Author's personal copy

Coma, Persistent Vegetative States, and Diminished

Consciousness
A Demertzi, S Laureys and M Boly, University of Liège, Liège, Belgium
ã 2009 Elsevier Inc. All rights reserved.

Glossary Neuron-specific enolase – The neuronal

form of the glycolytic enzyme enolase, which
Apnea testing – A test needed to confirm
is found almost exclusively in neurons and
brain death by checking whether the patient
cells of neuroendocrine origin and is used as
has a breathing reflex when disconnected
a marker of ischemic brain damage.
from the positive pressure ventilator.
Brain–computer interfaces (BCIs) – Real-
time muscular-independent systems that
permit the translation of the electrical activity
of the brain into commands, to control Introduction
devices.
Deep brain stimulation (DBS) – An invasive The management of coma and related disorders of
surgical treatment involving the implantation consciousness (DOC) is a major clinical challenge.
of a medical device (brain pacemaker), which Patients in a vegetative state and minimally con-
sends electrical impulses to specific parts of scious state continue to pose problems in terms of
the brain. their diagnosis, prognosis, and treatment. Bedside
Default mode network – A set of brain assessment remains the gold standard. Neuroimag-
areas, encompassing the posterior cingulate ing and electrophysiological measures can now
cortex/precuneus, the medial prefrontal identify signs of awareness inaccessible to clinical
cortex, and bilateral temporoparietal examination, which permit a better understanding
junctions, which seem to be activated in the of the mechanisms of human consciousness and
absence of any external stimulation, and improve our care of DOC patients.
show decreased activity during cognitive
processing.
Event-related potentials (ERPs) – Defining Consciousness
Averaged EEG signals that detect time-
locked responses to sensory, motor, or Consciousness is a first-person experience, which
cognitive activities. Short-latency or consists of two major components, wakefulness and
exogenous ERPs, ranging from 0 to 100 ms awareness. Wakefulness refers to the level of con-
after the presentation of a stimulus, sciousness and it is supported by the function of
correspond to the activation of the ascending the subcortical arousal systems in the brainstem,
pathways to the primary cortex. Cognitive or the midbrain, and the thalamus. Clinically, it is
endogenous ERPs are obtained after 100 ms indicated by opening of the eyes. Awareness refers
of the presentation of a stimulus, and reflect to the contents of consciousness and it is thought
both subcortical and cortical structures, to be supported by the functional integrity of the
including associative areas. cerebral cortex and its subcortical connections.
Functional connectivity – The temporal Awareness can be further reduced to awareness of
correlation of a neurophysiological index the environment and of self. Clinically, awareness
(i.e., cerebral metabolic rates of glucose, of the environment is assessed by evaluating com-
regional cerebral blood flow) measured in mand following and observing nonreflex motor
different remote brain areas. behavior, such as eye tracking and oriented

147

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148 Coma, Persistent Vegetative States, and Diminished Consciousness

responses to pain. Awareness of self, clinically a As a consequence, medicine was forced to redefine
more ill-defined concept, can be assessed by the death, using a neurological definition, that of brain
patients’ response to autoreferential stimuli, such death.
as the patients’ own face in the mirror. An illustra- In the 1960s, Fred Plum and Jerome Posner
tive example of the relationship between the two described for the first time the locked-in syndrome
components of consciousness is the transition from (LIS), to refer to fully conscious coma survivors who
full wakefulness to deep sleep: the less aroused we are unable to communicate due to physical paraly-
get, the less aware we become of our surroundings sis. In 1972, Bryan Jennet and Fred Plum published
and ourselves (see Figure 1). the clinical criteria of another artifact of modern
intensive care, the vegetative state (VS), a state of
‘wakefulness without awareness.’ In 2002, the Aspen
A Short History of Disorders of Neurobehavioral Conference Workgroup realized
Consciousness that clinical reality was yet more complicated.
Some patients showed signs of voluntary behavior,
About 50 years ago, before the era of neurocritical and therefore they were no longer vegetative, but
care, things were relatively simple. After a severe still remained unable to functionally communicate.
brain damage, comatose patients either died or, Based on these observations, they published the
more rarely, recovered with more or less cognitive diagnostic criteria of a new clinical entity, the mini-
deficits. The invention of the positive pressure mally conscious state (MCS).
mechanical ventilator by Bjorn Ibsen in the
1950s, and the widespread use of intensive care in
the 1960s, in the industrialized world, changed the Defining the Clinical Entities of
picture. They stated that severely brain damaged Consciousness
patients could now have their heartbeat and sys-
temic circulation sustained by artificial respiratory Brain Death
support. Such profound unconscious states had Brain death means human death determined by
never been encountered before as, until that time, neurological criteria. The current definition of
all these patients had died instantly from apnea. death is the permanent cessation of the critical
functions of the organism as a whole, such as,
neuroendocrine and homeostatic regulation, cir-
Conscious
culation, respiration, and consciousness. Most
countries, including the United States, require
Content of consciousness: awareness

