural
correlates of, for example, extinction to double stimulation
(Vallar et al., 1994; Karnath et al., 2003), anosognosia (Berti et
al., 2005; Karnath et al., 2005), directional hypokinesia (Sapir
Page 13 of 44
et al., 2007), perseveration on cancellation tasks (Nys et al.,

2006), and personal neglect (Committeri et al., 2007).
3.2 Anatomical basis of deficits in reaching tasks

The other major acquired spatial disorder is characterised by
deficits on reaching tasks. Lesions are usually located in the
superior parietal lobule, and the disorder typically involves the
contralateral limb in reaching to both sides of space
(Jeannerod 1997).
(p.774) 3.3 Discrepancies between data from humans and

monkeys
How do human and monkey data fit together? While there is
substantial agreement for disorders of reaching, there is a
clear discrepancy as far as the location of key lesions that
underpin neglect.
◆ In the monkey, neglect is more severe after ventral pre-

motor cortical lesions, than lesions in the superior temporal
sulcus.
◆ In humans, the manifestations of neglect are more severe

after parietal lesions (cf. Rizzolatti et al., 2000 and Bisiach
& Vallar 2000), but not primates.
Another important discrepancy is the hemispheric asymmetry

observed in humans and not in primates.
4 Functional anatomical studies of space perception

4.1 Visual and somatosensory space
Functional imaging has the advantage of allowing one to
explore the organisation of the healthy, as well as the diseased
human brain in vivo. Yet, it should be kept in mind that the
temporal and spatial resolution of imaging is not equivalent to
that of invasive electrophysiology in the primate brain. To give
an example of an area where imaging may be difficult to
compare to electrophysiology, the progressive making of
spatial representation from early sensory visual codes, may
prove difficult to demonstrate. With the current techniques it
has not been possible to isolate signals of neuronal
populations of cells associated with gaze-dependent visual
response, nor to isolate responses that can be plausibly
interpreted as real-position like. There are obvious reasons
why this may remain difficult with imaging. The cells are
present in small areas which contain other, simpler cells as
Page 14 of 44
well. Even in the primate brain, real-position cells coexist in

the same area as gaze-dependent cells.
In spite of these limitations, a substantial portion of the

detailed information derived from primate brains is
reproducible using functional imaging in humans. Large
numbers of retinotopically organized areas have been now
identified outside area V1 and area V2. Historically, the
existence of separate extrastriate areas which are specialized
in colour and motion perception, respectively, were the first to
be shown. These are likely homologues of monkey areas V4
and V5 (Zeki et al., 1991). An even more detailed cartography
of retinotopically-organized extrastriate areas has now been
described through the use of fMRI (see Fig. 37.3) (Sereno et
al., 1995). The receptive fields of the neurons within these
areas are increasingly complex, with neurons also mapping
the ipsilateral visual fields starting from area V3a and area
MT/V5 (Tootell et al., 1998). Together with the increasing
complexity of the visual receptive fields, an increasing
complexity of processing has been observed (e.g. in the ventral
stream: while posterior regions are preferentially activated by
object attributes such as colours or scrambled objects, more
anterior temporal lobe regions are activated by intact objects
or faces (cf. Kastner & Ungerleider 2000).
(p.775) The neural representation of somatosensory space

has been explored using a variety of approaches. Simple
experiments in which somatosensory stimuli were delivered to
the hands or feet have broadly confirmed the well-established
notion of somatotopic organization of area S1. A possible
somatotopic organization of area S2 has also been reported
(Ruben et al., 2001). In keeping with primate data, receptive
fields (RF) in S1 appear to be strictly unilateral, while bilateral
activation of area S2 is observed for stimuli delivered to either
sides of the body, suggesting the presence in the human S2 of
cells with at least bilateral, if not ipsilateral RFs (cf. Paulesu et
al., 1997).
4.2 The different frames of space as assessed by functional imaging
Page 15 of 44
With respect to higher-order spatial representations, one area

of enquiry which was addressed once functional imaging
became available, was the demonstration of a broad dichotomy
between two visual streams (the ‘what’ and ‘where’ pathways).
This proved a relatively easy task. Haxby et al., (1991) were
the first to compare a face matching task (a ventral ‘what’
stream task), with a dot location task (a spatial ‘where’ task).
A sensorimotor task with no relevant visual stimuli served as
the control task. Compared to baseline, both experimental
tasks showed activation of the lateral occipital cortex. Face
discrimination alone activated a region of the occipitotemporal
cortex, whereas the spatial location alone activated a region of
the lateral superior parietal cortex.
This dichotomy was demonstrated and further replicated

several times (Haxby et al., 1994), particularly with reference
to visual working memory. In keeping with electrophysiological
data in the monkey (Goldman-Rakic 1996), when visual
processing involves active maintenance of the spatial location
of visual stimuli and delayed response, a dorsolateral
prefrontal cortex activation is also observed (Courtney et al.,
1998). Consistent again with primate data (Wilson et al., 1993;
Chelazzi et al., 1993), active maintenance of object-oriented
visual information involves the more ventral parts of lateral
prefrontal cortex, together with the ventral visual cortex
(Courtney et al., 1996). Therefore, the what (ventral) and
where (dorsal) dichotomy is also present in frontal cortex (cf.
Ungerleider et al., 1998). The experiment of Haxby et al.,
(1991) involved extra-personal spatial co-ordinates. The
systematic exploration of other spatial frames has
subsequently become the focus of research in several
laboratories.
Page 16 of 44
4.2.1 Object-centred (allocentric) space

Interestingly, a number of tasks have been used in which
patients with spatial neglect may fail, showing either an
overall impairment or a specific and dissociated impairment,
depending on the nature of the task and the spatial frame
explored by it. Object-centred (allocentric) spatial judgements
have been studied in at least three experiments (Weiss et al.,
2000; Fink et al., 2000a; Galati et al., 2000). The stimuli used
were computerised variations of Milner’s landmark task in
which stimuli are pre-bisected segments. The subjects had to
judge whether the vertical bar that bisects a longer horizontal
segment is placed in the middle of the segment or not. A meta-
analysis of the main activations detected in the (p.776) right
hemisphere in these experiments is presented in Fig. 37.3.
Baseline tasks were designed to subtract components other
than spatial awareness. Activation foci are superimposed on a
standard stereotactic view of the right hemisphere. The
shaded areas represent the brain regions usually damaged in
unilateral neglect (Vallar 1998). The typical involvement of the
lateral extrastriate cortex, of the most dorsal part of area 40 in
the inferior parietal lobule, and the intraparietal sulcus, the
superior parietal lobule, and dorsal premotor cortex are
clearly evident. This network closely resembles the visuomotor
transformation network involved in reaching tasks in humans
and in monkeys (Jeannerod 1997).
In the same experiment, Galati and co-workers (2000) devised

an additional task in which subjects had to judge whether the
vertical bar was located to the left or right of the subjective
(egocentric) midsagittal plane of the body. In comparison with
the same baseline, a similar, yet larger, bilateral pattern of
activation emerged in the superior posterior parietal cortex
(mesial and lateral), in the dorsal premotor cortex (bilaterally),
and in left temporoparietal cortex emerged. The premotor
cortex, the medial dorsoparietal cortex, and the right
intraparietal cortex were more active when compared with the
‘allocentric’ task. In turn, there was a greater activation in the
medial ventral extrastriate cortex when the allocentric task
was compared to the egocentric one (not shown in Fig. 37.3).
This seems a reproducible result. A similar finding was
obtained by Fink et al., 2000b) when comparing a bisection
judgement performed on a one-dimensional object (a
segment), to a two-dimensional object (a square).
Page 17 of 44
Larger activation of the ventral occipital cortex was also

observed by Weiss et al., (2000), when comparing pointing
tasks (including bisection) in far, versus near space. On the
other hand, they found that the left hemispheric parietal
cortex, the dorsal occipital cortex, and the premotor cortices
were more active when comparing activations in near versus
far space.
4.2.2 Egocentric (personal) space

Representations for egocentric (personal) space have also
been explored recently using a different approach (Bottini et
al, 2001). As discussed in Section 2, a possible mechanism by
which spatial representations could be achieved, is through
integration via convergence of different afferent inputs. Within
this level of spatial body-centred description tactile, vestibular
and proprioceptive stimuli (including those conveyed by the
muscle spindles of the neck), play an important role. In the
monkey a perisylvian network of cortices including the
parietoinsular and retroinsular cortex, the ventral premotor
cortex, and the tip of the intraparietal sulcus all receive inputs
from the vestibule, the body surface and muscle spindles,
including those of the neck muscles. Using this rationale,
Bottini et al., (2001) mapped the cortical areas which are
activated by either vestibular signals, or by neck muscle
spindles; as appropriate stimulations of these systems can
induce spatial bias towards the stimulated side in healthy
controls, and reduce spatial disorder in unilateral neglect.
Specific to the monkey, the perisylvian somatosensory cortex
(retroinsular cortex, area S2, supramarginal gyrus) appears to
be a site of convergence of these inputs, suggesting that these
brain regions contribute to egocentric space representation
(Bottini et al., 2001).
Page 18 of 44
(p.777) 4.2.3 Is there dissociation between allocentric and

egocentric frames of reference?
The picture which emerges from the experiments detailed
above is not yet fully coherent in showing clear-cut
dissociations between allocentric and egocentric frames of
reference. This may be due to discrepancies between
experimental and baseline tasks used in the various
experiments (and to the assumption of lack of spatial demands
made when choosing such baselines). In addition, subjects
responded to the stimuli in different ways in each of the
experiments. There was button pressing in three experiments,
pointing with a laser light in one, and no response in another.
Taken together, however, the results of Fink et al., (2000a),
Galati et al., (2000), and Weiss et al., (2000) seem to indicate a
weak dissociation within a distributed, partially overlapping
system for spatial representation of peripersonal and
extrapersonal space.
◆ The visuomotor transformation network implied in

reaching behaviour is activated, with greater emphasis on
the dorsal parietal and premotor cortex, when the
experimental task implies attending to spatial locations that
are within reaching distance.
◆ Ventral retinotopically organized and object-based visual

cortices are more active when the comparisons of blood
flow maps isolate the processing of spatial locations (which
are either outside reaching distance (far space) or when
reaching is (relatively) de-emphasized).
The difference in results between the ‘egocentric’ task of

Galati et al., (2000) and the experiment of Bottini et al., (2001),
an experiment which takes into account the convergent
afferents which contribute to the representation of egocentric
space, remains particularly striking. It is likely that the task,
and its reference baseline, dominate the picture of activations
which can be observed via imaging; these factors alone may
explain the discrepancies. Alternatively, one may speculate on
the existence of multiple levels of neural/cognitive
representations for the same spatial frame. If this were the
case, behavioural dissociations based on lesion data would be
required to make this a more convincing possibility. The
consistency of each of the above observations with lesion data
of neglect will be discussed in Section 6.
Page 19 of 44
5 Spatial attention
The space surrounding us contains far too many items for the
brain to simultaneously process efficiently and consciously at
once. The mental ability which permits people to deal
explicitly with a subset of behaviourally relevant stimuli is
usually referred to as attention. In the definition of
psychologist William James (1890–1950), “Attention is…the
taking possession by the mind…of one out of what seem
several simultaneously possible objects or trains of thought.…
It implies withdrawal from some things in order to deal
effectively with others.” This definition emphasizes attention
as a process of selection.
The advantage of attention in perceptual/motor task can even

be appreciated introspectively. We know that we are more
efficient at responding to environmental stimuli when we
attend to them. In addition to introspection, there are
quantitative behavioural (p.778) techniques which measure
the advantage of attention. Various indices can be used:
reaction times are faster for responses to visual stimuli that
fall within attended parts of the visual field; discrimination of
stimuli is enhanced (cf. Umiltà 2000).
If we consider visual space, the process of orienting attention

usually implies fast saccadic eye movements, which are made
to bring the visual stimuli into foveal space. Yet there is
definitive evidence that spatial attention can also be oriented
without eye movements – covert (endogenous) orienting.
◆ Endogenous orienting of attention is frequently referred

to as a top-down or controlled process which is effortful and
depends on will. The classic paradigm devised by Posner
(1980) taps this form of attention (Umiltà 2000; Posner
1980). This paradigm, with small ad hoc adaptations, has
been used in a number of functional imaging experiments,
as is illustrated in Fig. 37.4.
◆ Spatial attention can also be attracted automatically by

the sudden appearance of a stimulus in the visual field, or
by the perceptual salience of a stimulus among others (e.g.
a vertical bar among other bars all tilted 30° to the right).
These other phenomena are called bottom-up or exogenous
processes (Fig. 37.5).
Page 20 of 44
Once attention has been oriented towards a stimulus, it may

become necessary to re-orient to a different spatial location,
which implies disengagement from the former, to re-orient
towards a different one.
5.1 Does spatial attention have a dedicated neural system in the

human brain?
The research into spatial attentional processes using
functional neuroimaging includes (see also Box 37.1):
◆ identification of brain regions involved in spatial attention

and assessment of the degree of overlap between
attentional, perceptual and premotor networks, particularly
with reference to the neural systems for eye movement;
◆ characterization of top-down processes (such as those

involved in covert, or endogenous, orienting), as opposed to
attentional phenomena based on perceptual salience
(bottom-up processes; exogenous orienting);
◆ assessment of orienting versus disengaging attention;
◆ space- versus object-based attention;
◆ global (diffuse) and local attentional processes.
Some of these issues have been investigated using functional

imaging.
The contribution of functional imaging to these fundamental

issues has been crucial to progress. Lesion data are
inconclusive because some disorders of spatial exploration and
representation (such as spatial neglect), are not universally
interpreted as being due to an attentional deficit (cf. Bisiach &
Vallar 2000). Event-related potentials are able to reveal
changes of brain response but they cannot tell in which part of
the brain these effects are generated. In a very influential
paper, Posner and Petersen (1990) summarized the (p.779)
Page 21 of 44
Fig. 37.4 Posner’s attentional

paradigm.
In Posner’s paradigm, subjects are
instructed by a symbolic central cue (an
arrow) that a target stimulus (a filled
circle) will occur with 80% of chance in a
given spatial location. Subjects are
instructed to fixate on a central mark, not
to move their eyes, and to press a key as
quickly as possible when the filled circle
appears. Covert attention is measured as
the reaction time benefit in responding to
the target which appears in the attended
location (valid trials) as opposed to
response for targets appearing in
unattended locations (invalid trials) or to
neutral trials, when another symbol (+)
indicates that the filled circle has a 50%
chance of appearing in either box (Posner
1980).
Page 22 of 44
(p.780) (p.
781) then
available
evidence,
including very
early
functional
imaging data,
on the
existence of
attentional
networks. They
proposed the Fig. 37.5 Difference between
following three
controlled and automatic attentional
tenets.
processes.
◆ The
attentional In display A, detection of a vertical
system is segment is a demanding attention-
seeking (top-down) process that can be
oriented endogenously or through verbal
instructions. Detection of a vertical
segment in display B is stimulus driven
and automatic (redrawn from Kastner
and Ungerleider 2000).
anatomically separate from the data-processing system, and

in this sense it is like other sensory and motor systems.
◆ The attentional system involves a distributed network:
— a posterior attentional system;
— an anterior attentional system;
— an ascending attentional system.
◆ Within the network, different components have different

specializations that can be described in cognitive terms.
Box 37.1 Attention from the neurophysiologist’s

perspective
Page 23 of 44
While psychologists characterize attentional effects in the

form of reaction time benefits or costs, the
neurophysiologist records the neuronal firing rate
associated with the presentation of a stimulus or with the
execution of a motoric response. Which response is then
interpreted as attentional by the neurophysiologist? The
most robust and established effects are ‘enhancement
effects’, increases of baseline activity, and suppression of
unwanted information.
◆ Enhancement effects. Goldberg and Wurtz (1972)

made the important observation that the firing rate of a
visual neuron of the superior colliculus can be enhanced
when a stimulus is delivered to the receptive field of
that neuron if the animal is covertly attending to that
spatial location. The enhancement effects in the
superior colliculus are present only when the animal is
about to generate a saccadic eye movement towards the
stimulus. Similar neurons can be found in cortical
structures involved in eye-movement control, such as
the frontal eye-fields (Goldberg & Bushnell 1981).
Importantly, in a given neuron, the ‘enhancement effect’
is not present if the saccadic eye movement is
performed towards a spatial location which lies outside
the receptive field of the neuron. Enhancement effects
are not necessarily associated with the generation of
saccadic eye movements. Such ‘purer’ enhanced
responses have been seen in the pulvinar, but also in
parietal cortex (Colby et al., 1996) and temporal cortex
(Chelazzi et al., 1993). In the cortex of the parietal lobe,
the enhancement is related to spatial location of the
stimulus. In the temporal lobe, enhancement effects are
related to stimulus attributes, rather than to its spatial
location.
◆ Increase of baseline activity. While the enhancement

effect occurs at the time the stimulus is presented,
increase of baseline activity has been observed in
neurons of area V2 or V4 even before the presentation
of a stimulus (providing that the experimental animal is
attending to the spatial location which corresponds to
the receptive field of the neuron (Luck et al., 1997)).
Page 24 of 44
◆ Filtering of unwanted information. When two objects

are present in the receptive field of the same neuron of
the temporal lobe (e.g. an object which activates the
neuron, and an object which activates it less strongly), a
mutual suppression of neural response is observed so
that the neural firing is roughly the average of the firing
rates induced by each separate object. This suppression
can be modulated by attention towards one of the two
objects so that the response is similar to that for an
object presented in isolation (Reynolds et al., 1999).
All of these general effects have been seen in humans

using functional imaging.
Enhancement effects have been seen in subjects who were

attending to particular visual features of a display, in
comparison to when they were passively viewing the same
display.
◆ Attention to colour was associated with enhanced

response in modality specific visual cortices such as
area V4.
◆ Attention to shape was associated with enhanced

response in area V3.
◆ Enhancement for speed and motion was associated

with area V5/MT (Corbetta et al., 1991).
A shift in baseline activity in specific cortical areas has

been described using fMRI. Even in the absence of any
actual change in visual stimulus, the baseline activities of
the visual motion area V5/MT or of the colour area V4, are
enhanced if subjects are expecting to detect a change of
motion or colour, in a visual display (Chawla et al., 1999).
Conversely, if subjects are distracted by a highly
demanding language task while observing a display of
moving dots, activation of area V5/MT disappears (contrary
to what happens in the same conditions when the
distracting task is an easy one (Rees et al., 1997b)). fMRI
data which are compatible with the filtering of unwanted
visual information by visual cortex have recently been
reported (Kastner et al., 1998).
The cognitive operations involved are:
Page 25 of 44
◆ orienting to sensory events;
◆ detecting signals for focal processing;
◆ maintaining vigilance.
In this account of spatial attention, each component has its

neural machinery.
◆ Orienting to sensory events usually implies the foveation

of a stimulus (overt orienting). The brain regions involved
are: the posterior parietal cortex (Goldberg & Bruce 1985);
the pulvinar nucleus of the thalamus (LaBerge &
Buchsbaum 1990); and the superior colliculus (Goldberg &
Wurtz 1972). These regions represent the posterior
attentional (p.782) system. Based on observation of
patients with parietal lesions (Posner et al., 1984), Posner &
Petersen (1990) maintain that:
— the posterior parietal cortex is involved in

disengagement from an attentional focus towards a
target located in the opposite direction to the side of
brain lesion;
— the superior colliculus would be also involved in

shifting attention, whether or not attention was
already focused elsewhere;
— the pulvinar nucleus is thought to contribute to

engagement with the new target location of the
attentional focus.
◆ Posner & Petersen (1990) also proposed that the anterior

(frontal and cingulate) cortical regions might represent an
amodal system which primes the posterior system to detect
signals for focal processing. The anterior system is
postulated to mediate selective attention and cognitive
control. Early PET experiments on divided attention and
control of response for conflicting stimuli (e.g. Stroop task)
support this assumption (Pardo et al., 1990; Corbetta et al.,
1991).
◆ Finally, Posner & Petersen (1990) proposed that alerting

is a function of the right hemisphere, and of the ascending
noradrenergic system (cf. Heilman et al., 1994).
This cognitive-anatomical model for attention is not

unanimously accepted. For example, it sharply contrasts with
a competing model which postulates that attentional networks
Page 26 of 44
are embedded within the same networks involved in

perception and action. One such model in fact, postulates that
spatial attention is the consequence of the activation (even in
the absence of overt motor response), of the neural system
that mediates sensory motor transformation (Rizzolatti et al.,
1994).
We will next discuss the extent to which assumptions proposed

by Petersen and Posner have been supported by the recent
imaging literature, together with a short review of other
relevant experiments on spatial attention.
5.2 The physiology of eye movements and spatial attention

