Apraxia: The Neural Network Model: Theodore Wasserman Lori Drucker Wasserman

Neural Network Model: Applications and Implications
Theodore Wasserman
Lori Drucker Wasserman
Apraxia:
The Neural
Network
Model
Neural Network Model: Applications
and Implications
Series Editor
Theodore Wasserman, Wasserman & Drucker PA, Boca Raton, FL, USA
Theodore Wasserman • Lori Drucker Wasserman
Apraxia: The Neural

Network Model
Theodore Wasserman Lori Drucker Wasserman
Wasserman & Drucker PA Wasserman & Drucker PA
Boca Raton, FL, USA Boca Raton, FL, USA
ISBN 978-3-031-24104-8 ISBN 978-3-031-24105-5 (eBook)

Neural Network Model: Applications and Implications
https://doi.org/10.1007/978-3-031-24105-5
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Introduction: Why Apraxia
There are many ways that can inspire in writing a book. One way, we suppose, is
that the book results from a long-standing desire to explore a particular concept or
idea. Another is that the book represented a continuation of a theme that was being
developed over a period of time and across several books. In the current instance,
both ways could be considered accurate. This book, about apraxia, is the continua-
tion of a series of works on how the idea of the neural network organization of the
way the human brain processes information can impact what we understand about
the disorders practitioners confront when something goes wrong. This book is the
third in our series on human neural network characteristics of the brain and disor-
ders thereof. In that vein, we will raise themes we have been developing over the
series of works that include two additional works the preceded the current series.
Among these themes is the idea that the current diagnostic nosology, the Diagnostic
and Statistical Manual of Mental Disorders and the behavioral grouping model
upon which it is based, is inadequate to the task and probably injurious to the devel-
opment of advancement of the true nature of most disorders of mental health.
Another theme is the ongoing pathologizing of behaviors and groups of behaviors
that may, in fact represent, normal, if atypical, variations of human behavior. Some
examples of this phenomenon include the recently added to the DSM 5, namely,
social engagement disorder and caffeine withdrawal disorders. Obviously, behavior
in the extreme in these areas can be problematic but where the line gets drawn in
practice will be an interesting process to observe.
One of the most striking things that stood out for us in preparing the material for
this book is how little things have changed regarding the understanding of apraxia
over the last 30 years. For the most part, apraxia remains described as the inability
to make purposeful movement of one part of the body or another. The various types
of apraxic conditions are essentially names of the part of the body or function that
is impacted. The major theme for us, of course, is that once you understand how the
neural network model explains the information processing of the brain and once you
understand what can go wrong with those networks that form the basis of informa-
tion processing, the basic understanding of disorders related to this system must
change. The change in understanding must accompany a change in awareness of
v
vi Introduction: Why Apraxia
what it means for the system to be disordered. This inevitably leads to a change in
understanding that nature and characteristics of the disorders themselves. What we
described for disorders of mental health and for difficulties in motivation will also
be very true for apraxia. We believe that it is long past time for a new understanding
of this very large group of disorders. We hope that this new understanding leads to
the formulation of newer and more neurologically accurate diagnostic categories
and the development of more efficient treatment approaches.
While the motivation described above is sort of accurate, that isn’t really what
happened. What happened was that good friends of ours had a grandchild with
delayed speech development and asked us for an opinion regarding etiology, poten-
tial treatment, and long-term prognosis. The youngster was about 18 months old and
speech development was not occurring in the anticipated manner. Both of us have
extensive experience in the assessment of children in the 0–3 age range, so this
request was well within our capability. After a thorough assessment and develop-
mental history, it was fairly clear that a diagnosis of developmental apraxia was
appropriate and the parents and grandparents were informed. Referral was made to
the local early intervention program to begin treatment, consisting of intensive
speech and language therapy. The family was able to supplement the treatment pro-
vided through the program, so the child received treatment several days a week from
providers who had experience in the area. So far, so good.
We have known this family for many years and had permission from the parents
to discuss the case with the grandparents, who were very involved and worried
about what the future may hold. As might be expected, one grandparent asked one
of us and the other asked the other of us. Then one night we all went out to dinner
and were chatting and trying to be supportive when it became obvious that the
grandparents did not receive exactly the same information regarding impact and
prognosis. One of us had described developmental apraxia as an issue of motor
dysregulation emphasizing the development of speech with a good prognosis, albeit
after a long and intensive program of treatment. The other of us, using neural net-
work modeling, had described a more far-reaching disorder, impacting many areas
of development and provided a more circumspect prognosis.
As you might imagine, there was a rather long discussion after we got home, and
we realized that what was true for many things in the world of mental health was
true for developmental apraxia. There wasn’t agreement on what it was other than a
description of behavior, and there were many different opinions about etiology,
comorbidity, and outcome. We began to wonder if what was true about developmen-
tal apraxia was true for the many other acquired apraxias as well. What we have
learned in line with the answers to those questions led to the creation of this book.
To preview what we have found, we would tell you that developmental apraxia is a
very different phenomena from the apraxia acquired during adulthood and perhaps
should be in a separate category by itself. We would also tell you, what husbands
have learned since the beginning of time, that perhaps it is better to listen to the wife
and not argue in the first place.
Introduction: Why Apraxia vii
There were many questions to be answered and many ideas to consider. Some of
these were:
In the instance of an acquired apraxia, Where a lesion to a network
component was the clear culprit, was the site of the lesion important?
Given the fact the apraxia is a complex behavioral dysfunction, usually resulting
from the disruption of a network consisting of interrelated components, it is logical
to assume that the downstream impact would be partially dependent on where in the
system the messaging was disrupted. While all cases of oral motor apraxia would
have the same core central behavior, might there be subtypes with different comor-
bidities dependent on the lesion site? It seemed to us that there might be.
Specifically, as we shall see, lesions to the brain which impair the ability to carry
out simple oral gestures on imitation include the frontal and central opercula, the
anterior insula, and a small area of the first temporal convolution of the left hemi-
sphere. All these areas contribute to the various components of a rather complex
oral motor movement related to speech. The disruption of speech is evident in all the
affected individuals but it is not all that happens. A lesion to the frontal opercula
produces comorbidities of disrupted function different to those that were produced
by a lesion to the anterior insula. Depending on the subnetworks involved, it seemed
likely that there would be numerous subtypes of oral motor apraxia, each with dif-
ferent complexities and with different impact and prognosis.
If one of the issues with developmental apraxia is the absence of an
identifiable lesion, and no observable muscle weakness, what else might
happen to produce the outcome?
What exactly caused developmental apraxia and was it just one thing, which we
considered unlikely, or was it a collection of things? What other issues affect the
ability of a neural network to carry information? What are the factors that impact the
development of a neural network in the first place? Is the prognosis for a network
that never develops at all different from one with only a focal point of damage in an
otherwise fully developed and functional system? For example, human speech
surely is one of the most complex tasks that we humans do and likely involves
numerous networks in its creation, development and expression. Disruption to any
one of those networks might produce the ultimate apraxic condition. The ongoing
question is whether the failure to develop one component of this system would be
more or less disruptive to language functioning as compared to damage to the
same component after the system had been fully functional.
Would a disrupted developmental unfolding of skills imply more complex and
far-reaching comorbidities that a localized lesion in an adult brain?
This question has been around for some time and we are not sure that the argument
about which is better or worse has been settled. We probably won’t settle it either,
but we intend to take a look at it.
How does resiliency and plasticity factor into the equation for developmental
apraxia and acquired apraxia?
Related to the question above, how do resilience and plasticity impact recovery of
function (or development of function)? Are there some areas of the brain that have
the ability to recover or adapt at a better rate than others?
viii Introduction: Why Apraxia
Would the idea of cognitive reserve be an important consideration in adult

acquired apraxia?
Is damage that occurs later in life more impactful because of all the previous life
course incidents that have transpired? What is the impact of a lesion in an already
compromised brain and are some brains more capable of recovering than others?
What factors contribute to the ability to recover?
We will explore these issues and more. We realized that apraxia would be an
ideal way of showing the power of a neural networking model to contribute to the
understanding of a complex disorder. Given our backgrounds, and the circumstances
surrounding the genesis of the book, it would be fair to say that we will have a heavy
emphasis on developmental apraxia of speech. This is probably fair, as it seems to
be the most complex of the issues to discuss. We will discuss in detail the other,
significant numbers of apraxic conditions. You will be excused if you think our
biases are showing, because they are. So, come along and find out why the wife was
right and basing our response on a neural networking model as explained to the
grandparents was the right way to go.
Contents
1 Apraxia, Dyspraxia, and Motor Coordination Disorders:

Definitions and Confounds�� 1
History and Current State of the Study of Apraxia�� 2
Current Definitions�� 4
Definitional Definitions and Confounds in Apraxia Research�� 6
Hypothetical Neural Mechanisms of Apraxia�� 10
Double-Duty Neurons and Apraxia �� 10
Recognized Apraxia Conditions�� 11
Limb-Kinetic Apraxia�� 11
Ideomotor Apraxia �� 12
Conceptual Apraxia�� 12
Ideational Apraxia�� 12
Buccofacial Apraxia�� 13
Constructional Apraxia�� 13
Oculomotor Apraxia�� 14
Orofacial Apraxia�� 15
Verbal Apraxia �� 16
Other Apraxia Conditions�� 16
Acquired Apraxia of Speech (AOS)�� 17
Newer Models of Speech Production�� 17
Childhood Apraxia of Speech�� 18
Neuropsychological Models of Apraxia�� 19
Dual-Stream Models and Types of Apraxia �� 21
References�� 21
2 he Etiology of Apraxia�� 25
T
Genetically Based Apraxia�� 26
Non-stroke-Related Progressive Apraxia of Speech�� 26
Apraxia Associated with Neurodevelopmental Disorders �� 28
Childhood Apraxia of Speech (CAS)�� 29
FOXP2/7q31.1 Deletion�� 30
ix
x Contents
GRIN2A�� 30
SETBP1�� 30
Microdeletions of BCL11A �� 31
KANSL1 or 17q21.31 Microdeletion Koolen-De Vries Syndrome
(KdVS)�� 31
ELKS/ERC1 and 12p13.33 Deletion �� 31
16 p11.2 Deletion�� 31
Corticobasal Degeneration (CBD) �� 32
References�� 33
3 he Human Connectome: An Overview�� 35
T
The Connectome and Neural Networks�� 36
The Importance of Understanding the Connectome�� 37
Hubs �� 37
Networks and Connectomics �� 38
Scaling�� 39
Degeneracy�� 39
Structural Plasticity�� 40
Challenges to Understanding the Connectome�� 40
The Relationship of Connectome to Clinical Diagnosis�� 41
Neural Response to the Disruption of Pathway Function�� 42
Diaschisis �� 42
Transneuronal Degeneration�� 45
Dedifferentiation�� 45
The Neural Networks of Apraxia�� 46
References�� 47
4 euronal Populations, Neural Nodes, and Apraxia�� 49
N
Apraxia and Neural Pathways�� 49
What Is the Neural Population Level? �� 50
Integrating Neural Populations into a Coherent Neural Network�� 51
Glossary �� 53
How the Neural Substrate Enables Integration of Distributed
Neural Information and Thus the Emergence of Coherent
Mental and Cognitive States�� 54
What Is the Interface of Network Structure and Praxis? �� 56
Neural Pathways and Structures Implicated in Apraxia Conditions�� 56
Limb-Kinetic Apraxia�� 56
Ideomotor Apraxia �� 57
Conceptual Apraxia�� 57
Ideational Apraxia�� 58
Buccofacial Apraxia�� 58
Oral Motor and Verbal Apraxia�� 58
Constructional Apraxia�� 58
Childhood Apraxia of Speech�� 59
References�� 61
Contents xi
5 I t Is Not Only Apraxia �� 63

The Structural Beginnings of Brain-Based Behavioral and Cognitive
Connections: A Theoretical Basis�� 63
The Development of Networks�� 64
Feedforward Impact �� 64
The Cerebral Cortex and Basal Ganglia�� 65
Neural Pathways Are Recruited for Multiple Functional Outcomes �� 67
Disruption of Early Domains Are Not Just Domain Specific�� 69
Limb-Kinetic Apraxia and Associated Conditions�� 70
Ideomotor Apraxia and Associated Conditions�� 70
Conceptual Apraxia and Associated Conditions�� 71
Ideational Apraxia and Related Conditions �� 71
Oral Motor and Verbal Apraxia and Related Conditions �� 71
Apraxic Conditions Rarely Occur in Isolation�� 72
White Matter Degeneration Following Injury�� 74
Neural Network Damage Models�� 75
References�� 76
6 evelopmental Coordination Disorder�� 79
D
Developmental Coordination Disorder (DCD)�� 80
The History of Developmental Coordination Disorder�� 80
DCD Early Signs and Phenotypical Presentations�� 81
Genetics Play a Role in Developmental Coordination Disorder�� 84
Neuroimaging and Brain Studies �� 84
DCD and the Impact on Other Neural Substrates�� 87
How Embedded in Other Systems Is the Motor System?�� 87
Motor Networks in the Newborn and Their Involvement
with Later Skills Development�� 90
Functional Expression in Later Development�� 91
Child Development: The Result of the Integration of Movement,
Language, and Cognitive Processes�� 92
When Does the Development of the Motor System Begin?�� 92
References�� 94
7 hildhood Apraxia of Speech�� 97
C
What Is Childhood Apraxia of Speech?�� 97
Is There a Difference Between CAS and Verbal Dyspraxia?�� 99
So, What Can We Definitively Say About the Definition of CAS? �� 100
The Idea of CAS Has Historically Been Controversial �� 100
What Are Some Comorbidity Associations?�� 101
Is CAS Underdiagnosed?�� 101
The Results of Definitional Confusion�� 102
Identifying the Speech Errors that Characterize CAS �� 105
Speech: Structure Versus Function�� 105
Genetics, Language Disorders, and CAS�� 107
References�� 109
xii Contents
8 Neural Network Components of Childhood Apraxia of Speech

and Associated Comorbidities�� 111
Hemispheres and History�� 111
Arcuate Fasciculus �� 112
Interconnections of the Arcuate Fasciculus �� 113
Hemispheres Do Not Operate in Isolation �� 114
Hemispheres and the Three Rs�� 114
The Connectome, Development, and CAS�� 116
CAS Is Multifactorial from a Network Perspective�� 117
The Dual Pathway Model�� 118
The Critical Contribution of the Dorsal Pathway�� 119
Cortical and Subcortical Involvement in Motor Speech�� 121
Prediction Errors and Motor Speech�� 122
Cerebellum and CAS �� 123
Cerebellar Dysfunction and CAS�� 125
Basal Ganglia and Procedural Memory �� 125
Broca’s Area, Basal Ganglia Loops, and the Supplementary
Motor Area (SMA)�� 128
Language and Motor Cortex in the Interpretation of Speech�� 130
In Summary�� 131
The Implications of Bottom-Up Development for the Functional
Implications of CAS�� 132
Treatment of CAS�� 133
9 Neuropsychological Assessment of Apraxia: Where Network
Reality and Domain Assessment Collide�� 139
How Many Domains Are There? �� 140
Domains Are Complex and Subsume Multiple Functions�� 141
Questionable Assumptions Concerning Ability
of Neuropsychological Tests�� 142
Pathognomonic Signs in the Assessment of Apraxia�� 146
Clinical Presentation�� 147
Developmental Apraxia of Speech and Pathognomonic Sign�� 148
What to Do, What to Do?�� 148
10 reatment for Apraxia: Plasticity and Regeneration�� 161
T
Lack of Consensus for the Selection of Treatments for Apraxia �� 162
Classes of Treatment for Apraxia�� 162
Restorative (Restitutive) Treatments�� 162
Compensatory (Substitutive) Treatments�� 163
Assistive Technology �� 163
Treatment Examples�� 163
Neural Plasticity�� 165
Contents xiii
Mechanisms of Neural Plasticity �� 167

Treatment That Supports Neural Plasticity�� 167
Brain Injury, Plasticity, and Functional Recovery �� 168
What Enhances Neural Plasticity? �� 169
Environmental Enrichment and Neural Plasticity�� 169
Regeneration�� 170
Limitations of Plasticity�� 170
Treatment Going Forward: Neurorehabilitation�� 171
11 nderstanding Apraxia Going Forward�� 183
U
The Problem of Diagnosis �� 184
Problems for Neuropsychologists�� 186
Staying in Our Lane �� 187
Understanding Disorders from a Neural Network Perspective�� 188
Network Theory and Complex Networks�� 188
Research Domain Criteria (RDoC) (Insel, 2014)�� 190
Diagnosing Apraxia: Why Make It Complicated? �� 191
Assess It All: Downstream and Upstream Impact of Network
Disruption�� 193
The Case for a Separate Diagnosis for Childhood Apraxia
of Speech�� 194
Genetics�� 195
The Problem of Treatment �� 196
“Testing” for Apraxia �� 197
Appendix I: Network Properties Breakdown of Ideational Apraxia�� 211
Index�� 217
Chapter 1
Apraxia, Dyspraxia, and Motor
Coordination Disorders: Definitions
and Confounds
Providing the reader with a cogent and agreed-upon definition of apraxia would
seem to be a valuable way to start any discussion of apraxia. We have discovered
however, as is the case for other diagnoses, that goal is elusive when discussing
apraxia and particularly so when addressing developmental coordination disorder or
childhood/developmental apraxia of speech. This is not simply a matter of “Let’s
agree to disagree.” The implications are significant. For those readers familiar with
our other work, they will be aware of our concerns with the state of diagnostic speci-
ficity and sensitivity. The implications reach the worlds of clinical psychological
practice, medical practice, neuropsychology, and neurology. Specifically, if we do
not agree about what we are defining, how are we defining, treating, and
researching it?
Before we begin our discussion of apraxia and its various forms, we wish to
highlight that we include developmental coordination disorder (DCD) in our discus-
sions and by extension, what is now a subcategory of DCD as listed in the DSM 5
(APA, 2013), childhood apraxia of speech (CAS). We do this because of the exten-
sive contribution of the motor networks that these disorders share. We do this to
demonstrate how disruption of motor networks is an integral part of what are cur-
rently considered discrete disorders but may in fact represent disruption of a unified
motor system with pervasive implications. We do this because if we can understand
the brain through its development, we should be better able to understand the impli-
cations of a disruption somewhere along the neural network pathways. Therefore,
we start at the beginning, that is, the childhood development of motor-based disor-
ders. The field has begun to understand this position as it has, in the DSM 5, grouped
DCD as a motor disorder. In addition, CAS is a further subcategory of DCD; both
are under the category of motor disorders falling under the larger umbrella of neu-
rodevelopmental disorders.
Although somewhat less so for an acquired apraxia, the definition of what con-
stitutes a given apraxia is often elusive and poorly defined. This may be even more
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 1

T. Wasserman, L. D. Wasserman, Apraxia: The Neural Network Model,
Neural Network Model: Applications and Implications,
https://doi.org/10.1007/978-3-031-24105-5_1
2 1 Apraxia, Dyspraxia, and Motor Coordination Disorders: Definitions and Confounds
so with regard to the etiology. Perhaps a better way to explain the problem is that
there are multiple problems. With regard to specificity, the definitions of apraxia are
largely behaviorally descriptive, but sometimes too confined. And sometimes they
are too ambiguous secondary to a phenotype. Often there is phenotypical overlap
across disorders. In addition, some disorders are based upon the magnitude of effect
(dyspraxia), sometimes.
As you will see, there is a multitude of apraxia, all ostensibly delineated by the
primary area of impact. Traditionally the diagnosis and treatment of apraxia focused
on a highly behaviorally segregated symptom. This is clearly understandable as
from a historical perspective it reflects the early observations of those noting and
then studying these phenomena which became known as apraxia. Early contribu-
tions were foundational; however, they also had a cortical and somewhat modular
bias. It is understood and appreciated that from a current perspective it allows clini-
cians to speak in short hand to each other about what is observable, impacted, and
where to begin intervention. But from a neural network model-based perspective,
there is a different reality: there is a multitude of potential areas of impact and
impacted processes, often treated as dissociable entities, complicated further by
questions about etiology being trauma based, genetic, or developmental. Hence, if
we consider this component, then does a diagnostic label, lacking in specificity, and
often sensitivity, really tell us with what we are dealing, and how to best intervene?
Further confusing the picture is how some of these identified apraxia or dys-
praxia associate with other disorders. This greatly muddles the designs and/or out-
comes of research. For example, it often results in confounds in population samples
which can produce “dubious” findings. An interesting, and we believe important,
observation of the current authors is that research papers often include a section on
“limitations of the study.” We believe that sometimes what is described as the
study’s limitations, rather than being confounds and limitations, are actually a
reflection of the diversity of the disorder, its phenotypical presentations, and mani-
festations across subjects rather than a limitation of the study itself. This point is
elaborated upon as we go through diagnostic research across chapters.
In summary, while the current state of definition might lead one to assume that
the impact is highly specific, in order to diagnose or treat a person impacted by an
apraxia, we must understand that it is not an isolated clinical finding. Humans are
much more sophisticated and the systems much more complicated. Neural network
modeling would have us understand that the impact of the network damage has
implications far in excess of the most obvious symptomology.
History and Current State of the Study of Apraxia
This is an area that has been under study for a long time. Looking at the history, we
can see that the definition of apraxia has evolved. Based upon observed behavior
and conjecture about underlying neurological functioning, the presumed mecha-
nisms initially were really quite different than that of our current understanding.
History and Current State of the Study of Apraxia 3
Assessment of this area began as early as the 1860s with a description of apraxia,
although not labeled as such, provided by John Hughlings Jackson (Pearce, 2009).
In 1871, Steinthal coined the term apraxia from the Greek term apraxia, meaning
inaction. It was assumed that the reason a person may fail to correctly perform pur-
poseful movements was that they were unable to recognize the object/tool associ-
ated with the desired movement (Pearce, 2009). In 1905, Arnold Pick introduced the
concept that the movement failure in apraxia was assumed to result from motor
“agnosia,” or motor manifestations of asymbolia.
Hugo Liepmann presented his first paper on the topic of apraxia in 1900
(Gonzales-Rothi & Heilman, 1996; Pearce, 2009). The paper described deficits of
motor function in a 48-year-old German imperial councilor whose initial presenta-
tion appeared to be dementia. The patient had difficulty with initiation and copying
of gestures, although spontaneous movements, such as using utensils while eating,
were normal. Liepmann suggested a disconnect of the visual, auditory, and somato-
sensory areas from the area of motor cortex, a disconnection of the hemispheres. He
predicted cortical lesions which were confirmed upon autopsy and presented in a
report in 1907. Liepmann’s work led to the conclusions that apraxia was a defect
dependent on lesions in the left hemisphere which contained the memory of skilled
movements. He believed that plan of movement is stored in the dominant left pari-
etal lobe. In order to execute a skilled movement, the space time plan had to be
retrieved, and via cortical connections in the left sensorimotorium (precentral and
postcentral gyri), the information was passed to the left primary motor areas and
then transfer was made through the corpus collosum in order to activate the right
motor cortex. He also concluded that lesions of the corpus callosum interrupted the
process of movement located in the left hemisphere from the motor area located in
the right hemisphere resulting in ideomotor apraxia of the left arm and hand.
Liepmann created categories which included the distinguishing of ideomotor
apraxia wherein the difficulty is with determining the nature of a single movement,
from limb-kinetic apraxia wherein the movements are awkward and slowed, and
ideational apraxia wherein the sequence of movements is disrupted. Liepmann’s
work was foundational, if not completely correct, in correlating cortical anatomy
with behavior. Geschwind who largely supported Liepmann’s ideas, believed the
“analyses of the mechanisms underlying disturbances in motor performances
(Geschwind, 1965) to be of greater importance than the listing of types of apraxia.”
He went on to create his own “disconnexion theory” for limb apraxia embracing
Liepmann’s work and Wernicke’s foundational disconnection theory model for
language.
Despite advances, Pearce (2009) points out that “Recent functional imaging
studies correlated with neuropsychological deficits have not clarified the fundamen-
tal nature of the many different patterns of apraxia in relation to its varied anatomi-
cal lesions.” He also posits that “brain diseases that damage the multiple parallel
parieto-frontal circuits devoted to specific sensorimotor transformations cause dif-
ferent praxis deficits depending on the context in which the movement is preformed
and the cognitive demands of the action.”
Current Definitions
There are currently several definitions of apraxia in use. These definitions revolve
around a couple of central themes. One medical definition of apraxia covers two
aspects: (1) apraxia is a disorder of the brain and nervous system and (2) a disorder
wherein a person is unable to perform tasks or movements when asked, even though
the request or command is understood. They are willing to perform the task and the
muscles needed to perform the task work properly (National Library of Medicine,
2022). However, people with apraxia cannot execute them. This definition goes on
to provide more detail. Apraxia is caused by damage to the brain. When apraxia
develops in a person who was previously able to perform the tasks or abilities, it is
called acquired apraxia. The most common causes of acquired apraxia are:
Brain tumor
Conditions that cause gradual worsening of the brain and nervous system (neurode-
generative illness)
Dementia
Stroke
Traumatic brain injury
Hydrocephalus
There are similar definitions encompassing more or less specificity. For instance,
“Apraxia which is a neurological disorder characterized by loss of the ability to
execute or carry out skilled movements and gestures, despite having the desire and
the physical ability to perform them.” The term “dyspraxia” is used if the presenta-
tion is considered mild. “Apraxia results from dysfunction of the cerebral hemi-
spheres of the brain, especially the parietal lobe, and can arise from many diseases
or damage to the brain” (National Institute of Neurologic Disorders and Strokes,
2022). This casts a wider etiologic net by using the term dysfunction, which can
refer to severity and/or etiology. This definition goes on to talk about difficulty coor-
dinating complex muscle movements to produce an action. Other definitions con-
centrate only on the particular outcome behavior that cannot be performed.
Some other definitions are simpler and often leave out the idea of intentionality
such as the following: “Apraxia is the loss or impairment of the ability to execute
complex coordinated movements without muscular or sensory impairment”
(Merriam-Webster, 2022). This definition leaves out etiology all together and
focuses on phenotype. A similar definitional orientation is provided by the National
Organization for Rare Diseases (2022): “Apraxia is a neurological disorder charac-
terized by the inability to perform learned (familiar) movements on command, even
though the command is understood and there is a willingness to perform the move-
ment.” Both the desire to move and the cognitive comprehension of the directive are
present, but the person simply cannot execute the act.
None of these definitions cover the case of developmental apraxia or childhood
apraxia of speech (CAS). Here, it is possible that a child has not yet developed
speech and it is the development of speech that is being impeded. In addition, as we
Current Definitions 5
write this, the cause of most developmental apraxia conditions is unknown. For
CAS, definitions like this example are common: “Childhood apraxia of speech
(CAS) is an uncommon speech disorder in which a child has difficulty making accu-
rate movements when speaking. In CAS, the brain struggles to develop plans for
speech movement. With this disorder, the speech muscles aren’t weak, but they
don’t perform normally because the brain has difficulty directing or coordinating
the movements” (Mayo Clinic, 2022). This definition, while alluding to brain-based
etiology, largely emphasizes the coordination of the muscle movement on speech.
Is childhood apraxia of speech a developmental disorder we should be defining
based upon the expressed phonology? According to the American Speech-Language-
Hearing Association apraxia may be developmental as in childhood apraxia of
speech, or the result of a medical or traumatic event, which is then an acquired
apraxia (ASHA, 2021; Diehl, 2022). With a concern that people not confuse devel-
opmental as implying a possibility of “outgrowing” the disorder, and stressing the
need for intervention services, ASHA states “Neither disability is something a per-
son will outgrow, or get over, but with careful instruction and hard work, it is both a
hope and belief that people with either disability can learn to work through their
challenges” (ASHA, 2021; Diehl, 2022).
Perhaps the most used definition of apraxia in the neuropsychological and medi-
cal literature was developed by Rothi and Heilman (1997). This definition defines
apraxia “as a neurological disorder of skilled movement that is not explained by
deficits of elemental motor or sensory system.” In other words, apraxia is consid-
ered as being independent from other stroke comorbidity symptoms such as hemi-
plegia (loss of proprioception and motor control over limb on one side) or visual
deficits such as hemianopia or neglect (Bieńkiewicz et al., 2014). Thus, to some
extent, apraxia is a diagnosis of exclusion; you use it when you are not exactly sure
what the specific etiology is.
Developmental coordination disorder (DCD) is another diagnostic category with
much confusion about presentation and etiology. According to the American
Psychiatric Association (APA, 2013), this disorder includes impairment in the
development of motor coordination, wherein “the acquisition and execution of
coordinated motor skills is substantially below that expected” with “difficulties
manifested as clumsiness, as well as slowness and inaccuracy of performance of
motor skills.” This disorder is also referred to in the manual as dyspraxia.
Additionally, these motor difficulties are not related to a medical condition or dis-
ease such as cerebral palsy. The disorder is listed in the DSM 5 under motor disor-
ders, under the larger category of neurodevelopmental disorders. The World Health
Organization (WHO, 1992) largely concurs with this overall definition and indi-
cates that a child with DCD must score two standard deviations below the mean
accompanied by academic and daily living impact. They note that there should not
be neurological disorder. Of course, the exclusion of a neurological disorder as a
prerequisite for being a neurodevelopmental disorder gives one pause.
Further complicating the picture, we should note that the terms apraxia and dys-
praxia are not technically synonymous. Nor are they utilized consistently across the
medical field and area of speech and language. Specifically,
1. In general, dyspraxia refers to the partial loss of the ability to coordinate and
perform skilled, purposeful movements and gestures with normal accuracy.
Apraxia is the term that is used to describe the complete loss of this ability. The
terms are, however, often used interchangeably. In addition, dysfunction of a
movement related to gross or fine motor movements, in isolation or a sequence,
is referred to in the literature as apraxia.
2. In contrast, ASHA utilizes the term dyspraxia to define a developmental disabil-
ity affecting gross and fine motor skills. ASHA utilizes the term apraxia to
describe a speech disability affecting verbal planning. In summary then, accord-
ing to ASHA “while dyspraxia is a broader term used to describe muscle plan-
ning developmental disabilities, apraxia is used to describe muscle planning
needed especially for speech.” Therefore, two professionals, a speech patholo-
gist and a physical therapist, working together on an interdisciplinary team,
would not agree as to the terminology for a child manifesting difficulty with, for
example, independent ambulation or self-care behaviors.
3. And to highlight additional sources of confusion, the term dyspraxia is utilized
in parts of Europe (Kirby, 2007) to describe children with what is generally
known as developmental coordination disorder. In a recent “white paper” on
guidelines for international practice (Blank, 2019), the consensus was for using
the term DCD in countries which follow the DSM 5. In countries which adhere
to the ICD, they recommend the term specific developmental disorder of motor
function.
At this point the reader must be wondering how to follow if we are we talking about
a motor problem or a speech problem, dyspraxia or apraxia? Rightly so. The current
authors utilize the larger medically accepted definition of apraxia as it relates to
gross and fine motor expression. As it relates to speech, the term childhood apraxia
of speech will be utilized.
Finally, we would point out that the definitional distinction between apraxia and
dyspraxia brings up some interesting issues for neural network modeling. At first
glance, one might assume that because the networks involved in both types of prob-
lems are shared, the result should be the same functional deficit, identical as it is
only the degree of disrupted function that is at issue. However, that is not the case
because these networks are complex and disruptions can happen in a number of
locations, thereby altering the final functional behavior and related comorbidities.
To be clear, effect can be in magnitude and/or reach the area of impact.
Definitional Definitions and Confounds in Apraxia Research
While there are some commonalities between current definitions, there are also
some striking differences. For example, consider this definition: “Apraxia desig-
nates the impaired ability to perform a gesture, in spite of preserved motor, somato-
sensory, and coordination functions in the limb engaged in the action” (De Renzi &
Definitional Definitions and Confounds in Apraxia Research 7
Faglioni, 1999). This definition represents a good example of a highly “confined”

definition alluded to previously. It specifies motor-based movement issues for the
research study currently referred to within a particular limb. There are even prob-
lems noted within this limited view as the authors state that “a unitary account of
apraxia and aphasia runs into the same difficulty that undermines the theory of a
common source for praxis skills and handedness, namely the occurrence of disso-
ciations in either direction.” This statement highlights difficulties in partitioning the
symptomology.
Zadikoff and Lang (2005) also take issue with the definition of apraxia noting
“The definition of apraxia specifies that the disturbance of performed skilled move-
ments cannot be explained by the more elemental motor disorders typical of patients
with movement disorders.” These authors go on to point out that “the term ‘apraxia’
has also been applied to other motor disturbances, such as ‘gait apraxia’ and ‘apraxia
of eyelid opening’, are perhaps misnomers, demonstrating the lack of a coherent
nomenclature in this field” (pg. 1480). We concur with their concern.
The authors go on to highlight a common theme when considering apraxia in that
it has a disease or injury emphasis. They note that diseases that cause the combina-
tion of apraxia and a primary movement disorder most often involve corticobasal
degeneration. Corticobasal degeneration is characterized by various apraxia and
particularly affects ideomotor and limb-kinetic apraxia (both of which are described
further on in this chapter) as well as buccofacial and oculomotor apraxia (also
described in this chapter). They point out that corticobasal syndrome may be caused
by a variety of central nervous system disorders such as Alzheimer’s disease,
dementias, and supranuclear palsy. Of importance, supranuclear palsy and
Parkinson’s disease can result in differing or varying degrees of the expression of
apraxia, particularly in those with more severe cognitive dysfunction. Is this then
better described as dyspraxia? Germane to their position on definition and identifi-
cation is that similar presentations of apraxia can involve a variety of cerebral corti-
cal sites as well as basal ganglia structures. This implies that they consider apraxia
and its movement components to possibly be dissociable and highlight the con-
founding that occurs in labeling something an apraxia when the etiology can be
multidetermined or wherein various disorders can produce similar symptomology.
Cassidy (2016) also notes the confusion as a result of how apraxia is defined not-
ing that it is “an inability to perform a motor task that cannot be adequately explained
by motor weakness, sensory loss or a lack of understanding.” This criterion has led
to a plethora of motor disorders being described as forms of apraxia, despite many
of these failing to capture the essence of what apraxia really is: a disorder of motor
cognition. To rectify this situation, greater specificity is proposed leading to a defi-
nition of apraxia that reflects an impairment of the storage and transformation of
motor representations in the brain, either through degradation of the semantic
knowledge of gestures and tool use or through the inability to translate the neural
representations of higher-level goals accurately into lower-level patterns of muscle
activation and inhibition (Cassidy, 2016).
The above only represents the confused state of affairs as regards limb and other
muscle movement disorders. It becomes even more confusing when developmental
disorders are included.
There are definitions of apraxia that include speech difficulties. Some refer to
speech, some to language. These are often regarded as a unique disorder in some
ways. At one recent point, “Apraxia of speech (AOS) has emerged as the term to
describe a motor speech disorder characterized by an impaired ability to coordinate
the sequential, articulatory movements necessary to produce speech sounds” (Ogar
et al., Apraxia of Speech An overview, 2005). Clearly, this definition requires defi-
ciencies in the motor components of speech making the two elements nondissocia-
ble. The authors go on to point out that “confusion in the literature around AOS
stems from the fact that terminology associated with this disorder has varied greatly.
Also, symptoms associated with AOS often co-occur or overlap with those caused
by neuromuscular deficits indicative of the dysarthrias and the linguistic errors asso-
ciated with aphasia” (pg. 427). An example of the overlap is as follows: childhood
dysarthria (CD) or childhood apraxia of speech (CAS) is suspected in children who,
in addition to such errors, have imprecise and/or unstable spatiotemporal distortions
of vowels and consonants, inappropriate prosody, and deficits in voice (Shriberg
et al., 2019).Despite this, the authors insist that “AOS is, however, a distinct motor
speech disorder.” A careful inspection of this definition would note that there were
disorders where speech was disrupted in exactly the same manner that it is with
apraxia, making discriminating between the two conditions a matter of art as
opposed to science. For example, they point out that “AOS is often confused with
conduction aphasia, perhaps because sound level errors (substitutions, additions,
transpositions or omissions) are prominent in both disorders. However, the nature of
errors is thought to be different” (pg. 429). As with the other disorder definitions we
have looked at, this definition is disease or insult based. The authors posit that while
vascular lesions are the most common cause of AOS, the disorder also results from
tumors and trauma.
To put a fine point on this discussion, we offer this from the online medical dic-
tionary which, based on an article from the American Journal of Speech-Language-
Pathology in 2003, provided the following description of the diagnostic problem:
“The diagnostic criteria used to identify developmental apraxia of speech (DAS)
have been at the center of controversy for decades. Despite the difficulty in deter-
mining the characteristics that differentiate DAS from other speech acquisition dis-
orders, many children are identified with this disorder. The current report presents
the criteria used by 75 speech-language pathologists to establish a diagnosis of
DAS. Although 50 different characteristics were identified, 6 of these characteris-
tics accounted for 51.5% of the responses. These characteristics included inconsis-
tent productions, general oral-motor difficulties, groping, inability to imitate sounds,
increasing difficulty with increased utterance length, and poor sequencing of
sounds. These results are consistent with the general ambiguity of the diagnostic
criteria of DAS and suggest that no single deficit is used among clinicians” (The
Medical Dictionary, 2021).
Definitional Definitions and Confounds in Apraxia Research 9
This led to the following definition: “Childhood Apraxia of Speech (CAS) is a

neurological childhood (pediatric) speech sound disorder in which the precision and
consistency of movements underlying speech are impaired in the absence of neuro-
muscular deficits (e.g. abnormal reflexes, abnormal tone). CAS may occur as a
result of known neurological impairment, in association with complex neurobehav-
ioral disorders of known and unknown origin, or as an idiopathic neurogenic speech
sound disorder. The core impairment in planning and/or programming spatiotempo-
ral parameters of movement sequences results in errors in speech sound production
and prosody” (ASHA, 2021).
“An understanding of developmental apraxia depends on consistent utilization of
a group of symptoms for diagnosis so that data-based results can be used to generate
inferences about the disorder” (Davis et al., 1998). This is a point which is also
made and is relevant to the diagnosis of developmental coordination disorder. The
criteria having been outlined above will not be repeated here. However, the current
point, consistency in distinguishing symptoms, is clearly problematic across these
two developmental disorders. In addition, as alluded to by Zadikoff and Lang (2005)
in reference to limb and ideational apraxia, etc., there are problems with confound-
ing variables including symptoms being caused by other disorders (etiology outside
this diagnostic category) and symptoms clouded by other disorders, e.g., separating
speech difficulties from other disorders, causing symptoms which may exacerbate
or confound those of the “identified” neurodevelopmental disorder.
These issues of definition and explanation clearly and succinctly articulate many
of the issues that motivated us to write this book. It suggests that what was called
developmental apraxia, and is now referred to as childhood apraxia of speech, or
developmental coordination disorder may well have been better described as devel-
opmental and, perhaps, represents a distinct and dissociable diagnostic entity.
Which brings us to what we consider a well-taken point, referred to previously
by the current authors and elucidated by Geuze et al. (2015): “Clinical and research
diagnostic criteria serve different purposes.” Clinical issues include “decisions
related to special education, treatment, remedial teaching, and reimbursement of
costs related to services rendered.” Research issues revolve around accurately iden-
tifying an entity, etiology, and presentation rather than a confounded construct. The
current authors would argue that the latter, rather than the former, is critical for
treatment. For example, the successful treatment of an attention-deficit disorder
requires a greater understanding than just the involvement of attention. In fact,
unless one understands the interplay of attention, motivation, reward circuitry, and
attention being specific to task, one is not really possessing a therapeutic under-
standing of the diagnosis.
In summary, it should be apparent that there are multiple definitions of apraxia,
all circulating around a central theme describing an inability to willfully move a
specific muscle group. Within that wide net, there are those disorders that are clearly
related to damage to the neurological integrity of the individual through either dis-
ease or insult and those disorders that are presumed to have damage, although no
damage is identifiable. There is a third group which constitutes disorders for which
there might not be damage from disease or insult at all. Arguably, there is yet a
fourth group for whom the skill never developed and the lack of integrity of the
neurological system is never clearly established.
Hypothetical Neural Mechanisms of Apraxia
Logically, apraxia is likely not a movement disorder with a solitary neurological or

neurobiological etiology. This is because apraxia conditions variously affect behav-
iors in relation to their nature and the modality through which the instructions elicit-
ing the appropriate motor responses are conveyed (De Renzi et al., 1982). This
understanding is increasingly complicated when, by using network modeling, it is
understood that a disruption of function can be caused by problems anywhere in the
network. Apraxia can be modality-specific, that is, contingent upon the selective
severing of a pathway or pathways linking one sensory association area with the
integration center where the movement is constructed. Whether there is one such
center or several is, as we shall see, a matter of conjecture, but it does seem logical
to guess at the likelihood that there are multiple centers representing specific classes
of output (limb movement, speech). It is understandable that in the majority of indi-
viduals, a lesion will result in apraxia appearing in every modality, either because it
destroys the programming center or because it interrupts all the pathways connect-
ing it with other sensory or motor areas. That, however, is not always the case. A
highly discrete injury may isolate a programming center from one type of informa-
tion and render the patient unable to execute the gesture when it is elicited by a
given sensory center but capable of performing it under the guidance of other
modalities.
Conceptually, there may be ways to think about apraxia based upon where the
disruption originates. For example, is there a difference between apraxias which are
caused by a disruption in pathways that supply specific elements of a complex
movement before they are integrated into a whole, as opposed to disruptions for the
pathways carrying the integrated whole to impact movement? What are the implica-
tions of each circumstance for remediation and recovery? Is there a way to concep-
tualize developmental apraxia in a way that does not imply brain injury or damage
to the network system? There are many of these questions that we will attempt to
address as we progress.
Double-Duty Neurons and Apraxia
Double-duty neurons are neurons that subserve more than one function or, to put it
another way, participate in more than one network. For example, processing of spa-
tial and object information is segregated into two discrete cortical visual pathways.
These activities have to be integrated at some point, but it is unclear where this
Recognized Apraxia Conditions 11
information is unified. Research demonstrates that, at least in monkeys, performing

tasks that involve saccadic eye movements, neurons in the tail of the caudate nucleus
(CDt) encode both object-specific and position-specific information of visual
objects. In addition, weak electrical stimulation in the CDt induced saccades, and
CDt neurons became active before saccades to particular positions and particular
objects. These findings suggest that CDt neurons guide saccades to particular visual
objects in particular locations (Tse, 2012). They do double duty. Clearly, injury to
an area such as this would impact more than one function or skill. This would imply
that if a double-duty neuron was injured, more than one function, such as apraxia,
would be implicated. An injury to this area would be unlike an injury to any other
part of the network. Thus, for a subgroup of people, with oral apraxia for example,
the apraxia, even though impacting the same overall network, would be accompa-
nied by other deficits.
Recognized Apraxia Conditions
There is no true consensus on all the different types of apraxia that have been identi-
fied in the literature. There are descriptions based on the dysfunction demonstrated
and some descriptions based on the area of the brain that is damaged, for example,
callosal apraxia (Watson & Heilman, 1983). The following is a list of some of the
most common and well-known apraxic conditions depending on the area of the
body or specific function affected.
Different types of apraxia affect the body in slightly different ways:
• Limb-kinetic apraxia
• Ideomotor apraxia
• Conceptual apraxia
• Ideational apraxia
• Buccofacial apraxia
• Constructional apraxia
• Oculomotor apraxia
• Verbal apraxia
Limb-Kinetic Apraxia
According to Liepmann (Liepmann & Mass, 1907), patients with limb-kinetic

apraxia (LKA) had a loss of upper limb deftness or dexterity. Originally, limb-
kinetic apraxia described a loss of the ability to make precise, independent, but
coordinated finger and hand movements (Foki et al., 2016). The definition has
expanded somewhat and now limb-kinetic apraxia indicates the inability to make
precise or exact movements with a finger, an arm, or a leg. An example of this type
of apraxia would be an individual who was familiar with the use of a wrench but
could not, after a cerebral insult, demonstrate the use of the wrench even when one
was placed in their hands. Limb-kinetic apraxia is frequently demonstrated in
patients with advanced Parkinson’s disease. It has to be delineated from the classical
forms of apraxia, namely, ideomotor and ideational/conceptual apraxia (Zadikoff &
Lang, 2005)
Ideomotor Apraxia
Ideomotor apraxia (IMA) is a disorder characterized by deficits in properly per-

forming tool-use pantomimes (e.g., pretending to use a hammer) and communica-
tive gestures (e.g., waving goodbye). These deficits are typically identified with
movements made to verbal command or imitation (Wheaton & Hallet, 2007). The
movements are spatially incorrect and may be abnormally slow and deliberate. It is
a basic motor coordination deficit, not explainable by more elemental deficits impli-
cating areas such as the cerebellum or corticospinal tract. The distinguishing factor
is that people with the disorder are able to convey knowledge of how to perform a
sequence task (e.g., making a ham sandwich), but they fail to properly order the ele-
ments of the task, for example, missing steps or doing steps out of order.
Conceptual Apraxia
Conceptual apraxia is the cousin of ideational apraxia. They both correspond to a

disruption of the conceptual component of the praxis system (i.e., action semantic
memory). The idea of conceptual apraxia was developed to describe content errors
in single actions, exclusive of sequence errors in multistage actions with tools
(Ochipa et al., 1992). For instance, Barbieiri and De Renzi (1984) report on a patient
who demonstrated eating with a toothbrush and brushing their teeth with a spoon
and a comb. Their inability to use tools could not be explained by a motor produc-
tion deficit that would characterize ideomotor apraxia. Remarkably, although this
person was able to name the tools and point to them on command, they could not
match the tools with the purpose. This set of behaviors hence was considered sug-
gestive of a loss of knowledge related to the use of tools.
Ideational Apraxia
Historically, ideational apraxia was defined as a disturbance in the conceptual orga-

nization of actions. People with ideational apraxia are not impaired in the action
execution per se but demonstrate inappropriate use of objects and may fail in
gesture discrimination and matching tasks. Ideational apraxia is regularly confused

with conceptual apraxia. It is characterized as a failure to sequence task elements
correctly. Conceptual problems are not the main issue. Ideational apraxia was first
assessed by performing purposive sequences of actions that require the use of vari-
ous objects in the correct order, such as starting a plant from a seed. This initial defi-
cit was expanded when it was recognized that ideational apraxia is not only
associated with complex actions but represented a larger deficit comprising the ini-
tiation of single actions. This circumstance is a theme to which we will return.
Network modeling would imply, at least for several apraxia conditions, that there
are far-reaching sequelae than the target and obvious motor movement.
Buccofacial Apraxia
Buccofacial apraxia (also called facial-oral apraxia) is characterized by the inabil-

ity to coordinate and carry out facial and lip movements such as whistling, wink-
ing, coughing, etc. on command. Buccofacial apraxia is considered a specific form
of verbal or speech developmental apraxia. As pertains to the thesis of this book,
there is some interesting research regarding the network characteristics of those
individuals with buccofacial apraxia. Specifically, individuals with buccofacial
apraxia, who are by definition impaired in performing specific gestures as described
above, are also impaired in recognizing sounds specifically linked to human actions
(Pazzaglia et al., 2008). This finding supports research demonstrating that sound-
producing actions are mapped on the same mirror circuits that are activated during
the visual recognition and execution of actions (Tettamanti et al., 2005; Bangert
et al., 2006).
Constructional Apraxia
Constructional apraxia is defined as an inability or difficulty to build, assemble, or

draw objects. It has become increasingly obvious that constructional apraxia is a
heterogeneous construct that can be assessed with very different tasks. These tasks
are not assessing the same thing. The tasks themselves are quite disparate and are
only mildly interconnected. These tasks tap various kinds of visuospatial, percep-
tual, attentional, planning, and motor mechanisms (Gainotti & Trojano, 2018).
Once considered entirely reflective of parietal lobe functioning, it is now recog-
nized that there is a plethora of constructional apraxia conditions reflecting both the
nature of the task itself and the plurality of functions and of processing streams
linking different parts of the parietal lobes to the occipital and frontal lobes
(Fig. 1.1).
Fig. 1.1 Severe

constructional apraxia
demonstrated by the copy
of a simple drawing.
https://www.researchgate.
net/profile/Gianluca-
Floris-2/
publication/221821714/
figure/fig2/
AS:61973700018176
1@1524768223720/
Severe-constructional-
apraxia-demonstrated-by-
the-copy-of-a-simple-
drawing.png
Oculomotor Apraxia
There are several different types of ocular motor apraxia, but all types have a core
group of problems revolving around an inability to move the eyes in a coordinated
fashion. Specifically, people with ocular motor apraxia have difficulty moving their
eyes horizontally and/or quickly. The main difficulty is considered to be saccade
initiation. There is also impaired cancellation of the vestibulo-ocular reflex (VOR).
The vestibulo-ocular reflex stabilizes gaze during head movement, with eye move-
ment due to activation of the vestibular system. The reflex serves to stabilize images
on the retinas of the eye during head movement. Gaze is held steadily on a location
by producing eye movements in the direction opposite that of the head movement.
Affected individuals have to turn their head in order to compensate for the lack
of eye movement initiation to follow an object or see objects in their peripheral
vision, but they often exceed their target. There is controversy regarding whether
OMA should be considered an apraxia, since apraxia is the inability to perform a
learned or skilled motor action to command, and saccade initiation is neither a
learned nor a skilled action (Malkani & Zadikoff, 2011).
In Cogan-type ocular motor apraxia, there is a defect in side-to-side (horizontal)

eye movements. The eyes do not move properly in response to stimuli or volun-
tarily. The disorder manifests in infancy. When impacted infants are asked to fixate
on an object to the side, their eyes will lag and then move in the opposite direction.
In order to compensate for this, the infants will sharply jerk their heads past the
desired object in an effort to bring the eyes to a position where they can see the
stimulus properly. When the eyes fixate on the object, the head will return to its
normal position. These jerking head movements are the most recognizable sign of
Cogan-type ocular motor apraxia. They are usually recognizable 3–4 months after
birth. Before these jerking head movements occur, an infant’s inability to fixate on
an object may sometimes be mistaken for blindness (NORD, 2021).
Type 1
Ataxia-oculomotor apraxia type 1 (AOA1) in most instances has an onset of symp-

toms during childhood. It is an autosomal recessive cerebellar ataxia (ARCA) asso-
ciated with hypoalbuminemia and hypercholesterolemia. Mutations in the APTX
gene have been identified to be responsible for AOA1. Sensorimotor axonal neu-
ropathy, as shown by nerve conduction velocity studies, is usually present. MRI
studies have shown cerebellar atrophy, mild brainstem atrophy, and, in advanced
cases, cortical atrophy associated with the disorder (Tarsy, 2012).
Ataxia-Oculomotor Apraxia Type 2 (AOA2)
This disorder is also known as spinocerebellar ataxia with axonal neuropathy type
2. It appears later in development, usually adolescence. It is characterized by cere-
bellar atrophy and peripheral neuropathy. Alterations in the SETX gene are respon-
sible. AOA2 causes a constellation of difficulties including cerebellar atrophy, loss
of Purkinje cells, and demyelination. In particular, there is a failure of the cerebro-
cerebellar circuit in AOA2. This circuit impact numerous skills related to the coor-
dination of complex cognitive functions such as working memory, executive
functions, speech, and sequence learning.
Orofacial Apraxia
Orofacial apraxia (Gross & Grossman, Update on Apraxia, 2008) is characterized

by an impairment of skilled movements involving the face, mouth, tongue, larynx,
and pharynx (e.g., blowing a kiss). It seems synonymous with Buccofacial apraxia
in most of its aspects. Research has associated orofacial apraxia with inferior fron-
tal, deep frontal white matter, insula, and basal ganglia lesions. As in ideomotor
limb apraxia, automatic movements of the same muscles are often preserved.
Usually, orofacial apraxia coexists with limb apraxia. Based on these observations,
orofacial apraxia has been considered a subtype of ideomotor apraxia. However,
orofacial and limb apraxia are dissociable, suggesting that the neural systems under-
lying these two disorders are at least partially separable.
Verbal Apraxia
Verbal apraxia is mainly described as an inability to respond properly to verbal

commands to make certain movements. It covers a wide range of problems all
related to motor-driven language output, although, as we shall see, there are motor
components to thinking where no language is produced.
Other Apraxia Conditions
Other apraxia conditions have been described. Admittedly, some of these may be
alternative names for other conditions. They are included here because they have
appeared in the literature.
Verbal–Motor Dissociation Apraxia
Individuals with the disorder fail to respond to verbal commands to make move-
ments and, at the same time, demonstrate inability to copy a gesture or posture
demonstrated by an examiner (visual input) or to execute a verbal command (audi-
tory input), even though that person could copy the position in which the examiner
placed their arm (Luzzi et al., 2010). This phenomenon has also been called disso-
ciation apraxia and has also been referred to as disassociation apraxia. Dissociation
is the preferred term. This disorder may be more involved with speech processing
than motor performance (Wheaton & Hallet, 2007). This is an issue to which we
will return as it directly relates to the discussion of developmental apraxia. There
are things that look like movement disorders but may in fact not be.
Tactile Apraxia
Tactile apraxia is a selective disturbance of active touch. Hand skills not related to
object exploration and manipulation are left intact. The disruption of function is not
specific for tool use but affects any use of the hand as a sense organ (Binkofsky
et al., 2001). Tactile apraxia represents a deficit in the programming of exploratory
finger movement-mediated network component located in the parietal lobe. The
comparison with lesions of other regions participating in the cortical network for
tactile exploration reveals that apraxia of exploratory movements in parietal lobe
Newer Models of Speech Production 17
lesions represents a disturbance distinct from elementary motor or sensory

abnormalities.
Of note, given the general orientation of this book, in the haptic domain, a double
dissociation can be proposed on the basis of neurological deficits between tactile
information for action, represented by tactile apraxia, and tactile information for
perception, represented by tactile agnosia. This dissociation comes from different
networks, both involving the anterior intraparietal area of the posterior parietal cor-
tex (Binkofsky et al., 2007). We mention this here only to highlight that disruption
anywhere in a group of interconnected networks can produce a separate and poten-
tially dissociable disruption of behavior that can look like apraxia.
Acquired Apraxia of Speech (AOS)
AOS (Whiteside et al., 2015) is a motor speech disorder that affects the implementa-
tion of articulatory gestures and the fluency and intelligibility of speech. In AOS
speech output is impacted by a range of disturbances that affect intelligibility.
Speech often appears effortful and under conscious control with a corresponding
loss of automaticity in the production of speech. There is often evidence of initiation
difficulties and articulatory groping. Groping involves visible preparatory and
sometimes audible speech movements and gestures. The temporal components of
speech may also be disrupted and features such as the voice onset time patterns of
plosives can be disturbed. A plosive denotes a consonant that is produced by a coor-
dinated stopping of airflow using the lips, teeth, or palate, which is then followed by
a sudden release of air.
Other temporal dimensions of speech can also be affected, with output display-
ing longer intersyllabic pauses, prolonged segment, and syllable durations.
Disrupted prosody is also manifested. Prosody is the patterns of stress and intona-
tion in a language. Furthermore, in AOS, the spatiotemporal dimensions of speech
are affected, and substitutions and distortions of articulatory targets are perceived as
a result of misdirected gestures. Finally, in AOS, the overlap of articulatory gestures
is reduced, resulting in lower levels of coarticulation.
AOS is an example of the wide range of dysfunction that is usually associated
with apraxia conditions. We believe that historically, only one main target symptom
was identified and other symptoms were minimized or ignored. This has led to con-
stricted research in this area.
Newer Models of Speech Production
Newer models of speech production may go a long way in clarifying the nature of
apraxia of speech (Van Der Merwe, 2020). At the current time, the complexity of
motor aspects of speech, particularly motor control, and the incomplete conceptual-
ization of phases in the transformation of the speech code from linguistic symbols
to a code amenable to a motor system tend to obscure the understanding of acquired

apraxia of speech (AOS). Van Der Merwe proposes a four-level framework (FLF) of
speech sensorimotor control which infers a differentiation between speech motor
planning, programming and execution, and locating the locus of disruption in AOS
in the motor planning phase. This suggests that AOS can occur with a disruption of
any one of these phases. As it stands now, terminological confusion and uncertainty
regarding phases in speech motor control still complicate the characteriza-
tion of AOS.
This four-level model differentiates two pre-execution phases and an execution
phase. The first pre-execution phase is controlled by a motor planner and involves a
reverse model, an efference copy, and a forward model for each sound or over
learned utterance. This phase also involves a forward predictive planner which
enables the system to handle the planning of several sounds and to plan coarticula-
tion of sounds. The motor planner is operating on an auxiliary forward model archi-
tecture. AOS is hypothesized as a breakdown at several possible points in the motor
planning phase. The second pre-execution phase is driven by a motor program gen-
erator and predictive controller that is governed by an integral forward model archi-
tecture. The final execution phase is portrayed as being driven by closed loop
control. As we shall see, models such as this correlate well with neural network
modeling and have a lot of diagnostic utility potential.
Childhood Apraxia of Speech
Childhood apraxia of speech (CAS) is a speech disorder, of presumed organic etiol-

ogy, characterized by deficits in planning verbal motor function with poor consis-
tency of oral-motor movements (Iuzzini, Inconsistency of Speech in Children with
Childhood Apraxia of Speech, Phonological Disorders, and Typical Speech, 2012).
In addition to the articulation and phonation problems, children with CAS are
known to have a high cooccurrence of developmental coordination disorder (DCD).
Affected children often have learning problems leading to various developmental
problems including cognitive impairment. Children with CAS also have a higher
risk of persistent reading and spelling disabilities, which in turn affects learning
abilities such as writing or reading. These developmental problems can cause sig-
nificant depression and anxiety, and they often have a low quality of life and lack
self-satisfaction even in adulthood (Yun et al., 2021).
Most apraxia has known network areas which, when damaged, produce the
apraxic condition. CAS does not. It appears as the child develops and there are no
certain indicators. This fact and the rationale that there is a high overlap with devel-
opmental coordination disorder play an important part of the story we intend to tell
in this book. Network disruptions are far reaching and long lasting in their implica-
tions. Understanding this will dramatically alter the way we diagnose and treat these
problems.
It could be argued that there are as many apraxia conditions as there are specific
motor dysfunctions. It could also be argued that there are as many apraxia
Neuropsychological Models of Apraxia 19
conditions as there are potential network sites to be lesioned. Clearly a case can be
made for either of these points of view. What is most accurate to say is that apraxia
emanates from a disruption of the motor circuitry in conjunction with circuitry
related to task-specific behavioral responses or to the motor components of human
functioning. That means that there are a lot of possibilities. In addition, the same
type of disrupted functioning can occur from damage to a number of structures that
are part of the responsible networks. Different lesion sites produce the same apraxia.
Does this situation have relevance for treatment or diagnosis? It might or might not.
As it stands now, most treatment for apraxia involves practice of the desired skill
with the hope of compensation and the creation of new network capacity. Clearly
that’s more difficult to expect in cases where the cause is genetic mutation as
opposed to specific lesion.
Given the fact that the motor components of networks are involved with apraxia
conditions, it is also likely that the sequelae of apraxia are far more reaching than
just the obvious observed movement disorders. We will examine this aspect of
apraxia in more detail.
Neuropsychological Models of Apraxia
Over the years there have been several attempts at developing neuropsychologically
based models that describe apraxia. The following is a brief summary of some of the
major conceptualizations.
Liepmann (1920) hypothesized that the representation of an action, or what he
termed a space-time plan, is retained in whole form, in the left parietal lobe. In order
to execute the action, the space-time plan is retrieved from memory, and, via the left
premotor cortex, plan information is carried to primary motor areas. For example,
for the left arm to perform an action, information crosses via the corpus callosum to
the right premotor areas. According to Liepmann, for patients with ideomotor
apraxia, motor representations and limb kinetics are intact. Their inability to act is
due to the disruption of frontoparietal connections. Ideational apraxia was thought
to result from disruption of action representations in the left parietal lobe and limb-
kinetic apraxia from disruption of “kinesthetic-innervatory engrams” in the left
frontal lobe.
Geschwind (1965) described apraxia of speech as a disconnection between
motor and more posterior language areas. The disruption was hypothesized to
involve the superior longitudinal fasciculus that connects Wernicke’s area to the left
frontal cortex. A lesion in this white matter pathway would compromise perfor-
mance of actions elicited by verbal command but not affect comprehension. To
account for impaired gesture imitation (which does not require intact language
function) in patients with apraxia, Geschwind proposed that visual association areas
and premotor cortex are connected via the same white matter tracts running between
language and motor areas, but this theory remains controversial (Gross & Grossman,
Update on Apraxia, 2008).
Dual-component models of apraxic conditions have been proposed. Heilman and