wakefulness
Lucid
dreaming Locked-in syndro
syndrome
rom death of the whole brain including the brainstem.
Drowsiness Some other countries, like the United Kingdom
REM
sleep Light sleep
and India, rely on the death of the brainstem only,
arguing that the brainstem is at once the through-
station for nearly all hemispheric input and output,
Deep sleep Minimally conscious state
the center generating wakefulness (an essential
General condition for conscious awareness), and the center
anesthesia
of respiration. Classically, brain death is caused by
Coma Vegetative state
a massive brain lesion, such as trauma, intracranial
Level of consciousness: wakefulness hemorrhage, or anoxia. Using the brainstem for-
Figure 1 Simplified illustration of the two major mulation of death, however, unusual but existing
components of consciousness and the way they cases of catastrophic brainstem lesions, usually of
correlate within the different physiological, hemorrhagic origin, sparing the thalami and cere-
pharmacological and pathological modulations of
bral cortex, can be declared brain dead in the
consciousness. Reproduced from Laureys S (2005)
The neural correlate of (un)awareness: Lessons from absence of clinical brainstem function, despite
the vegetative state. Trends in Cognitive Sciences 9: intact intracranial circulation. Hence, a patient
556–559. with a primary brainstem lesion who did not

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Coma, Persistent Vegetative States, and Diminished Consciousness 149

develop raised intracranial pressure might theoret- (see Figure 1). These patients regain sleep–wake
ically be declared dead by the UK doctrine, but not cycles. However, their motor, auditory, and visual
by the US doctrine. functions are restricted to mere reflexes and show no
In 1995, the American Academy of Neurology adapted emotional responses. The VS is usually
published the criteria for brain death, which have caused by diffuse lesions on the gray and white
been used to model many institutional policies. The matter. According to the 1994 Multi-Society Task
criteria are (1) demonstration of coma; (2) evidence Force on persistent vegetative state (PVS), the cri-
for the cause of coma; (3) absence of confounding teria for the diagnosis of VS are the following: (1) no
factors, including hypothermia, drugs, electrolyte, evidence of awareness of self or environment and an
and endorcrine disturbances; (4) absence of brain- inability to interact with others; (2) no evidence of
stem reflexes; (5) absent motor responses; (6) posi- sustained, reproducible, purposeful, or voluntary
tive apnea testing (see ‘Glossary’); (7) a repeat behavioral responses to visual, auditory, tactile, or
evaluation in 6 h is advised, but the time period noxious stimuli; (3) no evidence of language com-
is considered arbitrary; and (8) confirmatory labora- prehension or expression; (4) intermittent wakeful-
tory tests are only required when specific com- ness manifested by the presence of sleep–wake
ponents of the clinical testing cannot be reliably cycles; (5) sufficiently preserved hypothalamic and
evaluated. At present, no recovery from brain death brainstem autonomic functions to permit survival
has been reported. with medical and nursing care; (6) bowel and blad-
der incontinence; and (7) variably preserved cranial
Coma nerve and spinal reflexes.
The VS may be a transition to further recovery,
Patients that sustain severe brain damage may
or may be permanent. ‘Permanent’ VS refers to
spend some time in coma, which lasts for a couple
patients whose chances for recovery are close to
of days or weeks. Patients in coma cannot be awak-
zero. This is the case for VS that lasts more than
ened even when intensively stimulated and, hence,
1 year after traumatic, or 3 months after nontrau-
are not aware of the environment and of them-
matic (anoxic) injury. The VS is characterized as
selves (see Figure 1). Coma is distinguished from
‘persistent,’ when a patient is in this state for more
syncope or concussion in terms of its duration,
than 1 month. As both terms are abbreviated as
which is at least 1 h. Coma can result from bihemi-
‘PVS,’ it has been suggested to avoid these terms
spheric diffuse cortical or white matter damage or
and, instead, mention the etiology and the time
brainstem lesions bilaterally, affecting the subcor-
spent in VS. At present, there are no validated
tical reticular arousing systems. Many factors such
prognostic markers for individual patients except
as etiology, the patient’s general medical condi-
that the chances for recovery depend on patient’s
tion, age, clinical signs, and complementary exam-
age, etiology, and time spent in the VS.
inations influence the management and prognosis
of coma. Traumatic etiology is known to have a
better outcome than nontraumatic anoxic cases. In Minimally Conscious State
terms of clinical signs, after 3 days of observation, a
The MCS has been defined in 2002 by the Aspen
bad outcome is heralded by the absence of pupil-
Workgroup as a DOC in order to describe non-
lary or corneal reflexes, stereotyped or absent
communicating patients that show inconsistent,
motor response to noxious stimulation, bilateral
but discernible signs of behavioral activity that is
absent cortical responses of somatosensory-evoked
more than reflexive in at least one of the following
potentials (SEPs) (see ‘Glossary’), and (for anoxic
behavioral signs: (1) purposeful behavior, includ-
coma) biochemical markers, such as high levels of
ing movements or affective behavior that occurs in
serum neuron-specific enolase (see ‘Glossary’).
contingent relation to relevant environment sti-
muli and is not due to reflexive activity, such as:
Vegetative State
pursuit eye movement or sustained fixation occur-
In the VS there is dissociation between wakefulness, ring in direct response to moving or salient stimuli,
which is preserved, and awareness, which is absent smiling or crying in response to verbal or visual