A crucial test for Posner and Petersen’s (1990) model is the
assessment of the degree of independence of areas activated
by covert orienting of visual attention (as in Posner’s paradigm
illustrated in Fig. 37.4), and actual performance of saccadic
eye movements. Behavioural evidence would suggest that the
two systems are somewhat embedded (cf. Umiltà 2000, and
Corbetta 1998). On this particular issue there are a number of
specific functional imaging experiments (Corbetta et al., 1998;
Nobre et al., 2000) and detailed meta-analyses (Corbetta 1998;
Nobre et al., 1997).
In short, both covert orienting of attention (as in Posner’s

paradigm, see Fig. 37.4) and the generation of saccades, share
neural resources in:
◆ the parietal regions of the intraparietal sulcus and

superior parietal lobule;
◆ the dorsal lateral premotor cortex (human homologue of

frontal eye fields);
◆ the mesial dorsal premotor cortex (human supplementary

frontal eye-fields) (Fig. 37.6). (p.783)
Therefore, one
can reject the
complete
independence
of regions
involved in
covert
orienting and saccadic eye movements. However in the meta-
analysis of Corbetta et al., (1998), the overlap between the two
systems (while considerable), is clearly not perfect.
Page 27 of 44
◆ Eye Fig. 37.6 Meta-analysis of brain

movements regions activated during performance
are of saccadic eye movements and covert
associated orienting of peripheral attention.
with more
The picture shows areas for performance
extensive
of saccadic eye movements, for covert
orienting of peripheral attention, and
areas shared, at the macroscopic
anatomical level, by the two processes.
ips, Intraparietal sulcus; pocs, postcentral
sulcus; precs, precentral sulcus. (Source:
Corbetta 1998; Courtesy of Maurizio
Corbetta; Copyright 1998, National
Academy of Sciences, USA). (See also
‘Plates’ section).
involvement of regions near the primary motor and

somatosensory cortices.
◆ Covert orienting shows a larger involvement of

prefrontal, and of lateral occipitoparietal junction regions.
The additional areas seen in the saccadic eye movements can

be readily explained by the fact that subjects are actually
moving their eyes. The additional areas seen in covert
orienting may represent the more cognitive neural counterpart
of the task. Indeed, the discrepancy between the motor task
(saccadic eye movements), and the more controlled orienting
task, is reminiscent of the difference seen in tasks in which
one task involves more controlled and cognitive demanding
factors. For instance, in the case of articulation of a
stereotyped string of digits as opposed to random generation
of digits, the latter task also involves more anterior prefrontal
regions (Petrides et al., 1993). A meta-analysis performed by
Kastner & Ungerleider (2000) also shows that the distribution
of the activation during covert orienting of visual attention
while maintaining central fixation, is independent of the
specific requirements of the visuospatial task (i.e. detecting a
stimulus and discriminating or tracking its movement).
Interestingly, the pattern of activation resembles that
identified in the meta-analysis presented in Fig. 37.3.
Page 28 of 44
What is the impact of eye movements on the firing rate of

brain regions outside those directly implicated in the motor
commands? There is evidence for a substantial inhibition of
occipital visual areas during saccades. This has been seen for
reflexive saccades induced by vestibular stimuli, where the
lateralization of deactivation (on the side (p.784) opposite to
the areas of major activation by vestibular stimuli), suggests
that a specific neurobiological mechanism is involved. It is also
interesting that deactivations include, amongst others, the
visual motion perception area MT/V5. The modulatory effect of
eye movements on visual areas has also been described by
Paus et al., (1996). Volunteers lay in the dark and moved their
eyes at different rates during a series of scans. Activity in the
frontal eye fields was positively correlated with the rate of eye
movements. However, in visual cortex and visual association
areas, activity was negatively correlated with rate of eye
movements.
Fink and colleagues (1997) have explored another important

issue, which is the interaction of eye movements in object- as
opposed to space-based attention. They found that brain
activation during attention is modulated by eye movements,
particularly for object-based attention. Greater parietal
activations were seen when foveation was not allowed, as if
object-based attention in these conditions, becomes ‘more
spatial’ in nature. The stimuli used by Fink and colleagues
were devoid of any semantic content (simple lines with a
square, and no graspable objects or body segments were
used). Further studies are needed to address the same issue
using ecologically relevant objects, in two- and three-
dimensional presentations.
5.3 Top-down and bottom-up processes in spatial attention: where

is ‘the top’ and where is ‘the bottom’?
Whichever model of attention one considers, it is necessary to
consider whether there is anatomical distinction between
controlled and automatic orienting of attention. While there is
general consensus that enhancement effects observed in
extrastriate visual cortex (see Box above) may represent the
effects of top-down modulations from areas outside visual
cortex, the source of the modulation remains elusive.
Kastner and Ungerleider (2000) propose that the source of

top-down modulation may be in brain areas involved in covert
orienting of attention. The obvious way to test this assumption
Page 29 of 44
is to compare Posner’s task with another one in which spatial

attention is driven exogenously. This was tried by Nobre and
collaborators (1997). They compared a task in which a
peripheral visual cue indicated that a subsequent stimulus was
80% likely to occur in the same location, with a condition in
which the same cue indicated that a subsequent stimulus was
80% likely to occur in the opposite part of the visual field. (The
latter task is more closely associated with controlled
attentional processes, while the former is an exogenous
process.) However, the two tasks did not show any clear-cut
dichotomy, either when compared with a reference task, or
when the two tasks were compared directly to each other.
Both tasks were associated with a system compatible with that
described in Fig. 37.6.
Rees et al., (1997a) approached the same problem with an

experiment in which top-down factors were assessed with
respect to tonic biasing mechanisms versus stimulus-
dependent ones. This is not easy to achieve given the temporal
resolution of imaging techniques (Rees et al., 1997a).
However, by changing the rate of visual stimuli requiring (p.
785) attention, they were able to show that the inferior
temporal cortex had rate dependent changes of attention
induced activity, while activity in the right dorsal premotor
cortex (BA8) was independent of stimulus presentation rate.
This data is compatible with the idea that inferior temporal
cortex is a site of modulation, while the right premotor region
is a source of top-down modulatory effects on visual cortices.
Kastner et al., (1999) used fMRI to investigate patterns of

activation in the presence and absence of visual stimuli.
Sustained activity was observed, even in the absence of actual
stimulation in the dorsal parietal regions and premotor regions
usually involved in the covert orienting of attention. This
sustained activity was of the same magnitude as the activity
observed during stimulus presentation. On the other hand, in
ventral extrastriate visual areas, activity in the absence of
visual stimuli was comparatively smaller. This evidence
supports the notion that dorsal brain areas involved in
orienting of attention are the source of modulatory signals
directed towards ventral extrastriate visual areas. The role of
the superior parietal cortex in orienting attention (rather than
Page 30 of 44
stimulus detection), has recently been demonstrated by

Corbetta et al., (2000).
Is the source of these modulatory effects unique? We believe

that this is unlikely. Although direct imaging evidence remains
scanty, there is behavioural evidence which shows that biasing
effects in visual stimulus detection can be induced in tasks
which are very different from Posner’s covert orienting
paradigm (or from the other tasks used thus far in imaging
experiments). For instance, preparation of a given grasping
response, facilitates visual detection of objects which have a
shape which is compatible with that grip (Craighero et al.,
1999). Grasping and observation of grasping depend on
different and more ventral circuits in premotor and parietal
cortices than those involved in eye movements (Rizzolatti et
al., 2000). As a consequence, it can be speculated that the
source of biasing effects will move, according to the nature of
the task. This conjecture is supported by recent fMRI
evidence. Sustained attention to, and observation of, finger
movements modulates ventral premotor and rostral superior
parietal regions, involved in both the actual performance of
the movements, as well as in their observation. These are
regions, particularly the ventral premotor cortex, which are
well outside the network for eye movements, which suggests a
modular organization of the neural systems for attention
(Iacoboni et al., 1999).
6 A discrepancy between imaging data on spatial attention

and processing and the anatomy of spatial neglect
As noted by others (Kastner & Ungerleider 2000), the evolving
picture of the functional anatomy of spatial attention (and, of
spatial processing in general), presents a non trivial
discrepancy to the published anatomy of spatial neglect (Vallar
1998, 2001). The distribution of lesions typically observed in
neglect are summarized by the shaded areas in Fig. 37.3
(Vallar 1998). It is clear that the pattern of activations
reported for line bisection tasks (a sensitive test of spatial
neglect; see meta-analysis in Fig. 37.3) involve regions in the
parietal lobe; ones which are more dorsal overall. However,
the more ventral (p.786) regions are systematically seen in
experiments involving the central projections of the vestibular
system, an important finding given the well known ability of
vestibular signals to recalibrate spatial misperception (and
representation) in neglect patients (cf. Paulesu et al., 1997).
Page 31 of 44
The same point about the topography of parietal and premotor

activations applies to the anatomy of the covert orienting of
attention circuits (see Fig. 37.6) (Corbetta 1998), which
appears to be more dorsal (than the regions associated with
spatial neglect). Indeed, given the limited overlap between the
two anatomical patterns, the data seem to justify a view that
spatial neglect does not merely represent a disorder of
attention (cf. Bisiach & Vallar 2000).
Another source of nontrivial discrepancy with respect to the

anatomy of neglect pertains to the lateralization of cerebral
activations. A predominant activation of the right hemisphere
has been found in several studies of spatial attention (e.g.
Nobre et al., 1997), and of sustained attention (Pardo et al.,
1991). However, meta-analyses of experiments on covert
orienting of attention show substantially bilateral and
symmetrical patterns of dorsal premotor superior parietal, and
intraparietal activity (Kastner & Ungerleider 2000; Corbetta
1998). The functional predominance of the left hemisphere for
near space reported in the PET experiment of Weiss et al.,
(2000), awaits testing in brain-damaged patients.
Recently, Corbetta proposed a model which explains the

divergent results emerging from lesion data in neglect
patients, and fMRI studies of visuo-spatial orienting. The
bilateral dorsal fronto-parietal network, including the
intraparietal sulcus (IPS) and frontal eye field (FEF) is
involved in voluntary attention and in the selection of stimuli
and responses. The ventral network, including the temporo-
parietal junction (TPJ) and the inferior frontal gyrus (IFG)
(with a strong lateralization to the right hemisphere), is
involved in the detection of relevant stimuli (particularly when
subjects reorient attention toward a target which appears in
an unexpected location). Both these attentional networks
interact in normal subjects to permit visual orienting, and both
are damaged in patients with visuo-spatial neglect (Corbetta
1998; Corbetta et al., 2002).
Mismatch between functional imaging and lesion data is not

new. This has been seen previously for episodic memory, for
example (Dolan et al., 1997). Resolution of these discrepancies
in spatial neurocognition may contribute to better
understanding of spatial neglect, of normal spatial processing
and attention, and of the nature of right hemispheric
dominance in spatial processing. To achieve this, more studies
Page 32 of 44
on the anatomy of neglect are needed as well as on the spatial

processing of normal subjects and patients with acquired
lesions. The anatomy of neglect needs to be mapped with
patients performing a wider range of tasks, to reveal
dissociations of behavioural deficit. Indeed, the available data
thus far collected, has focused primarily on the cancellation
tasks (which cover spatial exploration in peripersonal space
alone). If the overall pattern of brain lesion in neglect can be
replicated using different tasks, then it becomes important to
characterize the spatial properties of those brain areas (in
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Page 44 of 44
The functional neuroanatomy of learning and memory


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The functional neuroanatomy of

learning and memory
Hans J. Markowitsch
Martina Piefke
DOI:10.1093/acprof:oso/9780199234110.003.038

This chapter describes the kinds of learning and memory
which are relevant for clinical practice and how they are
defined and delineated. Two main lines are followed: one
which divides information processing with respect to time, and
another with respect to contents. It addresses questions
concerning how information is transmitted in the brain
(encoded, stored, or represented), and how information is
retrieved. It describes the anatomical circuits and networks
engaged in these processes with references made to the
brain's biochemistry (transmitters, hormones), as far as it is
relevant for learning and memory, and such disorders.
Keywords: learning, memory, neuropsychological assessment, information

processing, brain circuits, brain biochemistry
Page 1 of 25
1 Introduction
This chapter describes the kinds of learning and memory
which are relevant for clinical practice and how they are
defined and delineated. Two main lines will be followed; one
which divides information processing with respect to time, and
another with respect to contents. Questions will be addressed
concerning how information is transmitted in the brain (
encoded, stored or represented), and how information is
retrieved. The anatomical circuits and networks engaged in
these processes will be described and reference made to the
brain’s biochemistry (transmitters, hormones), as far as
relevant for learning and memory and disorders thereof.
2 Learning and Memory - the behavioural view

Hering (1870) described the importance of memory by stating
that: “Memory connects innumerable single phenomena into a
whole, and just as the body would be scattered like dust in
countless atoms if the attraction of matter did not hold it
together so consciousness – without the connecting power of
memory – would fall apart in as many fragments as it contains
moments”.
Learning is a universal ability of invertebrates and

vertebrates. Accordingly, learning abilities range from simple
forms of adaptation to the environment, to sophisticated
inferential ones. Table 38.1 gives an overview of various forms
of learning. Learning and memory can, in general, be
conceptualized as defined in the box below.
Memory can be subdivided with respect to time and contents.

Specifications for both dimensions are given in Boxes on page
796 as well as in Figs. 38.1 and 38.2. The term anterograde
amnesia is used when the long-term acquisition (i.e., new
learning) of information is lost. The term retrograde amnesia is
applied when a patient is unable to retrieve information which
is already stored in long-term memory (see Fig. 38.3). In most
cases of amnesia, the term global amnesic syndrome, as
applied in early studies of memory loss, is no longer useful:
recent research has shown that patients usually have different
memory systems affected, and thus suffer from selective
deficits of distinct types of memory. (p.794)
Table 38.1 Taxonomy of learning according to

Gagné (1965)
Page 2 of 25
(1) Signal learning or classical conditioning

This form of learning became most well known as
Pavlovian conditioning. The dog, who after a few
pairings of a bell with a piece of meat soon salivates
already to the sound, is an example. In classical
conditioning, the unconditioned stimulus occurs
independent of the subject’s behaviour.
(2) Stimulus-response learning or instrumental
conditioning
Instrumental conditioning is dependent on the
subject’s behaviour. The subject learns the
association between a stimulus and a response.
(3) Chaining (including verbal association)
Chaining refers to several consecutive responses
where each response determines the next. (E.g.,
only several responses, which build up on each
other may lead to a reward.)
(4) Multiple discrimination
Learning to differentiate between stimuli, which
have one or more attributes in common.
(5) Concept learning
Learning to respond in the same way to a variety of
objects or attributes of objects, which have
something in common.
(6) Principle learning
Acquiring knowledge on how to master a set of
problems which have common attributes.
(7) Problem-solving
Making proper use of learned principles and having
insight (being able to draw inferences).
Gagné saw this sequence as hierarchical or as proceeding

from simple to complex forms of learning.
The hypothetical memory trace is named engram. With regard to

the retrieval of information from memory, the rather old concept of
ecphory has regained attention. Ecphory refers to the process
wherein retrieval cues interact with stored information such that a
representation of the searched information becomes activated.
Ecphory furthermore points at the fact that there are different
ways in which information can be retrieved. (p.795)
Page 3 of 25
(p.796)
Fig. 38.1 Sketch of the relations between

memory strength and duration for the
two principal time-related memory
systems, short-term and long-term
memory.
Fig. 38.2 The four principal memory

systems important for human information
processing. The episodic memory system
is context-specific with respect to time
and place. It allows a mental time travel.
Examples are episodes such as the last
vacation or the dinner of the previous
night. Declarative memory is context-free
and refers to general facts. It is termed
semantic memory or the knowledge
systems, as well. Procedural memory is
largely motor-based, but includes also
sensory and cognitive skills (“routines”).
Page 4 of 25
(p.797) The Priming refers to a higher likeliness of re-

most identifying previously perceived stimuli.
demanding
form is free
recall which
refers to the
voluntary
internally cued
recall of
learned
information
Fig. 38.3 Possible consequences of brain
without
external help injury on old and new memories.
or cueing.
Cued recall
refers to recall from memory with the help of external cues. The
most likely least demanding way of retrieving information is its
recognition by selecting a previously presented stimulus out of a
larger number of stimuli.
Box 38.1 Definition of learning and memory
Learning is a relatively permanent change in a

behavioural tendency that occurs as a result of reinforced
practice (Kimble, 1961).
Memory is the learning dependent storage of

ontogenetically acquired information. This information
integrates into phylogenetic neuronal structures
selectively and with respect to the given species so that it
can be retrieved at all times. This means that it can be
provided for situation-dependent behaviour. Generally
formulated, memory is based on conditioned changes of
the transfer properties in neuronal nets so that under
specific circumstances those system modifications
engrams) which correspond to neuromotoric signals and
behavioural tendencies become fully or partially
reproducable (Sinz 1979).
Box 38.2 The time dimension of memory
Page 5 of 25
Sensory memory Retaining of information
(‘iconic’, ‘echoic’ along the sensory channels

memory) (duration: ∼ 50–500 ms)
Short-term memory Storage of memory for

(online processing of seconds to a few minutes (7±2
information) bits of information)
Long-term memory Principally life-long retention

of information
Box 38.3 The time dimension of memory II (stages)
Registration Initial perception and transfer to

cortical routes
Encoding Further initial processing of information

(binding, associating)
Consolidation Deep encoding and embedding of

information (engram formation)
Storage Stable representation of information in

the nervous system
Retrieval Reproduction of information (recall)
Box 38.4 The content-dependent dimension of

memory
Episodic memory Context-embedded

(memory for episodes) autobiographical memory
allowing mental time travelling
Declarative memory Storage of context-free

(memory for facts) information
(knowledge system)
Procedural memory Memory for skills, rules,

sequences
Page 6 of 25
Priming Higher likelihood of re-

identifying previously
perceived stimuli
Other forms Lower forms of memory such

as classical conditioning or
sensitization
3 Disorders of learning and memory

Memory disorders represent a complex of symptoms which
occur most frequently after brain damage. Moreover, they may
arise as a consequence of a number of psychiatric illnesses.
The type of memory disorder and the severity of impairments
and their course may depend on the locus and extent of
damaged brain tissue. In this regard, one has to take into
account that in patients with psychiatric diseases, memory
disorders are also due to stable or temporary alterations in the
nervous system. These are in most cases due to changes in
neurotransmitter availability and distribution, or to changes in
hormones on the brain level. Indeed, recent neuroimaging
data have shown that memory disorders evoked by
psychological trauma can lead to lasting changes in brain
tissue metabolism (Markowitsch et al. 2000), and that there
may be considerable similarities to changed neural
metabolism found in amnesias occurring after organic brain
damage or psychiatric illnesses (Markowitsch 1999a, b, 2003).
Table 38. 2 gives an overview of patient groups who usually

show memory disturbances.
4 Anatomical bases of learning and memory

Much of current understanding of basic memory-related
neuronal changes and modifications stems from the pioneering
research of Eric Kandel and co-workers (Martin et al. 2000;
Kandel 1998) on the invertebrate marine mollusc Aplysia.
Aplysia contains only a limited number of neurons, many of
which are individually identified and labelled. Initially, simple
memory mechanisms such as sensitisation and habituation
were investigated. It could be demonstrated that there are
both short-term and long-term forms thereof. The
physiological correlates of short-term forms are facilitated
neuronal responses (increases in the magnitude of excitatory
postsynaptic potentials formed between sensory and motor
neurones). By contrast, the long-term forms (which were
Page 7 of 25
elicited by repeated stimulus applications) required new

ribonucleic acid (RNA) and protein synthesis, involving the
growth of new synaptic connections between sensory and
motor neurones.
Kandel’s group extended this work to include gene expression

and transcription factors; studies which made available new
insights into the genetic switch for memory consolidation and
storage. Other researchers on invertebrates and vertebrates
demonstrated, for example, that adenylyl cyclase is an
important enzyme for short-term memory (Zars et al. 2000)
and long-term potentiation (LTP), as well as long-term
depression (LTD); all important mechanisms for memory
consolidation (Lynch 2000). Others, however, have questioned
the necessity of such mechanisms for memory formation.
Zamanillo and (p.798)
Table 38.2 Overview of patient groups who

usually demonstrate memory disorders
Etiology Common lesion sites
Intra-cranial tumours Medial and anterior thalamus,

medial temporal lobe, posterior
cingulate cortex
Cerebral infarcts, Medial temporal lobe, limbic

ruptured aneurysms nuclei of the thalamus (Posterior
cerebral artery), orbitofrontal
cortex, basal forebrain (anterior
communicating artery)
Closed head injury Temporal pole, orbitofrontal and

prefrontal cortex
Viral infections (e.g., Hippocampal region, limbic and

herpes simplex paralimbic cortex
encephalitis)
Avitaminoses (e.g., B1 Limbic thalamus, mammillary

deficiency) bodies (e.g., Korsakoff''s disease)
Neurotoxin exposure Hippocampal formation
Temporal lobe epilepsy Hippocampus and medial

temporal lobe
Page 8 of 25
Etiology Common lesion sites
Anoxia or hypoxia Hippocampus (CA1 sector)