Rothi (2003) hypothesized anterior execution-production and posterior conceptual-
representational components. Knowledge and representations of objects and actions
are believed to be stored in the left parietal lobe, specifically the angular gyrus and
supramarginal gyrus, and then transformed into a signal by the premotor cortex
(including the supplementary motor area). This signal is then used by motor cortex
to carry out the action. According to the model, damage to anterior regions causes a
gesture production deficit. Individuals with posterior apraxia typically have impaired
movement production as well as difficulty with gesture comprehension and dis-
crimination of well- versus ill-formed gestures.
Buxbaum et al. provide a model where the left inferior parietal lobe and fronto-
parietal information processing system is proposed (Buxbaum et al., 2007).
According to this model, the inferior parietal lobe processes internal representations
of movements and body part position. The frontoparietal processing system is
responsible for spatial-motor transformation. Damage to this component results in
“dynamic apraxia” due to disruption of the process by which gesture representa-
tions, having incorporated information about current and intended body part posi-
tions, are transformed into motor programs for action.
Research on multiple pathways involved in apraxia has grown. Areas of the pari-
etal lobe have been identified that are involved in higher-order information process-
ing and integration. For example, object use involves information processed by the
ventral (occipitotemporal) and dorsal (parietooccipital) streams and that these two
types of information are integrated by the inferior parietal lobe (Gross & Grossman,
Update on Apraxia, 2008). In addition, Goldenberg and Hagmann (1997) found
evidence for impaired manipulation or elaboration of gesture representations in
patients with left angular gyrus lesions.
Gross and Grossman (2008) point out that the discovery of mirror neurons repre-
sents a significant advance in the understanding of how the brain processes action.
Neuronal populations have been identified that are activated when an action is pro-
duced and when an individual observes that same action. They note that these find-
ings may pose a challenge for models stipulating separate structures specialized for
action execution versus action recognition or comprehension. They speculate that
perhaps a new model would have to account for the dissociations between gesture
production and reception seen in individuals with a variety of underlying neuropa-
thologies. The mirror neuron system thus may have a substantial impact on how we
understand the relation between expressive and receptive praxis and how these are
integrated into a larger praxis network.
More recently, multiple pathway models have been proposed (Sperber et al.,
2019). They identified multiple areas that underlie high-order motor control and
participate in the various neural networks involved. These areas include inferior
parietal lobule, precentral gyrus, posterior parts of the middle temporal cortex, and
insula. Further, long association fibers were involved, such as the superior longitu-
dinal fascicle, inferior and superior occipito-frontal fascicle, and uncinated fascicle.
This data suggests multiple networks acting simultaneously to produce the complex
disruption of behavior associated with apraxia.
References 21
Dual-Stream Models and Types of Apraxia
The idea that an apraxic condition can arise from disruption of one of several path-
ways enables us to distinguish different etiologic factors in apraxia. For example,
the dual-stream hypothesis (Goodale & Milner, 1992) has been used to explain
separate categories of disruption depending on the neural network properties of the
information flow. According to this model, ideational apraxia is thought to relate to
a deficit in the concept of a movement (coded in the ventral stream). These patients
have difficulty using objects, sequencing actions to interact with them or pantomim-
ing their use. On the other hand, ideomotor apraxia is thought to arise from prob-
lems in the accurate implementation of movements within the dorsal stream.
Extending on the knowledge, Rounis and Humpreys (2015) developed the affor-
dance competition hypothesis as a way to explain certain apraxic conditions. They
note that one of the limitations in understanding apraxia is the failure by the clinical
literature to draw on knowledge of the factors determining actions in the environ-
ment. The cited work indicates that responses to stimuli are strongly influenced by
the actions that the objects “afford,” based on their physical properties and the inten-
tions of the actor. The concept of affordance postulates that interactive behavior
arises by a process of competition between possible actions elicited by the environ-
ment. “Affordance competition” plays a role in apraxia in that at least some aspects
of apraxia may reflect an abnormal sensitivity to competition when multiple affor-
dances are present and/or a poor ability to exert cognitive control over this competi-
tion occurs. We note that this model coincides nicely with the valuation and
behavioral economic modeling we identify as an essential feature of neural network
operation (Wasserman & Wasserman, 2019, 2020).
References
American Speech Hearing Association (ASHA). (2021). Childhood apraxia of speech. Retrieved
from ASHA / Practice Portal / Clinical Topics /. https://www.asha.org/practice-portal/
clinical-topics/childhood-apraxia-of-speech/
Bangert, M., Peschel, T., Schlaug, G., Rotte, M., Drescher, D., Hinrichs, H., et al. (2006). Shared
networks for auditory and motor processing in professional pianists: Evidence from fMRI con-
junction. Neuroimage, 30, 917–926.
Barbieiri, C., & De Renzi, E. (1984). THE Executive and ideational Components of Apraxia.
Cortex, (1988) 24, 535–542.
Bieńkiewicz, M., Brandi, M. G., Hughes, C., & Hermsdörfer, J. (2014, April 23). The tool in
the brain: Apraxia in ADL. Behavioral and neurological correlates of apraxia in daily living.
Frontiers in Psycholology. https://doi.org/10.3389/fpsyg.2014.00353, online.
Binkofsky, F., Kunesch, E., Classen, J., Seitz, R., & Freund, H. (2001). Tactile apraxia: Unimodal
apractic disorder of tactile object exploration associated with parietal lobe lesions. Rain,
124(1), 132–144. https://doi.org/10.1093/brain/124.1.132
Blank, R. b.-E. (2019). International clinical pactice guidelines on the definition, diagnosis,
assessment, intervention, and psychosocial aspecs of developmental coordination disorder.
Developmental Medicine and Child Neurology, 242–285. https://doi.org/10.1111/dmcn.14132
Buxbaum, L., Kyle, K., Grossman, M., & C. H. (2007). Left inferior parietal representations for
skilled hand-object interactions: evidence from stroke and corticobasal degeneration. Cortex,
43, 411–423.
Cassidy, A. (2016). The clinical assessment of apraxia. Practical Neurology, 16, 317–322.
Davis, B., Jakielski, K., & Marquardt, T. (1998). Developmental apraxia of speech: Determiners
of differential diagnosis. Clinical Linguistics & Phonetics, 12, 25–45. https://doi.
org/10.3109/02699209808985211
De Renzi, E., & Faglioni, P. (1999). Apraxia. In G. Denes & L. Pizzamiglio (Eds.), Handbook of clin-
ical and experimental psychiatry. Psychology Press. https://doi.org/10.4324/9781315791272
De Renzi, E., Faglioni, P., & Sorgato, P. (1982). Modality specific and supramodal mechanisms of
apraxia. Brain, 105, 301–312.
Diehl, E. (2022). Dyspraxia vs. Apraxia. Retrieved from Study.com: https://study.com/academy/
lesson/dyspraxia-vs-apraxia.html
Foki, T., Vanbellingen, C. T., Pirker, A. L., Bohlhalter, S., Nyffeler, T., Kraemmer, J., et al. (2016).
Limb-kinetic apraxia affects activities of daily living in Parkinson’s disease: A multi-center
study. European Journal of Neurology, 23(8), 1301–1307. https://doi.org/10.1111/ene.13021
Gainotti, G., & Trojano, L. (2018). Chapter 16 - Constructional apraxia. In G. Vallar & H. Coslett
(Eds.), Handbook of clinical neurology (Vol. 151, pp. 331–348). Elsevier. https://doi.
org/10.1016/B978-0-444-63622-5.00016-4
Geschwind, N. (1965). Disconnexion syndromes in animals and man. Brain Disconnexion syn-
dromes in animals and man, 237–294, 585–644.
Goldenberg, G., & Hagmann, S. (1997). The meaning of meaningless gestures: a study of visuo-
imitative apraxia. Neuropsychologia, 35, 333–341.
Gonzales-Rothi, L., & Heilman, K. (1996). Liepmann (1900 and 1905): A definition of apraxia
and a model of praxis. In C. Code, Y. Joanette, A. Roch-Lecours, & C. Wallesch (Eds.), Classic
cases in neuropsychology. Psychology Press.
Goodale, M. A., & Milner, D. (1992). Seaparate visual pathways for perception and vision. Trends
in Neuroscience 15, 20–25. https://doi.org/10.1016/0166-2236(92)90344-8
Gross, R., & Grossman, M. (2008). Update on apraxia. Current Neurology and Neuroscience
Reports, 8(6), 490–496. https://doi.org/10.1007/s11910-008-0078-y
Hamilton, J., Haaland, K., Adair, J., & Brandt, J. (2003). Ideomotor limb apraxia in Huntington’s
disease: Implications for corticostriate involvement. Neuropsychologia, 41, 614–621.
Heilman, K., & Rothi, L. (2003). Apraxia. In K. Heilman, & E. Valenstein, Clinical Neuropsychology
(pp. 215–235.). New York: Oxford University Press.
Iuzzini, J. (2012). Inconsistency of speech in children with childhood apraxia of speech, phono-
logical disorders and typical speech. Indiana University ProQuest Dissertations Publishing.
Kirby, A. S. (2007). Children with developmental coordination disorders. Journal of the Royal
Society of Medicine, 182–186.
Liepmann, S., & Mass, O. (1907). Fall von linksseitiger Agraphie und Apraxie bei rechtsseitiger
Lahmung. Journal of Psychology and Neurology, 10, 14.
Luzzi, S., Piccirilli, M., Pessalacia, M., Fabi, K., & Provincialia, L. (2010). Dissociation apraxia
secondary to right premotor stroke. Neuropsychologia, 48(1), 68–76. https://doi.org/10.1016/j.
neuropsychologia.2009.08.010
Malkani, R., & Zadikoff, C. (2011). The apraxias in movement disorders. In N. Galvaez-Jimenez,
P. Tuite, & K. Bhatia (Eds.), Uncommon causes of movement disorders (pp. 35–45). Cambridge
University Press.
Mayo Clinic. (2022). Childhood apraxia of speech. Retrieved from Mayo Clinic: https://www.
mayoclinic.org/diseases-conditions/childhood-apraxia-of-speech/diagnosis-treatment/
drc-20352051
Morgan, A., & Webster, R. (2018). Aetiology of childhood apraxia of speech: A clinical practice
update for paediatricians. Journal of Paediatrics and Child Health, 54, 1090–1095. https://doi.
org/10.1111/jpc.14150
References 23
NORD. (2021). Ocular Motor Apraxia, Cogan Type. Retrieved from National Organization of
Rare Disorders. https://rarediseases.org/rare-diseases/ocular-motor-apraxia-cogan-type/
Ochipa, C., Rothi, L. J., & Heilman, K. M. (1992). Conceptual apraxia in Alzheimer’s disease.
Brain, 115(Pt 4), 1061–1071.
Ogar, J., Slama, H., Dronkers, N., Amici, S., & Gorno-Tempini, M. (2005). Apraxia of speech: An
overview. Neurocase, 11, 427–432. https://doi.org/10.1080/13554790500263529
Pazzaglia, M., Pizzamiglio, L., Pes, E., & Aglioti, S. (2008). The sound of actions in apraxia.
Current Biology, 18(22), 1766–1772. https://doi.org/10.1016/j.cub.2008.09.061
Pearce, J. (2009). Hugo Karl Liepmann and apraxia. Clinical Medicine, 466–470.
Rothi, L., & Heilman, K. (1997). Apraxia: The Neuropsychology of Action. Hove, UK:
Psychology Press.
Rounis, E., & Humpreys, G. (2015). Limb apraxia and the “affordance competition hypothesis”.
Frontiers Human. Neuroscience, 28, online, https://doi.org/10.3389/fnhum.2015.00429
Shriberg, L., KwiatkowskiI, J., & Mabie, H. (2019). Estimates of the prevalence of motor speech
disorders in children with idiopathic speech delay. Clinical Linguistics & Phonetics, 33,
679–706. https://doi.org/10.1080/02699206.2019.1595731
Sperber, C., Weisen, D., Goldenberg, G., & Karnath, H. (2019). The network underlying human
higher-order motor control: Insights from machine learning-based lesion-behaviour mapping
inApraxia. Tübingen, Germany: bioRxiv https://doi.org/10.1101/536391
Tarsy, D. (2012). Movement disorders: A video atlas. Humana Press.
Tettamanti, M., Buccino, G., Saccuman, M., Gallese, V., Danna, M., Scifo, P., et al. (2005).
Listening to action-related sentences activates fronto-parietal motor circuits. Journal of
Cognitive Neuroscience, 17, 273–281.
The Medical Dictionary. (2021). Apraxia. Retrieved from The Medical Dictionary. http://the-
medical-dictionary.com/apraxia_article_2.htm
Tse, M. (2012). Double duty of tail caudate nucleus neurons. Nature Reviews Neuroscience, 13,
11005–11016. https://doi.org/10.1038/nrn3342
Van Der Merwe, A. (2020). New perspectives on speech motor planning and programming in the
context of the four- level model and its implications for understanding the pathophysiology
underlying apraxia of speech and other motor speech disorders. Aphasiology, online, https://
doi.org/10.1080/02687038.2020.1765306
Wasserman, T., & Wasserman, L. D. (2019). Therapy and the Neural Network Model. Wsitzerland:
Springer.
Wasserman, T. W. (2020). Motivation, Effort and the Neural Network Model. Switzerland:
Springer.
Watson, R., & Heilman, K. (1983). Callosal apraxia. Brain, 106(2), 391–403. https://doi.
org/10.1093/brain/106.2.391
Wheaton, L., & Hallet, M. (2007). Ideomotor apraxia: A review. Journal of the Neurological
Sciences, 260, 1–8. https://doi.org/10.1016/j.jns.2007.04.014
Whiteside, S., Dyson, L., Cowell, P., & Varley, R. (2015). The relationship between apraxia of
speech and oral apraxia: Association or dissociation? Archives of Clinical Neuropsychology,
30(7), 670–682. https://doi.org/10.1093/arclin/acv051
WHO, W. H. (1992). World Health Organization Classification of Mental and Behavioural
Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva.
Yun, J., Shin, S., & Son, S. (2021). Clinical utility of repeated urimal test of articulation and
phonation for patients with childhood apraxia of speech. Children, 8(12), 1–7. https://doi.
org/10.3390/children8121106
Zadikoff, C. L., & Lang, A. (2005). Apraxia in movement disorders. Brain, 128(7), 1480–1497.
https://doi.org/10.1093/brain/awh560
Chapter 2
The Etiology of Apraxia
Apraxia can be caused by congenital or idiopathic means, by trauma such as stroke,

as part of a neurodevelopmental disorder or associated with a neurodegenerative
disorder. Left hemispheric brain damage caused by ischemic or hemorrhagic stroke
is the most frequent neurological correlate of apraxia. Apraxia conditions can be
also observed in numerous neurodegenerative disorders such as Parkinson’s dis-
ease, Alzheimer’s disease, or posterior cortical atrophy. Apraxic behavior is also
known or occur as an effect of trauma such as anoxia and infection such as herpes
encephalitis (Bieńkiewicz et al., 2014).
Thus, the etiology of apraxia can be understood as either network insult (stroke,
penetrating wound, head injury, etc.) or genetic and related constitutional factors.
Research has demonstrated that more than 33 percent of left hemispheric stroke
patients in rehabilitation centers present some form of apraxia (Donkervoort &
Deelman, 2000). Stroke or other brain injuries are the most frequent causes of
apraxia of speech (Duffy, 2012). On face value it might seem that childhood apraxia
of speech (not to be confused with apraxia of speech) would be the almost sole
occupant of the genetic category, while almost every other apraxia would inhabit the
insult category. To an extent that statement remains largely accurate, although not
entirely so. As noted, apraxia also co-occurs with a number of genetically based
neurodegenerative disorders although the frequency of apraxia in these genetic con-
ditions is much lower than that of the brain insult category. These disorders produce
numerous symptoms related to the degradation of the neural network. Among those
symptoms are often apraxia. When movement disorders co-occur with known
genetic movement disorder etiology, they are frequently labeled something other
than apraxia.
What is true for movement disorders in general is also true of apraxia of speech.
As it currently stands, the most current and widely accepted defining clinical fea-
tures of apraxia of speech (AOS) are still not associated with any specific etiology.
That being said, stroke is the most frequent cause of AOS and the most frequent

26 2 The Etiology of Apraxia
etiology reported in the vast majority of historic and recently published studies from
which its diagnostic criteria have evolved (Duffy, 2012), Among nondegenerative
etiologies, stroke is also more likely to induce AOS in a predominant or “pure”
form, without the “contaminating” cognitive deficits or other motor speech disor-
ders induced by diffuse or multifocal conditions such as infection or trauma.
Genetically Based Apraxia
Another useful distinction occurs when confronting apraxic conditions that arise in
isolation, free of comorbidity from those apraxic conditions that occur because of
some general neurodegenerative process or disease. Looking at these disorders
might provide crucial details regarding the network components of many apraxic
conditions. In this chapter we will look at the known etiologies of apraxia and dis-
cuss the network implications.
Non-stroke-Related Progressive Apraxia of Speech
It has been recognized that AOS can be caused by neurodegenerative conditions that
emerge insidiously and progress slowly. In some cases, AOS is the only, or the most
prominent, indicator of neurodegenerative disease, or, in the alternative, it is the
major communication disorder when it coexists with primary progressive aphasia.
Progressive apraxia of speech (PAOS) is a neurodegenerative syndrome affecting
spoken communication (Josephs et al., 2021). It was first described in 1967 (Darley,
1967) as a motor speech disorder characterized by varying combinations of slow
speaking rate, abnormal prosody, speech sound simplifications, distorted sound sub-
stitutions, additions, repetitions, prolongations as well as segmentations between
syllables and words, and groping and trial-and-error articulatory movements.
Stroke-related AOS is generally described as improving over time and will be
discussed in a separate section. In the past three decades, a subtype of AOS has been
identified that is very subtle in onset and progressive in nature (Deramecourt, 2010).
This progressive AOS (PAOS) is frequently associated with progressive agrammatic
aphasia (Ogar et al., 2007) (AOS-PAA) or occurs as a feature of a more widespread
neurodegenerative syndrome, such as corticobasal syndrome (CBS) or amyotrophic
lateral sclerosis. The term primary progressive apraxia of speech (PPAOS) was later
developed to describe PAOS in the absence of aphasia and not embedded as a fea-
ture of a larger neurodegenerative syndrome (Duffy, 2006). The syndrome of PPAOS
was later more fully characterized and shown to relate to degeneration of a network
of regions that include the lateral premotor cortex and supplementary motor area
(SMA) (Josephs et al., 2012). The prevalence of PAOS, which encompasses PPAOS,
has been estimated to be about 4.4 per 100,000 individuals.
Non-stroke-Related Progressive Apraxia of Speech 27
Two types of PAOS have been described (Josephs, 2014). Type 1, the phonetic
subtype, is characterized by a predominance of articulatory distortions, distorted
sound substitutions or additions, and articulatory groping. This is the subtype that is
similar to what has been reported in patients with stroke. The second, type 2, the
prosodic subtype, is characterized by a predominance of slow speech rate and seg-
mentation within multi-syllabic words or across words. Type 2 has not been
described in stroke patients and was not previously formally identified. Features
supporting the validity of PAOS subtypes include the phonetic subtype being asso-
ciated with a significantly younger age at onset and more likely accompanied by
moderate to severe aphasia than the prosodic subtype. In fact, the literature describ-
ing PAOS accompanying aphasia, or AOS embedded in the context of a neurode-
generative syndrome, almost always reveals characteristics consistent with phonetic
AOS. Structurally, PAOS subtypes involve degeneration of the lateral premotor and
SMA, although the phonetic subtype appears to be more strongly linked to neocor-
tex while the prosodic subtype has been linked to noncortical regions, such as the
superior cerebellar peduncle (Utianski et al., 2018).
Research (Josephs et al., 2021) clearly indicates a genetic etiology for both PAOS
subtypes. PAOS is most often associated with a 4R tauopathy when it exists in isola-
tion or when it co-exists with aphasia. Four-repeat (4R-) tauopathies are a group of
neurodegenerative diseases The spectrum of tauopathy encompasses heterogenous
group of neurodegenerative disorders characterized by neural or glial deposition of
pathological protein tau. Clinically they can present as cognitive syndromes, move-
ment disorders, or motor neuron disease (Ganguly & Jog, 2020). On the contrary,
when AOS accompanies behavioral dyscontrol, executive dysfunction, or features
of motor neuron disease, the underlying pathology is heterogeneous, less commonly
4R tau, and may be related to a mutation in the GRN gene.
For our discussion here the point is that there is a heterogeneous group of hypoth-
esized genetic disorders that produce these conditions. The disease leaves a discern-
able footprint in terms of tau deposition on white matter and the result is apraxia that
on one hand replicates what is usually seen in brain injured patients and on the other
hand is unique. These are serious degenerative disorders and cause progressive dys-
function which makes them very different from what is understood to be general
apraxia. The disorders impact white matter functionality and resulting neural net-
work operation.
In 1952, Cogan (1952) described an apraxia wherein the person was unable to
initiate voluntary horizontal saccades. Head thrusts were utilized to facilitate the
necessary ocular refixation. He termed this ocular motor apraxia (OMA). OMA
may be congenital or acquired and idiopathic or associated with structural brain-
based abnormalities (such as cerebellar hypoplasia or agenesis of the corpus callo-
sum). In a study by Marr et al. (2005), a retrospective review of 34 children with
OMA was conducted. The OMA was categorized into four categories outlined
above. For three of the five children with acquired OMA, the impact was transitory
and the conditions were resolved. For the other two children, progressive deteriora-
tion over time was noted. Twenty-nine children were diagnosed with congenital
OMA. Fourteen of these children were diagnosed with isolated/idiopathic OMA
(normal birth and early history). Of the 14 children with congenital OMA without
associated abnormalities, all the children were found to have motor, language, edu-
cational, and/or behavioral problems. Fifteen of the twenty-nine children with con-
genital OMA were found to have associated abnormalities including seven with
structural abnormalities, six with perinatal insult, and two with a neurodegenerative
disorder. The most frequent finding was cerebellar hypoplasia. Historically, non-
idiopathic OMA was associated with neurodevelopmental disorders, and so risk
factors are associated with the underlying disorder, whereas children with idiopathic
OMA were considered to carry a limited neurological risk prognosis. The current
study, in contrast, concluded that for most, cerebellar involvement will be found.
Additionally, irrespective of labeled domain, all groups run a substantial risk of
neurodevelopmental disorders.
Advances in genetics have allowed for greater demarcation of some disorders.
Oculomotor apraxia mapped to chromosome 2p13 is a dominant genetic trait. In
this case, only a single copy of an abnormal gene, that is, from either the mother or
the father, is necessary to cause the emergence of the disease.
Ataxia with ocular motor apraxia type 1 (AOA1) associated with cerebellar
ataxia is an autosomal recessive cerebellar ataxia (ARCA) associated with oculo-
motor apraxia, hypoalbuminemia, and hypercholesterolemia. The gene APTX,
which encodes aprataxin, has been identified (Le Ber et al., 2003). Apraxic dysfunc-
tion occurs in the vast majority, but not all, of affected individuals. This is one of a
number of disorders which have apraxic dysfunction associated with it.
A related condition, ataxia with oculomotor apraxia type 2 (AOA2), is a rela-
tively recently described autosomal recessive cerebellar ataxia (ARCA) defined by
genetic location to 9q34. It is characterized by onset between the age of 10 and
22 years, cerebellar atrophy, peripheral neuropathy, and oculomotor apraxia. The
original research described just six families sharing gait ataxia, oculomotor apraxia,
and/or elevated α-foetoprotein (AFP) levels (Le Ber et al., 2004). Again, not all
families with the genetic disruption produce an apraxia, so the exact nature of the
process remains undetected. However, if Marr et al.’s (2005) data are predictive,
undetected does not mean without consequence.
Apraxia Associated with Neurodevelopmental Disorders
Looking at white matter implications of neurodegenerative disease can provide a

model to understand how a condition such as childhood apraxia might develop and
help understand how specific damage to white matter produces apraxia.
One such disorder is Friedreich ataxia (FRDA). It is the most common autosomal
recessive neurodegenerative disease among Europeans and people of European
descent. Friedreich ataxia is characterized by an early onset (usually before the age
of 25), progressive ataxia, sensory loss, absence of tendon reflexes, and pyramidal
Childhood Apraxia of Speech (CAS) 29
weakness of the legs (Date et al., 2001). It is linked to chromosome 9p13. Ocular
motor apraxia is often associated with this disorder. In FRDA, the proprioceptive
system appears to be affected early, with reduced number of dorsal root ganglion
(DRG) cells mediating proprioception and of their large, myelinated axons in
peripheral nerves, dorsal roots, and dorsal columns of the spinal cord. At the same
time, the dorsal spinocerebellar tracts, relaying proprioceptive information to the
cerebellum, are affected. Somewhat later in the disease, the dentate nucleus of the
cerebellum and, to some degree, the corticospinal tracts degenerate.
Ataxia oculomotor apraxia-1 (AOA1) is a neurological disorder caused by muta-
tions in the gene (APTX) encoding aprataxin (Ahel et al., 2006). It is also the
apraxia most often associated with FRDA. As such, the white matter pathways
would be the same. It is important to note that cases of oculomotor apraxia have
been caused by both stroke and tumor although the foci of damage would arguably
be the same.
Motor neuron disease (MND) is a neurodegenerative disease that typically
affects the upper motor neuron (UMN) and lower motor neuron (LMN) systems,
with subsequent symptoms and signs of spasticity and flaccid weakness. It usually
begins with limb involvement, but in about one quarter of cases, dysarthria is its first
manifestation. Its most serious representative disorder is amyotrophic lateral sclero-
sis (ALS) (Duffy et al., 2007). Apraxic symptomology usually involves poor initia-
tion of speech or stuttering as part of the overall clinical picture.
Moebius syndrome is a rare congenital disorder that results from underdevelop-
ment of the facial nerves that control some of the eye movements and facial expres-
sions. The condition can also affect the nerves responsible for speech, chewing,
and swallowing. Related symptoms can include severe congenital hypotonia, facial
diplegia, jaw ankylosis, velopharyngeal incoordination, pyramidal tract signs, and
ocular motor apraxia. Research demonstrates neuronal depletion of the IV, VII,
VIII, and IX cranial nerve nuclei and intact morphology of the cerebral hemi-
spheres. If the 7th nerve is involved, an individual with Moebius syndrome is
unable to smile, frown, pucker the lips, raise the eyebrows, or close the eyelids. If
the 6th nerve is affected, the eye cannot turn outward past the midline. Other
abnormalities include underdevelopment of the pectoral muscles and defects of the
limbs. When ocular motor apraxia is present, most of the nerve disruption occurs
in the brain stem (Roig et al., 2003). A genetic etiology is suspected but not clearly
established.
Childhood Apraxia of Speech (CAS)
The vast majority of cases of childhood apraxia of speech remain of uncertain etiol-
ogy. There are, however, recently identified genetic anomalies that have been shown
to produce the condition (Morgan & Webster, 2018). Among these are the following.
FOXP2/7q31.1 Deletion
FOXP2 was the first gene implicated in the absence of frank neurological lesion,
intellectual impairment, or other overt neurodevelopmental conditions. There are de
novo and inherited forms of the heterozygous FOXP2 mutations pathogenic for
CAS. Both have been reported. Individuals with the underlying genetic alteration of
“FOXP2-only” typically have a spared nonverbal intelligence compared to verbal
intelligence, appropriate social abilities, and typical fine and gross motor skills. This
being said mild cognitive impairment, mild motor impairments, autistic features
(but not a formal autism spectrum disorder (ASD) diagnosis), and even mild dys-
morphology (e.g., narrow palpebral fissures, mild finger pads, horizontal eyebrows,
large ears) have recently been reported in some cases with FOXP2-only mutations.
By contrast, individuals with FOXP2-plus genetic aberrations are more likely to
have global developmental and behavioral issues with oral-motor deficits, global
developmental delay, and ASD in addition to CAS. These additional phenotypes
may relate to disruptions of other genes neighboring FOXP2 in that region of chro-
mosome 7.
GRIN2A
GRIN2A has been long associated with speech and language disorders, particularly
aphasia. Recently, mutations or very small deletions in GRIN2A have been identi-
fied in patients with both focal epilepsy and speech and language dysfunction
(Carvill et al., 2013). In CAS, dysarthria and oral-motor impairments have been
consistently reported across families regardless of the associated form of epilepsy.
The speech phenotype may also occur in the absence of a seizure disorder, implying
an important role for GRIN2A in speech-motor function or CAS.
SETBP1
Chromosomal deletions and truncating mutations in SETBP1 are associated with

loss-of-function mutations with impaired expressive speech, relatively intact recep-
tive language abilities, decreased fine motor skills, hyperactivity/ADHD, autistic
traits, and subtle dysmorphism (Coe et al., 2014). The phenotype has been expanded
to specify broader neurodevelopmental phenotypes in children seen with childhood
apraxia of speech.
Childhood Apraxia of Speech (CAS) 31
Microdeletions of BCL11A
Microdeletions of BCL11A have been reported in association with CAS, dysarthria,

hypotonia, and general oral and gross motor dyspraxia. Associated features include
intellectual disability (ID) with related poor expressive language, growth retarda-
tion, ASD, craniofacial and skeletal dysmorphic traits, internal organ defects, abnor-
mal muscle tone, and gross motor delays.
ANSL1 or 17q21.31 Microdeletion Koolen-De Vries

K
Syndrome (KdVS)
This is a rare multi-system disorder associated with developmental delay, ID, hypo-
tonia, and facial dysmorphism. Speech development is impaired for children with
KdVS, particularly early in the developmental course. Early history includes hypo-
tonia, feeding difficulties, and delayed onset of first words, occurring between 2.5
and 3.5 years of age (Morgan & Webster, 2018). Almost all children with KdVS
receive a diagnosis of CAS, which is often comorbid with dysarthria and additional
articulation and phonological errors.
ELKS/ERC1 and 12p13.33 Deletion
This is a very rare deletion with a hypothetical relationship to CAS. Affected chil-
dren display delayed first words (36–42 months), delayed walking, and prominent
ear lobes. The primary study identified nine children with the deletion, five of which
displayed CAS (Thevenon et al. 2013). To presage a later discussion, the children
also demonstrated neurodevelopmental disorders beyond speech and language,
including intellectual impairment (5/9), psychiatric manifestations (5/9), behavioral
difficulties (7/9), ADHD (6/9), and ASD (2/9).
16p11.2 Deletion
The 16p11.2 is a relatively common deletion of about 1 in 5000 individuals. It can

occur either de novo or in inherited variants. Associated features include moderate
ID, ASD, poor cognitive and language ability, epilepsy, and macrocephaly. Other
brain abnormalities such as Chiari type 1 malformations or cerebellar ectopia have
been identified. Research have also confirmed the high penetrance of CAS in chil-
dren with this deletion (Mei et al. 2018). Of note, other speech profiles have also
been reported in 16p11.2 deletion in addition to CAS, including articulation and
phonological disorders, dysarthria, and minimal verbal output.
Corticobasal Degeneration (CBD)
Ideomotor apraxia occurs in corticobasal degeneration (CBD), a neurodegenerative

condition described as an asymmetric akinetic-rigid syndrome with cortical features
such as apraxia as well as the alien-limb phenomenon and cortical sensory loss.
Murray et al. (2015) showed that 40% of studied CBD patients had apraxia at dis-
ease onset, and 72% had apraxia at the time of death. Patients had predominantly
ideomotor limb apraxia, and fewer exhibited orofacial apraxia. CBD is character-
ized by atrophy and decreased metabolism in the network of frontal, parietal, and
basal ganglia structures thought to underlie apraxic conditions (Gross &
Grossman, 2008).
In addition to CBD, apraxia is also a component of various movement disorders,
Parkinson’s disease (Soliveri et al., 2005), progressive supranuclear palsy (Soliveri
et al., 2005), and Huntington’s disease (Hamilton et al., 2003), All of these disorders
compromise the basal ganglia. Proposed contributions of the basal ganglia to praxis
include sequencing, fine tuning of movements, selection of competing motor pro-
grams, and performance of automatic or overlearned movements (Gross &
Grossman, 2008). Interestingly, it is not clear that basal ganglia-specific dysfunc-
tion causes significant apraxia. Most cases of apraxia also involve the surrounding
white matter tracts and frontoparietal cortex.
There is a syndrome of parkinsonism and prominent apraxia which have been
designated as “corticobasal syndrome” (CBS). CBS may be occurring in a variety
of other central nervous system pathologies including progressive supranuclear
palsy (PSP), Alzheimer’s disease, dementia with Lewy bodies, and frontotemporal
dementias (Zadikof & Lang, 2005). In patients with left hemispheric stroke, for
example, apraxia has been reported to be prevalent in approximately one-third of
this population (Park, 2017).
Distinct from the CBS, Parkinson’s disease can also demonstrate degrees of
apraxia on selected tasks, especially in those patients whose cognitive functioning
is also severely compromised. Diseases that cause the combination of apraxia and a
primary movement disorder most often involve a variety of cerebral cortical sites as
well as basal ganglia structures. Clinical-pathological correlates and functional
imaging studies are confounded by both this diffuse involvement and the confusion
experienced in the clinical evaluation of apraxia in the face of the additional ele-
mental movement disorders. As far as a clear understanding of the apraxic elements
of these disorders, it should be recalled that the definition of apraxia specifies that
the disturbance of performed skilled movements cannot be explained by the more
elemental motor disorders typical of patients with movement disorders. In many
instances, this does not present a significant diagnostic problem when dealing with
“higher-level” apraxic disturbances (e.g., ideational apraxia), but it can be a major
confound in establishing the presence of limb-kinetic apraxia. The great majority of
motor disturbances characteristic of extrapyramidal disorders, particularly bradyki-
nesia and dystonia, will compromise the ability to establish the presence of loss of
dexterity and deftness that constitutes this subtype. The term “apraxia” has also
References 33
been applied to other motor disturbances, such as “gait apraxia” and “apraxia of
eyelid opening,” which, while clearly associated with parkinsonism, are perhaps
misnomers (Zadikof & Lang, 2005). This situation again demonstrates the lack of a
coherent nomenclature in this field, a situation we will review in detail later.
The above is not an exhaustive review. The sections and examples are presented
to make the point that apraxia, or apraxia-like behavior, can and does occur when
the white matter that controls related motor movement is disrupted. Any disorder
that disturbs the related white matter has the potential to produce an apraxic condi-
tion. Of note, this same functional disorder, apraxia, may occur in a child born with
a congenital disorder, resulting in damage to the child’s central nervous system, as
well as to the adult with a degenerative disorder, such as dementia. It leaves open the
possibility that one day the term apraxia, as a free-standing diagnosis, will be unnec-
essary as we will understand all of the neurophysiological causes of the various
movement disorders.
References
Ahel, I., Rass, U., El-Khamisy, S., Katyal, S., Celements, P., Mckinnon, P., et al. (2006). The neu-
rodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates. Nature,
443|12, 713-716. https://doi.org/10.1038/nature05164
Carvill, G., et al. (2013) GRIN2A mutations cause epilepsy-aphasia spectrum disorders. Nature
Genetics, 45, 1073–1076. https://doi.org/10.1038/ng.2727
Coe, B., Witherspoon, K., Rosenfeld, J., et al. (2014). Refining analyses of copy number variation
identifies specific genes associated with developmental delay. Nature Genetics, 46, 1053–1017.
Cogan, D. (1952). A type of congenital ocular motor apraxia presenting jerky head movements.
Transactions of the American Academy of Ophthalmology and Otolaryngology, 56, 579–588.
Darley, F. (1967). Lacunae and research approaches to them. In C. Miliken & F. Darley (Eds.),
Brain mechanisms underlying speech and language. Grune & Stratton.
Date, H., et al. (2001). Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is
caused by mutations in a new HIT superfamily gene. Nature Genetics, 29, 184–188. https://
doi.org/10.1038/ng1001-184
Deramecourt, V. (2010). Prediction of pathology in primary progressive language and speech dis-
orders. Neurology, 74, 42–49.
Donkervoort, M.-S., & Deelman, B. (2000). Prevalence of apraxia among patients with a first left
hemisphere stroke in rehabilitation centres and nursing homes. Clinical Rehabilitation, 14(2),
130–136.
Duffy, J. (2006). Apraxia of speech in degenerative neurologic disease. Aphasiology, 20, 511–527.
Duffy, J. R., Peach, R. K., & Strand, E. A. (2007). Progressive apraxia of speech as a sign of motor
neuron disease. American Journal of Speech and Language Pathology 16, 198–298.
Duffy, J. J. (2012). The diagnosis and understanding of apraxia of speech: Why including neurode-
generative etiologies may be important. Journal of Speech, Language and Hearing Research,
55(5), S1518–S1522. https://doi.org/10.1044/1092-4388(2012/11-0309)
Ganguly, J., & Jog, M. (2020). Tauopathy and movement disorders—unveiling the chameleons and
mimics. Frontiers in Neurology: Movement Disorders, 11, 599384. https://doi.org/10.3389/
fneur.2020.599384
Josephs, K. A., et al. (2012). Characterizing a neurodegenerative syndrome: primary progressive
apraxia of speech. Brain, 135, 1522–1536.
Josephs, K. A. (2014). The evolution of primary progressive apraxia of speech. Brain, 137,
2783–2795.
Josephs, K., Duffy, J., & Whirwell, J., et al. (2021). A molecular pathology, neurobiology, biochemi-
cal, genetic and neuroimaging study of progressive apraxia of speech. Nature Communications,
12, 3452. https://doi.org/10.1038/s41467-021-23687-8
Le Ber, I., et al. (2003). Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic
studies. Brain, 126(12), 2761–2772. https://doi.org/10.1093/brain/awg283
Le Ber, I., et al. (2004) Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2:
a clinical and genetic study in 18 patients Brain 127(Pt 4), 759–767. https://doi.org/10.1093/
brain/awh080. Epub 2004 Jan 21.
Marr, J., et al. (2005). Neurodevelopmental implications of ocular motor apraxia. Developmental
Medicine. https://doi.org/10.1111/j.1469-8749.2005.tb01086.x
Mei, S., Montanari, A., Nguyen, P. (2018). A mean field view of the landscapre of two layer neural
networks PNAS https://doi.org/10.1073/pnas.1806579115
Murray, E., McCabe, P., & Ballard, K. J. (2015). A randomized controlled trial for children
with childhood apraxia of speech comparing Rapid Syllable Transition treatment and the
Nuffield. Journal of Speech, Language, and Hearing Research, 58, 669–686. https://doi.
org/5810.1044/2015_JSLHR-S-13-0179
Morgan, A., & Webster, R. (2018). Aetiology of childhood apraxia of speech: A clinical practice.
Journal of Paediatrics and Child Health, 54, 1090–1095. https://doi.org/10.1111/jpc.14150
Ogar, J. M., Dronkers, N. F., Brambati, S. M., Miller, B. L., & Gorno-Tempini, M. L. (2007).
Progressive nonfluent aphasia and its characteristic motor speech deficits. Alzheimer Disease
and Associated Disorders, 21, 523–530.
Park, J. (2017). Apraxia: Review and update. Journal of Clinical Neurology, 13(4), 317–324.
https://doi.org/10.3988/jcn.2017.13.4.317
Roig, M., Gratacòs, M., Vazquez, E., del Toro, M., Foguet, A., Ferrer, I., & Macaya, A. (2003).
Brainstem dysgenesis: Report of five patients with congenital hypotonia, multiple cranial
nerve involvement and ocular motor apraxia. Developmental Medicine & Child Neurology,
45, 489–493.
Soliveri, P., Piacentini, S., & Girotti, F. (2005). Limb apraxia in corticobasal degeneration and
progressive supranuclear palsy. Neurology, 64, 448–453.
Thevenon, J., et al. (2013). Higher risk of death among MEN1 patients with mutations in the JunD
interacting domain: a Groupe d’étude des Tumeurs Endocrines (GTE) cohort study. Human
Molecular Genetics, 22(10), 1940–1948. https://doi.org/10.1093/hmg/ddt039
Utianski, R. L., et al. (2018). Prosodic and phonetic subtypes of primary progressive apraxia of
speech. Brain and Language, 184, 54–65.
Zadikof, C., & Lang, A. (2005). Apraxia in movement disorders. Brain, 128(7), 1480–1497.
Chapter 3
The Human Connectome: An Overview
Before we get into the specifics of brain connectivity and apraxia, it is probably use-
ful to provide an overview of the playing field. The human brain is frequently
referred to as the most intricate object in the world, if not the universe. The brain is
a network of nerve cells, regions, interconnected regions, and systems whose inter-
connections remain largely unmapped. Indeed, exploration of how these neural
interconnections are established has only fairly recently begun. To understand how
these networks are connected, it is critically important to understand how neural
elements exchange signals and influence each other dynamically, encode statistical
regularities present in the sensory environment, coordinate movement and behavior,
retain traces of the past, and predict future outcomes (Sporns, 2013). This task is
further complicated by the fact that these networks are, in many ways, unique to
each human being in terms of mapping their functional properties. While it is true
that the physiology and biochemistry of their operation are the same, the neural
components of each individual’s network is to some extent idiosyncratic. For exam-
ple, it is accurate to say that both Broca’s and Wernicke’s areas are involved in
human speech. How they are associated with each other and to other recruited net-
work components varies slightly from person to person.
Therefore, to understand the functioning of this network, it is important to under-
stand its elements and their interconnections. To understand the foundation of a
neural network, it is absolutely essential to understand the concept of the human
connectome (Sporns et al., The human connectome: A structural description of the
human brain, 2005). Conceptualizing the connectome allows one to better concep-
tualize the complexities of the multitude of potential associations between regions
of the brain and, by extension, their functional output.

36 3 The Human Connectome: An Overview
The Connectome and Neural Networks
As a point of both interest and clarification, the term neural network comes from the
work on artificial intelligence where networks are created to mimic the functioning
of the human brain. The concept is most helpful when considering research. It is a
term we generally now use to refer to the human brain proper as well.
A human neural network is composed of a group of chemically connected or
functionally associated neurons. A single neuron may be connected to many other
neurons, and the total number of neurons and connections in a network may be
extensive. Connections, called synapses, are usually formed from axons to den-
drites, though dendrodendritic synapses and other connections are possible. The
reason that these neurons are connected to each other is to allow the brain to plan
and carry out behaviors designed to reach goals.
Neural network models assume that neural circuit function arises from the acti-
vation of groups or ensembles of neurons. According to these models, these ensem-
bles generate emergent functional states that, by definition, cannot be identified by
studying one neuron at a time. In fact, it is thought that the brain, unlike other body
organs, could be specifically built to generate emergent functional states
(Yuste, 2015).
The term “neural network” refers to models of distributed neural circuits in
which neurons are abstracted into nodes and linked by connections that change
through learning rules. Typically, neurons in neural networks are connected in an
all-to-all or a random fashion and integrate inputs linearly, leading to a threshold
nonlinearity that causes the cell to fire and activates its outputs.
The term “connectome” was defined by Sporns et al. (2005) as a “comprehensive
structural description of the network of elements and connections forming the
human brain.” Sporns et al. called for a compilation of the connectome based upon
structural and functional mapping. The idea of “connectomic maps” was introduced
by Jeff Lichtman et al. also in 2005 (Sporns, 2013) wherein these connectivity maps
were defined as “connectivity maps in which multiple, or even all, neuronal connec-
tions are rendered.” Clearly, the notion was centered on recognizing the importance
of understanding the structure and function of the human brain. At its core, the
human connectome is still largely hypothetical in its comprehensive map of all of
the neural connections in the human brain. Conceptually, it represents what is a
“wiring diagram” of the brain’s organization. Fundamentally, the human brain/ner-
vous system is made up of neurons which communicate through synapses. A con-
nectome map is constructed by tracing the neuron in a nervous system and mapping
where neurons are connected through synapses. A connectome model of a human
brain remains a hypothetical construct because each human brain, while following
general principles of physiological connectivity, establishes these connections idio-
syncratically. No two human brains are “wired” in exactly the same fashion. Human
brains accomplish the same function across the population, but how they do that is
accomplished by a unique connectome for each human being (Sato et al., 2021).
The combinations and patterns of various brain structures and their connections
Hubs 37
exhibit significant variations between individuals, at every level of organization.

These individual variations can be due to genetic differences, others the result of
developmental and experiential history, gender differences, pathologies, or
responses to injury. Incorporating individual variations and developmental stages is
absolutely crucial in understanding the connectome in operation.
The Importance of Understanding the Connectome
Understanding how the connectome is organized leads to critical understanding

about how information, stimuli, and emotions are processed by the system it repre-
sents. This understanding is critically important because the significance of the con-
nectome stems from the knowledge that the structures and functions of the human
brain are intricately linked, through multiple levels and hubs of brain connectivity.
There are, of course, strong natural constraints on which neurons or neural popula-
tions can interact, or how strong or direct their interactions are. A connectome
model posits that the foundation of human cognition lies in the pattern of dynamic
interactions shaped by the connectome. This is not a direct linear relationship.
The emphasis on structure as the foundation of connectomics is important for
several reasons. Perhaps most importantly, the actual structure of the brain repre-
sents a true baseline. This is because these anatomical connections, whether they are
individual synapses or interregional pathways, define a large but finite set of rela-
tions among neural components that can be objectively verified and reliably mapped.
That is because anatomical connections either exist or don’t.
This anatomical certainty stands in sharp contrast to functional connections that
describe the operation and outcome of the systems operation. By and large these
outcomes are described as statistical dependencies derived from observations of
behaviors. These behaviors can be the firing of a single neuron or a complex
sequence of behaviors. The most functional connections demonstrate significant
temporal fluctuations, may or may not disclose true causal relations between neural
elements, and are highly dependent on measurement and analysis technique (Sporns,
2013). This is compounded by the fact that, for complex behaviors at a minimum,
the outcome can be obtained by similar but not identical networks that interconnect
the same brain regions using different neural connection maps.
Hubs
Essentially, network modeling of brain function implies that all domains of cogni-
tive function require the integration of distributed neural activity. As part of this
model, analysis of human brain network connectivity has regularly identified sets of
regions that are vitally important for supporting efficient neuronal signaling and
communication. The central embedding of these candidate regions or “brain hubs”
in anatomical networks supports their diverse functional roles across a broad range
of cognitive tasks and widespread dynamic coupling within and across functional
networks. The essential core of brain hubs also implies that they are points of vul-
nerability that are susceptible to disconnection and dysfunction in brain disorders
such as apraxia (van den Heuvel & Sporns, 2013).
Several different types of hubs have been described. Connector hubs filter and
route information between brain regions. They coordinate and integrate the flow of
data so that brain networks dedicated to specific roles, such as vision and move-
ment, can focus on their jobs while at the same time integrate with other networks
to develop complex functional behaviors. More than two dozen connector hubs have
been identified. These play a key role in complex cognitive tasks and are also vul-
nerable to brain damage and dysfunction. Provincial hubs facilitate coordinated
action within a specific region of the brain. They facilitate a subset of skills such a
visual or processing (Sporns et al., 2007). There are many more of these hubs dis-
tributed throughout the brain.
Networks and Connectomics
Numerous studies have reported on the relation of synaptic connectivity in neuronal

circuits and observed patterns in neural dynamics, especially the correlations
observed in large neuronal populations (Sporns, 2013). Similar research has demon-
strated a strong and robust relationship between large-scale patterns of long-distance
connections between brain regions and their functional connectivity. It is clear that
these white matter systems are the “highways” along which information travels
between areas of the brain responsible for different behavioral components of coor-
dinated and complex action. Data indicate that the presence and strength of a struc-
tural connection partially predicted the strength of a functional connection between
various brain nodes (Honey et al., 2009). This same line of research also demon-
strated strong network connectivity between certain brains nodes that did not appear
functionally connected. This implies that there are, in place, potential brain resources
for future connectivity should the situation arises. This also suggests that merely
identifying connectivity patterns will not clearly establish functional properties of a
specific brain. What remains clear is that anatomic architecture conditions do not
determine the functional neural network dynamic. The functional connectivity of a
human brain cannot be explained only considering the anatomical substrate (Batista-
García-Ramó & Fernández-Verdecia, 2018). More specifically, anatomic architec-
ture determines, but not strictly, network dynamics, meaning that part of functional
connectivity cannot be explained by considering only anatomical connectivity.
Other factors are at work.
Degeneracy 39
Scaling
Sporns (2013) discussed the idea of scaling. It is the idea that many complex sys-
tems are themselves composed of subscales. “This mode of organization implies
that the system can be partially decomposed into coherent functional components at
different spatial scales” (Sporn, 2013). When discussing brain behavior functional
relationships, this implies that there can be hypothetically almost and unlimited
amount of subcomponent scales that contribute to a complex behavior, each
impacted by degeneracy and plasticity. This can extend down from a functional
network to a component consisting of one neuron. “Consider, for example, a full
description of the human cerebral cortex at cellular or system levels. Given current
best estimates for the number of neurons and number of synaptic connections (on
the order of 1010–1011 and 1014–1015, respectively), the microscale connectome
map would be extremely sparse: fewer than one in a million (less than one ten thou-
sandth of a percent) of all possible synaptic connections actually exist. However, at
system scale tracing and imaging studies of structural anatomy of regions and their
projections suggest that around 20–40% of all interregional pathways (and possibly
up to 60%; can be found” (Sporns, 2013, pg. 56). This issue of scale is closely asso-
ciated with the problem of “node definition” which is essential for understanding
networks from human imaging data derived from either diffusion or fMRI data.
Based upon small world hub models, node definition is critical for defining a net-
work’s basic elements. Research has shown that topological features of networks
revealed by graph theory methods sensitively depend on how the brain is broken
down or parcellated into components.
Degeneracy
Degeneracy (Edelman & Gally, 2001) has been defined as the ability of elements
that are structurally different to perform the same function or yield the same output.
Degeneracy means “many to one” in that many combinations of neurons can pro-
duce the same outcome. A high degree of degeneracy, as is the case with many
outcomes of complex cognitive operations, makes it difficult to detect consistent
underlying structure to function relations. Therefore, the wiring diagram of indi-
vidual exemplars of neural circuits would not be sufficient for “reading out” or
decoding how it actually functions. There are exceptions to this principle, for exam-
ple, the more primitive and basic “always on” neural networks” display remarkable
anatomical consistency.
It is important to note that the differences in wiring connectivity can and do pro-
duce sometimes subtle and sometimes significant differences in the functional prop-
erties of the outcome behaviors (Baldassare et al., 2012)
Structural Plasticity
All molecular and cellular components of the nervous system are being continually
remodeled, replaced, resynthesized, and reconfigured. This of course includes all
structural elements of the human connectome. These structural changes are under-
pinned by numerous mechanisms, from synaptic modifications to neuronal growth
and structural plasticity, operating not only during early development but across the
life span. Research suggests that the structural arrangement of neuronal circuits,
including their connection topology, can undergo significant and rapid alterations in
the adult brain on a regular basis (Holtmaat & Svoboda, 2009). There is a multiplic-
ity of forces that cause these changes, most significantly the person’s interaction
with and feedback from the environment. Even essentially similar networks at the
beginning of life will demonstrate considerable degeneracy as the individual’s life
experiences diverge. The chapters on childhood apraxia of speech and motor coor-
dination disorder provide an understanding of the significant implications when
considering the impact of developmental apraxia on the development of the child. It
is one of the many reasons that developmental apraxia cannot be understood utiliz-
ing an adult “damage” model. In the damage model, the already developed func-
tional system is disrupted. Therefore, that impact may be mitigated. In the
developmental situation, that functional system has not yet developed, is not devel-
oping appropriately, and through its aberrant development will disrupt all down-
stream operations dependent upon it.
Neurons grow and extend out to connect to other neurons, thereby establishing
connections. One neuron can connect to many other neurons should the necessity
arise. This is called neuroplasticity. Neuroplasticity allows new connections to be
created or areas to move and change function. The same neuron can participate in
several different functions. This is particularly true of motor neurons, which partici-
pate in most cognitive functions (Koziol et al., 2012). Synapses may strengthen or
weaken based on their importance. The adage neurons that fire together, wire
together may not be totally accurate but nevertheless represent the idea that neurons
involved in the completion of a particular task will have connections that strengthen.
Learning involves building on information that is already stored in the brain. As our
knowledge deepens by repetition and during sleep, tasks that once required a focus
can be executed automatically once mastered. Humans rely on this automaticity for
much of their everyday functioning.
Challenges to Understanding the Connectome
Conceptualizing the human connectome faces two unique significant challenges.

First, the human brain is a highly complex organ with a great number of structurally
distinct, heterogeneous components. As discussed, these components are intercon-
nected in a generally similar, yet idiosyncratic pattern. Conceptually, the
The Relationship of Connectome to Clinical Diagnosis 41
connectome is a structural substrate for understanding the basis of human cognitive

function. Each connectome is unique and brain areas of importance are intercon-
nected in slightly different ways, rendering the making of an authoritative, static
reference map impossible.
In addition to the individualized white matter connectivity patterns, human
brains demonstrate structural variability in mass and volume. Folding patterns of
cortical surfaces, and the absolute and relative sizes of brain regions and projec-
tions, have all been shown to differ across individuals. It is still unclear how these
differences affect connectivity and function as they are influenced by individual
differences, age, gender, environmental influences, and sometimes pathologies.
A second challenge is that basic structural elements of the human brain, in terms
of network nodes and connections, are difficult to define and standardize. Different
kinds of structural descriptions could target at least three rather distinct levels of
organization ranging from single neurons and synapses (microscale) to the level of
anatomically distinct brain regions and interregional pathways (macroscale).
Between these two levels is the level of neuronal groups or populations (mesoscale)
(Sporns et al., The human connectome: A structural description of the human brain,
2005). Moving forward, understanding how these levels interact with each other will
be essential for understanding how a network model informs our understanding of
human cognitive and emotional functioning (Wasserman & Wasserman, 2017,
2019a, b).
The Relationship of Connectome to Clinical Diagnosis
Much of what modern psychiatry and psychology do is to attempt to understand

how our developed model of psychopathology conforms to the operation of this
network. We make a diagnosis based on behavioral clusters and then make
connectome- based hypotheses concerning their etiology. The neurotransmitter
models of depression and obsessive-compulsive disorder are examples of this prac-
tice. For example, as we have written about (Wasserman & Wasserman, 2016),
much of the current behaviorally based understanding and classification of human
psychopathology do not conform to the operation of the human connectome. A
recent finding (Moncrieff, 2022) invalidate the long-held belief that depression was
the result of serotonin abnormalities, specifically low levels. This can be problem-
atic as demonstrated by the facts that prescriptions for antidepressants have risen
dramatically in the past three decades with people being administered a medication
under the belief that it speaks to the etiology of their disorder. In fact, it does not.
When it comes to apraxia, the parallel is largely the same. While it is accurate to say
that in the case of stroke an area of connectomic disruption can readily be identified,
there are apraxias, childhood apraxia of speech being the primary example, where
no specific connectomic disruption has been identified and alternate areas of disrup-
tion may cause the same functional outcome. As we shall see, even in the case of the
acquired apraxia, the connectomic implications are often overlooked.
The study of developmental apraxia, specifically, offers unique insight into the
relationship between the properties of the connectome and the development of dis-
orders related to it. It illuminates a feedforward model of the effects of develop-
ment/aberrant development on the connectome. Research suggests that damage to
topologically central brain regions is associated with widespread effects on network
function. The functional impact of these effects will vary depending on the topo-
logical role of the affected region. For example, dysfunction of provincial hubs is
expected to produce specific deficits, whereas dysfunction of connector hubs is pro-
posed to impair multiple behavioral domains. As we shall see, this finding has sig-
nificant implications for the development of children with developmental apraxia.
The sequelae of dysfunctional neural pathway operation are rarely confined to a
single locus. Rather, they often spread via axonal pathways to influence other regions
that share the operational network pathway. Patterns of such disordered development
are, to a degree, constrained by the extraordinarily complex, yet highly organized,
topology of the underlying neural architecture. Thus, network organization fundamen-
tally influences brain disease, and a connectomic approach grounded in network sci-
ence is integral to understanding neuropathology (Fornito et al., 2015). This necessity
can be easily conceptualized when considering disorders such as schizophrenia, atten-
tion-deficit disorder, autism, and diseases such as Huntington’s and dementias (Fig. 3.1).
Neural Response to the Disruption of Pathway Function
In line with our discussion, we think it bears mentioning that a disruption at any
level of network integrity could produce a disruption of complex, integrated, func-
tion, such as is experienced in apraxia. While the functional outcome disruption
could look the same, the underlying connectome causes could be very different. We
believe that these connectome differences, although potentially producing func-
tional disorders which on the surface appear indistinct, actually do produce distinct
and dissociable disorders, each with its own unique sequelae and associated comor-
bidities. There are several reasons for this belief, even when only considering
acquired apraxia. Disruption of functional outcomes can be understood by identify-
ing and understanding the various responses of the brain to a traumatic event and
how neural network topology constrains these responses. Knowledge of these pro-
cesses can inform our understanding of the impact of brain injury on the developing
constellation of problems associated in acquired apraxia.
Diaschisis
Diaschisis is a temporary interruption of function in an interconnected region that is

remote from an injured site. Diaschisis is now a well-established phenomenon, par-
ticularly following stroke. It has been observed in the forebrain after damage to the
Diaschisis 43
Fig. 3.1 Basic network attributes. (a) Brain networks can be described and analyzed as graphs
comprising a collection of nodes (describing neurons/brain regions) and a collection of edges
(describing structural connections or functional relationships). The arrangement of nodes and
edges defines the topological organization of the network. (b) A path corresponds to a sequence of
unique edges that are crossed when traveling between two nodes in the network. Low-degree nodes
are nodes that have a relatively low number of edges; high-degree nodes (often referred to as hubs)
are nodes that have a relatively high number of edges. (c) A module includes a subset of nodes of
the network that show a relatively high level of within-module connectivity and a relatively low
level of intermodule connectivity. “Provincial hubs” are high-degree nodes that primarily connect
to nodes in the same module. “Connector hubs” are high-degree nodes that show a diverse con-
nectivity profile by connecting to several different modules within the network (van den Heuvel &
Sporns, 2013)
brainstem or cerebellum, in cortical regions following subcortical infarction, and in

contralesional cortex following focal cortical insult (Fornito et al., 2015; Rehme &
Grefkes, 2012). These distributed changes seem to be circuit specific. Brain model-
ing has indicated that highly specific lesions can have a diffuse effect on interre-
gional synchronization dynamics that extend well beyond the impacted site and in a
way that critically depends on the connection topology of the damaged region
(Honey & Sporns, 2008). Research suggests that the severity of behavioral dysfunc-
tion that follows focal neural damage often correlates with the extent of activation
and connectivity changes in regions remote from the site of the lesion. These asso-
ciations between behavior and altered network functional connectivity occur even if
anatomical connectivity between damaged and undamaged regions is intact (van
Fig. 3.2 Types of

diaschisis. Types of
diaschisis before (left) and
after (right) a focal brain
lesion (black). Diaschisis
at rest: a focal lesion
induces a remote reduction
of metabolism (red).
Functional diaschisis:
normal brain activations
(yellow) during a selected
task may be altered, either
increased (green) or
decreased (red) after a
lesion. Connectional
diaschisis: distant strengths
and directions of
connections in a selected
network may be increased
(green) or decreased (red).
Connectomal diaschisis: a
lesion of the connectome
induces widespread
changes in brain network
organization including
decrease (red) or increase
(green) in connectivity
(Carrera & Tononi, 2014,
https://doi.org/10.1093/
brain/awu101)
Meer et al., 2010). This finding implies that a “functional deafferentation” of remote
sites may be sufficient to impair behavior. Nonetheless, damage to anatomical path-
ways linking the lesioned area to unaffected regions seems to compound the sever-
ity of behavioral impairment (He et al. 2007) (Fig. 3.2).
Dedifferentiation 45
All of this would, of course, imply associated dysfunction related to acquired

apraxia. One mechanism identified with such a possibility is the research suggesting
functional depression of the cerebellum which, in turn, causes reduced excitatory
drive from the damaged cerebellum to associated down/upstream networks (Gold &
Lauritzen, 2002).
Transneuronal Degeneration
While diaschisis is an interruption of function in a region that is remote from a

lesion, it is presumed that that region remains intact and undamaged. It is a connec-
tivity problem. Transneuronal degeneration represents actual structural deteriora-
tion of regions downstream from the area of initial insult. This damage occurs over
time. Transneuronal degeneration can be either anterograde (damage or dysfunction
of one neuron causes the degeneration of its postsynaptic target) or retrograde (a
presynaptic neuron deteriorates because of reduced trophic support from an injured
or necrotic postsynaptic target). The form of degeneration can vary and encom-
passes changes such as neuronal shrinkage, reductions in dendrite and synapse
number, alterations of axonal myelin content and fiber number, and neuronal death.
Both anterograde and retrograde degeneration have been identified in numerous
neural circuits (Fornito et al., 2015).
Several mechanisms can cause transneuronal degeneration. Pathology in any
single area can disrupt interactions with other regions, causing irregular firing and
metabolic stress in the connected site (Saxena & Caroni, 2011). Degeneration of
remote regions may also result from diminished excitatory input or a loss of trophic
support from damaged presynaptic neurons.
Dedifferentiation
Dedifferentiation is the widespread, nonspecific recruitment of unnecessary brain

regions to perform a task. It occurs as a result from a breakdown of usually special-
ized and segregated neural activity and is associated with aberrant neural plasticity
or by a focal cortical pathology that disrupts the balance between excitation and
inhibition within a specific neural system. Persistence of a dedifferentiated state is
associated with poorer recovery of motor function following stroke (Fornito
et al., 2015).
All of the above provide clear theoretical possibilities for the idea that acquired
apraxia (of speech) is probably not only a speech dysfunction but is also related to
other impairments in associated motor driven networks. This clarity is absent for
developmental apraxia because there is no clear evidence of specifically damaged
networks. We will discuss the implications of this dichotomy in some detail later on.
There are some important properties of these networks that have implications for
the study of apraxia. For example, in neural network models, action is an emergent
collective property, carried out by the assembly of neurons rather than by single
cells. Individual neurons can participate in different functional groups, flexibly reor-
ganizing themselves. This flexibility is a natural consequence of synaptic plasticity,
and it also allows the modular composition of small assemblies into larger ones.
Because of this flexibility, neural circuits may never be able to be in the same func-
tional state twice, responding slightly differently even if the exact same sensory
stimulus is presented. Many of these circuits are task dependent and created in the
moment. They “cease to exist” as soon as the task is completed. They, of course, can
be recreated if the same or similar task arises again, although the components, at the
neuronal level, are likely never exactly the same.
The Neural Networks of Apraxia
The motor-based praxis system is comprised of component functions associated

with particular brain regions and related structures. The brain regions work together
to process action. This network of structures underlying praxis includes the frontal
and parietal cortex, basal ganglia, and white matter tracts containing projections
between these areas (Gross & Grossman, 2008). Indeed, white matter-based dys-
connectivity between brain regions has recently been identified in gesture difficulty
related to limb apraxia (Rosenzopf et al., 2022). They found pathological white
matter alterations in a densely connected fronto-temporo-parietal network of short
and long association fibers. This indicated involvement of middle and superior tem-
poral lobe disconnection, including temporo-temporal short association fibers sug-
gesting strong involvement of the temporal lobe in the praxis network.
The basal ganglia also play an essential role in praxis, via connections with fron-
tal and parietal cortices (Zadikoff, 2005). Specific functions of the basal ganglia
related to praxis include sequencing, fine tuning of movements, selection of com-
peting motor programs, and performance of automatic or overlearned movements.
It is important to note that isolated basal ganglia dysfunction by itself does not seem
to cause significant apraxia. Most apraxias also involve surrounding white matter
tracts and frontoparietal cortex.
Apraxia represents a disruption of a complex behavior, and as a result praxis
depends on a complex, large-scale network of structures recruited collectively to
accomplish the desired task. Imaging studies involving connectivity analysis
revealed two coherent circuits: one involving the parietal cortex, supplementary
motor area, and motor cortex and the other involving the parietal, lateral premotor,
and motor areas involved in many apraxic conditions (Wheaton et al., 2005).
All of the above has significant implications for the study of apraxia. A complex
output such as speech is dependent on multiple networks and their subserving net-
works. Many of these networks are involved in the product of other complex behav-
iors. Motor networks are involved in most human activities. Damage to a motor
References 47
network would have implications far in excess of one particular outcome. Clinically
speaking, this implies that if the clinician “sees” apraxia, it is very, very likely that
there will be comorbid conditions that are directed related to, and caused by, the
disruption causing the apraxia.
All of this indicates that while we may be able to understand how connectivity
and network properties of the human brain contribute to the problems associated
with apraxia, we will never be able to, on a case-by-case basis, identify how a spe-
cific connectivity problem causes a particular individual to manifest apraxia. This
statement is probably much truer for those children with development apraxia as
compared to those adults that demonstrate apraxia secondary to a traumatic brain
insult. We will explore the implications of this hypothesis in some detail later.
Suffice it to say here that, as we have indicated, the nature of dysfunction in the
developing network would have significantly greater impact on a multiplicity of
systems and behaviors that rely upon a typical and uninterrupted developmental
progression. Simply stated, we would expect a far wider range of disrupted and
dysfunctional behavior associated with developmental apraxia.
We can no longer think that a person that has apraxia just has apraxia. Damage
anywhere in the complex integration of networks that produce an outcome has the
possibility of impacting the production of the outcome. We can no longer be sure
that we know where the lesion is by knowing what is not working. Damage to the
same area of a network can produce a different pattern of comorbidities depending
on the pattern of connectivity unique to that individual.
References
Baldassare, A., Lewis, C., Committeri, G., Romani, G. L., & Corbetta, M. (2012). Individual vari-
ability in functional connectivity predicts performance of a perceptual task. Proceedings of the
National Academy of Sciences of the United States of America, 109, 3516–3521.
Batista-García-Ramó, K., & Fernández-Verdecia, C. (2018). What we know about the brain struc-
ture–function relationship. Behavioral Science, 8(39), 1–14. https://doi.org/10.3390/bs8040039
Carrera, E., & Tononi, D. (2014). Diaschisis: Past, present, future. Brain, 137(9), 2408–2422.
https://doi.org/10.1093/brain/awu101
Edelman, G., & Gally, J. (2001). Degeneracy and complexity in biological systems. Proceedings
of the National Academy of Sciences of the United States of America, 98(24), 13763–13768.
Fornito, A., Zalesky, A., & Breakspear, M. (2015). The connectomics of brain disorders. Nature
Reviews Neuroscience, 16, 150–172.
Gold, L., & Lauritzen, M. N. (2002). Neuronal deactivisation explains decreased cerebellar blood
flow in response to focal cerebral ischemia or suppressed neocortical function. Proceedings of
the National Academy of Sciences of the United States of America, 99, 7699–7704.
He, B. J. (2007). Breakdown of functional connectivity in frontoparietal networks underlies behav-
ioral deficits in spatial neglect. Neuron, 53, 905–918.
Holtmaat, A., & Svoboda, K. (2009). Experience-dependent structural synaptic plasticity in the
mammalian brain. National Review Neuroscience, 10, 647–658.
Honey, C. J., & Sporns, O. (2008). Dynamical consequences of lesions in cortical networks.
Human Brain Mapping, 29, 802–809.
Honey, C., Sporns, O., Cammoun, G. X., Thiran, J., et al. (2009). Predicting human resting-state
functional connectivity from structural connectivity. Proceedings of the National Academy of
Sciences of the United States of America, 106, 2035–2040.
Koziol, L., Budding, D., & Chidekel, D. (2012). From movement to thought: Executive function,
embodied cognition, and the cerebellum. Cerebellum, 11(2), 505–525. https://doi.org/10.1007/
s12311-011-0321-y
Moncrieff, J. C. (2022). The serotonin theory of depression: A systematic umbrella review of the
evidence. Molecular Psychiatry. https://doi.org/10.1038/s41380-022-01661-0
Rehme, A. K., & Grefkes, C. (2012). Cerebral network disorders after stroke: Evidence from
imaging-based connectivity analyses of active and resting brain states in humans. Journal of
Physiology, 591, 17–51.
Rosenzopf, H., Wiesen, D., Basilakos, A., Yourganov, G., Bonilha, L., Fridriksson, J., . . . Sperber,
C. (2022). Mapping the human praxis network: An investigation of white matter disconnection
in limb apraxia of gesture production Brain Communications 4 (1) https://doi.org/10.1093/
braincomms/fcac004, 1–14.
Sato, J., Biazoli, C. E., Zugman, A., Pan, P., Bueno, A., Moura, L., & Affon, R. (2021). Long-
term stability of the cortical volumetric profile and the functional human connectome through-
out childhood and adolescence. European Journal of Neuroscience, 6187–6201. https://doi.
org/10.1111/ejn.15435
Saxena, S., & Caroni, P. (2011). Selective neuronal vulnerability in neurodegenerative diseases:
From stressor thresholds to degeneration. Neuron, 71, 35–48.
Sporns, O. (2013). The human connectome: Origins and challenges. NeuroImage, 80, 53–61.
https://doi.org/10.1016/j.neuroimage.2013.03.023
Sporns, O., Tononi, G., & Kötter, R. (2005). The human connectome: A structural description of
the human brain. PLoS Computational Biology. https://doi.org/10.1371/journal.pcbi.0010042
Sporns, O., Honey, C., & Kotter, R. (2007). Identification and classification of hubs in brain net-
works. PLoS ONE, 2(10), e1049. https://doi.org/10.1371/journal.pone.0001049
van den Heuvel, M., & Sporns, O. (2013). Network hubs in the human brain. Trends in Cognitive
Sciences, 17(12), 683–696. https://doi.org/10.1016/j.tics.2013.09.012
van Meer, M. P., et al. (2010). Recovery of sensorimotor function after experimental stroke cor-
relates with restoration of resting-state interhemispheric functional connectivity. Journal of
Neuroscience, 30, 3964–3972.
Wasserman, T., & Wasserman, L. (2016). Depathologizing psychopathology. Springer.
Wasserman, T., & Wasserman, L. (2017). Neurocognitive learning therapy: Theory and practice.
Springer.
Wasserman, T., & Wasserman, L. (2019a). Neural networks series, therapy. Springer.
Wasserman, T., & Wasserman, L. (2019b). Therapy and the neural network model. Springer.
Wheaton, L., Nolte, G., Bohlhalter, S., et al. (2005). Synchronization of parietal and premotor
areas during preparation and execution of praxis hand movements. Clinical Neurophysiology,
1382–1390.
Yuste, R. (2015). From the neuron doctrine to neural networks. Nature Reviews Neuroscience, 16,
1-11. https://doi.org/10.1038/nrn3962
Zadikoff, C. L. (2005). Apraxia in movement disorders. Brain, 1480–1497.
Chapter 4
Neuronal Populations, Neural Nodes,
and Apraxia
Population coding is a method to represent signals by the joint activities of a number

of neurons. In population coding, each neuron has a distribution of responses over
some set of inputs, and the responses of many neurons may be combined to deter-
mine the value about the inputs. Biologically, the idea of neuronal populations refer-
ences nodes within a network that are connected to multiple other nodes. We are
going to look at this level of brain organization, nodes, in detail because understand-
ing this modeling is important in understanding the potentially far-reaching conse-
quences of any one of a number of apraxia conditions (Fig. 4.1).
An important thing to remember is that any one node may participate in an
almost unlimited number of specific networks. This is particularly true to nodes
involved in motor activity. Since each of these population centers participates in
multiple types of motor responses, damage to any one of them affects all of the
downstream activities emanating from them. This implies that an individual with
apraxia will experience potentially numerous disruptions in behavior related to the
area of neuronal population that is dysfunctional. The resultant disrupted behavior
will not only be the “apraxic” motor movement” that originally brought the indi-
vidual to clinical attention but other impacted behaviors anywhere along the motor
circuit as well. This disruption, by association, can also lead to disruption of cogni-
tive functions.
Apraxia and Neural Pathways
Historically, researchers have ascribed independent encoding functions to the activ-

ity of single neurons (Evarts, 1868) or groups of neurons (Humphrey & Thompson,
1970). Research reflective of this line of thinking searched for correlations between