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150 Coma, Persistent Vegetative States, and Diminished Consciousness

emotional but not neutral stimuli, reaching for Once an LIS patient becomes medically stable,
objects, demonstrating a relationship between and given appropriate medical care, life expec-
object location and direction of reach, touching tancy now is for several decades. Even if the
or holding objects in a manner that accommodates chances of good motor recovery are very limited,
the size and shape of the object, and vocalizations existing eye-controlled, computer-based commu-
or gestures occurring in direct response to the nication technology (i.e., BCI, see ‘Glossary’) cur-
linguistic content of questions, (2) following sim- rently allows these patient to control their
ple commands; (3) gestural or verbal yes/no environment. Neuropsychological testing batteries
response, regardless of accuracy; and (4) intelligi- adapted and validated for eye-response communi-
ble verbalization. cation, have shown preserved intellectual capaci-
Like the VS, the MCS may be chronic and ties in LIS patients, whose lesions are restricted to
sometimes permanent. Emergence from the MCS brainstem pathology. Recent surveys show that
is defined by the ability to exhibit functional inter- chronic LIS patients self-report a meaningful
active communication or functional use of objects. quality of life and the demand for euthanasia,
Given that the criteria for the MCS have only albeit existing, is infrequent.
recently been introduced, there are few clinical
studies of patients in this condition. Similar to
the VS, traumatic etiology has a better prognosis
Evaluation of the Disorders of
than nontraumatic anoxic brain injuries. Prelimi-
Consciousness
nary data show that the overall outcome in the
MCS is more favorable than in the VS.
Good medical management starts with good diag-
nosis. However, as awareness is a first-person per-
The Locked-In Syndrome spective, its objective assessment is difficult. For
that reason, at the bedside, clinicians need to infer
The LIS describes patients who are awake and
it via the evaluation of motor activity and command
conscious, but have no means of producing speech,
following. Diagnosing DOC correctly is extremely
limb, or facial movements, resembling patients in a
challenging. This is mainly because these patients
VS. LIS most commonly results from lesions to the
are usually deprived of the capacity to make nor-
brainstem. According to the 1995 American Con-
mal physical movements and may show limited
gress of Rehabilitation Medicine criteria, LIS
attentional capacities. Aphasia, apraxia, and corti-
patients demonstrate: (1) sustained eye-opening
cal deafness or blindness are other possible con-
(bilateral ptosis should be ruled out as a compli-
founders in the assessment of DOC. This, in
cating factor), (2) quadriplegia or quadriparesis,
combination with the difficulty to define uncertain
(3) aphonia or hypophonia, (4) a primary mode
behavioral signs as voluntary or reflexive, can par-
of communication that uses vertical or lateral eye
tially explain the high rate of incorrect diagnosis of
movement or blinking of the upper eyelid to signal
DOC, which has been estimated to be around 40%
yes/no responses, and (5) preserved cognitive abil-
of the cases. Besides these difficulties, one should
ities. Since there is only motor output problem,
also consider that some of the diagnostic criteria for
LIS is not a DOC, but it is included here as
VS and MCS do not share international consensus,
it can be misdiagnosed as one. Based on motor
such as, visual fixation, eye tracking, blinking
capacities, LIS can be divided into three cate-
to visual threat, and oriented motor responses to
gories: (1) classic LIS, which is characterized by
noxious stimuli.
quadriplegia and anarthria with eye-coded com-
munication; (2) incomplete LIS, which is chara-
cterized by remnants of voluntary responsiveness
Behavioral Evaluation
other than eye movement; and (3) total LIS, which
is characterized by complete immobility includ- In 1974, Teasdale and Jennett’s Glasgow coma scale
ing all eye movements, combined with preserved (GCS) was published in ‘The Lancet.’ This stan-
consciousness. dardized bedside tool to quantify consciousness