(e.g., after a heart
attack or drowning)
Degenerative diseases Temporal and other association

of the CNS (e.g., cortices
Alzheimer's or Pick's
diseases)
Drugs (e.g., Limbic system

anticholinergics,
benzodiazepines)
Electroconvulsive Probably limbic system

therapy
Transient global Probably medial temporal lobe

amnesia and/or medial thalamus (when an
etiology is found)
Paraneoplastic limbic Limbic structure in medial

encephalitis temporal lobe
Mnestic block Massive glucocorticoid release

syndrome leading to a disruption in the
memory processing pathways of
the medial temporal lobe
Dissociative disorders Amnesia possibly due to hormonal

changes in the brain
co-workers (1999), for example, provided evidence against LTP as

an essential prerequisite for memory formation.
On the vertebrate, and especially the mammalian level,
important questions concern not only the issue of how
information is processed, but where it is processed, and in
what different kinds. From the initial stages of information
registration, the brain is, of course involved. However, both
the time and the content dimensions of memory interact in the
neural processing of information. This complicates the
delineation of the neural pathways, circuits, and networks
which are implicated in information processing. Firstly, the
neural bases of simple forms of memory will be briefly
depicted. Thereafter, complex kinds of memory such as
semantic and episodic will be described.
Page 9 of 25
Classical conditioning and other simple correlates of memory

largely take place within the spinal cord and brain stem;
certain other subtypes, however, may engage structures in
various other loci of the brain. Fear conditioning, for example,
involves the amygdala. Priming (a non-reflected unconscious
transmission of information) activates cortical (p.799) areas -
largely, though probably not exclusively, within the particular
modality of the stimulus (‘unimodal’ primary and association
cortex). Procedural memory engages the basal ganglia; it may
also involve portions of the cerebellum, though the evidence is
mixed.
More complex brain circuits are recruited by perceptual,

semantic and episodic memory (Tulving & Markowitsch 1998;
Tulving 2005; Buckner & Carroll 2007). For these forms, it is
necessary to differentiate between the stages of information
transfer listed in Box 38.3.
Information of the declarative and episodic memory systems

enters the brain via the sensory channels, and is then stored
online or short-term (Box 38.1) in cortical association areas,
particularly of the lateral parietal cortex (Markowitsch 2000,
2005). From there it is transmitted to the limbic system.
Within the various structures and fibre networks involved in
this system, the processes of selecting, binding, associating,
and assigning occur. The hippocampal formation can be
regarded as the core of the limbic system. However, there are
several other important components; Table 38.3 lists the most
relevant ones.
Most of the case reports on patients who, in former times,

were declared globally amnesic, had bilateral damage to
either medial temporal lobe or medial diencephalic regions.
The most well-known example is patient H.M., who, in 1953,
received bilateral resection of the medial temporal lobes due
to otherwise intractable epilepsy attacks (Fig. 38.4) (Scoville &
Milner 1957). While the attacks were largely reduced after
surgery, H.M. suffered from persistent anterograde amnesia.
Medial diencephalic infarcts may also cause bilateral

hippocampal damage (Fig. 38.5). This type of amnesia is
largely the same as that seen after bilateral medial temporal
lesion: However, after medial diencephalic infarct, a patient’s
capacity for conscious reflection on his memory impairment is,
in most cases, also disturbed (Markowitsch 2000, 2008). While
Page 10 of 25
H.M. stated “Every day is alone, whatever enjoyment I've had,

and whatever sorrow I've had”, another patient with bilateral
diencephalic damage was unable to acknowledge his severe
amnesia, and instead considered his memory to be
‘normal’ (Markowitsch et al. 1993).
These two examples are more or less representative of the two

principal groups of patients with major and lasting
anterograde amnesia in the episodic and semantic domains –
the medial diencephalic, and the medial temporal group. The
contribution of distinct parts of nuclei or areas of the medial
diencephalon and the medial temporal lobe to memory
functions is still a matter of debate (Table 38.2). The issue
cannot easily be clarified by lesion studies and
neuropsychological testing, since, in amnesic patients, there is
rarely damage confined to any single structure. The
hippocampal formation may represent an exception; the
hippocampus or individual hippocampal sectors are often
selectively damaged after hypoxic or toxic states. The high
vulnerability of the so-called Sommer’s sector of the
hippocampus to epilepsy or hypoxia was noted by 1880
(Sommer 1880).
The basal forebrain also constitutes a region which is

important for unimpaired episodic and semantic memory
function. This is, at least in part, due to its intimate
connections with other memory-related neural networks (e.g.
via the fornix). The basal forebrain is composed of a number of
components of divergent evolutionary origin including (p.
800)
Table 38.3 Structures of the limbic system and

their principal functional implications
Structure Functional involvement(s)
Diencephalon
Anterior nuclear (anterograde) memory, emotion,

complex attention
Mediodorsal nucleus (anterograde) memory,

consciousness, sleep, emotion
Non-specific thalamic consciousness?, (anterograde)

nuclei memory?
Page 11 of 25
Structure Functional involvement(s)
Mammillary bodies (anterograde) memory, emotion?
Telencephalon
(subcortical)
Basal forebrain emotional evaluation,

(anterograde) memory
Amygdaloid body emotional evaluation of

information, motivations, olfaction
Telencephalon
(cortical)
Hippocampal (anterograde) memory, spatial-

formation temporal integration
Entorhinal region (anterograde) memory
Cingulate gyrus attention, drive, pain perception
Associated regions
Medial and emotional evaluation, social

orbitofrontal cortex behaviour, initiative (initiation of
retrieval of information)
Insula sensory-motivational integration?
Temporal pole memory-related sensory

integration, initiation of retrieval,
recruitment of engrams
Fiber systems
Fornix (anterograde) memory?
Medial internal (anterograde) memory?

lamina
Mammillothalamic (anterograde) memory?

tract
Uncinate fascicle retrograde memory?
fibre connections. With regard to biochemistry, the cholinergic

system (basal nucleus of Meynert, septal nuclei, diagonal band of
Broca, the nucleus accumbens, and other parts of the ventral
striatum) plays an important role. The cholinergic system has long
been implicated in the highest cognitive functions, including
memory and consciousness (Perry et al. 1999).
5 Brain circuits for encoding and consolidating
Page 12 of 25
A common view of information processing assumes that

information enters the brain via the sensory organs and is then
stored short-term, most likely in portions of the parietal and
also possibly the prefrontal cortices. Information is thereafter
transmitted to the limbic system, a phylogenetically old system
of structures and fibre connections. It had (p.801)
originally been
associated with
olfaction and
with emotions
in a more
general sense.
Currently, it is
thought to be
implicated in
the processing
of both
emotional and
cognitive forms
of information.
In particular, it
is assumed
that the limbic
system is
involved in the
evaluation of
incoming (and
short-term Fig. 38.4 Drawings of the extent of the
stored) principal surgical removal within H.M.’s
information, temporal lobe. Part (a) shows a basal
and in
view of his brain and part (b) gives
assigning this
coronal sections at the levels A-D
information to
indicated in (a). The extent of the surgical
final storage
networks. With resection is blackened on the left side of
respect to the brain only, though the removal was
episodic and bilateral and symmetrical. (After Fig. 2 of
semantic Scoville and Milner, 1957.)
memories,
these are most
likely represented in distributed in cortical circuits. (p.802)
Page 13 of 25
There are
several
structures
within the
limbic system
which have a
closer relation
to emotional-
affective
information
processing Fig. 38.5 The extent of bilateral
(e.g., the
diencephalic damage in a patient with
amygdala and
preserved intelligence, but severe and
the septum),
persistent anterograde amnesia. (After
than others,
which are Figure 2 of Markowitsch et al. 1993).
more involved
on the
cognitive side (e.g., the hippocampal formation). It is thus
conceivable that there exist two different circuits for information
selection, binding, and transfer (Fig. 38.6). One of them is named
the medial circuit (or Papez-circuit), and the other the basolateral
limbic circuit. The basolateral limbic circuit is composed of three
structures and their interconnecting fibres. The structures are the
amygdala, the mediodorsal thalamus, and the subcallosal area
within the basal forebrain. The unidirectional ventral
amygdalofugal pathway leads from the amygdala to the
mediodorsal thalamus. From there, fibres reach the subcallosal
area which then projects via the bandeletta diagonalis back into the
amygdaloid body. The basolateral limbic circuit evaluates the
affective aspects of incoming information. Importantly, it interacts
with the medial “cognitive” circuit.
The traditional view includes four structures in the medial
circuit: the mammillary bodies, the anterior thalamus, the
cingulate cortex, and the hippocampal formation. The
cingulate cortex can perhaps be omitted because of both its
functional engagement (e.g., Barch et al. 2001; Botvinick et al.
1999; Piefke et al. 2003; Shah et al. 2001; Sugiura et al. 2005)
and the existence of direct projections between the anterior
thalamus and parts of the hippocampal formation. The
interconnecting fibres are given in Fig. 38.6. The medial
circuit is regarded as the circuit which mediates the cognitive
evaluation, binding, and assignment of information for long-
term storage.
Page 14 of 25
It is evident that both the medial temporal lobe and the medial
diencephalic system are embedded in these limbic circuits.
Note that there exist most likely more structures which are of
relevance for the limbic system (in addition to those directly
belonging to the (p.803)
basolateral and
the medial
circuits). With
regard to the
limbic system,
there is
ongoing
discussion as
to what is
included in it.
Structures
within the
basal forebrain
are example
candidates.
Others are
located within
the medial
temporal lobe
system and
contain
hierarchically
organised
allocortical structures which converge on subdivisions of the
hippocampus (Fig. 38.7).
After the encoding of information and its transfer to the
neocortex for long-term storage, the memory engram is not
yet fixed. Instead, memories are further consolidated by
matching the recently encoded pieces of information with
already existing ones, and by (p.804)
Page 15 of 25
Fig. 38.6 The medial (or Papez-) and the

basolateral limbic circuit. The medial
circuit is probably more relevant for the
cognitive acts of memory processing, the
basolateral one for the affective
evaluation of information. Both circuits
interact with each other. The Papez-
circuit interconnects the hippocampal
formation via the (postcommissural)
fornix to the mammillary bodies, these via
the mammillothalamic tract (or tractus
Vicq d’Azyr) to the anterior thalamus, the
anterior thalamus with its cortical
projection targets reaches the cingulate
gyrus and the subicular part of the
hippocampal formation and the cingulum
fibres in addition project back from the
cingulate gyrus into the hippocampal
formation. (The precommissural fornix in
addition provides a bidirectional
connection between the hippocampal
formation and the basal forebrain.) The
basolateral limbic circuit links the
amygdala, mediodorsal thalamic nucleus,
and area subcallosa with each other by
distinct fibre projections, namely the
ventral amygdalofugal pathway, the
inferior thalamic peduncle and the
bandeletta diagonalis.
Page 16 of 25
further
assimilating,
assigning, and
embedding
recently
encoded
information
within the
wealth of
already stored
engrams. The
mind appears
to have a
tendency to
form a
congruent and
consistent
Gestalt of its
memory
repertoire
(Markowitsch
Fig. 38.7 The hierarchical organisation
2008; Piefke
2007). within the medial temporal lobe
5.1 Brain (according to Squire and Knowlton 2000).
circuits for
memory
storage
Overall, information is assumed to be stored in widespread
neural networks. For episodic and semantic information, these
networks are mainly situated within neocortical structures
(association cortex, polysensory cortex). However, the storage
of these forms of memory may additionally recruit allocortical
and subcortical regions. Episodic autobiographical
information, which is usually associated with emotions,
typically requires input from the amygdala and/or the septal
region. As episodic memories are by definition consciously
reflected (Tulving & Markowitsch 1998; Tulving 2005), they
furthermore depend on a neuronal pathway from the brain
stem reticular formation to the neocortex (Markowitsch 2001).
5.2 Brain circuits for memory retrieval

The retrieval of more complex, episodic-autobiographical
information is usually reconstructive in nature, that is,
retrieved materials need not be identical to the originally
encoded information. Interactions of situational cues and a
person’s mood state at the (p.805) time of retrieval may, for
example, interact with stored memory engrams such that an
Page 17 of 25
“updated” representation of the memory may evolve (see the

above definition of the process of ecphory). Functional
neuroimaging data have shown that portions of the prefrontal
and medial temporal cortices are recruited during the
recollection of autobiographic episodes (Fink et al. 1996;
Markowitsch et al. 2003; Piefke et al. 2003). It is conceivable
that the prefrontal cortex provides the impetus or trigger
signal to retrieve memories which are largely stored in
networks of the posterior association cortices. The regions
within the medial temporal lobe may then become active to
accomplish the emotional evaluation of retrieved episodes.
Moreover, the hippocampal formation may (in particular)
mediate the re-encoding of retrieved information. Fig. 38.8
provides an example of the brain regions activated during
autobiographical recollection.
6 The brain’s biochemistry and psychogenic amnesia

It has long been known that memory and other forms of
cognitive processing can not only be impaired after structural
brain lesions, but also that psychiatric illnesses may lead to an
impaired memory. Neurotransmitter and hormonal alterations,
that is, changes in the brains biochemistry, and alcohol or drug
abuse may frequently yield psychiatric or neurological
disorders. The effects of drugs (as well as hormonal and
neurotransmitter alterations) have been the subject of
numerous studies in animals and humans (Dujardin & Laurent
2003; Hallam et al. 2004; Hasselmo et al. 1996). In particular,
the process of memory consolidation can be influenced by a
wide range of pharmacological substances (Lynch 1998).
Changes in the brain’s neurochemistry may lead to well known

neurological syndromes such as Parkinson’s disease where a
lack of dopamine causes motor impairments and occasional
procedural memory problems. There is also substantial
evidence for an involvement of acetylcholine in memory
processing (Hasselmo 1999; Perry et al. 1999), and for the
view that cholinergic dysfunction may lead to both
neurological (Babic 1999) and psychiatric diseases (Sarter &
Bruno 1999). Other transmitters such as gamma-amino butyric
acid (Kalueff & Nutt 1996), glutamate, serotonin, and
noradrenalin have numerous interacting effects especially in
the memory related regions such as the hippocampus (Vizi &
Kiss 1998). Histamines have been found to enhance memory
Page 18 of 25
processing (Passani et al. 2000). Vizi and Kiss (1998)

suggested that even transmitter release without synaptic
contact plays an important role in the fine tuning of
communication between neurones within a given circuit.
Kaufer et al. (1998) found that changes in cholinergic gene

expression may be induced by stress, and Markowitsch et al.
(1999, 2000) hypothesized that the acute or chronic release of
glucocorticoids (i.e., stress hormones) on the brain level may
lead to psychogenic amnesia (also named ‘mnestic block
syndrome’). Psychogenic amnesia may occur in or after
stressful phases of life or after traumatic situations such as
severe accidents or violent assaults. Posttraumatic stress
disorder, which can often be observed in individuals who
experience a traumatic event, is also associated with memory
impairments. Typically, these are psychogenic amnesias for
the trauma and/or intrusive memories (p.806)
Page 19 of 25
(p.807) Fig. 38.8 Positron emission tomographic

(Markowitsch
results, showing activated brain regions
et al., 1998;
of an individual, imaging episodes of his
Piefke et al.
2008).
past.
Psychogenic
amnesia may
include an inability to retrieve old, or to acquire new information
long-term, or both. The syndrome may be transient (Markowitsch et
al. 2000; Markowitsch 2003), but frequently persists over time. In
the latter, slight improvements can sometimes be observed. The
occurrence of psychogenic amnesia is an example of the manifold
ways in which the environment influences the brain’s ability to
code and re-code signals (for related aspects of neural plasticity, cf.
Piefke 2007; Pascual-Leone et al. 2005).
7 Conclusions
The nervous system allows the individual to respond flexibly
and to adapt to the demands of the environment. Its functions
thus help to improve an organism’s possibility of long-term
survival. Animals learn to distinguish between edible and
poisonous foods and to keep smells in mind in order to
distinguish, for example, between dangerous members and
putative sexual partners of its own species. Such emotion-
related messages are initially processed by the limbic system.
The limbic system may thus be referred to as a primary centre
for memory control. This is also the case for episodic
autobiographical memory in humans where complex
interactions between retrieval cues and already stored
information during ecphory have to be taken into account.
Unconscious forms of memory such as priming and procedural
memory are particularly useful in everyday routines, as they
increase an organism’s adaptability to the environment.
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Page 25 of 25
Functional neuroanatomy of language disorders


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Functional neuroanatomy of
language disorders
Reproduced from Handbook of Clinical Neuropsychology,
(2003). Oxford University Press.
Claudius Bartels
Claus-W. Wallesch
DOI:10.1093/acprof:oso/9780199234110.003.039

This chapter presents a synopsis of the representation of
language functions in the brain with a focus on disorders
based on three sources of information: lesion studies (i.e.,
what is known from the effects of pathology upon language
behaviour in patients); the anatomical interpretation of normal
function based on physiological measurements during
language operations in healthy subjects; and a combination of
the two; namely, physiological measurements recorded during
language processing in aphasic patients.
Keywords: language functions, functional imaging, lesion studies, brain

function, neuropsychological assessments, aphasic patients, language
processing
1 Introduction
Page 1 of 18
This chapter will attempt a synopsis of the representation of

language functions in the brain with a focus on disorders
based on three sources of information:
◆ lesion studies (i.e. what is known from the effects of

pathology upon language behaviour in patients);
◆ the anatomical interpretation of normal function based on

physiological measurements during language operations in
healthy subjects;
◆ a combination of the two; namely, physiological

measurements recorded during language processing in
aphasic patients.
Computer-generated three-dimensional brain images into

which imaging software places coloured regions of increased
or decreased ‘function’ have great appeal and are well suited
for title pages of scientific and other journals. However, the
underlying methodology is highly complex and prone to
artefacts and misinterpretations. Therefore we shall include a
brief discussion of functional imaging methodology.
2 Basic anatomy
The hemispheric surface is divided into the frontal, temporal,
parietal, and occipital lobes (Fig. 39.1). The depth of the
sylvian fissure, which separates the temporal from the parietal
and frontal lobes, harbours a hidden part of cerebral cortex,
the insula, which is covered by lips (the opercula) of the
adjacent lobes.
The forebrain is walnut-shaped with one strong (the corpus

callosum) and two minor (commissura anterior and posterior)
interconnections between the hemispheres. The core of the
medial surface of the hemispheres does not continue the lobar
structure. One single large gyrus, the cingulum, surrounds the
corpus callosum.
Cortical processing interacts with the function of subcortical

neuronal structures, the basal ganglia and the thalamus, by
reciprocal connections with specific nuclei of the latter, and
loop systems that include both the basal ganglia and the
specific thalamic nuclei (Alexander et al. 1986). A similar
action upon cortex has been proposed by (p.811)
Page 2 of 18
Schmahmann
and Pandya
(1997) for the
cerebellum.
The basal
ganglia consist
of the putamen
and caudate
nucleus, the
pallidum, the
subthalamic Fig. 39.1 The surface of the left
nucleus, and a hemisphere. Of special interest for
number of language representations are the
minor nuclei
following structures of the left
that need not
hemisphere: the insular cortex and a
be considered
number of cortical areas that are close to
here. The
thalamus the sylvian fissure, namely, Broca’s area
contains more in the foot of the second and third frontal
than 30 nuclei convolution, Wernicke’s area in the
that subserve posterior third of the first temporal
different relay convolution, and, surrounding the
functions: in posterior end of the sylvian fissure, the
cortico–
supramarginal and angular gyrus (see the
subcortico–
text for a discussion of lateralization of
cortical loops;
language representations).
in ascending
sensory and
cerebellar
projections; and in non-specific ascending pathways that subserve,
e.g. cortical activation and the awake state (Fig. 39.2).
In most subjects, almost all right-handers and a majority of
left-handers, the left hemisphere dominates language
processing, although the degree of cerebral dominance differs
interindividually. Anatomically, the planum temporale, which
corresponds to the core of Wernicke’s area, is larger on the
left in about 75 % of normal people (Steinmetz 1996). This
asymmetry seems genetically predetermined and can be found
in fetuses (Chi et al. 1977). (p.812)
Page 3 of 18
Nevertheless,
whether or not
the planum
temporale is an
area that is
inherently
specialized for
language
function is
currently being
debated both
on
neurobiological
and on
neurolinguistic
grounds
(Démonet et
al., 2005;
Marshall
2000).
Fig. 39.2 The subcortical nuclei of the

cerebral hemispheres.
Localization of functions within the brain
The extent to which functions can be localized in the brain

is variable. The primary sensory and motor areas are quite
circumscribed. The more cognitive a function is, the less
well it can be assigned to defined cortical areas. Cerebral
maps even of primary areas are not fixed representations
but may vary in response to functional demand (Merzenich
et al. 1983). It has been proposed that neuronal networks
are a general feature of cerebral organization with quite
distributed networks for cognitive functions (McClelland
and Rumelhart 1986; Harley 1996). The extent of such
networks has been demonstrated by functional magnetic
resonance imaging (fMRI; Carpenter and Just 1999).
Page 4 of 18
The temporal lobe association cortex, of which Wernicke’s

area is a part, integrates auditory, visual, and even
somatosensory information. It is closely interconnected with
the temporal limbic cortex and the amygdalohippocampal
system that subserve both memory and emotional functions.
Broca’s area is part of the precentral association cortex, which
is located between the cortical motor strip and the prefrontal
cortex. The precentral cortex is involved in movement
preparation, but the exact function of Broca’s area is still
under debate. Another frontal lobe cortical area, the left
supplementary motor area at the medial aspect of the frontal
lobe, is involved in language production, especially in the
initiation of speech acts. Functionally, this area is part of the
anterior cingulum. (See box below for a discussion of
localization of functions in the brain.)
3 The anatomical foundation of aphasia

The most common cause of aphasia is stroke in the area of
supply of the middle cerebral artery. Stroke results in
circumscribed lesions, the anatomical analysis of which is
rather unambiguous. Damage to some regions is more likely to
cause lasting aphasia than damage to others, and there is
some interaction between lesion configuration and chronic
aphasia syndromes. Poeck et al. (1984) found core lesions for
Broca’s aphasia in the anterior insula, frontal operculum, and
the underlying white matter; for (p.813) Wernicke’s aphasia
in the posterior superior temporal lobe (Wernicke’s area); and
for global aphasia in the middle and posterior insula and a
much larger white matter lesion including the deep white
matter. Naeser et al. (1987) confirmed the association between
Wernicke’s area lesion and Wernicke’s aphasia, and stressed
the role of deep white matter pathways for the pathogenesis of
global aphasia (Naeser et al. 1989). Whether or not the deep
lesion in global aphasia signifies involvement of white matter
pathways or rather a lesion of the basal ganglia that combines
detrimentally with a cortical lesion is under debate (Wallesch
1997). A recent investigation based on magnetic resonance
(MR)-documented lesions came to the following conclusions
(Kreisler et al. 2000).
◆ Nonfluent aphasia depends on the presence of frontal or

putaminal lesions.
Page 5 of 18
◆ Repetition disorder depends on insular or external

capsule lesions.
◆ Comprehension disorder depends on posterior lesions of

the temporal gyri.
◆ Verbal paraphasia depends on temporal or caudate

lesions.
We will not discuss in detail the anatomy of lesions that may

lead to transient aphasia. It may suffice that almost any lesion
in the area of supply of the left middle cerebral artery, but also
of the left anterior cerebral artery, and lesions of the left
thalamus may cause transient speech or language
disturbances. Lesions of the left supplementary motor area
(SMA) transiently lead to mutism that progresses to
transcortical motor aphasia and finally to normal language
production with some nonfluency. With bilateral lesions,
mustim may persist. There is some agreement that the
cingular region, of which the SMA is part, is not involved in
linguistic processes, but rather in the initiation of speech (von
Stockert 1975).
Kertesz and Wallesch (1993) summarized why the functional

neuroanatomy must be different between acute and chronic
aphasia: ‘The early deficit that may be related to edema,
cellular dysfunction, transient ischemia, etc., is followed by a
great deal of early spontaneous recovery in trauma or stroke.
The chronic deficit is related not only to a loss of function, but
to compensatory changes by functionally connected structures
such as homologous contralateral areas or neighbouring areas
during subsequent stages of recovery’.
Of interest for the issue of lateralization and more widespread,

bilateral representations of language functions are cases of
aphasia in right-handers with right hemisphere lesions
(crossed aphasia). In some well analysed cases an anomalous
pattern of lateralization was found, with some linguistic
functions lateralized to the right, although for most functions
the left hemisphere was dominant (Alexander and Annett
1996). The occurrence of such individual lateralization
patterns may explain why the aphasic symptomatology cannot
be predicted from imaging data.
Page 6 of 18
There are some language functions that suffer greater

impairment from right than from left hemisphere damage (cf.
Joanette and Goulet 1993):
◆ the identification of emotional words and sentences