50 4 Neuronal Populations, Neural Nodes, and Apraxia
Fig. 4.1 Neural nodes. In the context of brain networks in this study, every anatomical region of
interest is a node, whereas the connection between nodes is termed as an edge. (Handiru et al., 2021)
specific neural activity and specific movement parameters. The belief was that neu-
ral activity would encode particular parameters in a consistent and highly predict-
able manner. There were some problems with this logic. For example, research
demonstrated considerable variability in the activity patterns across neurons
(Churchland & Shenoy, 2007) and instability of movement parameter encoding by
single neurons across different conditions (Scott & Kalaska, 1997).
More recent research has not been based on the independent modulation of sin-
gle neurons but rather activities performed at the population level by networks of
interconnected neurons. This is likely to be the place to look when considering the
etiology of many apraxia conditions.
Populations of cortical neurons flexibly perform different functions; for the pri-
mary motor cortex (M1), this means they are involved in a rich repertoire of motor
behaviors (Gallego et al., 2018). While each specific motor-involved task requires
different patterns of muscle and single unit activity, there are considerable similari-
ties at the neural population level among the areas involved for different tasks. In
sum, research has demonstrated that the structure and activity of the neural nodes
are largely preserved across tasks.
What Is the Neural Population Level?
The brain contains many millions of neurons that are organized in different brain
areas. Within any specific brain area are different subregions. Each of these subre-
gions is composed of different layers and inside each layer are various cell types.
The neuron doctrine (Yuste, 2015) held that the neuron was the structural and
functional unit of the nervous system. However, multineuronal recording methods
have now revealed that it ensembles of neurons, rather than individual cells, which
can form physiological units which serve to generate emergent functional properties
Integrating Neural Populations into a Coherent Neural Network 51
and states. This new paradigm creates neural network models which potentially bet-
ter understand how emergent functional states generate behavior and cognition. By
extension, this understanding of normal development and function can also then be
applied to understanding disease and the results of trauma.
While much research then has historically focused on the operation of a single
neuron, these populations of neurons, at the subregion level (neuronal populations),
have characteristic properties that are derived from their working collaboratively.
Theory suggests a relationship between neuron responses and psychophysical deci-
sions which may prove useful for identifying cell populations underlying specific
perceptual capacities (Zohary et al., 1994). That allows for modeling that includes
the unique response properties of these specific populations.
For example, rather than looking at the response time of a single neuron which
belongs to a certain cell class at a certain level, a number of questions might be
reasonably asked. So, for example, supposing a human brain receives a certain type
of stimulus, what is the activity of all the cells in a particular layer of the subregion
processing the response? What is the activity of the population class of cells in that
layer of the subregion? Finally, what is the response of this subregion as a whole?
This of course leads to the question, what is the response of a brain area? In other
words, at any of the scales of spatial resolution, it is productive to look at the
response of the neuronal population as a whole rather than the activities of an indi-
vidual neuron (Gerstner et al., 2014) (Fig. 4.2).
I ntegrating Neural Populations into a Coherent

Neural Network
Now that we understand that there are groups of neurons that essentially operate
together as part of a larger network to produce behavior and cognition, how can we
integrate that knowledge into a network model that would help explain what the
clinician is seeing in apraxia? How these neuronal populations are related to the
well-established hub and node model is critical for understanding how neural net-
works operate.
Effectively every domain of cognitive function in the human brain requires the
integration of distributed neural activity. Network analysis of human brain connec-
tivity has routinely identified sets of regions that are essential for enabling efficient
neuronal signaling and communication. These areas have been termed brain hubs or
nodes. The central embedding of these candidate “brain hubs” in anatomical net-
works supports their diverse functional roles across a broad range of cognitive tasks
and widespread dynamic coupling within and across functional networks. The high
level of centrality and importance of these brain hubs also makes them points of
vulnerability that are susceptible to disconnection and dysfunction in brain disor-
ders (van den Heuvel & Sporns, 2013). The relationship between a neural node,
neural population, and neural hub can be defined as follows. A neural node can be
as small as a single neuron and is a network component that has one or more input
Fig. 4.2 Cortical population activity within a preserved neural manifold underlies multiple motor
behaviors. Hypothesis: Varied motor behaviors are caused by the flexible activation of combina-
tions of neural modes. (a) The connectivity of the cortical network results in neural modes whose
combined activity explains the specific activity of individual neurons. (b) The neural space for the
three neurons recorded in (a). The time-dependent population activity is represented by a trajec-
tory (in black, arrow indicates time direction) mostly confined to a two-dimensional neural mani-
fold (gray plane) spanned by two neural modes (green u1 and blue u2 basis vectors). (Gallego et al.
(2018). https://doi.org/10.1038/s41467-018-06560-z)
connections, a transfer function that combines the inputs in some way, and an output
connection. In the context of a network, a hub is a node with a large number of con-
nections with many other nodes. A neural population is essentially a highly inte-
grated complex hub consisting of a large number of individual neurons operating in
a synchronized manner. As regards our current discussion, damage or disruption of
any of these components will impact the network of which they are a part.
There are a good number of terms that are associated with this modeling, and we
are providing the reader with a glossary of these terms. This glossary was generated
by van den Heuvel and Sporns (2013):
Glossary 53
Glossary
Brain connectivity: description of structural or functional connectivity

between brain network elements (i.e., brain regions,
neurons).
Centrality: measures of the relative importance of a node or edge
within the overall architecture of a network. Several
centrality metrics have been proposed, including
(among many others) degree, betweenness, closeness,
eigenvector, and PageRank centrality.
Clustering: the tendency of small groups of nodes to form con-
nected triangles. Many triangles around a central node
imply that the connected neighbors of the node are
also neighbors of each other, forming a cluster
or clique.
Community: in networks, communities refer to modules, densely
interconnected sets of nodes.
Connection matrix: a summary of all pairwise associations (connections)
between network nodes, rendered in the form of a
square matrix.
Connection: expresses the existence and/or strength of a relation-
ship, interaction, or dependency between two nodes in
the network. Connections can be binary or weighted
and they can be directed or undirected. Connections
are also referred to as edges.
Connectome: a comprehensive network map of the anatomical con-
nections of a species’ nervous system.
Connector hub: a high-degree network node that displays a diverse
connectivity profile across several different modules
in a network.
Core: a group of nodes that share a large number of mutual
connections, rendering them resistant to damage.
Cores are identified by using a recursive procedure
that prunes away weakly connected nodes.
Degree: the number of edges attached to a given node.
Directed network: a network comprising directed connections (edges).
Edge: a term for a network connection.
Functional connectivity: measured as the statistical dependence between the
time series of two network nodes (e.g., brain regions,
neurons).
Graph: a mathematical description of a network, comprising a
collection of nodes and a collection of edges.
Hub: a node occupying a central position in the overall
organization of a network.
Module: a group of nodes that maintain a large number of

mutual connections and a small number of connec-
tions to nodes outside their module.
Parcellation: a subdivision of the brain into anatomically or func-
tionally distinct areas or regions.
Participation coefficient: a graph-theoretical measure that expresses the distri-
bution of edges of a node across all modules in a
network.
Provincial hub: a high-degree network node that mostly connects to
nodes within its own module.
Resting-state network: a set of brain regions that show coherent functional
connectivity during task-free spontaneous brain
activity.
Rich-club organization: the propensity of a set of high-degree nodes in a net-
work to be more densely interconnected than expected
on the basis of their node degree alone.
Scale-free organization: a network with a degree distribution that follows a
power-law function.
Shortest path length: the shortest path length between two nodes reflects the
minimal number of links that have to be crossed to
travel from one node to another node in the network.
Small-world organization: a network that shows a level of clustering higher than
that observed in random networks and an average
shortest path length that is equal to that observed in
random networks.
Structural connectivity: a description of the anatomical connections between
network nodes (i.e., brain regions, neurons), for exam-
ple, reconstructed anatomical projections derived
from diffusion MRI, directed anatomical pathways
derived from neural tract tracing, or synaptic connec-
tions between individual neurons.
Undirected network: a network comprising undirected connections (edges)
(Fig. 4.3).
ow the Neural Substrate Enables Integration of Distributed

H
Neural Information and Thus the Emergence of Coherent
Mental and Cognitive States
Two aspects of brain organization appear essential in the understanding of how the
brain generates complex action or thought. First, integration depends on neural
communication among specialized brain regions, unfolding within a network of
interregional projections (Fuster, 1997), which gives rise to large-scale patterns of
How the Neural Substrate Enables Integration of Distributed... 55
Fig. 4.3 Basic network attributes. (a) Brain networks can be described and analyzed as graphs
comprising a collection of nodes (describing neurons/brain regions) and a collection of edges
(describing structural connections or functional relationships). The arrangement of nodes and
edges defines the topological organization of the network. (b) A path corresponds to a sequence of
unique edges that are crossed when traveling between two nodes in the network. Low-degree nodes
are nodes that have a relatively low number of edges; high-degree nodes (often referred to as hubs)
are nodes that have a relatively high number of edges. (c) A module includes a subset of nodes of
the network that show a relatively high level of within-module connectivity and a relatively low
level of intermodule connectivity. “Provincial hubs” are high-degree nodes that primarily connect
to nodes in the same module. “Connector hubs” are high-degree nodes that show a diverse con-
nectivity profile by connecting to several different modules within the network. (Published in
Trends in Cognitive Sciences 2013 Network hubs in the human brain M. V. D. Heuvel, O. Sporns)
coordinated activity (Singer, 1993) between connected elements of the network.

Second, important integrative functions are performed by a specific set of brain
regions and their anatomical connections. These regions are capable of complex and
diverse responses and represent focal points of convergence or divergence of more
specialized neural information (“confluence zones”) (Meyer & Damasio, 2009).
Very recently, research has suggested that some of this integration happens at the
subcortical level. For instance, subcortical visual areas such as the dorsal lateral
geniculate nucleus (dLGN) or the superior colliculus (SC) have long been held as
basic structures responsible for a stable, integrated, and defined function. The dLGN
can be considered as a relay for visual information traveling from the retina to
cortical areas and the SC as a sensory integrator orienting body movements toward
visual targets. Findings suggest that both dLGN and SC neurons express functional
plasticity, adding unexplored layers of complexity to their previously attributed
functions (Duménieu et al., 2021).
What Is the Interface of Network Structure and Praxis?
Praxis is defined as an accepted practice or custom, or an idea translated into action.

It is widely understood that the praxis network system of the human brain is made
up of component functions associated with specific brain regions. These brain
regions are recruited in response to specific task demands and work together to
produce action. The network of structures underlying praxis is thought to include
the frontal and parietal cortex, basal ganglia, and white matter tracts containing
projections between these areas (Gross & Grossman, 2008). A disruption anywhere
in that system, cortical or subcortical, or anywhere in the variously recruited loops,
has the potential to disrupt praxis and produce an apraxic condition.
eural Pathways and Structures Implicated

N
in Apraxia Conditions
Now that we have an idea of the architecture of the neural network transmission
system, let’s look at what is known and accepted as the various network structures
implicated in the forms of apraxia we have already reviewed. We will emphasize the
common elements in bold when identified. For the purposes of the discussion at this
point, we will omit apraxia conditions caused by genetic abnormalities as they tend
to cause more widespread disruption in the various network systems.
Limb-Kinetic Apraxia
Please note that these areas cover a lot of cortical ground and that the literature is
not talking about specific areas within these structures. Limb-kinetic apraxia (limb
apraxia is often associated with left frontal and parietal brain damage than with right
brain damage) (Pazzaglia et al., 2008b). Limb-kinetic apraxia is not explained by
elemental motor or sensory systems or by defects in language comprehension. It
typically affects both the ipsilesional and the contralesional limbs. Conceptual and
production components of gestural organization may be differentially affected and
may lead to ideational and ideomotor apraxia. We highlight the idea that within the
category of limb-kinetic apraxia, the symptomology is not identical and the
Neural Pathways and Structures Implicated in Apraxia Conditions 57
downstream effects differ. We would suggest that it is because the site of the damage
to the network is different and the resultant downstream impact unique.
There is some data to suggest that this is the case. The discovery in the monkey
frontal and parietal cortices of complex double-duty neurons that are activated dur-
ing both action execution and observation (mirror neurons) suggests very strong
connections between the perceptual and the motor components of an action (Fogassi
et al., 2005). Additionally, early studies in patients with limb-kinetic apraxia
reported an association between the inability to perform gestures and understand
their meaning and left parietal lesions (Heilman et al., 1982).
Ideomotor Apraxia
An analogous situation arises when looking at the data of ideomotor apraxia (IMA).
“If we consider the map of lesions in patients with ideomotor apraxia, we find some-
thing approximating to the classical notion of apraxia localization within the left
hemisphere-namely, in the anterior, central, and suprasylvian retrorolandic areas
disconnection of which from the central executor region has been regarded as
responsible for apraxia” (Basso et al., 1980). Here again, it is not one specific area
but several. It is also highlighted that it is the disconnection of these areas from the
network that is the critical component of the problem.
A wider review of ideomotor apraxia highlights the numerous and diverse areas
that have been noted to produce the condition. Studies of IMA and lesion location
suggested that subcortical damage to white matter tracts was most critical (Wheaton
& Hallet, 2007). This finding has occurred in the face of research on white matter
lesions in general which indicated that white matter lesions are not more common
in IMA patients than in others. In fact, lesions in deeper brain areas (e.g., white mat-
ter, thalamus, and basal ganglia) are more common in nonapraxia groups. This is
not a surprising discrepancy as regards white matter because of both the amount and
multiple functions of white matter, not all of which subserves motor functioning. It
is clear that white matter damage is found in studies showing that subcortical dis-
connection of the parietal and premotor areas may cause apraxia (Kertes & Ferro,
1984). In addition, damage to cortical structures, particularly the angular gyrus or
the supramarginal gyrus, has been observed in cases of apraxia.
Conceptual Apraxia
Conceptual deficits can be seen in patients with dementia and have been associated
with lesions of posterior regions of the left hemisphere (Ochipa et al., 1992). There
is research that suggests that conceptual apraxia is a subset of ideational apraxia,
where the ability to conceptualize is impaired (Gross & Grossman, 2008). This
would again suggest that it depends where in the underlying shared networks the
difficulty was.
Ideational Apraxia
Ideational apraxia is usually demonstrated in people with extensive left hemisphere

damage, dementia, or delirium (Heilman & Rothi, 2003). It is possible that the dif-
ficulty sequencing actions demonstrated by individuals impacted with this disorder
may not represent a higher-order motor programming deficit, but rather, this deficit
may be due to a combination of executive, language, and memory limitations
(Weintraub, 2000) or to a general limitation in cognitive resources (Giovannetti
et al., 2002)].
Buccofacial Apraxia
In buccofacial apraxia, the lesion is usually in or near area 44 or Broca’s area as it

is commonly known. Broca’s area, located in the frontal cortex, plans the process of
speech by interacting with the temporal cortex, where sensory information is pro-
cessed, and the motor cortex, which controls movements of the mouth.
Oral Motor and Verbal Apraxia
The insula has been established as the area that is significantly impaired in both
forms of oral and verbal apraxia and different severities and prominent forms of
both of these apraxias. Broca’s area was involved, but to a slightly less extent, than
insula in two forms of apraxia (Yadegari et al., 2014). The insular (also known as
insula and insular lobe) is a portion of the cerebral cortex folded deep within the
lateral sulcus (the fissure separating the temporal lobe from the parietal and frontal
lobes) within each hemisphere of the brain.
Constructional Apraxia
Constructional apraxia is thought to be caused by lesions in the parietal lobe fol-

lowing stroke. Its appearance may also serve as an indicator for Alzheimer’s dis-
ease. Constructional apraxia occurs after injury to either cerebral hemisphere. Most,
but not all, lesions are parietal. The nature of constructional apraxia differs accord-
ing to the hemisphere injured. Individuals with left-sided lesions improve their
drawings when aided by visual cues, whereas patients with right-sided lesions do
not (Sharma & Wong, 2022).
We can see, as discussed, that most apraxic conditions arise from damage some-
where in the frontal, left temporal, or parietal lobes and to a lesser extent Broca’s
Neural Pathways and Structures Implicated in Apraxia Conditions 59
area. We suggest that “somewhere” is the operative word and that where the disrup-
tion occurs is essential in determining the downstream impact of the lesion. What is
very likely is that there will always be associated disruption of function in addition
to the primary motor impact, or apraxia.
This group of disorders is clearly dissociable from the apraxia condition of
unknown etiology or those with genetic deficiencies where the impact is more spe-
cific, or in some instances more global. It is likely that there are considerably more
sequelae for these disorders. We hope to show this to be especially true in childhood
apraxia of speech whose etiology remains poorly understood. It should be clear that
disruption in the motor network produces most acquired apraxic conditions. We will
explore if that holds true for congenital or developmental apraxias.
As we have seen, childhood apraxia of speech (developmental apraxia) is different.

In this case it is different because in contrast, most adult apraxias are the result of
damage, injury, or insult to a specific brain area that produces specific and predict-
able functional deficits. Even though the specific network or group of networks
cannot be demonstrated, the general area of damage usually predicts to some degree
the type of dysfunction to follow. This is not the case for childhood apraxia of
speech as to date, there is no evidence that unilateral damage can result in apraxia
of speech or that left hemisphere lesions are more likely to result in dysarthria than
lesion to the right. There are relatively few studies looking at the issue of etiology
based on network principles. Those that do report on childhood apraxia of speech
coalesced toward morphological, structural, metabolic, or epileptic anomalies
affecting the basal ganglia, perisylvian, and rolandic cortices bilaterally. On a
related note, persistent dysarthria was commonly reported in individuals with syn-
dromes and conditions affecting these same structures bilaterally. In sum, the
research suggests that long-term and severe childhood speech disorders result pre-
dominantly from bilateral disruption of several neural networks involved in speech
production and could be caused by disruption anywhere in this network (Liégeoisa
& Morgan, 2012).
Couple this research with the definition of childhood apraxia of speech and fur-
ther difficulties arise. Childhood apraxia of speech (CAS) is an impairment in the
programming and realization of intact motor units of speech (American Speech-
Language-Hearing Association., 2007). Further, differential diagnosis of apraxia of
speech is based on perceptual judgment (based on observation) of specific speech
symptoms in the absence of fundamental neuromuscular, cognitive, or linguistic
impairments (McNeil, 2011). In other words, there is no diagnostic emphasis
regarding the involvement of neural networks, or any other brain-related area neces-
sary for the diagnosis of childhood apraxia of speech. All that is necessary is that the
requisite behavioral symptoms be present. There are three core symptoms used to
differentiate apraxia of speech from other speech sound disorders: (a) prolongation
of speech sounds including increase in segment and intersegment duration, (b)

inconsistent distortion of speech sounds, with consistency in distortion type, (c) and
abnormal prosody, characterized by inappropriate stressing of syllables and sounds
(Murray et al., 2015).
Interestingly, while the literature is somewhat sparse on the network properties
of CAS, there is research to suggest several single genes and copy number-variant
conditions are associated with CAS either in relative isolation, as in the case of
FOXP2 variants, or most typically in association with other neurodevelopmental
conditions, such as epilepsy, intellectual disability, motor impairment, and autism
(Morgan & Webster, 2018). This is not to say that these genetic differences do not
impact network functioning; they probably do. The extant research is just not clear
on the issue.
In this chapter we have taken a tour of the brain structures and network properties
of the neural network system associated with the various forms of apraxia. It should
be clear that historically, and as a consequence of a cortical bias, much of the extant
research and conceptualization of apraxia has focused on large-scale, gray matter
brain regions or specific smaller regions associated with speech (Broca’s area,
Wernicke’s area). It should be clear that the historical research has not focused on
white matter connectivity issues associated with the various apraxic conditions
despite the fact that a very persuasive case can be made for a white matter contribu-
tion to the etiology of the various disorders. Current and emerging neuroimaging
techniques, coupled with connectome models, are facilitating the establishment of
this cortico-subcortical model as the standard.
Our point of view would express the belief that an apraxia is a functional end
stage of a complex integrated network-based response. As such it could be produced
by a disruption anywhere in one of the networks that contribute to the final behavior.
Take, for example, the multiple pathways associated with apraxia of eyelid opening.
In general, the pathogenesis of apraxia of eyelid opening and blepharospasm
remains poorly understood. There are a few hypotheses based on animal model
studies that suggest multiple etiologies dependent on the neural pathways involved.
Among these are nigrostriatal basal ganglia pathways that seem to project to the
premotor control of eyelid coordination. Therefore, it is associated with dysfunction
in the corticothalamic, basal ganglia, and focal cranial nerve circuitry. Structures
involved include sensorimotor cortical regions, substantia nigra pars reticulata, and
brainstem motor nuclei (Cabrero & De Jesus, 2021).
In addition, depending on where the disruption is, other behaviors, which are
dependent on the same connectivity patterns, would logically be impacted as well.
In other words, for most apraxic conditions there would be several associated behav-
ioral and perhaps emotional problems. The is clearly demonstrated in developmen-
tal apraxia where the research demonstrates that the most prevalent functional
problems in addition to communication were attention (focus), vestibular function,
temperament, fine hand use, maintaining attention, and learning to write. In addi-
tion, cognitive and learning problems, social communication difficulties, behavioral
dysregulation, and other oral motor problems have been identified. More than 50%
had health, mental health, and developmental conditions (Teverovsky et al., 2009).
References 61
Given the rather broad nature of the network disruption in CAS, these findings are
not surprising. It is likely that the adult apraxic conditions, given an already estab-
lished connectome, with possibly more restricted damage, have considerably less
associated functional behavioral disruption related to the locus and severity of the
damage causing the problem in the first place.
References
American Speech-Language-Hearing Association. (2007). Childhood apraxia of speech (Position

Statement). Retrieved from American Speech-Language-Hearing Association. www.Asha.
org/policy
Basso, A., Luzzatti, C., & Spinler, H. (1980). Is ideomotor apraxia the outcome of damage to well-
defined regions of the left hemisphere? Journal of Neurology, Neurosurgery, and Psychiatry,
43, 118–126.
Cabrero, F., & De Jesus, O. (2021, August 30). Apraxia of lid opening. Retrieved from National
Library of Medicine: https://www.ncbi.nlm.nih.gov/books/NBK560542/
Churchland, M. M., & Shenoy, K. V. (2007). Temporal complexity and heterogeneity of single-
neuron activity in premotor and motor cortex. Journal of Neurophysiology, 97, 4235–4257.
Duménieu, M., Marquèze-Pouey, B., Russier, M., & Debanne, D. (2021). Mechanisms of plasticity
in subcortical visual areas. Cell, 10(11), 3162. https://doi.org/10.3390/cells10113162
Evarts, E. V. (1868). Relation of pyramidal tract activity to force exerted during voluntary move-
ment. Journal of Neurophysiology, 31, 14–27.
Fogassi, L., Ferrari, P., Gesierich, B., Rozzi, S., Chersi, F., & Rizzolatti, G. (2005). Parietal lobe:
From action organization to intention understanding. Science, 308, 662–667.
Fuster, J. (1997). Network memory. Trends in Neuroscience, 20(10), 451–459. https://doi.
org/10.1016/S0166-2236(97)01128-4
Gallego, J., Perich, M., Naufel, S., Ethier, C., Solla, S., & Miller, E. (2018). Cortical popula-
tion activity within a preserved neural manifold underlies multiple motor behaviors. Nature
Communications, 9, 4233. https://doi.org/10.1038/s41467-018-06560-z
Gerstner, W., Kistler, W., Naud, R., & Paninsk, L. (2014). Neuronal populations. In W. Gerstner,
W. Kistler, R. Naud, & L. Paninsk (Eds.), Neuronal dynamics from single neurons to networks
and models of cognition (pp. 291–322). Cambridge University Press.
Giovannetti, T., Libon, D., Buxbaum, L., & Schwartz, M. (2002). Naturalistic action impairments
in dementia. Neuropsychologia, 40, 1220–1232.
Handiru, V., Alivar, A., Hoxa, A., Saleh, S., Suviseshamuthu, E. S., Yue, G., & Allexandre,
D. (2021). Graph-theoretical analysis of EEG functional connectivity during balance pertur-
bation in traumatic brain injury: A pilot study. Human Brain Mapping, 14(42), 4427–4447.
https://doi.org/10.1002/hbm.25554
Heilman, K., Rothi, L., & Valenstein, E. (1982). Two forms of ideomotor apraxia. Neurology, 32,
342–346.
Heilman, K., & Rothi, L. (2003). Apraxia. In K. Heilman & E. Valenstein (Eds.), Clinical neuro-
psychology (pp. 215–235). Oxford University Press.
Humphrey, D. R., & Thompson, W. D. (1970). Predicting measures of motor performance from
multiple cortical spike trains. Science, 170(7), 758–762.
Kertes, A., & Ferro, J. (1984). Lesion size and location in ideomotor apraxia. Brain, 107(92), 1–33.
Liegeoisa, F., & Morgan, A. (2012). Neural bases of childhood speech disorders: Lateralization
and plassticity for seech functions during development. Neuroscience & Behavioral Reviews,
36(1), 439–458. https://doi.org/10.1016/j.neubiorev.2011.07.011
McNeil, M. (2011). Clinical management of sensorimotor speech disorders. Thieme.

Meyer, K., & Damasio, A. (2009). Convergence and divergence in a architecture for recognition and
memory. Trends in Neuroscience, 32(7), 376–382. https://doi.org/10.1016/j.tins.2009.04.002
org/10.1111/jpc.14150
with childhood apraxia of speech comparing rapid syllable transition treatment and the
org/10.1044/2015_JSLHR-S-13-0179
Ochipa, C., Rothi, L., & Heilman, K. (1992). Conceptual apraxia in Alzheimer’s disease. Brain,
Pazzaglia, M., Smania, N., Corato, E., & Aglioti, S. (2008b). Neural underpinnings of gesture
discrimination in patients with limb apraxia. The Journal of Neuroscience, 28(12), 3030–3041.
https://doi.org/10.1523/JNEUROSCI.5748-07.2008
Scott, S. H., & Kalaska, J. F. (1997). Reaching movements with similar hand paths but different
arm orientations. I. Activity of individual cells in motor cortex. Journal of Neurophysiology,
77, 826–852.
Sharma, V., & Wong, L. (2022). Middle cerebral artery disease. In J. Grotta, G. Albers, J. Broderick,
S. Kasner, R. Sacco, A. Day, et al. (Eds.), Stroke (seventh edition) pathophysiology, diagno-
sis, and management (pp. 317–346). Elsevier. https://doi.org/10.1016/B978-0-323-69424-
7.00024-7
Singer, W. (1993). Synchronization of cortical activity and its putative. Annual Review of
Teverovsky, E., Bickel, J., & Feldman, H. (2009). Functional characteristics of children diagnosed
with childhood apraxia of speech. Disability and Rehabilitation, 31(2), 94–102. https://doi.
org/10.1080/09638280701795030
Weintraub, S. (2000). Neuropsychological assessment of mental state. In I. M. Mesulam (Ed.),
Principles of behavioral and cognitive neurology (pp. 135–136). Oxford University Press.
Yadegari, F., Azimian, M., Rahgozar, M., & Shekarchi, B. (2014). Brain areas impaired in oral and
verbal apraxic patients. Iranian Journal of Neurology, 13(2), 77–82.
Yuste, R. (2015). From the neuron doctrine to neural networks. Nature Reviews. Neuroscience, 16,
Zohary, E., Shadlen, M., & Newsome, W. (1994). Correlated neuronal discharge rate and its impli-
cations for psychophysical performance. Nature, 370, 140–143.
Chapter 5
It Is Not Only Apraxia
If the network model, for the functional impact of the damage that causes apraxia,
based on white matter connectivity problems is plausible, then it stands to reason
that disruption of a network pathway would not only produce a localized functional
disruption but also produce problems with other functional behaviors dependent on
(downstream from) that pathway for their operation. In apraxia caused by brain
injury or damage due to stroke, it is likely that any behavior directly reliant on the
affected pathway would be impacted. In apraxia of speech, where there are likely
numerous etiologic agents, it is likely there would be numerous potential comorbid
conditions. Understanding how those interconnections originate and develop would
be critical for understanding the functional impact of apraxic conditions.
he Structural Beginnings of Brain-Based Behavioral

T
and Cognitive Connections: A Theoretical Basis
At the general practice level, much of what we talk about in the fields of neuropsy-
chology, adult occupational therapy and physical therapy and related fields, most
often is our attempt to assess and remediate damage. In order to facilitate this dis-
cussion, we offer this section as a theoretical basis for understanding the sophistica-
tion and complexity of human communication. It is our hope that by doing so we
can move the discussion from “you have apraxia, and you need therapy to address
the sole sequelae of that disorder” to a more comprehensive understanding of the
potential impact apraxia might entail.
Communication in humans recruits all areas of the brain depending upon the task
and how familiar with the task we are (novel vs. automaticity). We recruit language,
but, at the same time, we also recruit pathways associated with attention, memory,
and executive function as part of the complicated communication process. As

64 5 It Is Not Only Apraxia
mentioned elsewhere in this book, motor behavior and motor-sensory development

predates cognitive language and also comprises an integral part of communication.
If the premise that disruption of a neural pathway would, as a rule, cause disrup-
tion further down the pathway, then it would stand to reason that those pathways
would develop in an interconnected manner. In addition, structures within the path-
way would be recruited for multiple other functional outcomes. By extension, dam-
age to the earlier structures, developed earlier ontogenically, would cause disruption
to the development of multiple functional outcomes.
The Development of Networks
A developmental perspective is invaluable for understanding how functional brain

networks come into existence. The current imaging studies are providing insight
into how these functional brain networks develop from childhood. We have talked
about how brain networks start out as locally segregated small world hubs. The
basic anatomical structure is largely in place by 2 years of age (Menon, 2013). This
is not to imply that nothing goes on before that time because that is not the case. It
is accurate to say that by age of 2, the basic structure of future network operations
is in place. As we develop, the shorter-range connections in children evolve between
these segregated hubs, becoming, with practice and repetition, stronger long-range
connections, ultimately creating a large-scale connectome. There is a body of evi-
dence indicating that while gray matter changes over the course of development, the
development of white matter actually undergoes a more intensive change than gray
matter (Menon, 2013). This maturation then includes cortical subcortical reconfigu-
rations. This vertical brain model, from a developmental perspective, allows us to
consider how microstructural changes in white matter and changes from local to
long-range white matter development impact both the integrity and reach of these
neural network connections. By understanding how intensively neural pathways are
associated, we can better understand how maturation involves broad regions of the
brain and how multiple regions must be incorporated on a task-specific (functional)
basis. And by extension, we can also understand how disruption to any part of the
connectome will impact the larger connectome, or functional outcomes.
Feedforward Impact
The principle of a feedforward impact in the face of disruption applies to develop-

mental and trauma-based impact. A feedforward neural network is a computerized
network model wherein node connections do not form a loop. Feedforward neural
networks are so named because information flows in a forward manner only. These
networks develop across domains such as motor, cognitive, working memory, lan-
guage, and functionally to academic and daily living skills. In summary, “A
The Cerebral Cortex and Basal Ganglia 65
thorough characterization of the development of large-scale brain networks requires

the integration of multiple structural and functional measures. The complexities of
this effort, including linking brain structure, anatomical connectivity, task and con-
text specific functional connectivity and characterizing their dynamic maturation
with age” (Menon, 2013) is all to be considered.
The Cerebral Cortex and Basal Ganglia
“The cerebral cortex is a six layered structure that performs a wide range of highly
specialized operations” (Koziol & Budding, 2009, pg. 41). “These operations can be
divided into two broad categories. First, posterior cortices are involved in sensory
perceptual information processing and storage. These cortical areas are the occipi-
tal, parietal, and temporal lobes. Second, the anterior cortices, or the frontal lobes,
are involved in the processing or programming and retention of movement and
action patterns. The products of the information processing computations performed
by the cortex remain represented within the cortex” (pg. 41).
The basal ganglia receive afferents from nearly all cortical regions while sending
efferent signals back to those same cortical regions through the thalamic nuclei
(Middleton & Strick, 2000). The basal ganglia do not directly participate in the
computations performed by the cortex. They are involved in gating or selecting the
representations that are processed by the cortex so that these representations become
active or can be expressed. Hence, the basal ganglia are the gatekeepers which
enable the frontal cortex to execute the appropriate motor plan at the appropriate
time (Frank et al., 2001).
As part of this process, we can extrapolate how this cortical-subcortical process
impacts working memory. Let us first state that working memory, a cognitive task,
may be considered the mainstay of executive function. Koziol and Budding (2009)
ask and answer: How can an activity that seems so uniquely cognitive be analogous
to motor behavior in any way? For the business of the basal ganglia, motor function-
ing and cognition are similar or even parallel processes. They further state that they
believe that the basal ganglia interact in the same way with the presentation of plans
and goals that reside in the prefrontal cortex. In this way, the processes that guide
motor functioning have much in common with the cognition of working memory
that ultimately guides behavior. The processes that guide movement manage many
of the same requirements that are essential for manipulating the contents of working
memory. “The cognitive control system is likely and evolutionary extension of the
frontal basal ganglia motor control system” (Hazy, 2007) which includes working
memory or “the set of cognitive processes for holding goals and subgoals in mind in
the service of planning and executing complex behaviors. In other words, the basal
ganglia select and gate movement, and they also gate cognitions: they do the same
things for cognition that they do for movement. Koziel (2009) highlights that this is
the underpinning of self-directed, controlled behavior.
The same modeling applies to speech as well. Koziol and Budding (2009) note
that just as gesturing requires movements to be expressed in a certain order, vocal
sound sequences also rely on an organized sequence to express a particular mean-
ing. This ties the connection between motor sequencing and verbal sequencing. In
fact, this also ties into the subcortical-cortical nature of the process with basal
ganglia-cortical loops providing a unique neural architecture for the necessary foun-
dations for sequencing the structure, or rules across gestures and vocalizations.
From an evolutionary standing, these structures already existed and were special-
ized over time so that the result is that language is dependent upon the basal ganglia
for sequential learning and upon the frontal cortex for the necessary motor
programming.
In fact, the current authors wish to remind the reader that intention predates lan-
guage development. During the motor-sensory period, infants demonstrate the
innate reflex of curiosity (Wasserman & Wasserman, 2020), the expression of which
results in the execution of intent through motor movement. This movement is rein-
forced and thereby found to be rewarding to the infant-seeking behavior. We also
know that categorization precedes language (Rakison, 2010), setting the stage for
language development. We should also remember that this exploration involves the
salience network and, by inclusion, attention. In this way we can see that attention,
intent (goal-directed behavior), working memory, motivation, language, and motor
movement are inexorably linked in human development and remain interconnected
in more complex human cognition. The potential exists for these interconnected
systems to be disrupted by a brain insult that produces an apraxic event with impact
to a potential multitude of functional areas.
For example, with respect to speech, Hickok et al. (2011) proposed a model
incorporating the dorsal stream, emphasizing the role of internal forward models in
speech motor control. They posited that these relevant neural systems make forward
predictions about the future state of the motor articulators and the sensory conse-
quences of the predicted actions in order to control desired functional action. The
predictions are generated by an internal model that receives efferent copies of motor
commands and integrates them with information being received about the current
state of the system. This allows for a mechanism for detecting and correcting motor
errors, that is, motor actions that fail to hit their sensory targets. The ability to sup-
press errors, whether motor or language based, is very important. This process,
which requires defining a target and implementation of corresponding behavior,
whether this is behavioral or speech based, requires inhibition of attention or
attempts of other behaviors, that is, monitoring and necessary inhibition. It is likely
within the cerebellum that this constant and highly sophisticated computational
monitoring takes place. It is within the basal ganglia that inhibition is initiated,
strengthening the inter-association of the motor areas acting in concert with the
cerebellum and basal ganglia loops (Hickok, 2012). The reader will note the expan-
sion of the originally cortical centric model to a cortical subcortical model incorpo-
rating constant modulation and monitoring of the inhibition and expression of
behaviors.
Neural Pathways Are Recruited for Multiple Functional Outcomes 67
Changes to this excitatory-inhibitory process then, at some phase of develop-

ment, not only impacts the local circuit excitability but can also alter large-scale
brain connectivity resulting in atypical development of functional neural associa-
tions and process (Menon, 2013). This then provides the physiological hypothesis
for deviant neural development and that this imbalance underlies aberrant brain
connectivity in many developmental psychopathologies (Menon, 2013).
Aberrations in the neurodevelopment of the cortico-subcortical process has been
linked to multiple neurodevelopmental disorders including autism, attention-deficit
disorder, emotional disorders, schizophrenia (Menon, 2013), and sensory integra-
tion disorder (Koziol, 2009). A large focus of multiple chapters of this volume is to
emphasize that abnormal neurodevelopment is the base of developmental coordina-
tion disorder and childhood apraxia of speech, with implications going far beyond
what might be assumed if limiting ourselves to the nomenclature of the diagnos-
tic label.
All of the above is reported so that the reader understands that, looking at both
neurodevelopmental disorders and apraxias which occur as a result of trauma, the
basis of the disorder is complex reflecting highly integrated and associated areas of
both cortex and subcortex. Damage, whether from a developmental source or as the
result of acquired trauma, will impact these systems in multiple and complex ways.
Both the integrity of the system and their associated functional behaviors will be
negatively affected.
eural Pathways Are Recruited for Multiple

N
Functional Outcomes
There is research that indicates that recruitment of network and network-related

systems is the rule rather than the exception, and this makes sense. For example,
dopamine (DA)-producing neurons are critically involved in the production of
motor behaviors in multiple circuits that are conserved from basal vertebrates to
mammals (Barrios, Weng, England, Reifenberg, & Douglass, 2020). Similarly,
exposure to drug-related cues in human addicts results in drug craving and localized
activation of central circuits that are known to mediate cue-induced reinstatement of
drug-seeking behavior in animal models of relapse. Similar regional activation pat-
terns occur in humans in response to cues associated with foods (Kelley, Shiltz, &
Landry, 2005).
Similar examples of shared network working are found in motor circuits. For
example, numerous muscle groups would be common among a variety of related
functional behaviors. There is clear evidence that the modular control of muscles in
groups, often referred to as muscle synergies, provides a motor repertoire of actions
for the robust control of movement. This research demonstrates that a common pool
of spatially fixed locomotor muscle synergies is recruited by different neural path-
ways, including the central pattern generator for walking, brainstem pathways for
balance control, and cortical pathways mediating voluntary gait modifications.

These muscle synergies provide a repository of motor subtasks that can be flexibly
recruited by parallel descending pathways to generate a variety of complex natural
movements in the upper and lower limbs (Chvatal & Ting, 2012). Similarly, phrenic
motor neurons are recruited across a range of motor behaviors. These motor units
are recruited in a fixed order across a range of motor behaviors. These motor neu-
rons were recruited for different motor behaviors, i.e., eupnea, hypoxia-hypercapnia,
deep breaths, sustained airway occlusion, and sneezing (Seven, Mantilla, &
Sieck, 2014).
Other research may also have direct implication for apraxia as well as conditions
such as tic disorder and obsessive-compulsive disorder. Research has clearly indi-
cated that unexpected events recruit a fronto-basal-ganglia network for stopping.
Elements of this network include specific prefrontal cortical nodes and is thought to
project to the subthalamic nucleus, with a putative global suppressive effect on
basal-ganglia output. This is a global suppressive network. Its existence provides a
common mechanistic basis for different types of unexpected events; links the litera-
tures on motor inhibition, performance monitoring, attention, and working memory;
and is relevant for understanding clinical symptoms of distractibility and mental
inflexibility (Wessel & Aron, 2017).
In fact, we have already had a hint as to the impact of shared networks in cases
of childhood apraxia of speech (CAS) where the research has shown numerous
functional problems in addition to communication. We know CAS affects phonetic-
motoric planning of speech. What is now clear is that the motor control impairment
of CAS and apraxia of speech (AOS) extends beyond speech and is manifest in
nonspeech movements of the oral structures (Kirrie, Granier, & Robin, 2008).
Associated problems include difficulty with attention (focus), vestibular function,
temperament, fine hand use, maintaining attention, and learning to write. In addi-
tion, cognitive and learning problems, social communication difficulties, behavioral
dysregulation, and other oral motor problems have been identified. More than 50%
of AOS patients had health, mental health, and developmental conditions
(Teverovsky, Bickel, & Feldman, 2009). Estimates suggest that approximately only
4% of individuals diagnosed with an acquired neurological communication disorder
present with AOS as the primary disorder and individuals with stroke-induced AOS
as their only communication impairment are rarely reported in the literature. In
patients with AOS, there is an estimated co-occurrence of aphasia in 81%, dysar-
thria in 29–47%, and nonverbal oral apraxia in 48–75% of cases (Moser, Basilakos,
Fillmore, & Fridriksson, 2016).
It could be argued that both AOS and CAS clearly have significant discrepancies
from the other forms of apraxia so that they represent outliers. It would be, there-
fore, beneficial to see whether other forms of acquired apraxia, that is, apraxia
caused by brain insult or injury, would demonstrate the same properties regarding
the implications of shared neural networks. There is striking evidence that the prop-
erties of disrupted neural network activity are quite different.
Disruption of Early Domains Are Not Just Domain Specific 69
Disruption of Early Domains Are Not Just Domain Specific
Again, returning to a developmental framework, we must ask how these functional

trajectories work by association. In a study of the developmental relationship
between language and motor behavior (Wang, 2014b), multiple important questions
were asked. The first is how is research impacted by looking at a single variable
rather than associated developmental domains. The second are the trajectories and
cross-associations for these domains. Wang (2014a) attempted to look at three per-
spectives, namely, co-occurrence of difficulties, stability of each domain across
time, and the predictive power of each across time. They found that language at
3 years of age was a better predictor of later language skills than gross motor skills,
indicating stability within the domain. However, they also found an increase over
time for shared variance with both fine and gross motor development with language
development. Language at 3 years of age was significantly associated with later fine
and gross motor performance. They conclude that these findings support the hypoth-
esis that motor and language are developmentally associated trajectories. Also
important was the combining of their earlier study (Wang, 2014a, b) with the cur-
rent study for a greater longitudinal perspective. They found that language did not
predict motor development from 18 months to 3 years of age; however, from 3 to
5 years of age, this association was found to be significant. In contrast, there was a
significant association from 18 months of age to 3 years of age between motor skill
development and later language performance, although neither gross motor nor fine
motor development at 3 years of age was predictive for late language development
(age 5). These are important findings for many reasons. First, it demonstrates stabil-
ity within domains. Second, it highlights a difference in development at different
stages of development for domains with associations greater and lesser at different
ages. Specifically, language was not predictive of motor skills early on (18 months
to 3 years) but was found to be more highly associated between ages 3 and 5. In
contrast, early motor skills (18 months to 3 years) were found predictive of later
language skills, although the predictive power of gross and fine motor skills dropped
off for language development for the 3–5-year-old age group. Therefore, early
motor development and later language development were significantly associated.
For the older age group, motor development did not predict language development,
although for the 3–5 age group, the association was significant.
These findings also suggest that a disorder, such as developmental coordination
disorder, can be assessed earlier on, and should be, as aberrant motor development
can affect language development. The findings also suggest that by age 3, develop-
ment in one domain is highly associated with development in the second domain
supporting the idea that disruption at that point can impact more than one area of
development. Given what we have discussed with respect to early architecture being
in place by age 2, with following connectivity alterations, the call for early interven-
tion becomes all the clearer.
As we have just seen, it is likely that apraxic conditions are associated with other
dysfunctions, so let’s take a look at what is known.
Limb-Kinetic Apraxia and Associated Conditions
Limb-kinetic apraxia seems to be particularly relevant for activities of daily living

especially those requiring dexterity skills (Foki, et al., 2016). Limb apraxia is pri-
marily classified by the nature of the errors made by the individual and the pathways
through which these errors are elicited. It is based on a two-system model for the
organization of action: a conceptual system and a production system (Leiguarda &
Marsden, 2000). These systems are dissociable, and each has its own constellation
of downstream effects. Deficits include, but are not limited to, visual and somato-
sensory transformations for reaching; transformation of information about the loca-
tion of body parts necessary for the control of movements; somatosensory
transformation for posture; visual transformation for grasping; and internal repre-
sentation of actions. Problems with sensory motor integration have been noted.
Ideomotor Apraxia and Associated Conditions
As we have seen, ideomotor apraxia (IMA) is a disorder of skilled, purposeful

movement, characterized by spatiotemporal deficits during a variety of actions.
Historically, these deficits have been attributed to damage to, or impaired retrieval
of, stored representations of learned actions, especially object-related movements.
This however is not the only available possibility. These same deficits might be
caused by impaired visuomotor transformation mechanisms that operate in parallel
to or downstream from mechanisms for storage of action representations. These
transformation processes convert extrinsic visual information into intrinsic neural
commands appropriate for the desired motion. These processes are essential for
movement planning process and performance errors due to inadequate transforma-
tions. If this model is correct, we could predict that patients with ideomotor apraxia
would demonstrate planning deficits when reaching to visual targets, especially
when the coordination and/or dynamic requirements of the task increase. This is
indeed the case (Mutha, Sainburg, & Haaland, 2010).
In addition, much research has demonstrated that spatiotemporal deficits in
apraxia are not limited to object-use movements. For example, apraxic patients
make errors that are consistent with impaired integration of spatial and temporal
features of movements during reaching and sequencing. Apraxic patients also make
more errors than non-apraxic patients and healthy subjects when asked to imitate
meaningless movements, such as touching the nose, and also intransitive gestures,
such as saluting. Overall, research results have demonstrated that deficits in ideo-
motor apraxia are present during movements made in a variety of contexts and are
not simply limited to object-use actions. Finally, there is research to suggest that a
central deficit in IMA may be impaired postural representation causing inability to
solve the problem of how to manipulate objects where neither affordance nor mem-
ory can dictate action (Sunderland & Shiner, 2007).
Conceptual Apraxia and Associated Conditions
Conceptual apraxia has two domains: associative knowledge (tool-action associa-

tions such as hammer pound; tool-object associations such as hammer nail) and
mechanical knowledge such as knowing the advantage that tools afford (Heilman,
Maher, Greenwald, & Rothi, 1997). It is likely that these two domains share some
network components but are nevertheless dissociable from each other. Problems in
either of these very broad domains are different from one another.
While it is known that conceptual praxis representations are stored in the left
hemisphere, analysis of lesion sites in various research studies fails to clearly estab-
lish where in the left hemisphere they may be stored. This can be due to a number
of reasons not the least of which is the possibility that these representations are not
stored as integrated constructs but are reintegrated at the time the task demand is
presented. Conceptual apraxia has been associated with problems with semantic
memory (Dumont, Ska, & Joanette, 2000).
Ideational Apraxia and Related Conditions
There is some evidence to suggest that ideational apraxia, like conceptual apraxia,
is related to semantic memory and may not be a disorder of defective motor control
at all (De Renzi & Lucchelli, 1988). It has also been argued that ideational apraxia
reflects a generalized disturbance of object representations that are held to trigger
action schemas (Cooper, 2007). The point here is that semantic memory deficits, at
a minimum, accompany ideational apraxia. It is not clear where in the process of
memory reconfiguration these semantic problems arise and that means that there
might be more than one etiological factor.
Other problems have been regularly associated with ideational apraxia. The abil-
ity of ideational apraxic patients to perform simple tasks involving multiple objects
is typically characterized by a variety of errors. Some of these errors concern the
sequential organization of action through time; many others are related to the mis-
use of, or failure to use, necessary or appropriate tools.
Oral Motor and Verbal Apraxia and Related Conditions
This is a wide and poorly defined area, with the research often mixing childhood
apraxia of speech and adult acquired oral motor apraxia. As we saw from the brief
discussion of childhood apraxia of speech, there are numerous downstream effects
that accompany CAS. In adults oral motor apraxia is frequently comorbid with
aphasia (Conterno, et al., 2021) and other issues related to disrupted speech.
Apraxic Conditions Rarely Occur in Isolation
The point of this discussion is that it highlights the fact that apraxic conditions of all
types rarely occur in isolation and are often accompanied by other forms of dys-
regulated behavior. From a network perspective, this makes sense. Research demon-
strating that apraxia can be due to deep subcortical lesions, including damage to the
basal ganglia or thalamus would clearly imply multiple potential downstream
behavioral difficulties (Pramstaller & Marsden, 1996). What’s more, far from being
a disorder confined to discrete gray matter structures in the brain, apraxia can be
caused by disruption of while matter located subcortically. Pramstaller and Marsden,
in their research, indicated that apraxia was most seen when there were lesions in
the lenticular nucleus or putamen with additional involvement of capsular, particu-
larly of periventricular or peristriatal, white matter. While lesions of the globus pal-
lidus or caudate nucleus rarely caused apraxia, the caudate lesions also had white
matter involvement. Finally, involvement of periventricular or peristriatal white
matter alone caused apraxia in their subject population. In other words, an unidenti-
fied subset of apraxic conditions resulted from white matter-based connectivity
issues. On a functional behavioral level, these two causes (gray and white matter)
produced similar if not identical disrupted outcome. The downstream effects from
each etiology can be expected to be different. If a primary structure, such as Broca’s
area, was impacted, all downstream functions from Broca’s areas would be impacted.
If it were a white matter connectivity issue, then it could at least be anticipated that
certain functional behavior would be impacted and other behavior spared.
How complicated can this get? Multiple overlapping white matter networks are
involved in most higher-order cognitive functions.
If we are to conjecture that a disruption of a pathway, as can happen in acquired
apraxia, can have far-reaching impact on the function outcome capacity of a person,
it would require us to take a look at one system in detail to serve as the basis for a
model. For example, communication in humans activates almost every part of the
brain. Obviously, the known language gray areas predominate, but other cognitive
functions associated with language, such as attention, memory, emotion, and execu-
tive processes, are also involved. In order to explain how our brain actually utilizes
language to understand, speak, and write and in order to rehabilitate things like
apraxic or aphasic disorders, neuroscience is just beginning to recognize that it must
understand the responsible neural networks (Nasios, Dardiostis, & Messinis, 2019).
Part of the recognition is that we cannot base our understanding of how this lan-
guage system operates based upon an outdated model of the modular organization
of the brain. Over the last three decades, neuroscience based on new imaging,
recording, and manipulation techniques for brain research developed a new model
of the functional neuroanatomy of language. The dual-stream model, consisting of
two interacting networks (“streams”)—one ventral, bilaterally organized, for lan-
guage comprehension, and one dorsal, left hemisphere dominant, for language pro-
duction—was identified.
These “streams” (network) are very complex and involve a multiplicity of struc-
tures. According to the dual-stream model, the dorsal pathway involves the left
hemispheric structures in the posterior frontal lobe, the posterior dorsal temporal
lobe, and the parietal operculum, including long white matter (WM) tracts connect-
ing the frontal to the temporal and parietal lobes, specifically the articulate fascicu-
lus (AF), and the indirect anterior and indirect posterior components of the superior
longitudinal fascicle (SLF). The core anterior (frontal) hubs of the dorsal pathway
include the inferior frontal gyrus (opercular and triangular part), the ventral portions
of the precentral gyrus, and the anterior portions of the insula (forming together the
left frontal operculum (L-FO)). Posteriorly, the main hubs are the posterior sector of
the insula, the ventral portions of the supramarginal gyrus, and Sylvian parietal
temporal region (Spt), forming, together with the upper parts of the posterior supe-
rior temporal gyrus and sulcus, the left temporoparietal junction (L-TPJ). Area Spt
is located in the posterior part of the left planum temporale (PT) region, where
speech perception and production systems converge.
In contrast to these left dominant structures and networks, ventral pathways are
bilaterally distributed into both hemispheres, and the major hubs include the supe-
rior temporal gyrus (STG), superior temporal sulcus (STS), middle and inferior
temporal gyri (MTG/ITG), and the anterior temporal lobe (ATL). The ventral stream
connects the frontal cortices to the occipital, parietal, and temporal lobes, via long
white matter (WM) tracts, including the external capsule (EC), the inferior fronto-
occipital fascicle (IFOF), the inferior longitudinal fascicle (ILF), and the uncinate
fascicle (UF).
Traditionally, neuropsychologists and other neuroscientists concentrated their
research on specific small elements of language processing. What is now known is
that the human organizes its interactions for communication under in a situationally
specific manner involving multifunctional processing of multimodal input from the
environment. Different groups of words, forming different groups of meanings,
connected with different emotional aspects, involve different parts of our brain, far
beyond the strictly defined language networks (Huth, W, Griffiths, Theunissen, &
Gallant, 2016). They found that the distribution of semantically selective areas
within the semantic system was relatively symmetrical across the two cerebral
hemispheres. A finding that is inconsistent with human lesion studies that support
the idea that semantic representation is lateralized to the left hemisphere but, how-
ever, completely in line with the bilateral distribution of the ventral stream of the
dual-stream model.
The point here is that these networks are incredibly complex and disruption in
any component may produce a verbal apraxia or related language difficulty. To the
extent that these same structures, many of them motoric, are recruited in other cog-
nitive activities, we can reasonably expect that damage to one of them would pro-
duce multiple downstream effects in addition to the apraxic condition that is the
focus of this book.
White Matter Degeneration Following Injury
If we are going to have a model that speculates on downstream damage, it would be

useful to identify mechanisms on just how this might occur. In addition to the “line
being broken” with no information being able to be processed below the point of the
break, there are physiological effects that follow injury to white matter. For exam-
ple, following an initial impact after spinal cord injury (SCI), a cascade of down-
stream events has been identified. These have been term termed “secondary injury,”
which culminate in progressive degenerative events in the spinal cord. These sec-
ondary injury mechanisms include, in part, ischemia, inflammation, free radical-
induced cell death, glutamate excitotoxicity, cytoskeletal degradation, and induction
of extrinsic and intrinsic apoptotic pathways. There is expanding evidence that glu-
tamate excitotoxicity plays a key role not only in neuronal cell death but also in
delayed posttraumatic spinal cord white matter degeneration (Park, Velumian, &
Fehlings, 2004). Cortically, immune-inflammatory processes and the response to
several trigger factors such as trauma, hemorrhage, or ischemia cause the release of
active inflammatory substances such as cytokines, which are the basis of second-
level brain damage. Secondary injury mechanisms include processes such as altera-
tion of ionic homeostasis, increase of neurotransmitter levels, neuronal cellular
death, lipid degradation, and immune-inflammatory activation Disruption of motor
and cognitive functioning has been reported as associated with this secondary dam-
age (Tuttolomondo, Pecoraro, & Pinto, 2014). It is possible to associate specific
disfunction with this secondary damage. For example, Wasserman and Mion (2019)
identified cortical white matter degeneration attributable to white matter degenera-
tion causing memory loss. Thus, there is every reason to believe that further damage
and function loss might be attributable to a lesion that initially causes apraxia. In
addition, there is every reason to believe that there might be apraxic events second-
ary to lesions that initially do not cause apraxia.
In addition, there is evidence, much of it from animal studies, that suggests that
the system that experiences the insult can react to the disruption in unpredictable
ways. For example, after damage to the cochlear, the acoustic system can, in some
cases, respond by recalibrating itself to partially accommodate the sensory input
loss (Salvi, Wang, & Ding, 2000). How these compensatory adjustments might con-
tribute to a particular apraxic condition is not entirely clear, but it is possible that
such recalibrations might negatively impact fluidity. The same research clearly
identifies a multiplicity of follow-on difficulty associated from cochlear damage.
Cochlear damage results in neuronal shrinkage, axonal pruning, trans-synaptic
degeneration new growth of axons, formation of new synapses, and modifications to
the distribution of ascending neural projections. Further, cochlear damage also
alters the neurochemistry of the central auditory pathway. Protein synthesis is sig-
nificantly and rapidly downregulated after cochlear destruction or inactivation and
glucose metabolism are modified. Neurotransmission in the central auditory path-
way is also altered by cochlear damage. This information is presented to highlight
the point that downstream and, in some cases, upstream changes are the rule rather
than the exception when disruption of a neural pathway occurs.
Neural Network Damage Models 75
Neural Network Damage Models
As might be implied from the above, there are at least two ways to look at possible
effects from damage to a neural network component. The first is to look at damage
to the major gray matter components of any particular system. The second is to look
at damage to the white matter connectivity components of the system (Farah,
O’Reilly, & Vecera, 1993). Logically, this leads to a third possibility: situations
where both gray and white matter are damaged. These three possibilities do not
even address all the possibilities when discussing apraxia. We must consider the
situation, such as in developmental apraxia, where there is not observable damage
to the system and yet the system does not function as it should.
There is substantial and expanding literature on gray matter and white matter
damage after head injury and insult (Fu, et al., 2021). This research indicates that
the pathophysiological presentation of white matter damage involves axonal dam-
age, demyelination, and mature oligodendrocyte loss. Studies of a variety of other
acute brain insults have indicated that white matter damage is strongly correlated
with cognitive deficits, neurological deficits, and depression. (Mutha, Sainburg, &
Haaland, 2010). As we have pointed out, white matter damage in the basal ganglia
has been associated with apraxic sequelae (Pramstaller & Marsden, 1996). White
matter damage has been identified as the major etiological factor in ideomotor(limb)
apraxia (Leiguarda.R., 2001).
The extant research provides a clear delineation for the role of the basal ganglia
in the presentation of apraxic symptomology. The hypothetical multiple roles of the
basal ganglia in object-oriented action and, as a result, praxis would include among
others (a) the selection of the kinematic parameters and the direction of arm move-
ments, (b) working as a core element of brain systems involved in the timing and
representation of action sequences, (c) encoding behavioral context, and (d) work-
ing as a subcortical component of the parieto-frontal circuits dedicated to senso-
rimotor transformation.
Interestingly, multiple studies suggest that basal ganglia pathology per se may
not be the proximal cause of overt apraxia. It is when it is combined with dysfunc-
tion of the cortical components of the neural systems involved in sequencing, sen-
sorimotor transformation, and response selection that different types of ideomotor
praxis deficits would become clinically manifested.
This makes the point rather clearly. Here a component network of a more com-
plex and integrated network system dedicated to purposeful movement is damaged
and the downstream impact is apraxia. That while matter damage could occur at
multiple sites in the subcortical complex and, as long as the same cortical areas were
involved, the resultant functional behavioral disruption would be the same. When
combined with different cortical areas involved in different areas of function, such
as speech, these same subcortical white matter deficiencies would result in different
forms of praxis.
It should be recalled that as far as a clear understanding of the apraxic elements
of these disorders, it should be recalled that one of the definitions of apraxia
specifies that the disruption of ability to perform skilled movements cannot be