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Coma, Persistent Vegetative States, and Diminished Consciousness 151

became a medical classic, thanks mainly to its short In Search for Objective Markers of
and simple administration. The GCS measures eye, Consciousness
verbal, and motor responsiveness. There may be Electrophysiology
some concern as to what extent eye-opening The EEG allows recording of the spontaneous
is sufficient evidence for assessing brainstem func- electrical brain activity, permitting the identifica-
tion. Additionally, the verbal responses are impossi- tion of the level of vigilance and the detection of
ble to be measured in cases of intubation and functional cerebral anomalies, such as seizures or
tracheotomy. Most importantly, the GCS is not encephalopathy. In brain death, the EEG shows
sensitive enough to detect transition from the VS absent electrocortical activity with a sensitivity
toward the MCS. and specificity of around 90%. In coma, a burst
To differentiate VS patients from MCS suppression in the EEG heralds a bad outcome. In
patients, the most appropriate scale is the coma the VS, the EEG often shows a diffuse slowing and
recovery scale-revised (CRS-R). The CRS-R has a it is only sporadically isoelectric. Similarly, in
similar structure to the GCS, containing, in addi- MCS there is a general slowing on the EEG. In
tion to motor, eye, and verbal subscales, also audi- LIS, the EEG does not reliably distinguish these
tory, arousal, and communication subscales. patients from VS patients. However, a close-to-
Despite its longer administration (i.e., c. 20 min) normal EEG should have the physician consider
as compared to the GCS and the full outline of the possibility of LIS.
unresponsiveness (FOUR), it is the most sensitive The use of ERPs (see ‘Glossary’) is useful to
in differentiating VS patients from MCS patients. predict the outcome in DOC. Bilateral absence of
This is because it assesses every behavior accord- cortical potentials (i.e., N20) or SEPs heralds a bad
ing to the diagnostic criteria of the VS and the outcome in coma. The presence of ‘mismatch neg-
MCS, such as, the presence of visual pursuit and ativity’ (MMN), a late cognitive ERP component
visual fixation. Importantly, the way we assess that is elicited in auditory ‘oddball’ paradigms, is
these behavioral signs need to be standardized predictive of recovery of consciousness. In VS,
and uniform, permitting between-centers com- SEPs may show preserved primary somatosensory
parisons. For example, for the assessment of visual cortical potentials (SEPs), and brainstem auditory-
pursuit, some scales use an object or finger evoked potentials (BAEPs) often show preserved
(FOUR), some use a mirror, a person, an object, brainstem potentials. Endogenous-evoked poten-
and a picture (Western Neuro-Sensory Stimula- tials, measuring the brain’s response to complex
tion Profile), some use an object and a person auditory stimuli, such as the patient’s own name
(Wessex Head Injury Matrix; Sensory Modalities (as compared to other names) permits to record a
Assessment and Rehabilitation Technique), and P300 response, which delayed in DOC patients
some a moving person (Coma/Near Coma Scale). when compared to controls. However, a P300 is
We have shown that the use of a mirror is more not a reliable marker of consciousness as it can also
sensitive in detecting eye tracking and, hence, be detected during deep sleep and anesthesia.
identify MCS patients. These findings stress that
self-referential stimuli have attention-grabbing
properties and are important in the assessment Resting cerebral metabolism
of DOC. Cortical metabolism in coma survivors is reduced
Despite their pros and cons, each scale contri- on an average to 50%–70% of the normal values.
butes differently in establishing the diagnosis and A global depression of cerebral metabolism is not
prognosis of DOC. The administration and inter- unique to coma. When anesthetic drugs are
pretation of findings should be decided and dis- titrated to the point of unresponsiveness, the
cussed in terms of the person who uses the scale, resulting reduction in brain metabolism is similar
the place where it is administered (e.g., intensive to that observed in pathological coma. Another
care vs. chronic rehabilitation settings), and the example of transient metabolic depression can be
reasons for administration (e.g., clinical routine observed during slow-wave sleep. In this daily
vs. research purposes). physiological condition, the cortical cerebral