(Borod et al. 1992);
◆ the production of effective prosody in a tonal (Thai)

language (Gandour et al. 1995).
(p.814) When analysing the clinical imaging data of large

numbers of aphasic patients it becomes apparent that some
linguistic functions (e.g. grammaticalization) seem to be
focally represented in the left periinsular cortex, whereas
others, e.g. the processes that underlie naming and word
finding, are more broadly distributed in the brain. It is often
argued that the clinical symptomatology should not be
attributed to the damaged region but to other undamaged
structures that subserve the respective functions after the
lesion occurred. This view is based on a localization
assumption, namely, that brain regions subserve a function
and, if they are destroyed, other brain areas, which originally
subserved another function, have to compensate, or that there
is redundancy in the system. In recent years, another theory
has gained ground, namely, that cognitive functions have a
distributed representation in neural networks, which have
compensatory facilities of their own. The properties of the
network may explain the symptomatology (Plaut 1995).
The role of the basal ganglia and the thalamus in the

pathogenesis of aphasic symptoms is still controversial. A
central reason is that exact lesion anatomy is difficult to define
because of common vascular supply to various structures and
anatomical variability. Physiologically, a role for the loop
systems, which run from cortex via basal ganglia and thalamus
back to executive cortex and which execute an output gating is
plausible and can explain the symptoms of so-called
subcortical aphasia (Wallesch 1997).
4 The functional neuroanatomy of normal language

processing
Literally hundreds of positron emission tomography (PET) and
fMRI studies have been published since the landmark
investigation of Petersen et al. (1988) that described the
activation of brain areas in normal subjects during language
tasks. With respect to many assumed representations of
Page 7 of 18
language functions, the data are conflicting. The studies can

be replicated only if the experimental setting is exactly
reproduced (for a discussion of methodology, see Section 6).
However, certain aspects of language-related activations
converge between studies, and some of these are briefly
outlined in the box below. Furthermore, PET (Absher et al.
2000) and fMRI activations have been found to correlate with
electrophysiological event-related potentials, which indicates
their validity. In general, fMRI seems more sensitive than PET
due to its superior signal-to-noise ratio (Sadato et al. 1998). In
this review, we shall not separate PET from fMRI studies.
Electrophysiologically, some language processes, especially

those that can be analysed by the comparison of two stimuli
with identical structure over time and a discrete event that
separates them, can be analysed by the method of averaged
event-related potentials (ERPs). Of special interest for
psycholinguistic analysis is the N400 wave, with which
subjects react to semantic or syntactic incompatibility. These
phenomena are highly interesting for the physiology of
language processing, but give little evidence for its underlying
anatomy, even when the method of brain mapping is employed
(for further details, see Rugg and Coles 1995). (p.815)
5 The functional neuroanatomy of language processing in

aphasics
Some language-related activations of brain areas
PET studies using language comprehension (story

listening) and production (covert verb generation to a
semantically related noun) paradigms and analysing their
covariance in comparison to a resting state were able to
identify three areas involved in language processing,
roughly the regions of Broca’s and Wernicke’s area, and
the anterior part of the left inferior temporal gyrus
(Papathanassiou et al. 2000).
Activation of Broca’a area has been found with receptive

syntactic processing (Caplan et al. 2000). Broca’s area was
not activated by word repetition, but rather the left
Page 8 of 18
anterior insula and lateral premotor cortex were activated

(Wise et al. 1999).
Lexical–semantic processing of words activates an

extensive, mainly left hemisphere network of brain
structures (Perani et al. 1999a, see Fig. 39.3), with a larger
left frontal activation for verbs than nouns. A number of
studies have found a left fusiform gyrus (a
parahippocampal structure of the temporal lobe) activation
with semantic access (Murtha et al; 1999, Kuperberg et al.
2000). With respect to semantic category judgements,
Perani et al. (1999b) found a left fusiform gyrus activation
with the processing of living things, and of the left middle
temporal gyrus for tools. It can be expected that abundant
information on the cerebral basis of semantics will be
available from fMRI studies in the near future. It can also
be expected that future studies will reveal a great degree
of interindividual variability, as subgroups of normal
subjects show bilateral temporal activation with semantic
retrieval (Warburton et al. 1999).
The lesions underlying aphasia interfere with task-related

activation of the affected brain structures. However, functional
imaging demonstrated changes in the functional organization
of language processing in aphasics. Depending on the
language task, aphasic patients seem to activate ipsi- and
contralesional cortical areas in addition to spared structures
(Ohyama et al. 1996). The superior repetition performance in
transcortical aphasia seems to be based on right hemisphere
mechanisms (Berthier et al. 1991). Alterations in language
processing in aphasic patients can also be demonstrated by
neurophysiological analysis. ERP and MEG
(magnetoencephalography) studies have the advantage of
superior temporal resolution over fMRI and PET (but inferior
spatial resolution). Friederici et al. (1998) were able to show
that ERP-correlates of the automatic analysis of syntactic
structures were absent in Broca’s aphasia.
Recovery from aphasia seems to depend mainly upon three

functional anatomical mechanisms:
◆ recruitment of perilesional left cortical areas for language

processing (Warburton et al. 1999);
Page 9 of 18
◆ an activation of the left supplementary motor area;
◆ an activation of contralesional homologues in the right

hemisphere. (p.816)
(p.817) Some
studies suggest
that early
recovery is
related to left
and long-term
improvement
to right
hemisphere
activation
(Karbe et al.
1998). Patients
who were able
to recruit
dominant
language
structures
exhibited
better recovery
(Heiss et al.
1999). It has
been proposed
that speech
therapy may
aid in the
activation of
the dominant Fig. 39.3 Activation of cortical regions by
hemisphere
reading words of different class and
and that right
concreteness versus pseudowords in a
hemisphere
lexical decision task: a) activation by
activation may
be words compared to pseudowords; b)
dysfunctional commonalities of activation by all words;
(Belin et al. c) verbs compared to nouns; d) abstract
1996). On the words compared to concrete words.
other hand, (Taken with permission from Perani et al.
improvement 1999a, Fig. 1.)
with intensive
comprehension
training in Wernicke’s aphasia was shown to correlate with task-
dependent activation in the posterior part of the right superior
temporal gyrus (Musso et al. 1999).
Page 10 of 18
Pizzamiglio et al. (2001) pointed out that the function-related

changes in cerebral activation patterns after lesion may have
different meanings.
◆ In some cases, spared neuronal populations involved in a

given function may undergo reorganization providing the
basis for functional recovery.
◆ In other cases, different regions of the brain, which

process information in a completely different way, are
recruited after a lesion to compensate for a functional loss.
6 Methodological problems of functional imaging

Functional images represent spatially and temporally
integrated measures of regional cerebral blood flow during the
performance of a task in contrast to flow distribution during
another task (or a resting state). A detailed discussion of the
methodological aspects of functional language studies is given
by Grabowski and Damasio (2000). These authors’ summary of
items to be included in processing the complex data includes:
◆ modelling and removal of artefacts;
◆ spatial transformation to a standard anatomical space

(usually based upon Talairach and Tournoux 1988);
◆ spatial filtering to improve signal-to-noise ratio, to

overcome anatomical variability, and to meet parametric
assumptions of statistical analysis (see end of this section);
◆ statistical analysis;
◆ construction of a statistical parametric map;
◆ significance thresholding of the test statistic images;
◆ inference;
◆ representations of the results (Grabowski and Damasio

2000, pp. 430–2).
The method is based on a number of assumptions that are

difficult to control.
◆ It supposes that the experimental task states differ only

with respect to the tasks (problems, e.g. effort, demand on
working memory, subjective reaction).
Page 11 of 18
◆ Brains differ anatomically and cannot completely be

mapped upon a standard anatomical space (Rajkowska and
Goldman-Rakic 1995).
◆ It is assumed that the experimental tasks isolate a single

cognitive function.
(p.818)
◆ It is assumed that task-related activation is insensitive to
practice effects.
In fact, practice changes activation patterns. Furthermore, the

sheer rate of presentation of stimuli affects activation (Raichle
et al. 1994).
In many experiments, the crucial experimental task differed in

a number of aspects (e.g. difficulty, propositionality, size, and
number of activated semantic fields) from those it was
compared with. Generally, the so-called subtraction method
assumes that cognitive variables that affect different stages of
processing are simply added and can be revealed by the
subtraction of two states, one that includes the process in
question from a similar other that does not. This approach was
very fruitful in the analysis of reaction times. The use of this
method with language tasks poses many problems, among
which the following cause the greatest concern.
◆ Automatic activation of language processing even when

subjects are instructed not to pay attention to linguistic
content.
◆ Changes in activation may be a characteristic of the

control task.
◆ The assumption of addition of a processing state may be

inherently false (Friston et al. 1996).
Parametric designs are able to overcome some of these

problems. Statistical parametric mapping is based upon
spatially extended statistical processes that compare spatially
distributed events with a probabilistic distribution. Improbable
effects within the map are interpreted as regionally specific
effects due to the experimental manipulation. ‘The
fundamental difference between subtractive and parametric
approaches lies in treating a cognitive process not as a
categorical invariant but as a dimension or attribute that can
be expressed to a greater or a lesser extent’ (Friston 1997). An
important next step is the introduction of nonparametric
Page 12 of 18
statistics (‘statistical nonparametric mapping’; Poline et al.

1997). Functional connectivity between two regions can be
statistically established by factorial designs (Friston et al.
1997).
7 Summary
From the above discussion, it becomes obvious that the
methodological problems of functional imaging are not settled.
Although experiments can be replicated, if the exact situation
is restaged, results are still conflicting, depend upon the
strategy of analysis, and cannot be generalized yet (Friston et
al. 1997; Grabowski and Damasio 2000). However, it is also
clear that functional imaging, especially fMRI, has a great
potential for the analysis of cerebral processes, particularly
those that are involved in cognition and emotion. In our
opinion, the analysis of interindividual differences will become
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Wallesch, C.W. (1997). Symptomatology of subcortical

aphasia. J. Neurolinguistics 10, 267–75.
Warburton, E., Price, C.J., Swinburn, K., and Wise, R.J.

(1999). Mechanisms of recovery from aphasia: evidence from
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Page 18 of 18
Functional neuroanatomy of executive process


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Functional neuroanatomy of
executive process
Joaquín M. Fuster
DOI:10.1093/acprof:oso/9780199234110.003.40

This chapter considers the executive functions of the lateral
prefrontal cortex (LPC). Topics discussed include the anatomy
and connectivity of the prefrontal cortex, neuropsychology of
the prefrontal cortex, temporal integration and its ancillary
executive functions, and the perception-action cycle.
Keywords: lateral prefrontal cortex, executive functions, brain functions,

temporal integration
Page 1 of 18
1 Introduction
The cortex of the frontal lobe contains the highest stages of
the hierarchy of neural structures dedicated to motor
representation and processing. The lowest stage of that
hierarchy consists of motor neurons in the anterior horns of
the spinal cord. Above, in ascending order, are the motor
nuclei of the brainstem, the cerebellum, and the diencephalon,
including nuclei of the hypothalamus, the thalamus, and the
basal ganglia. The cortex of the convexity of the frontal lobe is
itself hierarchically organized and devoted to motor actions. At
the bottom of the cortical motor hierarchy lies the primary
motor cortex, for the representation and execution of
elementary skeletal movements. Above it lies the premotor
cortex, for more complex movements, which are defined by
goal and trajectory. Some premotor areas are involved in
speech organization. At the top is the cortex of association of
the frontal lobe, commonly called prefrontal cortex. This
cortex, especially in its lateral region, contains neuronal
networks that represent broad schemas and plans of
sequential action and are crucially involved in their
enactment. Thus, the lateral prefrontal cortex (LPC) has been
sometimes identified with the ‘central executive’ and also
called ‘the executive of the brain’. In this chapter, the
executive functions of the LPC are considered (see Chapters
18 and 19). Before dealing with them, the chapter deals with
the anatomy, the connectivity, and the neuropsychology of the
prefrontal cortex in general.
2 Anatomy and connectivity of the prefrontal cortex

The prefrontal cortex is one of latest regions of the neocortex
to develop, phylogenetically as well as ontogenetically. In
evolution, it reaches its greatest relative expansion in the
brain of the human, where it constitutes almost one-third of
the neocortex. Most of that expansion takes place in the
lateral convexity of the frontal lobe, that is, in the LPC. In
ontogeny, the prefrontal cortex—the LPC in particular—is one
of the last regions to reach full myelination of afferent,
efferent, and intrinsic fibres. The LPC is also late in reaching
maturity by other indices, e.g. number and volume of neurons,
and size and number of dendritic spines. In the normal human
subject, the prefrontal cortex does not reach full
morphological maturation until late adolescence. The late
Page 2 of 18
maturation of the LPC is probably related to the late

maturation of its cognitive functions.
(p.823) The prefrontal cortex is profusely connected with

other brain structures. It receives afferent fibres from the
brainstem, the hypothalamus, the limbic system (especially
amygdala and hippocampus), the thalamus, the basal ganglia,
and other areas of the neocortex, especially the association
cortex behind the sylvian fissure (parietal, temporal, and
occipital regions).
◆ The afferents from the brainstem, the hypothalamus, and

limbic formations bring the prefrontal cortex information
about the internal milieu.
◆ The inputs from the hippocampus are probably essential

for the formation of motor or executive memory.
◆ The afferents from posterior association cortex appear to

be involved in higher-order sensorimotor integrations.
The prefrontal cortex reciprocates afferent inputs from all

those cerebral structures with efferent outputs to them.
Several neurotransmitter systems of brainstem origin

converge on various areas of the prefrontal cortex. They
mediate interactions at the synaptic level between subcortical
structures and that cortex. The most prominent among them
are the dopamine systems, which vary in terms of the types of
receptors by which they mediate the transmission of
information between cells.
◆ Dopamine plays an important role in orbital prefrontal

cortex, where it mediates neural transactions related to
rewards and emotional behaviour. Furthermore,
dopaminergic prefrontal pathways mediate motor behaviour
through the basal ganglia.
◆ Noradrenaline (norepinephrine) and serotonin, with

sparser distributions in the prefrontal cortex, are probably
involved in cortical arousal and attention mechanisms.
◆ A powerful cholinergic system, originating in the basal

nucleus of Meynert and widely distributed throughout the
neocortex, is most probably also involved in those attention
mechanisms and in short-term memory.
Page 3 of 18
◆ In the prefrontal cortex, as in other parts of the cortex, γ-

aminobutyric acid (GABA) is the most abundant inhibitory
neurotransmitter. It participates in the filtering or
exclusionary mechanisms of attention and working memory.
◆ Glutaminergic neurotransmitters, such as those operating

on N-methyl-D-aspartate (NMDA) receptors, most probably
play a role in the formation of executive memory in the
prefrontal cortex.
Intervening in this process are probably the reciprocal

connections between the hippocampus and the LPC, which
have been demonstrated in the monkey.
3 Neuropsychology of the prefrontal cortex

For more than a century, the study of the behavioural and
cognitive effects of prefrontal damage from disease or trauma
has been a major source of knowledge about the functions of
the prefrontal cortex. This knowledge is largely inferential,
based on the assumption that the deficit from the lesion of a
cerebral structure such as the prefrontal cortex results from
(p.824) the interference with the normal function(s) of that
structure. This assumption is not always tenable, because the
lesion may secondarily and imponderably affect other—
neighbouring or connected—structures. Furthermore, the
deficit is commonly relative, i.e. only quantitatively different
from the dysfunction induced by lesions elsewhere in the
brain. In any event, the inferences from clinical lesion are
generally confounded by considerable individual variability—in
terms of the extent and location of the lesion as well as its
effects. Nonetheless, a massive literature is now available on
the clinical and psychological manifestations of frontal-lobe
injury. This literature allows us to characterize those
manifestations with considerable confidence. A particular
cluster of symptoms and signs can be reliably observed after
damage to each of the three principal regions of the prefrontal
cortex (Fig. 40.1):
◆ medial;
◆ orbital;
◆ lateral (LPC).
3.1 Medial/cingulate region
Page 4 of 18
The lesions of the medial region of the prefrontal cortex

induce disorders of drive and motivation. Apathy and
disinterest are the dominant manifestations of medial
prefrontal damage.
(p.825)
Related to
them is the
lack of
spontaneity in
all domains of
action,
including
speech. The
patient is
generally
hypokinetic. In
cases with
large lesions of
medial
prefrontal Fig. 40.1 Diagram of the human cerebral
cortex, cortex. The areas of the three prefrontal
hypokinesia regions are numbered in accord with
turns into Brodmann’s cytoarchitectonic map.
akinesia
(akinetic
mutism when speech is involved). Circumscribed lesions of the
anterior cingulate cortex (areas 24 and 32) commonly result in
deficits of attention. The patient with such a lesion has difficulty
focusing on the performance of tasks that require sizeable effort
and attention to detail. Thus the patient appears not only
neglectful, but also unable to gather the energy to respond to
cognitively challenging situations.
In all probability, the lack of interest, the aspontaneity, and the
inattentiveness of patients with medial/anterior-cingulate
lesion reflect the disruption of a general adaptive function of
goal-directed drive that is indispensable for selective
attention. The connectivity of medial prefrontal cortex with
limbic structures probably plays a role in that general
function. Mesulam (1981) has postulated an ‘anterior
attentional system’, of which the anterior cingulate region
would be a crucial part. That system also includes gaze-control
areas of parietal and lateral prefrontal cortex.
3.2 Orbital region
Page 5 of 18
Lesions of ventral (orbital) prefrontal cortex ordinarily induce

a relatively uniform syndrome. An attentional disorder is here
again in the foreground, but this one is not so much
characterized by absence of drive as by failure of the
exclusionary aspect of attention. The patient is abnormally
distractable, unable to inhibit the interference from external
stimuli that are extraneous to the action in progress, whatever
that may be. Together with distractability, and probably
related to it, is a general tendency to hyperactivity and
hyperreactivity. On formal testing, the patient commonly fails
to perform correctly the Stroop task, the Wisconsin Card
Sorting Test (WCST), and other tests that require the
attentional suppression of interference.
Furthermore, the affect of the orbital patient is labile and

unpredictable. Together with a sporadic tendency to euphoria,
the patient commonly exhibits inappropriate and coarse
humour. In addition, he or she is unable to inhibit instinctive
drives, and thus inclined to frequent displays of
quarrelsomeness, hypersexuality and hyperphagia. The
disinhibition of instinct, accompanied by lack of moral
judgement, often leads the patient to unruly behaviour and
conflict with the law. Sociopathy is almost the hallmark of the
orbital syndrome.
In brief, the patient with damage of the orbital prefrontal

cortex commonly exhibits a variety of abnormalities of
emotional and social behaviour (Damasio et al. 1994; Fuster
1997). At the root of these abnormalities, there appears to be
a deficit in the inhibitory control functions of this cortex. In
normal attentive processing, inhibitory control is probably
exerted through efferent connections of orbital cortex upon
the thalamus and upon areas of frontal and posterior
association cortex. In normal social behaviour, that control is
exerted upon the hypothalamus and other limbic structures.
Both kinds of control fail in the patient with orbitofrontal
damage.
Page 6 of 18
3.3 Lateral region (LPC)