explained by the more fundamental motor disorders typical of patients with move-
ment disorders with clear etiology (i.e., Parkinson’s). That is to say, that the same
disrupted movement caused by disruption of the same circuitry would be labeled as
a praxis if the individual did not have a movement disorder that explained it.
The above is not meant to imply that it is only white matter disconnection in
subcortical areas that contributes to praxis. That is not the case. Research demon-
strates that pathological white matter alterations in a densely connected fronto-
temporo-parietal network of short and long association fibers is associated with
limb apraxia deficits. Major disconnection affected temporo-parietal and temporo-
temporal connections. Gray matter areas with a high number of disconnections
included inferior parietal lobe, middle and superior temporal gyrus, inferior and
middle frontal lobe, precentral gyrus, putamen, and caudate nucleus (Rosenzoph,
et al., 2020).
References
Barrios, J., Weng, W., England, R., Reifenberg, E., & Douglass, A. (2020). Hypothalamic dopa-
mine neurons control sensorimotor behavior by modulating brainstem premotor nuclei in
zebrafish. Current Biology, 30(23), 4606–4619. https://doi.org/10.1016/j.cub.2020.09.002
Chvatal, S., & Ting, L. (2012). Voluntary and reactive recruitment of locomotor muscle syner-
gies during perturbed walking. The Journal of Neuroscience, 32(35), 12237–12250. https://doi.
org/10.1523/JNEUROSCI.6344-11.2012
Conterno, M., Kümmerer, D., Dressing, A., Glauche, V., Urbach, H., Weiler, C., & Rijntjes,
R. (2021). Speech apraxia and oral apraxia: Association or dissociation? A multivariate lesion–
symptom mapping study in acute stroke patients. Experimental Brain Research, 240, 39.
https://doi.org/10.1007/s00221-021-06224-3
Cooper, R. (2007). Tool use and related errors in ideational apraxia: The quantitative simulation of
patient error profiles. Cortex, 43(3), 319–337.
De Renzi, E., & Lucchelli, F. (1988). Ideational apraxia. Brain, 111(5), 1173–1185. https://doi.
org/10.1093/brain/111.5.1173
Dumont, C., Ska, B., & Joanette, Y. (2000). Conceptual apraxia and semantic memory defi-
cit in Alzheimer’s disease: Two sides of the same coin? Journal of the International
Neuropsychological Society, 6(6), 693–703. https://doi.org/10.1017/S1355617700666079
Farah, M. J., O’Reilly, R. C., & Vecera, S. P. (1993). Dissociated overt and covert recognition as
an emergent property of a lesioned neural network. Psychological Review, 100(4), 571–588.
https://doi.org/10.1037/0033-295X.100.4.571
Frank, M., Loughry, B., O’Reilly, R. (2001). Interactions between frontal cortex and basal ganglia in
working memory: A computational model. Cognitive, Affective, & Behavioral Neuroscience, 1,
137–160. https://doi.org/10.3758/CABN.1.2.137
Fu, X., Zhou, G., Zhuang, J., Xu, C., Zhou, H., Peng, Y., et al. (2021). White matter injury
after intracerebral hemorrhage. Frontiers in Neurology, 12, 562090. https://doi.org/10.3389/
fneur.2021.562090
Hazy, T. F. (2007). Towards an executive without a homunculus: Computational models of the
prefrontal cortex/basal ganglia system. Philosophical Transactions of the Royal Society of
London. Series B, Biological Sciences, 362, 1601–1613.
References 77
Heilman, K., Maher, L., Greenwald, M., & Rothi, L. (1997). Conceptualized apraxia from lateral-
ized esions. Neurology, 49(2), 10.1212/WNL.49.2.457.
Hickok, G., Houde, J., & Rong, F. (2011). Sensorimotor integration in speech processing: com-
putational basis and neural organization. Neuron, 69(3), 407–422. https://doi.org/10.1016/j.
neuron.2011.01.019
Hickok, G. (2012). The cortical organization of speech processing: Feedback control and predic-
tive coding the context of a dual-stream model. Journal of Communication Disorders, 45(6),
393–403. https://doi.org/10.1016/j.jcomdis.2012.06.004
Huth, A., de Heer, W. A., Griffiths, W., Theunissen, F., & Gallant, J. (2016). Natural speech reveals
the semantic maps that tile human cerebral cortex. Nature, 532(7600), 453–459. https://doi.
org/10.1038/nature17637
Kelley, A., Shiltz, C., & Landry, C. (2005). Neural systems recruited by drug- and food-related
cues: Studies of gene activation in corticolimbic regions. Physiology & Behavior, 86(1–2),
11–14. https://doi.org/10.1016/j.physbeh.2005.06.018
Kirrie, B., Granier, J., & Robin, D. (2008). Understanding the nature of apraxia of speech: Theory,
analysis, and treatment. Neuropsychological Trends, 4, 7–44.
Koziol, L. B. (2009). Subcortical structures and cognition. Springer.
Koziol, L., & Budding, D. (2009). Subcortical structures and cognition. Springer.
Leiguarda, C. D., & Marsden, C. (2000). Limb apraxias: Higher-order disorders of sensorimotor
integration. Brain, 123(Pt 5), 650–879. https://doi.org/10.1093/brain/123.5.860
Leiguarda, R. (2001). Limb apraxia: Cortical or subcortical. NeuroImage, 14(1), 5137–5141.
https://doi.org/10.1006/nimg.2001.0833
Menon, V. (2013). Developmental pathways to functional brain networks: Emerging principles.
Trends in Cognitive Sciences, 17. https://doi.org/10.1016/j.tics.2013.09.015
Middleton, F., & Strick, P. (2000). Basal ganglia output and cognition: Evidence from anatomical,
behavioral, and clinical studies. Brain and Cognition, 42(2), 183–200. https://doi.org/10.1006/
brcg.1999.1099
Moser, D., Basilakos, A., Fillmore, P., & Fridriksson, J. (2016). Brain damage associated with
apraxia of speech: Evidence from case studies. Neurocase, 22(4), 346–356. https://doi.org/1
0.1080/13554794.2016.1172645
Mutha, P., Sainburg, R., & Haaland, K. (2010). Coordination deficits in ideomotor apraxia dur-
ing visually targeted reaching reflect impaired visuomotor transformations. Neuropsychologia,
48(13), 3855–3867. https://doi.org/10.1016/j.neuropsychologia.2010.09.018
Nasios, G., Dardiostis, E., & Messinis, L. (2019). From Broca and Wernicke to the neuromodula-
tion era: Insights of brain language networks for neurorehabilitation. Behavioural Neurology,
2019. https://doi.org/10.1155/2019/9894571
Park, E., Velumian, A., & Fehlings, M. (2004). Mechanisms of spinal cord injury: A review with
an emphasis on the implications for white matter degeneration. Journal of Neurotrauma, 21(6).
https://doi.org/10.1089/0897715041269641, on line.
Pramstaller, P., & Marsden, C. (1996). The basal ganglia and apraxia. Brain, 119(1), 319–340.
https://doi.org/10.1093/brain/119.1.319
Rakison, D. (2010). Perceptual categorization and concepts. In G. Bremner & T. Wachs (Eds.), The
Wiley-Blackwell handbook of infant. Wiley. https://doi.org/10.1002/9781444327564.ch7
Rosenzopf, H., Wiesen, D., Basilakos, A., Yourganov, G., Bonilha, L., Fridriksson, J., …
Sperber, C. (2022). Mapping the human praxis network: an investigation of white matter dis-
connection in limb apraxia of gesture production. Brain Communications, 4(1), 1–14. https://
doi.org/10.1093/braincomms/fcac004
Salvi, R., Wang, J., & Ding, D. (2000). Auditory plasticity and hyperactivity following cochlear
damage. Hearing Research, 147, 261–274.
Seven, Y., Mantilla, C., & Sieck, G. (2014). Recruitment of rat diaphragm motor units across
motor behaviors with different levels of diaphragm activation. Journal of Applied Physiology,
117(11), 1308–1316. https://doi.org/10.1152/japplphysiol.01395.2013
Sunderland, A., & Shiner, C. (2007). Ideomotor apraxia and functional ability. Cortex, 43(3),
359–367. https://doi.org/10.1016/S0010-9452(08)70461-1
with childhood apraxia of speech. Disability and Rehabilitation, 31(2), 94–102. https://doi.
org/10.1080/09638280701795030
Tuttolomondo, A., Pecoraro, R., & Pinto, A. (2014). Studies of selective TNF inhibitors in the
treatment of brain injury from stroke and trauma: A review of the evidence to date. Drug
Design, Development and Therapy, 8, 2221–2238. https://doi.org/10.2147/DDDT.S67655
Wang, M. L. (2014a). Co-occurring development of early childhood communication and
motor skills: Results from a population based longitudinal study. Child: Care, Health and
Development, 77–84.
Wang, M. L. (2014b). The developmental relationship between language and motor performance
from 3 to 5 years of age: A prospective longitudinal population study. BMC Psychology, 2, 34.
Wasserman, T., & Mion, A. (2019). The progression of memory loss secondary to TBI-induced
white matter attenuation: A review of the literature and case exemplar. Journal of Pediatric
Neuropsychology, 5(1–2), 31–40.
Wasserman, T., & Wasserman, L. D. (2020). Motivation, effort and the neural network model.
Springer.
Wessel, J., & Aron, A. (2017). On the globality of motor suppression: Unexpected events and
their influence on behavior and cognition. Neuron, 93(2), 259–280. https://doi.org/10.1016/j.
neuron.2016.12.013
Chapter 6
Developmental Coordination Disorder
One way of looking at the etiology of apraxia from a developmental perspective is

to look at what happens when a functional circuit is disrupted by injury or disease.
There is another way to consider. What happens when core motor circuits fail to
initiate or develop appropriately? Neural network modeling would suggest that
when this occurs, the ongoing, forward development of the individual could be neg-
atively affected in multiple ways, to varying degrees, resulting in numerous disor-
ders arising later in the developmental sequence. Some of these movement disorders
may, in fact, be classified as apraxic conditions. In summary, these early motor
networks comprise the foundation of more complex motor-based actions in syn-
chrony with other neural pathways. Finally, it should be remembered that these
newborn present neural networks are recruited for the numerous complex cognitive
and motor skills that develop as we progress toward adulthood. As such, we can
expect that if one of these foundational networks is disrupted, its inclusion in the
network configuration for more complex behaviors would result in disruptions to
the expression of all those subsequent behaviors, as well as impacting other network
configurations secondary to their shared pathways. We cannot overstate the impor-
tance of considering this perspective. For those of us in the world of pediatric neu-
ropsychology, whether it is in research, clinical practice, or neuropsychological
evaluations, we must begin to look at the developing brain of a child differently than
we do that of an adult. We must understand that applying a measure, whether in a
neuropsychological testing or in research, that is, labeling a deficit rather than
attending to areas of weakness, may cause us to miss the effects of a single or more
likely multiple areas of impact on the cognitive and daily functioning of a develop-
ing child. As motor pathways and behaviors are developing even prenatally, we
stress that disruption to this system is not a standalone disruption.

80 6 Developmental Coordination Disorder
Developmental Coordination Disorder (DCD)
Developmental coordination disorder refers to a neurodevelopmental disorder char-

acterized by deficits in both gross and fine motor skills. DCD is a heterogenous
disorder with various phenotypical presentations. DCD is a condition involving
limitations in gross motor, postural, and/or fine motor performance that are not
attributable to other neurological disorders. Presentation varied across children and
depends, in part, on their level of anticipatory motor control, response to specific
task demands, and ability to attend to feedback to achieve flexible, adaptive move-
ment. Children with DCD rely primarily on vision for feedback, frequently use
“fixing” strategies, and exhibit limited motor repertoires. As a result of their move-
ment problems, they tend to avoid physical activity and are prone to secondary
impairments, including decreased strength and power (Missiuna et al., 2003). DCD
affects a child’s ability to execute voluntary coordinated motor actions. This results
in poorly articulated, clumsy, slow, or inaccurate motor expression. Four main
hypotheses have been postulated to explain DCD in terms of deficits in visuospatial
functions, procedural learning, internal modeling, or executive functions.
Neuroimaging studies are limited but have underlined several brain regions, includ-
ing the parietal, frontal, and cerebellar cortices (Biotteau, 2020).
The History of Developmental Coordination Disorder
A developmental disorder affecting motor movement was initially termed “develop-

mental dyspraxia” (Langford, 1955) and described motor difficulties and gestural
and visuospatial dyspraxia. Attempts at describing the same disorder included labels
such as developmental apraxia, childhood dyspraxia, and sensory motor integration
disorder (Biotteau, 2020). Sensory integration disorder, currently termed Ayres
Sensory Integration (ASI), was hypothesized to result from inefficient integration or
organization of sensory information within the central nervous system (Ayres, 1972)
established well before contemporary neuroimaging techniques were available, and
remains a cornerstone treatment for occupational therapy interventions.
The DSM V describes developmental coordination disorder (DCD) as a neurode-
velopmental disorder (American Psychiatric Association, 2013) along with other
stereotypic and tic disorders. This neurodevelopmental umbrella also includes
childhood apraxia of speech, which is highlighted in another chapter in this volume,
referred to as speech sound disorders under the subheading of “Associated Features”
and described as a disorder for which “other areas of motor coordination may be
impaired as in developmental coordination disorder.” In short, developmental coor-
dination disorder is seen as the “umbrella” disorder under which other motor disor-
ders fall, including childhood apraxia of speech. While the DSM V refers to
overlapping phenotypes, this chapter is designed to highlight shared neural net-
works as a means of better understanding the often-shared phenotypical features
DCD Early Signs and Phenotypical Presentations 81
found across these diagnostic categories and to highlight how neural network theory
explains the ramifications developmentally, academically, and socially which often
accompany this diagnostic category.
As we have highlighted elsewhere, confusion and ambiguity in definitional terms
abound for many of the diagnostic categories. In an attempt to address the confu-
sion, the World Health Organization, in 1992, termed the disorder “specific devel-
opmental disorder of motor function.” In 1987, the term developmental coordination
disorder was adopted by the American Psychiatric Association. While we laud the
DSM V recognition of the disorders having neurodevelopmental underpinnings,
including possible genetic and biomarker risk factors, the DSM V remains largely
atheoretical and descriptive. In other words, ultimately, the DSM V lists a “disor-
der” based upon phenotype. Developmental coordination disorder is no exception.
Estimates of the prevalence of DCD vary according to the population of subjects
and the definition utilized and range roughly from 5 to 8 percent, with a predomi-
nance of males diagnosed ranging from 2:1 to 3:1 (Biotteau, 2020).
DCD Early Signs and Phenotypical Presentations
Expressed (phenotype) difficulties as a result of DCD vary across ages but are
observed early in the developmental course (Biotteau, 2020). Our current bent is to
often adapt a “wait and see” attitude with early development and we provide a wide
berth for the appearance of developmental milestones. Although we can applaud the
acceptance and implementation of early intervention programs, even those are
based upon the idea remediation rather than interception. However, there is research
to suggest that developmental coordination disorder provides risk factor signs early.
A recent study (Hua et al., 2022) looked at the association between onset of crawl-
ing and of independent walking with later motor development. The population was
a total of 8395 children between the ages of 3 and 6 in China who were assessed at
3–4 and at 5–6 years old via the Movement Assessment Battery for Children, sec-
ond Edition. The groups were categorized into “significant motor impairment” and
“at risk” compared to typically developing children. They found that a 1-month
delay in crawling increased the risk of significant overall (total score on MABC-2)
motor impairment by 5.3 percent when compared to typically developing children.
Compared to typically developing children, a 1-month delay in the onset of inde-
pendent walking increased the risk of overall motor impairment by 7.7 percent. The
risk became more pronounced with a 21.7 percent increase for “significant motor
impairment” group and by 11.9 percent for the at risk of motor impairment group.
The study confirms an association between delayed gross motor milestone achieve-
ment, crawling and walking, and subsequent motor impairment. Hua et al. extrapo-
late this association with other findings indicating that neurological evidence for the
crawling milestone has been shown to be accompanied by neural changes which
lead to cortical organization efficiency.
Phenotypical signs include poor postural control as noted by hypertonia or hypo-

tonia, poor distal control and hand coordination, impaired balance, and difficulty in
motor-based skills learning. Sensorimotor coordination is noted by poor sequencing
of movement, poor use of movement feedback mechanisms, timing, and anticipa-
tion (prior to actual movement). As a result, areas of difficulty can include skills in
dressing, utilizing tools such as scissors and eating utensils, tools, writing, playing
sports, etc. (Gueze, 2001). Children with developmental coordination disorder often
have lower academic achievement, reduced participation in social activities, which
can lead to a more sedentary lifestyle and social isolation (Rinat, 2020). In addition,
there are higher rates of anxiety and depression (Harrowell, 2017). While the pre-
dominant feature of DCD is motor learning and expression, difficulties with gross
or fine motor, or both. And while the diagnostic category of developmental coordi-
nation disorder is a standalone diagnosis, DCD often co-occurs with language
impairment and learning disabilities (Zwicker, 2009). In fact, children with DCD
often have at least one other diagnosis including attention-deficit hyperactivity dis-
order, autism spectrum disorder, learning disabilities, and specific language impair-
ment. ADHD is believed to be the most common comorbidly occurring disorder,
with a prevalence of over 50 percent of DCD children also presenting with ADHD
(Watemberg, 2007). The fact that there is a shared genetic component suggests that
developmental coordination disorder is likely sharing etiological components with
other developmental disorders as well (Martin, 2006). The shared phenotype pre-
sentations suggest shared connectome pathways.
A meta-analysis conducted by Wilson and McKenzie (1998) looked at “percep-
tual motor” problems in children with DCD, highlighting their difficulties in areas
of visualizing movement and visual spatial analysis. In fact, they found that the
greatest area of deficit was in visual processing, regardless of whether or not the
task included a motor component.
Conversely, a study looking at the relationship between cognitive function and
motor skills and their relation to school performance in students ages 8–14
(Fernandes, 2016) found a positive relationship between motor coordination and
total score on the academic achievement test as well as on the block design and
cancelation tests of the Wechsler Intelligence Scale for Children-IV. The authors
conclude that visual motor coordination and visual selective attention, although not
agility, are positively associated with academic achievement and cognitive function.
This makes a great deal of sense to the current authors as it speaks to the need for
visual motor coordination and visual selection in order to be successful in many
areas of academic skills including scanning reading pages, scanning mathematical
formulas, and writing.
As noted above, phenotyping varies. In an attempt to better define the presenting
phenotypes as they present in DCD, Green (2008) looked at intervention for chil-
dren grouped by level of severity of motor involvement and perceptual skills. They
found support for subtyping particularly five subgroups based upon perceptual and
motor performance. For example, one subtype was explored based upon the magni-
tude of movement difficulties and whether or not fine motor problems exceeded that
DCD Early Signs and Phenotypical Presentations 83
of gross motor problems as well as complex motor skills grouping. They found that
groups of children with visual perceptual deficits and with both visual perceptual
and motor impairment presented with higher impact of motor impairment. The
authors (Green, 2008) point out that there was considerable overlap and confound-
ing secondary to comorbidities, which might be considered a weakness in terms of
the particular study. However, for the purposes of this discussion, this speaks to how
difficult it is to find a child for whom only a single domain is impacted. That finding
a child for whom the impact is restricted to a single domain is the exception rather
than the rule.
The concept of executive function as a single domain has been discussed by the
current authors elsewhere. However, for the purposes of the current discussion, let
us agree to look at executive function as a means of looking at multiple areas of
functioning. Toward addressing the long-term trajectory of executive function com-
ponents, Bernardi et al. (2018) looked at children between the ages of 7 and 11.
They were assessed twice, 2 years apart. The authors found that developmental
gains were similar between the DCD group and controls. However, the gains still
reflected a gap between groups, that is, the children diagnosed with DCD performed
more poorly than the control group of children on all nonverbal executive function
tasks and the verbal fluency tasks at both times of assessment, 2 years apart. Of
course, the obvious point of importance for the purposes of this volume is the nota-
bility that these children, diagnosed with observable motor deficits, are presenting
with deficits well beyond the realm of motor.
The aforementioned study also included a group of children who presented with
poor motor skills but no formal diagnosis. These children showed less pervasive
executive function problems than those formally diagnosed. However, they did
show difficulties, particularly in the areas of fluency and working memory.
In reality then, can we say that although we utilize a diagnostic category, we may
be missing the impact of the identified area on other areas of functioning by labeling
an area of deficit without understanding or educating others, such as parents and
teachers, as to the extent of impact because of interrelatedness of neural pathways
(connectome). In our effort to address this, we often list multiple diagnostic catego-
ries to account for the multiple areas of deficit. However, are we truly providing a
deep as well as wide picture of a given child we have observed or evaluated if we
are, again, not explaining the neural pathway interrelatedness of brain-based behav-
ior and skill sets?
And what about the child who is at risk, but not presenting with weakness of suf-
ficient severity to warrant a diagnosis? If under research paradigms we are looking
at whole groups of children with undiagnosed weaknesses, but expressed weak-
nesses, are we not thereby ignoring the impact of the weaknesses on their academic
and social performance? Again, the current authors wish to highlight the importance
of recognizing the possibility, or probability, that soft signs, areas of weakness
rather than outright deficit, are likely concomitant areas of concern with significant
consequences.
Genetics Play a Role in Developmental Coordination Disorder
Genetic research as to etiology is still limited. The available research does point to
a genetic role in the etiology of the disorder. A summary of the available data and
research is provided: A family cluster (Gaines, 2008) was found in a Canadian fam-
ily consisting of a (married) mother and eight children, five of whom met the criteria
for DCD. These children also presented with speech articulation difficulties. Five of
the seven children did not crawl and milestone attainment for independent walking
was at the late end of normal. Four of the five children were late in attaining lan-
guage milestones such as (no) two-word utterances by 2 years of age and presenting
with limited vocabulary. The results of psychologist performed intellectual assess-
ment indicated normal intellectual functioning, with a common weakness of pro-
cessing speed. The authors discuss the likelihood of shared genetic causality across
disorders.
There has been some modest attention to a region of chromosome 16. For exam-
ple, the CNV 16p11.2 deletion, which results in childhood apraxia of speech, is also
implicated in motor coordination difficulties (Cunningham, 2019). Another study
looked at copy number variations (CNVs) (Mosca, 2016) in 82 children with DCD,
with or without ADHD and/or a reading disorder. They found an increased rate of
large and rare genic CNVs. Of these, 26 percent were found to have de novo rare
CNV. Of the inherited CNVs, 64 percent were inherited from a parent with a neuro-
developmental disorder. In addition, twin studies have revealed genetic contribution
estimates from 0.44 (Moruzzi, 2010) to 0.8 (Martin, 2006). Mountford (2021) point
out that the effect of any individual CNV is difficult to determine and that individual
CNVs may result in highly heterogeneous phenotypes.
Neuroimaging and Brain Studies
Following the course of study outlined for most disorders discussed in this volume,
the hunt for the etiology of DCD commenced with assumptions about lesions. As
far back as the 1960s, works by neurologists and neuropsychologists were looking
at the possible involvement of cortical areas. Work by Geschwind et al., (1975)
talked about possible disconnection syndromes. An assessment by Luria (Luria,
1973) talked about the role of the basal ganglia, parietal, and frontal lobes in motor
deficits. The underdevelopment of the cerebellum in premature infants led Lesny
(Lesny, 1980) to suggest the involvement of the cerebellum.
Children with developmental coordination disorder present with functional dif-
ficulties in posture, motor learning, and sensorimotor coordination (Zwicker, 2009).
A comprehensive review article by Zwicker (2009) considers the role of neural cor-
relates, including the cerebellum, parietal lobe, basal ganglia, and corpus callosum.
Considering the role of the cerebellum in motor coordination, balance, and posture,
the cerebellum is a likely choice for cortical involvement (Zwicker, 2009). Further,
Neuroimaging and Brain Studies 85
consideration of the role of the parietal lobe in processing visual spatial informa-
tion, coupled with research indicating visual spatial dysfunction in children with
DCD (Green, 2008), makes the parietal lobe another neural contender for involve-
ment in DCD.
A study by Querne et al. (2008) can be used to highlight an important point when
considering the neurophysiological integrity of a child’s brain-based behaviors for
example, during a neuropsychological evaluation or more cursory, perhaps age-
based pediatrician visit. Querne et al. were interested in looking at the impact of
DCD on neural connectivity during a go/no-go task. Utilizing fMRI they found that
children with DCD scored similarly to controls on a measure of correct inhibition.
However, their responses were slower and more variable. Utilizing structural equa-
tion modeling, they found an increase in path coefficients from both middle frontal
cortex and anterior cingulate cortex to inferior parietal cortex, particularly in the left
hemisphere in the DCD children. They found that path coefficients between the
striatum and parietal cortex decreased in the right hemisphere. Based upon this data,
Querne et al. hypothesize that DCD may reflect developmentally abnormal brain
hemispheric specialization. They also hypothesized that the connectivity issue
found in the middle frontal cortex-anterior cingulate cortex to inferior parietal cor-
tex network pathway indicates that children with DCD have a greater difficulty in
easily or promptly switching between initiation (go) and inhibition (no-go)
responses. Perhaps most interestingly, they hypothesize that children with develop-
mental coordination disorder compensate for the poor efficiency of the aforemen-
tioned neural network pathway through an increased engagement of the anterior
cingulate cortex. This strategy would prevent excessive commission errors. This
hypothesis is interesting for two reasons. Firstly, it speaks to neural plasticity in
allowing for one cortical region to compensate for another. Secondly, it raises the
question of when a child, with risk factors or mild connectivity issues, would pres-
ent with compensatory behaviors versus when the system would become over-
whelmed and pathognomonic signs are expressed. In other words, how many
children do we work with who may be experiencing compromised neural pathway
integrity but are able to compensate up to a given point, often masking the neural
compromise? What happens when this compensatory system is stressed? Are we
perhaps looking at the child who in a resting state appears fine, but when asked to
sit upright and write classroom notes, or write an essay under timed conditions, that
is, to maintain postural control and engage in a task requiring rapid fine motor coor-
dination skills, begins to decompensate? The implications for this with respect to
neuropsychological evaluation as well as the question of a child’s upward limit in an
academic setting should be given strong consideration.
The current state of affairs for very preterm infants reflects drastic increases in
survival rates. We are, however, first understanding what the degree of prematurity
may have on the developing brain. For example, a recent study looked at motor
brain areas in very preterm infants that was defined as infants with a gestational age
under 30 weeks and a birthweight under 1250 grams. Volumetric imaging was per-
formed at the infant’s term equivalent age. At 7 years of age, volumetric imaging
was repeated and diffusion tensor imaging was performed. At the term age
equivalent (Dewey, 2019), smaller brain volume was found for total volume, corti-
cal gray matter, cerebellum, caudate accumbens, pallidum, and thalamus in children
deemed at risk for DCD. The authors also found similar patterns when the children
were reevaluated at 7 years of age, that is, there was no catchup for brain growth in
the at-risk population. In fact, the children in the at-risk group presented with altered
microstructure in multiple white matter tracts. This was particularly true for the
motor areas.
Returning to neuroimaging studies, a later review of MRI such as neuroimaging
studies (Biotteau, 2016) indicated that the brains of children with developmental
coordination disorder present with atypical neuroanatomy. The findings point to an
extensive neural network involving the parietal and frontal regions, the basal gan-
glia, the cerebellum, the parietal lobe, and parts of the frontal lobe. Biotteau et al.
(2016) report on the literature associated with DCD and that which strongly sug-
gests the involvement of the cerebellum and its network connections. Their review
includes findings of visual distortions performed during motor tasks, difficulty with
touching finger to nose, and rapid alternating hand movements among those finding
pointing to the cerebellum or cerebellar loops being involved in DCD. Biotteau
(2016) also contend that the cerebellum is not the only neural structure involved.
They suggest that the basal ganglia, with associations with regulation of movement,
are also correlates of neural involvement. Taken together Biotteau (2016) hypothe-
sizes cortico-striatal and cortico-cerebellar network dysfunction.
Utilizing another major area of child development as an example, let us look at
the evidence for neural connection between motor network and language and the
implications for disturbances by association. In an interesting study, Jäncke (2007)
utilized voxel-based morphometry from high-resolution MRI scans, to search for
anomalies outside the typical language-based cortical areas. In this study of 42 chil-
dren, 21 with developmental language disorder and 21 typical children, the com-
parison of white to gray matter was assessed. In addition, simple hand motor tests
were used to assess for possible motor impairments in the children with develop-
mental language disorder. The results are noteworthy. Jancke et al. found decreased
white matter volume in a left hemisphere network which comprises the motor cor-
tex, dorsal premotor cortex, ventral premotor cortex, and planum polare on the
superior temporal gyrus. Specifically, these results are strongly indicative of the fact
that children with a developmental language disorder have “anomalous anatomy” in
a left-sided network which is comprised of both motor and language areas, indicat-
ing regionally identical areas for both domains. This provides stronger support to
the current authors’ contention that the current direction of looking for and identify-
ing individual domains of dysfunction, to correlate with, for example, the DSM
diagnostic categories, misses the probable impact of early disruption to any one area
of the associated neural pathways and larger connectome regions.
In addition to measures of functional activity, some studies have looked at mac-
rostructure or volume. These studies have been focused on cortical regions. For
example, one study (Langevin et al., 2015) looked at cortical thickness in children
with co-occurring attention-deficit disorder. As mentioned elsewhere, ADHD co-
occurs with DCD in up to 50 percent of cases. Their interest was in assessing
DCD and the Impact on Other Neural Substrates 87
whether the effects of the co-occurring neurodevelopmental disorders affected the

pattern of cortical development in a manner distinct from having a single disorder.
Langevin et al. found greater and more widespread reduced cortical thickness in
children with co-occurring DCD and ADHD than found for children with DCD or
ADHD alone. The cortical thinning was found to be widespread, with concentra-
tions in the frontal, parietal, and temporal lobes, and was correlated with measures
of motor functioning and attentional functioning. This finding is compelling all on
its own. We now have to look at the rate of ADHD co-occurring with DCD. And
while the current authors do not have the answer, we do wonder about how many of
these children have impact on reward and attention circuitry without meeting crite-
ria for a formal diagnosis of ADHD.
(Note: Both the cerebellum and the basal ganglia are discussed in greater detail
elsewhere in this volume. The reader is encouraged to review these sections in order
to better understand the involvement of these cortical and subcortical regions in the
initiation and regulation of voluntary motor movement and coordination. In particu-
lar, the reader will be directed to the implications of these regions as mechanisms
working in unison in the developing brain and the expression of deficits in associ-
ated disabilities such as childhood apraxia of speech.)
DCD and the Impact on Other Neural Substrates
How Embedded in Other Systems Is the Motor System?
Historically, as we have discussed, the brain was considered to be composed of

modular systems that were discrete and dissociable from each other. Seminal work
by Wernicke and Broca, based upon lesion models, ascribed functional properties to
specific area of the brain (i.e., the left hemisphere and language). The motor net-
works were no exception as they were considered to be an independent domain.
Traditionally then, the neural substrates serving language functions and actions
were considered dissociable and independent of the motor functional systems
(Mirabella, 2017).
That thinking, however, began to change following advances in neuroscience and
neuroimaging. An early overview in the work of Koziol et al. (2012) and others
outlined how these neural network systems were integrated and that this integration
was essential for complex human behavior. For example, Bak’s disease model of
motor neuron disease symptom presentation (Bak, 2012) proposed that the cogni-
tive and motor symptoms which present in motor neuron disease reflect the same
neurodegenerative process spreading along functional connections.
The current authors wish to suggest that just as the neurodegenerative process of
motor neuron disease affects the closest functional links to the motor system, includ-
ing the processing of verbs and action words, this model provides a back-tracing
ability to understand how language function and embedded meaning advanced in
the developing brain. To date, there is a full body of research to indicate that the
motor system is highly associated with constructs and their subserving neural path-
ways including executive function (Wilson, 2020), attention (Kirst et al., 2017),
learning disabilities (Zwicker, 2009), language, and autism spectrum disorder
(Fulceri et al., 2019).
Toward this point, using a longitudinal study, Wilson et al. (2020) looked at 186
children who met the DCD criteria based upon the DSM 5. They were screened with
McCarron Assessment of Neuromuscular Development at two periods over the
course of 2 years. The Groton Maze Learning Test served as the measure of execu-
tive function. They found that 41 percent of the children diagnosed with DCD
showed significantly lower levels of executive functioning as compared to children
with typical motor development. This was true for both time points. This finding
suggests that children with persisting DCD (which we know can persist into adult-
hood) demonstrated poorer executive function development than those with typical
motor development or who demonstrated remitting DCD. We use this example
because despite differences about the discussion of executive function as a stand-
alone domain, this speaks to how skills associated with executive function, such as
attention, motivation, persistence, etc., can theoretically be affected as the effect of
motor coordination disorder impacts developing neural connections (Wasserman &
Wasserman, 2013).
In a study (Piek, 2008) designed to assess the merits of utilizing measures of
motor performance for children between 4 months and 4 years of age to predict
motor and cognitive performance at school age, parents were asked to complete the
Ages and Stages Questionnaires (ASQ). At school age both motor and cognitive
ability were assessed using the McCarron Assessment of Neuromuscular
Development for fine and gross motor abilities and the Wechsler Intelligence Scale
for Children-IV for cognitive ability assessment. In a sample of 33 children, after
controlling for SES, the fine motor trajectory information was not found to account
for a significant proportion of variance for fine motor performance or cognitive
performance. However, with controlling for SES, the ASQ gross motor trajectory
did account for a significant proportion of the variance for cognitive performance.
In addition, a significant predictive relationship for the gross motor trajectory infor-
mation and the subtests on the Wechsler Scales for working memory and processing
speed may be considered components of, or impacting the components of, executive
function and efficiency on specific tasks. This study adds to the body of research
supporting the potential impact of early gross motor development on later develop-
ing cognitive skills.
In addition, there is some evidence to indicate that an impacted motor system is
associated with action-based language processing. Utilizing a go/no-go task, the
processing of action verbs in children with developmental coordination disorder
was compared to that of typical children. Two versions of the go/no-go task were
utilized in which verbs expressing hand, foot, or abstract action were presented. In
the “semantic” task, arm-reaching movement toward a target is required when either
hand or foot actions are presented. The subjects are to refrain from reaching when
DCD and the Impact on Other Neural Substrates 89
abstract verbs are presented. A second version of the paradigm was also presented
wherein the subjects were asked to utilize color discrimination rather than the
semantic meaning of the verb to decide on whether to reach or not. That is to say,
the decision to move is based upon the color of the verb presented rather than the
semantic meaning of the verb presented. The results indicated that children with
DCD did not demonstrate any difference between verb categories. Typically devel-
oping children, in contrast, showed an increase in reaction time to a verb involved
in the same effector used to give the response. That is to say, when the meaning of
the verb was the cue for reaching, both reaction time and percentage of error
increased for typically developing children. The authors (Mirabella, 2017) conclude
that this is a pathognomonic sign of the motor system impacting language processing.
Are there risk factors that don’t meet pathognomonic levels? What are the poten-
tial implications? Some of these questions were considered in a published doctoral
dissertation by Goyen (Goyen, 2005) who noted that infants born under 29 weeks
gestation (extremely premature) or extremely low birth weight (under 1000 grams)
are at high risk for major and minor sequelae, but the research on these children is
often limited to assessing for major deficits. The majority of these children are often
termed “apparently normal” with “normal intelligence” and no major sensorineural
disabilities. However, Goyen (2005) notes that these children present with “minor
motor dysfunction,” the impact of which is not investigated. Using an embedded
multiple study paradigm, Goyen found the following: in a longitudinal study, chil-
dren were assessed with the Peabody Developmental Motor Scales at the corrected
(for prematurity) age of 18 months and again at 3 and then 5 years of age. Goyen
found that 64 percent of the children presented with persistent fine motor problems
throughout this time frame. In addition, the proportion of children with gross motor
deficits actually increased from 18 months (corrected) to the 5-year mark with 81
percent of the children now showing gross motor impact. The second study looked
at the impact of motor function in school-aged children from an “apparently nor-
mal” high-risk group. This included children with an IQ < 85 and no identified
sensorineural disability. The results indicated a significantly higher presentation of
DCD compared to the control group. That is to say, utilizing the Movement
Assessment Battery for Children and a battery of sensorimotor tests, the high-risk
group presented with 42 percent falling in the DCD category compared to 8 percent
in the control group. Of note, it was what are considered “neurological soft signs”
that contributed to the diagnosis of developmental coordination disorder in the high-
risk group. This included postural praxis and sequencing praxis. These findings
speak to often unrecognized weakness children must endure or compensate for but
ones which most certainly impact the quality of their everyday efforts. In fact, study
3 did find poorer handwriting legibility and speed in comparison to the children’s
controls in a classroom setting. These children were the same studied in the prior
sub-study allowing for an assessment of comorbidity between DCD and handwrit-
ing dysfunction. The finding was that of the high-risk children identified as meeting
the criteria for DCD, there was a 43 percent comorbidity level for handwriting
dysfunction.
otor Networks in the Newborn and Their Involvement

M
with Later Skills Development
The question of whether movement is produced by active (motor programs) or

reactive (reflex) means is quite literally an age-old question, dating back to
Aristotle. More recently, this question was fueled by the studies of Ivan Pavlov.
Pavlov developed a theory of inborn and conditioned reflexes, according to which
all movement is an extension of inborn or conditioned reflexes. He posited that
new movement emerges as a result of the creation of repetitive excitation neurons
creating new neural pathways. Also highly influential was the work of a neuro-
physiologist, Sir Charles Sherrington, who posited that movement is modulated
by the parameters of reflexes. For example, he discovered muscle spindles which
initiate the stretch reflex, a reflex he maintained was necessary for posture and
balance. It was Sherrington who coined the terms “synapse” and “neurons,” and
his work helped to shape our understanding of the brain and spinal cord, as well
as efferent and afferent nerve fibers (Latash, 2008). In contrast was the argument
by Bernstein (2003) for motor programs. This theory of generalized motor pro-
grams posited that patterns of mechanical variables of muscle and joint torque
were encoded in the central nervous system (Latash, 2008). In this paradigm, a
motor pattern is associated with a motor program. This brings us to the equilib-
rium-point hypothesis (Feldman & Levin, 1995) which combines elements of the
reflex model and the motor program model. A detailed review of the studies ema-
nating from these models, looking at muscles, enervation, equilibrium and multi
joint, whole body movement, is far beyond the scope of this chapter and, can be
found in the work of Latash (2008).
From the perspective of child development and neural pathways, we can agree
that core systems of the brain are established during the gestational course and are
foundational to infants’ emerging developmental competencies. Among the earliest
to mature are the motor and sensory systems, which support the ability of the infant
to interact with and receive input from the world (Thomason et al., 2018). From
their formation these neural systems are highly malleable which supports a learned
fit between the early environment and the infant brain. The brain is primed at birth
to receive inputs from sensory organs, and the signals received play an essential role
in advancing neurodevelopmental processes. Experimental disruption to normal
occurrence and propagation of activity through sensorimotor systems leads to per-
manent loss of function in those systems and lasting atypical cortical organization.
Thus, sensorimotor systems are present at birth, and receptive to signals from the
environment, which instruct further developmental patterning of neural systems.
Moreover, these systems can produce behavior, enabling the developing organism,
or infant, to build representations of stimulus-response properties through interac-
tion with the environment.
What are the elements of the network? Thanks to advances in neuroimaging and
the neurosciences, there is ample data to demonstrate that this robust fetal
Functional Expression in Later Development 91
sensorimotor neural network includes regions of the motor and sensory cortices,
cerebellum, thalamus, posterior cingulate cortex, and striatum. Also included are
regions of the posterior cingulate cortex, supplementary motor cortex, medial tem-
poral lobe, and superior frontal gyrus (Thomason et al., 2018).
Functional Expression in Later Development
Although once considered to possibly remediate on its own through maturation,

there is ample evidence that DCD can persist into adolescence and adulthood.
Studies clearly indicate that deficits in motor coordination extend into adulthood
with resulting effects on academic functioning, non-academic functioning, with
concomitant impact on the emotional state of the affected persons (Tal-Saba,
2012). A study by Cousins and Smyth (2003) recruited individual between the
ages of 18 and 65 who had been diagnosed previously with DCD or dyspraxia.
The participants were assessed on motor dexterity, handwriting, construction, bal-
ance, avoidance of obstacles, reaction time, movement time, and sequencing. The
performance of the DCD participants was marked by greater slowness and vari-
ability of movement. Many of the participants had difficulties with sequencing.
The data indicates that motor difficulties, and its associated complications, do
persist into adulthood.
As mentioned previously, there is a high degree of associated features between
DCD and ADHD (Watemberg, 2007). Looking at the concept of executive function
in young adults with developmental coordination disorder as compared to controls
(Tal Saban, 2014), participants with DCD completed the BRIEF-A to assess execu-
tive function skills and the WURS questionnaire to assess attention issues. The
executive function profiles of persons with DCD and borderline DCD indicated
significantly poorer functioning than those of the control group, and no significant
differences regarding attention issues were found between the DCD and borderline
DCD groups. The results of the study also suggest that executive functions can be
affected with or without concomitant attention issues.
Also of interest is a study (Cleaton et al., 2021) specifically intending to look at
gender differences in presentation. Cleaton et al. found that in adults (aged 16–25)
diagnosed with DCD, women reported more impact in gross and non-motor activi-
ties. They also reported a negative impact on participation in activities. In contrast,
men reported greater fine motor difficulties. There are so many fascinating ques-
tions that can be asked given this kind of information. For example, given the age of
the groups, were boys identified because of school-based behavior, specifically the
typical need in a classroom to take notes? Are women more easily able to state that
they are not good in sports? Did these weaknesses impact social and/or attention
areas of functioning? Gender provides one more area of interest for consideration
when looking at phenotype presentations.
hild Development: The Result of the Integration

C
of Movement, Language, and Cognitive Processes
Action understanding is a critical foundation for developing social cognitive con-

structs. The ability to understand actions is at the base of empathy, theory of mind,
cooperation, and other skills including language (Salo, 2019). Actions are behavior
and motor based. Salo (2019) suggest that activation of the motor system during the
observation of actions underlies both action understanding and the larger construct
of communication.
When Does the Development of the Motor System Begin?
In a study of fetal movement and development (Einspieler et al., 2021), a point,

perhaps central to this chapter, is highlighted. Einspieler et al. state “The term sen-
sory is always used first when we discuss the central nervous system (sensori-motor)
as a functional unit” followed by “but the actual ontogeny of behaviour is quite the
opposite. The developing nervous system in its early stages ought to be seen as a
motor-sensory organ, therefore we should put the term motor first.” They cite mul-
tiple sources, dating back to 1885, and confirmed by modern technology, which
establishes that spontaneous motility occurs in utero, even preceding external (sen-
sory) input. The term “central pattern generator” refers to the underlying neural
circuitry of the endogenously generated activity, which, modulated by the periph-
ery, is not triggered by external sensory stimulation. Of great significance is the
term “rhythmicity,” a term we have stressed the importance of in the chapter on
language, stressed here for motor movement. Specifically, rhythmicity, “which is
inherent not only in alternating movements for locomotion, sucking and breathing
movements, but also in the alternation of short phases of activity followed by longer
phases of inactivity,” is a typical pattern of fetal behavior. They point out that con-
trary to popular notions, the fetus is not typically in a fixed, flexed position. Rather,
there are a multitude of fetal movement patterns which are spontaneously gener-
ated, and these movement patterns are closely associated with development of
peripheral and central structures. That is to say, these movement patterns are inte-
gral to muscular neural development. Many of these movements already reflect an
integrating system. For example, at 8–10 weeks gestation, the entire body move-
ment is observed. Actually, there are two movement patterns observed. There are
startles that initiated in the limbs which spread to the neck and trunk. There are also
slower, more complex movements called general movements. Their presentation is
simultaneous and points to an adaptive pattern since startles often induce a general
movement. This is a good example of early modulation, a process necessary for
almost every conceivable human behavior.
Some motor movements can be seen in utero and become a function later on. For
example, yawning, a behavior occurring across species, is hypothesized to impact
When Does the Development of the Motor System Begin? 93
arousal and communication as it increases cerebrospinal fluid circulation. Beginning

at 14 weeks gestation, rhythmic jaw openings and closings followed by swallowing
movements can be observed. The neuronal network is formed and functional by
28 weeks gestation and consists of suck-swallow-breathe patterns reflecting a rhyth-
mic motor sequence (Shandley, 2021), again, complex motor sequences with func-
tional purpose later. Einsplier et al. (2021) point out that fetal sucking changes the
composition of the fluid in the nasal and laryngeal pathways which is critical for
chemo-sensation development. In addition, there is considerable literature indicat-
ing that suck ability serves not only as a marker for oral feeding skills but for its
association with neuromotor integrity, neuromodulation, and sensorimotor systems
(Poore, 2009) as well as later speech-language disorders.
Pointing has also been observed in utero (Einspieler et al., 2021) and is a motor
behavior, sophisticated in that it requires digital isolation, and is later used as a com-
munication strategy.
“Embryonic/fetal movements are an integral part of typical development, as
skeletal, muscular, and neural developments in particular are activity-dependent. If
embryonic/fetal neuromuscular activity is silenced pharmacologically or by dis-
ease, the population of spinal motor neurons, the transmitter specification, the pat-
tern of neuromuscular synaptic contact, and genetically determined cell death
develop atypically.” The impact of these factors can be observed in the fetus. “In
case of brain dysfunction, fetal general movements alter their sequence and gestalt,
which suggests a dysfunction of the developing nervous system” (Einspieler et al.,
2021). While one might not initially conceive of this as apraxia, it clearly relates to
disturbed motor behavior perhaps affected by external factors such as maternal drug
use, which in turn can be impacting central nervous system development. The
expression is noted by alterations in motor sequences and presentations in utero.
From the perspective of neuropsychology and child development, the implica-
tions are huge. First, motor development precedes cognition. Second, motor devel-
opment “even” in utero is showing patterns of behaviors which are later directed to
be functional in the expression and reception of communication as well as the pro-
cessing of incoming information. Third, modulation of go/no-go behavior begins in
utero with motor behavior. We have the beginnings of neural substrates critical for
integrating all aspects of human behavior.
By perceiving this period through the early stages of child development as sim-
ply “developmental,” we are missing critical information necessary for a complete
understanding of a child’s brain-based behavior.
From a pediatric neuropsychology perspective, we are potentially underestimat-
ing the impact of soft signs on a child’s academic, social, and physical development.
That is to say, the error of waiting for pathognomonic signs to emerge as measured
by “standardized” norms. As regards the ability of a neuropsychologist to assess
these functions, it is accurate to say that they can be assessed, but perhaps not
“tested” as far as normative instruments are concerned. It is the integrity of these
motor-sensory systems that can be assessed using procedures such as in the Neonatal
Behavioral Assessment Scale (Brazelton, 1973) which provides useful qualitative
data on early neural integrity, by assessing response patterns to sensory input, and
the results of which can be extrapolated to future cognitive activity. This knowledge
can be used to generate intervention plans when necessary, thereby allowing neuro-
psychologists to meaningfully participate in the care of these at-risk infants.
With regard to neuropsychological assessment at later points in a child’s devel-
opment, many neuropsychologists often make what we would consider to be a mis-
take, that of under-inquiring about and/or observational testing of early motor
development and tying that to other domains and to the presenting reason for refer-
ral. Observation is one of our strengths. While we are focusing training on the utili-
zation of tests as measures, we need to also remember to observe. When he was
stringing beads, was he successful? But did he have to balance both string and hands
on a hard surface or was he able to elevate his hand? Was the stringing smooth or
did he drop one or two beads first? How did that child descend the stairs? Was he
sure of his movements and talking at the same time or did he run his foot along the
edge of the stair and rotate his body toward the banister for more security? Was he
able to stand on one foot or did he reach for a surface to lean on first? These indica-
tors may not be on a standardized measure, but they are diagnostic. And if they are
on a standardized measure, be careful on how you score it. Is getting the bead on the
string the point? Or is the quality of the sequencing and movements the impor-
tant factor?
From a clinical standpoint, this may mean underestimating the impact of dys-
functional systems such as dyspraxia vs. apraxia. From a societal perspective, it
means we may be missing a vital period for intervention services which may, if
delivered during early developmental critical periods, afford greater remediation
than if delivered later.
References
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders
fifth edition.
Ayres, J. (1972). Types of sensory integrative dysfunction among disabled learners. American
Journal of Occupational Therapy, 26(1), 13–18.
Bak, T. H. (2012). What wires together dies together: Verbs, actions and neurodegeneration in
motor neuron disease. Cortex, 48(7), 936–944.
Bernardi, M. L. (2018). Executive functions in children with developmental coordination disorder:
a 2-year follow-up study. Developmental Medicine and Child Neurology, 306–313.
Bernstein, N. (2003). Contemporary studies on the physiology of the of the neural process. Smysl.
Biotteau, M. C. (2016). Neural signature of DCD: A critical review of MRI neuroimaging studies.
Frontiers in Neurology. https://doi.org/10.3389/fneur.2016.00227
Biotteau, M. A. (2020). Developemental coordination disorder. In A. B. Gallagher (Ed.), Handbook
of clinical neurology. Vol 174 Neurocognitive development: Disorder and disabilities (pp.
3–20). Elsevier.
Brazelton, T. B. (1973). Neonatal behavioral assessment scale.
Cleaton, A. T.-S., Tal-Saban, M., Hill, E. L., & Kirby, A. (2021). Gender and age differences in the
presentation of at-risk or probable developmental coordination disorder in adults. Research in
Developmental Disabilities, 115, 104010. https://doi.org/10.1016/j.ridd.2021.104010
References 95
Cousins, M. & Smyth, M. M. (2003). Developmental coordination impairments in adulthood.

Human Movement Science, 22, 433–459. https://doi.org/10.1016/j.humov.2003.09.003. PMID:
14624827.
Cunningham, A. C. (2019). Coordination difficulties, IQ and psychopathology in children with
high-risk copy number variants. Psychological Medicine, 51, 290–299. https://doi.org/10.1017/
S0033291719003210
Dewey, D. T. (2019). Very preterm children at risk for developmental coordination disorder have
brain alterations in motor areas. Acta Paediatrica, 108(9), 1649. https://doi.org/10.1111/
apa.14786
Einspieler, C. P., Prayer, D., & Marschik, P. B. (2021). Fetal movements; the origin of human
behaviour. Developmental Medicine & Child Neurology, 63(10), 1142–1148.
Feldman, A. G., & Levin, M. F. (1995). Positional frames of reference in motor control: Their
origin and use. Behavioral and Brain Sciences, 18, 723–806.
Fernandes, W. S.-P. (2016). Motor coordination correlates with academic achievement and cogni-
tive function in children. Frontiers in Psychology, 7. https://doi.org/10.3389/fpsyg.2016.00318
Fulceri, F., Grossi, E., Contaldo, A., Narzisa, A., Apicella, F., Parrini, I., et al. (2019, January 9).
Motor skills as moderators of core symptoms in autism spectrum disorders: Preliminary data
from an exploratory analysis with artificial neural networks. Frontiers in Psychology. https://
doi.org/10.3389/fpsyg.2018.02683
Gaines, R. C. (2008). Clinical expression of developmental coordination disorder in a large
Canadian family. Paediatrics and Child Health, 13, 763–768.
Geshwind, H., Tenaillon, A., Samii, K., Nitenberg, G., & Farah, E. (1975). Evaluation des lesions
tricuspidiennes par la cineangiographie. Coeur, 6, 687–703.
Goyen, T. (2005). Motor dysfunction in apparently normal high-risk children. Academia.edu. https://
www.academia.edu/27667038/Motor_dysfunction_in_apparently_normal_high_risk_children
Green, D. C. (2008). Does subtype of developmental coordination disorder count: Is there a dif-
ferential effect on outcome following intervention? Human Movement Science, 27, 363. https://
doi.org/10.1016/j.humov.2008.02.009
Gueze, R. J.-E. (2001). Clinical and research diagnostic criteria for developmental coordination
disorder: A review and discussion. Human Movement Science, 20(1-2), 7–47.
Harrowell, I. H. (2017). Mental health outcomes of developmental coordination disorder in late
adolescence. Developmental Medicine & Child Neurology, 59(9), 973–979.
Hua, J. W., Williams GJ, Jin H, Chen J, Xu M, Zhou Y, Gu G, Du W (2022). Early motor milestones
in infancy and later motor impairments: A population-based data linkage study. Psychiatry.
https://doi.org/10.3389/fpsyt.2022.809181
Jäncke, L. S. (2007). Decreased white-matter density in a left-sided fronto-temporal network in
children with developmental language disorder: Evidence for anatomical anomalies in a motor-
language network. Brain and Language, 91–98.
Kirst, C., Modes, C., & Magnasco, M. (2017). Shifting attention to dynamics: Self-reconfiguration
of neural networks. Current Opinion in Systems Biology, 3, 132–140. https://doi.org/10.1016/j.
coisb.2017.04.006
s12311-011-0321-y
Langevin, L. M., MacMaster, F. P., & Dewey, D. (2015). Distinct patterns of cortical thinning in
concurrent motor and attention disorders. Developmental Medicine and Child Neurology, 3,
257–264.
Langford, W. (1955). Developmental dyspraxia – Abnormal clumsiness. Bulletin of the Orton
Society, 5, 3–7.
Latash, M. (2008). Evolution of motor control: From reflexes and motor programs to the
equilibrium-point hypothesis. Journal of Human Kinetics, 19, 3–24.
Lesny, I. (1980). Developmental dyspraxia-dysgnosia as a cause of congenital children’s clumsi-
ness. Brain Development, 2, 69–71. https://doi.org/10.1016/S0387-7604(80)80009-X
Luria, A. (1973). The working brain. Basic Books.
Martin, N. P. (2006). DCD and ADHD: A genetic study of their shared aetiology. Human Movement
Science, 25, 110–124.
Mirabella, G. D. (2017). Developpmental coordination disorder affects the processing of action
relate verbs. Frontiers in Human Neuroscience, 10. https://doi.org/10.3389/fnhum.2016.00661
Missiuna, C., Rivard, L., & Bartlett, D. (2003). Early identification and risk management of chil-
dren with developmental coordination disorder. Pediatric Physical Therapy, 15(1), 32–38.
Moruzzi, S. P.-G. (2010). Clumsiness and psychopathology: Causation or shared etiology? A twin
study with the CBCL 6–18 questionnaire in a general school-age population sample. Human
Movement Science, 29, 326–338. https://doi.org/10.1016/j.humov.2010.01.005
Mosca, S. L. (2016). Copy-number variations are enriched for neurodevelopmental genes in chil-
dren with developmental coordination disorder. Journal of Medical Genetics, 53(12), 812–819.
https://doi.org/10.1136/jmedgenet-2016-103818
Mountford, H. H. (2021). Genome-wide association study of motor coordination. Frontiers in
Human Neuroscience. https://doi.org/10.3389/fnhum.2021.669902
Piek, J. D. (2008). The role of early fine and gross motor development on later motor and cognitive
ability. Human Movement Science, 5, 668–681.
Poore, M. B. (2009). Suck predicts neuromotor integrity and developmental outcomes. Perspective
on speech and Orofacial Disorders., 19, 44. https://doi.org/10.1044/ssod19.1.44
Querne, L., & Berquin, P. (2008, 1244). Dysfunction of the attentional brain network in children
with Developmental Coordination Disorder: A fMRI study. Brain Research, 89–102.
Rinat, S. I.-N. (2020). Children with developmental coordination disorder show altered func-
tional connectivity compared to peers. Neuroimage: Clinical, 27. https://doi.org/10.1016/j.
nicl.2020.102309
Salo, V. F. (2019). The role of the motor system in action understanding and communication:
Evidence from human infants and non human primates. Developmental Psychobiology, 61(3),
390–401.
Shandley, S. C. (2021). Abnormal nutritive sucking as an indicator of neonatal brain injury.
Frontiers in Pediatrics, 8. https://doi.org/10.3389/fped.2020.599633
Tal Saban, M. O. (2014). Executive function and attention in young adults with and without
Developmental Coordination Disorder – A comparative study. Research in Developmental
Disabilities, 35, 2644–2650.
Tal-Saba, M. Z. (2012). The functional profile of young adults with suspected developmental coor-
dination disorder (DCD). Research in Developmental Disabilities, 33, 2193–2202. https://doi.
org/10.1016/j.ridd.2012.06.005
Thomason, M., Hect, J., Waller, R., Manning, J., Stacks, A., Beeghly, M., et al. (2018). Prenatal
neural origins of infant motor development: Associations between fetal brain and infant motor
development. Developmental Psychopathology, 30(3), 763–772. https://doi.org/10.1017/
S095457941800072X
Wasserman, T., & Wasserman, L. (2013). Towards a unifying model of executive function. Applied
Neuropsychology: Child, 2(2), 88–96. https://doi.org/10.1080/21622965.2013.748394
Watemberg, N. W.-S. (2007). Developmental coordination disorder in children with attention-
deficit–hyperactivity disorder and physical therapy intervention. Developmental Medicine &
Child Neurology, 920-925(49), 12.
Wilson, P. H., & McKenzie, B. E. (1998). Information processing eficits associated with develop-
mental coordination disorder: A meta-analysis of research findings. Jornal of Child Psychology,
39, 829–840.
Wilson, P. R.-G. (2020). Cognitive and motor function in developmental coordination disorder.
Developmental Medicine and Child Neurology, 1317–1323.
Zwicker, J. M. (2009). Neural correlates of developmental coordination disorder: A review of
hypotheses. Child Neurology, 24, 1273–1281.
Chapter 7
Since, as we have reported, the inspiration for this book was a child with childhood
apraxia of speech, we thought it’s only fitting to cover this apraxic condition in more
detail. We also note that the developmental nature of the disorder and the lack, in
most cases, of an identifiable etiology provide fertile ground for a discussion of
neural network modeling. Specifically, this chapter will review the current under-
standings of CAS based upon descriptive diagnostic characteristics, followed by an
integration of neuroimaging and genetic information. Following this a second chap-
ter will detail our understanding of neural network development and how brain-
based development may be affected by and impact the expression of unfolding
developmental skills across language, cognitive, academic, and social venues.
What Is Childhood Apraxia of Speech?
Based on the phenotypical nature of the existing definitions, this seems like a
straightforward question. However, just as there is much confusion about the defini-
tion of apraxia proper, ambiguity extends into the discussion of what is a childhood
apraxia of speech.
According to the American Speech-Language-Hearing Association (ASHA)
(American Speech Hearing Association, 2022), childhood apraxia of speech (CAS)
is a neurological childhood (pediatric) speech sound disorder in which the precision
and consistency of movements underlying speech are impaired in the absence of
neuromuscular deficits (e.g., abnormal reflexes, abnormal tone). As stated in this
definition, CAS may occur as a result of known neurological impairment, in asso-
ciation with complex neurobehavioral disorders of known and unknown origin, or
as an idiopathic neurogenic speech sound disorder. The core impairment in planning

98 7 Childhood Apraxia of Speech
and/or programming spatiotemporal parameters of movement sequences results in

errors in speech sound production and prosody (Childhood Apraxia of Speech, 2022).
The term childhood apraxia of speech (CAS), as used by ASHA, covers all forms
and presentations of apraxia of speech in childhood whether or not the etiology is
congenital or acquired and whether or not it is associated with a specific etiology.
ASHA prefers CAS over other terms used for this disorder, including “develop-
mental apraxia of speech” and “developmental verbal dyspraxia,” which typically
refer to idiopathic presentations and not to acquired neurological etiologies. The
rationale, as described on their website, states that they are concerned that the
“inclusion of the term ‘developmental’ in reference to childhood apraxia might be
incorrectly interpreted as indicating that children can ‘grow out of’ this disorder.”
Unlike a speech delay, they note that the characteristics of CAS are likely to persist
past the developmental period (Lewis et al., 2004). Other expert sources make note
of the definition. For example, the Mayo Clinic website (Mayo Clinic, 2022) notes
that “CAS is sometimes referred to as Developmental Apraxia. They agree with
ASHA when they go on to say that children with CAS don’t necessarily grow out of
CAS as they develop. They highlight critical differences when they point out that,
as compared to children with delayed speech or developmental language disorders
where children follow usual patterns in development of speech and sounds, but they
develop more slowly than usual.” Children with CAS don’t make typical develop-
mental sound errors. It is not an issue of delayed development.
A formalized definition of CAS is presented in the Diagnostic and Statistical
Manual of Mental Disorders, 5th edition (American Psychiatric Association, 2013)
which includes CAS in the category of speech sound disorder. According to the
DSM 5 which prefers the term verbal dyspraxia, CAS is defined as:
(A) Persistent difficulty with speech sound production that interferes with speech
intelligibility or prevents verbal communication of messages.
(B) The disturbance causes limitations in effective communication that interfere
with social participation, academic achievement, or occupational performance,
individually or in any combination.
(C) Onset of symptoms is in the early developmental period.
(D) The difficulties are not attributable to congenital or acquired conditions, such
as cerebral palsy, cleft palate, deafness or hearing loss, traumatic brain injury,
or other medical or neurological conditions.
The DSM 5 goes on to describe how speech production describes the clear
articulation of the phonemes that, in combination, make up spoken words. It notes
how “speech sound production requires both the phonological knowledge of
speech sounds and the ability to coordinate the movements of the articulators (i.e.,
jaw, tongue, and lips) with breathing and vocalizing for speech.” It goes on to
clarify that “Children with speech production difficulties may experience difficulty
with phonological knowledge of speech sounds or the ability to coordinate move-
ments for speech in varying degrees.” Speech sound disorder is thus heterogenous
Is There a Difference Between CAS and Verbal Dyspraxia? 99
and multidimensional in its underlying mechanisms and includes phonological dis-

order and articulation disorder.
Under the “associated features supporting diagnosis” section in the DSM 5, it is
noted that a language disorder, particularly expressive deficits, may be found to co-
occur with speech sound disorder. Thus, it is considered possible that CAS can
occur in the absence of disordered language. While this is possible, we believe this
occurrence to be rare.
The DSM 5 also suggests that “If the ability to rapidly coordinate the articulators
is a particular aspect of difficulty, there may be history of delay or incoordination
acquiring skills that also utilize the articulators and related facial musculature;
among others, these skills include chewing, maintaining mouth closure, and blow-
ing the nose. Other areas of motor coordination may be impaired. Verbal dyspraxia
is described in the DSM 5 as a disorder in which other areas of motor coordination
may be impaired, as in Developmental Coordination Disorder.” From a neural net-
work perspective, these associated conditions are not surprising. It suggests that a
thorough assessment of verbal dyspraxia (CAS) routinely includes assessment of all
aspects of motor coordination.
Is There a Difference Between CAS and Verbal Dyspraxia?
If we refer back to the ASHA definition, we see that there are three categories of
etiologies of CAS:
(A) CAS can occur as a result of a neurological impairment (i.e., stroke, traumatic
brain injury, infection). As this apraxia would be the result of trauma, one could
expect there to be positive findings on brain MRI scans.
(B) CAS can occur as a result of a neurobehavioral disorder, that is, genetic, meta-
bolic, and/or mitochondrial disorders. This group assumes that CAS then
occurs as a result of conditions such as chromosome disorders or in association
with disorders such as autism.
(C) CAS can occur as an idiopathic speech sound disorder. This means that the
apraxia is of unknown origin, so there is no evidence of either a neurological
impairment or neurobehavioral condition.
ASHA clarifies that they use the term childhood apraxia of speech (CAS) as an
umbrella term for all presentations of apraxia of speech in childhood, whether the
etiology is congenital or acquired. In contrast, The DSM 5 focuses on the present
disorder manifestations but recognizes a potential association to the larger issue of
motor dysfunction. In both cases, the presentation is the focus irrespective of
etiology.
o, What Can We Definitively Say About