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152 Coma, Persistent Vegetative States, and Diminished Consciousness

metabolism can drop to nearly 40% of the normal identified a dysfunction in a wide frontoparietal
values – while in REM-sleep, the metabolism network encompassing the polymodal associative
returns to normal waking values (see Figure 2). cortices: bilateral lateral frontal regions, parieto-
In brain death the so-called ‘empty-skull sign’ is temporal and posterior parietal areas, mesiofrontal,
observed, denoting functional decapitation. VS posterior cingulate, and precuneal cortices (see
patients show substantially reduced, but not absent, Figure 3). However, awareness seems not to be
overall cortical metabolism, up to 40%–50% of exclusively related to the activity in this ‘global
the normal values. In some VS patients who subse- workspace’ cortical network, but, as importantly,
quently recovered, global metabolic rates for glu- to the functional connectivity within this system
cose metabolism did not show substantial changes. and with the thalami. Long-range, frontoparietal,
Hence, the relationship between the global levels and thalamocortical ‘functional disconnections,’
of brain function and the presence or absence of with nonspecific intralaminar thalamic nuclei,
awareness is not absolute. It rather seems that some have been identified in the VS. Moreover, recovery
areas in the brain are more important than others is paralleled by a functional restoration of this
for its emergence. Statistical analyses of metabolic frontoparietal network and part of its thalamocor-
positron emission tomography (PET) data have tical connections.

100
90
80
Global metabolism (%)

70
60
50
40
30
20
10
0
Normal Brain Deep REM General Recovery Vegetative Recovery
consciousness death sleep sleep anesthesia from state from vegetative
anesthesia state
Figure 2 Global cerebral metabolism in healthy, pharmacological and disorders of consciousness. Adapted from
Laureys S, Owen AM, and Schiff ND (2004) Brain function in coma, vegetative state, and related disorders. Lancet
Neurology 3: 537–546.

Figure 3 The frontoparietal ‘‘awareness network’’ (orange) is systematically the most impaired region in the
vegetative state. The blue arrows represent the functional disconnections within this ‘‘awareness network’’ and with
the thalami. The green area represents the relatively spared activity in the brainstem and hypothalamus. Adapted from
Laureys, et al. (1999), NeuroImage.

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Coma, Persistent Vegetative States, and Diminished Consciousness 153