The most characteristic cognitive deficits from frontal-lobe
injury are those that result from damage to the associative
cortex of the lateral frontal convexity—the LPC. (p.826) In
subjects with a large LPC lesion, the most common disorder is
the inability to conceptualize and to carry out plans and goal-
directed sequences of actions. It is from this disorder that the
notion emerged of a critical role of the LPC in the
representation and execution of organized behaviour (Luria
1966; Fuster 1997). The planning deficit,which extends to the
representation and construction of language (Luria 1970), is
now generally considered a consistent manifestation of large
lateral LPC lesion. One aspect of this deficit is a difficulty in
mentally representing sequences of speech or behaviour.
Another is a difficulty in executing them in orderly fashion.
The aggregate of these difficulties constitutes what Baddeley
(1986) calls the ‘dysexecutive syndrome’. This syndrome, like
the medial and orbital syndromes, usually includes a severe
attentional disorder, though this disorder differs qualitatively
from those that result from medial or orbital lesion. Shallice
(1988) characterizes the LPC disorder as the failure of
‘supervisory attentional control’. By this he means the inability
to summon and sustain selective attention on a series of goal-
directed actions. This aspect of attention is essential to
executive initiative, decision-making, and the temporal
organization of novel and complex behaviour.
Any reasonable analysis of the functions of the LPC must

distinguish between its representational role and its
operational role. The former can be inferred from the
deleterious effects of LPC lesions on the mental
representations of plans and schemata of sequential action.
The study of these effects has led to the concept of the LPC as
the substrate of executive memory, which includes the
schemata or plans of past or future action. Plans can be
considered ‘memory’ inasmuch as they consist of fragmentary
representations of previous actions—rearranged for future
planning. Executive memory is held in wide arrays of
interconnected neuronal networks of the LPC (Fuster 1995).
The operational role of the LPC essentially consists of the

orderly activation of those networks in the construction of
goal-directed sequences or temporal ‘gestalts’ of executive
action. Temporal integration is the most general function of
the LPC. This operation is served by at least four cognitive
Page 7 of 18
functions that this cortex controls in cooperation with

subcortical structures and with other regions of the neocortex.
Those functions are:
◆ attention;
◆ working memory;
◆ prospective set;
◆ response monitoring.
They are closely entwined and cannot be extricated from one

another physiologically. None is represented exclusively in any
discrete LPC area. Any demonstrable specialization of LPC
areas is not so much attributable to the topographical
distribution of those cognitive functions as to the kind of
executive information they process. Thus some areas are
dedicated to motor actions, others to eye movement, and still
others to speech. In any given area, all four cognitive functions
operate at the service of the temporal integration of the kind
of executive information in which the area specializes. (p.
827)
4 Temporal integration and its ancillary executive

functions
Page 8 of 18
Temporal
integration,
i.e. the
capacity to
integrate
information
across time, is
the essence of
temporal
order. This Fig. 40.2 Temporal sequencing of acts
applies to (a1 … an) toward a goal. (Above) Chain of
behaviour, acts in a routine and well-practised
speech, and sequence. Contingencies (arrows) are
logical present only between successive acts.
reasoning. (Below) A novel and complex sequence of
The central acts that necessitates the mediation of
role of the cross-temporal contingencies, a function
LPC in the of the LPC.
organization
of actions in
those three domains is crucially based on its ability to mediate
contingencies across time (‘if now this, then later that; if
earlier that, then now this’). Both the choice and the timing of
an act in a goal-directed sequence are contingent on the plan
of action, on the goal, and on other acts that have preceded
that act or are expected to succeed it (Fig. 40.2). Inasmuch as
the LPC is needed for the mediation of cross-temporal
contingencies, it is needed for the temporal organization of
behavioural, linguistic, and cognitive actions.
The most widely used behavioural paradigms for testing the

role of LPC in temporal integration are the so-called ‘delay
tasks’, e.g. delayed response, delayed matching- to-sample. In
these tasks, the subject is required to retain a discrete item of
information in order to execute, a few seconds later, an action
that is contingent on that information. For correct
performance, therefore, each trial requires the integration of
information across time, i.e. across the delay. It has long been
known (Jacobsen 1931) that monkeys that have sustained
lesions of LPC are rendered incapable of learning and
performing delay tasks, especially when the information is
complex and the delay long (>10 seconds).
Page 9 of 18
In the past 30 years, electrophysiology and neuroimaging have

established the operational role of the LPC in all four of its
temporal integrative functions. Many of the studies
contributing the supporting evidence have been carried out in
monkeys or humans performing delay tasks.
4.1 Sensory attention

Attention is the selective allocation of neural resources to
behaviour and cognition. It operates at many levels of sensory
and motor systems. It is essential in the cerebral cortex (p.
828) for the efficient processing of information in its vast
systems of intersecting networks. For a behavioural sequence
to attain its goal, continuous selective attention is required on
the sensory stimuli that guide it and on the motor actions that
constitute it. This is fundamentally a cortical function. Its
mechanisms are still poorly understood and they can be
assumed to include excitation as well as inhibition. The results
of their operation are:
◆ selective focusing;
◆ enhanced contrast;
◆ suppression of extraneous information.
All forms of attention required for the organization of

behavioural and cognitive sequences are under executive
prefrontal control. As noted in Section 3, medial and cingulate
areas contribute to the motivational aspects of attention and
orbital areas to the inhibitory control of interference or
distraction. Areas of the LPC, on the other hand, contribute to
the aspects of attention more directly related to temporal
integration. Sensory attention is one of them. Several LPC
areas—notably area 8—are involved in visual attention, as they
specialize in the control of gaze and eye movements. Lesions
of these areas lead to visual neglect and to the inability to shift
attention between locations in the visual field. Functional
neuroimaging provides further evidence for the role of LPC in
selective sensory attention, as it supports a variety of temporal
integrative tasks (Duncan and Owen 2000).
Working memory and prospective set, the two LPC functions

that are essential to bridge time (see Sections 4.2 and 4.3),
can also be considered forms of selective attention. Both
constitute attention that is directed to internal
Page 10 of 18
representations. Both appear to depend on the selective

activation of cortical and subcortical structures under the
control of the LPC (Desimone and Duncan 1995; Fuster 1995).
4.2 Working memory

Working memory (Baddeley 1986) is the temporary retention
of information for the performance of an act that is contingent
on that information. All forms of cognitive and behavioural
performance requiring the mediation of cross-temporal
contingencies depend to some degree on working memory.
Working memory is the first cognitive function of the LPC to
have been substantiated at the neuronal level by
microelectrode methods. In delay tasks, during the retention
of a sensory cue for a prospective action, neurons in the
dorsolateral prefrontal cortex of the monkey exhibit sustained
elevated discharge (Fuster 1973). This discharge, which may
last anywhere between a few seconds and 2 or 3 minutes, is
correlated with accuracy of performance and can be
obliterated or attenuated by distraction. Cells with these
characteristics have been called ‘memory cells’. During the
performance of spatial delayed-response tasks, in which the
animal must retain the position of a visual cue, some LPC cells
are involved in the retention of spatial information. In other
kinds of delay tasks, memory cells have been found for
colours, auditory cues, and tactile information. In any case, the
participation of LPC cells in working memory seems strictly
related to the need to retain information for an action that is
contingent on that information.
(p.829) In the human, the use of functional neuroimaging by

positron emission tomography (PET) or magnetic resonance
(MR) reveals the activation of the LPC in a number of working
memory tasks (Grasby et al. 1993; Petrides et al. 1993; Smith
et al. 1996). The activation has a different topography
depending on the nature of the memorandum or information
that the subject must temporarily retain. It is reasonable to
assume that the activation reflects the excitation of large
assemblies or networks of memory cells that encode that
information in working memory. LPC networks have been thus
substantiated for visuospatial, visual–nonspatial, and verbal
memoranda.
4.3 Prospective set
Page 11 of 18
Prospective or preparatory set is another form of internalized

attention under LPC control. Like working memory, it helps
the organism to mediate cross-temporal contingencies.
Whereas working memory is retrospective memory,
prospective set is ‘memory of the future’. It is attention
focused on the representation of prospective action. Thus, the
prospective-set function can be considered a kind of motor, or
executive, attention. By this function and mechanisms that are
still unknown, the LPC primes executive systems for
anticipated action.
A well-known electrical correlate of prospective set is the

contingent negative variation (CNV), a slow surface potential
that develops over the frontal lobe in the interval between a
sensory stimulus and a motor response that depends on it
(Brunia et al. 1985). Another such correlate is the
Bereitschaftspotential or ‘readiness potential’, which develops
over motor cortex immediately before the response. In
monkeys performing a delay task in which the animal had to
remember a colour for a hand movement to the right or to the
left, some LPC were found to react specifically to colours and
others to direction of manual response (Quintana and Fuster
1999). During the delay or memory period, the cells of the first
type (colour-coupled) showed a gradual descent of discharge
(Fig. 40.3). Conversely, those of the second type (direction-
coupled) showed an acceleration of discharge. Furthermore,
the degree of that acceleration varied in proportion to the
certainty with which the animal could predict response
direction (different colours predicted direction with different
degrees of probability).
To sum up, the slow potentials in anticipation of an action, and

the presence of cells in LPC that seem to predict the action,
indicate that the LPC participates in the preparation of the
motor apparatus to act. At lower stages, that apparatus
includes structures such as the premotor cortex, the basal
ganglia, and the pyramidal system. All may take part in the
preparatory modulation of motor systems under LPC control.
That kind of preparatory control can also be inferred from the
activation of the LPC observed by neuroimaging during
planning tasks (Partiot et al. 1995; Baker et al. 1996).
4.4 Response monitoring
Page 12 of 18
Response monitoring is a fourth integrative function of the

LPC. This function is based on both internal and external
feedback arriving in this cortex during organized action. The
internal feedback consists of signals from internal receptors
activated by movement. (p.830)
Such signals
include inputs
from the motor
system in the
form of so-
called ‘efferent
copies’ of
muscular
movement and
inputs from
proprioceptors.
The aggregate
of these
internal signals
related to Fig. 40.3 Discharge of LPC cells during
movement
the delay between a colour and the
generates in
manual response associated with it (C,
the LPC what
colour; R, response). (Left) Discharge of
has been
termed colour-coupled memory cells. (Right)
corollary Discharge of direction-coupled cells. The
discharge latter cells anticipate the response with
(Teuber 1972). an acceleration of firing that is greatest
This consists of (top graph) when the animal can predict
neural response direction with certainty.
impulses that
flow into
sensory systems and prepare them for changes resulting from
anticipated movement. Corollary discharge would thus stabilize
perception despite changes in the relative position of sensory
receptors with respect to the environment.
In addition, various kinds of feedback from sensory receptors
carry to the LPC information about the changes that actions in
a behavioural sequence induce in the environment. Thus a
more or less continuous stream of sensory signals arrive in
LPC with information on the consequences of one’s successive
actions. These signals include indicators of the success or
failure of each act with respect to the goal of the sequence.
The LPC will integrate that information to prepare the
Page 13 of 18
organism for subsequent actions and to induce in them

corrective modifications.
Neuroimaging supports the involvement of the LPC in

response monitoring (Petrides et al. 1993; Fink et al. 1999).
Further evidence of this involvement comes from (p.831)
electrophysiology in patients with LPC lesions (Gehring and
Knight 2000). Both imaging and electrophysiology also
indicate a parallel role of the anterior cingulate cortex in the
monitoring of response errors.
5 The perception–action cycle

All four integrative functions of the LPC just mentioned
operate within the broad physiological framework of the
perception–action cycle (Fuster 1997). This physiological cycle
constitutes the extension into the cerebral cortex—and thus
into the cognitive sphere—of a basic physiological principle of
sensorimotor adaptation of the organism to its environment. It
may be considered to be part of the ‘homeostatic’ mechanisms
of the organism inasmuch as adaptation to the environment
protects stability of the internal milieu. The cycle is made of
the circular cybernetic flow of information between the
environment, sensory structures, and motor structures. Those
neural structures are hierarchically organized along the nerve
axis, and so are the levels of the cycle that unites them. The
LPC and the posterior association cortex are at the summit of
the perception–action cycle (Fig. 40.4).
In the course of a goal-directed sequence of behavioural acts,

the sensory information that guides the sequence is processed
upward in successive stages of the hierarchy of sensory
cortical areas. That processing leads to outputs to motor
areas, where actions are integrated. (p.832)
Page 14 of 18
The actions
induce changes
in the
environment,
which generate
new sensory
inputs, which
lead to new
actions, and so
on. Automatic
and routine
behaviours can
be integrated
at lower stages
of sensory and
motor
hierarchies,
without need
for Fig. 40.4 Schematic diagram of the
intervention of perception–action cycle.
higher
cortices. Novel
and complex behaviours, however, require processing at the
highest levels of the perception–action cycle and thus involve the
prefrontal cortex and the cortex of polymodal sensory association.
The LPC intervenes whenever those behaviours necessitate the
mediation of cross-temporal contingencies. Temporal integration,
and thus the temporal organization of those behaviours, are then
made possible by the executive functions of the LPC summarized
above.
As can be gleaned from the structure and operations of the
perception–action cycle and the position of the LPC in it, the
latter performs its executive functions in close cooperation
with other cortical regions (Fuster 2001).
◆ The LPC controls the focus of attention by its modulation

of sensory association areas of posterior cortex.
◆ Working memory is maintained by reverberation of

activity in connective loops that link the LPC with those
areas.
◆ Prospective set involves the downflow of priming

influences from LPC upon premotor and motor cortices.
◆ Finally, the monitoring of motor responses and their

consequences is in large part mediated by signals that
Page 15 of 18
arrive in LPC after being processed in hierarchically lower

sensory and motor cortices.
6 Conclusions
The neural substrate for executive processing is organized
hierarchically. At every level of the hierarchy, neuronal
assemblies serve both the representation and the execution of
actions. In the upward progression of executive levels, from
the spinal cord to the neocortex, the actions represented and
executed increase in complexity, as well as in the spatial and
temporal remoteness of their goal. The association cortex of
the convexity of the frontal lobes, or lateral prefrontal cortex
(LPC), constitutes the highest level of that hierarchy. Its
primary function is the temporal organization of goal-directed
behaviour, speech, and reasoning. The organization of actions
in those domains is essentially based on the capacity of the
LPC to integrate temporally discontinuous information. In that
process of temporal integration, the LPC mediates
contingencies across time by cooperating with other cortical
structures in the cognitive functions of the perception–action
cycle, which include attention, working memory, prospective
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dorsolateral frontal cortex in memory processing. Proc. Natl
Acad. Sci., USA 90, 873–7.
Quintana, J. and Fuster, J.M. (1999). From perception to

action: Temporal integrative functions of prefrontal and
parietal neurons. Cerebral Cortex. 9, 213–21.

structure. Cambridge University Press, New York.
Smith, E.E., Jonides, J., and Koeppe, R.A. (1996).

Dissociating verbal and spatial working memory using PET.
Cerebral Cortex. 6, 11–20.
Teuber, H.L. (1972). Unity and diversity of frontal lobe

function. Acta Neurobiolagiae Experimentalis. 32, 615–56. (p.
834)
Page 18 of 18
Clinical and laboratory examinations relevant to clinical neuropsychology


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Clinical and laboratory examinations

relevant to clinical neuropsychology
Udo Kischka
DOI:10.1093/acprof:oso/9780199234110.003.041

This chapter describes the methods used by clinicians to gain
insight into the structure and the functions of a patient's
nervous system. Computerized tomography and magnetic
resonance imaging are the methods of choice to demonstrate
the anatomical structure and deviations thereof, such as
trauma, stroke, tumour, or inflammation. They help visualize
where a lesion is localized. All the other methods mentioned in
the chapter are used to examine the extent of functioning of
parts of the nervous system.
Keywords: computerized tomography, magnetic resonance imaging,

neuropsychological assessments, trauma, stroke, tumour, inflammation
Page 1 of 17
1 Introduction
The methods described in this chapter are used by clinicians
to gain insight into the structure and the functions of a
patient’s nervous system. Computerized tomography (CT) and
magnetic resonance imaging (MRI) are the methods of choice
to demonstrate the anatomical structure and deviations
thereof, such as trauma, stroke, tumour, or inflammation. They
help visualize where a lesion is localized. All the other
methods mentioned in this chapter are used to examine the
extent of functioning of parts of the nervous system. In the
context of this handbook, only those methods that deal with
the brain rather than the spinal cord and the peripheral
nervous system will be considered.
For the neuropsychologist, the outcomes of these examinations

are relevant for several different reasons.
◆ The intactness of a patient’s sensory and motor functions

influences his/her performance in the neuropsychological
tests. For instance, a visual field defect renders tests that
require reading more difficult, and a weakness ( paresis) or
clumsiness ( ataxia) in the responding arm will put the
patient at a disadvantage in a test demanding motor
responses. Thus, the knowledge of a clinical neurological
deficit informs the choice of the neuropsychological tests
that can be used and can help with the interpretation of
their results.
◆ If a patient’s cognitive performance fluctuates

significantly within a short period of time, he/she might be
suffering from partial complex epileptic seizures, whereby
consciousness is altered for some minutes without being
lost completely. In this case, an EEG may provide
confirmation of the clinical suspicion of seizures.
◆ The MRI and CT scans make it possible to relate findings

of neuropsychological deficits to damaged brain structures.
◆ A patient who displays a slow cognitive decline might

suffer from one of a variety of possible neurological
conditions, (e.g. tumour, recurring strokes, or progressive
brain atrophy in Alzheimer’s disease). A CT or MRI scan
then demonstrates the nature and extent of the pathological
brain process.
Page 2 of 17
Some of the methods described in this chapter (MRI, CT,

electroencephalography (EEG), and parts of the clinical
neurological examination) therefore, yield results that can (p.
838) be related to neuropsychological findings. In addition,
several other methods are briefly described and explained
(where such direct links are not possible), which are likely to
be encountered by neuropsychologists in their clinical work.
2 The clinical neurological examination

The full clinical neurological assessment includes taking a
history, observing the patient’s behaviour, and carrying out a
formal neurological examination of his/her motor, sensory, and
reflex functions. A brief mental status examination also
comprises part of this assessment. In about two-thirds of
cases, this clinical information alone will enable the
neurologist to make a correct anatomical diagnosis regarding
the localization of the lesion, and a pathological diagnosis as
to the nature of the underlying disease.
2.1 History
Taking the patient’s history provides us with important clues
about the nature of the disease, and also the patient’s ability
to cope with it. In addition to listening to the patient’s account,
the following kinds of questions need to be asked.
◆ What is the precise description (quality) of the

complaints?
◆ Where are they localized?
◆ When did they first start?
◆ How did they start, suddenly or gradually?
◆ What course have they taken?
◆ Which situations trigger or relieve them?
◆ What treatment has been tried?
In conditions that affect the patient’s cognitive functions

temporarily (such as epilepsy) or continuously (such as
dementia), it is necessary to get a relative’s or partner’s
history of the patient.
2.2 Observation of the patient’s behaviour

The observation of the patient’s spontaneous behaviour
comprises the way he/she walks, moves, and talks. Important
criteria include the following.
Page 3 of 17
◆ Level of alertness. Sleepiness is called somnolence when

it is mild and stupor when it is more severe. Coma is
enduring complete loss of consciousness.
◆ Speed of movements and speech. Unusual slowness of

movement is called bradykinesia.
◆ Involuntary movements. Tremor is a rhythmic shaking of

the limbs, the head, or, rarely, the whole body. Depending
on the underlying disease, it can be most pronounced in
rest, in holding the limbs outstretched, or during active
movements.
◆ Dystonia, dyskinesia, chorea, and athetosis are different

types of involuntary movements that are not rhythmic.
◆ Speech. Aphasia is the disturbed production and/or

understanding of language; dysarthria is a defect in
articulation, making the speech slurred.
(p.839)
◆ Structuring of the patient’s account of his problems.
◆ Social appropriateness.
2.3 Neurological assessment
The neurological examination usually starts with the head and
assessment of the 12 cranial nerves and then proceeds to the
motor functions, sensations, and reflexes of the limbs and
trunk. It should also include a brief mental status examination.
2.3.1 The 12 cranial nerves

The 12 cranial nerves relay motor functions, senses, and
reflexes of the head.
◆ Motor functions:
— facial expression: weakness of facial muscles is

called facial palsy;
— gaze: disturbed control of eye movements can lead

to double vision or nystagmus (rhythmic movements
of the eyes);
— speaking (see Section 2.2);
— swallowing: disturbed swallowing can cause

choking;
Page 4 of 17
— turning of the head.
◆ Senses:
— vision: blindness is called amaurosis; a loss of half

the visual field within one or both eyes is called
hemianopia;
— smell: loss of smell is called anosmia;
— taste: loss of taste is called ageusia;
— hearing: reduced hearing is called hypacusis,

deafness is called anacusis;
— feeling: see Section 2.3.3;
◆ The vestibular system in the inner ear senses the position

and movements of the head and therefore plays an
important part in maintaining equilibrium.
◆ Reflexes. The most widely used reflex is the light reflex of

the pupils.
2.3.2 Motor functions of the body

◆ Muscle power. The maximum power of each muscle group
is described on a scale from 0 (no muscle contraction) to 5
(full power) according to the Medical Research Council.
Muscle weakness is called paresis or paralysis; complete
loss of force is called plegia. Hemiparesis is weakness of
one side of the body, paraparesis weakness of both legs, and
tetraparesis or quadriparesis weakness of all four limbs.
◆ Coordination. The dexterity of both coarse and fine

movements is tested by the finger–nose test (touching his/
her own nose with his/her index finger) and the shin–heel–
test (moving the heel to the opposite knee and along the
shin). Clumsiness in these tests is called ataxia.
◆ Muscle tone. Increased tone can be either spasticity or

rigor; reduced tone is called flaccid.
◆ Posture and gait. Observe whether the patient stands

straight or bent, secure or insecure, and whether the
movements seem clumsy ( ataxic) or asymmetrical.
(p.840) 2.3.3 Sensation

The sensory modalities are:
◆ touch;
Page 5 of 17
◆ pain;
◆ temperature;
◆ vibration;
◆ position of limbs.
Reduction of sensation is called hypaesthesia, complete loss

anaesthesia. The feeling of pins and needles is called
paraesthesia.
2.3.4 Reflexes
The most commonly tested reflexes are the biceps and triceps
reflexes in the arms and the knee jerk and the ankle jerk in the
legs. Note whether the reflexes are unusually weak or brisk,
whether there are side differences, or differences between the
reflexes of the arms and those of the legs.
Pathological reflexes indicate a lesion within the central

nervous system. The Babinski reflex is the most widely used,
whereby scratching of the outer side of the foot sole causes a
dorsal extension (upward movement) of the big toe.
2.3.5 Cognitive functions

Every patient with known or suspected brain injury or disease
should have a brief mental status examination. This detects
signs of attentional, memory, or constructional deficits,
aphasia, apraxia, agnosia, neglect, or executive dysfunction.
This assessment falls under the term cognitive neurology (in
the UK) or behavioral neurology (in the USA). A full
neuropsychological examination will then provide a more
detailed analysis of the nature and extent of the patient’s
cognitive deficits.
3 Laboratory examinations
3.1 Computerized tomography (CT)
Computerized tomography uses the extent of absorption of X-
rays to demonstrate pathological changes in the body.
In a CT scanner, X-rays are transmitted through the head from

different sides, and their strength measured by detectors on
the opposite side. The X-rays’ weakening (absorption) during
the passage through the head depends on the density of the
different tissues within and around the brain. The information
from these different projections is transformed by a computer
into a series of two-dimensional pictures that show air as
Page 6 of 17
black, bone as white, and brain tissue in different shades of

grey (Fig. 41.1(a)).
The main criteria for analysing CT scans are:
◆ Hypodense areas which are darker than the surrounding

tissue. These indicate ischaemic infarctions, oedema,
inflammation, or certain tumours.
(p.841)
◆
Fig. 41.1 Brain (a) CT and (b) MRI scans

of a 57-year-old man 4 months after an
ischaemic stroke in the right occipital
lobe.
He suffered from left hemianopia and
hemineglect as well as other visuospatial
deficits. There are additional small
subcortical infarcts (arrows) that the MRI
with its higher resolution shows more
clearly than the CT scan.
Hyperdense areas which are lighter than the surrounding

tissue. These indicate a fresh bleeding, calcification, or
certain tumours.
◆ Size of the ventricles. An increase in size indicates either

hydrocephalus or brain atrophy; a decrease in size indicates
brain oedema (swelling of the brain).
◆ Shape and width of gyri and sulci of the cortical surface.