S
the Definition of CAS?
Let’s start by defining the process of speech. The National Institute on Deafness and
Other Communication Disorders (National Institute of Deafness and Other
Communication Disorders, 2022) describes speech in the following manner: speech
is produced through a series of precisely coordinated muscle movements involving
breathing, phonation (voice production), and articulation (movement of the throat,
palate, tongue, and lips).
We know that estimations of delays in speech and language acquisition in 5-year-
old children are at approximately 10–12 percent for speech and language, 7 percent
for language only, and 8 percent for speech delay only (Law, 2000; Norbury, 2016).
Of this population the presentation rate for CAS has been estimated to be 2.4 per-
cent for the idiopathic subset and 4.3 percent when associated with complex neuro-
developmental disorder (Shriberg, 2019). We also know that CAS is considered a
disorder affecting speech.
The prevalence of CAS has reportedly increased substantially during the past
decades. For example, in a study of 12,000 to 15,000 estimated diagnostic outcomes
for children referred with speech delay of unknown origin from 1998 to 2004, a staff
of 15 speech language pathologists in a large metropolitan hospital diagnosed 516
(3.4–4.3%) of these children as having suspected CAS (Delaney & Kent, 2004).
There are several reasons given for this increase. Among them are Birth-to-Three
Legislation, increased information and recognition, and reimbursement require-
ments that are based on diagnostic codes (ASHA, 2007).
The Idea of CAS Has Historically Been Controversial
From a historical perspective, the term CAS has been quite controversial as a clini-
cal diagnosis. In 1981, Guyette and Diedrich (1981) reviewed more than 100 stud-
ies. They found inconsistencies with each aspect of the studies, that is, population
characteristics and diagnostic inconsistencies. CAS was noted to be reflective of a
neurological issue that precedes speech but one wherein specificity of pathogno-
monic markers was absent, resulting in the authors labeling CAS as a “label in
search of a population.” Perhaps more eloquently, from a pediatric developmental
perspective, Malmenholt (2020) described CAS as “confusing as we were using the
term apraxia for a developmental speech problem, indicating the loss of a skill not
yet acquired.” It is an interesting observation that causes us, or should cause us, as
treating or diagnostic clinicians, to pay attention to risk factors which may not yet
be pathognomonic signs.
Apraxia of speech was the model, and we believe, quite different from a pediatric
one. As we will talk about later, the model for many areas of neuropsychology was
damage to adults. This assumes an already developed system with acquired damage
Is CAS Underdiagnosed? 101
to an already developed cerebral connectome. Clinicians with a pediatric bent will

immediately recognize the folly of this conceptualization. Children are developing
organisms, and as such, difficulties presenting at a particular age would be assumed
to impact future development of the neural pathways and subsequent behavioral
outcomes. However, the current diagnostic model clusters behavior into a diagnos-
tic label.
This behavioral descriptor model, while understood to be necessary for commu-
nication among clinicians, reflects how behaviors can be found in more than one
disorder, or not at all for some in a particular disorder. Hence, we end up with the
DSM model which points to the association of disorders, or rather, the possible
association of disorders because of the possibility of shared behaviors across diag-
nostic labels. Specifically, the reader is asked to refer back to the DSM description
of a verbal apraxia and its possible relationship to phonological disorders, apraxia,
and motor coordination disorders. To be very clear, it is the intent of the current
authors to highlight that models have been based upon developed or adult systems.
A child is not a developed neurophysiological organism. Rather, a child is develop-
ing, and there is potential for any disorder, because of its location or etiology, to
impact all or some forward-moving systems.
What Are Some Comorbidity Associations?
Children diagnosed with CAS often have concomitant issues. In a review of litera-
ture, Iuzzini-Siegel (2017) found that greater than 50% of children with CAS also
present with fine and gross motor deficits. There are estimates of children with CAS
having comorbid language impairments ranging from 46 to 82 percent (Murray,
2018) with better receptive than expressive skill capabilities. Children with CAS
may also have comorbid dysarthria or a phonological disorder which makes analyz-
ing which symptoms belong to which disorder challenging (Iuzzini-Siegel, 2017).
Reading and writing impairments often develop (Lewis, 2004). In fact, one study
(Miller et al., 2019) found that in a group of young people, aged 7–17 years of age,
diagnosed with either CAS or speech sound disorder, 65 percent of the CAS group,
compared to 24 percent of the speech sound disorder group, was classified as low-
proficiency readers based upon nonsense and single-word decoding. Within the
larger group of low-proficiency readers, no difference was found on overall reading
or oral language, or phonological awareness.
Is CAS Underdiagnosed?
A question arises as to whether this is a diagnosis which is underdiagnosed. In the

current authors’ opinion, this largely remains true with many diagnosticians seem-
ingly reluctant to make the diagnosis, preferring speech delay or specific language
impairment. Does this speak to the ambiguity of the diagnostic markers; the current
mindset to diagnose based upon the modular, behavioral presentation; or a reluc-
tance to be the diagnostician who has to speak to the parents of a young child about
the potential breadth and length, that is, the developmental implications, of the
impact of the disorder upon future language, academic, and cognitive development
based upon the presenting risk factors which can be sensitive, but not necessarily
specific? We cannot say. It is, however, a topic worthy of discussion. What we can
point out is that the lack of a highly specific, agreed-upon, diagnostic criteria is
likely to contribute to the disorder being underdiagnosed. For example, returning to
our issue of definition, we see the confusion within the term. Note that ASHA refers
to a childhood apraxia and rejects the inclusion of the term “developmental,” while
developmental verbal dyspraxia is the term preferred in Ireland and the UK, and
verbal dyspraxia is the preferred term in the DSM, although it is included in the
section for disorders appearing in childhood.
The current authors wish to highlight that, consistent with the overall DSM diag-
nostic system, apraxia of speech is diagnosed based upon its overt presentation of
disordered speech. In addition, the symptoms of CAS can change both over time
and in presentation as a result of treatment (Maasen, 2002). The younger child may
present with limited phonetic skills, speech inconsistency, and sequencing difficul-
ties, which may later present as residual prosody and resonance issues. The distinc-
tions, or rather the ambiguity of definitions between the different developmental
language disorders (speech delay and language disorder), further contribute to the
confusion as to which disorder we are seeing and how these disorders are accounted
for in research paradigms.
As can be noted from the latter part of this statement, the definition has gone
from the ASHA description to a larger conceptualization involving potential Mu
speech focused scale coordination issues, hearing, and touch. The question has
arisen as to whether this co-occurrence of speech and language disorders, including
CAS with motor disorders, was the result of speech motor difficulties affecting lan-
guage or a co-occurrence of both speech and language disorder (Murray, 2018).
The Results of Definitional Confusion
Part of the difficulty with being able to define CAS with greater precision lies with
the fact that CAS is a low prevalence disorder. Due to its ambiguous definition, stud-
ies of CAS often include children with similar, but non-CAS-based language defi-
cits. There is an ongoing inability to delineate the disorder with specificity, that is,
the inability to identify CAS as one might do on a particular bacterial infection or
identify a genetic biomarker associated with the syndrome. As noted by Allison
et al. (2020), disordered speech is the hallmark of both childhood apraxia of speech
and apraxia of speech. Differential diagnosis of the disorder in adults and children
continues to present major clinical and research challenges (Allison et al., 2020).
This is because while both disorders are defined by difficulties presumed to be with
The Results of Definitional Confusion 103
motor planning and programming of speech movements, there are no biomarkers

for apraxia of speech or childhood apraxia of speech.
Confounded phenotyping also impacts genetic research (Mountford et al., 2022).
Again, within this domain the lack of a consensus with respect to diagnostic criteria
results in comparisons across research studies difficult. In addition, the definitions
and criteria impact sample sizes, further impacting genetic studies.
With respect to developmental speech disorders, various systems have been
attempted. The Shriberg Speech Disorders Classification System (Shriberg et al.,
2012), which attempted to base the classifications upon presumed etiology, consists
of eight subcategories which attempted to base the model on the linking of “etio-
logical process.” Level I consisted of distal causes, level II consists of proximal
causes including presentation and execution of speech mediated by feedforward and
feedback processes, level III attempted behavioral phenotypes which consists of the
expressed behavioral markers, and level IV consists of the critical signs of the phe-
notypes. Shriberg’s goal was to identify a conclusive diagnostic marker at each step
of the way with attention to both sensitivity and specificity. The resulting model,
however, is largely symptomatic descriptions (Terband et al., (2019)) at the behav-
ioral level. Terband et al. (2019) note a similar difficulty with the Stackhouse and
Wells Psycholinguistic Framework whose categories are based on the proximal
cause (processing) rather than at the core etiology and result in subcategories of
phonological disorders based, again, on symptomology. Terband et al. (2019) went
on to argue that core impairment, while not clearly distinguishable from each other,
nonetheless requires an understanding of the complex interactions between causa-
tion. By way of an example, they offer substitution errors which can be viewed as a
feature component, a speech-motor component, or a sequencing error component.
The absence of diagnostic markers which are both sensitive and specific then
requires the diagnosis be made based upon clinical symptomology. However, there
is no satisfactory consensus as to a core of speech symptoms which would reflect
sensitive diagnostic criteria. Differential diagnosis is subsequently compromised by
the overlap of symptoms across various speech disorders. That is, there is a signifi-
cant overlap in speech disorder phenotypes.
Specifying this disorder in children becomes further compromised over the
course of a child’s development as “a congenital speech disorder in children pre-
senting as a motor speech disorder influences a child’s development of phonological
presentation” (Stackhouse, 1997) “further rendering a lack of specificity in linguis-
tic models” (Maassen, 2002).
The ASHA Technical Report of 2007 (page 4) noted that “Whereas some of the
definitions of CAS reviewed by the Committee view the core problem as one of
planning and programming (cognitive level) the spatiotemporal properties of move-
ment sequences (behavioral level) underlying speech sound production, others pro-
pose that the deficit extends to representational level (cognitive) segmental and or
suprasegmental units in both input processing and production.” Asha goes on to say
that “there is no validated list of diagnostic features that differentiates this symptom
complex from other types of childhood speech sound disorders.” The Technical
Report raised three speech characteristics which were consistent and considered
specific to childhood apraxia of speech. They are:
1. Inconsistent error of consonants and vowels in repeated productions of syllables
or words
2. Lengthened and disrupted coarticulatory transitions between sounds and
syllables
3. Inappropriate prosody, especially in the realization of lexical or phrasal stress,
which is “a core impairment in planning and/or programming spatiotemporal
parameters of movement sequences”
An attempt to operationally define CAS was undertaken by Iuzzini-Seigel and
Murray (2017). They created a 12-feature checklist of CAS symptoms expanding
upon ASHA’s primary criteria. Iuzzini-Seigel and Murray (2017) attempted to use
the International Classification of Functioning framework to provide improved
operationally defined criteria to better assess for the presence of CAS. They included
the following speech features commonly associated with CAS: with respect to the
first primary criteria as established by ASHA (2007):
1. Vowel error (a vowel production error in which the vowel is substituted for
another vowel or not produced accurately)
2. Consonant distortion (a consonant production error in which a speech sound is
recognizable as a consonant, but not produced accurately)
3. Speech sound inconsistency, and nasal resonance (resonance sounds are either
hyponasal, in which there is not enough airflow out the nose, or hypernasal in
which there is too much airflow out of the nose for non-nasal phonemes)
4. Expanding upon lengthened and disrupted co-articulatory transitions, the
included intrusive schwa (the insertion of a schwa sound between consonants)
5. Difficulty achieving initial articulatory configurations (initiation of utterance or
initial speech sound may be difficult for a child to produce and may sound
lengthened or uncoordinated)
6. Groping (prevocal articulatory searching prior to onset of phonation or extrane-
ous oral movements during nonspeech oral motor tasks) for sounds
7. Increased difficulty with multi-syllabic words (a disproportionately increased
number of errors as the number of syllables increases)
8. With regard to the third ASHA criteria of inappropriate prosody, they included
9. Stress errors (an error in which appropriate stress is not produced correctly at
the lexical (word) or sentence levels)
10. Syllable segregation (a brief or lengthy pause between sound syllables or words)
11. Slow rate
Each was operationally defined, for example, nasal resonance was defined as
hypo- or hypernasal resonance. In addition to the mandatory presence of the three
primary criteria, additional five characteristics were required for the diagnosis.
They contend that children who produced 5 or more features out of the possible 11,
as well as speech inconsistency, warrant the CAS diagnosis. Therefore, a cutoff of
five features was used. However, they found that school-aged children with a diag-
nosis of CAS actually tended to present with an average of eight features. This was
Speech: Structure Versus Function 105
in contrast to children with speech delay who tended to present with three features
and with typically developing children who presented with an average of one fea-
ture. They go on to remind us that the features are not pathognomonic. This again
presents the difficulty of specificity and sensitivity when discussing a valid and reli-
able diagnosis of CAS (*definitions provided by Iuzzini-Seigel and Murray 2017).
Identifying the Speech Errors that Characterize CAS
In fact, there have been multiple studies which have attempted to standardize which
speech characteristics are affected in children with CAS. For example, variable pro-
duction of a phoneme (phonemic inconsistency) across multiple options both within
and across word positions differentiates children with suspected CAS from phono-
logical disorder (Iuzzini, Inconsistency of speech in children with childhood apraxia
of speech, phonological disorders and typical speech, 2012). There is also research
(Lewis, 2004) which has found that 100 percent of children with CAS evidenced
vowel errors compared with 8 percent of children with an isolated speech sound
disorder or a combined speech and language disorder. At school age, 90 percent of
the children with CAS continued to make vowel sound errors, whereas 0 percent of
the other group did.
For example, in a review of neuroimaging studies, Liegeois et al. (2014) noted
that traditionally, both language and speech disorders have been defined as idio-
pathic. Turning to the burgeoning field of neuroimaging, Liegeois, Mayes, and
Morgan note that neuroimaging studies “have uncovered functional and sub-
macroscopic structural anomalies within brain systems.” They reviewed articles
published between 2008 and 2013. Of note, 2602 abstracts were initially identified.
Following their exclusion criteria, wherein MRI was required for inclusion, only ten
articles remained, five for speech disorder and five for language disorder. However,
speaking to the aforementioned problem of specificity and how that impacts
research, Mayes and Morgan noted how the “recruitment samples in both SD and
LD studies were heterogenous with regard to diagnosis.” Further, for speech disor-
der studies, diagnostic criteria ranged across childhood apraxia of speech, phonetic
and phonemic level errors, and articulatory deficits. For language disorder the crite-
ria included a history of language delay, syntax errors, receptive, expressive, lexical,
and/or mixed disorders. Again, the lack of specificity is confounding an already
confounding syndrome.
Speech: Structure Versus Function
Dr. Edythe Strand (Strand, 2018) of the Mayo Clinic notes that CAS is believed to
be the result of deficits in planning and programming of movement gestures for
speech production, that it often occurs in conjunction with language and
phonological impairment, and that the definition relates to the ability to specify the
parameters of movement. She the elaborates: “As a speaker gets ready to talk, par-
ticular muscle groups are selected to begin to contract at very specific times to cause
structures to begin to move at a certain time in a particular direction, at a certain
speed with a certain amount of force, using a specified amount of muscle tension”
(Strand, 2018). Although most of us take this process for granted, hearing it broken
down as such allows us to appreciate the complexities involved in speech production.
CAS is associated with functional rather than structural deficits (Iuzzini-Seigel,
2017). Children with CAS have no structural impairment which would impact their
speech systems. However, they present with difficulties in motor planning and pro-
gramming across speech systems, including phonation, articulation, respiration,
resonance, and prosody (Iuzzini-Seigel, 2017). Iuzzini et al. state that evaluation is
conducted through assessment of speech production of single words, such as on the
Goldman-Fristoe Test of Articulation, as well as repeated words and phrases and
connected speech. Murray (2018) note that polysyllable words and diadochokinetic
tasks stress the child’s motor system. However, children with speech delay and pho-
nological disorders may also present with errors such as poor accuracy and incon-
sistencies on polysyllabic words.
One study looking at difficulty in the production of complex phonetic sequences
in CAS through observation of coordination between the lips and jaw during speech
production was undertaken (Moss, 2012) using a single-syllable, two-syllable, and
three-syllable “real words.” Support for the hypothesis of disordered speech motor
control in CAS was implied by the difficulty noted in children with CAS in their
attempts at longer or more complex syllable imitation (three syllables in contrast to
a single syllable). Another attempt (Iuzzini-Siegel, 2017) was made to determine if
speech inconsistency was a core feature of CAS or driven by a comorbid language
impairment and whether speech inconsistency is both sensitive and specific as a
diagnostic marker. They found that a token-token inconsistency of monosyllabic
words and a phrase (buy Bobby a puppy) was both sensitive and specific in differ-
entiating children with CAS and speech delay, whereas inconsistency using other
stimuli was less so, leading to the conclusion that speech inconsistency was sensi-
tive but not specific as it depended upon the stimulus presented.
A not too dissimilar question has arisen with respect to dyslexia. Developmental
dyslexia is believed to affect approximately 5 percent of children (Ramus, 2003).
Was dyslexia caused by a cognitive deficit specific to representations and process-
ing of speech sounds (phonological theory) or a general sensory motor deficit? This
latter theory might include a cerebellar/motor component. Ramus (2003) noted the
antagonistic nature of the theories and the fluctuations across theories over time,
with each supported by empirical evidence. He concludes that “sensory and motor
disorders are present in a significant proportion of developmental dyslexics but play
only a limited role in the etiology of reading disability.” As we shall see as we con-
tinue, ignoring the contribution of sensory motor involvement may be a mistake
with respect to both assessment practices and intervention strategies.
Genetics, Language Disorders, and CAS 107
1. The current authors stress the importance of developmental factors in assess-

ment, whether that be a neuropsychological assessment or a language assess-
ment. Knowing the developmental history of a child’s language and motor
development offers us valuable information in piecing together the developmen-
tal trajectory of the child’s skills by being able to look at risk factors.
2. We know that reading also relies upon fluid phonemic processing. Both children
with dyslexia and children with CAS appear to have difficulty with single-word
decoding.
3. The automaticity, the fluidity arising from overlearned behaviors, has been dis-
cussed elsewhere by the current authors and will be given attention further on in
this chapter. For now, the importance lies in recognizing automaticity of reading,
in part, on automaticity in motor behaviors, such as those required in rapid nam-
ing, a deficit often associated with reading difficulties.
Genetics, Language Disorders, and CAS
Genetic involvement in language disorders has been under study for several decades
at this point, with multiple genetic loci and possible genes. Language disorders are
considered to be highly heritable and represent complex interactions between
genetic and environmental factors (Mountford et al., 2022), a synergy termed epi-
genetics. That language disorders are highly heritable is overwhelmingly accepted
(Mountford et al., 2022). Nonetheless, there is an underwhelming understanding of
how genetic coding variability and epigenetics affect language disorders. Genetic
etiology is difficult to pinpoint secondary to variations between individuals and
complex patterns of inheritability (Andres, 2022). While there have been over 30
genes identified which are associated with speech and/or language disorders, there
is still a paucity of explanation of the underlying genetic cause of developmental
language disorder (Mountford et al., 2022). It is hypothesized (Andres, 2022) that
“the genes suggested [previously] explain a portion of the dynamic process of lan-
guage acquisition or the complexity of skills that represent language ability.” An
intriguing additional hypothesis (Andres, 2022) is that because of the complexity of
using language, a combination of genes with variable effect size may better explain
the both the acquisition of language and why skill acquisition may be disordered.
The study of genetic disorders as related to language disorders falls into one of
two categories: monogenic disorders reflect a single change in the DNA which is
sufficient to cause a disorder. Complex disorders refer to multiple genetic variations
which combine to contribute to a disorder which is also impacted by environment.
Monogenic disorders have traditionally been studied within families. Complex
genetic disorders incorporate genetic association methodologies.
Monogenetic inheritance reflects when a disorder arises from either recessive or
dominant inheritance. Monogenetic variants are extremely rare. The monogenetic
variants have a negative effect on the protein for which they encode which in turn
results in a deficit in the cell, resulting in the disorder (Mountford et al., 2022).
FOXP2 is one such monogenetic example. The impact of FOXP2 and its impact
on the KE family have been highly published and cited (Morgan et al., 2016). It is
of importance to note that variants in FOXP2 show dominant inheritance (one copy
of the variant) are extremely rare and account for approximately 2 percent of chil-
dren with CAS. Children impacted by reduced levels of the FOXP2 protein display
typical to low-average intelligence and both receptive and expressive language defi-
cits. Gross and fine motor domains are not considered to be impacted. At the current
time, FOXP2 variants are not believed to be contributing to other language disor-
ders. Nonetheless, FOXP2 controls the expression of a series of regulating genes for
language and motor function, thereby affecting speech motor learning. In fact, in its
role as a transcription factor, FOXP2 variants have been shown to affect develop-
ment of the cerebellum, striatum, and motor cortex, thus involved with cortical and
subcortical regions. Shriberg et al. (2012) showed associations between FOXP2 and
speech, prosody, voice, cognition, and language.
Assessing a single family, followed since 1993, and in this case had childhood
apraxia of speech ruled out, Andres (2022) identified co-segregating rare variants in
three genes, with variants in BUD13 reaching genome-wide significance for SLI.
Robinson Crusoe Island is home to a population with a high incidence of speech
language impairment. Molecular genetic techniques were used to identify eight
coding variants of significance. By then comparing to a larger population outside of
this area (UK), Villanueva et al. (2015) found the impact of NFXL1 gene in both
populations. They conclude that coding variants within the NFLX1 gene are associ-
ated with speech language impairment “within a complex genetic model.”
A recent evaluation of children with CAS (Hildebrand, 2020) found a causative
variant in 11 of 33 participants in 10 genes. The implication is that as many as 33
percent of children with CAS may have a causative genetic variant which has
resulted in their CAS.
In addition, there are copy number variants, which are deletions or duplications
of regions of genetic code. Copy number variants can be of little consequence, and
some can cause disease. Some copy number variants affect global development, and
some have been linked to language disorders. Deletions of chromosome 16p11 have
been linked to childhood apraxia of speech (Mountford et al., 2022).
Other genes have been implicated in specific language impairment populations.
It may be fully reasonable to anticipate the involvement of multiple genes impacting
the phenotype of childhood apraxia of speech as well. Genetics may look to a
“genetic complex model” (Mountford et al., 2022) with each variant contributing
incrementally to the potential development or expression of disease. Through
genetic linkage studies to identify regions of genetic code shared by affected indi-
viduals, the specific language impairment consortium found regions on 16q24 and
19q13 highly associated with SLI. Using this technique (Newbury, 2009), it was
found that C-Mad inducing protein was associated with language and reading and
spelling which was interpreted as impacting language on a larger scale. The list goes
on and the reader is referred to the review article by Mountford et al. (2022) for a
more comprehensive read. For our current purposes, it is important to note that what
References 109
has been largely a phenotypically identified disorder is being assessed on a genetic

coding level and potentially reflects a developmental rather than a lesioned disease
model per se.
This more comprehensive view of CAS was meant to emphasize the complex
and heterogeneous nature of CAS. Obviously, the neural network system that under-
lies this disorder is also complex, containing many sub-networks operating in an
interconnected fashion to produce speech, and disruption in a large number of
places within this system will produce disrupted motor speech. We now turn our
attention to those motor speech networks.
References
Allison, K., Cordella, C., Iuzzini-Seigel, J., & Green, J. (2020). Differential diagnosis of apraxia
of speech in children and adults: A scoping view. Journal of Speech, Language, and Hearing
Research, 2952–2994.
American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders
(5th ed.).
American Speech Hearing Association. (2022). Retrieved from Childhood Apraxia of Speech:
http://ASHA.org
Andres, E. E. (2022). Family based whole exome analysis of specific language impairment
identifies rare variants in BUD13, a component of the retention and splicing complex. Brain
Sciences, 12, 47.
Childhood Apraxia of Speech. (2022). Retrieved from American Speech-Language Hearing
Association: ASHA.org
Delaney, A. L., & Kent, R. D. (2004). Developmental profiles of children diagnosed with apraxia
of speech. The annual convention of the American-Speech-Language-Hearing Association.
Poster. Philadelphia: American-Speech-Language-Hearing Association.
Guyette, T. W., & Diedrich, M. (1981). A critical review of developmental apraxia of speech.
Speech and Language, 1–49.
Hildebrand, M. J. (2020). Severe childhood speech disorder. Neurology, 94, 2148–2167. https://
doi.org/10.1212/WNL.0000000000009441
Iuzzini-Seigel, J. (2017). Speech assessment in children with childhood apraxia of speech.
Perspectives of the ASHA Special Interest Groups, 2, 47.
Iuzzini-Seigel, J., & Murray, E. (2017). Speech assessment in children with childhood apraxia of
speech. In Perspectives of the ASHA Special Interest Groups (pp. 47–60). American Speech
Language Hearing Association.
Law, J. B. (2000). Prevalence and natural history. International Journal of Language &
Communication Disorders, 35(2), 165–188.
Lewis, B., Fairbairn, L., Hanson, A., Ivengar, S., & Taylor, H. (2004). School age follow up of chil-
dren with childhood apraxia of speech. Language, Speech, and Hearing Services in Schools,
122–140.
Liegeois, F., Mayes, A., & Morgan, A. (2014). Neural correlates of developmental speech and
language disorders: Evidence from neuroimaging. Current Developmental Disorders Reports,
215–227.
Maassen, B. (2002). Issues contrasting adult acquired versus developmental apraxia of speech.
Seminars in Speech and Language, 257–266.
Malmenholt, A. (2020). Exploring childhood apraxia of speech: Speech and language profiles in 5
year olds with suspected apraxia of speech or cleft palate. Karolinska Instituet Department of
Clinical Science, Intervention and Technology.
drc-20352051
Miller, G., Lewis, B., Benchek, P., & Freebaim, L. (2019). Reading outcomes for individuals with
histories of suspected childhood apraxia of speech. American Journal of Speech-Language
Pathology, 1432–1447.
Morgan, A., Fisher, S., Scheffer, I., & Hildebrand, M. (2016). FOXP2-related speech and language
disorders. In M. A. Adam (Ed.), Gene reviews. University of Washington.
Moss, A. G. (2012). Interarticulatory coordination of the lips and jaw in childhood apraxia of
speech. Journal of Medical Speech-Language Pathology, 20(4), 127–132.
Mountford, H., Braden, R., Newbury, D., & Morgan, A. (2022). The genetic and molecular basis of
developmental language, 9(5), 586. https://doi.org/10.3390/children9050586
Murray, E. T. (2018). Comorbid morphological disorder apparent in some children aged 4-5 years
with childhood apraxia of speech: Findings from standardised testing. Clinical Linguistics &
Phonetics, 1–18.
Murray, E., & Iuzzini-Seigel, J. (2017). Efficacious treatment of children with childhood apraxia of
speech according to the International Classification of Functioning. ASHA Speech Pathology
and Audiology Faculty Research and Publications.
National Institute of Deafness and Other Communication Disorders. (2022). Home page. Retrieved
from National Institute of Deafness and Other Communication Disorders: https://www.nidcd.
nih.gov/
Newbury, D. W. (2009). CMIP and ATP2C2 modulate phonological short term memory in lan-
guage impairment. American Journal of Human Genetics, 264–272.
Norbury, C. F. (2016). The impact of nonverbal ability on prevalence and clinical presentation of
and clinical presentation of language disorder: Evidence from a population study. Journal of
Child Psychology and Psychiatry, 1247–1257.
Ramus, F. (2003). Developmental dyslexia: Specific phonological deficit or general sensorimotor
dysfunction. Current Opinion in Neurobiology, 13, 212–218.
Shriberg, L. D. (2019). Estimates of prevalence of speech and motor speech disorders in per-
sons with complex neurodevelopmental disorders. Clinical Linguistics & Phonetics, 33(8),
707–736.
Shriberg, L., Lohmeier, H., Strand, E., & Jakielskic, K. (2012). Encoding, memory, and transcod-
ing deficits in childhood apraxia of speech. Clinical Linguistics & Phonetics, 445–482.
Stackhouse, J. W. (1997). Children’s speech and literacy difficulties 1: A psycholinguistic frame-
work. Wurr.
Strand, E. (2018, January 9). Diagnosis and management of CAS. Retrieved from youTube: https://
www.youtube.com/watch?v=T8nPckWfvG0&ab_channel=ChildhoodApraxiaofSpeechInfo
Terband, H. M., Maasen, B., & Maas, E. (2019). A psycholinguistic framework for diagnosis and
treatment planning of developmental speech disorders. Folia Phoniatrica et Logopaedica, 71,
216–227.
Villanueva, R., Nudel, A., Hoischen, M., Fernandex, M., & Simpson, N. (2015). Exome sequenc-
ing in an admixed isolated population indicates NFLX1 variants confer a risk of specific lan-
guage impairment. Genetics. https://doi.org/10.1371/journal.pgen.1004925
Chapter 8
Neural Network Components of Childhood
Apraxia of Speech and Associated
Comorbidities
Given the focus on childhood apraxia of speech, we will now turn our attention to
the various neural networks, particularly, the motor networks that comprise the
underpinning of motor speech. We are mindful that the same extensive analysis
could be done for any of the other apraxia but chose this area due to the lack of
specificity as to the etiology of most childhood apraxia of speech, interrelatedness
and complexity of the network interactions involved, and potential neural and func-
tional associations to other clinical conditions.
Hemispheres and History
The history of our knowledge of the relationship between areas of the cortex and
speech can unequivocally be traced back to the work of Broca and Wernicke. In
1861, a neurosurgeon, Paul Broca, reported on the brain of a deceased patient who
had been able to understand language, but could not express a full sentence verbally
or in writing. Upon autopsy Broca identified a lesion in the left inferior frontal cor-
tex, which came to be known as the Broca’s area, known to be responsible for
speech processing and comprehension. Broca came to announce “We speak with the
left hemisphere” which became the basis for the belief that the “language center was
housed in the left hemisphere.” In 1871 the German neurologist Carl Wernicke iden-
tified the superior temporal lobe as responsible for processing speech through hear-
ing. Lesions at this location impacted the quality of speech. That is, the person could
speak, but the speech was incoherent. This area became known as the Wernicke’s
area. These finding essentially cemented the idea of lateralized language. Note that
these models are lesion based in adults. They are also cortico-centric. Wernicke’s
model was updated by Norman Geschwind and has become known as the
112 8 Neural Network Components of Childhood Apraxia of Speech and Associated…
Wernicke-Geschwind model. The model attempted to explain the process of speech

through related areas of cortex. The model held that information travelled from the
ear to the auditory cortex, to the Wernicke’s area, to the Broca’s area, and to the
motor cortex. As the field has progressed, we now know that the two areas are con-
nected by a large nerve fiber bundle, the arcuate fasciculus. This loop does present
in the left hemisphere for most right-handed persons. In order to pronounce a word,
or series of phonemes, the information is transmitted via the arcuate fasciculus to
the Broca’s area and on to the motor cortex. The model is not without complications
revisions and exceptions but provides a rudimentary schema for the reader for the
current time.
Nonetheless, the language center does not operate in isolation or produce fully
formulated speech on its own. Various brain regions contribute critical elements of
speech. For example, the left hemisphere is largely responsible for comprehension
of the spoken words. The right hemisphere is largely responsible for the emotional
connotation as it interprets the tone, rhythm and inflection, or prosody of the spoken
language. The right hemisphere also allows for the manipulation and integration of
categorical information, which facilitates divergent novel thinking. The left hemi-
sphere focuses on individual events. So, for example, where the right might see the
forest, the left sees the tree. How might this translate into higher cognitive thinking?
It is not only these large gray matter structures that contribute to speech. These
structures must be connected by white matter pathways so that their various func-
tions can be integrated. Figure 8.1 is provided to give the reader an idea of the
complexity of structural organization that must be achieved in order to achieve one
aspect of motor speech.
Arcuate Fasciculus
In a landmark diffusion tensor imaging study, conducted by Catani and de Scholten

(2008), 12 right-handed subjects were used to perform 3D tractography images of
white matter tracts and in vivo dissections of the major tracts of the brain. Their
resulting atlas includes vivid images of numerous tracts. Included is the arcuate
fasciculus. The arcuate fasciculus is a white matter bundle that contains both long
and short fibers. It is a major anterior/posterior tract that connects the frontal, pari-
etal, and temporal lobes. Two pathways have been identified: The medial pathway
connects the Wernicke’s region in the temporal lobe to the Broca’s region in the
frontal lobe. The second is the indirect pathway which is comprised of two seg-
ments, the anterior and the posterior. The anterior pathway segment provides a link
between the Broca’s region in the frontal lobe and the Geschwind’s region housed
in the inferior parietal lobe. The posterior segment is the link between the
Geschwind’s region and Wernicke’s region. Here we have yet another and seem-
ingly very important example of white matter tracts connecting regions highly asso-
ciated with language, sensorimotor learning, hand movements, and basic math
operations among others. We point this out here to highlight the fact that the white
Interconnections of the Arcuate Fasciculus 113
Fig. 8.1 Hierarchical organization of the dual pathway of central voice control
Hierarchical organization of the dual pathway of central voice control. The lowest level (sub-
system I) is represented by the sensorimotor phonatory nuclei in the brainstem and spinal
cord, which control laryngeal, articulatory, and respiratory muscles during production of
innate vocalizations. The higher level within this system (subsystem II) is represented by the
periaqueductal gray, cingulate cortex and limbic input structures that control vocalization
initiation and motivation as well as voluntary emotional vocalizations. The highest level (sub-
system III) is represented by the laryngeal/orofacial motor cortex in the vSMC with its input
and output regions that are responsible for voluntary motor control of speech production.
Dotted lines indicate direct connections between different regions within the voice-control-
ling system. (Simonyan et al., 2016)
matter motor structures are recruited for numerous tasks and a disruption of func-
tion based in one of these regions would likely have negative impact on a number of
output skills in addition to apraxia.
Interconnections of the Arcuate Fasciculus
In fact, the arcuate fasciculus, together with posterior portions of the middle tempo-
ral gyrus, presents with differences in humans as compared to other primates and is
considered to be a crucial difference in how human language evolved (Sierpowska
et al., 2022). They found that connectivity in the posterior temporal lobe, via the
arcuate fasciculus, expanded bilaterally to frontal and parietal cortices in humans.
In contrast, the ventral tracts show stronger connection to posterior temporal regions
in chimpanzees as compared to humans.
They further found that the medial direct pathway, or direct long segment, is
larger in the left hemisphere in approximately 80% of the population (Catani et al.,
2007). They found interhemispheric differences with greater symmetrical connec-
tions were better overall at remembering words (verbal recall) using semantic asso-
ciation. They also found a gender difference, with females tending to be more likely
to have this symmetrical pattern of connection.
A longitudinal study by Gao et al. (2022) looked at the vocabulary trajectories of
three groups of children ranked as consistently good, catch up, and consistently
poor, between the ages of 4 and 10. At age 14, diffusion tensor imaging, using
region of interest (ROI)-based tractography, found significantly reduced fractional
anisotropy in the left arcuate fasciculus of children in the consistently poor group.
The finding was in the posterior and direct segments of the arcuate fasciculus. No
differences between groups appeared for the right hemisphere nor in the left anterior
segment. Through regression analysis, Yue et al. showed that it was the rate of
vocabulary development, rather than initial size of vocabulary, which was a specific
predictor of connectivity. The current authors highlight that this may speak to our
concern regarding breadth and long-term impact of early developmental disruption.
Hemispheres Do Not Operate in Isolation
As we have pointed out, these neural networks do not operate in isolation, and no
one area is responsible for the production of fully functional speech. Neural net-
work modeling posits that these areas, which are responsible for differently and
discretely defined functions, are integrated. This integration is made possible by the
complex white matter networks that together form the connectome.
Koziol (2014) provided an example of how this might work in practice. He
argued that because the right hemisphere can take in the whole scene, so to speak, it
becomes possible for this gestalt type processing to set the framework for solving
problems that might have similar yet different characteristics. It allows us to take a
particular thought or piece of information and use it in a more abstract application
to a novel situation. In the process we generate new information. That new informa-
tion has been acquired through the cross-interactions of both hemispheres. In this
way, semantic systems are important not only for language but also for the manipu-
lation of the categories for the divergent thinking often necessary for problem solv-
ing. Following this line of thinking, interruption to this process has the potential to
disrupt higher-order cognitive thought.
Hemispheres and the Three Rs
A recent study speaks nicely to our discussion of hemispheric function, its interre-
latedness, and impact of one area on other cognitive area, in other words possible
comorbidities or associations of CAS and comorbid conditions.
Hemispheres and the Three Rs 115
We have a good deal of research talking about phonology both for CAS and lit-
eracy. We addressed that aspects of language have a strong left hemisphere base.
There is research indicating that addition and subtraction are both left lateralized or
bilateral (Semenza & Benavides-Varela, 2018) as the visual symbols require inter-
pretation as would a phoneme. The left hemisphere would utilize lexical mecha-
nisms for identifying and producing spoken numerals. Semenza and Benavides-Varela
(2018) contend that these lexical mechanisms would be implemented in the “clas-
sic” language (Broca’s and Wernicke’s) areas including the inferior frontal and the
superior and middle temporal gyri, as well as basal ganglia and thalamic nuclei.”
That is, disruption of the pathway at one of several locations may impact math skills
as well as reading skills.
While it is not the intent of this chapter to comprehensively address dyslexia, we
would note that developmental dyslexia is the most commonly diagnosed learning
disorder (Shaywitz, 2005). Although it exists independent of intellectual standing,
reading difficulty is often comorbid with dyscalculia (McNorgan, 2021). McNorgan
discussed how reading is a process transforming visual or orthographic representa-
tions to phonological ones. For those with a reading difficulty, relative to controls,
dyslexics show an under activation of the left temporo-parietal cortex and are argued
to reflect a failure of audiovisual integration within functionally specialized regions.
Interestingly, they also show increased connectivity to posterior right hemisphere
areas, specifically the right occipitotemporal cortex and anterior inferior temporal
gyrus, possibly a compensatory mechanism (Shaywitz, 2005).
The McNorgan (2021) study also looked at the feedforward neural networks to
distinguish between poor and highly skilled readers and between word and pseudo-
word processing. He mapped multiple functional connectivity networks participat-
ing in multiple predictive functional connections. Of interest to our current
discussion, McNorgan found three adjacent nodes operating as a functional cluster
which spanned the right occipital pole and right calcarine sulcus. They appeared to
be terminal points of multiple functional connections within the right hemisphere,
which are and are predictive of the poor readers. He also found adjacent nodes
belonging to a functional neural cluster in the left occipitotemporal cortex which
were terminal points of multiple functional connections with within and across
hemispheres predictive of skilled readers. That is, disruption of the pathway may
impact reading skills as well.
Why discuss this information in a discussion of CAS? We discuss this for many
reasons, firstly, it is because it speaks to a developmental process taking into account
the fact that functional networks operate as needed and cross hemispheres. (A com-
prehensive discussion of connectomes and functional networks may be found in
another chapter of this book, and the reader is strongly encouraged to be familiar
with the model and current research, largely from neuroimaging, which is currently
available). As dyslexia is a more readily defined diagnostic group and is more fre-
quent in presentation than CAS, it allows for larger sample sizes (for that diagnosis)
for study and, for our purposes, allows for consideration of a model which high-
lights bilateral cortical implications. The results of the neuroimaging studies are
clear in implicating both hemispheres in processing reading requirements. It ties the
process to phonological processing, a process involved in CAS as well, as well as

associations to sensorimotor involvement (Ramus, 2003). Associations between
reading and math issues are well established. When we look at the aggregate data
then, we are afforded a look at how feedforward processes are impacted in a devel-
opmental disorder, which, while not CAS, shares components of associated skills
and impact. It is then not unreasonable to hypothesize that the impact of a develop-
mental speech apraxia, affecting phonological processing, with known associations
to reading and cognitive development, goes well beyond what might be assumed if
conceptualizing CAS as “merely” a motor programming problem affecting the pro-
duction of phonemic sequences.
The Connectome, Development, and CAS
The current authors have discussed elsewhere (Wasserman & Wasserman, 2019)
how the regions of the brain are connected by a connectome. This connectome starts
out with more localized interconnectivity (small world hubs) and expands across
regions as we are exposed to and incorporate information. In fact, neuroimaging
studies have revealed structural changes in white matter after learning complex
tasks. That is, the neural pathways of the brain are altering in response to stimuli.
This is known as a functional network as the network is ever-changing in response
to the demands of a particular task. This then, in turn, impacts information process-
ing and performance (Fields, 2010) across cognition, learning, and motor skills
development. Fields (2010) states that when new skills are being acquired, the
amount of myelin insulating an axon increases, improving the ability of that neuron
to fire. This then leads to the potential for more efficient learning and for more effi-
cient learning to lead to the automaticity of the learned behavior. Would it not be
reasonable then to assume that if there is a disruption to the process of learning a
new skill, this disruption impacts the myelin insulation occurring or that which
should be occurring, after the site of impact, thereby impacting the ability to learn
higher-order skills more typically associated with that pathway.
Neural pathways also undergo neuronal pruning at various developmental stages.
Preston et al. (2014), utilizing voxel-based morphometry, compared gray and white
matter volume for children with residual speech sound disorders. The results indi-
cated greater white matter in the corpus callosum for the speech sound error sub-
jects and less white matter in the right occipital gyrus. They speculate that this may
reflect an error in developmental pruning.
We know that in adults, apraxia of speech is strongly related to lesions of the left
hemisphere; however, in contrast, the majority of children with CAS were found to
have normal MRI brain imaging utilizing conventional imaging (Fiori et al., 2016).
This suggests that the cerebral anomalies in CAS may be too subtle for detection by
standard MRI. More recent research has begun to address this issue. In fact, in chil-
dren with CAS, using voxel-based morphometry, morphological abnormalities were
found in the supramarginal gyrus, Heschel’s gyrus, and bilaterally planum
CAS Is Multifactorial from a Network Perspective 117
temporale (Preston et al., 2014). Kadis et al. (2014) found a thicker left supramar-
ginal gyrus, compared to controls, in the absence of macroscopic lesions in this
same population of children with CAS.
In an effort to assess connectome connectivity, Fiori et al. (2016) compared frac-
tional anisotropy as a measure of white matter connectivity in children with
CAS. They utilized a whole brain tractography, based on diffusion imaging analy-
sis. The final sample included 13 children with a mean age of 7 years. Fiori et al.
found significant differences in fractional anisotropy (FA) in three subnetworks,
with FA reduced in children with idiopathic CAS. Two subnetworks were intra-
hemispheric with one in each hemisphere, and one subnetwork was inter-
hemispheric. Fiori notes that this is consistent with prior hypotheses of altered
development of connectivity in CAS (Preston et al., 2014) as well as studies sug-
gesting that it is necessary to have bilateral hemispheric involvement to result in
symptomatic apraxia of speech in children (Liegeois & Morgan, 2012).
CAS Is Multifactorial from a Network Perspective
We tend to think in terms of domains. That is, speech and language may be different
from each other and different from another domain such as motor development. But
we know that there is a very close and undeniable association between early motor
development and what the current authors believe are widespread areas of develop-
ment which transcend our artificially defined constructs or domains. For example,
relevant to our current discussion of CAS, it is clear that despite much overlap and
lack of specificity, we are discussing neuromotor integrity.
The information provided with respect to cortical involvement, subcortical
involvement, and genetic involvement defies our quest for a single agent of causa-
tion. It does, however, also point to and highlight the complexity of the human
system. Just as there may not be a single genetic variation accounting for speech or
language phenotypes, the same can be hypothesized true for a single-entry level of
absence or damage. In fact, this position is strongly supported by the current authors;
damage from the point of origin impacts all systems moving forward from a vertical
brain model perspective.
During the last decade, research has suggested that developmental communica-
tion disorders have multifactorial origins at different levels of aggregation (Maassen,
2015). As a developmental disorder, it is unlike adult, acquired disorders (Bishop,
1997). Dysfunction in children will affect the development of other functions, skills,
and development which relies on the preceding function being intact from a devel-
opmental perspective. Furthermore, Maassen believes the influence of these levels
on the resulting behavior is interactive rather than unidirectional. Maassen proposed
a developmentally based, perceptual motor model of Childhood Apraxia of Speech.
Using a multi-level, multifactorial concept as its foundation, he begins with a dis-
cussion of the global outlines of the interactive multi-level model, followed by a
discussion of each of the four levels as they relate to CAS, including the interactions
between the levels. Acknowledging that little is known about the genetic and neuro-
logical background of CAS, Masson’s focus is on perceptual-motor level, including
to some extent higher cognitive functions such as lexical retrieval. From this devel-
opmental perspective, babbling and sensorimotor learning is the foundation for
more abstract phonological understanding. Maassen’s model begins with phono-
logical encoding in which sensorimotor targets which constitute speech are selected
and sequenced in a series. The next stage is motor planning which comprises the
selection and sequencing of the articulatory movements necessary to produce these
sounds. During the next stage, motor programming is implemented. Maassen (2002)
makes the assumption that the core deficit of CAS is a reduced sensorimotor learn-
ing capacity. This then leads to poor articulation and poor auditory and somatosen-
sory representation and eventually impacts higher-level processing.
Some have raised the question of whether or not the core problem is with trans-
coding (planning and programming) or with deficits in auditory perceptual encod-
ing (representational) and/or memory (storage and retrieval). Expanding upon
Shriberg’s et al. (2019) work, the Syllable Repetition Task (SRT), an 18-item task of
non-word repetition (Shriberg et al., 2012), was administered to four groups based
upon speech classifications of typical speech, speech delay-typical language, speech
delay-language impairment, and CAS. The finding was of lower SRT encoding (the
transforming of auditory information into phonemic representation), memory (the
storage and retrieval of the representations), and transcoding (the process of plan-
ning and programming the representations for expression as a motor gesture such as
speech or signing) scores than controls. Velleman (2011), in a review, noted how
impact in CAS is cognitive-linguistic in addition to motor planning as noted by the
extension of problems with perception and production of vowels, rhymes, and pho-
neme sequences and further extending into word attack and spelling skills.
In summary, through vastly improved neuroimaging, our more recent knowledge
of connectomes allows us to better understand how, although research may need to
focus on one aspect of CAS presentations at a time, the impact of disruption at any
given point along the network, and/or within given hubs, can be more localized but
can absolutely be more pervasive.
The Dual Pathway Model
In fact, the co-occurrence of language and gross and fine motor skills in children
with language disorder has been well documented (DiDonato, 2014). One hypoth-
esis for this finding is a dual stream model of speech processing. The dual stream
model is based on the fact that the brain has two processes to utilize with speech
(Hickok, 2012). On the one hand, speech must be understood, also described as
acoustic sound linking to conceptual-semantic representation. On the other hand,
speech is spoken and therefore has to be linked to a motor system. The fact that
these are separable pathways can be inferred from the fact that one does not pre-
clude the other. We are capable of uttering nonsense words as an example of motor
The Critical Contribution of the Dorsal Pathway 119
speech without comprehension, and we are sometimes able to comprehend speech

without being able to reproduce it.
This dual route model posits that a ventral stream is involved in processing
speech for comprehension, i.e., semantic and phonological processing, sound rec-
ognition, and the long-term storage of semantic information. The ventral stream
involves the superior and middle portions of the temporal lobe.
The dorsal stream is involved in the sensory motor integration which includes
articulation of speech sounds. It is an auditory to motor translation. The dorsal
stream also is associated with syntactic analysis and phonological memory. The
dorsal stream involves the posterior planum temporale and posterior frontal lobe.
The dorsal stream is largely left dominant. And while there is a long history of
attributing speech to the left hemisphere, the current data indicates that the ventral
stream is actually bilaterally organized (Hickok, 2012). In his article (2012) Hickok
offers a comprehensive and elucidating review of current neuroimaging findings
and contradictions. These will not be repeated here. However, what is largely undis-
puted is the need for auditory motor integration. The link between auditory and
motor interaction dates to Wernicke and remains an important foundational fact for
current studies and theory.
The Critical Contribution of the Dorsal Pathway
While both systems are necessary for fully functional speech, Hickok and Poeppel
(2007) point to the primacy of the dorsal pathway because “learning to speak is
essentially a motor learning task. The primary input to this is sensory, speech in
particular. So, there must be a neural mechanism that both codes and maintains
instances of speech sounds and can use these sensory traces to guide the tuning of
speech gestures so that the sounds are accurately reproduced.”
Recent research (Flinker, 2015), rather than using neuroimaging, utilized direct
intracranial cortical recordings, through both written and spoken modalities to
assess the role of the Broca’s area during spoken word operations. They found that
by the time actual speech commenced, activation in the Broca’s area was quiet, but
activity in the motor cortex was apparent. This suggests that the Broca’s area contri-
bution is limited to pre-articulatory stages rather than online coordination of the
speech articulators.
The beginning of the dorsal pathway is located at the boundary of the temporal
and parietal lobes near the Sylvian fissure. The first step of the dorsal pathway
begins in the sensory motor interface located in the left Sylvian fissure where the
temporal and parietal lobes interface. The Sylvian parietal-temporal area is impor-
tant for perceiving and reproducing sounds and for phonological short-term mem-
ory. Without this area, language acquisition is impaired. The information then
moves on to the articulatory network, which is divided into two separate parts. The
articulatory network consists of one part which processes motor syllable programs,
and the second articulatory network is for motor phoneme programs. In summary,
the white matter tracts support different processing with the arcuate fascicle having
primary involvement in phonology and articulation and the extreme capsule (EmC)
involved in semantics.
In a review of the research, suggested that the dual pathway model adds to our
understanding and has valid components; however, the independence of the streams
may have been overemphasized. A synergistic relationship between these white
matter tracts for language processing and function is more likely. However, research
into how cortical and subcortical areas interact is fairly new, and how these systems
interact is a current focus. Rolheiser et al. (2011) attempted to assess the contribu-
tion of the white matter tracts, with the primary focus on those directly connecting
frontal and temporal regions—the arcuate fascicle (AF) and the extreme capsule
(EmC). Using a combination of neuropsychological inference, DTI, and compre-
hensive language testing, Rolheiser et al. (2011) demonstrated that involvement of
either the arcuate fascicle, which connects the Wernicke’s area and Broca’s area, or
the extreme capsule is contingent upon the varying demands of different compo-
nents of language function. This model is very important as it one speaks to the
current author’s contention (Wasserman & Wasserman, 2020) that neural network
recruitment is task specific and provides a portion of the model into understanding
how disruption of the development of a neural pathway in developing children can
alter the impact or expression of language-based problems in some instances,
enough to cause pathognomonic signs and, in others, to cause overlapping behav-
ioral expression. Rolheiser’s (2011) results contribute to understanding the interac-
tive nature of neural pathways and, specifically, the contribution of white matter to
language by documenting how performance of phonology, morphology, semantics,
and syntax makes use of the neural pathways essential for receptive and expressive
communication. Rolheiser’s work demonstrated a relationship between white mat-
ter and behavior which reveals task-specific variability. They conclude that this
data, in conjunction with recent studies documenting indirect and secondary white
matter pathways relevant to language, demonstrates that it is likely that relevant
frontotemporal language connections operate in a collaborative manner. They posit
that ultimately behavior emerges as a product of coordinated gray matter activity, as
a result of working in conjunction with white matter pathways. And again, that
recruitment of pathways is task specific. The current authors would agree.
In fact, the current authors would argue that this is largely the point: that is, child-
hood development reflects an ever-expanding network of neural pathways. While
the mature brain is organized into more functional networks which are altered by
being task specific or, put another way, reflect a flexibility in recruitment in order to
support various cognitive processes, the developing brain represents an emerging
model. The developmental phases represent changes in sensory, motor, and cogni-
tive abilities, and the goal of developmental cognitive neuroscience is to better
understand the link between neural substrates and these complex developmental
milestones. Fair et al. (2009) documented the now generally accepted fact that brain
regions in children communicate with other brain regions on a more local level.
That is, regions communicate with closer regions. As the child develops, the cortical
Cortical and Subcortical Involvement in Motor Speech 121
communication becomes more distributed (across hubs) ultimately moving from

“local” distribution to a highly correlated distributed network, commonly seen in
the adult brain.
Cortical and Subcortical Involvement in Motor Speech
The current authors would like to direct the reader to previous work for a moment
wherein we have attempted to tie the connectome to motivation (Wasserman &
Wasserman, 2020) and the principles of therapy (Wasserman & Wasserman, 2019),
as well as the work of Koziol (2014) in tying the vertical brain model to executive
functioning. Inherent in all these works is a fundamental understanding of child/
human development, learning, and automaticity. While these works literally encom-
pass volumes, there is a core attention to the inclusionary nature of multiple pro-
cesses which include, but are not limited to, the inclusion of curiosity; directed
attention; directed movement and feedback, that is, moving toward; and corrective
inhibition of movement, to produce automaticity of learned skills. The analogy to
speech and language demands notation. Specifically, consider the process and pur-
pose of movement. Movement requires the arousal of the ventral attention network
(Koziol, 2014) for object identification, including arousal of the reward network,
and the dorsal attention network for identifying how things work. These two net-
works interact with the frontoparietal network for goal-directed behavioral control
processing, working in unison to create the action control network. The visual sys-
tem then interacts to sustain attention to a particular object or goal while suppress-
ing attention and movement toward others. The sensory motor network then executes
the motor portion of the process. A corresponding process exists for speech. Whereas
a shiny red ball may have been the object of curiosity, arousal, and goal-directed
behavior for the infant in our prior example, in the speech domain, the object or goal
is replaced by an internal representation of the phonological pattern of a word
(Hickok, 2012). Hickok posits that the targets are known to be auditory in nature
because of work demonstrating that alterations in auditory feedback result in com-
pensatory speech sounds. He points to the work of Guenther et al. (1998) to help
demonstrate that a person talking will modify their motor articulations in order to
“hit” an auditory target or speech sound, thereby indicating that the target is the
sound rather than the motor configuration.
Koziol et al. (2012) note that just as gesturing requires movements to be expressed
in a certain order, vocal sound sequences also rely on an organized sequence in
order to express a particular meaning. This ties the connection between motor
sequencing and verbal sequencing. In fact, this also ties into the subcortical-cortical
nature of the process with basal ganglia-cortical loops providing a unique neural
architecture for the necessary foundations for sequencing the structure or rules
across gestures and vocalizations. From an evolutionary standing, these structures
already existed and were specialized over time so that the result is that language is
dependent upon the basal ganglia for sequential learning and upon the frontal cortex
for the necessary motor programming.
In fact, the current authors wish to remind the reader that intention predates lan-
guage development. During the sensory motor period, infants begin to demonstrate
what appears to be the innate reflex of curiosity (Wasserman & Wasserman, 2020),
which results in execution of intent through motor movement. This movement is
reinforced and thereby found to be rewarding to the infant-seeking behavior. We
also know that categorization precedes language (Rakison & Yermolayeva, 2010)
but sets the stage for language development. In this way we can see that language
and motor movement are inexorably linked in human development.
Some more recent theoretical work has clarified the underlying auditory motor
integration (Hickok et al., 2011) in the dorsal stream. Through recent advances in
understanding motor control, speech research has emphasized the role of internal
forward models in speech motor control. The basic idea (Hickok et al., 2011) is that
the nervous system makes forward predictions about the future state of the motor
articulators and the sensory consequences of the predicted actions to control action.
The predictions are assumed to be generated by an internal model that receives
efference copies of motor commands and then integrates them with information
about the current state of the system and past experience of the relation between
particular motor commands and their sensory consequences. This internal model
allows for a mechanism for detecting and correcting motor errors, that is, motor
actions that fail to hit their sensory targets. The ability to suppress errors whether in
motor action or speech is very important. It allows us to fine-tune our intent and
product. This process of attention to a target and its implementation of behavior,
whether behavioral or speech, requires inhibition from attention to or attempts of
other behaviors. This inhibition initiates with the basal ganglia, elevating the impor-
tance of this subcortical structure to commensurate importance with the cortically
based frontal cortices. It is within the cerebellum that this finely tuned computa-
tional arithmetic takes place cementing the necessary interplay of the motor areas
acting in concert with the cerebellum and basal ganglia loops (Hickok, 2012). The
reader will note the expansion of the originally cortical centric model to a cortical
subcortical model.
Prediction Errors and Motor Speech
Let us take a moment and review the potential importance of the reference to
“detecting and correcting motor errors, that is, motor actions that fail to hit their
sensory targets” (Hickok, 2012). Hickok correctly notes that this principle applies
to behavior and to speech behavior. In fact, there is a significant body of recent
research highlighting the role of prediction errors, the discrepancy between pre-
dicted and actual information, and the neural mechanisms engaged as it related to
speech in general and CAS in specific. Other researchers also suggest increased
prediction error as a factor in CAS.
The current authors refer to the importance of the concept of prediction errors
and its role in learning, reward, and motivation (Wasserman & Wasserman, 2020)
Cerebellum and CAS 123
and the concurrent importance of dopamine in the incorporation and support of

brain networks involved in motivation, as well as orienting and cognition. They note
that “Models incorporating prediction errors have been invoked to explain complex
phenomena such as the transition from goal directed to habitual behavior,” a con-
cept which the current authors wish to highlight as applicable to speech production
as well. In fact, error prediction is described as “controlling and learning self-
directed motor behaviors {as it} involves both an implicit forward model of the
effector and explicit model of the task.” Also of importance, Popa and Ebner (2019)
note that “self-directed motor behavior cannot be cleanly separated from the under-
lying cognitive context.”
Cerebellum and CAS
Much of what was learned about cerebellum function, as with other cerebral areas,
originally came from studying the effects of lesions in the area. The cerebellum
evolved to allow for the organism to anticipate sensorimotor feedback in order to
facilitate rapid execution of behaviors, typically ones which have become auto-
matic. For a long time, the cerebellum’s contribution was considered to be limited
to proprioception. More recent data indicates that this is a disservice to the cerebel-
lum. The cerebellum is a very old structure evolutionarily speaking. It clearly served
a function and was retained. Leiner et al. (1994) noted that during this phylogenic
evolution, the growth of the neocortex and cerebral association areas was matched
by growth of the lateral cerebellar hemispheres and the dentate nucleus and associa-
tion connections between these areas. The cerebellum is in fact believed to contain
three times as many neurons as the neocortex. Leiner hypothesized that these mul-
tiple bilateral cerebro-cortical connections allowed for the engagement of the cere-
bellum in human cognitive and language functioning.
This was followed by a seminal study by Schmahmann and Sherman (1998)
conducted with patients with cerebellar damage, which described symptoms which
they termed cerebellar cognitive affective syndrome which included cognitive,
visual spatial, emotional impairment, and language impact including agrammatisms
and dysprosody. This sparked interest in the cerebellum and its relationship to other
subcortical and cortical functions. In addition to other areas such as working mem-
ory, executive function, visuospatial function, and affective regulation, research
began to look at the role of the cerebellum and language. The cerebellum is charac-
terized by linguistic lateralization, and, from a neuroanatomical perspective, the
cerebellum’s right hemisphere, which has multiple connections with cerebral cortex
language areas, is important for language functions. In fact, there is ample evidence
supporting the role of the cerebellum in the production of language, particularly its
role in facilitating the serial order of linguistic units or phonemes by regulating the
accuracy, speed, and rhythm.
The cerebellum is organized by area. Overlearned or automatic motor behaviors
are facilitated within the anterior lobes of the cerebellum. The learning of new
sensory motor behaviors, as well as cognitions, is regulated by the posterior and

inferior lobes of the cerebellum. The cerebellum assists with behavioral corrections
and the predicted outcome of movements. That is, the olivary portion of the cerebel-
lum detects errors and refines its feedback prediction of feedback with each move-
ment. As a coordinated effort, this allows for the organism, or speaking to origination,
the brain of the organism, to execute the behavior with increasing precision and
accuracy. By informing the neocortex, the cerebro-cerebellar circuit allows for rapid
coordination of intention and movement prediction. A sound neurotypical cerebel-
lum then interfaces sensory and motor components, refining the program each time
a movement is repeated. In essence, it learns from practice, allowing the behavior or
behavioral sequence, to become more precise and automatic. It informs the cerebral
cortex about the predicted outcome of movements which can then be stored in the
motor and premotor cortex to allow for rapid execution of the behavior (Koziol,
2014). Schmahmann described the cerebellum’s role in the regulation of language
function as analogous to its role in motor regulation. Likewise, he described the
impairment of cerebellar prediction and regulation as a “dysmetria of thought”
(1998). The cerebellum has also been implicated in dyslexia, dysgraphia, and
aphasia.
Let us consider a possible outcome of cerebellum damage with regard to its role
in feedback for movement. The cerebellum’s role is modulation of behavior. It does
not initiate movement. The cortex is the primary processor of sensory and motor
information which the cerebellum modulates. The damage to the cerebellum would
result in an inability to compute errors for accuracy. The cerebellum would not be
able to perform an online analysis modulating excitatory and inhibitory processes.
It would not be able to perform error prediction analysis. For a larger motor move-
ment, the movements would be released through the cortex-basal ganglia loops,
e.g., reaching for an object, but without the support from the cerebellum, the move-
ments would be erratic and uncoordinated (Koziol, 2014).
The association of the cerebellum and language regulation is derived from the
found neural connections between the cerebellum and neocortex, specifically the
Broca’s area. Each cerebellar hemisphere both receives and sends information to the
contralateral hemisphere. These corticocerebellar tracts connect the lateral parts of
the cerebellum with the frontal lobe through ascending and descending pathways.
The ascending pathway begins in the dentate nucleus in the cerebellum and goes to
the thalamus and to the contralateral areas of the frontal lobe. The motor cortex
receives information from the dentate nucleus, and the prefrontal cortex receives
information from the ventro-lateral areas. As described elsewhere in this section, the
cerebellum is then involved in many aspects of cognition, which are not motor
based, including language.
The work of Ackerman et al. (2007) looked at the neural correlates related to the
cerebellum with respect to speech, sound perception, and production. The cerebel-
lum also plays a vital role in both gesturing (motor) and speech. The authors note at
least two main roles of the cerebellum with respect to language. Ackerman et al.
(2007) contend that the cerebellum contributes to the temporal organization of the
sound structure of verbal utterances by supporting online sequencing of syllables
Basal Ganglia and Procedural Memory 125
during overt speech production. They also have evidence for the cerebellum partici-
pating in the generation of internal speech through a pre-articulatory verbal code.
These changes have been linked to mutations in the FoxP2 gene in particular.
Cerebellar Dysfunction and CAS
Additional studies have specifically assessed the association of cerebellar dysfunc-

tion in CAS, attempting to assess cerebellar function in tasks requiring greater com-
plexity and integration. Peter et al. (2020) compared the motor performance of 18
children and adolescents diagnosed with CAS and 11 controls to that of an adult
with a likely history of CAS and to an adult with a cerebellar stroke. The first set of
conditions included a rapid syllable repetition for repeated same or monosyllables
(papapa), disyllables (patapata), and trisyllables (patakapataka). They then included
a key tapping task involving tapping the same key with one finger vs tapping two
keys with two fingers, alternating the finger taps. A third task assessed fine and gross
motor skills and balance. Peter et al. found that the children with CAS have the
greatest difficulty, with rapid syllable repetition for the two-syllable condition and
less difficulty when switching among three different syllables. They indicated no
difficulty when repeating the same syllable. The participant with the cerebella
stroke showed deficits in tests of both fine and gross motor ability, as well as in bal-
ance. Both repetitive and alternating key tapping was slow in the ipsilateral hand
relative to the stroke. Peter concludes that the results are consistent with persisting
cerebellar dysfunction that is persisting into adulthood. A similar pattern was found
in the key tapping condition with children and adolescents showing difficulty with
alternating, but not repetitive key tapping. The subject with CAS performed less
well on a test of fine motor ability where the tasks required rapid integration of
complex hand movement sequences. Peter et al. (2020) found that the adult with the
probable historical diagnosis of CAS obtained motor performance scores similar to
those found in the children and adolescents with CAS.
Basal Ganglia and Procedural Memory
There is recognition that a goal of human learning is to make much learning “routin-
ized” or automatic (Koziol, 2009). The repetition of a particular activity and its
progressive consolidation of the memory trace of the skills involved in this activity
leading to their automaticity are a process known as procedural memory. Procedural
memory is involved in daily activities such as driving a car or throwing a ball. There
is conflicting data on when the procedural memory system is matured, but it is
clearly present early on developmentally speaking. The neural correlates of proce-
dural memory are the subcortical structures, the basal ganglia, and the cerebellum.
Grammar and syntax are rule governed and routinized through the processes of
basal ganglia “binding” operations (Koziol, 2014).
The basal ganglia are a group of bilateral subcortical nuclei. The nuclei consist
of the striatum, which has a dorsal and ventral component, the globus pallidus, the
subthalamic nucleus, and substantia nigra. They do not direct the cortex. Rather,
they are a gating mechanism. This cortico-striatal system modulates both behavior
and cognition through neural pathways, or loops, by helping in the selection of
which behaviors will be executed and which will be suppressed. The basal ganglia
gating is not limited to overt behavior. Rather, visual and auditory association areas
also project into the striatum.
Ullman and Pierpont (2005) hypothesized a model known as the declarative-
procedural model. This model proposes two domains: the mental lexicon and the
mental grammar domains. The mental lexicon is comprised of non-rule-based infor-
mation, our lexicon, or dictionary reserve of words we know as well as words, for
example, which need to be memorized such as irregular verbs (buy-buying-bought
vs buyed), as well as interpretation of idioms. The mental lexicon is considered to
be declarative memory associated and as such temporal lobe (cortical) based. The
procedural memory system is associated with rule-based grammar. This domain is
associated with cortical-subcortical circuits allowing for us to combine words into
complex ideation as well as allowing us to interpret these complex representational
strings of words. Rule-based grammar develops early in children and is believed to
be based upon procedural learning (Koziol, 2009). Other aspects of language may
also be learned in procedural memory, when the knowledge is implicit and involves
learning to predict things such as the implicit learning of word boundaries in a
stream of speech. There is also a suggestion that procedural memory is impacted in
specific language impairment. Children with the diagnosis of specific language
impairments have difficulties with the acquisition of grammatical rules. Some have
difficulties with motor sequencing. These children have been found to abnormal
activation in frontal cortices and specifically the left supplementary motor area as
well as in the basal ganglia. The two types of memory are associated within frontal
systems, depending on the task. This seems to beg the question of whether impact
in the procedural learning system learning will impact declarative memory with
implied impact on language comprehension as well as speech production.
Basal ganglia loops are commonly conceptualized to originate and terminate in
a given area of cerebral cortex that has direct connectivity with the striatum, which
includes the caudate nucleus and the putamen (Bohali et al., 2016). Loops are dis-
tinguished based upon cortical origination and termination areas. These areas are
usually, but not always, located in the frontal lobe. Recent conceptual work by
Bohsali and Crosson (2016) emphasizes three types of basal ganglia loops, each
having some common components with others originating from the same cortical
area. The direct loop starts in one of several areas of cortex that share direct con-
nectivity with striatal components from the striatum. The direct pathway releases
behavior. These loops project to the medial global pallidus and from the medial
global pallidus to a thalamic nucleus. The thalamic nucleus projects back to the area
of cortex from which the loop originates. Cortico-striatal and thalamic cortical
Basal Ganglia and Procedural Memory 127
connections are excitatory, and striato-palladal and pallido-thalamic connections

are inhibitory. The fourth pathway, the striosomal pathway, projects from the
cortical-based paralimbic system to the substantia nigra. This is then providing the
basal ganglia with necessary information, information which the basal ganglia uses
in the process of learning of new motor behaviors and in lending support for the
aforementioned rule-based grammar systems.
Indirect and hyper-direct loops also begin in specific area of cortex. For the indi-
rect loops, the cortex projects to the striatum, similar to direct loops, which are
glutamate excitatory connections. However, in this loop, the striatum projects to the
lateral global pallidus (gabinergic/inhibitory connections) which in turn projects to
the subthalamic nucleus (inhibitory connections). Then the subthalamic nucleus
projects back to the medial global pallidus. The medial global pallidus projects to
one of the thalamic nuclei mentioned above, and finally the thalamus projects back
to the cortical component from which the loop originated.
Like the direct and indirect loops, the hyper-direct loop originates in one of the
cortical areas projecting to the basal ganglia, but it differs from these loops by
bypassing the striatum. Instead, the cortical component of the loop projects directly
to the subthalamic nucleus. In turn, the subthalamic nucleus projects back to the
medial global pallidus. The medial global pallidus projects to one of the thalamic
nuclei mentioned above and completing the loop. The thalamus projects back to the
cortical component from which the loop originated. Basal ganglia models often sug-
gested that loops associated with functionally distinct cortical areas should project
to separate and non-overlapping regions within the basal ganglia. Alexander et al.
(1986) implied that loops are segregated from one another. Additional studies, how-
ever, provide evidence that some basal ganglia loops are integrative, allowing cross-
communication between discrete functional networks. Silveri (2021) notes that the
cerebellum and the basal ganglia area reciprocally interconnected. It is therefore
quite plausible that when damage involves one of these structures, one can likely see
the remote effects of abnormal activity in the other. That is, in a functional network,
disruption in one area can result in pathology in more remote areas. The current
authors would remind the reader that from a developmental perspective, damage to
one area would likely impact any neural development in a feedforward program,
thus potentially disrupting both neural and behavioral development from that area
of disruption forward across integrated networks and subsequently functions.
The neural substrates of the cerebellar, cortex, and association areas represent
the cerebellar non-motor functions. The cerebellum and the cerebral cortex, as
noted elsewhere, are connected by feedforward cerebellum-thalamus-cortico-ponto-
cerebellar pathway. Of importance, segregated functional zones from the cerebel-
lum to heterogenous extra-cerebellar structures are densely connected on a
subcortical level. Both the cerebellum and the basal ganglia project to the same
primary motor areas; however, most projections are to other areas including the
premotor cortex and temporal and parietal areas. This system reflects closed loop
architecture with exchanged information between neocortical areas, the basal gan-
glia, and the cerebellum. The cerebellum, as discussed elsewhere in this section, is
believed to compare the current, actual movement with predicted movement it has
stored, or learned, through sensory feedback. This model also extends to the cogni-
tive domains. Overall, the recent research indicates that the cerebellum and basal
ganglia are indeed part of this highly integrated cortical-subcortical functional net-
work and is involved in motor control as well as associated with cognition and affect.
roca’s Area, Basal Ganglia Loops, and the Supplementary