Cortical activation to passive external functional neuroimaging results must be used with
stimulation caution as proof or disproof of awareness in severely
In brain death, external stimulation does not lead to brain-damaged patients. Recently, Adrian Owen
any neural activation. In coma and VS patients, nox- from Cambridge University in collaboration with
ious stimulation was shown to activate only low- our laboratory proposed a more powerful approach
level primary cortices. Hierarchically higher-order to identify ‘volition without action’ in noncommu-
areas of the pain matrix, encompassing the anterior nicative brain-damaged patients. Rather than using
cingulate cortex, failed to activate. Importantly, the passive external stimulation paradigms, patients
activated cortex was shown to be isolated and func- were being scanned while asked to perform a mental
tionally disconnected from the frontoparietal net- imagery task. In one exceptional VS patient, task-
work, considered critical for conscious perception. specific activation was observed, unequivocally
Similarly, auditory stimulation in VS was found demonstrating consciousness in the absence of
to activate primary auditory cortices, but not behavioral signs of consciousness. Interestingly, the
higher-order, multimodal areas, from which they patient subsequently recovered. Other studies also
were disconnected (see Figure 4). In MCS, the showed that VS patients with atypical brain activa-
activation was more widespread and there was an tion patterns, after functional neuroimaging, showed
integrate functional connectivity between primary clinical signs of recovery of consciousness – albeit
auditory cortices and the posterior temporal/tem- sometimes many months later.
poroparietal and prefrontal associative areas.
Emotionally complex auditory stimuli, such as
stories told by a familiar voice, lead to more wide- Treatment
spread brain activation as compared to meaning-
less noise. Such context-dependent, higher-order To date, there are no ‘standards of care’ for thera-
auditory processing in MCS, often not assessable peutic management in DOC. Many studies have
at the patient’s bedside, indicate that content does been conducted under suboptimal or uncontrolled
matter when talking to these patients. settings, and for that reason, no evidence-based
However, given the absence of a thorough under- recommendations can be made. MCS patients,
standing of the neural correlates of consciousness, however, were shown to benefit more than VS

Controls Vegetative Minimally conscious

(n = 15) (n = 15) (n = 15)

Disconnected Connected

Figure 4 External stimuli still induce robust activation in primary sensory areas in vegetative patients. In the minimally
conscious state, the activation is more widespread extending to multimodal associative areas. Functional
connectivity studies (see ‘Glossary’) show that the activity of the primary cortex is isolated and disconnected from the
rest of the brain, like the parahippocampal gyrus (red areas in the left inset). In the minimally conscious state, we
observe a more integrated processing with preserved functional connectivity between low-level sensory areas and
frontalparietal regions, which are thought to be involved in the emergence of conscious perception (blue areas in the
right inset). Adapted from Boly, et al. (2004), Archives of Neurology.

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154 Coma, Persistent Vegetative States, and Diminished Consciousness

after invasive treatment with DBS (see ‘Glossary’). is senior research associate at the Belgian Fonds
More particularly, bilateral thalamic stimulation, National de la Recherche Scientifique (FNRS).
implanted over 6 years after acute trauma, has just Melanie Boly is research fellow at FNRS. This
been shown to cognitively improve an MCS research was funded by the European Commis-
patient, resulting in stimulation-related recovery sion, Mind Science Foundation, James McDonnell
of functional object use and intelligible verbaliza- Foundation, French Speaking Community Con-
tion. In the VS, despite some sparse evidence that certed Research Action, and Fondation Médicale
DBS may benefit these patients, its effectiveness to Reine Elisabeth.
this population is limited, mainly due to uncon-
trolled experimental settings. In any case, the tech- See also: Ethical Implications: Pain, Coma, and
nique awaits confirmation from studies on larger Related Disorders; General Anesthesia.
cohorts of patients, but illustrates that DBS in
well-chosen patients, selected on the basis of func-
tional neuroimaging results, can offer a real thera- Suggested Readings
peutic option, at least in chronic MCS patients.
Pharmaceutical interventions with amantadine, American Congress of Rehabilitation Medicine (1995)
mainly a dopaminergic agent, was shown to Recommendations for use of uniform nomenclature
pertinent to patients with severe alterations of
increase metabolic activity in a chronic MCS consciousness. Archives of Physical Medicine and
patient. Similarly, zolpidem, a nonbenzodiazepine Rehabilitation 76: 205–209.
sedative drug, may improve arousal and cognition Boly M, Phillips C, Tshibanda L, et al. (2008) Instrinsic brain
activity in altered states of consciousness: how conscious
in some brain-injured patients. However, placebo is the default mode of brain function? Annals of the New
controlled randomized trials are needed before we York Academy of Sciences 1129: 119–129.
making assertive conclusions about the effective- Boly M, Faymoville ME, Schnakers C, et al. (2008)
Preception of pain in the minimally conscious state with
ness of the drug in DOC patients. PET activation: an observational study. Lancet Neurology
7(11): 1013–1020.
Boveroux P, Bonhomme V, Boly M, et al. (2008) Brain
Conclusion function in physiologically, pharmacologically, and
pathologically altered states of consciousness.
International Anesthesiology Clinics 46(3): 131–146.
Currently, it is an exciting time for the study of Demertzi A, Vanhaudenhuyse A, Bruno MA, et al. (2008)
DOC. The gray zone transitions between them, in Is there anybody in there? Detecting awareness in
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to be better defined by adding powerful imaging Di H, Boly M, Weng X, et al. (2008) Neuroimaging activation
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Acknowledgments Laureys S, Owen AM, and Schiff ND (2004) Brain function in
coma, vegetative state, and related disorders. Lancet
Neurology 3: 537–546.
Athena Demertzi is funded by the DISCOS Marie Laureys S, Pellas F, Van Eeckhout P, et al. (2005) The
Curie research Training Network. Steven Laureys locked-in syndrome: What is it like to be conscious but