Widened sulci and shrunken gyri indicate brain atrophy;
swollen gyri with disappearing sulci indicate brain oedema.
Contrast enhancement can be achieved by intravenous

injection of iodide-containing substances. This emphasizes
Page 7 of 17
natural and pathological blood vessels, and also areas of

disrupted blood–brain barrier, such as infarctions after 2–3
days, abscesses, and some tumours.
The relevance of CT in the context of clinical neuropsychology

lies in its ability to depict the anatomical structure of the brain
and associated pathologies (Fig. 41.2). These pathologies can
be related to findings of neuropsychological deficits. For
instance, a patient’s expressive aphasia (see Chapter 13) can
be explained by the CT finding of a stroke involving Broca’s
area, and another patient’s left hemineglect (see Chapter 5)
may correspond to a right parietal tumour. The spatial
resolution of CT is approximately 2 mm, which means that
anatomical structures or pathological processes have to be at
least that big to be detected. CT does not assess the
functioning of the brain or its parts. (p.842)
Page 8 of 17
3.2 Magnetic resonance imaging (MRI)

MRI uses the
magnetic
properties of
hydrogen
protons (H+)
in brain tissue
to generate
images of the
brain.
Hydrogen
protons Fig. 41.2 Brain CT scans of a 32-year-old
constantly woman who suffered a left hemisphere
rotate (‘spin’) haemorrhagic stroke (arrows) from an
and therefore arteriovenous malformation (AVM).She
act as had expressive aphasia and a right
electrical hemiparesis. (a) The CT on the day of the
dipoles. The stroke shows fresh blood as hyperdense
MRI scanner (white) areas. The AVM is not visible
creates a here, but was surgically removed after 3
powerful weeks. (b) On the CT scan 8 months later,
magnetic field the blood is completely resorbed, and the
that forces all resulting brain lesion shows up as
these protons hypodense (dark).
into a single
direction.
Their direction is briefly diverted by short electromagnetic
impulses and, when they return to their previous state, they
emit high-frequency radiation (‘echo’) that can be measured
by the MRI scanner. The characteristic of each proton’s echo is
influenced by the tissue immediately surrounding it, which
allows the computer to generate high-resolution pictures of
the different parts of the brain. These images look similar to
those of CT, but show in much more detail pathological
processes such as ischaemic infarctions (Fig. 41.1(b)),
bleedings, inflammation, tumours, pathological blood vessels,
hydrocephalus, brain oedema, or atrophy (see Section 3.1).
Small lesions that are missed by CT, such as areas of
inflammation in multiple sclerosis, can be demonstrated
precisely in MRI.
Just as with CT, MRI can be used to examine any part of the
body, and the main use of MRI is the depiction of anatomical
structures and pathological processes of the brain (Fig. 41.3).
Page 9 of 17
The spatial resolution of MRI is better than that of CT,

approximately 1 mm. Like CT, MRI does not give us
information about the functioning of the brain. Due to the use
of a strong magnet, people with pacemakers or with metal
implants in their brain or inner ears must not be examined
with MRI. (p.843)
3.3 Functional MRI (fMRI)

Functional
MRI is not a
method used
in routine
clinical
practice, but
a method of
brain
research that
shows in
which brain Fig. 41.3 Brain scans of a 46-year-old
areas the woman with a meningioma in the left
blood flow lateral ventricle.(a) MRI scan before the
increases operation. (b) CT scan 7 days after
while the surgical removal of the tumour. The right
subject hemisphere was chosen as the surgical
performs a access route in order to spare speech-
certain related brain areas. Note the blood in this
activity. It region (arrow). After the operation, the
achieves this patient has moderate left-sided
by making use hemineglect and verbal and nonverbal
of the memory deficits but no disorder of
different speech.
magnetic
properties of
oxygenated haemoglobin and deoxygenated haemoglobin in
the bloodstream. An increased blood flow in a certain brain
area is interpreted as a sign of increased activity in this area.
In contrast to MRI itself, fMRI allows us to deduce the
functioning of different brain areas.
3.4 Single-photon emission computer tomography (SPECT) and

positron emission tomography (PET)
Page 10 of 17
Both SPECT and PET use radioactive substances (‘tracers’)

that are either injected into the person’s bloodstream or
inhaled, and are taken up preferentially into those parts of the
brain which are most active. SPECT and PET therefore provide
images of the blood flow and activity of different brain areas.
They are, however, less suited than MRI and CT to provide a
detailed anatomical picture of the brain. Both methods are
increasingly used in clinical routine, e.g. in the evaluation of
patients with epilepsy before surgery, in certain tumours, and
in situations where a patient is suspected of having a mild
ischaemia or traumatic brain injury that could not be detected
with CT or MRI scanning.
(p.844) 3.4.1 SPECT

SPECT uses radioactive technetium (99mTc-HMPAO
(hexamethyl propyleneamine oxime)), iodine (123I-IMP (inosine
5’-phosphate)), or 133xenon as its radioactive tracers. During
their radioactive decay, they emit photons (γ-quanta), which
are measured by one of many γ-cameras which are arranged
in a circle around the person’s head. From the distribution
patterns of the measured γ-quanta, the regional cerebral blood
flow (rCBF) in the different parts of the brain can be
estimated. The spatial resolution of SPECT is 1–2 cm and the
temporal resolution is 30 minutes.
An alternative use of SPECT lies in the use of radioactive

tracers that bind specifically to certain receptors. An example
of this is the use of 123I-benzamide (IBZM) which binds to D2
dopamine receptors and therefore provides us with
information about the density of these receptors in subjects
with (suspected) Parkinson’s disease or related conditions.
3.4.2 PET
PET uses radioactive oxygen (H2 15O), glucose (18F-
deoxyglucose), carbon (11C), or nitrogen (13N) as tracers. They
are much more unstable than the tracers used in SPECT and
emit positrons during their radioactive decay. When one of
these positrons collides with a nearby electron, 2 photons (γ-
quanta) are released that travel in precisely the opposite
direction to each other. Simultaneous measurement of these
photons by two γ-cameras on opposite sides of the head
(‘coincidence measurement’) gives information about their
source which is more precise than that provided by SPECT.
With PET, rCBF and regional cerebral metabolic rate (rCMR)
Page 11 of 17
can be estimated. The spatial resolution of PET is 0.5– cm and

the temporal resolution approximately 2 minutes.
Like SPECT, PET allows for receptor-binding studies and has

been used to examine D2 dopamine receptors, benzodiazepine
receptors, serotonin receptors, and opiate receptors. Because
of the fast decay of the tracers used in PET, this method
depends on a nearby cyclotron to provide the radioactive
substances.
3.5 Angiography
Angiography or arteriography uses conventional X-ray
examination after the injection of iodine-containing contrast
substance to visualize the arteries and veins. In neurology, one
is mostly interested in the arteries and veins of the brain or,
sometimes, the spinal cord. Angiography is most useful in
showing:
◆ stenosis (narrowing) of an artery;
◆ occlusion of an artery or vein;
◆ aneurysm: a bulging of an artery by a weakness of the

artery wall;
◆ arteriovenous malformation or angioma: a tangle of

pathological blood vessels;
◆ pathological vessels in a brain tumour.

3.6 Electroencephalography (EEG)
This method measures the electrical activity of the cerebral
cortex with electrodes that are placed on the scalp (Fig.
41.4(b)). (p.845)
Page 12 of 17
The neurons
generate
action
potentials that
spread across
the axons and
dendrites, and
the multitude
of action
potentials of
the cortical
neurons adds
up to electrical
field potentials
that can be
measured.
These field
potentials
Fig. 41.4 (a) Electroencephalogram
show regular
rhythms that
(EEG) of a 29-year-old patient with
are classified recurring epileptic seizures. The upper
as: four traces demonstrate a normal alpha
◆ beta, 14– rhythm over the right hemisphere. The
30 Hz; fifth trace is from the frontal part of the
left hemisphere and is also normal. The
◆ alpha, 8–
lower three traces are from the posterior
13 Hz;
part of the left hemisphere and show
◆ theta, 4– spike-wave complexes, indicative of an
7 Hz; epileptogenic focus in the left temporo-
occipital region. (b) The positioning of the
◆ delta, 1–
EEG electrodes on the skull.
3 Hz.
These
rhythms are probably caused by synch ronization of the
cortical activity mediated by the thalamus. In rest with the
eyes closed, alpha is the predominant rhythm in the (p.846)
healthy adult. During sleep, the slower frequencies become
more prominent and sleep-specific wave-forms appear: sleep
spindles, vertex sharp transients, and K-complexes.
The EEG gives indications for pathological processes in the

brain if the following patterns are found:
◆ General slowing of the EEG with diffuse theta- and delta-

activity occurs in degenerative diseases such as Alzheimer’s
disease, intoxication, and metabolic encephalopathy (e.g. in
Page 13 of 17
liver or kidney dysfunction). In the latter case, the EEG

activity can sometimes take the shape of ‘triphasic waves’
with high amplitude and delta frequency.
◆ Frontal intermittent rhythmic delta activity (FIRDA) is

mainly found in lesions of deep brain structures such as the
thalamus.
◆ Focal changes of rhythm or shape of the EEG waves (e.g.

only left parietal) are a sign of an underlying pathological
process such as stroke, traumatic brain injury, or brain
tumour.
◆ Epileptic activity is indicated by rhythmic slow waves of

unusually high amplitude or by ‘sharp waves’ that have a
pointed rather than sinusoid shape (Fig. 41.4(a)). ‘Sharp/
slow wave complexes’, which show a sharp wave
immediately followed by a high-amplitude delta wave, are
regarded as proof of epilepsy.
Searching for signs of epileptic activity is by far the most

important use of EEG. However, even patients with proven
epilepsy can have normal EEG recordings between seizures
(inter-ictal EEG). A normal EEG therefore does not exclude
epilepsy. If there is sufficient clinical evidence, either a sleep
EEG after a wakeful night or a 24-hour EEG recording can
then sometimes provide the signs of epileptic activity.
3.7 Evoked responses

Evoked responses are electrical potentials that are recorded
from the scalp surface as a response to an external stimulus.
They give us information about the functioning of sensory
pathways within the nervous system. Visual, auditory, or
somatosensory stimuli can be used, and they have in common
that hundreds of consecutive stimuli are applied before a
reliable evoked response can be measured. The evoked
responses consist of a series of waves. The latencies,
amplitudes, and shapes of these waves are altered when a
sensory system is damaged and therefore allow inferences as
to the part of the sensory system that is dysfunctional. A
special case is motor-evoked potentials induced by
transcranial magnetic stimulation, which are used to examine
the functioning of the motor pathways.
Page 14 of 17
◆ Visual evoked responses (VER) use a flickering

draughtboard (checkerboard) for the patient to watch, and
they are recorded occipitally over the visual cortical areas.
◆ Brainstem auditory evoked responses (BAER) are

recorded over the mastoid or from the earlobe while the
patient listens to click stimuli through headphones.
◆ Somatosensory evoked responses (SSER) are recorded

after stimulation of the median nerve, tibial nerve, peroneal
nerve, trigeminal nerve, or pudendal nerve. In addition to
(p.847) recordings from the scalp over the corresponding
somatosensory cortical areas, SSER can also be recorded
over the cervical spinal cord.
◆ Motor-evoked potentials (MEP): this method uses

electromagnetic impulses to the motor cortex through the
scalp (transcranial magnetic stimulation) to elicit electrical
potentials in certain target muscles. Their amplitude,
shape, and latency give information about the functioning
of the motor pathways.
3.8 Event-related potentials (ERPs)
Unlike the evoked responses, which document the reaction of
primary cortical areas to an external stimulus, event-related
potentials record the responses of secondary cortical areas
that occur slightly later. The ERPs are therefore considered to
represent cognitive processes such as focusing of attention,
detection of a stimulus, and reacting to an unexpected
stimulus. The most commonly analysed ERPs are:
◆ P 300: a positive potential with its maximum 300

milliseconds after the stimulus, it can be found during tasks
in which the subject is required to watch (or listen to) a
series of identical stimuli and recognize occasionally
interspersed different stimuli.
◆ N 400: in a task in which the subject reads or listens to

sentences, an unexpected word that does not fit into the
semantic context and therefore violates expectation is
followed by a negative potential 400 milliseconds later.
In spite of intensive research, the precise meaning of the

different ERPs is still unclear. They are therefore not
commonly used in routine clinical practice.
3.9 Doppler ultrasound
Page 15 of 17
Doppler ultrasound is used to detect a stenosis (narrowing) of

an artery that leads blood to the brain: the internal carotid
artery or the vertebral artery. A probe is pressed on to the skin
above one of these arteries in the neck area. It emits
ultrasound, which is bounced back from the blood cells and
recorded by the same probe. The character of the returning
ultrasound signal depends on the speed of the flow of blood
cells. This makes it possible to determine where in the
underlying artery the speed of the bloodstream is increased,
which is an indication of a stenosis in this area. With
transcranial Doppler ultrasound, it is even possible to measure
the speed of the bloodstream in intracranial arteries,
particularly the middle cerebral artery. The finding of a
stenosis indicates that the blood supply to a part of the brain
may be compromised.
3.10 Cerebrospinal fluid (CSF)

CSF is usually collected by lumbar puncture between the 3rd
and 4th or between the 4th and 5th lumbar vertebrae. The
analysis of the CSF helps in the diagnosis of the following
conditions.
◆ Hydrocephalus: the hydrostatic CSF pressure is

increased.
◆ Subarachnoid haemorrhage: the CSF is tainted with

blood.
(p.848)
◆ Inflammation (meningitis or encephalitis): the amount of
protein and the number of leukocytes in the CSF are
increased. Multiple sclerosis is characterized by oligoclonal
bands, with an increase of only a few types of
immunoglobulines.
◆ Tumours: pathological tumour cells can sometimes be

found in the CSF.
Bradley, W.G., Daroff, R.B., Fenichel, G.M., and Marsden,

C.M. (eds.) (2000). Neurology in clinical practice.
Butterworth Heinemann, Oxford.
Page 16 of 17
Donaghy, M. (ed.) (2001). Brain’s diseases of the nervous

system. Oxford University Press, Oxford.
Gilman, S. (1999). Clinical examination of the nervous system.

McGraw-Hill, London.
Lee, S.H., Rao, K.C., and Zimmermann, R.A. (1996).

Cranial and spinal MRI and CT. McGraw-Hill.
Misulis, K.E. (1997). Essentials of clinical neurophysiology.

Butterworth-Heinemann, Oxford.
Strub, R.L. and Black, W. (1999). The mental status

examination in neurology. F.A. Davis.
Page 17 of 17
Neuropsychological deficits within the World Health Organization’s model of illness
(ICIDH-2)


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
Neuropsychological deficits within

the World Health Organization’s
model of illness (ICIDH-2)
Derick T. Wade
DOI:10.1093/acprof:oso/9780199234110.003.042

Rehabilitation practice needs a conceptual model or
framework in which to work. One advance over the last twenty
years has been the growing awareness and acceptance, in
research practice at least, of the World Health Organization's
model of illness embodied in the original International
Classification of Impairments, Disabilities, and Handicaps
(ICIDH) and more recently revised, expanded, and renamed
(as the International Classification of Functioning or ICF) but
still referred to as the ICIDH-2 model. This chapter focuses on
the ICIDH-2 framework.
Keywords: cognitive rehabilitation, neuropsychological deficits, ICIDH model,

ICIDH-2 framework
1 Introduction
Rehabilitation practice needs a conceptual model or
framework in which to work. In the past many health
professions developed or employed their own model, some
explicitly (e.g. Roper’s model of nursing), but most less so (e.g.
Page 1 of 13
(ICIDH-2)
the so-called medical model and the so-called psychosocial

model). One advance over the last 20 years has been the
growing awareness and acceptance, in research practice at
least, of the World Health Organization’s (WHO) model of
illness embodied in the original International Classification of
Impairments, Disabilities, and Handicaps (ICIDH) and more
recently revised, expanded, and renamed (as the International
Classification of Functioning or ICF) but still referred to as the
ICIDH-2 model (Wade and de Jong 2000).
Although widely known in some circles, this model of illness is

not always fully understood or used by other health
professionals. The WHO’s ICIDH is not without controversy
and there exist differences of opinion about how certain
deficits should be classified. In particular, many clinicians have
difficulty placing cognitive difficulties within the WHO’s
ICIDH-2 model. This appendix provides a possible framework.
The basic ICIDH-2 is shown in Table 42.1 with a revised

version in Table 42.2 and Fig. 42.1. This is a slightly revised
version that acknowledges that there are subjective (personal
to the patient) and objective (observed by outside observers)
aspects of most illness (Wade 2001). In addition this version
includes pathology (i.e. disease) that is not covered in the ICF,
since disease is already covered in the WHO’s International
Classification of Disease (ICD-10). Finally, the framework
includes some acknowledgement of the concept of quality of
life (Post et al. 1999). Otherwise, the model is essentially the
same as the ICIDH-2.
The framework is intended to be used when considering and

describing problems faced by patients with brain damage
(including cognitive deficits) and provides a common and
consistent language between medical and paramedical
professionals. Patients seen by clinical neuropsychologists will
often (but not necessarily) have an underlying pathology such
as frontal lobe infarction (stroke), diffuse axonal injury (after
head injury), or degeneration in specific neuronal groups (e.g.
Huntington’s disease).
(p.850) 2 Impairments, disabilities, and handicaps

Table 42.1 The WHO’s ICIDH-2 framework
Page 2 of 13
(ICIDH-2)
Level of Level of illness

description
Term Synonym Comment
Pathology Disease/ Refers to abnormalities or

diagnosis changes in the structure
and/or function of an organ or
organ system
Impairment Symptoms/ Refers to abnormalities or

signs changes in the structure and/
or function of the whole body
set in a personal context
Activity (was Function/ Refers to abnormalities,

disability) observed changes, or restrictions in
behaviour the interaction between a
person and his/her
environment or physical
context (i.e. changes in the
quality or quantity of
behaviour)
Participation Social Refers to changes, limitation,

(was positions/ or abnormalities in the
handicap) roles position of the person in their
social context
Contextual factors
Domain Examples Comment
Personal Previous Primarily refers to attitudes, beliefs,

illness and expectations, often arising from
previous experience of illness in self
or others, but also to personal
characteristics
Physical House, Primarily refers to local physical

local structurers but also
shops, includes people as carers (not as
carers social partners)
Social Laws, Primarily refers to legal and local

friends, cultural setting,
family including expectations of important
others
2.1 Impairments
Page 3 of 13
(ICIDH-2)
Abnormal structure or function of the brain (i.e. abnormal

neuroanatomy and/or neurophysiology) should be recognized
as one cause of impairment to cognitive skills or functions.
Emotional disturbance is another potent cause and often a
contributing factor. Some patients may have many cognitive
impairments such as:
◆ reduced initiation;
◆ reduced ability to recall and/or lay down new memories;
◆ reducing learning;
◆ increased distractability;
◆ inability to shift attention to the left side of space;
◆ inability to use language, etc.
It is difficult to construct a comprehensive framework to

encompass all possible cognitive impairments. More
importantly, it is crucial to remember that almost all apparent
cognitive impairments are extrapolated psychological
constructs, largely derived to (p.851)
Table 42.2 Expanded model of illness
System Experience/location
Subjective/internal Objective/external
Level of illness
Person’s Disease: label Diagnosis: label

organ: attached by person, attached by others,
pathology usually on basis of usually on basis of
belief investigation
Person’s Symptoms: somatic Signs: observable

body: sensation, abnormalities
impairment experienced moods, (absence or change),
thoughts, etc. explicit or implicit
Person in Perceived ability: Disability/activities:

environment: what person feels What others note
behaviour they can do, and that person does do;
feeling about quality quantification of that
of performance performance
Page 4 of 13
(ICIDH-2)
Person in Role satisfaction: Handicap/

society: roles person’s judgement participation:
(valuation) of their judgement
own role (valuation) of
performance (what important others
and how well) (local culture) on
role performance
(what and how well)
Context of illness
Internal, Personality: person’s Past history:

personal beliefs, attitudes, observed/recorded
context expectations, goals, behaviour prior to
etc. and early on in this
illness
External, Salience: person’s Resources:

physical attitudes towards description of
context specific people, physical (buildings,
locations, etc. equipment, etc.) and
personal (carers,
etc.) resources
available
External/ Local culture: the Society: the society

social context people and lived in and the laws,
organizations duties and
important to person responsibilities
and their culture; expected from and
especially family and the rights of
people in same members of that
accommodation society
Totality of illness
Quality of life: Happiness: person’s Status: society’s

summation of assessment of and judgement on
effects reaction to success in life;
achievement of or material possessions
failure to reach
important goals and
Page 5 of 13
(ICIDH-2)
sense of being a
worthwhile person
explain constrained and naturalistic observed behaviour. As pointed

out by Halligan and Marshall (1992), there is, for example, no
single brain centre or naturally occurring entity that corresponds
to the clinically well established neuropsychological constructs of
neglect or aphasia. Both represent constructs employed post hoc by
clinicians and researchers to refer to specific deficits observed to
occur in spatial awareness and language production after right and
left brain damage, respectively.
2.2 Disability
Patients may suffer some limitation on or change in the quality
of their behaviour (disability or alteration in or limitation of
their activities). This can cover anything from maintaining
continence through personal activities such as dressing and
washing to (p.852)
complex
activities such
as working,
shopping, or
participating in
conversations.
The changes in
activities may
arise from
several
different
underlying
impairments,
often in
combination.
The nature and
extent of
changes in
these activities
is greatly
influenced by
the particular
Fig. 42.1 A expanded framework for
person’s
ICIDH-2.
physical,
personal, and
social context
(see Section 3).
Page 6 of 13
(ICIDH-2)
Some activities of daily living are more likely to be affected by

cognitive impairments, but few if any are exclusively and only
due to cognitive impairment. Hence it is important to
recognize that there are no cognitive disabilities, only
disabilities that may be attributable to cognitive impairments
that are typically demonstrated on clinical or experimental
tests.
2.3 Handicap
In illness, patients may experience a change in or limitation on
their participation within society, once known as a change at
the level of handicap. As for disability, cognitive impairments
may be a contributing and, indeed, major factor, but there are
no exclusively cognitive handicaps.
Page 7 of 13
(ICIDH-2)
(p.853) 3 The relevance of context