B
Motor Area (SMA)
As discussed above, research of recent decades has been providing evidence sup-
porting the notion of Broca’s area basal ganglia loops (Ullman, 2006). Functional
neuroimaging studies measuring regional blood flow effects associated with test
performance implicated Broca’s area in the basal ganglia to support an overlapping
set of language functions. Specifically, both regions are thought to be involved in
lexical selection and retrieval, syntax, phonology, as well as higher-order language
processing. Functional connectivity studies modeling modulatory relationships
between patterns of activation and gray matter regions have shown direct functional
connectivity between Broca’s area and putamen, pointing to its role of potentially
supporting articulatory control and identification of phonological representations of
lexical items. Research has, as discussed above, identified pathways connecting
Broca’s area with the striatum.
The supplementary motor area (SMA) has been shown to be the center for motor
planning. This includes motor planning for speech. The supplementary motor area
(SMA) occupies the posterior one third of the superior frontal gyrus. Supplementary
motor area (SMA) syndrome is defined as temporary paralysis and mutism follow-
ing damage to the SMA. Although paralysis induced by SMA syndrome is severe
during the acute phase, recovery usually occurs within relatively short periods and
rarely results in a permanent deficit. There is also a pre-SMA area. The pre-SMA
and SMA are differentially involved in the sequencing and initiation of movements,
with the pre-SMA acting at a more abstract level than the more motoric SMA (Toga,
2015). One of the first bits of evidence regarding a pre-SMA basal ganglia loop
involved in language came from the study of fMRI data to determine frontal, basal
ganglia, and thalamic contributions during three facets of language usage: lexical
items, semantic vs. phonological information, and rate of generation. The subjects
performed four tasks. They had subjects generate lexical/category members for cat-
egories. For example, subjects might be asked to generate as many birds as they
could, to which they might reply “parakeet, hawk,” etc. To determine whether activ-
ity was attributable to the semantic nature of this task, subjects also generated words
that rhymed with the stimulus word. For example, subjects might be asked to gener-
ate as many words as they could that rhymed with rap. Finally, to determine whether
activity was unique to the lexical nature of the task, subjects were tasked with gen-
erating as many nonsense syllables as they could that began with the beginning and
ending consonant blend, for example, “st” at two different rates of generation speed.
Broca’s Area, Basal Ganglia Loops, and the Supplementary Motor Area (SMA) 129
They found that a part of the left pre-SMA-dorsal caudate nucleus—ventral anterior
thalamic loop—was active during the task for generating words either to a category
or to rhyming cues; the loop was not active during the task requiring nonsense syl-
lable generation. They concluded that the loop is associated with the retrieval of
words from the lexical library. In addition, diffuse activity in the right basal ganglia
(caudate nucleus and putamen) was active during word generation, but not for non-
sense syllable generation. The absence of right frontal activity during the word gen-
eration task was interpreted to mean that the right basal ganglia activity is used to
suppress right frontal activity which in turn prevents right frontal structures from
interfering with language production.
With respect to connections between the pre-SMA and Broca’s area (Ford et al.,
2010), found an anterior-to-posterior gradient with connections between the Broca’s
area, the Brodmann’s area, the supplementary motor area, and the pre-supplementary
motor area (SMA). They tied this finding to other findings of the anterior Broca’s
area being associated with semantics and the posterior Broca’s area associated with
syntax and phonology. Connectivity between the Broca’s area and SMA presents a
plausible structural interface for interaction between basal ganglia loops involving
these cortical areas. The clear role of the Broca’s area in speech production coupled
with data indicating SMA involvement in word selection provides support that these
basal ganglia loops may interact, providing modulation feedback to ensure the opti-
mal level of speed and accuracy for speech. Broca’s area pre-SMA connectivity
may be the likely candidate for this mechanism.
Bohasali and Crosson (2016) provide a compelling potential model for Broca’s
region basal ganglia loop processing. They tie the findings that the Broca’s area was
modulating activity in the putamen, implicating the putamen to speech initiation
and articulation as well as the cortical initiation of phonological representations, a
finding supported by prior data. They conclude that the Broca’s area is crucially
involved in articulatory and phonological processing with a specific emphasis on
this circuit, including the putamen, as it supports phonological/articulatory process-
ing. Specifically, phonological representations are likely to be activated within the
Broca’s area-auditory association area network based on contextual content estab-
lished by the temporal and inferior parietal cortical networks. They propose that the
basal ganglia may be “sharpening the signal to noise ratio of the most contextually
appropriate lexical items, There phonological representations, in corresponding
articulatory motor programs via the direct loop, while suppressing competing pho-
nological items via the indirect loop” (Bohali et al., 2016). The hyper-direct loop
could be resetting the system after the most appropriate phonological representation
has been selected, tying this to other pathways within the loops. They propose that
Broca’s area basal ganglia loops are acting in concert with another basal ganglia
loop, specifically the pre-SMA loop to ensure the accuracy of the speech produced
so that the actual verbal output both matches the intended expression and addresses
processing speed to promote fluidity of the expressed speech.
Citing research from Crosson et al. (2004) and Hagoort (2005), they then suggest
that we should be talking about Broca’s region rather than Broca’s area in particular.
This larger region would include the Broca’s area, lateral premotor cortex, and pars
orbitalis which would be termed the language unification hub of the brain. In fact,
Hagoort proposed that the language hub actually consists of three language unifica-
tion components. The first is syntactic unification. This syntactic unification repre-
sents the linking of lexical components into multi-word components utilizing the
rules of grammar. The second component is the unification component. This domain
unifies our lexical strands into phrases accompanied by appropriate prosody. For
example, much social convention is implicated in the phrase “How are you” depend-
ing upon the intonation accent on the word “are” vs the word “you.” The semantic
unification component allows for the understanding of a lexical item within context.
These components follow an anterior to posterior functional gradient with subsec-
tions of Broca’s region supporting various aspects of language, working in unison
to support fluid, well-timed speech production. Bohsali and Crosson (2016) suggest
that Broca’s area and pre-SMA basal ganglia loops work together, combined into
the Broca’s region, to allow for the transfer of information so that appropriate mean-
ing is assigned (semantic unification) and the items are organized in grammatically
correct phrases (syntactic unification) with appropriate intonation applied and with
appropriate phonological and articulation initiation.
Language and Motor Cortex in the Interpretation of Speech
The association between motor cortex and spoken speech should be fairly obvious
as to the need to move orofacial areas and articulators. Poeppel and Assaneo (2020)
wondered whether motor cortex is also involved in interpreting speech. Recognizing
that the entrained signals, or the chunking or coupling of oscillating systems, in the
auditory cortex are usually hovering at about 4.5 Hz and that this is the average rate
of syllables spoken across languages, they attempted to ascertain if there was a neu-
rophysiological basis. They had subjects listen to syllables for nonsense words at
rates between 2 and 7 Hz. In fact, they tracked the entrained signal from the auditory
cortex to the motor cortex, another example of how various regions of the brain
synchronize across tasks, in this case, language perception.
It is interesting to note that the research indicates that, although to a lesser degree,
deaf children who sign can also stutter, which seems to concretize the association
between language and motor areas, rather than vocalizing areas per se.
Iuzzini-Seigel (2019) looked at whether children with childhood apraxia of
speech and other speech disorders and typically developing children would show
differences in motor skill attainment in general. Children were classified by lan-
guage ability and assessed with the Movement Assessment Battery for Children—
Second Edition. The results found that children with CAS performed below the
normal limit on all components of the motor battery and more poorly than the typi-
cal and speech sound disordered children on measures of aiming and catching as
well as balance. Iuzzini-Seigel notes how this pattern may impact social, academic,
and later on vocational functioning. Iuzzini-Seigel also suggests that what we may
be looking at in children with CAS is a “higher order deficit that mediates
In Summary 131
cognitive-linguistic and motor impairments” in this group. This finding again sug-
gests that the comprised motor system in CAS is also recruited for other motor-
driven tasks, and as such this system being compromised will lead to dysfunction in
other motor-driven areas. Since, as we have demonstrated, the motor areas are an
essential component to most, if not all cognitive activities, this disruption of func-
tion should be anticipated to be extensive.
In making our argument that childhood apraxia of speech involves much more
than simple disruption of the motor system, we should consider what happens when
the semantic/categorical process is disrupted thereby affecting a lack of automatic-
ity for phonemes and sound production. This would result in increasingly disor-
dered cognitive processing utilized to interpret incoming information and to encode
it to support developmentally appropriate growth of abstract reasoning. The fact
that this system is further impacted, through the process of ongoing develop-
ment, reflecting increasingly cognitive load, should also be considered.
In Summary
The treatise of both chapters detailing the global nature of CAS is that child devel-
opment is in effect a bottom-up/feedforward process which potentially impacts
multiple areas, and impact in one area potentially impacts other areas depending
upon where in the neurophysiological system the problem arises. We have traced
potential impact from their genetic etiology in some cases to their behavioral mani-
festations and then to neural pathway modeling to demonstrate the complexity and
the global reach of the potential problems associated with CAS. Where in this
course of development the lack of appropriate unfolding of processes occurs will,
logically, impact children in somewhat different ways. We may observe the sensitiv-
ity and lose the diagnosis because of a lack of specificity.
This addresses both why there is so much confusion as to the pathognomonic
signs across disorders and why relying solely on behavioral descriptors is problem-
atic. We need to consider the impact of this diagnostic model on how we end up in a
circumlocutious state of diagnosis and behavioral descriptors. That is, we describe
descriptors, which sound muddled because of our attempts to put processing issues
into a modular diagnostic framework and end up with descriptors of diagnostic cat-
egories which do little else than list descriptors. This can be problematic when work-
ing with children because we intervene only when pathognomonic signs are fully
apparent. And often times we intervene within the domain most notably impacted
without an appreciation for the impact in other developmental domains, seeing them
as separate and often not targeted if they do not reach the “cutoff” for deficit status.
This then impacts intervention with what the current authors believe to be an impor-
tant fact, the interrelatedness of the identified area with other domains and the need
to address the areas presenting with “softer signs.” If these two chapters have done
their jobs, they will have raised the reader’s awareness of an often underdiagnosed
disorder, which is not limited to motor planning in the orofacial area, but rather has
cortical relatedness to many other areas of child development of skills.
he Implications of Bottom-Up Development

T
for the Functional Implications of CAS
Childhood apraxia of speech represents a developmental disorder. Adult lesion-

based studies may have limited applicability in terms of modeling. It is rather
important for us to understand the “bottom-up” development of the brain, to truly
appreciate the significance of subcortical structures and functions to the higher-level
cognitive processes. For example, we know that if a child’s behaviors are generated
by maturational lags in cerebellar development during the course of early childhood
development, a child’s presentations may be marked by the manifestation of rela-
tively mild motor difficulty. Actually, motor skill and the quality of motor skills,
both gross and fine, can be impacted. For example, the child may have delayed early
milestones such as in sitting independently and walking independently. The child
may show signs of hypotonia or low muscle tone. This can lead to problems with
fine muscular and motor control early on as meeting early developmental mile-
stones and later as impacting how the child sits and writes. Speech production
requires fine oral motor control. This is required for articulation of oral motor
sequencing in the production of expressing a speech sound and motor associations.
Developmental anomalies within these aspects of language system can easily gener-
ate phonological processing deficits, and as we know, phonology is a critical foun-
dation for reading and speech production or language. On a pragmatic level, the
magnitude of impact would affect the conscious effort required to accomplish
reading-related tasks because of “even subtle motor difficulties, reading related
tasks would be performed slowly, while in aggregate the diminished allocation of
cognitive resources.” More effortful cognitive processing would take an additional
toll on reading automaticity and comprehension. These observations enable the cli-
nician to understand language and reading development. “They are not pathogno-
monic signs that indirectly identify a particular disorder. Instead, these are risk
factors that serve to predict an increased likelihood of a future diagnosis of dyslexia.
This is a critical distinction” (Koziol, 2014). The same can be said for childhood
apraxia of speech. That is, childhood apraxia of speech is a developmental disorder
with early motor development having a potential association to phonological pro-
cessing difficulties and subsequent language difficulties with accompanying impact
in fine or gross motor behavior or both. Again, these are not pathognomonic signs,
but rather risk factors which should alert professionals to the potential benefit of
early intervention.
For example, when conducting a neuropsychological evaluation, we should not
rely solely on the achieved standard scores. We should be looking at possible risk
factors. Other similarly developmental risk factors include difficulty with early
identification of letters and letter sound associations, such as asking the child to
identify which word in a group has a different starting letter (e.g., bat-ball-doll) or
sound blends (br-br-bl). These types of sound word association games require
speech, sound awareness, or phonological processing that can be more formally
assessed during neuropsychological evaluations. “Performance on these tasks is
Treatment of CAS 133
presumably dependent upon the integrity of frontal parietal networks. However,

dependent upon the specific task, numerous other brain regions can be recruited,
characterized by changing patterns of functional connectivity in both the left and
right cerebral hemispheres.”
Treatment of CAS
There are some general principles finding agreement regarding the treatment of
CAS. Firstly, it is largely agreed that some activities, although part of the speech
pathologist’s tool box and of potential face validity, for example, blowing bubbles,
are not translating into effective treatment practices for children with CAS. Secondly,
CAS is recognized as a “neurological speech sound disorder in which the precision
and consistency of movements are impaired” (ASHA, 2022). ASHA emphasizes the
need for repetitive planning, programming, and production necessitating the need
for intensive and individualized intervention. ASHA highlights a need for both
motor programming-based approaches and linguistic approaches. Therefore, there
is stress on speech sound movements with the goal of the child developing speech
sound skills which are accurate and consistent and which reach a level of automatic-
ity. The linguistic aspect incorporates an emphasis on how to make the speech
sounds and how to make sequences of speech sounds and the rules for when sounds
and sequences are used. The following is a brief description of motor-based treat-
ment approaches.
The Dynamic Temporal and Tactile Cueing approach uses a cueing hierarchy
which is systematically diminished as the child progresses. The system is designed
to shape movement gestures. It begins with direct imitation and moves to simultane-
ous production with provided tactile or gestural cues if direct imitation was not
successful. Cues are then faded and the cycle repeats. This approach is recom-
mended for very young children with severe childhood apraxia of speech.
The Nuffield Dyspraxia Program emphasizes the development of phonemes—
single speech sounds and simple syllables. The phonological skills are then incor-
porated into simple word pairs. The goal is a solid “core.”
The Rapid Syllable Transition (ReST) program aims to train motor planning
flexibility through the repetition of varied sequences of either real or nonsense syl-
lables. This method aims for accurate speech production, rapid and fluent transition
across sounds, and accurate syllable stress within words.
The current authors wish to note that other programs exist. For example, the
PROMPT program aims to provide Prompts for Restructuring Oral Muscular
Phonetic Targets. This program is not limited to children with CAS. Linguistic
methods are complementary to motor programs. They emphasize speech function
with the aim of helping the child internalize phonological rules. Prosodic facilita-
tion aims to improve intonation. Through rhyming and rhythmic activities, the child
is taught to use appropriate intonation to train functional phrases.
As noted elsewhere in this chapter, for some children, difficulties with residual
issues including difficulties with unfamiliar multisyllable words, persistent speech
sound errors, and struggles with prosody may persist into adulthood. This empha-
sizes the need for both early identification and intervention.
No doubt many reading this chapter on childhood apraxia of speech will ask
since treatment is currently practice-practice-practice, why is this level of under-
standing important? The authors believe that one of the most important reasons for
this level of understanding of the disorder is to debunk the myth that CAS is “sim-
ply” a disorder of speech motor dysfunction. It is the hope of the current authors that
readers will come a way with a deeper understanding of the need to move away
from a behavioral description of CAS as a disorder of phonology to an understand-
ing of how the phonology is intercorrelated with other functions, including motor
integration, language comprehension, reading, and arithmetic. There are implica-
tions for the trajectory of CAS impacting many other areas of development includ-
ing social and academic. CAS is not “just” a speech motor disorder.
Secondly, it is hoped that the reader, as a clinician or practitioner, will be more
aware of the implications of underdiagnosing this disorder. Treatment for CAS is
not a short-term or low-frequency-based intervention. Treatment of CAS requires
the overriding of genetic coding, the establishment of neural connections of greater
integrity as they traverse from local to larger network integration, and the establish-
ment of greater automaticity for these developmental skills.
Thirdly, it is important for the child and their families to understand that this
disorder is not self-limiting. There are implications for all academic areas, and
unless the clinician understands the connection between brain-based development
and the expression of developmental readiness for academic skill attainment, the
family and related teaches will not either.
Fourth is the need to understand the associations of CAS to disordered reading
and arithmetic as interpreted by brain-based processes so that the child is supported
in areas not typically viewed as directly associated with “a speech problem.”
It is important for the clinician to help family and teachers to understand how this
“speech” disorder may impact both receptive and expressive language and language
communications.
Lastly, there are implications for school-based support services for children with
CAS. We currently have a system which affords services to children who show a
deficit in a particular academic area. What the current chapter clearly indicates is
that supports will potentially be necessary in multiple areas, for although they may
not be deficit per se, they are likely impacted. This may mean occupational therapy
supports for lingering motor coordination weaknesses to supports for learning to
“read” numbers and mathematic signs. Those areas of weakness represent associ-
ated processing weaknesses which collectively impact the success of any child.
Owing to the historical professional trajectory of the current authors, we side on
the error of caution. We believe strongly in early intervention. We believe strongly
that the early years are critical formation years. We believe that it is better to ascer-
tain if there is a presence of risk factor signs coupled with a behavioral expression
References 135
of multiple signs of CAS and offer intervention services before they become pathog-
nomonic, before they impact a child’s social and academic progress and ultimately
their self-esteem.
References
Ackermann, H., Mathiak, K., & Riecker, A. (2007). The contribution of the cerebellum to speech
production and speech perception: Clinical and functional imaging data. Cerebellum, 6(3),
202–213.
Alexander, M. D., DeLong, M. R., & Strick, P. L. (1986). Parallel organization of functionally
segregated circuits linking the basal ganglia and cortex. Annual Review of Neuroscience, 9,
357–381.
ASHA. (2022). Childhood Apraxia of Speech. Retrieved from ASHA: ASHA.ORG
Bishop, D. (1997). Uncommon understanding: Development and disorders of language compre-
hension in children. Taylor & Francis.
Bohali, A., Gullet, J., Mareci, T., Crosson, B., FitzGerald, D., White, K., & Nadeau, S. (2016).
Structural connectivity of Broca’s region (I7.004). Neurology, 86(16 Supplement), I7.004.
Bohsali, A., & Crosson, B. (2016). The basal ganglia and language: A tale of two loops.
In J. Soghomonian (Ed.), Innovations in Cognitive Neuroscience. Springer. https://doi.
org/10.1007/978-3-319-42743-0_10
Catani, M., & de Schotten, M. T. (2008). A diffusion tensor imaging tractography atlas for virtual
in vivo dissections. Cortex, 44(8), 1105–1132. https://doi.org/10.1016/j.cortex.2008.05.004
Catani, M., Allin, M. P., Husain, M., Pugliese, L., Mesulam, M. M., Murray, R. M., & Jones,
D. K. (2007). Symmetries in human brain language pathways correlate with verbal recall.
Proceedings of the Nationall Academy of Sciences U S A, 104(43), 17163–17168. https://doi.
org/10.1073/pnas.0702116104. Epub 2007 Oct 15. PMI.
Crosson, B., et al. (2004). Left and right basal ganglia and frontal activity during language gen-
eration: Contributions to lexical, semantic, and phonological processes (pp. 1061–1067).
Cambridge University Press.
David, D. H., & Rakison, D., Yermolayeva, Y. (2010). Infant categorization. WIREs Cognitive
Science, 1, 894–905.
DiDonato, A. (2014, May). New directions in social competence research: Examining develop-
mental trajectories and language minority populations. Retrieved from ASU.edu: https://keep.
lib.asu.edu/_flysystem/fedora/c7/114024/DiDonato_asu_0010E_14024.pdf
Fair, D., Cohen, A., Power, J., Dosenbach, N., Church, J., & Meizen, F., et al. (2009). Functional
brain networks develop from a “local to distributed” organization. PLoS Computational
Biology. https://doi.org/10.1371/journal.pcbi.1000381
Fields, D. (2010). Change in the brain’s white matter; the role of the brain’s white matter in active
learning and memory may be underestimated. Science, 330(6005), 768–769.
Fiori, S. G., Guzzetta, A., Mitra, J., Pannek, K., Pasquariello, R., Cipriani, P., Tosetti, M., Cioni, G.,
Rose, S. E., & Chilosi, A. (2016). Neuroanatomical correlates of childhood apraxia of speech:
A connectomic approach. NeuroImage: Clinical, 12, 894–901.
Flinker, A. K. (2015). Redefining the role of Broca’s area in speech. Proceedings of the National
Academy of Sciences, 112, 2871–2875. https://doi.org/10.1073/pnas.1414491112
Ford, A., McGregor, K. C., Crosson, B., & White, K. D. (2010). Structural connectivity of Broca’s
area and medial frontal cortex. NeuroImage, 52(4), 1230–1237. https://doi.org/10.1016/j.
neuroimage.2010.05.018
Gao, Y., Meng, X., Bai, Z., Liu, X., Zhang, M., Li, H., Ding, G., Liu, L., & Booth, J. R. (2022).
Left and right arcuate fasciculi are uniquely related to word reading skills in Chinese-
English bilingual children. Neurobiology of Language, 3, 109–131. https://doi.org/10.1162/
nol_a_00051
Guenther, F., Hanpson, M., & Johnson, D. (1998). A theoretical investigation of reference frames
for the planning of speech movements. Psychological Review, 05(4), 611–633. https://doi.
org/10.1037/0033-295X.105.4.611-633
Hagoort, P. (2005). On Broca, brain, and binding. Trends in Cognitive Science, 9(9), 416–423.
Hickok, G. (2012). The cortical organization of speech processing: Feedback control and predic-
tive coding the context of a dual stream model. Journal of Communication Disorders, 45(6),
393–402.
Hickok, G., & Poeppel, D. (2007). The cortical organization of speech processing. Nature Review
Neuroscience, 8(5), 393–402.
Hickok, G., Houde, J., & Rong, F. (2011). Sensorimotor integration in speech processing:
Computational basis and neural organization. Neuron, 69, 407–422.
Iuzzini-Seigel, J. (2019). Motor performance in children with childhood apraxia of speech and
speech sound disorders. Journal of Speech, Language and Hearing Research, 62(9), 3220–3233.
Kadis, D. S., Goshulak, D., Namasivayam, A., Pukonen, M., Kroll, R., De Nil, L. F., Pang,
E. W., & Lerch, J. P. (2014). Cortical thickness in children receiving intensive therapy for
idiopathic apraxia of speech. Brain Topography, 27(2), 240–247. https://doi.org/10.1007/
s10548-013-0308-8. Published online 2013 Aug 24.
Koziol, L. (2014). The myth of executive functioning: Missing elements in conceptualization, eval-
uation, and assessment. Springer International Publishing.
s12311-011-0321-y
Leiner, H. C., Leiner, A. L., & Dow, R. S. (1994). The underestimated cerebellum. Human Brain
Mapping, 2(4), 244–254.
Liegeois, F. J., & Morgan, A. T. (2012). Neural bases of childhood speech disorders: Lateralization
and plasticity for speech functions during development. Neuroscience & Biobehavioral
Reviews, 36, 439–458.
Maassen, B. (2002). Issues contrasting adult acquired versus developmental apraxia of speech.
Seminars in Speech and Language, 23, 257–266.
Maassen, B. (2015). Developmental models of childhood apraxia of speech. In I. R. S. Bahr (Ed.),
Routledge handbook of communication disorders (pp. 124–133). Routledge/Unesco.
McNorgan, C. (2021). The connectivity fingerprints of highly-skilled and disordered reading per-
sist across cognitive domains. Frontiers in Computational Neuroscience, 15, 590093. https://
doi.org/10.3389/fncom.2021.590093
Peter, B., Bruce, L., Raaz, C., Williams, E., Pfeiffer, A., & Rogalsky, C. (2020). Comparing global
motor characteristics in children and adults with childhood apraxia of speech to a cerebellar
stroke patient: Evidence for the cerebellar hypothesis in a developmental motor speech disor-
der. Clinical Linguistics and Phonetics, 35(4), 368–392.
Poeppel, D., & Assaneo, M. F. (2020). Speech rhythms and their neural foundations. Nature
Reviews Neuroscience, 21(6), 322–334.
Popa, L., & Ebner, T. (2019). Cerebellum, predictions and errors. Frontiers in Cellular
Neuroscience. https://doi.org/10.3389/fncel.2018.00524
Preston, J. L., Molfese, P. J., Mencl, W. E., Frost, S. J., Hoeft, F., Fulbright, R. K., Landi, N.,
Grigorenko, E. L., Seki, A., Felsenfeld, S., & Pugh, K. R. (2014). Structural brain differences
in school-age children with residual speech sound errors. Brain and Language, 128(1), 25–33.
https://doi.org/10.1016/j.bandl.2013.11.001
dysfunction. Current Opinion in Neurobiology, 13(2), 212–218.
Rolheiser, T., Stamatakis, E. A., & Tyler, L. K. (2011). Dynamic processing in the human lan-
guage system: Synergy between the arcuate fascicle and extreme capsule. The Journal of
Neuroscience, 31(47), 16949–16957.
Schmahmann, J. D., & Sherman, J. C. (1998). The cerebellar cognitive affective syndrome. Brain,
121(4), 561–579.
References 137
Semenza, C., & Benavides-Varela, S. (2018). Reassessing lateralization in calculation. Royal

Society: Biological Sciences.
Shaywitz, S. S. (2005). Dyslexia. Biological Psychiatry, 1–13.
Shriberg, L. D., Lohmeier, H. L., Strand, E. A., & Jakielski, K. J. (2012). Encoding, memory, and
transcoding deficits in childhood apraxia of speech. Clinical Linguistics & Phonetics, 26(5),
445–482.
Shriberg, L. D., Strand, E. A., Jakielski, K. J., & Mabie, H. L. (2019). Estimates of prevalence of
speech and motor speech disorders in persons with complex neurodevelopmental disorders.
Clinical Linguistics & Phonetics, 33(8), 707–736.
Sierpowska, J., Bryant, K., Jannsen, N., & Piai, V. (2022). Comparing human and chimpanzee
temporal lobe neuroanatomy reveals modifications to human language hubs beyond the fron-
totemporal arcuate fasciculus. Proceedings of the National Academy of Sciences, 119(28),
e2118295119. https://doi.org/10.1073/pnas.2118295119
Silveri, M. (2021). Contribution of the cerebellum and the basal ganglia to language production:
Speech, word fluency, and sentence construction - evidence from pathology. Cerebellum,
20(2), 282–294.
Simonyan, K., Ackermann, H., Chang, E., & Greenlee, J. (2016). New developments in under-
standing the complexity of human speech production. Journal of Neuroscience, 36(45),
11440–11448. https://doi.org/10.1523/JNEUROSCI.2424-16.2016
Toga, W. (2015). Brain Mapping. Elsevier Inc, Academic Press.
Ullman, M. (2006). Is Broca’s area part of a basal ganglia thalamocortical circuit? Cortex, 42(4),
480–485.
Ullman, M., & Pierpont, E. I. (2005). Specific language impairment is not specific to language:
The procedural deficit hypothesis. Cortex, 41(3), 399–433.
Velleman, S. (2011). Lexical and phonological development in children with childhood apraxia of
speech – A commentary on Stoel-Gammon’s ‘relationships between lexical and phonological
development in young children’. Journal of Child Language, 38(1), 82–86.
Wasserman, T., & Wasserman, L. D. (2019). Therapy and the neural network model. Springer.
Wasserman, T., & Wasserman, L. D. (2020). Motivation, effort and the neural network model.
Springer.
Chapter 9
Neuropsychological Assessment
of Apraxia: Where Network Reality
and Domain Assessment Collide
Neuropsychological assessment is based on the premise that neuropsychological

functioning in humans consists of the operation and integration of skill-specific
domains. Neuropsychological testing is often cognitively heavy. For example, most
neuropsychological assessments will attempt to describe the functioning of lan-
guage, visuospatial skills, attention, memory, and sensorimotor domains (Koziol,
2014). Each of these domains is responsible for processing (cognitive) information.
This processing is broken down into a set of specific activities. Six such activities
have been identified:
1. Remembering: Recall or retrieve previous learned information. Example is
recite a story that you just read.
2. Understanding: Comprehending the meaning, intention, interpolation, and inter-
pretation of instructions, reading material, and presented problems.
3. Applying: Use a concept/newly learned material in a new situation or unprompted
use of an abstraction.
4. Analyzing: Separating material or concepts into component parts so that its
organizational structure may be understood. This also includes distinguishing
between facts and inferences.
5. Evaluating: Make judgments about the value of ideas or materials.
6. Creating: Builds a structure or pattern from numerous elements. Putting parts
together to form a whole, with emphasis on creating a new meaning or structure.
There are other things to consider. Blooms taxonomy, for example (Armstrong,
2010), has areas of psychomotor consideration. These include the following:
1. Perception (awareness): The ability to use sensory cues to guide motor activity.
This ranges from sensory stimulation, through cue selection, to translation.
2. Set: Readiness to act. It includes mental, physical, and emotional sets. These
three sets are dispositions that predetermine a person’s response to different situ-
ations. By extension, this can be considered intentionality and therefore poten-
tially related to some forms of apraxia.
3. Guided response: The early stages in learning a complex skill that includes imi-
tation and trial and error. Adequacy of performance is achieved by practicing.
140 9 Neuropsychological Assessment of Apraxia: Where Network Reality and Domain…
4. Mechanism (basic proficiency): This is the intermediate stage in learning a com-

plex skill. Learned responses have become habitual, and the movements can be
performed with some confidence and proficiency.
5. Complex overt response (expert): The skillful performance of motor acts that
involve complex movement patterns. Proficiency is indicated by a quick, accu-
rate, and highly coordinated performance, requiring a minimum of energy. This
category includes performing without hesitation and automatic performance.
6. Adaptation: Skills are well developed, and the individual can modify movement
patterns to fit special requirements.
7. Origination: Creating new movement patterns to fit a particular situation or spe-
cific problem. Learning outcomes emphasize creativity based upon highly devel-
oped skills.
At first glance, these psychomotor areas would appear to have relevance in identify-
ing treatment approaches that would facilitate the development of the various skills.
Neuropsychological assessment would appear to focus on the first set of cognitively
based skills and much less on these psychomotor skills. We will be highlighting the
value of focusing on the psychomotor skills and suggest ways for neuropsycholo-
gists to include them, in a more comprehensive and systematic manner, in their
ongoing assessments.
How Many Domains Are There?
As with everything else, there is general agreement as to the concept, but some dis-
agreement as to the exact number of domains. For the purpose of classifying neuro-
cognitive disorders, the Neurocognitive Work Group of the DSM 5 (American
Psychiatric Association, 2013) agreed on six principal domains of cognitive func-
tion: (1) memory and learning, (2) language, (3) executive functions, (4) complex
attention, (5) social cognition, and (6) perceptual and motor functions. Meta-
analytic reviews have identified up to seven cognitive domains: attention/working
memory, executive functioning, language, verbal memory, visual memory, visuo-
motor ability, and visuospatial ability (McGinty et al., 2014). Most psychological
tests identify four, including verbal skills, visual motor skills, memory, and percep-
tual motor skills being the most common. As psychological assessment follows the
descriptors proffered by the American Psychiatric Association, the six cognitive
domains (complex attention, executive function, learning and memory, language,
perceptual-motor function, and social cognition) have found themselves an integral
part of neuropsychological assessment.
When it comes to the assessment of most apraxic conditions, it seems apparent
that the emphasis on cognitive domain assessment that characterizes neuropsycho-
logical assessment is not clearly relatable in the assessment of apraxia. Given the
fundamental motor nature of apraxic conditions, it behooves us to look at whether
neuropsychological tests are designed to assess the conditions that comprise apraxia.
Domains Are Complex and Subsume Multiple Functions 141
Briefly, this does not seem to be the case. The motor tests that are typically included
in a neuropsychological test battery look at how effectively the individual is able to
coordinate hand-eye movements, finger dexterity, balance, and motor speed in gen-
eral (Weintraub, 2000b). For the most part, these assessments are based on behav-
ioral observation, which is fine, or assessments of basic motor speed, which is fine,
but do not seem to be geared to assessing white matter dysregulation of motor func-
tioning and conceptualizing how this disruption is functionally important. That is
why, with the possible exception of childhood apraxia of speech, most neuropsy-
chologists, if they assess apraxia in the first place, content themselves to a descrip-
tion of an observable motor skill dysfunction and leave the treatment to someone
else. Given, as we have seen, that based upon network modeling, downstream
effects in general, and cognitive effects in particular, of an apraxia producing lesion
should be anticipated, perhaps it is wise for neuropsychologists to better develop
tools and skills to assess the far-reaching consequences of apraxia in its several
forms. Specifically, neuropsychologists have to do better than merely administering
tests and reporting standard scores. This is a field based upon the premise that
behavior is brain based and it is the purpose of the neuropsychologist to understand
and help others understand how this process is unfolding or disrupted in any given
individual referred for assessment.
Domains Are Complex and Subsume Multiple Functions
There are issues with domain-based assessment that should be considered. As

should be readily apparent, each domain supports a wide variety of activities and
knowledge. We can never assess the functioning of an entire domain no matter how
many tests we give. We can only sample certain of the many complex skills. What
is more concerning from a network perspective is that these domains are considered
discrete and largely dissociable from each other. That is, neuropsychologists, for
example, believe that there is the ability to assess only visual motor, or receptive
language, or memory skills without contamination from other skill areas. As we
have demonstrated elsewhere (Wasserman & Wasserman, 2017), there are problems
with these ideas. Basically, network modeling is based on the idea, and neuroimag-
ing confirms that networks constantly interact with one another to produce an out-
come. Based on that assumption, it would be highly unlikely that we would ever be
able to assess only one discrete area of functioning, because the possbility that just
one independent network controls the complex functioning assessed by neuropsy-
chological tests is infinitesimally small.
Let’s take a look at some of these areas of concern in detail.
uestionable Assumptions Concerning Ability

Q
of Neuropsychological Tests
The neuropsychological assessment of apraxia is hampered by certain assumptions

that have traditionally characterized neuropsychological test function. Examining
these assumptions and challenging them based upon networking principles will
point to the way forward for including apraxias into neuropsychological testing
considerations.
ssumption: Most Disorders Are Produced by Discrete and Dissociable

A
Neuropsychological Deficits
There is an assumption that once we diagnose a specific clinical condition, ADHD,

for example, we somehow understand what has gone wrong with the neural network
underpinning that skill. For example, if a person is diagnosed as having ADHD, we
often provide feedback detaining the same descriptors presented in the DSM though
that is an explanation of brain-based behavior. Child has been referred for inatten-
tiveness and impulsivity, diagnosed with ADHD, and parent receives the explana-
tion that child has ADHD so he is inattentive and impulsive. A more neural-based
explanation would allow one to reliably assume fronto-striatal network abnormali-
ties contributing to ADHD (Bush, 2010) or that the deficits are specifically related
to dysfunction of the reticular activating system which is a basal ganglia structure
that is the major relay system among the many pathways that enter and leave the
brain. Only this assumption is not entirely accurate.
Neuropsychological studies of attention-deficit hyperactivity disorder (ADHD)
actually identify a broad range of processes that are dysregulated in attention-deficit
hyperactivity disorder. These include areas of executive dysfunction including
inhibitory and working memory deficits, as well as non-executive deficits (percep-
tion; memory timing) (Sonuga-Barke et al., 2010). Alterations in motivational and
reward processes have also been identified (Wasserman & Wasserman, 2015).
Moreover, even the most robust neuropsychological effects are only moderate in
size and often fall short of the level required for diagnosis. Sonuga-Barke et al. point
out that Nigg et al. (2005) found only 30% of patients with deficits on at least three
tasks on a large executive function assessment battery. They believed that this pat-
tern of limited associations across distinct domains highlights the neuropsychologi-
cal heterogeneity in ADHD.
Originally, the dual pathway model of attention-deficit hyperactivity disorder
(Sonuga-Barke, 2003) posited that this heterogeneity was the result of two, more or
less, independent patterns of deficit each affecting some ADHD patients and not
others: one grounded in dorsal fronto-striatal dysregulation mediated by inhibitory-
based executive function and the other underpinned by ventral fronto-striatal cir-
cuits and linked to altered signaling of delayed rewards, manifest as delay aversion.
There were still a group of patients for which neither of these circumstances were
identified. They proposed a third dissociable system based on temporal processing

deficits in conjunction with basal ganglia. As we have suggested, later research has
identified still others. The point here is that there is not one clear dysfunctional sys-
tem in ADHD or in many other disorders. There are many. If you diagnose ADHD
on behavioral criteria, which is how it is done, you have no knowledge which of the
many potential causal systems are implicated.
There is research to suggest that the same issue arises when attempting to assess
the role of executive function (EF) in psychopathology. Research investigating phe-
notypic and genetic overlap of three EF latent variables (a common EF factor pre-
dicting response inhibition, working memory updating, and mental set shifting tasks
and updating- and shifting-specific factors) with five impulsivity dimensions (nega-
tive and positive urgency, lack of premeditation and perseverance, and sensation
seeking) found common EF and multiple impulsivity dimensions, particularly nega-
tive urgency, independently predicted externalizing psychopathology. The research
demonstrated that multiple impulsivity dimensions, but not common EF, predicted
internalizing psychopathology (Friedman et al., 2020). These results suggested that
EFs and self-reported impulsivity tap different aspects of control that are both rele-
vant for psychopathology. EFs and impulsivity appear to “capture somewhat over-
lapping but phenotypically and genetically separable constructs. Importantly, they
are both valid measures of individual differences that are independently relevant for
understanding externalizing psychopathology. Thus, EF and impulsivity are not
interchangeable” (pg536). Assessing this accurately means that assessment has the
ability to discretely and accurately assess each construct. Given the confusion in
multiple definitions of both constructs, the answer is at best ambiguous (Bickel,
2012). This research suggested that EF and impulsivity are generally considered
conceptually distinct, but, in fact, they may be antipodes (i.e., widely separated on
a common continuum, upon which they are related). The authors highlight a quote
by Hermann Hesse “Scientific thought often progresses by recognizing heterogene-
ity in phenomena formally considered homogenous. This evolution sometimes
involves identifying small components and conceptualizing how they fit together to
produce larger phenomena” (pg361). We concur. If you identify a person as having
ADHD using behavioral criteria, then that’s what you know. You do not know for
sure what the specific neurological underpinning is as it could be several things or a
combination of several things.
The same situation pertains to understanding the neuropsychological underpin-
ning of obsessive-compulsive disorder. For example, a multi-parameter MRI study
revealed specific white matter abnormalities in OCD suggesting tract disorganiza-
tion as main feature, reflected by local changes in fiber directionality. This altered
anatomical connectivity might play a specific role in OCD pathophysiology
(Garibotto et al., 2010). Specifically, OCD patients showed significantly lower frac-
tional anisotropy values and altered principal diffusion direction along a wide range
of network structures. These included the corpus callosum, cingulum, superior lon-
gitudinal fasciculus, and inferior fronto-occipital fasciculus bilaterally. In addition,
a track-based analysis of the inferior fronto-occipital fasciculus confirmed a signifi-
cant bilateral FA reduction. Lower FA values in the inferior fronto-occipital
fasciculus, superior longitudinal fasciculus, and corpus callosum correlated with

symptom severity and neuropsychological performance. Here we have a suggestion
of a rather complex network with many components that is somehow dysfunctional.
We do not know how or why, and we do not know if the problem emanates from a
specific place or that the entire network is somehow compromised. More recent
research confirmed this idea by demonstrating that OCD patients presented wide-
spread microstructural abnormalities in distributed working memory tracts and that
heterogeneity of dysfunction characterized their findings (Zang et al., 2021).
Finally, there is research to suggest that the problems associated with OCD are
related to white matter myelination as opposed to a structural or neural transmitter-
based dysfunction (Maleki et al., 2020). They found no significant group differ-
ences in brain structures were observed between OCD and healthy controls. Rather,
they found that MTR, an indicator of myelination, was positively associated with
OCD symptom severity in numerous regions including the OFC, striatum, CC,
insula, and cingulum. Specifically, they found that higher myelination was found in
certain brain regions in more severe OCD patients.
In summary, existing functional connectivity studies of obsessive-compulsive
disorder (OCD) provide considerable support for a model of network dysfunction.
That being said, these group-level observations have failed to yield neuroimaging
biomarkers sufficient to serve as a test for the OCD diagnosis, predict current or
future symptoms, or predict treatment response, perhaps because these studies
failed to account for the substantial intersubject variability in structural and func-
tional brain organization (Brennan et al., 2019).
This situation becomes more problematic when it is recognized that you cannot
assess discrete elements of a neural pathway independently of its other component
parts or from the task you are using to assess it.
ssumption: We Can Assess Components of a Neural Network

A
Independently of Its Other Components
We have stated that many constructs that are taken for granted in modern neuropsy-
chology, fluid intelligence, and executive function among them can best be explained
by conceptionalizing them as a collection of task-specific processes engaged in an
integrated recruited network involved in problem solving. However, fractionalizing
an organically integrated network in an attempt to describe elements of its function
leads to arbitrarily defined segments that may be interesting to discuss abstractly,
but never occur independently in the real-world operation of the system itself
(Wasserman & Wasserman, 2017). This would suggest that you cannot assess the
functioning of just one component of a highly integrated network recruited to solve
a particular task. For example, our meta-analytic review of tests of attention deficit
disorder concluded that the assessment of executive functioning by neuropsycho-
logical tests inevitably leads to assessment of cortical-subcortical circuitry common
to many forms of executive function and, by implication, behavioral functioning
(Wasserman & Wasserman, 2013).
As a result of the shared nature of network components, any finding you would
generate would be “contaminated” by the operation of other network components
that were recruited to solve the particular task used in the assessment. You would be
confronted by the problem that network recruitment is task specific, and it is highly
probable that no two tasks recruit exactly the same network. For example, when
attempting to measure attention, you can use paying attention to an image as a mea-
sure of sustained attention. Clearly, the nature of the picture is a factor with indi-
vidual implications to the viewer. Not all pictures evoke the same emotional
responses, and some may not evoke any at all. The addition of an emotional compo-
nent brings onboard networks associated with reward recognition. Thus a similar
task might involve the recruitment of dissimilar networks due to the history of the
individual being asked to solve the task.
This has wider implications as well. For example, all of the domains of cognition
that have been found to relate to motor learning can broadly be classified as fluid
cognitive abilities, which are a global cognitive measure reflecting one’s abilities for
problem solving and learning new things in the absence of prior experience. Thus,
it is possible that global fluid cognition, rather than visuospatial working memory
specifically, is related to motor learning, and it is impossible to disentangle the two
(French et al., 2021).
ssumption: Neuropsychological Tests Were Designed to Assess

A
Brain Function
It is generally accepted that the historical purpose of clinical neuropsychology was

to assist in the diagnosis of brain pathology (Chaytor & Schmitter-Edgecombe,
2003). In general, neuropsychological tests were successful in doing so (Long &
Kibby, 1995). With the expansion and development of imaging techniques, the role
of neuropsychological testing has changed. There are, of course, some disorders,
like apraxia, that are not readily diagnosed using imaging techniques or testing.
There are also certain disorders, such as cognitive delay, which still require the use
of testing to aid in diagnosis. The number of disorders that require testing for iden-
tification continues to diminish.
Neuropsychologists have adapted to these changes by broadening the range of
neuropsychology practice. Where traditionally physicians have customarily been
the primary referral source for neuropsychological assessments, other agencies
(schools, employers, lawyers, and insurance companies) now utilize neuropsychol-
ogy more frequently. As might be expected, this redefinition of scope of practice has
brought about a change in the types of questions that neuropsychologists are asked
to address. Referrals are moving away from diagnostic questions to questions about
cognitive abilities and disabilities, such as the suitability for advanced educational
programming, rehabilitation programs, and ability to work, live independently,
manage finances, and drive. While the questions have changed, most clinicians con-
tinue to utilize test data as the basis of the conclusions they reach regarding the
answer to these new questions. The tests themselves have not changed along with
the referral questions. That is, the same tests that were developed to answer injury-
related diagnostic questions are now used to answer different questions, for which
they were not designed. Neuropsychologists have responded by attempting to asso-
ciate neuropsychological test performance to very specific brain function (Hale
et al., 2010). Nevertheless, current neuropsychological tests were not designed to
assess neural network functioning and are likely too blunt to do so.
ssumption: Neuropsychological Tests Can Identify Specific, Discrete,

A
and Dissociable Brain-Based Deficits
We are not suggesting that neuropsychological tests do not measure brain function;
they clearly do. The question is what are we identifying? Firstly, we need to ques-
tion whether a function has been accurately identified. Most of us are taught that we
are testing a particular function. We administer the tests and report on the function
using the domain name of the test. There are, however, many examples of tests
“with the same domain name” and poor correlation coefficients ostensibly because
the task demands are just slightly different (Koziol, 2014).
What we are saying is that our tests tend to measure the operation of a broad set
of networks recruited to solve a particular task. Some psychologists write their
reports from a domain-based perspective and speak about deficits specific to that
domain, for example, visual spatial deficits or verbal memory deficits. We posit that
these are neither discrete nor dissociable domains. Two different but related tasks
would likely result in the recruitment of two different but related networks. It is
questionable whether it is even possible to independently measure a specific sub-
component of a construct such as executive function (Wasserman &
Wasserman, 2017).
Pathognomonic Signs in the Assessment of Apraxia
It should be fairly obvious by now that the available neuropsychological assessment

instruments possess neither the sensitivity nor specificity to determine the specific
functional neuropsychological deficit associated with the apraxic condition we are
attempting to assess. Fundamentally, that is because any particular apraxic condi-
tion can be due to a disruption of function anywhere in a complex network. The
same condition can be produced by lesions to different sites. That is not to say, the
neuropsychological assessment data is not useful. It is. Once determined that an
individual is experiencing an apraxic condition, test data can provide a thorough
look at associated academic and intellectual functioning that reflects large-scale
integrated network operation.
How should the practicing neuropsychologist diagnose apraxia? We have long
held that neuropsychology is not based on getting the answers from the test. It is
Pathognomonic Signs in the Assessment of Apraxia 147
using the test data, in conjunction with our body of knowledge, to arrive at a conclu-
sion. This leads us to a discussion of pathognomonic signs.
The term “pathognomonic sign” describes a sign, symptom, or a group of signs
or symptoms that is indicative of a specific physical or mental disorder and not
associated with other disorders. The sign is a particular sign whose presence means
that a particular disease is present beyond any doubt. To those of us who are in clini-
cal work, the pathognomonic sign approach is essentially everyday practice. The
behavioral symptom clusters associated with the diagnosis of mental health condi-
tions are essentially a list of hypothetically discriminating pathognomonic signs of
a particular disorder. The system certainly has its detractors, including the present
authors. The fact remains that certain currently used clinical conditions are so broad,
vague, and overlapped with other clinical conditions that identifying them by
pathognomonic sign is the only available option. Such is also the case for apraxia,
especially developmental apraxia. We have argued elsewhere (Wasserman &
Wasserman, 2016) that this state of affairs is not conducive to good science and that
the system should be replaced with one that classifies dysfunction based upon the
underlying neuropsychology. We will argue here for the same thing as regards
apraxia. However, as it stands now, the underlying dysfunction of many apraxic
conditions is not currently identifiable. There are exceptions of course, such as in
the case of adult stroke or brain injury. However, the specific etiology of develop-
mental apraxia and other related language impairments has not been elucidated.
That leaves us with pathognomonic sign approach.
If only it was that easy. The following is from the ICD-10-CM (World Health
Organization(WHO), 1993), and it highlights the problem. Apraxia is identified as
a “group of cognitive disorders characterized by the inability to perform previously
learned skills that cannot be attributed to deficits of motor or sensory function. The
two major subtypes of this condition are ideomotor (see apraxia, ideomotor) and
ideational apraxia, which refers to loss of the ability to mentally formulate the pro-
cesses involved with performing an action. For example, dressing apraxia may
result from an inability to mentally formulate the act of placing clothes on the body.”
The major point is that apraxia does not describe one specific disorder but rather a
group of disorders characterized by the inability to do a motor task. Although the
description goes on to say that “aparaxias are generally associated with lesions of
the dominant parietal lobe and supramarginal gyrus,” that is not always the case.
Interestingly, the above definition excludes aparaxias caused by cardiovascular dis-
ease, although it does not say why.
Clinical Presentation
So maybe pathognomonic sign approach is not exactly the best idea which leaves
the idea of clinical presentation. How does it look to the clinician trying to assess it?
What it looks like is a motor disorder wherein a person cannot perform a motor task
that they previously could perform. It does get a bit more specific, especially when
apraxic disorders of speech are considered. For example, “the most common AOS
errors involve place of articulation, with affricates and fricatives most affected (e.g.,
a word with affricate sounds such as the ‘ch’ in ‘church’ will be more difficult to say
for apraxic speakers than a word with bilabial phonemes, such as the ‘m’ in ‘mom’).
Errors are more common on consonant clusters, rather than singleton consonants
(e.g., ‘strict’ will be more difficult than ‘sit’) and patients with AOS are more likely
to produce errors when asked to repeat nonsense words, as opposed to meaningful
words. Patients with AOS often assign equal stress to each word. Pauses between
syllables and words are common, as is an overall slowed rate of speech” (Ogar
et al., 2005). The problem with this is that these particular abilities are the purview
of speech and language pathologists. They are not generally included in a standard
neuropsychological assessment and not part of training for most psychologists or
neuropsychologists. Perhaps that needs to change.
Developmental Apraxia of Speech and Pathognomonic Sign
There are problems with the pathognomonic sign approach when it comes to devel-
opmental apraxia; namely, there do not appear to be a stable set of pathognomonic
signs. Research continues to demonstrate, as we have been saying, that develop-
mental communication disorders have multi-factorial origins at different levels of
organization (genetic, environmental, neurological, behavioral). Moreover, the
influence of these levels of organization on the resulting behavioral output is inter-
active rather than uni-directional (Maassen, 2015). In addition, relatively little is
known about the contribution of two of these factors, the genetic and neurological
factors. All of this is further compounded by the possibility that developmental
apraxia and acquired apraxia are doubly dissociable disorders and separate entities
(Karmiloff-Smith et al., 2003). A thorough review of this issue is in a separate chap-
ter in this volume.
What to Do, What to Do?
As regards apraxia, given the unsatisfactory state of affairs regarding the typical
procedures used by neuropsychologists to assess for dysfunction associated with
apraxia, what do neuropsychologists have to utilize to accomplish the diagnostic
task? The answer is that you assess the functional behavior that manifests as a result
of the impairment. Specifically, what does an apraxic individual do that a neurotypi-
cal individual does not do. It is not that a practicing neuropsychologist cannot dis-
cern behaviors related to a praxis. We are trained observers of behavior. It is that we
have been conditioned to think that the observation is not sufficient, norms based,
reliable, or valid. We are taught that the only way to validate our work is to have a
normed test score. We do not agree. In fact, in a system based on behavioral cluster
What to Do, What to Do? 149
analysis, the only ecologically valid assessment is assessment of individualized