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Biographical Sketch

Athena Demertzi, MSc, PhD student, graduated from the Faculty of Psychology at the Aristotle University of Thessaloniki,
Greece in 2005. Soon after, she pursued her research master’s in cognitive neuroscience, neuropsychology, and psychopathology,
at Maastricht University, The Netherlands, where she specialized in the field of neuropsychology. During her master’s, she
conducted her research internship at the Blixembosch Rehabilitation Centre, Eindhoven, The Netherlands, where she studied
self-awareness deficits in everyday life following brain injury. She graduated in August 2007, and next joined the Coma Science
Group as an early stage researcher appointed by the Marie Curie Research Training Network ‘DISCOS’ – Disorders and
Coherence of the Embodied Self. Under the supervision of Steven Laureys, she investigates the neural basis of the elementary
personal identity in patients with altered states of consciousness, such as vegetative and minimally conscious patients.

Encyclopedia of Consciousness (2009), vol. 1, pp. 147-156

 Author's personal copy

156 Coma, Persistent Vegetative States, and Diminished Consciousness

Steven Laureys, MD, PhD, is a senior research associate at the Belgian National Fund of Scientific Research (FNRS) and Clinical
Professor at the Department of Neurology, Sart Tilman Liège University Hospital. He graduated as a medical doctor from the
Vrije Universiteit Brussel, Belgium. While specializing in neurology he entered his research career and obtained his MSc in
pharmaceutical medicine working on pain and stroke, using in vivo microdialysis and diffusion magnetic resonance imaging (MRI)
in the rat (1997). Drawn by functional neuroimaging, he moved to the Cyclotron Research Center at the University of Liège,
Belgium, where he obtained his PhD (2000) and his ‘thèse d’agrégation de l’enseignement supérieur’ (2007), studying residual
brain function in coma, vegetative, minimally conscious, and locked-in states. He is board-certified in neurology (1998), and in
palliative and end-of-life medicine (2004). A recipient of the William James Prize (2004) from the Association for the Scientific
Study of Consciousness (ASSC) and the Cognitive Neuroscience Society (CNS) young investigator award (2007), he recently
published The Boundaries of Consciousness (Elsevier 2005) and The Neurology of Consciousness (Academic Press 2009). He
nowadays leads the Coma Science Group at the Cyclotron Research Centre at the University of Liège, Belgium.

Melanie Boly, MD, PhD student, is currently a research fellow at the Belgian National Funds for Scientific Research (FNRS) and
Neurologist in training at the University Hospital CHU Sart Tilman. Under Steven Laureys’ supervision, she performed several
studies comparing auditory and noxious stimuli cerebral processing in minimally conscious and vegetative state patients. In
collaboration with the team of Adrian Owen in Cambridge, she also elaborated a method to assess the presence of voluntary brain
activity, and thus of consciousness, in noncommunicative, brain-injured patients. This method has already proven to be of
potential interest in the early detection of signs of awareness in patients previously diagnosed as being in a vegetative state. Her
interests include the study of recovery of neurological disability and of neuronal plasticity by means of multimodal functional
neuroimaging (EEG-fMRI, PET, and MEG), and behavioral assessment in severely brain-damaged patients with altered states of
consciousness.

Encyclopedia of Consciousness (2009), vol. 1, pp. 147-156