All patients live within a context that is important for
understanding and interpreting the significance of the
acquired impairments.
◆ They have a personal context (experiences, beliefs,

expectations, attitudes, response styles, etc.). This personal
context might be altered by cognitive impairments (but
probably less than we expect!). Personal context certainly
influences the relationship between cognitive impairment
and the resultant disability and handicap.
◆ Patients also have a physical context. The complexity of

the environment might well have an influence on how much
effect cognitive impairments have and vice versa. For
example, an overstimulating environment with complex
perceptual demands might lead to aggression in someone
with marked cognitive impairments, whereas a well
structured environment might help someone.
◆ Patients have a social context. Again this might influence

the effect of cognitive impairment. For example, a
predictable, stable social context might ameliorate the
effects of impaired planning and initiation.
To provide a specific example, a patient might have a

subarachnoid haemorrhage (primary pathology) with
secondary frontal lobe infarction (secondary pathology)
leading to impairment in planning, initiation, and self-
awareness (cognitive impairments). In the context of work as a
manager in a hospital (social and physical contexts) the person
might fail in activities such as chairing meetings or organizing
duty rosters, but, at home, in the context of wife and daughter
(social and personal contexts), the person might not show any
problems and be able to help with such activities as washing
dishes. However, if the person’s husband fell ill, she might not
be able to look after the house.
4 Implications for treatment

Treatments can focus on several components and are not
mutually exclusive (see Table 42.3), but typically take the form
of one of the following four types.
Page 8 of 13
(ICIDH-2)
◆ Some treatments attempt to directly reduce the

impairment, usually through repetitive practice of the
assumed cognitive domain. Usually, this involves a
structured set of activities that are thought to need good
function in the impaired domain. Examples within the area
of cognitive deficits are the programmes that are supposed
to reduce neglect or improve memory.
◆ Other treatments focus more on improving the functional

activities that are affected, again through repeated practice
in the specific activities affected. For example, someone
with neglect might practise dressing or cooking until able
to achieve these activities safely and independently, without
the practice being targeted at the assumed impairment.
◆ Yet other treatments may try to alter the context, e.g.

through providing external prompts and cues (post-it notes,
alarms) or through ensuring a predictable (p.854)
Table 42.3 Rehabilitation interventions—some

examples
Page 9 of 13
(ICIDH-2)
Level (term) Intervention Comment
Level of illness
Organ ◆ Prevent Important to know

(pathology) disease pathology for
prognosis and likely
◆ Reverse or
impairments; cure
remove
often not possible
pathology
NB. Pathology is not
◆ Replace lost always present in an
physiological illness
function (e.g.
insulin)
◆ Give
information
and advice
Person ◆ Prevent May use therapy,

(impairment) occurrence or drugs, orthoses,
worsening of prostheses, surgery,
impairment etc.; may learn
technique to
◆ Reverse or
overcome loss NB.
improve
Impairment may
impaired skill
improve secondary
◆ Replace lost to functional
skill or part practice
with external
or internal aid
Person in ◆ Prevent Involves altering

environment patient behaviour in one
(activities) learning way or another. Will
abnormal often also involve
behaviours changing the
environment. May
◆ Teach how to
involve changing
undertake
patient’s goals or
activities in
goals of others NB.
presence of
This takes time and
immutable
depends upon
impairments
learning
Page 10 of 13
(ICIDH-2)

◆ Practise
activities,
advising on
risks,
techniques,
etc.
Person in ◆ Prevent loss Will almost always

environment of social involve other people.
(participation) contacts and May involve change
roles in accommodation.
For most people
◆ Help identify
work is a central
new roles and
role NB. This takes a
how to develop
long time
them
◆ Ensure
patient has
opportunities
to develop new
or maintain old
roles
Context of illness
Personal ◆ Prevent Beliefs and

context development of expectations are
maladaptive major determinants
beliefs and of behaviour, but
expectations consequences of
behaviour may also
◆ Alter beliefs
affect beliefs and
and
expectations
expectations if
necessary,
usually
through giving
information
and
psychological
therapy
Page 11 of 13
(ICIDH-2)
Physical ◆ Avoid loss of Could include

context familiar environmental
environment if control equipment,
possible mobility aids,
housing adaptations,
◆ Adjust
etc.
environment
physically,
including
providing
support from
other people
Social context ◆ Adjust or Usually strongly

help patient linked to
find new social accommodation and
context or help work
adapt to new
social context
Totality of illness
Quality of life ◆ Full

rehabilitation
(p.855) routine through the day. This may involve other

people. Many patients with persistent cognitive impairments are
best helped in this way.
◆ Lastly, one may try to alter expectations and beliefs, and

to find alternative roles and ways of participating in society.
This analysis emphasized that there is no separate cognitive

rehabilitation. There is rehabilitation for people with cognitive
impairments, rehabilitation that might include trying to reduce
the impairment itself but that will include many other
interventions. It is also worth noting that much of all
rehabilitation involves altering behaviour, a process that
depends upon learning, which is a cognitive skill or function.
Thus, all rehabilitation is cognitive. It is not surprising,
therefore, that patients with neurological disease are perhaps
the most difficult to rehabilitate. The very organ and skill
needed to succeed in rehabilitation (i.e. the brain and an
Page 12 of 13
(ICIDH-2)
ability to learn and adapt) are themselves damaged, which

often slows the process.
Halligan, P.W. and Marshall, J.C. (1992). Left visuo-spatial

neglect: a meaningless entity?. Cortex 28 (4), 525–35.
Post, M.W.M., de Witte, L.P., and Schrijvers, A.J.P. (1999).

Quality of life and the ICIDH: towards an integrated
conceptual model for rehabilitation outcomes research. Clin.
Rehabil. 13, 5–15.
Wade, D.T. (2001). Disability, rehabilitation and spinal injury.

In Brain’s diseases of the nervous system (ed. M. Donaghy),
pp. 185–209. Oxford University Press, Oxford.
Wade, D.T. and de Jong, B. (2000). Recent advances in

rehabilitation. Br. Med. J. 320, 1385–8.
Page 13 of 13
The internet and clinical neuropsychology: privacy, personal safety and effective
internet use


Print ISBN-13: 9780199234110
DOI: 10.1093/acprof:oso/9780199234110.001.0001
The internet and clinical

neuropsychology: privacy, personal
safety and effective internet use
Vaughan Bell
DOI:10.1093/acprof:oso/9780199234110.003.043

The internet is the single largest and most diverse resource
available to clinical neuropsychologists and remains a
powerful ally for any patient focused practitioner. It is useful
not only because it provides convenient access to a vast array
of clinical and scientific information, but also because it allows
disparate individuals to widen the informal networks that
provide the bedrock of mutual co-operation and education that
characterizes contemporary clinical science. This chapter
provides practical advice so the internet can be used
effectively, whilst giving an outline of the additional ethical
considerations that internet communication presents. Topics
discussed include personal safety and privacy, e-mail
communication and etiquette, using the web, effective use of
internet software, and ethics of internet communication.
Keywords: clinical neuropsychology, internet use, e-mail, internet

communication, personal privacy
1 Introduction
Page 1 of 24
internet use
Although only five years have passed since the original version
of this chapter was written, it is clear that an update is greatly
needed owing to the rapid change in internet technology and
culture. This transformation has included the demographics
and sophistication of the users, the capabilities of the
technology, and the waxing and waning of fashions in both
online pursuits and attempts at regulation. To a far greater
extent than when the first edition was written, clinical work
relies on the internet, and so is increasingly subject to its
advantages, problems and dangers. This revised version has a
significantly greater focus on personal privacy and safety
online, as dangers have become more apparent, and on the
diversity and range of internet tools, as the technological
possibilities have expanded.
The internet is the single largest and most diverse resource

available to clinical neuropsychologists and remains a
powerful ally for any patient focused practitioner. It is useful
not only because it provides convenient access to a vast array
of clinical and scientific information, but also because it allows
disparate individuals to widen the informal networks that
provide the bedrock of mutual co-operation and education that
characterises contemporary clinical science.
This silver lining does not however, come without an

accompanying cloud and as with any clinical tool, there are
practical and ethical issues that have to be addressed.
Increasingly, clinicians need to be aware of the impact of the
internet on their privacy and personal safety, as patients,
public and other professionals will routinely search for
personal information online. Similarly, whilst no clinician
would dream of using a novel practice without fully
understanding its implications it is not unusual for even the
most accomplished of clinical scientists to understand only
enough of the internet to facilitate its use without being able
to address these issues. This inevitably leads at best to wasted
time and frustration, and at worst to serious implications for
the welfare of patients (Alejandro et al., 2000).
This chapter aims to provide practical advice so the internet

can be used effectively, whilst giving an outline of the
additional ethical considerations that internet communication
presents.
(p.857) 2 Personal safety and privacy
Page 2 of 24
internet use
Clinicians have more reasons than most for needing to be

competent in managing their online privacy. At the most
extreme end, stalking of clinicians has been cited as an
‘underrecognised problem’ (McIvor and Petch, 2006) and most
professionals are unaware of how much personal information
can be acquired using the internet. Perhaps less dramatically,
clinicians may simply not want their private lives available to
anyone who searches for it, and might be concerned that
views, opinions or accounts of their participation in informal
social events might influence the impression they prefer to
portray in their professional lives.
This information comes from two main sources. The first is

information that is not intended to be available publicly, but
which can be found through unobvious or ‘grey’ sources; the
second is information that is public and appropriate for one
audience, but which might be considered inappropriate when
found by another.
Many websites or commercial services request personal

information and promise to keep it private. Key questions to
ask yourself when you enter personal information is ‘private
from whom?’ and ‘can I trust the organisation to be honest and
competent in their data security?’. It is important to read
instructions carefully when entering such information as it
may automatically be passed on to other companies
(potentially companies who specialise in selling databases of
personal information for marketing purposes). Furthermore,
the company may be lax in its security, either in terms of its
computer facilities (large scale ‘personal information theft’
from major companies is now a regular occurrence) or its
vetting and management of employees. Each individual
request should be evaluated in detail, and you may wish to
consider using a pseudonym, entering non-identifying details
or using a ‘throwaway’ free webmail account if privacy is of
key concern. It is also worth remembering that some online
companies specialise in providing access (usually for a fee) to
databases of personal information taken from the electoral
roll, phone book, or professional registers that would not
otherwise be available.
The popularity of online journals, message boards, photo

sharing sites, social networking tools and internet dating has
meant that people are now revealing much more personal
information that was ever possible before. While the majority
Page 3 of 24
internet use
of this is routine and even banal, the ‘ghost of internet past’

has come back to haunt certain individuals when
circumstances change or unimagined viewers see the material.
For example, several high profile cases have been reported
where individuals have published fairly unremarkable informal
pictures online only to be fired because their employers found
them unacceptable. Notably, the law is unclear on the legality
of these moves, but if not legally problematic, the unimagined
professional or social consequences may be at least
uncomfortable.
Clinicians wanting to better control their online privacy need

to both be careful of what information they put online, as well
as regularly monitor what personal information is available.
Any personal information should be filtered through a

consideration of what might be the worst case scenario of the
information getting into the wrong hands. While this may seem
overly cautious, several projects are now attempting to archive
all publicly available (p.858) internet information, so while
the risk now may be minimal, it has to be considered that the
information will potentially be available in searchable form
indefinitely.
It is also wise to conduct regular internet searches for yourself

—searching for your name, email address or titles of personal
online resources with popular internet search engines. While
some may feel awkward about doing this because of notions
about seeming vain, it is an important step in managing your
online privacy and will give you an idea of what information
can be obtained about you by casual browsers. You may also
wish to try with popular ‘grey sources’ (e.g. online phone
directories or registers; 192.com is popular UK service which
includes the electoral roll). Notably, many services now have
provision for removal of personal information on application.
Importantly, people with uncommon names are at greater risk

of being individually identified. A ‘Dr Jane Smith’ is less at risk
of having her privacy breached than a ‘Dr Xavier Rubicon’, not
because she has less personal information online, but because
it is less easy to tie specific information with one of the many
individuals who share her name.
Page 4 of 24
internet use
In terms of patient privacy, patient information is increasingly

stored on hospital, service or district-wide databases. While
the main responsibility of securing this information from
public view and ensuring patient privacy will rest with
technical department, choosing secure passwords, not logging
in from potentially insecure computers (such as internet cafes)
and not printing out unnecessary information will likely to
ensure patient confidentiality. One additional concern,
however, is that these electronic records are potentially
available to a larger number of staff than with paper and file
notes. Because records are likely to be stored indefinitely, you
may wish to think carefully about what information is entered
into these notes, as, for example, details of psychological
therapy sessions may contain private details that the person
may not want anyone outside their immediate care team to
know about.
3 E-mail communication and etiquette
Page 5 of 24
internet use
E-mail has always been the lingua franca of internet

communication by virtue of its ubiquitous nature and
flexibility. The utility of a system that allows electronic
messages to be delivered to an individual, usually within
minutes and regardless of their physical location, would seem
to be self evident. As Smith and Senior (2001) have noted, e-
mail is becoming the preferred method of communication for
the psychologist, and clinical neuropsychologists will
undoubtedly find this facility as useful, if not more so, than any
other e-mail user. For this reason it is important that clinicians
should be fully aware of the facilities, pitfalls and customs that
accompany e-mail communication.
Notably, in many countries a ‘freedom of information’ law may

require organisations to make employee emails available to
anyone who requests it. Clinicians should therefore be aware
that their work emails may become publicly available and are
increasingly used as evidence in court. Awareness of this
should guide both the style and clarity of writing, as well as
decisions about which personal information and
communications would be better left to an email system not
operated by the employer.
(p.859) Furthermore, email attachments are a major source

of viruses and ‘malware’: malicious software specifically
designed to damage the computer software or steal personal
information. Adequate and up-to-date antivirus software
should be available and you should be aware that sending non-
work material on an employers system is often a dismissible
breach of guidelines, regardless of whether anyone takes
offence. Similarly, unsolicited email is now a fact of life and
much contains innocent looking links to what turns out to be
pornographic material or sites designed to fool you into
revealing personal information or installing malicious
software. Any email from a commercial company (especially a
bank) asking you to re-enter login details or payment should
be considered highly suspicious. Anything which looks too
good to be true probably is. If you are suspicious, searching
for the title or text of the email in an internet search engine
often reveals the most common (and, only the most common)
hoaxes and scams.
3.1 One-to-one email communication
Page 6 of 24
internet use
As with any sort of communication, messages must be

appropriate to their recipient and so content and style may
differ accordingly. However, there are several ways of using
the medium to its best advantage for the benefit of both
parties.
3.1.1 Write clearly and provide context

Whilst an email may be perfectly understandable in the
context of an ongoing dialogue, when read some months or
even weeks later it may make little sense. This may not be
such an issue for informal communication, but exchanges
concerning issues of importance may be referred back to as is
frequently the case in clinical settings.
One simple way of doing this is to use context quoting, where

the relevant section of the received e-mail is quoted with the
response added below, like thus:
> I still haven’t found the amnesia paper I was after.
Not to worry, I found a copy and will post it to you.
This allows your reply to be concise whilst maintaining context

and avoiding the unnecessary bulk of including the whole of
the previous email. Quoting or including the whole email may
be necessary in some instances (and is becoming increasingly
common as fast internet connections are more widely used),
but be aware that this can quickly lead to long and confusing
emails which may hinder rather than help comprehension of
the dialogue.
3.1.2 Use the lowest common denominator

Plain text is preferable to any form of embellishment that an
email program may provide such as sending HTML mail
(creating and sending email as web pages). Everyone on the
internet can read plain text email, not everyone may be able to
read any additional features that may be added. Even if you
know that the person you are writing to can read your special
format of email, this might prevent someone else from reading
it if it gets forwarded on as is often the case in the team
environments that clinical neuropsychologists commonly work
in.
(p.860) 3.1.3 Attachments must be appropriate
Page 7 of 24
internet use
Internet connections are becoming faster by the year, and

there is no hard and fast rule about what a maximum
attachment size should be, but try and be aware of how large
attachments are likely to be slower to download and more
difficult to manage when retrieved. When sending an
attachment state its size and type clearly, as this may not
always be obvious to the recipient (e.g. ‘the attached paper is
a 940k Microsoft Word 2007 file’). If you are technically able
and the attachment does not contain private information, it is
often better to upload the file to the web and pass on the link
to it, so the recipient can download it in their preferred
manner.
3.1.4 Remember, email is not written speech

Due to the nature of text based communication many of the
subtleties of face to face communication are easily lost,
leading to a message being misinterpreted. Particular caution
must be taken when using sarcasm, humour or ambiguous
statements. Similarly, short functional replies may be
interpreted as irritable. Sentences or phrases can be
emphasised or softened by the use of punctuation such as
asterisks (‘I really must *stress* this point’) or by using
emoticons or 'smileys' to indicate the emotional context of a
statement. Excessive use of emoticons is considered a little
gauche and most people stick to simplified versions such as:)
to indicate positive emotion, for example:
I really enjoyed your talk:)
or:(to indicate a negative emotion, for example:
That's the third time this week:(
3.2 One-to-many email communication

Discussion lists, where email is used to continue an ongoing
dialogue with a group of people, can be a source of practical
help, support and inspiration as well as a distraction and
annoyance. One enquiring email to a group of similarly
focused professionals can be worth many hours searching
through databases or on the phone, and such lists may also
serve as a source of news and announcements and as a way of
forming informal associations that can lead to valuable
collaborations. Internet discussion lists are however, notorious
for bringing out the worst in people, not least because e-mail
Page 8 of 24
internet use
can so easily be misinterpreted, but also because it is often

difficult to fathom the unwritten rules of the group without
accidentally violating them.
Simple guidelines (colloquially called 'netiquette') have been

formulated to facilitate group interaction in internet
discussion groups and include the points covered in our
discussion for one to one email communication, with a few
additions and alterations.
3.2.1 Attachments should not be sent to a discussion list

Such lists may involve hundreds of subscribers, many of which
will not appreciate having to receive a large file that may only
be of interest to a minority. If you have a file you wish to
disseminate, either ask who wishes to receive it and mail it to
them personally, or if possible upload it to a web site and post
the location so subscribers can download it at their leisure.
(p.861) 3.2.2 Watch who you are replying to

Additional recipients can be included in an email and by
clicking the 'Reply' button you may inadvertently reply to them
all. Similarly, if you wish to respond to a public email privately,
make sure you are doing so and not accidentally mailing the
whole list. Sending a personal email to a public list can be a
cause of embarrassment, or in a clinical environment, a
potential breach of confidentiality.
Page 9 of 24
internet use
3.2.3 Group emails should be of group benefit

Discussion lists are measured by their signal to noise ratio.
Lots of irrelevant chatter and 'content-free' contributions
encourage an overall decrease in useful interaction and cause
genuinely interested people to unsubscribe. That's not to say
you necessarily always have to stick exactly to the list topic,
but signal heavy content is usually much preferred. In some
cases, the discussion list will be moderated so irrelevant
messages will not reach the mailing list at all. Furthermore,
users often mentally note who sends out useful emails, so
sending large numbers of low-relevance messages makes your
more important ones less likely to be read.
Recently ethical concerns have been raised about people

asking for advice on discussion lists with emails that contain
information that may identify the patient (Benkhe, 2007). This
is obviously a breach of patient confidentiality and should, of
course, be avoided. It is also worth remembering that some
comments that will be taken as obviously light-hearted by
colleagues may not be similarly appreciated when taken out of
context or discovered by later subscribers or people searching
the archives.
3.2.4 Don't fan the flames

'Flaming' or the descent into vitriolic argument seems to be a
fact of life on internet discussion lists. Clinical practice is, for
most practitioners, a passionate interest and is likely to cause
heated debate. Whilst it may seem churlish to remind
competent professionals that other list members should be
treated with respect, I have yet to find a discussion list where
this has not happened at least once. Such heated exchanges
are usually the result of a perceived but unintended slight, or
when the participants do not realise that their exchange has
gone beyond an informative debate of general interest into
petty pedantry.
4 Using the web