behavior. Group normed tests are not designed to that. This leads to the idea that
neuropsychologists should be defined by their knowledge of how the brain works as
opposed to obtaining a reliable test score. Tests should be part of our tool kit, but our
opinions and diagnoses should, when appropriate, be based on our body of
knowledge.
Fortunately, models are available to instruct us in this regard. Speech and lan-
guage pathologists have identified a cluster of behaviors that characterize acquired
apraxia of speech, for example. Apraxia of speech (AOS) has been described as a
disorder affecting the ability to translate well-formed and filled phonological frames
into accurate movement programs to generate speech. The intra- and inter-articulator
timing and spatial errors that characterize the disorder result in core perceptual fea-
tures used for clinical diagnosis: increased segment and inter-segment durations,
distorted phonemes, consistent error type across repeated productions of words,
segmentation of syllables, and more equal stress over words and/or sentences
(Ballard et al., 2014). This would, of course, imply that the neuropsychologist is, or
should be, knowledgeable about these aspects of speech and their assessment. It
would also imply that either the current range of neuropsychological tests assesses
for these aspects of speech, which they do not, or neuropsychologists expand the
range and types of assessment tools they utilize.
We realize that we go into some detail on the speech aparaxias, but the same
system is utilized for most other aparaxias as well, for example, limb apraxia. Limb
apraxia is a heterogeneous disorder historically defined by exclusion: deficits in
skilled movement not caused by weakness, deafferentation, abnormal tone or pos-
ture, tremors or chorea, intellectual deterioration, or poor comprehension (Baumard
& Le Gall, 2021). Interestingly, research suggests that aparaxias like limb apraxia
are not task specific but instead reflect a general inability to move the limb under
many and dissociable task conditions (Belanger et al., 1996). This would argue for
the disruption of basic motor circuitry.
We realize that this form of assessment sounds distinctly like the type of cluster
analysis utilized in the DSM system. This likely represents the current state of the
art. We would argue that is somewhat unsatisfactory; however in that there is no
identification of the networks involved and no recognition of the fact that the resul-
tant core behaviors could be caused by numerous forms of disruption to the system.
The etiology of the various forms of apraxic conditions affecting speech remains
unclear. Investigators have speculated about whether the neurological damage in
apraxia is affecting the integrity of existing stored speech motor programs, forward
modeling, the feedback processes of error detection and/or correction, gradual tun-
ing of motor programs, and/or producing sequences of motor programs. These are
clearly components of a complex and integrated network system. It is possible that
understanding the exact nature of the apraxic condition will lead to more refined
treatment techniques. Of course, it is also possible that what is true for many skills
is also true for apraxia; practice repetition and the eventual automaticity of appro-
priate behavior are the best way to go. At the current time, we just do not have
enough information to know.
References
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders
(5th ed.). American Psychiatric Association.
443(12), 713–716. https://doi.org/10.1038/nature05164
Allison, K. C.-S. (2020). Differential diagnosis of apraxia of speech in children and adults: A scop-
ing view. Journal of Speech, Language, and Hearing Research, 63, 2952–2994.
Statement). Retrieved from American Speech-Language-Hearing Association: www.Asha.
org/policy
Andres, E. E. (2022). Family based whole exome analysis of specific language impairment
Sciences, 47.
Armstrong, P. (2010). Bloom’s taxonomy. Retrieved from Vanderbilt University Center for
Teaching: https://cft.vanderbilt.edu/guides-sub-pages/blooms-taxonomy/
ASHA. (2007). Childhood apraxia of speech technical report. American Speech and Language
Association.
ASHA. (2021). Childhood apraxia of speech. Retrieved from ASHA/Practice Portal/Clinical
Topics/: https://www.asha.org/practice-portal/clinical-topics/childhood-apraxia-of-speech/
Baldassare, A., Lewis, C., Committeri, G., Snyder, A. Z., Romani, G., & Corbetta, M. (2012).
Individual variability in functional connectivity predicts performance of a perceptual task.
Proceedings of the National Acadamey Scence U. S. A., 109, 3516–3521.
Ballard, K., Tourville, J., & Robin, D. (2014). Behavioral, computational, and neuroimaging stud-
ies of acquired apraxia of speech. Frontiers in Human Neuroscience. https://doi.org/10.3389/
fnhum.2014.00892
junction. NeuroImage, 30, 917–926.
43, 118–126.
Batista-García-Ramó, K., & Fernández-Verdecia, C. (2018). What we know about the brain
structure–function relationship. Behavioral Sciences, 8(39), 1–14. https://doi.org/10.3390/
bs8040039
Baumard, J., & Le Gall, D. (2021). The challenge of apraxia: Toward an operational definition?
Cortex, 141, 55–80. https://doi.org/10.1016/j.cortex.2021.04.001
Belanger, S., Duffy, R., & Coelho, D. (1996). The assessment of limb apraxia: An investigation
of task effects and their cause. Brain and Cognition, 32(3), 384–404. https://doi.org/10.1006/
brcg.1996.0072
References 151
Bickel, W. (2012). Are executive function and impulsivity antipodes? A conceptual reconstruction
with special reference to addiction. Psychopharmacology (Berl)., 221(3), 361–387. https://doi.
org/10.1007/s00213-012-2689-x
Bieńkiewicz, M., Brandi, M. G., Hughes, C., & Hermsdörfer, J. (2014). The tool in the brain:
Apraxia in ADL. Behavioral and neurological correlates of apraxia in daily living. Frontiers in
Psycholology. https://doi.org/10.3389/fpsyg.2014.00353, on line.
Brennan, B., Wang, D., Li, M., Perriello, C. R., Elias, J., Van Kirk, N., et al. (2019). Use of an
individual-level approach to identify cortical connectivity biomarkers in obsessive-compulsive
disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 4(1), 27–38.
https://doi.org/10.1016/j.bpsc.2018.07.014
Bush, G. (2010). Attention-deficit/hyperactivity disorder and attention networks.
Neuropsychopharmacology, 35(1), 278–300. https://doi.org/10.1038/npp.2009.120
Chaytor, N., & Schmitter-Edgecombe, M. (2003). The ecological validity of neuropsychological
tests: A review of the literature on everyday cognitive skills. Neuropsychology Review, 13(4),
181–187.
Association: ASHA.ORG.
org/10.1523/JNEUROSCI.6344-11.2012
Cleaton, A. T.-S. (2021). Gender and age differences in the presentation of at-risk or probable
developmental coordination disorder in adults. Research in Developmental Disabilities, 115.
https://doi.org/10.1016/j.ridd.2021.104010
Transactions of the American Academy of Ophthalmology and Otolaryngology, 56, 579–588.
symptom mapping study in acute stroke patients. Experimental Brain Research, 240, 39.
Cousins, M. S. (2003). Developmental coordination impairments in adulthood. Human Movement
Science, 22, 433–459. https://doi.org/10.1016/j.humov.2003.09.003
S0033291719003210
org/10.3109/02699209808985211
org/10.1093/brain/111.5.1173
of speech. In The annual convention of the American-Speech-Language-Hearing Association.
Poster. American-Speech-Language-Hearing Association.
brain alterations in motor areas. Acta Paediatrica, 108, 9. https://doi.org/10.1111/apa.14786
130–136.
in subcortical visual areas. Cells, 10(11), 3162. https://doi.org/10.3390/cells10113162
cit in Alzheimer's disease: Two sides of the same coin? Journal of the International
Edelman, G., & Gally, J. (2001). Degeneracy and complexity in biological systems. Proceedings
of the National Academy of Sciences, 98(24), 13763–13768.
Einspieler, C. P. (2021). Fetal movements; the origin of human behaviour. Developmental Medicine
& Child Neurology, 63(10), 1142–1148.
Farah, M. J., O'Reilly, R. C., & Vecera, S. P. (1993). Dissociated overt and covert recognition as
origin and use. Behavioral and Brain Sciences., 18, 723–806.
tive function in children. Frontiers in Psychology, 7. https://doi.org/10.3389/fpsyg.2016.00318
Reviews|Neuroscience, 16, 150–172.
French, M., Cohen, M., Pohlig, R., & Reisman, D. (2021). Fluid cognitive abilities are
important for learning and retention of a new, explicitly-learned walking pattern in indi-
viduals after stroke. Neurorehabilitation Neural Repair, 35(5), 419–430. https://doi.
org/10.1177/15459683211001025
Friedman, N., Hatoum, A., Gustavson, D., Corley, R., Hewitt, J., & Young, S. (2020). Executive
functions and impulsivity are genetically distinct and independently predict psychopathology:
References 153
Results from two adult twin studies. Clinical Psychological Science, 8(3), 519–536. https://doi.
org/10.1177/2167702619898814
fneur.2021.562090
Fulceri, F., Grossi, E., Contaldo, A., Narzisa, A., Apicella, F., Parrini, I., et al. (2019). Motor
skills as moderators of core symptoms in autism spectrum disorders: Preliminary data from
an exploratory analysis with artificial neural networks. Frontiers in Psychology, 9. https://doi.
org/10.3389/fpsyg.2018.02683
org/10.1016/S0166-2236(97)01128-4
Gainotti, G., & Trojano, L. (2018). Chapter 16 – Constructional apraxia. In G. Vallar & H. Coslett
org/10.1016/B978-0-444-63622-5.00016-4
Communications, 9, 4233. https://doi.org/10.1038/s41467-018-06560-z
Ganguly, J., & Jog, M. (2020). Tauopathy and movement disorders—Unveiling the chame-
leons and mimics. Frontiers in Neurology: Movement Disorders. https://doi.org/10.3389/
fneur.2020.599384
Garibotto, V., Scifo, P., Gorini, A., Alonso, C., Brambati, S., Bellodi, L., & Perani, D. (2010).
Disorganization of anatomical connectivity in obsessive compulsive disorder: A multi-
parameter diffusion tensor imaging study in a subpopulation of patients. Neurobiology of
Disease, 37(2), 468–476. https://doi.org/10.1016/j.nbd.2009.11.003
the National Academy Science U. S. A., 99, 7699–7704.
Green, D. C. (2008). Does subtype of developmental coordination disordrere count: Is there a dif-
ferential effect on outcome following intervention? Human Movement Science, 27, 363. https://
doi.org/10.1016/j.humov.2008.02.009
Gross, R., & Grossman, M. (2008). Update on apraxia. Current Neurology and Neuroscince
Guyette, T. W., & Diedrich, W. M. (1981). A critical review of developmental apraxia of speech.
In Speech and Language (pp. 1–49).
Hale, J., Alfonso, V., Berninger, V., Bracken, B., Christo, C., Clark, E., et al. (2010). Critical issues
in response-to-intervention, comprehensive evaluation, and specific learning disabilities iden-
tification and intervention: An expert white paper consensus. Learning Disability Quarterly,
33(3), 223–236.
disease: Implications for corticostriate involvement. Neuropsychologia, 614–621.
Handiru, V., Alivar, A., Hoxa, A., Saleh, S., Suviseshamuthu, E. S., Yue, G., & Allexandre,
prefrontal cortex/basal ganglia system. Philosophical Transactions of the Royal Society of
London. Series B, Biological Sciences, 362, 1601–1613.
Heilman, K., Maher, L., Greenwald, M., & Rothi, L. (1997). Conceptualized apraxia from lateral-
ized lesions. Neurology, 49(2). https://doi.org/10.1212/WNL.49.2.457
342–346.
Hildebrand, M. J. (2020). Severe childhood speech disorder. Neurology, 94, 2148–2167.
Science U. S. A., 106, 2035–2040.
Hua, J. W. (2022). Early motor milestones in infancy and later motor impairments: A population-
based data linkage study. Psychiatry. https://doi.org/10.3389/fpsyt.2022.809181
Huth, A., de Heer, W. A., Griffiths, W., Theunissen, F., & Gallant, J. (2016). Natural speech reveals
the semantic maps that tile human cerebral cortex. Nature, 532(7600), 453–459. https://doi.
org/10.1038/nature17637
logical disorders, and typical speech. Indiana University ProQuest Dissertations Publishing.
Iuzzini-Seigel, J. M. (2017). Speech assessment in children with childhood apraxia of speech.
In Perspectives of the ASHA special interest groups (pp. 47–60). American Speech Langauge
Hearing Association.
Iuzzini-Siegel, J. H. (2017). Speech inconsistency in children with childhood apraxia of speech,
language impairment and speech delay: Depends on the stimuli. Journal of Speech Language
and Hearing Research, 1194–1220.
Karmiloff-Smith, A., Scerif, G., & Ansari, D. (2003). Double dissociations in developmental disor-
ders? Theoretically misconceived, empirically dubious. Cortex, 39, 161–163.
coisb.2017.04.006
uation and assessment. Springer.
Koziol, L. B. (2009). Subcortical structures and cognition. Springer.
embodied cognition, and the cerebellum. Cerebellum., 11(2), 505–525. https://doi.org/10.1007/
s12311-011-0321-y
References 155
Langevin, L. M. (2015). Distinct patterns of cortical thinning in concurrent motor and attention
disorders. Developmental Medicine and Child Neurology, (3), 257–264.
Latash, M. (2008). Evolution of motor control: From reflexes and motor programs to the
equilibrium-point hypothesis. Journal of Human Kinetics, 19(19), 3–24.
Lewis, B. F. (2004). School-age follow up of children with childhood apraxia of speech. Language,
Speech, and Hearing Services in Schools, 35, 122–140.
Long, C. J., & Kibby, M. Y. (1995). Ecological validity of neuropsychological tests: A look at
neuropsychology’s past and the impact. Advances Medical Psychotherapy, 8, 59–78.
Maasen, B. (2002). Issues contrasting adult acquired versus developmentla apraxia of speech.
Semin Speech Language, 257–266.
Maassen, B. (2015). Developmental models of childhood apraxia of speech. In R. Barr &
E. Sillimen (Eds.), Routledge handbook of communication disorder (pp. 124–133). Routledge.
Maleki, S., Chye, Y., Zhang, X., Parkes, L., Chamberlain, S., Fontenelle, L., et al. (2020). Neural
correlates of symptom severity in obsessive-compulsive disorder using magnetization transfer
and diffusion tensor imaging. Psychiatry Research: Neuroimaging, 298, 111046. https://doi.
org/10.1016/j.pscychresns.2020.111046
University Press.
Science, 110–124.
mayoclinic.org/diseases-c onditions/childhood-a praxia-o f-s peech/diagnosis-t reatment/
drc-20352051
McGinty, H., Phillips, K., Jim, H., Cessna, J., Asvat, Y., Cases, M., et al. (2014). Cognitive func-
tioning in men receiving androgen deprivation therapy for prostate cancer: A systematic
review and meta-analysis. Support Cancer Care, 22(8), 2271–2280. https://doi.org/10.1007/
s00520-014-2285-1
Trends in Cognitive Sciences, 17, 627. https://doi.org/10.1016/j.tics.2013.09.015
brcg.1999.1099
Miller, G. L.-H. (2019). Reading outcomes for individuals with histories of suspected childhood
apraxia of speech. American Journal of Speech Lanuage Pathology, 1432–1447.
Mirabella, G. D. (2017). Developmental coordination disorder affects the processing of action

relate verbs. Frontiers in Human Neuroscience, 10. https://doi.org/10.3389/fnhum.2016.00661
evidence. Molecular Psychiatry, 1. https://doi.org/10.1038/s41380-022-01661-0
Movement Science, 326–338. https://doi.org/10.1016/j.humov.2010.01.005
dren with developmental coordination disorder. Journal of Medical Genetics, 12, 812–819.
apraxia of speech: Evidence from case studies. Neurocase., 22(4), 346–356. https://doi.org/1
0.1080/13554794.2016.1172645
speech. Journal of Medical Speech-Language Pathology., 20(4), 127–132.
Mountford, H. B. (2022). The genetic and molecular basis of developmental language.
Children, 586.
org/10.1044/2015_JSLHR-S-13-0179
nih.gov/
Newbury, D. W. (2009). CMIP and ATP2C2 modulate phonological short term memory in lan-
guage impairment. American Journal of Human Genetics, 85, 264–272.
Nigg, J., Willcutt, E., Doyle, A., & Sonuga-Barke, E. (2005). Causal heterogeneity in attention-def-
icit/hyperactivity disorder: Do we need neuropsychologically impaired subtypes? Biological
Psychiatry, 57, 1224–1230.
Child Psychology and Psychiatry, 57, 1247–1257.
NORD. (2021). Ocular motor apraxia, cogan type. Retrieved from National Organization of Rare
Disorders: https://rarediseases.org/rare-diseases/ocular-motor-apraxia-cogan-type/
Ochipa, C., & Rothi, L. (1992). Conceptual apraxia in alzheimer’s disease. Brain, 115(Pt 4),
1061–1071.
and Associated Disorders, 523–530.
References 157
an emphasis on the implications for white matter degeneration. Journal of Neurotrauma, 21(6).
https://doi.org/10.1089/0897715041269641, on line.
Pazzaglia, M., Pizzamiglio, L., Pes, E., & Aglioti, S. (2008). The sound of actions in apraxia.
Pazzaglia, M., Smania, N., Corato, E., & Aglioti, S. (2008). Neural underpinnings of gesture dis-
crimination in patients with limb apraxia. The Journal of Neuroscience, 28(12), 3030–3041.
ability. Human Movement Science, 5, 668–681.
on Speech and Orofacial Disorders, 19, 44. https://doi.org/10.1044/ssod19.1.44
sysfunction. Current Opinion in Neurobiology, 13, 212–218.
45, 489–493.
Rosenzopf, H., Wiesen, D., Basilakos, A., Yourganov, G., Bonilha, L., Fridriksson, J., et al. (2022).
Mapping the human praxis network: An investigation of white matter disconnection in limb
apraxia of gesture production. Brain Communications, 4(1), 1–14. https://doi.org/10.1093/
braincomms/fcac004
Rosenzoph, H., Weisen, D., Basilakos, A., Yourganov, G., Bonilha, L., Rorden, C., et al. (2020,
April 17). Mapping the Human Praxis Network: An investigation of white matter disconnec-
tion in limb apraxia. Retrieved from bioRxiv.org: https://doi.org/10.1101/2020.04.14.041442
Salo, V. F. (2019). The role of the motor stem in action understanding and communication:
390–401.
Sato, J., Biazoli, C. E., Jr., Zugman, A., Pan, P., Bueno, A., Moura, L., et al. (2021). Long-term
stability of the cortical volumetric profile and the functional human connectome throughvout
childhood and adolescence. European Journal of Neuroscience, 54, 6187–6201. https://doi.
org/10.1111/ejn.15435
826–852.
Frontiers in Pediatrics, 8. https://doi.org/10.3389/fped.2020.599633
Sharma, V., & Wong, L. (2022). Middle cerebral artery disease. In J. Grotta, G. Albers, J. Broderick,
S. Kasner, R. Sacco, A. Day, et al. (Eds.), Stroke (seventh edition) pathophysiology, diagno-
sis, and management (pp. 317–346). Elsevier. https://doi.org/10.1016/B978-0-323-69424-7.

00024-7
Shriberg, L. D., & Fourakis, M. (2010). Extensions to the speech disorders classification system
(SDCS). Clinical Linguistics & Phonetics, 24, 795.
707–736.
Sonuga-Barke, E. (2003). The dual pathway model of AD/HD: An elaboration of neuro-
developmental characteristics. Neuroscience Biobehavioral Review, 27, 593–604.
Sonuga-Barke, E., Bitsakou, P., & Thompson, M. (2010). Beyond the dual pathway model:
Evidence for the dissociation of timing, inhibitory and delay-related impairments in attention
deficit/hyperactivity disorder. Journal of Child and Adolescent Psychiatry, 345-355. https://doi.
org/10.1016/j.jaac.2009.12.018
Sporns, O., Tononi, G., & Kötter, R. (2005). The human connectome: A structural description
of the human brain. PLoS Computational Biology, 1, e42. https://doi.org/10.1371/journal.
pcbi.0010042
Stackhouse, J. W. (1997). Children's speech and literacy difficulties 1: A psycholinguistic frame-
work. Wurr.
Strand, E. (2019, January 9). Diagnosis and management of CAS.
developmental coordination disorder – A comparative study. Research in Developmental
Disabilities, (35), 2644–2650.
Tal-Saba, M. Z. (2012). The functional profile of young adults with suspected developmental
coordination disorder (DCD). Research In Developmental Disabilities, 2193–2202. https://doi.
org/10.1016/j.ridd.2012.06.005
Terband, H. M. (2019). A psycholinguistic framework for diagnosis and treatment planning of
developmental speech disorders. Folia Phoniatrica et Logopaedica, 5–6, 216–227.
with childhood apraxia of speech. Disability and rehabilitation, 31(2), 94–102. https://doi.
org/10.1080/09638280701795030
The Medical Dictionary. (2021). Apraxia. Retrieved from The Medical Dictionary: http://the-
medical-dictionary.com/apraxia_article_2.htm
S095457941800072X
References 159
Development, 77–84.
Wasserman, T., & Wasserman, L. (2015). The misnomer of attention deficit hyperactivity dis-
order. Applied Neuropsychology: Child, 4(2), 116–122. https://doi.org/10.1080/2162296
5.2015.1005487
Wasserman, T., & Wasserman, L. (2016). Depathologizing psychopathology. Springer.
Wasserman, T., & Wasserman, L. (2017). Touching the elephant: The search for fluid intel-
ligence. Applied Neuropsychology Child., 6(3), 228–236. https://doi.org/10.1080/2162296
5.2017.1317489
Child Neurology, 920–925(49), 12.
org/10.1093/brain/106.2.391
Weintraub, S. (2000a). Neuropsychological assessment of mental state. In M. Mesulam (Ed.),
Weintraub, S. (2000b). Neuropsychological assessment of mental state. In I. M. Mesulam (Ed.),
Principles of behavioral and cognitive neurology (p. 121). Oxford University Press.
neuron.2016.12.013
Whiteside, S., Dyson, L., Cowell, P., & Varley, R. (2015). The rlationship between apraxia of
Wilson, P. M. (1998). Information processing deficits associated with developmental coordination
disorder: A meta-analysis of research findings. Joornal of Child Psychology, 829–840.
World Health Organization (WHO). (1993). The ICD-10 classification of mental and behavioural
disorders. World Health Organization (WHO).
Yuste, R. (2015). From the neuron doctrine to neural networks. Nature Reviews. Neuroscience, 16,
Zadikoff, C., & Lang, A. (2005). Apraxia in movement disorders. Brain, 128(7), 1480–1497.
Zang, Z., Ping, L., Zhai, A., & Zhou, Z. (2021). Microstructural white matter abnormalities in
obsessive-compulsive disorder: A coordinate-based meta-analysis of diffusion tensor imaging
studies. Asian Journal of Psychiatry, 55, 102467. https://doi.org/10.1016/j.ajp.2020.102467
hypotheses. Child Neurology, 1–9.
Chapter 10
Treatment for Apraxia: Plasticity
and Regeneration
Treatment for many apraxia conditions has remained remarkably the same for quite
some time. Essentially, the apraxic individual, usually under the guidance of a
skilled professional, practices the desired motor sequence until automaticity of the
desired sequence is achieved. Treatment relies on neural plasticity to achieve the
desired outcome.
Treatment for apraxia conditions of all types represents a significant effort in
most rehabilitation facilities. Studies evaluating the level of autonomy in brain-
damaged patients have shown how apraxia significantly reduces their levels of
autonomy in carrying out everyday activities. Caregivers have reported the need for
more assistance with apraxia patients engaged in these activities than with those
suffering from other neuropsychological deficits. Apraxic deficit slows down motor
rehabilitation in patients with hemiparesis and reduces the ability of patients with
severe aphasia to communicate by gesturing (Cantagallo et al., 2013).
Treatment efficacy research is limited. Given the association of apraxia to long-
term disability, the evidence base for effective treatment is also surprisingly limited.
There are several reasons for this being the case. Perhaps one of the most significant
is that apraxia is not a single disorder and successful intervention requires an under-
standing of what is to be rehabilitated (Worthington, 2016). In addition, for many
intervention studies, there is also the lack of a clear theoretical rationale. Although
all start with an assessment of apraxia to identify specific cases, these assessments
often lack a theoretical basis and lack reliability across studies. Even more signifi-
cantly, the assessments are rarely used to inform the intervention. In part this is
because there is no standard diagnostic process, universal taxonomy of apraxia sub-
types, or theoretical consensus regarding potential subtypes (Molloy & Jagoe,
2019). That is not to say that attempts are not being made. For example, there is the
Apraxia Battery for Adults, a measure of apraxia in which participants perform vari-
ous tasks and are assessed on diadochokinetic rate, increasing word length, limb and
oral apraxia, latency and utterance time for polysyllabic words, repeated trials test,
162 10 Treatment for Apraxia: Plasticity and Regeneration
and inventory of articulation characteristics. The test was however normed using a
sample of 40 persons with apraxia and 49 persons for normative speech, ranging in
age from 33 to 93. This limits the instrument in applicability to younger persons,
although the test recommends use for persons 9 years and above, and reports noted
difficulties in identifying less than severe apraxia, which is interpreted as typical
aphasia (“due to language difficulties”) (Dabul, 2000).
Additionally, treatment efficacy studies are compromised by the heterogeneous
grouping of apraxia within an identified subtype. For example, children diagnosed
with speech sound disorders comprise a heterogeneous group who differ in terms of
the severity of their condition, underlying cause, speech errors, involvement of other
aspects of the linguistic system, and treatment response. Even now, there is no uni-
versal and agreed upon classification system for the subtype. Instead, several theo-
retically differing classification systems have been proposed based on either an
etiological (medical) approach, a descriptive-linguistic approach, or a processing
approach (Waring & Knight, 2013).
Lack of Consensus for the Selection of Treatments for Apraxia
Perhaps as a result of the issues identified, there is a lack of consensus among treat-
ing professionals. For example, in a recent survey of professional speech and lan-
guage pathologists in the USA and Canada who treat apraxia of speech, respondents
reported frequently using an eclectic approach to treat CAS (USA 85%; Canada
89%). That implies that these professionals select multiple and various techniques
they deemed effective. From the perspective of hypothesis testing, this means
numerous treatment approaches that would complicate any analysis. In the survey
no intervention emerged as the most preferred primary treatment for CAS. There
were a couple of treatment models that served as core components of many treat-
ment packages. US-based clinicians more commonly reported using the Kaufman
Speech to Language Protocol (K-SLP) (33%) and Dynamic, Temporal, and Tactile
Cueing (DTTC) (28%), while clinicians in Canada used PROMPT ® (31%) (Gomez
et al., 2022). These approaches share common elements.
Classes of Treatment for Apraxia
There are several classes of treatment for apraxia conditions summarized below:
Restorative (Restitutive) Treatments
These interventions attempt to restore impaired processing back to normal function.

This has been attempted by trying to improve sensory integration, perceptuo-motor
performance, and selective attention. The sensory approach is somewhat unique, as
Treatment Examples 163
it emanated from perspectives on developmental dyspraxia and was underpinned by

the idea that apraxia is due to failure to attend to or integrate functionally appropri-
ate sensory information.
Compensatory (Substitutive) Treatments
Compensatory methods focus on the disability associated with the apraxia and do
not attempt to address the underlying impairment. They attempt to teach work
arounds or ways of compensating for the disability. One such approach is strategy
training (Cantagallo et al., 2013). Strategy training relies on teaching internal strate-
gies and therefore is informatively characterized as a form of metacognitive
intervention.
Assistive Technology
Assistive technology is designed to reduce the need for expensive and hard to find
professional treatment provided at an intensity that would be effective in the treat-
ment of apraxia conditions. An example of such technology is the coach system
(Mihailidis et al., 2006). Coach is a computerized device which attempts to address
difficulties with sequencing action subtasks, that is, everyday activities such as
handwashing or cutting using a knife via camera, and provides audio and video
cues. In between is a complex process of determining the intentions (belief states)
of the user on a probabilistic basis to deliver cues effectively.
Treatment Examples
Multiple disciplines including speech therapy, physical therapy, and occupational

therapy offer treatment for apraxia conditions. In the area of apraxia of speech,
including childhood apraxia of speech, there is a myriad of techniques employed to
help an individual recover or develop function. The interesting point about treat-
ment for speech-related apraxic conditions is while there are many specific types of
treatment that target different aspects of speech production, the core of these treat-
ments remains the same. For example, “for both children and adults, the treatment
for AOS involves speech-language therapy. The specific approach is customized to
the individual and considers the severity of their condition and the specific difficul-
ties they have with speech. All of the approaches share core elements. Amongst
these elements are:
• Asking for the same word or phrase to be repeated multiple times
• Practicing saying specific syllables or words to the individual learn to move from
one sound to another
• Having the individual carefully observe how the therapist’s mouth moves when
they say words or phrases
• Using visual cues, such as practicing speech in front of a mirror, to remind the
individual how to move their mouth to say specific words or phrases”
(HealthLine, 2022)
These are the general principles to be sure, but they can be observed in most
treatment approaches, including those with research support. For example, the
PROMPT Program (Hayden et al., 2010) is a tactile kinesthetic -based treatment
method that has been effective in treating motor speech disorders in adults and in
children (Dale & Hayden, 2014). Although the PROMPT program is known for its
use of tactile information, and its use of the core approaches identified above, there
are several other core elements that collectively distinguish it from other treatment
programs. These include the following (shared techniques are bolded for emphasis):
• Determination of a communication focus for treatment, that is, an aspect of
development in which to embed and focus communication intervention, such as
prelinguistic skills, speech subsystem development or rebalancing, activities of
daily living, self-help skills, interactive communication routines, play skills, or
preacademic or academic learning
• Determination of the uses of PROMPT, such as to develop an interactive focus
for oral communication; to map in cognitive-linguistic concepts; or to develop,
balance, or restructure speech subsystems and determine sensory modalities
most needed in treatment (TKP, visual-auditory)
• Development of goals and objectives that embody the communication focus and
work toward motor, language, cognitive, and social function. This entails the use
of reciprocal turn taking, including cognitively appropriate words, objects,
actions, interactions, and social interaction and/or choice making in almost every
interaction between the child and therapist
• Ensuring within each session a high degree of motorphoneme rehearsal (mass
practice using prompts for accuracy of production) organized so that (a) these
motor-phonemes are generalized across various vowel contexts and transitions
(distributed practice) and are embedded into novel syllables and words within
naturalistic activities and (b) immediate use and transfer of the newly learned
PROMPT lexicon are embedded in activities and the natural environment for use
with parents, caregivers, or peers.
It is clear that the PROMPT program is highly organized and planned and just as
clear that it relies on systematic practice to produce a result. The current authors
applaud the emphasis on the development of cognitive linguistic function, thereby
recognizing the association of language production with other cognitive domains.
A review of treatments for motor apraxic conditions (West et al., 2008) yielded
the same pattern of treatment intervention, one that relied heavily on motor practice
(common elements are bolded):
• Strategy training in daily living activities: this technique teaches internal (e.g.,
the patient is taught to verbalize and implement the task steps at the same time)
Neural Plasticity 165
or external (e.g., when aids are used to overcome a functional barrier) compensa-
tory strategies that enable a functional task to be completed. These strategies will
not have been used prior to the stroke.
• Sensory stimulation: stimulations including deep pressure, sharp, and soft touch
are applied to the patients’ limbs.
• Proprioceptive stimulation: the patient leans on and puts weight through their
upper and lower limbs.
• Cueing, verbal, or physical prompts given to enable each stage of the task to be
completed.
• Chaining (forward or backward): the task is broken down into its component
parts. Using backward chaining the task is completed with facilitation from the
therapist apart from the final component, which the patient carries out unaided.
If successful next time, further steps are introduced. Forward chaining is the
reverse of backward chaining.
• Normal movement approaches: the therapist facilitates the body through normal
movement patterns.
As indicated, what these techniques all have in common is that they rely on prac-
tice of the target behavior until that practice encourages the development of a profi-
cient target behavior. To get that development, they rely on the principles involved
with neural plasticity and neural regeneration as the basis for the development of the
desired skill.
Neural Plasticity
A central premise of network modeling is that behavior is a result of underlying

activity in an individual’s nervous system. The primary functional unit of the ner-
vous system is the neuron, although there are numerous other cells. A person’s
behavioral repertoire is a manifestation of activity in their neural circuits. Following
on, changes in a person’s behavior is caused by changes to the process of the opera-
tion of the neural circuitry. This is true in relation to function loss that the system
experiences as a result of damage or disrupted development or, on a more positive
note, what occurs with learning. All of this change must be significantly subserved
by an underlying change in neuronal connectivity.
Much of the communication between neurons in the nervous system occurs at
synapses, and, as a result, changes in behavior are ultimately followed by alterations
in the nature, strength, or number of interneuronal synaptic contacts. Repetitive
stimulation of synapses can cause long-term potentiation or long-term depression of
neurotransmission (Galvan, 2010). The capacity for modifications of synaptic con-
nections between neurons is referred to as synaptic plasticity. Synaptic plasticity
therefore subserves learning and memory in its positive forms and apraxia and other
disorders when something goes awry. In the case of apraxia, therefore, synaptic
plasticity is a likely candidate for a mechanism underlying behavior-modifying
changes in neuronal connectivity that mediates treatment and repair of function.

There are non-synaptic forms of alterations in neural function. This refers to neuro-
nal plasticity and accounts for phenomena such as intrinsic excitability, cell-wide
changes in synaptic composition, and homeostatic plasticity (Sweatt, 2016).
Neural plasticity is defined as the ability to alter a neuronal response to environ-
mental stimuli and is the foundation of learning and memory (Kozubski et al.,
2021). Neuronal plasticity is a basic property of the central nervous system. It
ensures both the brain’s normal functioning and its capacity for partial regeneration.
Plasticity encompasses both synaptogenesis during early development and compen-
satory and corrective plasticity in the adult brain. One way to understand neural
plasticity is the ability of the central nervous system (CNS) to adjust in response to
changes in the environment (learning), lesions (damage), or acquired dysfunction.
This capability of the CNS can involve modifications in overall cognitive strategies
to successfully cope with new challenges (i.e., attention, behavioral compensation),
recruitment of new/different neural networks, or changes in strength of such con-
nections or specific brain areas in charge of carrying out a particular task such as
movement, language, vision, or hearing (Sharma et al., 2013). At the neuronal level,
this implies reorienting of the connections between various neurons that create new
pathways or networks. At a cellular level, neuronal circuits consist of synaptic con-
nections between axons and dendrites. As these circuits extend over the brain, there
is the potential for many possible interactive combinations allowing for great flexi-
bility. Modification of sensory input may induce rapid changes in cortical represen-
tations through various mechanisms including unmasking of connections that exist,
but are not utilized in the premorbid (pre-rehabilitation) state. At the cellular level,
plasticity involves changes in membrane excitability, synaptic plasticity, as well as
structural changes in dendritic and axonal anatomy. Plasticity within and across dif-
ferent brain regions is thought to represent the neural basis underlying sensory sub-
stitution, in cases of blindness and deafness as well as in the recovery of motor
function after cortical lesions like stroke (Nudo et al., 1996). The plastic nature of
the human brain lends itself to experience and training-based structural changes
leading to functional recovery (Chatterjeea et al., 2021).
Neural plasticity is notable for its adaptive value. It allows the compensatory
changes induced by experience to occur in the CNS continuously. It is these experi-
ences that form the basis of treatment which target specific skills or subcomponents
of different skills.
The mechanisms of neural plasticity are quite varied. They can vary from exten-
sive morphological modifications, such as those observed in the regeneration of
axons and new synapse formation, to subtle molecular changes that alter the cellular
response to neurotransmitters (Merceron-Martinez et al., 2021). Functional plastic-
ity can include neurogenesis, regeneration, axonal collateral formation, and reactive
synaptogenesis. There is also research that suggests that plasticity takes on different
forms as we age. For example, as opposed to new synaptic connections, research
suggests that recruitment of wider brain networks in the elderly and after stroke may
play a beneficial role in maintaining the ability of individuals to carry out specific
tasks or even in facilitating re-learning (Hummel et al., 2010).
Treatment That Supports Neural Plasticity 167
Mechanisms of Neural Plasticity
If neural plasticity is the underlying mechanism for functional recovery from

apraxia, then it stands to reason that treatment techniques purposefully target activi-
ties that would support plasticity. Neuroplasticity can be broken down into two
major mechanisms:
• Neuronal regeneration/collateral sprouting: This includes concepts such as syn-
aptic plasticity and neurogenesis.
• Functional reorganization: This includes concepts such as diaschisis, equipoten-
tiality, and vicariation.
We have covered some of these terms already. Of those that we haven’t yet men-
tioned is equipotentiality. Equipotentiality is the theory that the brain has the capac-
ity (in the case of injury) to transfer functional memory from the damaged portion
of the brain to other undamaged portions of the brain. Essentially, large areas of
cerebral cortex have similar potential to perform particular functions, including
learning and other complex processes, so that intact cortical areas may take over
functions of damaged or destroyed areas. Vicariation, on the other hand, is the idea
that the brain can reorganize and recruit other portions of the brain to accommodate
functions that they were not intended to. Diaschisis refers to the concept that dam-
age to one part of the brain could cause a loss of function in another area due to
some connected pathway.
As a side note, perhaps a portent of things to come, a very recent finding from the
world of anthropology and genetics suggests that what differentiated the modern
human brain from that of archaic hominids is a genetic mutation (Pinson, 2022).
The finding is that modern human transketolase (TKTL1) mutated from a lysine to
arginine amino acid substitution. Thus, while the brain size of the neanderthal and
modern human is similar, this modern human variant results in an increase in the
abundance of basal radial glia, resulting in the generation of more neocortical neu-
rons than the original variant. Can this genetic information be harnessed for regen-
eration? There is a considerable amount of inquiry into this potential rehabilitation
source. For example, research into using adult neural progenitor cells as a source of
cell replacement is being looked at for their clinical application as autologous cell
replacement for neurologic diseases such as Parkinson’s, trauma such as stroke, and
cell-based gene therapy for neurometabolic diseases (Xenia Lojewski, 2014).
Treatment That Supports Neural Plasticity
Although not directly related to existing treatments for apraxia, there are treatments
that support neural plasticity. We review them here to show overlap of these treat-
ment approaches with existing treatments for apraxia.
Clinically, several treatment options have been used to facilitate neuroplasticity

in restoring function and eliminating unwanted symptoms. For example, mirror
therapy is a technique used in phantom limb pain. The individual uses a mirror to
cover their amputation and focuses on watching their intact limb perform activities
while imaging that both limbs are performing the same activity. The idea is that a
patient with phantom limb pain can feel the same sense or emotion of their corre-
sponding normal body part by observing the mirror image. This has been shown to
have increased activation and functional connectivity in the frontoparietal network.
One of the most researched rehabilitation techniques is constraint-induced move-
ment therapy (CIMT). This technique is commonly used in patients recovering from
stroke. The core technique is to constrain the functional limb and engage the affected
limb in repetitive task practice and behavioral shaping. Using functional magnetic
resonance imaging (fMRI) technology, patients who engage in this therapy have
been shown to have increased activity in their contralateral premotor and secondary
somatosensory cortex in association with improved function (Johansen-Berg
et al., 2002).
Research has also been focused on influencing neuroplasticity through the modi-
fication of environmental factors. Music therapy has been shown to influence neu-
roplasticity positively. It has been shown to improve cognition and other executive
functions. Exercise has been shown to improve episodic memory and processing
speed in addition to decrease age-related atrophy of the hippocampus. A healthy
diet has also been shown to be helpful for this (The Health Jade Team, 2022).
Brain Injury, Plasticity, and Functional Recovery
It is known that brain insults, such as those that produce apraxic conditions, cause
rapid cell death and a disruption of functional circuits, in the affected neural net-
works including white matter. During and immediately after stroke, neurological
functions associated with the infracted (see glossary) area are lost. As the damaged
system attempts to recover loss of function associated with cell death, regenerative
processes are activated that lead to a varying degree of functional recovery. Factors
produced by new neurons and glia, axonal sprouting of surviving neurons, and new
synapse formation help to re-establish some of the lost functions. The timing and
location of such events are crucial in the success of the regenerative process
(Wielock & Nikolich, 2006).
Recovery of function involves three distinct phases: first, reversal of diaschisis
and activation of cell repair; second, functional cell plasticity, that is, changing the
properties of existing neuronal pathways; and third, neuroanatomical plasticity
leading to the formation of new connections. Steps two and three are the basis of
normal learning as well as recovery. In humans, recovery processes primarily
engage ipsilateral brain regions, although if the damage is severe, contralateral brain
areas are also involved.
What Enhances Neural Plasticity? 169
What Enhances Neural Plasticity?
Environmental Enrichment and Neural Plasticity
Since recovery is, at least in part, based on neural plasticity, treatment approaches
should incorporate factors that encourage its development.
Functional recovery is encouraged by experience-driven re-learning. This re-
learning can be facilitated by professionals in a systematic way. An experience-rich
environment has numerous biological effects that account for plasticity and its posi-
tive effect on recovery of function. For example. it enhances dendritic arborization
and spine density on the contralateral pyramidal neurons, supporting the notion that
the contralateral hemisphere is particularly involved in the recovery process when
stimulated by an enriched environment (Johansson, 2004). Research suggests that
the recovery-enhancing effect on sensorimotor function after stroke by an enriched
environment is not due to generation and recruitment of new neurons to the periin-
farct or remote cortical areas. Rather, the increased proliferation of glial cells and
neuroblasts might enhance recovery by releasing regenerative factors or by provid-
ing cellular constituents, in particular lipids, for axonal growth (Wielock &
Nikolich, 2006).
As indicated most forms of intervention for apraxia can be considered a form of
environment enrichment, education, or re-education. These interventions consist of
targeted practice of the requisite skill until the individual learns to do the skill in a
highly automatic efficient manner. Research has demonstrated that many forms of
environmental enrichment produce significant changes to components of the net-
work systems. These include improvement in cortical weight and thickness and an
increase of dendritic branching and length, the number of dendritic spines, and the
size of synapses of some neuronal populations. Additionally, at the molecular level,
environmental enrichment induces the expression of brain-derived neurotrophic
factor (BDNF) and nerve growth factor (NGF), synaptic proteins (SP), and NMDA
(N-methyld-aspartate) and AMPA (-amino-3-hydroxy-5- methyl-4-isoxazole propi-
onic acid) receptor subunits. More importantly, environmental enrichment improves
learning and memory at the behavioral level. Environmental enrichment enhances
learning and memory in models of neurodegenerative diseases (Merceron-Martinez
et al., 2021). These environmental enrichment activities and treatments have the
benefit of inducing task-specific change. In sum, there is substantive research evi-
dence that training and practice encourage neural plasticity with the likely outcome
of regaining (in the case of brain damage) or acquiring (in the case of childhood
apraxia of speech) appropriate function (Bootsma et al., 2021).
There are other factors that can contribute to plasticity. These include the admin-
istration of stem cells and the administration of growth factors such as erythropoetin
which stimulates the development of new blood vessels and neurons and increases
the levels of other growth factors. These, however, are non-targeted improvements,
and the research is not yet clear whether merely adding new neurons and blood
vessels will improve a specific function impaired by damage. So for the moment, for
the practitioner only enriched environments offer the possibility of targeted recov-
ery of function.
Regeneration
Thus far, we have spoken about synaptic and neuronal plasticity. That is the modifi-
cation or recruitment of new pathways to reclaim function after injury to the origi-
nal functional pathway, as in the case with many apraxias. There is another, less
common, mechanism for the reacquisition of functioning. That is neuronal regen-
eration. Regeneration of the nervous system requires either the repair or replace-
ment of nerve cells that have been damaged by injury or disease (Steward et al.,
2013). There is evidence that neurons can regrow, albeit, slowly and in some cases
assist in recovery of function (Stoll & Muller, 1998).
Injuries or damage secondary to illness, to neural network nerves, can result in
partial or total loss of motor, sensory, and autonomic functions as in the case of
apraxia. This can occur due to the interruption of axons, degeneration of distal nerve
fibers, and eventual death of axotomized neurons. Research has demonstrated that
functional deficits caused by nerve injuries can be compensated by reinnervation of
denervated targets by regenerating injured axons or by collateral branching of
undamaged axons, and, as we have discussed, remodeling of nervous system cir-
cuitry related to the lost functions. We have hypothesized that plasticity, in the form
of rerouting or recruiting, functionally underpins most treatment for apraxia.
Regeneration is potentially another way that functional recovery might theoretically
be obtained. That promise has not yet been realized.
Limitations of Plasticity
We have seen how plasticity of central connections may compensate functionally

for the lack of adequate target reinnervation. There are, however, some limitations.
Plasticity has limited effects on disturbed sensory localization or fine motor control
after injuries and may even result in maladaptive changes, such as neuropathic pain
and hyperreflexia. This is because after being damaged, neurons shift from a trans-
mitter to a regenerative phenotype, activating molecular pathways that support neu-
ronal survival and axonal regeneration. Nerve injuries also induce a cascade of
events, at the molecular, cellular, and system levels, initiated by the injury and pro-
gressing throughout plastic changes at the spinal cord, brainstem nuclei, thalamus,
and brain cortex. Mechanisms involved in these changes include neurochemical
changes, functional alterations of excitatory and inhibitory synaptic connections,
sprouting of new connections, and reorganization of sensory and motor central
maps. At the current time, it is unclear how therapeutic strategies that enhance axo-
nal regeneration promote selective target reinnervation (Naxarro, 2009).
References 171
Treatment Going Forward: Neurorehabilitation
Until now, language representation in the brain was considered as being modular,
and under this concept, speech treatment was limited to linguistic tasks and con-
ducted separately for each module (i.e., naming or syntax). Given that we now know
that language functions stream widely throughout our brain and are interconnected
with many other brain functions, we can also recognize the brain’s multifunctional-
ity and the mechanisms for its functional reorganization. This new knowledge, cou-
pled with technological progress, with new sophisticated and widely available and
affordable tools for neuroimaging and neuromodulation, as well as telerehabilita-
tion, has the potential to shift clinical neuroscience to an era of improved therapeu-
tic strategies for people living with language and communication disorders including
apraxia. Approaching poststroke apraxia or aphasia in terms of disrupted networks
coupled with understanding how mechanisms of ischemic brain injury may be influ-
enced by therapeutic interventions can offer better treatment strategies of poststroke
language disruption such as apraxia in the future. We now know that recovery from
many forms of language disruption including apraxia relies upon supportive, ancil-
lary networks, serving in a role supporting the brain’s cognitive reserve. The brain
must therefore be functionally reorganized, and when these supportive brain regions
involved in recovery remain intact, the outcome is more favorable. As we have seen,
neuroplasticity is the driving force for this functional reorganization, and neurore-
habilitation is the science of enhancing it (Nasios et al., 2019).
References
443(12), 713–716. https://doi.org/10.1038/nature05164
ing view. Journal of Speech, Language, and Hearing Research, 63, 2952–2994.
American Speech Hearing Association (ASHA). (2007). Childhood apraxia of speech technical
report. American Speech and Language Association.
American Speech Hearing Association (ASHA). (2022). Retrieved from Childhood Apraxia of
Speech. http://ASHA.org
Statement). Retrieved from American Speech-Language-Hearing Association. www.Asha.
org/policy
Andres, E. E. (2022). Family based shole exome analysis of specific language impairment iden-
tifies rare variants in BUD13, a component of the retention and splicing complex. Brain
Sciences, 12, 47.
Armstrong, P. (2010). Bloom’s Taxonomy. Retrieved from Vanderbilt University Center for
Teaching. https://cft.vanderbilt.edu/guides-sub-pages/blooms-taxonomy/
Baldassarre, A., Lewis, C. M., Committeri, G., Snyder, A. Z., Romani, G. L., & Corbetta,
M. (2012). Individual variability in functional connectivity predicts performance of a percep-
tual task. Proceedings of the National Acadamey Science U. S. A., 109, 3516–3521.
Ballard, K., Tourville, J., & Robin, D. (2014, November 3). Behavioral, computational, and neuro-
imaging studies of acquired apraxia of speech. Frontiers in Human Neuroscience. https://doi.
org/10.3389/fnhum.2014.00892
junction. Neuroimage, 30, 917–926.
43, 118–126.
Batista-García-Ramó, K., & Fernández-Verdecia, C. (2018). What we know about the brain
structure–Function relationship. Behavioral Sciences, 8(39), 1–14. https://doi.org/10.3390/
bs8040039
Belanger, S., Duffy, R., & Coelho, D. (1996). The assessment of limb apraxia: An investigation
brcg.1996.0072
with special reference to addiction. Psychopharmacology (Berl), 221(3), 361–387. https://doi.
org/10.1007/s00213-012-2689-x
Bootsma, J., Caljouw, S., Veldman, M., Maurits, N., Rothwell, J., & Hortobágyi, T. (2021). Neural
correlates of motor skill learning are dependent on both age and task difficulty. Frontiers in
Aging Neuroscience, 22. https://doi.org/10.3389/fnagi.2021.643132
individual-level approach to identify cortical connectivity biomarkers in obsessive-compul-
sive disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 4(1), 27–38.
Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK560542/
Cantagallo, A., Maini, M., & Rumiati, R. (2013). The cognitive rehabilitation of limb apraxia in
patients with stroke. Neuropsychological Rehabilitation, 22(3), 473–488.
Chatterjeea, D., Hegdeb, S., & Thaut, M. (2021). Neural plasticity: The substratum of music-
based interventions in neurorehabilitation. Neurorehabilitation, 48, 155–166. https://doi.
org/10.3233/NRE-208011
References 173

181–187.
Association: ASHA.ORG
org/10.1523/JNEUROSCI.6344-11.2012
presentation of at-risk or probable Developmental Coordination Disorder in adults. Research in
Developmental Disabilities, 115. https://doi.org/10.1016/j.ridd.2021.104010
Transactions - American Academy of Ophthalmology and Otolaryngology, 56, 579–588.
symptom mapping study in acute stroke patients. Experimental Brain Research. https://doi.
org/10.1007/s00221-021-06224-3
Cousins, M. Smyth, M. M (2003). Developmental coordination impairments in adulthood.
Human Movement Science, 22, 433–459. https://doi.org/10.1016/j.humov.2003.09.003. PMID:
14624827.
S0033291719003210
Dabul, B. (2000). Apraxia battery for adults - Second Edition. Pro-ed.
Dale, P., & Hayden, D. (2014). Treating speech subsystems in childhood apraxia of speech with
tactual input: The PROMPT approach. American Journal of Speech-Language Pathology,
644–661. https://doi.org/10.1044/1058-0360(2013/12-0055)
org/10.3109/02699209808985211
org/10.1093/brain/111.5.1173
Apraxia. Brain, 105, 301–312.
brain alterations in motor areas. Acta Paediatrica, 108(9). https://doi.org/10.1111/apa.14786
130–136.
Edelman, G., & Gally, J. (2001). Degeneracy and Complexity in Biological Systems. Proceedings
Einspieler, C. P., Prayer, D., & Marschik, P. B. (2021). Fetal movements; The origin of human
behaviour. Developmental Medicine & Child Neurology, 63(10), 1142–1148.
tive function in children. Frontiers in Psychology. https://doi.org/10.3389/fpsyg.2016.00318
Reviews | Neuroscience, 16, 150–172.
org/10.1177/15459683211001025
org/10.1177/2167702619898814
fneur.2021.562090
Fulceri, F., Grossi, E., Contaldo, A., Narzisa, A., Apicella, F., Parrini, I., et al. (2019, January 9).
Motor skills as moderators of core symptoms in autism spectrum disorders: Preliminary data
from an exploratory analysis with artificial neural networks. Frontiers in Psychology. https://
doi.org/10.3389/fpsyg.2018.02683
org/10.1016/S0166-2236(97)01128-4
org/10.1016/B978-0-444-63622-5.00016-4
Communication, 9, 4233. https://doi.org/10.1038/s41467-018-06560-z
References 175
Galvan, A. (2010). Neural plasticity of development and learning. Human Brain Mapping, 31(6),
879–890. https://doi.org/10.1002/hbm.21029
Ganguly, J., & Jog, M. (2020). Tauopathy and movement disorders—Unveiling the chame-
leons and mimics. Frontiers in Neurology: Movement Disorders. https://doi.org/10.3389/
fneur.2020.599384
Disorganization of anatomical connectivity in obsessive compulsive disorder: A multi-param-
eter diffusion tensor imaging study in a subpopulation of patients. Neurobiology of Disease,
37(2), 468–476. https://doi.org/10.1016/j.nbd.2009.11.003
the. Natlonal Academy. Sciience USA, 99, 7699–7704.
Gomez, M., McCabe, P., & Purcell, A. (2022). A survey of the clinical management of childhood
apraxia of speech in the United States and Canada. Journal of Communication Disorders, 96,
106193. https://doi.org/10.1016/j.jcomdis.2022.106193
Green, D. C. (2008). Does subtype of developmental coordination disorder Count: Is there a dif-
ferential effect on outcome following intervention? Human Movement Science. https://doi.
org/10.1016/j.humov.2008.02.009
Speech and Language, 1–49.
tification and intervention: An expert white paper consensus. Learning Disability Quarterly,
33(3), 223–238.
Handiru, S. V., Alivar, A., Hoxha, A., Saleh, S., Suviseshamuthu, E. S., Yue, G. H., & Allexandre,
Hayden, D., Eigen, J., Walker, A., & Olsen, L. (2010). Prompt: A tactually grounded model for
the treatment of childhood in speech production disorders. In L. Williams, S. McCleod, &
R. McCauley (Eds.), Treatment for speech sound disorders in children (pp. 453–474). Brooks.
prefrontal cortex/basal ganglia system. Philosophical Transactions of the Royal Society B:
Biological Sciences, 362, 1601–1613.
HealthLine. (2022). What’s the treatment for apraxia of speech? Retrieved from Healthline.
https://www.healthline.com/health/apraxia-of-speech#treatment
Heilman, K., Rothi, L., & Valenstein, E. (1982). Two forms of ideomotor Apraxia. Neurology, 32,
342–346.
Heilman, K., Maher, L., Greenwald, M., & Rothi, L. (1997). Conceptual apraxia from lateralized
lesions. Neurology, 49(2). https://doi.org/10.1212/WNL.49.2.457
Science USA, 106, 2035–2040.
Hua, J. W. Williams GJ, Jin H, Chen J, Xu M, Zhou Y, Gu G, Du W (2022). Early motor milestones
in infancy and later motor impairments: A population-based data linkage study. Psychiatry.
https://doi.org/10.3389/fpsyt.2022.809181
Hummel, F., Heise, K., Celnik, P., et al. (2010). Facilitating skilled right hand motor function
in older subjects by anodal polarization over the left primary motor cortex. Neurociological
Aging, 31, 2160–2168.
Huth, A. G., De Heer, W. A., Griffiths, T. L., Theunissen, F. E., & Gallant, J. L. (2016). Natural
speech reveals the semantic maps that tile human cerebral cortex. Nature, 532(7600), 453–459.
https://doi.org/10.1038/nature17637
Iuzzini-Seigel, J. M. (2017a). Speech assessment in children with childhood apraxia of speech.
In Perspectives of the ASHA Special Interest Groups (pp. 47–60). American Speech Language
Iuzzini-Seigel, J. H. (2017b). Speech inconsistency in children with childhood apraxia of speech.
In Language impairment and Speech Delay: Depends on the Stimuli. J Speech Lang Hear Res,
1194–1220.
Johansen‐Berg, H., Dawes, H., Guy, C., Smith, S. M., Wade, D. T., & Matthews, P. M. (2002).
Correlation between motor improvements and altered fMRI activity after rehabilitative therapy.
Brain, 125, 2731–2742. https://doi.org/10.1093/brain/awf282
Johansson, B. (2004). Functional and cellular effects of environmental enrichment after experi-
mental brain infarcts. Restorative Neuroscience, 22, 163–174.
coisb.2017.04.006
Koziol, L. B. (2009). Subcortical structures and cognition. Springe.
Koziol, L. (2014). The myth of executive functioning: Missing elements in conceptualization, eva-
laution and assessment. Springer.
s12311-011-0321-y
References 177
Kozubski, W., Ong, K., Waleszczyk, W., Zabel, M., & Dorszewska, J. (2021). Molecular factors
mediating neural cell plasticity changes in dementia brain diseases. Neural Plasticity, 2021,
Langevin, L. M., MacMaster, F. P., & Dewey, D. (2015). Distinct patterns of cortical thinning in
concurrent motor and attention disorders. Developmental Medicine and Child Neurology, 3,
257–264.
Latash, M. (2008). Evolution of motor control: From reflexes and motor programs to the equilib-
rium-point hypothesis. Journal of Human Kinetics, 19, 3–24.
ness. Brain Development, 69–71. https://doi.org/10.1016/S0387-7604(80)80009-X
Lewis, B. A., Freebairn, L., Hansen, A., Iyengar, S., & Taylor, H. (2004). School-age follow-up
of children with childhood apraxia of speech. Language, Speech, and Hearing in Schools, 35,
122–140.
neuropsychology’s past and the impact. Advances in Medical Psychotherapy, 8, 59–78.
Maasen, B. (2002). Issues contrasting adult acquired versus developmentla apraxia of speech.
Seminars in Speech Language, 35, 257–266.
Maasen, B. (2015). Developmental models of childhood apraxia of speech. In I. R. Barr &
Maleki, S., Chye, Y., Zhang, X., Parkes, L., Chamberlain, S., Fontenelle, L. F., et al. (2020). Neural
University Press.
Science, 25, 110–124.
Mayo Clinic. (2022). Childhood apraxia of speech. Retrieved from Mayo Clinic. https://www.
drc-20352051
tioning in men receiving androgen deprivation therapy for prostate cancer: A systematic review
and meta-analysis. Supportive Care in Cancer, 22(8), 2271–2280. https://doi.org/10.1007/
s00520-014-2285-1
Trends in Cognitive Sciences, 17. https://doi.org/10.1016/j.tics.2013.09.015
Merceron-Martinez, D., Ibaceta-Gonzalez, C., Salazr, C., Almaguer-Melian, W., Bergado-Rosado,
J., & Palacios, A. (2021). Alzheimer’s disease, neural plasticity, and functional recovery.
Journal of Alzheimer’s Disease. https://doi.org/10.3233/JAD-201178, In press.
brcg.1999.1099
Mihailidis, A., Boger, J. N., Craig, T., & Hoey, J. (2006). The COACH prompting systems to assist
older adults with dementia through handwashing: An efficacy study. BMC Geriatrics, 8, 28.
http://www.biomedcentral.com1471-2318/8/28
apraxia of speech. American Journal of Speech Language Pathology, 28, 1432–1447.
Mirabella, G. D. (2017). Developmental coordination disorder affects the processing of action
relate verbs. Frontiers in Human Neuroscience. https://doi.org/10.3389/fnhum.2016.00661
Molloy, J., & Jagoe, C. (2019). Use of diverse diagnostic criteria for acquired apraxia of speech:
A scoping review. International Journal of Language and Communication Disorders, 54(6),
875–893. https://doi.org/10.1111/1460-6984.12494
org/10.1111/jpc.14150
0.1080/13554794.2016.1172645
Mountford, H. B. (2022). The genetic and molecular basis of developmental language disorder: A
review. Children, 9, 586.
org/10.1044/2015_JSLHR-S-13-0179
from National Institute of Deafness and Other Communication Disorders. https://www.nidcd.
nih.gov/
Naxarro, X. (2009). Chapter 27 Neural plasticity after nerve injury and regeneration. International
Review of Neurobiology, 87, 483–505. https://doi.org/10.1016/S0074-7742(09)87027-X
References 179
Newbury, D. W. (2009). CMIP and ATP2C2 Modulate phonological short term memory in lan-
guage impairment. The American Journal of Human Genetics, 85, 264–272.
Rare Disorders. https://rarediseases.org/rare-diseases/ocular-motor-apraxia-cogan-type/
Nudo, R., Wise, B., SiFuentes, F., et al. (1996). Neural substrates for the effects of rehabilitative
training on motor recovery after ischemic infarct. Science, 272, 1791–1794.
Brain, 115(Pt 4), 1061–1071.
and Associated Disorders, 523–530.
an emphasis on the implications for white matter degeneration. Journal of Neurotrauma, 21(6),
Reviews https://doi.org/10.1089/0897715041269641, online.
Pazzaglia, M., Pizzamiglio, L., Pes, E., & Aglioti, S. (2008a). The sound of actions in apraxia.
ability. Human Movement Science, 27(5), 668–681.
Pinson, A. X. (2022). Human TKTL1 implies greater neurogenesis in frontal neocortex of modern
humans than Neanderthals. Science, 377. https://doi.org/10.1126/science.abl6422
on speech and Orofacial Disorders. https://doi.org/10.1044/ssod19.1.44.
Ramus, F. (2003). Developmental Dyslexia: Specific phonological deficit or general sensorimotor
sysfunction. Current Opinion in Neurobiology, 13, 212–218.
45, 489–493.
Rosenzoph, H., Weisen, D., Basilakos, A., Yourganov, G., Bonilha, L., Rorden, C., … Sperber,
C. (2020, April 17). Mapping the Human Praxis Network: An investigation of white matter discon-
nection in limb apraxia. Retrieved from bioRxiv.org. https://doi.org/10.1101/2020.04.14.041442
Rosenzoph, H., Wiesen, D., Basilakos, A., Yourganov, G., Bonilha, L., Fridriksson, J., et al. (2022).
braincomms/fcac004
Salo, V. F. (2019). The role of the motor system in action understanding and communication:
390–401.
Sato, J. R., Biazoli Jr., C. E., Zugman, A., Pan, P. M., Bueno, A. P. A., Moura, L. M., … & Jackowski,
A. P. (2021). Long-term stability of the cortical volumetric profile and the functional human
connectome throughout childhood and adolescence. European Journal of Neuroscience,
6187–6201. https://doi.org/10.1111/ejn.15435
77, 826–852.
Frontiers in Pediatrics. https://doi.org/10.3389/fped.2020.599633
Sharma, V., & Wong, L. (2022). Middle cerebral artery disease. In J. Grotta, G. Albers,
J. Broderick, S. Kasner, R. Sacco, A. Day, et al. (Eds.), Stroke (Seventh edition) patho-
physiology, diagnosis, and management (pp. 317–346). Elsevier. https://doi.org/10.1016/
B978-0-323-69424-7.00024-7
Sharma, N., Classen, J., & Cohen, L. (2013). Neural plasticity and its contribution to func-
tional recovery. Handbook of Clinical Neurology, 110, 3–12. https://doi.org/10.1016/
B978-0-444-52901-5.00001-0
707–736.
Shriberg, L. D., Fourakis, M., Hall, S. D., Karlsson, H. B., Lohmeier, H. L., McSweeny, J. L.,
Potter, N. L., Scheer-Cohen, A. R., Strand, E. A., Tilkens, C. M., & Wilson, D. L. (2010).
Extensions to the speech disorders classification system (SDCS). Clinical Linguistics &
Phonetics, 24, 795–824.
Sonuga-Barke, E. (2003). The dual pathway model of AD/HD: An elaboration of neuro-develop-
mental characteristics. Neuroscience Biobehavioral Review, 27, 593–604.
Evidence for the dissociation of timing,inhibitory and delay-related impairments in Attention
Deficit/Hyperactivity disorder. Journal of Child and Adolescent Psychiatry, 345–355. https://
doi.org/10.1016/j.jaac.2009.12.018
the human brain. PLOS Computational Biology. https://doi.org/10.1371/journal.pcbi.0010042
work. Wurr.
Steward, M., Sridhar, A., & Meyer, J. (2013). Neural regeneration. Current Topics in Microbiology
and Immunology, 367, 153–191. https://doi.org/10.1007/82_2012_302
Stoll, G., & Muller, H. (1998). Nerve injury, axonal degeneration and neural regeneration: Basic
insights. Brain Pathology, 9, 313–325. https://doi.org/10.1111/j.1750-3639.1999.tb00229.x
References 181
Sweatt, D. (2016). Neural plasticity and behavior- Sixty years of conceptual advances. Journal of
Neuroshemistry, 139(2), 179–199. https://doi.org/10.1111/jnc.13580
Tal Saban, M. Z. (2012). The functional profile of young adults with suspected developmental
coordination disorder (DCD). Research in Developmental Disabilities, 33, 2193–2202. https://
doi.org/10.1016/j.ridd.2012.06.005
Disabilities, 35, 2644–2650.
developmental speech disorders. Folia Phoniatrica et Logopaedica, 71(5–6), 216–227.
with Childhood Apraxia of Speech. Disability and Rehabilitation, 31(2), 94–102. https://doi.
org/10.1080/09638280701795030
The Health Jade Team. (2022). Brain plasticity. Retrieved from Health Jade. https://healthjade.net/
brain-plasticity/
The Medical Dictionary. (2021). Apraxia. Retrieved from The Medical Dictionary. http://the-med-
ical-dictionary.com/apraxia_article_2.htm
S095457941800072X
Development, 40, 77–84.
Waring, R., & Knight, R. (2013). How should children with speech sound disorders be classi-
fied? A review and critical evaluation of current classification systems. Journal of Language
& Communication Disorders, 48(1), 25–40. https://doi.org/10.1111/j.1460-6984.2012.00195.x
ligence. Applied Neuropsychology Child, 6(3), 228–236. https://doi.org/10.1080/2162296
5.2017.1317489
Child Neurology, 49(12), 920–925.
org/10.1093/brain/106.2.391