The world wide web has two major advantages for clinical
neuropsychologists. Firstly that it allows the targeted retrieval
of relevant clinical and scientific information and secondly that
it allows information to be easily disseminated with the burden
of acquisition placed upon the retriever. Documents, pictures,
video or any other sort of digital information need only to be
placed on the web, and their existence flagged so interested
Page 10 of 24
internet use
parties can access them, all without further intervention from

the author.
4.1 Targeted searching

It is worth noting that there is more to effective searching
than being familiar with the tools. The internet can be thought
of as a town. Whilst you may be perfectly competent at (p.
862) buying items in a shop, it is your knowledge of the town
that makes this ability useful. Similarly, spending time to
overview the general internet resources available to clinical
neuropsychologists is often useful for the same reason that
general theoretical overviews are useful in any science. Whilst
you may not have the information to hand, at least you know
the best place to go and find it, saving you valuable time and
frustration along the way.
The most useful skill in searching the web for relevant

information is not fishing out the gold but filtering out the
rubbish. Search engines use entered keywords to identify
pages that contain those words somewhere on the page, and
hence the best strategy is often not to use words which best
describe what you want to find, but to use words which are
most likely to appear on pages containing the information you
require. For example, searching the web using the keyword
'amnesia' brings up lots of irrelevant information as it is often
used as a catchy name for everything from nightclubs to
novels. However, a similar search using the keywords 'memory
loss' returns lots of highly relevant references.
Humans are inevitably better at evaluating small amounts of

information for relevancy than computers, so another useful
technique is to use search engines to narrow the field or to
give leads. In fields such a clinical neuropsychology where the
sources of information may be limited, it is often the case that
you may find yourself searching for pages that will then point
you to the information you are eventually hoping to find. For
example, if I wanted to find information about the notional
conference ‘Neuropsychology and the Internet’ entering these
terms may produce a great deal of irrelevant results, either
because there may be many pages containing these words
which have nothing to do with the conference I wish to find, or
because the conference web pages are either non-existent, or
have not been catalogued by the search engines' databases. A
preferred approach may be to search using the keywords
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‘Neuropsychology Conferences’ to find a page that lists

conferences relevant to neuropsychologists (of which there are
many) and look for a listing made by an ever reliable human.
Some search engines, and many online databases may allow

searches to be made specific by searching for an exact phrase,
or by using terms such as AND, OR and NOT. The use of such
terms is out of the scope of this particular chapter but almost
all facilities that allow such searches have online help and
guides in their use. Users of longstanding electronic databases
such as PsychINFO/PsychLIT or Medline/PubMed who
recognise these terms may find that they can use exactly the
same or very similar syntax on many popular internet search
engines. These services now typically allow an email alerting
service that will regularly run your chosen search and send
you any new matching papers added during the week.
One of the key concepts behind the way search engines

display their results is an algorithm that works out the
popularity of each page that matches the search terms, based
on how many other pages link to it. This has now been applied
to searches for academic material by using citations rather
than links (the most popular being Google Scholar;
scholar.google.com). This can be a powerful way of quickly
getting an overview of an area. For example, if you want to
know the key review papers in ‘addiction’, entering this (p.
863) term will give you a list of which are the most cited (i.e.
influential) papers in the field. It is also a useful way of
tracking how many citations any particular paper receives
over time.
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4.2 The power of ‘social bookmarking’ sites

More recent innovations have included the development of
‘social bookmarking’ websites. These allow users to maintain
an online list of links or references and to add your own
keywords to each one. Crucially, it also allows you to search
the entire database of all users by a specific keyword. This
means when you ask for references tagged ‘aphasia’, you get
all the papers tagged by others as relevant to aphasia.
Essentially, you are sampling the distribution of what the user
population thinks is relevant and this can often point you
towards new conceptual connections or relevant work from
other fields. There are now such sites aimed at cataloguing
general internet links (e.g. del.icio.us; reddit.com; digg.com)
as well as those specifically designed for academic references
(e.g. CiteULike.org; Connotea.org). This concept is now
standard on many sites that catalogue everything from
personal photos to experimental data and can be a powerful
way of determining both the depth and breadth of a field or
conceptual area.
4.3 Subscribing to ‘feeds’

Regularly updated sites often publish ‘feeds’ or ‘RSS feeds’, a
data format that allows your web browser or dedicated ‘feed
reader’ software to quickly gather and summarise new content
(such as new articles, news items or editions of radio
programmes) without you having to go to each individual web
site to check for updates. These can be integrated into the web
browser, work as specific online services (e.g. Google Reader;
reader.google.com) or as standalone software packages. How
to subscribe to each feed varies by method, but an up-to-date
list of methods and software is keep on the ‘feed reader’ page
on Wikipedia (en.wikipedia.org/wiki/Feed_reader).
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4.4 Creating web pages

Internet publishing can, in principal, simplify a great deal of
the information distribution problem. Attendees can download
notes from your talk, colleagues can retrieve minutes of
meetings and important documentation such as ethics forms
and other administrative templates, while you can do the same
without having to chase after the person with the keys to the
right filing cabinet.
In practice, it is a lot more difficult, largely because the easy

to use click-and-go tools are not yet available for web
publishing as they are for web searching. To publish
effectively on the web you either need to put some time and
effort into learning the necessary steps, or if working in a
suitable institution, have the support of suitably skilled
computer or internet technicians.
One of the most important innovations during the last five

years has been the widespread use of ‘wikis’—websites that
use a simplified notation system so users can edit webpage.
The most well known is Wikipedia (en.wikipedia.org for the
English version), (p.864) an online encyclopaedia where
anyone can edit the entries. What sounds like a recipe for
disaster actually works remarkably well and demonstrates the
power of collective knowledge archiving. Wikis are particularly
good for organising information for things like conferences or
group projects and work like virtual notice boards that anyone
can add useful information to. There are now several services
on the net that allow you to set up your own wiki, either for
free (e.g. wikia.com) or for a fee (e.g. most commercial
internet companies) and often allow you to set the degree of
access, so its possible to restrict editing to certain users or
administrators if necessary.
To create more complex web sites it is pointless trying to

outline all the necessary steps here, both because they will
vary wildly depending on the web page hosting arrangements
available (institutions own/commercial services/free services)
and because high quality easy to understand guides are
regularly published in internet magazines and provided by
web hosting companies, who often have support lines to aid in
technical issues.
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As with most technological issues the initial curve is the

hardest to climb but once completed, web publishing can be as
painless as sending an email.
Some desirable features may or may not be available and it

might be worth checking if you feel these might be necessary.
Such features may include: password protection for areas or
particular documents within your web site, large amounts of
storage space, particularly if you wish to disseminate video
data, and the ability to run interactive programs, if you wish to
make use of certain types of online questionnaires and data
collection.
When creating public web pages, you may wish to consider

some of the aspects that allow pages to be successfully found
via search engines, such as including your own keywords and
all the relevant names if a theory, concept or object has
alternative naming conventions. Similarly, you may use your
own experience of what is pleasant to read and navigate when
designing your layout or consult the growing range of books
which attempt to explain good web page design to non-
computer professionals.
4.5 Making video available online

There are now a multitude of sites (e.g. YouTube.com;
video.google.com) which allow video to be uploaded to the
web free of charge which can be viewed online, but usually not
downloaded to be watched when not connected to the
internet. These are often a useful and cheap way of
distributing otherwise large video files but bear in mind the
quality may be poor in some cases and you may need some
assistance with video editing to get optimal results if you are
not familiar with the process.
4.6 Blogs and online journals

Blogs are online journals that allow a simple and
straightforward way of publishing on the web. There are now a
huge number of services that will host your blog for free (with
accompanying adverts) and many that will do the same
without adverts for only a few dollars a month. Blogs vary in
their purpose with some being individual streams of
consciousness and others being more journalistic and news-
focused. A regular insight into the specialist world of clinical
neuropsycholgy can be a powerful way of communicating facts
and commentary about recent developments either to a
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professional or lay audience. (p.865) Nevertheless, special

care must be taken if you intend to write about your work. A
code of ethics has been developed for health care workers who
write online (medbloggercode.com) although it is voluntary
and has no official status. It is probably worth being aware
that while your typical audience may only be a handful of
people, anything that is deemed controversial or unwise may
have a potential audience of millions so extra care must be
taken to ensure that all ethical guidelines are followed. On a
more pragmatic level, as blogs can be set up in a matter of
minutes with minimal cost they are often a useful way of
creating instant news sites for conferences, events, classes or
interest groups.
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5 Effective use of internet software

There are two main problems which may affect a useful
internet work session. The first is poor design or broken
technology on the remote web site or resource, the second is
inefficient use of web browser software.
Frequently, there is little a user can do about remote web site

failures or errors, frustrating as they might be. It is however,
often worth sending the site administrator a short email
pointing out the problem you have encountered. System
administrators tend to be somewhat overburdened and are
unable to spend vast amounts of time checking every nook and
cranny of a complex web site to make sure it still works after
every alteration. A polite email pointing out an error in the site
is often useful for them, and may mean your required
information is fixed within a matter of hours. On a less positive
note, technically competent people (especially the overworked
ones who are contacted out of the blue), tend to attribute
problems to stupidity in the first instance and stop
investigating a reported problem (rightly or wrongly) at the
first sign that a user might not understand the technology.
Less confident users may wish to quickly check with a more
experienced colleague that their problem is genuinely with the
web site, and not their usage of the software, to increase the
chances of a helpful response.
One alternative solution to missing or broken pages is to make

use of internet search engines. If you click on a link which
leads nowhere, or a web address you have been given does not
work, try typing the title of the page into a search engine. If
the page has moved, the search engine may have catalogued
its new location. Another useful feature, pioneered by the
search engine Google (www.google.com) is a system which
stores copies of all the pages it knows about. Even if a page
has been deleted from its original location, Google may still
have a copy in its cache. Simply search for the page as normal,
and click the ‘Cached’ link to see the saved version. A web site
called the Way Back Machine (www.archive.org), solely exists
for this purpose and has archives of web pages stretching
back some years. It is also worth remembering that such
archives are kept by third parties if you are considering
putting personal or sensitive information on the web. You may
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be able to remove your own web pages, but will not be able to
remove the same information from external archives.
The problem of inefficient web browser use can greatly affect

the speed and ease of an internet work session. In the early
days of the web, browsers were fairly small and lightweight.
They had only limited functionality as web sites were relatively
unsophisticated. More recently, due to the demands of newer
web site technology, increased multimedia (p.866) usage and
(it has to be said) poor design, browsers have obtained a
reputation for being slow, buggy and monolithic. Whilst this
situation is gradually improving, a good grasp of how to
maximise browser performance may save you a great deal of
time and hair-loss.
There are some good practices that apply to almost all

computer software you will use. Firstly, it is important to get a
good overview of the software, a good habit is to read through
all the main menus and familiarise yourself with the options
before you start using any new piece of software. This will give
you an instant overview of the package’s functionality, and will
also make any additional documentation (like the electronic
help files) much more understandable. Secondly, try and load
or enable only the software, features or options that you need.
If you feel competent in software configuration, experiment
and see which options improve your usage. Often there are
many like minded users on the internet, some of which kindly
publish their gems of wisdom. A web search using the name of
your software package and the word ‘hack’ or
‘optimisation’ (or ‘optimization’ to retrieve pages using the
American spelling) as key words will often give you a wealth of
information.
An excellent review article by Al-Shahu et al. (2002) has lots of

useful pointers in this regard, and the table below (Table 43.1)
is derived from their paper.
6 Ethics of internet communication

The use of internet communication by clinical
neuropsychologists causes some novel ethical dilemmas
because of two major considerations. The first is the privacy
implications of using the internet and internet software
(notorious for their lack of adequate security) for information
which you may be legally and ethically bound to keep
confidential. The second is the issue of copyright and its use to
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restrict the dissemination of information which could aid the

treatment of patients or education of clinicians, when such
dissemination can be conducted for near zero cost when
conducted via the internet.
6.1 Internet security and confidentiality

The idea that a patient's medical information should only be
available to people directly involved in their medical care, and
that it is the carers responsibility to maintain this
confidentiality, are core values in the health care system. It
will perhaps come as a surprise to many clinicians that
sending information over the internet is as confidential as
discussing a patient's details on a crowded bus. It may be true
that no-one is interested but that does not change the fact that
the information is available to many people to whom the
patient has not consented access.
With easily available software, any person can intercept and

store all of the unencrypted information on your local network
without being detected. Government agencies routinely
intercept internet traffic, and while this may not be considered
a major concern for the majority of patients, it must be noted
that in the recent case of General Augusto Pinochet's
extradition from the UK, the decision rested on a
neuropsychology assessment of his mental fitness. Whilst not
all such ethical dilemmas might be as dramatic, each patient
should be able to rely on the confidentiality of their clinical
records or related information, including when they are
communicated via the internet. (p.867)
Table 43.1 Enhance your use of a browser
Maintain software
◆ Use the latest version of your browser (determine
which version you are using under the ‘Help’ menu,
‘About’ in Windows, or Apple menu ‘About’ on the
Macintosh)
◆ Check for new browser software monthly for the

latest security patches.
◆ Use the latest versions of free software to view

multimedia content.
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◆ Install virus protection software and keep it up to

date.
Shorten the time you spend on line

◆ For downloading large amounts of data, use the
internet before global use rises (between midnight and
noon in Europe).
◆ If available, use mirror sites (exact copies of web

sites) located in, or close to, your own country.
◆ If the web site allows it, select text-only or low

bandwidth options and omit multimedia content if the
bandwidth of your connection is low.
◆ If network response is sluggish, open pages in their

own windows and continue working or browsing other
pages, and return to them later.
Minimise memory use

◆ Choose to install only the components of the browser
that are essential to you (a full installation can consume
many megabytes of disk space)
◆ Close down browser windows and applications you

are no longer using.
◆ Optimise the size of your cache or “Temporary

Internet Files” folder.
Customise your browser

◆ Set your browser’s home page to a blank page
(about:blank) or the web site you use the most.
◆ Organise your ‘Favorites’ or ‘Bookmarks’ into folders.
◆ Set your preferred font type and size (under ‘Text

Size’ on the ‘View’ menu)
◆ Maximise the viewable area in your browser by

removing the explorer bar and customising toolbars to
show only the functions you use (as small icons).
Take short cuts

◆ When typing web addresses, omit ‘http://’, as your
browser will automatically append it.
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◆ Use copy and paste functions to transfer web

addresses between documents and browser.
◆ Right click (Windows) or click and hold (Macintosh)

with your mouse to save images, sounds, or videos from
a web site to your hard drive.
◆ If a web site cannot be found with the web address

you have entered use a search engine to see if it
available at an alternative location.
◆ Learn the shortcut keys that allow you to directly type

in a web address without having to click on the location
bar.
Similarly, much common internet software is susceptible to viruses

which can also breach such confidentiality agreements. In the case
of one particular virus which exploits vulnerabilities in popular
email software, a document is randomly selected and mailed to
everyone in the user's address book. This author has personally
received a confidential case report which got mailed by this virus to
a public mailing list which happened to be listed in the infected
user's email address book.
(p.868) One way of assuming responsibility for clinical
confidentiality is to ensure that adequate advice is taken on
the implications of using particular software and taking
precautions to prevent unhappy accidents, such as running up-
to-date anti-virus software. In the case of internet
communication the use of encryption software to scramble the
contents of messages so only the intended recipient can
decrypt or unscramble the potentially sensitive information is
currently the best method to ensure private communication.
The use of encryption software is, unfortunately, still scarcely

used, and not as user friendly as it could be. However, this is
rapidly changing, and is becoming accessible to motivated
individuals willing to spend a little time learning the ropes.
Any clinical neuropsychologists who are provided with their
internet access by an employer or institution should push for
encryption to be common practice rather than the exception
and take good advice from competent computer professionals
on suitable software for this purpose.
Clinicians may also wish to consider encryption for storing

files on the local disk in case of theft. Luckily, software which
creates secure password protected areas is considerably more
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user-friendly and is readily available. TrueCrypt is a

particularly good example of a well-designed, secure and free
software package available to do exactly this (truecrypt.org).
6.2 Electronic publishing

The debate over the ownership of scientific literature has
recently become particularly salient (see Laporte and Hibbitts,
1996, for an excellent analysis), largely because the traditional
role of publishers as the cog wheels of journal distribution is
becoming increasingly redundant as the internet becomes the
preferred method for information dissemination. Since
information can be distributed across the internet for near
zero cost, questions have been raised about the ethics of using
copyright to restrict information which could be used for the
benefit of the patient and society at large (Bachrach et al.,
1998).
However, whilst no-one would doubt the benefits of peer

review in scientific and clinical research, doubts have been
raised about the possible decline in quality that may occur if
copyright for clinical and scientific journals is abolished
(Bloom, 1998).
Clinical neuropsychologists may also face similar dilemmas

when producing standardised neuropsychological tests. The
question of whether it is ethical to cede copyright to a
publisher who may charge large sums of money for a copy of a
potentially beneficial clinical test is a thorny issue. For some
tests (such as the Block Design subscale of the Wechsler Adult
Intelligence Scale) that may require specifically prepared
materials that cannot be simply provided as digital templates,
it would seem that a third party publisher may be the best
method of effective distribution. Many neuropsychological
tests are however, produced by publically funded
neuropsychologists and can easily be distributed as digital
copies to appropriate recipients. Many would argue that to
restrict and charge for clinical tests that may be used directly
in a patient's care, or in valuable clinical research when a near
zero cost distribution method is available, could be considered
as unethical, or at the very least, obstructive.
(p.869) One issue increasingly important issue is the

availability of information about neuropsychological tests on
the internet which may compromise their validity. Recent
surveys of information on medical examinations and tests of
Page 22 of 24
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malingering found that potentially compromising information

was not common, but was available online (Bauer and
McCaffrey, 2006; Horwitz and McCaffrey, 2006). Clinicians
should be careful not to inadvertently release such information
when discussing their work online, and should also attempt to
design tests that are not compromised by the material being
made available.
References
Alejandro R., Jadad, R., Haynes, B., Hunt, D., Browman, G. P.

(2000) The Internet and evidence-based decision-making: a
needed synergy for efficient knowledge management in health
care. Canadian Medical Association Journal, 162 (3), 362–5.
Al-Shahi, R., Sadler, M., Rees, G. & Bateman, D. (2002)

Review: The internet. Journal of Neurology, Neurosurgery and
Bachrach, S. et al . (1998) Intellectual Property: Who Should

Own Scientific Papers?. Science , 281 (5382), 1459–1460.
Bauer L., McCaffrey R.J. (2006) Coverage of the Test of

Memory Malingering, Victoria Symptom Validity Test, and
Word Memory Test on the Internet: is test security
threatened?. Archives of Clinical Neuropsychology, 21 (1),
121–6.
Behnke, S. (2007) Ethics and the Internet: Requesting clinical

consultations over listservs. Monitor on Psychology, 38 (7), 62.
Retrieved from http://www.apa.org/monitor/julaug07/
ethicsrounds.html/
Bloom, F. (1998) Editorial: The Rightness of Copyright.

Science , 281, (5382), 1451.
Horwitz, J.E., McCaffrey, R.J. (2006) A review of internet sites

regarding independent medical examinations: implications for
clinical neuropsychological practitioners. Applied
Neuropsychology, 13 (3), 175–9.
Laporte, R. & Hibbitts, B. (1996) Rights, wrongs and journals

in the age of cyberspace. British Medical Journal, 313, 1609–
1612.
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McIvor, R.J. & Petch, E. (2006) Stalking of mental health

professionals: an underrecognised problem. British Journal of
Smith, M.A. & Senior, C. (2001) The internet and clinical

psychology: A general review of the implications. Clinical
Psychology Review, 21 (1), 129–136. (p.870)
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Neuropsychology: past, present, and future

University Press Scholarship Online

Oxford Scholarship Online

The Handbook of Clinical Neuropsychology

Print publication date: 2010

Neuropsychology: past, present, and

Abstract and Keywords

Keywords: clinical neuropsychology, cognitive disorders, neuropsychological

It ought to be generally known that the source of our

Aristotle (384–322 BCE), who believed that the brain merely

Nonetheless, it was another two millennia before relatively

memory), eventuality (memory for facts), time, music, and

(p.4) Inspired by Gall’s achievements, the first golden age of

For the most part, classical neuropsychology was based upon

service as a consultant neurologist in France during World

Classical neuropsychology had also taken an interest in

too little of various neurotransmitters was implicated in many

The further integration of psychology (and psychologists) into

Hécaen in Paris, and Ennio De Renzi in Milan, sometimes in

Building upon the achievements of these seminal figures, the

Clinical neuropsychology is now a recognized profession with

Cognitive neuropsychology also underwent a renaissance in

(p.7) Seen in this light, the study of pathologies of cognition

◆ Neuropathological fractionations of cognition impose

◆ The interpretation of pathological performance by

◆ In any complex system, identical overt failures and errors

The relevance of this framework to the practical concerns of

the overt signs and symptoms of cognitive breakdown. Initially,

Progress was first made in the description and interpretation

Early work that mapped the performance of individual patients

functions, and the way in which it drove justified changes to

Current work has to a large extent preserved a keen distrust

With respect to rehabilitation, the 1970s and 80s saw the

This single-case approach to therapy for cognitive

performance of individual patients and case-series. The

(p.9) It is not yet clear whether long-term, generalized gains

Populations (in the developed world at least) are growing ever

The paradigms characteristic of cognitive neuropsychology

clinical applications. Advances in the calculation of functional

(p.10) We can also look forward to further insights into the

Berndt, R.S. and Mitchum, C.C. (eds.) (1995). Cognitive

Brothers, L. (1997). Friday’s footprint: how society shapes

Butterworth, B. (1999). The mathematical brain. Macmillan,

Cabeza, R. and Kingstone, A. (eds.) (2001). Handbook of

Cacioppo, J.T., Berntson, G.G., and Adolphs, R. (eds.)

Caplan, D. and Hildebrandt, N. (1988). Disorders of

Coltheart, M., Curtis, B., Atkins, P., and Haller, M. (1993).

Damasio, A.R. (1999). The feeling of what happens: body and

David, R., Enderby, P., and Bainton, D. (1982). Treatment

Denes, G. and Pizzamiglio, L. (eds.) (1999). Handbook of

Duncan, J., Burgess, P.W., and Emslie, H. (1995). Fluid

Farah, M. (1990). Visual agnosia. MIT Press, Cambridge,

Foundas, A.L., Macauley, B.L., Ramer, A.M., Maher, L.M.,

(p.11) Frackowiak, R.S.J., Friston, K.J., Frith, C.D.,

Frith, C.D. (1992). The cognitive neuropsychology of

Goldstein, K. (1942). After effects of brain injuries in war.

Gurd, J.M. (2000). Verbal fluency deficits in Parkinson’s

Halligan, P.W., Bass, C., and Marshall, J.C. (eds.) (2001).

Howard, D. and Hatfield, F.M. (1987). Aphasia therapy:

LeDoux, J.E. (1992). The emotional brain. Simon and