Weintraub, S. (2000b). Neuropsychological assessment of mental state. In M. Mesulam (Ed.),
neuron.2016.12.013
West, C., Bowen, A., Hesketh, A., & Vail, A. (2008). Interventions for motor apraxia follow-
ing stroke. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.
CD004132.pub2
Wielock, T., & Nikolich, K. (2006). Mechanisms of neural plasticity following brain injury.
Current Opinion in Neurobiology, 16(3), 258–264.
Wilson, P. M. (1998). information processing deficits associated with developmental coordination
disorder: A meta-analysis of research findings. Journal of Child Psychology, 39, 829–840.
Worthington, A. (2016). Treatments and technologies in the rehabilitation of apraxia and action
disorganisation syndrome: A review. Neurorehabilitation, 39(1), 163–174. https://doi.
org/10.3233/NRE-161348
Xenia Lojewski, L. X.-B.-E. (2014). Human adult white matter progenitor cells are multipotent
neuroprogenitors similar to adult hippocampal progenitors. Stem Cells Translational Medicine,
3(4), 458–469.
Chapter 11
Understanding Apraxia Going Forward
Perhaps the clearest thing that we can conclude is that currently the science
surrounding apraxia remains largely behaviorally defined. However, as we have
emphasized, this state of affairs limits the development of new clinical applications.
In addition, defining things behaviorally means that we conduct research based
upon their behavioral definitions, and as we have seen, these definitions lack both
specificity and sensitivity when considered from a neural network perspective.
Some of this rests with inconsistencies in many of the behavioral definitions for all
but the most isolated apraxia (i.e., eye blink apraxia), such as apraxia and childhood
apraxia of speech. The current labels merely describe the behavioral manifestation
of a particular type of behavioral dysfunction.
From a neural network perspective, the current diagnostic label of apraxia is
bereft of meaning past the idea that a certain complex motor function is not taking
place as it should. There are presumptions related to these diagnostic labels to be
sure. The presumption is that there is underlying neurological damage and, as we
have seen, there is research that identifies certain areas of the brain in relation to
certain types of apraxic conditions. However, despite significant gains in research
and neuroimaging studies, this is insufficient to clarify the situation, that is, the
specificity of the etiology of the disorder, as multiple areas of insult can result in
similar behavioral disorders and, the inverse, many of these brain networks overlap
several apraxic conditions. In sum, we have difficulties in the area of sensitivity of
diagnostic labels for some apraxia and specificity for most.
From a mental health perspective, this should not be surprising as the totality of
our current nosology is based on behaviorally classified manifestations of a disor-
der. We recognize that this has value in that the system provides a common language
with which to discuss these issues and facilitates discussion between professionals.
There is also a potential benefit emanating from the fact that these behaviorally
defined clusters may represent an underlying commonality that might be identified
in the future.
T. Wasserman, L. D. Wasserman, Apraxia: The Neural Network Model, Neural
Network Model: Applications and Implications,
184 11 Understanding Apraxia Going Forward
From a neurological perspective, the current state of affairs reflects a great deal
of informative research as compared to the original hypotheses concerning neocor-
tex-based lesions. Nonetheless, much work remains to be done, specifically, improv-
ing specificity and sensitivity in identifying specific network dysfunction associated
with specific behavioral outcomes. Despite this research, etiology remains unclear.
While it is true to say that a person with verbal apraxia has certain specific dys-
functional behaviors, it is also true to say that those behaviors could be produced by
a variety of lesions to locations among the constituent networks involved in this
very complex behavior. A review of the etiology of patients identified with apraxia
of speech (AOS) can provide an illustration: while patients identified as having
apraxia of speech (AOS), defined as an articulatory disorder, were found to have
damage to the left superior precentral gyrus of the insula (Ogar et al., 2006), addi-
tional involvement of neighboring brain areas was associated with more severe
forms of both AOS and related language deficits, such as aphasia. In other words,
while the core of apraxia of speech might be one area, the actual variety of clinical
manifestations and dysfunction is associated with other areas that are somewhat
more diffusely distributed. This would make understanding the underlying network
dysfunction in verbal apraxia somewhat identifiable if it were not for the fact that
there have been suggestions that apraxia can be due to deep subcortical lesions,
which raises the question as to whether damage to the basal ganglia or thalamus can
cause apraxia as well (Pramstaller & Marsden, 1996). This, of course, makes sense
given the motor components that are central to apraxic conditions.
A similar situation exists in other forms of apraxia. For example, research dem-
onstrates that although conceptual praxis representations are stored in the left hemi-
sphere, analysis of lesion sites does not reveal where in the left hemisphere they
may be stored (Heilman et al., 1997). Thus, disruption anywhere in this complex
system could produce the same output dysfunction.
The Problem of Diagnosis
We have written about what we perceive is the multiplicity of problems associated

with the currently used behaviorally based diagnostic nosologies (Wasserman &
Wasserman, 2016). Among our concerns is the issue of the inability of the current
nosology’s ability to contribute to the advance of brain behavior science, particu-
larly neural network science. Perhaps the science surrounding the etiology of
apraxia in general and developmental apraxia in specific provides one of the clearest
examples of our ongoing concerns. The diagnosis and understanding of apraxia
conditions have not changed much at all in the last 50 years and not enough from
when it was described 100 years ago. The diagnosis of apraxia is made based upon
the inability to functionally coordinate the movement or intentionality of a specific
muscle group to produce a desired outcome. The gold standard for diagnosing
things such as childhood apraxia of speech (CAS) remains expert judgment of per-
ceptual features (Murray et al., 2015a). Treatment in the form of practice or muscle
The Problem of Diagnosis 185
strengthening follows. There is no need to understand the underlying neurological/

neuropsychological dysfunction although it is assumed that there is damage some-
where in the networks contributing to the final target movement.
Given what we know about apraxia, perhaps this is as good as it gets, and we do
not require anything fancier. Diagnosis, after all, should inform treatment. As far as
apraxia conditions are concerned, treatment is based on behavioral practice designed
to encourage the automation of the desired behavior. As it stands, at the current
time, from a treatment perspective, it may not be necessary to know where in a neu-
ral network the dysfunction arises, as that knowledge may not contribute to treat-
ment. After all, if there was damage to a particular white matter network component,
for example, the solution would be to foster neural plasticity by practicing func-
tional movement anyway. The exact location or general type of insult, apart from a
malignant tumor, would make little or no difference as far as treatment goes. We
cannot target a specific area. We know, however, that repeated practice will, in some
instances, lead to functional recovery. Perhaps this is a satisfactory circumstance as
it is all that is needed for treatment. For us, this is not the case.
Our most far-reaching concern regards the failure of a behavioral system to gen-
erate research that would identify and expand our knowledge concerning how dam-
age of dysfunction of the white matter networks that subserve function causes the
problems that identify themselves for treatment. In fact, we have argued and stand
by our concerns that these behavioral descriptors, which may have clinical utility,
actually impede research. This concern is evident in both treatment of and research
concerning ADHD. The melding of dozens of potential combinations of behavioral
clusters confounds our understanding of the individual, confounds treatment medi-
cally and clinically, and confounds research secondary to a conglomeration of fac-
tors which should not be considered a unitary concept.
As we have demonstrated, multiple issues remain unresolved. Within the realm
of neural networks, we do not yet know whether or how damage to different com-
ponents of the same system produces the same behavioral dysfunction, let alone
how damage to the different parts of the same network produces disorders that differ
slightly from each other. We do not yet know if we can repair or encourage repair of
damaged white matter networks, and we have little knowledge of, other than prac-
tice, how to encourage neural plasticity in order to recover function. All of this
contributes to the problem of classifying disruptions of motor coordination as rep-
resenting apraxia or some separate condition.
Take for example a phenomenon labeled as swallowing apraxia (Daniels, 2000).
Swallowing apraxia is a disorder of lingual, labial, and mandibular coordination,
which has been observed before bolus transfer during the oral stage of swallowing.
It is extensively discussed in the literature on dysphagia. To date, the possible mech-
anisms and neural networks of swallowing apraxia have not been identified, although
similarities with other apraxia are evident. Daniels (2000), in a review of the litera-
ture, identified possible similarities as greater occurrence upon command, transitive
nature of the action, and evidence of spatial errors. Differences such as hemispheric
lateralization and multiple gesture assessment seem to exist between swallowing
apraxia and more traditional forms of apraxia. The author concludes the review by
noting “until discrete error patterns of swallowing apraxia are identified and pre-
cisely measured, the nature of this disorder and its relationship with the praxis sys-
tem will continue to remain elusive” (pg. 159). Similarly, Van Der Merwe (2020)
states that the complexity of speech motor control and the incomplete conceptual-
ization of phases in the transformation of the speech code from linguistic symbols
to a code amenable to a motor system tend to obscure the understanding of acquired
apraxia of speech (AOS). Taken together, these comments state the case succinctly.
Until now, all that was necessary is for the clinician to observe the speech or swal-
lowing difficulty. That is clearly not enough to establish whether a particular disor-
der is a condition of praxis or not, probably because the exact neural network basis
of apraxia has not been elucidated.
Problems for Neuropsychologists
One of our major concerns as far as the future of neuropsychology is that the current
practice of neuropsychology has led to a diminishing role for neuropsychologists in
the treatment of many disorders. It seems that the standard of care at the current
time is that many practicing neuropsychologists want to conduct an evaluation to
determine if the person meets the behavioral criteria. It the person does not meet the
cutoffs, there is likely no formal intervention as there is not pathology deemed pres-
ent. On the other hand, when a person meets the criteria, often the best we do is refer
out; I have found out that the individual is apraxic and sent them to a qualified
speech and language therapist or occupational therapist. I have done my job! The
situation is analogous to diagnosing a reading disorder in a child sent to us for
assessment of reading difficulties noted at home or in school. We test reading level,
substantiate that the child is “behind” (the parents knew that anyway; that’s why
they brought the child to you in the first place), and then send the child to a reading
specialist for treatment. This recommendation is often unaccompanied by any infor-
mation regarding what type of reading difficulties or practices the child is engaging
in, how their reading is impacted, which other cognitive or academic areas may be
impacted, nor, other than generic recommendations, which interventions might be
appropriate for that child and why. The schools have noticed this sort of circular
reasoning and have, as Response To Intervention has shown, decided that they can
do without our services in many instances. The current process would appear to
represent clinical practice, not science. If we continue, without being able to offer
meaningful treatment intervention advice, the result for instances of apraxia will be
the same as for reading; people will decide that they don’t need us. We are not alone
in expressing the concern that the current behaviorally based process does not rep-
resent science (McLaren, 2010; Hofmann et al., 2016). We believe we have to do
better. We need to be able to tell our clients if the identified disorder is associated
with other areas of noted weakness, what are the implications, and which of
the numerous treatment approaches available in the marketplace have been scien-
tifically validated. We would profit from knowing and sharing what impact there
Staying in Our Lane 187
may be in, for example, associated skills or activities of daily living and types of
intervention which may be useful for the particular client we have assessed.
Staying in Our Lane
Historically, the domain of neuropsychology has been cognition. Many of our tests
are designed to assess cognition directly. When there is a motor component, it is
most often motor speed as a reflection of cognitive processing speed or a functional
assessment of a skill like handwriting. Perhaps this focus on one particular domain
made sense when we believed that we could reliably assess one domain indepen-
dently of the impact on other domains. Since research clearly suggests that motor
networks play a role in almost all human cognitive activity, sustaining this idea no
longer corresponds with what the science is telling us. As we have seen, this has
implications for the assessment of functionality related to acquired apraxic condi-
tions in terms of comorbid conditions that should be investigated. The same motor
basis of complex cognition has even greater implications for the assessment of a
child with childhood apraxia of speech (CAS).
As regards CAS, what the science is telling us is that there is a complex and
predictable relationship between early motor integrity and later cognitive perfor-
mance. This relationship is impacted by numerous factors all worth of investigation.
For example, Piek et al. (2008) demonstrated that socio-economic status (SES) pre-
dicted fine motor performance and three of four cognitive domains at school age in
a typically developing population. After controlling for SES, fine motor trajectory
information did not account for a significant proportion of the variance in school-
aged fine motor performance or cognitive performance. However, gross motor tra-
jectory did account for a significant proportion of the variance for cognitive
performance once SES was controlled for. Analysis showed a significant predictive
relationship for gross motor trajectory information and the subtests of working
memory and processing speed on standard psychological tests. Similarly, research
has indicated that attention, fine motor skills, and general knowledge are much
stronger overall predictors of later math, reading, and science scores than early math
and reading scores alone (Grissmer et al., 2010). More specifically, children with
CAS are at risk for persistent reading and spelling disorders in addition to their
spoken communication difficulties (Gillon & Moriarty, 2007). They identify four
factors that increase the risk of written language disorder in this population: (1) the
nature of the speech disorder, (2) the presence of phonological awareness difficul-
ties, (3) genetic risk factors, and (4) the negative impact of early reading difficulty
on later written language development. A complete diagnostic interview can assess
for these factors and aid the neuropsychologist in establishing treatment protocols.
It is true that these are not test scores, but the information is just as valid. Finally,
there is evidence to suggest that speech-motor programming difficulties may also
contribute to reading, writing, and spelling difficulties. Children lacking the motor
control to pronounce a word, either aloud or covertly, may have difficulty with seg-
mentation tasks. Children with CAS are generally poorer spellers than children with
normal articulation. These spelling deficits of the CAS group could not be attributed
to an inability to pronounce words or a difficulty with phoneme-grapheme corre-
spondences (Lewis et al., 2004). Earlier in this volume, the associated impact was
addressed from the perspective of dyslexia, academic difficulties, and neurodevel-
opmental disorders.
Collectively, this research suggests that life course circumstances in conjunction
with early motor competence will impact later higher-order cognitive functioning.
The research also suggests that neuropsychologists should be conversant in assess-
ing motor functionality early on. This is because motor function is a core compo-
nent of later higher-order cognitive activity. This research also suggests that the
distinction between early “developmental” assessment and later cognitive or neuro-
psychological assessment is arbitrary at best, reflecting limitations of test construc-
tion rather than substantial differences in what is being assessed.
Understanding Disorders from a Neural Network Perspective
Given the increasing concerns regarding the scientific utility of the current behav-
iorally based nosologies, there have been suggestions for alternative systems. For
example, Hofmann et al. (2016) offer a complex network approach to diagnoses as
an alternative to the latent disease model. This model may offer better utility for
understanding the neural network components of disorders such as apraxia.
According to this model, symptoms do not indicate a solitary underlying latent dis-
ease that causes their appearance and co-occurrence. Rather, the disorders are mani-
festations of interrelated elements of networks. Symptoms are the actual components
of, not reflective, of the disorder. A disorder constitutes a network of symptoms that
interact in ways that tend to sustain and reinforce themselves. For example, a stress-
ful event does not activate an underlying entity called anxiety, which then causes the
emergence of symptoms. Stressful events activate certain elements that in turn acti-
vate other elements, and when a critical mass of these elements occur, an episode of
disorder may be diagnosable. They posit that “Depending on the structure of the
network, change can occur abruptly once the network reaches a critical threshold
(the tipping point).” This model also provides a framework for therapeutic change
as “Homogeneous and highly connected networks often recover more slowly from
local perturbations when the network approaches the tipping point, potentially mak-
ing it possible to predict treatment change, relapse, and recovery.”
Network Theory and Complex Networks
Hofmann et al. (2016) offer a comprehensive contrast and comparison of latent

disease vs. complex network theory. The latent disease model will not be reviewed
here as the current authors assume the reader has both training in and experience
with the current working model of latent disease. To understand the newer proposal,
Network Theory and Complex Networks 189
it is necessary to understand that the origins of network theory lie a branch of math-
ematics, specifically a subset of graph theory. This subset is concerned with the
visual representation of a set of objects and the links connecting pairs of objects. As
we have discussed in our discussions of the connectome, networks contain two
components: nodes representing objects (e.g., individual persons, neurons, symp-
toms, nations) and edges – lines that connect these two objects, thereby representing
the association between them (e.g., the relationship between apples and oranges in
a network of fruit). An unweighted network depicts whether two nodes are con-
nected. A weighted network also represents the strength of the connection.
Network theory permits the computation of the importance of a particular node
in the operation of a network. This is known as centrality. “A highly central node is
one, when activated, is likely to spread activation throughout the network via the
multiple edges connecting it to other nodes. For example, a node high on degree
centrality is one with many edges connected to it (e.g., a highly popular person in a
social network). A node high on strength centrality in a weighted network is one
having many edges connected to it that are great in terms of their magnitude of
associations (e.g., the Pearson’s r of each edge is large). A node high on between-
ness centrality is one that often lies on the shortest pathway between two other)”
(Hofmann et al., 2016, pg. 598).
Complex networks comprise many nodes whose connections are neither random
nor uniform in their connectiveness with other nodes in the network. That is, the
structure of the network varies; some nodes cluster in subgroups, whereas others
have few or weak connections with other nodes. Complex networks are the empiri-
cal norm in sociology, neuroscience, and psychopathology.
This network perspective directs attention to the defining features of the pathol-
ogy (nodes) and their functional interconnections (edges) and away from a search
for an underlying common cause of the activated elements, expressed as a sum
score designed to index severity. It intends a search for mechanisms (or biomarkers)
causing specific elements (e.g., failure to coordinate movement of the tongue),
instead of disorders (apraxia). It does not eliminate the need of categorical diagnosis
but rather adds a scientific element to it.
This neural network model views symptom heterogeneity as patterns suggestive
of causal links between features of a disorder. It would enable the clinician to under-
stand that there may be core elements (symptoms) to every disorder of a certain
class while acknowledging that different features may produce different patterns of
related elements or symptoms. This analysis would produce a different form of dif-
ferential diagnosis and related understanding. It would look at subtypes of the core
disorder based on their associated features and perhaps provide an understanding of
how the component neural networks are participating in the dysfunction. Finally,
this would entail a different perspective on comorbidity in that comorbidity would
be looked at as shared patterns of network contribution between various disorders.
Instead of diagnosing depression and anxiety as discrete disorders, this method
would look at their shared properties and perhaps, along the way, identify a latent
class disorder that explains them both. This is at odd with the current diagnostic
system which views the significant overlap between depression and anxiety as a
confound that both complicates diagnosis and muddies research.
Research Domain Criteria (RDoC) (Insel, 2014)
RDoC is a research framework designed to improve research approaches regarding

mental disorders. It emanates from a discussion and the research on precision medi-
cine which deconstructs current diagnostic groups with specific biomarkers that
predict and improve treatment methodology. It integrates many levels of informa-
tion (from genomics and circuits to behavior and self-report) to explore basic
dimensions of functioning that span the full range of human behavior from normal
to abnormal.
RDoC is not meant to replace the current diagnostic system nor does it serve as
diagnostic guide. The goal, as far as psychology and neuropsychology is concerned,
is to understand the nature of mental health and illness in terms of variable degrees
of dysfunction across and within psychological and biological systems.
The currently in use DSM and ICD systems are diagnostic manuals and are
based upon behaviorally articulated classes. There are problems in this approach.
One of the primary problems is that there are very significant limitations in the sci-
entific application of heterogeneous syndromes where the defining psychopatholo-
gies are not unique to the diagnostic class and vary within categories between cases.
RDoC seeks to avoid this problem. What RDoC does, instead, is to establish a set of
principles for deriving and studying biobehavioral constructs implicated in psychi-
atric disorders (Carpenter, 2016). The issue is not whether RDoC is an alternative
diagnostic approach but whether the paradigm will promote information that
informs nosology and facilitates application of brain science in clinical diagnostic
concepts. The RDoC framework attempts to alert investigators to the fallacy of
methods that equate diagnosis with a specific disease. Rather, researchers are
encouraged to focus on psychopathology in the context of hypothesized neural cir-
cuits and behavioral constructs (Cuthbert & Insel, 2013). Clearly this approach is
very much in line with the focus of this book.
The RDoC model has been used to describe motor-based language deficiencies
such as apraxia (Appendix 1). It describes the sensorimotor systems involved in
language apraxia as a “multifaceted construct comprising the processes that must be
engaged during the planning and execution of a motor action in a context-appropri-
ate manner. Component processes include action planning and selection, sensorim-
otor dynamics, initiation, execution, and inhibition and termination. Each of these
components have their associated networks identified and outlined. Of note, these
processes will often be recruited in conjunction with motivational processes
described in other domains, as when appetitive motivations drive approach behav-
iors (Wasserman & Wasserman, 2020). As for developmental apraxia, the construct
explicitly includes the modulation and refinement of actions during development
and learning” (National Institute of Mental Health, 2022).
Diagnosing Apraxia: Why Make It Complicated? 191
Recently, other researchers seeking greater clarity have proposed alternative

diagnostic models for some or all apraxic conditions. For example, Baumard and Le
Gall (2021) note that the diagnosis of limb apraxia relies mainly on exclusion crite-
ria (e.g., elementary motor or sensory deficits, aphasia). This is certainly true for
most apraxic conditions. That points out that the plethora of apraxia definitions and
assessment methods cause different diagnostic outcomes. Specifically, patients may
or may not show apraxia depending on the chosen assessment method or theory,
making the definition of apraxia somewhat arbitrary. They note that, as a result,
“apraxia” may be diagnosed in patients with different cognitive impairments,
hypothesizing that the current situation is the result of an evolution from a task-
based approach toward a process-based approach. This process approach is based
on the deconstruction of the conceptual or production systems of action into multi-
ple cognitive processes: language, executive functions, working memory, semantic
memory, body schema, body image, visual-spatial skills, social cognition, visual-
kinesthetic engrams, manipulation knowledge, technical reasoning, structural infer-
ence, and categorical apprehension. The fact that both these systems of diagnosis
coexist in the current literature represents, in their view, a major challenge that
stands in the way of a scientific definition of apraxia. To eliminate this problem,
they suggest a focus on symptoms and on two complementary definition criteria (in
addition with traditional exclusion criteria): specifically, is apraxia explained by the
alteration of cognitive processes specifically dedicated to gesture production and
consistency, as in whether the gesture production impairment is consistent across
tasks. They conclude that after a century of Liepmann’s demonstration of the auton-
omy of apraxia toward language, the autonomy of this syndrome toward the rest of
cognition remains an open question and that this lack of clarity continues to pose
new challenges to apraxia studies.
Diagnosing Apraxia: Why Make It Complicated?
There is an argument to be made that clinical diagnosis is a process separate and

distinct from the process of researching the underlying mechanisms of a disorder of
any type. This argument is as follows: Clinical and research diagnostic criteria serve
different purposes. Clinical criteria should be used to diagnose referred cases and to
confirm suspected cases arising from screening tests. In these situations, appropriate
diagnosis and labeling is a necessity for decisions related to access to things like
special education, treatment, remedial teaching, and reimbursement of costs related
to services rendered by medical insurance programs. On the other hand, the use of
research diagnostic criteria ensures the selection of a sample that is optimally suited
for answering the research question. The sample is as free of confounds as can be
achieved and independent of the source from which children are selected, the main
sources being clinical referrals and screening procedures. Research diagnostic cri-
teria should be carefully tuned to the research questions addressed (Geuze et al.,
2015). This view attempts to bridge the gap between the two processes arguing that
each has its place in science.
We have taken notice of what seems to be a strategic tension between applied

science and basic research science. This occurs in all areas of science where both
possibilities exist, and it is certainly present in neuropsychology. Basically, basic
research science increases the knowledge base of a field of research while applied
science uses that knowledge to solve specific problems. As regards the etiology of
disease process, both positions have their supporters. It would be fair to say that the
authors of the present volume are split as to the wisdom of each approach. It would
also be fair to say that we have argued in the past, and will continue to advocate, for
the wisdom of having basic science to inform diagnostic process.
More than 100 years ago, Joseph Henery, in his presidential address to the
American Association of Science, stated “The incessant call in this country for prac-
tical results and the confounding of mechanical inventions with scientific discover-
ies has a very prejudicial influence on science... A single scientific principle may
include a thousand applications and is therefore, though if not of immediate use, of
vastly more importance even in a practical view” (Trigilio, 2013). The other posi-
tion could be stated thusly: applied science is important as it enables science to be
more applicable in the real life. Without it, great scientific discoveries may be lim-
ited as human knowledge will increase, but be underutilized. Every invention, medi-
cine, and even buildings are a result of applied science. Certainly, it can be argued
that neuropsychology respects both positions, but, to a large extent, much of neuro-
psychology is an applied science. When it comes to apraxia, as in other topics but
perhaps more so here, the divide is clear. We diagnose apraxia based on an observed
dysfunction of a particular motor system. Nothing more is required. Once I know
that the particular system is not working correctly, all I really want to know is how
to fix it.
We have seen lots of examples of this sort of thinking, and we have come to
believe that it has become detrimental to neuropsychology. For example, to diag-
nose dyslexia we give tests of phonetic reading and reading comprehension. We
“discover” that the child is “behind” based on national norms. We really don’t know
why, but it is not necessary because all we are going to do is refer to a reading spe-
cialist for remediation. Job is done. The same happens with speech and language
deficits and motor deficits when we refer to speech and language pathologists or
occupational therapists. This process ignores the obvious. In almost every instance,
the referral to us for assessment was made because the parents and the school
already knew the child was “behind” and they wanted to know why, which is the one
thing we often fail to explain and what the current diagnostic nosologies do not
require of us to know. It is sort of like telling a parent whose child is crawling that
the child is in the crawling phase. They already knew that. It was logic like this, we
believe, that resulted in “Response to Intervention” and the diminished importance
of psychological testing in the special education process.
We believe that neuropsychologists and others must be able to say why some-
thing is happening not simply that it is just happening. We often read professional
chat room or conference discussions about how long a report should be or how
much information should be provided to a parent, often advocating to “keep it sim-
ple.” While we agree that “length of report” does not correlate with our professional
Assess It All: Downstream and Upstream Impact of Network Disruption 193
value, we strongly believe that we must provide more and better etiological infor-
mation to our clients and referral sources. This is so we can continue to provide
current information on effective treatment. It is insufficient merely to say that some-
thing is wrong and go to another person to fix it without telling the client what they
should ask for treatment wise and why. We must do this, or we become obsolete. For
example, a recent evaluation feedback explained to a parent how their child’s early
gross motor oddities, their diagnosed dyslexia, and their child’s attention issues and
spelling issues and difficulty reading math equations and slow writing output speed
(previously explained to her as slow processing) were all related, helped her to an
“aha” moment.
While at the current time it might be very true that the only effective treatment
for apraxia is to encourage neural plasticity by providing massed practice, more
effective treatment options might be available if we look for them. For example, by
understanding that neural networks are at the core of the disorder, are there more
effective ways of encouraging the growth and repair to these networks than simply
massed practice? Can we develop ways to target network growth? Can we discover
how these networks become disrupted in the first place?
We believe that neuropsychology has the potential to do this. In his review Bunge
(1985) examined the three main strategies for the study of behavior and mentation:
behaviorism, mentalism, and psychobiology. “Behaviorism is found wanting for
eschewing most of the problems that traditional psychology posed but left unsolved.”
Two kinds of mentalism are distinguished: traditional and cognitivist (or informa-
tion-theoretic). Both are found wanting for ignoring the nervous system and beg-
ging the question, since they postulate the mind instead of explaining it. Only the
psychobiological (or neuropsychological) approach, which regards the mind as a
collection of brain functions, is found promising for studying that which guides
behavior and does the mentation, namely, the brain. It is also shown to have the
advantage of promoting the union of psychology with biology and of bridging psy-
chiatry to neurology, neurophysiology, and neurochemistry. It is argued that this
approach is the only fully “scientific” one (pg. 115). We could not agree more. To
support this process, our applied branch must incorporate more basic science into
their everyday work. We believe that this is essential to establish and maintain our
credibility with our client and referral base.
ssess It All: Downstream and Upstream Impact

A
of Network Disruption
We have suggested at several points that disruptions of a neural network affect not
only the target or most observable behavior but potentially all other aspects of
behavioral function dependent on that network component. That implies functions
that are part of the network related to the target behavior (i.e., apraxia of speech) but
also other functions that rely on recruiting the impacted network. So, let’s provide
an example to illustrate. Damage to dominant dorsolateral prefrontal cortex has

been reported to cause disordered speech motor control because of disrupted plan-
ning and programming of articulatory performance (anarthria or apraxia of speech).
However, more recent data provide some evidence that apraxia of speech may be
caused by dysfunction of the dominant anterior insula (Riecker et al., 2005). So, it
is clear that damage to this area causes disruption in the planning, pacing, and tim-
ing of speech to be sure, but what other cognitive functions might we reasonably
expect to be impacted? It turns out that there are quite a few. Lesions of the dorso-
lateral PFC (DLPFC), consisting of Brodmann areas (BA) 9 and 46, can result in
deficits across a wide range of functions, including working memory, rule-learning,
planning, attention, and motivation (Szczepanski & Knight, 2014). In other words,
if you are assessing for apraxia based on observation of speech production and you
find it, you would be very judicious to consider the fact that your client may have
had disruption of function, to some degree, in all those areas as well, and that treat-
ment might be much more extensive than it initially appeared. Given the number of
systems involved in most apraxic conditions (see Appendix 1 for an example),
expectations like this should be the rule rather than the exception. Indeed, just diag-
nosing the apraxia may be doing an injustice to your client.
he Case for a Separate Diagnosis for Childhood Apraxia

T
of Speech
As we have discussed, there are significant differences functionally and etiologi-

cally between childhood (developmental) apraxia of speech (CAS) and its adult
counterpart. On an operational level, not initiating speech is not initiating speech;
therefore they are both apraxia.
However, there is research that clearly indicates that the network operation that
leads to the production of speech changes across the developmental course. There is
also a lack of consensus as to what causes developmental apraxia in the first place.
Indeed, multiple etiologies have been identified (Maassen, 2015). Whereas adult-
onset apraxia conditions are caused by brain insult of identifiable origin, the great
preponderance of childhood apraxia is not. Multiple genetic contributors, white
matter developmental issues, and environmental issues have all been identified as
contributing to the development of childhood apraxia of speech. A summary of the
arguments describing the differences between adult and childhood apraxia has been
provided by Maassen (2015). He notes that dissociation, or more importantly dou-
ble dissociation, does not apply to developmental disorders. Double dissociation is
the ideal neuropsychological/cognitive neuroscience evidentiary standard in the
study of acquired disorders in adults. Double dissociation is when two related men-
tal processes are shown to be functionally independent of each other. A clear exam-
ple of double dissociation related to speech and language occurs when examining
damage to the Broca’s area and Wernicke’s area in adults. When Broca’s area is
damaged, affected patients may still understand language, but be unable to speak
Genetics 195
fluently. They know what they want to say but are unable to say it. When Wernicke’s
area is damaged, patients may still speak fluently, but be unable to understand lan-
guage. This results in properly constructed but nonsensical sentences (AlleyDog.
com, 2022). There are multiple reasons for the failure to demonstrate double dis-
sociation in children, but the primary one is that a disruption in language develop-
ment in a developing child will affect the development and emergence of other
functions and skills in the future that partly depend on this function being intact in
the first place. In developmental disorders, it is more common to identify associa-
tions between functions rather than dissociations (Karmiloff-Smith et al., 2003).
A second difference between childhood and adult apraxia is that research sug-
gests that speech and language production during infancy and early childhood can
be characterized by a more simplified model, consisting of fewer processing stages
than what is seen with the full-fledged adult system (Maassen, 2002). At the earliest
stage of speech development, children have at their disposition a restricted set of
articulatory forms the size of a syllable. At a later developmental stage, under the
communicative pressure of the growing vocabulary, the phonological system
expands and takes advantage of the more productive phonological combination
rules of the adult system. As a result, a word forms lexicon and a phonological
encoding system develops (Levelt et al., 1999). These differences have major impli-
cations for treatment planning and intervention purposes. In therapy for AOS in an
adult population, higher-level psycholinguistic, phonological, skills have been
acquired prior to the injury and can be utilized to facilitate treatment. As a result, use
can be made of their linguistic knowledge, of written material, for instance, and the
treatment can appeal to available syntactic, lexical, and phonological skills. In ther-
apy with children, many of these skills have not yet developed, and as a result, no
previously acquired or less stable higher-level knowledge is available. These very
skills must be acquired by the child via the problematic speech production and per-
ception networks. This implies that more explicit attention during therapy must be
devoted to these higher-level skills, which otherwise do not emerge.
Genetics
Perhaps the most compelling argument for separating the diagnosis of childhood
apraxia of speech from the other adult apraxia is the etiology argument. While
adult-onset apraxia are almost entirely a function of brain insult, childhood apraxia
is a neurodevelopmental disorder frequently caused by genetic mutations. Indeed,
clinical MRI scans fail to reveal overt neural anomalies in individual cases with
CAS (Morgan & Webster, 2018). Genetic causes include both de novo genetic con-
ditions and familial inherited conditions. Research findings support the likelihood
of heterogeneous genomic pathways associated with childhood apraxia of speech.
In addition to the well-known FOXP2 mutation, at least ten chromosomes have been
identified as involved in childhood apraxia, several of which have two or three
candidate sites. In some instances, multiple copy variations occur on more than one
chromosome in the same individual (Laffin et al., 2012).
CAS is a complex disorder, defined as a higher-order motor system deficit of
motor planning and programming. More specifically, motor planning involves
transforming abstract sound representations into speech-motor goals or commands,
and it also involves further specifying the specific movement or acoustic parameters
within each articulator for speech production. There is general consensus regarding
three core diagnostic features for CAS: (I) inconsistent speech errors (e.g., produc-
ing the same syllable or word differently across repetitions of the same word), (2)
lengthened and disrupted co-articulatory transitions (e.g., oral groping during
speech; difficulty sequencing sounds and syllables, including frequent omissions of
sounds in some cases; marked vowel errors; or hypernasality due to poor online
planning and programming of velum (palatal) movements for denoting oral/nasal
contrasts); and (3) inappropriate prosody (e.g., disrupted rhythm and intonation of
speech, such as placing stress on a typically unstressed syllable of a word or placing
equal stress across all syllables). A CAS diagnosis is based on differentiating the
speech presentation from other developmental speech impairments of articulation
disorder, phonological disorder, stuttering, or dysarthria. In addition, CAS often
occurs in association with other neurodevelopmental conditions, such as epilepsy,
intellectual disability, motor impairment, and autism.
There appear to be clear and significant differences between childhood and adult
apraxia in etiology, network operation, and treatment methodology that would be
obscured by incorporating them together under one general behaviorally based
descriptor.
The Problem of Treatment
Currently, the treatment of all apraxic conditions is based on the idea that massed
practice of the desired skill outcome will, by dint of neural plasticity, couple in the
case of CAS with continued development and produce a repair or acquisition in the
case of CAS of language function. When it comes to childhood apraxia of speech,
statements like this are common: for children with suspected CAS, or children who
have been identified with planning and sequencing issues, approaches that target
motor learning principles such as mass and distributed practice, concrete stepped
learning with high intensity, and functional lexicons that have noncomplex motor
movements are now being recommended (Dale & Hayden, 2013). These approaches
consider speech production to be a motor skill like any other human (fine) motor
skill; it is learned following repeated practice under certain conditions. The authors
go on to state that a wide range of treatment approaches have been proposed for
CAS, although little rigorous evaluation research has been conducted and no com-
parative studies have been reported. The situation for most other apraxic conditions
is the same.
“Testing” for Apraxia 197
It is difficult to believe that we have reached a permanent state of the art in terms
of treatment for apraxia. It is likely that we will not reach beyond this condition if
we retain the current diagnostic model and its implications. In fact, it is incumbent
upon neuropsychologists, as well as other disciplines, to keep abreast and integrate
information from these other disciplines. As mentioned throughout this volume,
genetics and neuroimaging are fields with increasingly applicable findings. Much
information from neuroimaging has been allowing for an increasing and more com-
prehensive understanding of how systems in the connectome interact and are
impacted by disorders or trauma. Genetics may prove to be not only diagnostic but
to have rehabilitative components. The information provided elsewhere in this vol-
ume is of specific relevance. That is, for example, research into using adult neural
progenitor cells for clinical application, specifically as a source of autologous cell
replacement for neurologic diseases such as Parkinson’s, trauma such as stroke, and
cell-based gene therapy for neurometabolic diseases (Xenia Lojewski, 2014).
“Testing” for Apraxia
Apraxia is diagnosed based on behavioral disorder, and, as a result, behavioral

assessment is required. Specifically, assessment of motor functioning is required.
Currently neuropsychological testing instruments are not designed to pick up
apraxia. They may pick up comorbid conditions, and, from a network perspective,
this would be a great step forward toward demonstrating the interplay of the various
neural networks in a specific individual if the results were understood in this way.
This inability of current neuropsychological tests to assess apraxia should not be
disconcerting to the practicing neuropsychologist. Neuropsychology practice is not
synonymous with neuropsychological tests. It represents knowledge about how the
brain functions to produce behavior, and this functioning can be assessed in many
ways. Standard neurological assessment includes assessment of neural functioning
based on specific behavioral responses to stimuli. We suggest that it would probably
be wise to expand the training of neuropsychologists to include this methodology as
part of their toolkit.
All of this presupposes that it is the neuropsychologist who is doing the observ-
ing of the responses. It should be clear that normative test data, as it is currently
comprised, will not be able to assess for apraxia and that the diagnosis for the fore-
seeable future will be based on the assessment of observed behavior. To observe it,
you have to be there, and by implication, that means that you do not allocate the
assessment process to a technician. We have no wish to wade into the ongoing dis-
cussion about the wisdom of utilizing technicians to collect certain data. We will
report to you that, especially because we are pediatric neuropsychologists, we do
not use them. We passionately believe that the observations we make on the behav-
ior of the children we assess provide a critical and irreplaceable source of informa-
tion. It is our practice to meet the youngsters coming for evaluation in the waiting
room. We walk behind them as they walk toward the clinician’s office. This practice
was how one of us caught the little boy somewhat dragging his right foot, not too
blatantly, but enough for the parents to have reported that they had asked pediatri-
cian about it. Ot the little boy who descending the stairs after the eval was noted to
hold on to the bannister and use his foot to feel the edge of the steps before descend-
ing. In the case of apraxia, perhaps especially apraxia of speech, these observations
are invaluable. As far as assessments for apraxia are concerned, observation of
behavior is the only way that a neuropsychologist, neurologist, speech pathologist,
or occupational therapist is going to do to obtain the data necessary to make the
diagnosis.
To go a step further, we suggest that the clinician conducting the assessment
understands the neural network implications of the behavior that they are observing.
In this way, they are more likely to understand the extended network implications of
what they are seeing and speak authoritatively helpfully about the various comorbid
conditions that might reasonably be expected. And perhaps, that is the clearest point
this volume aspired to.
References
Ahel, I., Rass, U., El-Khamisy, S., Katyal, S., Celements, P., Mckinnon, P., Caldecott, K. W., &
West, S. (2006). The neurodegenerative disease protein aprataxin resolves abortive DNA liga-
tion intermediates. Nature, 443(7112), 713–716. https://doi.org/10.1038/nature05164
AlleyDog.com. (2022). Double dissociation. Retrieved from AlleyDog.com.: https://alleydog.
com/glossary/definition.php?term=Double+Dissociation
ing view. Journal of Speech, Language, and Hearing Research, 63(9), 2952–2994.
Statement). Retrieved from American Speech-Language-Hearing Association. Asha.org/policy
Andres, E. E. (2022). Family based whole exome Analysis of Specific Language Impairment
Sciences, 12, 47.
Armstrong, P. (2010). Bloom’s taxonomy. Retrieved from Vanderbilt University Center for
Teaching. https://cft.vanderbilt.edu/guides-sub-pages/blooms-taxonomy/.
ASHA. (2007). Childhood apraxia of speech technical report. American Speech and Language
Association.
ASHA. (2021). Childhood apraxia of speech. Retrieved from ASHA/Practice Portal/Clinical
Topics/. https://www.asha.org/practice-portal/clinical-topics/childhood-apraxia-of-speech/
Baldassare, A., Lewis, C., Committeri, G., Snyder, A. Z., Romani, G. L., & Corbetta, M. (2012).
Individual variability in functional connectivity predicts performance of a perceptual task.
Proceedings of the National Academy of Science U. S. A., 109, 3516–3521.
Ballard, K., Tourville, J., & Robin, D. (2014, November 3). Behavioral, computational, and neuro-
imaging studies of acquired apraxia of speech. Frontiers in Human Neuroscience. https://doi.
org/10.3389/fnhum.2014.00892
References 199
Bangert, M., Peschel, T., Schlaug, G., Rotte, M., Drescher, D., Hinrichs, H., Heinze, H. J., &
Altenmüller, E. (2006). Shared networks for auditory and motor processing in professional
pianists: Evidence from fMRI conjunction. Neuroimage, 30, 917–926.
43, 118–126.
Batista-García-Ramó, K., & Fernández-Verdecia, C. (2018). What we know about the brain struc-
ture–function relationship. Behavioral Sciences, 8(4), 39. https://doi.org/10.3390/bs8040039
Belanger, S., Duffy, R., & Coelho, D. (1996). The Assessment of limb apraxia: An investigation
brcg.1996.0072
Bernstein, N. (2003). Contemporary studies on the physiology of the neural process. Smysl.
with special reference to addiction. Psychopharmacology (Berl), 221(3), 361–387. https://doi.
org/10.1007/s00213-012-2689-x
Bootsma, J., Caljouw, S., Veldman, M., Maurits, N., Rothwell, J., & Hortobágyi, T. (2021). Neural
correlates of motor skill learning are dependent on both age and task difficulty. Frontiers in
Aging Neuroscience, 22. https://doi.org/10.3389/fnagi.2021.643132
Brazelton, T. B., & Nugent, J. K. (2011). The neonatal behavioral assessment scale. Mac Keith
Press, Cambridge.
individual-level approach to identify cortical connectivity biomarkers in obsessive-compul-
sive disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 4(1), 27–38.
Bunge, M. (1985). From mindless neuroscience and brainless psychology to neuropsychology. In
K. Madsen & L. Mos (Eds.), Annals of theoretical psychology (pp. 115–133). Springer. https://
doi.org/10.1007/978-1-4613-2487-4_7
Cantagallo, A., Maini, M., & Rumiati, R. (2013). The cognitive rehabilitation of limb apraxia in
patients with stroke. Neuropsychological Rehabilitation, 22(3), 473–488.
Carpenter, W. (2016). The RDoC controversy: Alternate paradigm. American Journal of Psychiatry,
173(6), 562–563. https://doi.org/10.1176/appi.ajp.2016.16030347
Chatterjeea, D., Hegdeb, S., & Thaut, M. (2021). Neural plasticity: The substratum of music-
based interventions in neurorehabilitation. NeuroRehabilitation, 48, 155–166. https://doi.
org/10.3233/NRE-208011

181–187.
Association: ASHA.ORG
org/10.1523/JNEUROSCI.6344-11.2012
presentation of at-risk or probable Developmental Coordination Disorder in adults. Research in
Developmental Disabilities., 115, 104010. https://doi.org/10.1016/j.ridd.2021.104010
Coe, B., Witherspoon, K., Rosenfeld, J., & al., e. (2014). Refining analyses of copy number
variation identifies specific genes associated with developmental delay. Nature Genetics, 46,
1053–1017.
Transactions - American Academy of Ophthalmology and Otolaryngology, 56, 579–588.
symptom mapping study in acute stroke patients. Experimental Brain Research. https://doi.
org/10.1007/s00221-021-06224-3
Cousins, M. S. (2003). Developmental coordination impairments in adulthood. Human Movement
Science, 22, 433–459. https://doi.org/10.1016/j.humov.2003.09.003
S0033291719003210
Cuthbert, B., & Insel, T. (2013). Toward the future of psychiatric diagnosis: The seven pillars of
RDoC. BMC Medicine, 11, 126–133.
Dabul, B. (2000). Apraxia battery for adults - Second edition. Pro-ed.
Dale, P., & Hayden, D. (2013). Treating speech subsystems in childhood: Apraxia of speech with
tactual input: The PROMPT approach. American Journal of Speech-Language Pathology, 22,
Dale, P., & Hayden, D. (2014). Treating speech subsystems in childhood apraxia of speech with
tactual input: The PROMPT approach. American Journal of Speech-Language Pathology,
Daniels, S. (2000). Swallowing apraxia: A disorder of the praxis system? Dysphagia, 15, 159–166.
https://doi.org/10.1007/s004550010019
org/10.3109/02699209808985211
org/10.1093/brain/111.5.1173
References 201
brain alterations in motor areas. Acta Paediatrica, 108(9), 1649. https://doi.org/10.1111/
apa.14786
130–136.
Duffy, J. (2006). Apraxia of Speech in degenerative neurologic disease. Aphasiology, 20, 511–527.
Edelman, G., & Gally, J. (2001). Degeneracy and Complexity in Biological Systems. Proceedings
Einspieler, C. P. (2021). Fetal movements; the origin of human behaviour. Developmental Medicine
& Child Neurology, 63(10), 1142–1148.
tive function in children. Frontiers in Psychology. https://doi.org/10.3389/fpsyg.2016.00318
Reviews | Neuroscience, 16, 150–172.
org/10.1177/15459683211001025
org/10.1177/2167702619898814
fneur.2021.562090
Fulceri, F., Grossi, E., Contaldo, A., Narzisa, A., Apicella, F., Parrini, I., et al. (2019). Motor
skills as moderators of core symptoms in autism spectrum disorders: Preliminary data from an
exploratory analysis with artificial neural networks. Frontiers in Psychology, 9, 2683. https://
doi.org/10.3389/fpsyg.2018.02683
org/10.1016/S0166-2236(97)01128-4

org/10.1016/B978-0-444-63622-5.00016-4
Communication, 9, 4233. https://doi.org/10.1038/s41467-018-06560-z
Galvan, A. (2010). Neural plasticity of development and learning. Human Brain Mapping, 31(6),
879–890. https://doi.org/10.1002/hbm.21029
Ganguly, J., & Jog, M. (2020). Tauopathy and movement disorders—unveiling the chameleons and
mimics. Frontiers in Neurology: Movement Disorders, 11, 599384. https://doi.org/10.3389/
fneur.2020.599384
Disorganization of anatomical connectivity in obsessive compulsive disorder: A multi-param-
eter diffusion tensor imaging study in a subpopulation of patients. Neurobiology of Disease,
37(2), 468–476. https://doi.org/10.1016/j.nbd.2009.11.003
Geuze, R., Shoemaker, M., & Smits-Engelsman, B. (2015). Clinical and research criteria for devel-
opmental coordination disorder—Should they be one and the same? Current Developmental
Disorders Reports, 2, 127–130. https://doi.org/10.1007/s40474-015-0043-9
Gillon, G., & Moriarty, B. (2007). Childhood apraxia of speech: Children at risk for persistent
reading and spelling disorder. Seminars in Speech and Language, 28(1), 48–57. https://doi.
org/10.1055/s-2007-967929
the National Academy of Science USA, 99, 7699–7704.
Gomez, M., McCabe, P., & Purcell, A. (2022). A survey of the clinical management of childhood
apraxia of speech in the United States and Canada. Journal of Communication Disorders, 96,
106193. https://doi.org/10.1016/j.jcomdis.2022.106193
Gonzales-Rothi, L., & Heilman, K. (1996). Liepmann (1900 and 1905): A definition of apraxia and
a model of praxis. In I. C. Code, Y. Joanette, A. Roch- Lecours, & C. Wallesch (Eds.), Classic
Green, D. C. (2008). Does subtype of developmental coordination disorder Count: Is there a dif-
ferential effect on outcome following intervention? Human Movement Science. https://doi.
org/10.1016/j.humov.2008.02.009
Grissmer, G., Grimm, K., Aiyer, S., Murrah, W., & Steele, J. (2010). Fine motor skills and early
comprehension of the world: Two new school readiness indicators. Developmental Psychology,
46(5), 1008–1017. https://doi.org/10.1037/a0020104
Speech and Language, 5, 1–49.
tification and intervention: An expert white paper commodus. Learning Disability Quarterly,
33(3), 223–238.
References 203
disease: Implications for corticostriate involvement. Neuropsychologia., 41, 614–621.
Handiru, V., Alivar, A., Hoxa, A., Saleh, S., Suviseshamuthu, E. S., Yue, G. H., & Allexandre,
Hayden, D., Eigen, J., Walker, A., & Olsen, L. (2010). Prompt: A tactually grounded model for
the treatment of childhood in speech production disorders. In L. Williams, S. McCleod, &
R. McCauley (Eds.), Treatment for speech sound disorders in children (pp. 453–474). Brooks.
Hazy, T. F. (2007). Towards an executive without a homunculus: computational models of the
prefrontal cortex/basal ganglia system. Philosophical Transactions of the Royal Society B:
Biological Sciences, 362, 1601–1613.
HealthLine. (2022). What’s the treatment for apraxia of speech? Retrieved from Healthline:
https://www.healthline.com/health/apraxia-of-speech#treatment
342–346.
Heilman, K., Maher, L., Greenwald, M., & Rothi, L. (1997). Conceptual apraxia from lateralized
lesions. Neurology, 49(2), 457. https://doi.org/10.1212/WNL.49.2.457
Hofmann, S., Curtiss, J., & McNally, R. (2016). A complex network perspective on clini-
cal science. Perspectives in Psychological Science, 11(5), 597–605. https://doi.
org/10.1177/1745691616639283
mammalian brain. National Review Neuroscience., 10, 647–658.
Science USA, 106, 2035–2040.
Hua, J. W. (2022). Early motor milestones in infancy and later motor impairments: A population-
based data linkage study. Psychiatry. https://doi.org/10.3389/fpsyt.2022.809181
Huth, A., De Heer, W. A., Griffiths, T. L., Theunissen, F. E., & Gallant, J. L. (2016). Natural speech
reveals the semantic maps that tile human cerebral cortex. Nature, 532(7600), 453–459. https://
doi.org/10.1038/nature17637
Insel, T. (2014). The NIMH Research Domain Criteria (RDoC) project: Precision medicine for
psychiatry. The American Journal of Psychiatry, 171(4), 395–397. https://doi.org/10.1176/
appi.ajp.2014.14020138
Iuzzini, J. (2012a). Inconsistency of speech in children with childhood apraxia of speech, phono-
logical disorders and typical speech. Indiana University.
Iuzzini, J. (2012b). Inconsistency of speech in children with childhood apraxia of speech, phono-
Iuzzini-Seigel, J. M. (2017). Speech assessment in children with childhood apraxia of speech. In
Perspectives of the ASHA Special Interest Groups (pp. 47–60). American Speech Language
Iuzzini-Siegel, J. H. (2017). Speech inconsistency in children with childhood apraxia of speech,
language impairment and speech delay: Depends on the stimuli. Journal of Speech, Language,
and Hearing Research, 60, 1194–1220.
Johansen-Berg, H., Dawes, H., Guy, C., Smith, S. M., Wade, D. T., & Matthews, P. M. (2002).
Correlation between motor improvements and altered fMRI activity after rehabilitative therapy.
Brain, 125, 2731–2742. https://doi.org/10.1093/brain/awf282
Johansson, B. (2004). Functional and cellular effects of environmental enrichment after experi-
mental brain infarcts. Restorative Neuroscience, 22, 163–174.
coisb.2017.04.006
Koziol, L. B. (2009). Subcortical structures and cognition. Springe.
uation and assessment. Springer.
s12311-011-0321-y
Kozubski, W., Ong, K., Waleszczyk, W., Zabel, M., & Dorszewska, J. (2021). Molecular factors
mediating neural cell plasticity changes in dementia brain diseases. Neural Plasticity, 2021,
Laffin, J., Raca, G., Jackson, C., Strand, E., Jakielski, K., & Shriberg, L. (2012). Novel candidate
genes and regions for childhood apraxia of speech identified by array comparative genomic
hybridization. Genetic Medecine, 14(11), 928–936. https://doi.org/10.1038/gim.2012.72
Langevin, L. M. (2015). Distinct patterns of cortical thinning in concurrent motor and attention
disorders. Developmental Medicine and Child Neurology, 3, 257–264.
Latash, M. (2008). Evolution of motor control: From reflexes and motor programs to the equilib-
rium-point hypothesis. Journal of Human Kinetics, 19, 3–24.
Levelt, C., Schiller, N., & Levelt, W. (1999). A developmental grammar for syllable structure in the
production of child language. Brain and language, 68, 201–299.
Lewis, B., Freebairn, L., Hansen, A., Iyengar, S., & Taylor, H. (2004). School-age follow up
of children with childhood apraxia of speech. Language, Speech, and Hearing Services in
Schools, 35, 122–140.
neuropsychology’s past and the impact. Advances in Medical Psychotherapy, 8, 59–78.
References 205
Maasen, B. (2002). Issues contrasting adult acquired versus developmental apraxia of speech.
Semin Speech Language, 23, 257–266.
Maassen, B. (2015). Developmental models of childhood apraxia of speech. In R. Barr &
Maleki, S., Chye, Y., Zhang, X., Parkes, L., Chamberlain, S., FFontenelle, L., et al. (2020). Neural
University Press.
Science, 110–124.
drc-20352051
tioning in men receiving androgen deprivation therapy for prostate cancer: A systematic review
and meta-analysis. Supportive Care in Cancer, 22(8), 2271–2280. https://doi.org/10.1007/
s00520-014-2285-1
McLaren, N. (2010). The DSM-V project: Bad science produces bad psychiatry. Ethical Human
Psychology and Psychiatry, 12(3), 189–199. https://doi.org/10.1891/1559-4343.12.3.189
Trends in Cognitive Sciences, 17(12), 627–640. https://doi.org/10.1016/j.tics.2013.09.015
Merceron-Martinez, D., Ibaceta-Gonzalez, C., Salazr, C., Almaguer-Melian, W., Bergado-Rosado,
J., & Palacios, A. (2021). Alzheimer’s disease, neural plasticity, and functional recovery.
Journal of Alzheimer’s Disease, 82(s1), S37–S50. https://doi.org/10.3233/JAD-201178
brcg.1999.1099
Mihailidis, A., Boger, J. N., Craig, T., & Hoey, J. (2006). The COACH prompting systems to assist
older adults with dementia through handwashing: An efficacy study. BMC Geriatrics, 8, 28.
http://www.biomedcentral.com. https://doi.org/10.1186/1471-2318-8-28
apraxia of speech. American Journal of Speech Language Pathology, 28, 1432–1447.
Mirabella, G. D. (2017). Developmental coordination disorder affects the processing of action relate
verbs. Frontiers in Human Neuroscience, 10, 661. https://doi.org/10.3389/fnhum.2016.00661
Missiuna, C., Rivard, L., & Bartlett, D. (2003). Early identification and risk management of children
with developmental coordination disorder. Pediatric Physical Therapy: Spring, 15(1), 32–38.
Molloy, J., & Jagoe, C. (2019). Use of diverse diagnostic criteria for acquired apraxia of speech:
A scoping review. International Journal of Language and Communication Disorders, 54(6),
875–893. https://doi.org/10.1111/1460-6984.12494
0.1080/13554794.2016.1172645
Mountford, H. B. (2022). The genetic and molecular basis of developmental language.
Children, 9, 586.
Murray, E., McCabe, P., & Ballard, K. (2015a). Differential diagnosis of children with suspected
childhood apraxia of speech. Journal of Speech, Language, and Hearing Research, 58(1),
43–60. https://doi.org/10.1044/2014_JSLHR-S-12-0358
Murray, E., McCabe, P., & Ballard, K. J. (2015b). A randomized controlled trial for children
org/10.1044/2015_JSLHR-S-13-0179
nih.gov/
National Institute of Mental Health. (2022). Motor actions. Retrieved from National Institute
of mental Health National Research Design Criteria Initiative: https://www.nimh.nih.gov/
research/research-funded-by-nimh/rdoc/constructs/motor-actions
Naxarro, X. (2009). Chapter 27 Neural plasticity after nerve injury and regeneration. International
Review of Neurobiology, 87, 483–505. https://doi.org/10.1016/S0074-7742(09)87027-X
Newbury, D. W. (2009). CMIP and ATP2C2 Modulate phonological short term memory in lan-
guage impairment. The American Journal of Human Genetics, 85, 264–272.
Rare Disorders: https://rarediseases.org/rare-diseases/ocular-motor-apraxia-cogan-type/
Brain, 115(Pt 4), 1061–1071.
Ogar, J., Slama, H., Dronkers, N., Amici, S., & Gorno-Tempini, M. (2005). Apraxia of Speech: An
Ogar, J., Willock, S., Baldo, J., Wilkins, D., Ludy, C., & Dronkers, N. (2006). Clinical and ana-
tomical correlates of apraxia of speech. Brain and Language, 97(3), 343–350. https://doi.
org/10.1016/j.bandl.2006.01.008Get
and Associated Disorders, 21, S23–S30.
an emphasis on the implications for white matter degeneration. Journal of Neurotrauma, 21(6),
Reviews. https://doi.org/10.1089/0897715041269641, online.
References 207
Pazzaglia, M., Pizzamiglio, L., Pes, E., & Aglioti, S. (2008a). The sound of actions in apraxia.
Piek, J. P., Dawson, L., Smith, L. M., & Gasson, N. (2008). The role of early fine and gross motor
development on later motor and cognitive ability. Human Movement Science, 27(5), 668–681.
Pinson, A. X. (2022). Human TKTL1 implies greater neurogenesis in frontal neocortex of modern
humans than Neanderthals. Science, 377, eabl6422. https://doi.org/10.1126/science.abl6422
on Speech and Orofacial Disorders. https://doi.org/10.1044/ssod19.1.44
Ramus, F. (2003). Developmental Dyslexia: Specific phonological deficit or general sensorimotor
dysfunction. Current Opinion in Neurobiology, 13, 212–218.
Renzi, D. E., Faglioni, P., & Sorgato, P. (1982). Modality specific and supramodal mechanisms of
Riecker, A., Mathiak, K., Wildgruber, D., Erb, M., Hertfich, I., Grodd, W., & Ackermann, H. (2005).
fMRI reveals two distinct cerebral networks subserving speech motor control. Neurology, 64,
700–706.
45, 489–493.
Rosenzopf, H., Wiesen, D., Basilakos, A., Yourganov, G., Bonilha, L., Fridriksson, J., et al. (2022).
braincomms/fcac004
Rosenzoph, H., Weisen, D., Basilakos, A., Yourganov, G., Bonilha, L., Rorden, C., et al. (2020,
April 17). Mapping the Human Praxis Network: An investigation of white matter disconnec-
tion in limb apraxia. Retrieved from bioRxiv.org: https://doi.org/10.1101/2020.04.14.041442
Salo, V. F. (2019). The role of the motor stem in action understanding and communication:
390–401.
Sato, J. R., Biazoli, C. E., Jr., Zugman, A., Pan, P. M., Bueno, A. P. A., Moura, L. M., et al. (2021).
Long-term stability of the cortical volumetric profile and the functional human connectome
throughout childhood and adolescence. European Journal of Neuroscience, 54, 6187–6201.
https://doi.org/10.1111/ejn.15435
77, 826–852.
Frontiers in Pediatrics. https://doi.org/10.3389/fped.2020.599633
Sharma, V., & Wong, L. (2022). Middle cerebral artery disease. In J. Grotta, G. Albers,
J. Broderick, S. Kasner, R. Sacco, A. Day, et al. (Eds.), Stroke (Seventh edition) patho-
physiology, diagnosis, and management (pp. 317–346). Elsevier. https://doi.org/10.1016/
B978-0-323-69424-7.00024-7
Sharma, N., Classen, J., & Cohen, L. (2013). Neural plasticity and its contribution to func-
tional recovery. Handbook of Clinical Neurology, 110, 3–12. https://doi.org/10.1016/
B978-0-444-52901-5.00001-0
707–736.
Shriberg, L. D., Fourakis, M., Hall, S. D., Karlsson, H. B., Lohmeier, H. L., McSweeny, J. L.,
Potter, N. L., Scheer-Cohen, A. R., Strand, E. A., Tilkens, C. M., & Wilson, D. L. (2010).
Extensions to the speech disorders classification system (SDCS). Clinical Linguistics &
Phonetics, 24, 795–824.
Sonuga-Barke, E. (2003). The dual pathway model of AD/HD: An elaboration of neuro-develop-
mental characteristics. Neuroscience Biobehavioral Review, 27, 593–604.
Evidence for the dissociation of timing, inhibitory and delay-related impairments in Attention
Deficit/Hyperactivity disorder. Journal of Child and Adolescent Psychiatry, 49, 345–355.
https://doi.org/10.1016/j.jaac.2009.12.018
the human brain. PLOS Computational Biology. https://doi.org/10.1371/journal.pcbi.0010042
work. Wurr.
Steward, M., Sridhar, A., & Meyer, J. (2013). Neural regeneration. Current Topics in Microbiology
and Immunology, 367, 153–191. https://doi.org/10.1007/82_2012_302
Stoll, G., & Muller, H. (1998). Nerve injury, axonal degeneration and neural regeneration: Basic
insights. Brain Pathology, 9, 313–325. https://doi.org/10.1111/j.1750-3639.1999.tb00229.x
Sweatt, D. (2016). Neural Plasticity and Behavior- sixty years of conceptual advances. Journal of
Neurochemistry, 139(2), 179–199. https://doi.org/10.1111/jnc.13580
Szczepanski, S., & Knight, R. (2014). Insights into human behavior from lesions to the prefrontal
cortex. Neuron., 83(5), 1002–1018. https://doi.org/10.1016/j.neuron.2014.08.011
Disabilities., 35, 2644–2650.
Tal-Saba, M. Z. (2012). The functional profile of young adults with suspected developmental coor-
dination disorder (DCD). Research in Developmental Disabilities, 33, 2193–2202. https://doi.
org/10.1016/j.ridd.2012.06.005
developmental speech disorders. Folia Phoniatrica et Logopaedica, 71(5–6), 216–227.
References 209
with Childhood Apraxia of Speech. Disability and Rehabilitation, 31(2), 94–102. https://doi.
org/10.1080/09638280701795030
The Health Jade Team. (2022). Brain plasticity. Retrieved from Health Jade: https://healthjade.
net/brain-plasticity/
The Medical Dictionary. (2021). Apraxia. Retrieved from The Medical Dictionary: http://the-med-
ical-dictionary.com/apraxia_article_2.htm
S095457941800072X
Trigilio, M. (2013, December 3). A Smithsonian dilemma: Pure scientific research, “A thousand
applications,” or both? Retrieved from National Museum of American History. https://ameri-
canhistory.si.edu/blog/2013/12/a-smithsonian-dilemma-pure-scientific-research-a-thousand-
applications-or-both.html
Van Der Merwe, A. (2020). New perspectives on speech motor planning and programming in the
context of the four-level model and its implications for understanding the pathophysiology
underlying apraxia of speech and other motor speech disorders. Aphasiology. https://doi.org/1
0.1080/02687038.2020.1765306, online.
Development, 40, 77–84.
Waring, R., & Knight, R. (2013). How should children with speech sound disorders be classi-
fied? A review and critical evaluation of current classification systems. Journal of Language
& Communication Disorders, 48(1), 25–40. https://doi.org/10.1111/j.1460-6984.2012.00195.x
Wasserman, T., & Wasserman, L. (2016). Depathologizing Psychopathology. Springer.
ligence. Applied Neuropsychology Child, 6(3), 228–236. https://doi.org/10.1080/2162296
5.2017.1317489
Wasserman, T., & Wasserman, L. (2020). Neural network series: Motivation, effort and the neural
network system. Springer Nature.
Child Neurology, 49(12), 920–925.
org/10.1093/brain/106.2.391
Weintraub, S. (2000b). Neuropsychological assessment of mental state. In M. Mesulam (Ed.),
neuron.2016.12.013
West, C., Bowen, A., Hesketh, A., & Vail, A. (2008). Interventions for motor apraxia follow-
ing stroke. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.
CD004132.pub2
Wielock, T., & Nikolich, K. (2006). Mechanisms of neural plasticity following brain injury.
Current Opinion in Neurobiology, 2(16), 1–7.
Wilson, P. M. (1998). information processing deficits associated with developmental coordination
disorder: A meta-analysis of research findings. Journal of Child Psychology, 39, 829–840.
Worthington, A. (2016). Treatments and technologies in the rehabilitation of apraxia and action
disorganisation syndrome: A review. Neurorehabilitation, 39(1), 163–174. https://doi.
org/10.3233/NRE-161348
Xenia Lojewski, L. X.-B.-E. (2014). Human adult white matter progenitor cells are multipotent
neuroprogenitors similar to adult hippocampal progenitors. Stem Cells Translational Medicine,
3(4), 458–469.
ppendix I: Network Properties Breakdown
A
of Ideational Apraxia
Research Domain Criteria
The following is extrapolated from the Research Domain Initiative of the National
Institute of Mental Health (National Institute of Mental Health, 2022). It is pre-
sented here to give the reader an idea of the complexity of networks and interactions
and the potential magnitude of effect a disruption of one or several components can
produce in one type of apraxia, in this example, an ideational apraxia.
Ideational Apraxia
Type of Element Behavior
Domain Sensorimotor Systems

Sensorimotor systems are primarily responsible for the control and execution of
motor behaviors and their refinement during learning and development.
Construct Motor Actions
A multifaceted construct is comprised of the processes that must be engaged dur-
ing the planning and execution of a motor action in a context-appropriate manner.
Component processes include action planning and selection, sensorimotor dynam-
ics, initiation, execution, and inhibition and termination. Of note, these processes
will often be recruited in conjunction with motivational processes described in other
domains, as when appetitive motivations drive approach behaviors. This construct
explicitly includes the modulation and refinement of actions during development
© The Editor(s) (if applicable) and The Author(s), under exclusive license to 211
Springer Nature Switzerland AG 2023
212 Appendix I: Network Properties Breakdown of Ideational Apraxia
and learning. The list of subconstructs is not intended to imply a specific order or
sequence.
Subconstruct Action Planning and Selection
Processes whereby an individual engages a plan for spatial and temporal compo-
nents of possible purposeful movements, which match internal and external con-
straints to achieve a goal. This may also include cost-benefit calculations in the
development and selection of motor plans.
Circuits Involved
Inferior Parietal Cortex
Posterior Parietal Cortex: Goal Selection

Goal selection refers to the cognitive process of choosing among potential out-
comes, actions, or behaviors and can be considered as a component process of cog-
nitive control.
Goal updating involves refreshing the cognitive content related to specific poten-
tial outcomes, actions, or behaviors and can be considered a component process of
cognitive control.
Circuits Involved in Goal Selection
Frontopolar/Anterior LPFC (BA10)
Inhibition of the Default Mode Network (DMN)
The DMN is a set of brain regions that exhibit strong low-frequency oscillations
coherent during resting state and is thought to be activated when individuals are
focused on their internal mental state processes, such as self-referential process-
ing, interoception, autobiographical memory retrieval, or imagining future events.
Premotor Cortex
The premotor cortex is an area of the motor cortex lying within the frontal lobe of
the brain just anterior to the primary motor cortex. The premotor cortex, as might be
expected, is involved in a number of apraxic conditions including conceptual
apraxia, ideational apraxia, limb kinetic apraxia, and ideomotor apraxia. Within it
lies Broca’s area a region in the frontal lobe of the dominant hemisphere, usually the
left, of the brain with functions linked to speech production.
Appendix I: Network Properties Breakdown of Ideational Apraxia 213
Superior Temporal Sulcus
Involved in motor apraxic conditions such as conceptual apraxia, ideational apraxia,

limb kinetic apraxia, and ideomotor apraxia. This circuit contains mirror neurons
which are involved in the sense that one is initiating, executing, and in control of
their volitional actions and their sensory consequences and the sense that one’s body
or body parts belong to oneself. This may include the comparison of the predicted
and actual sensory consequences of one’s action, awareness of the intention to
move, temporal binding of self-generated action and their immediate effects, and
attenuation of sensory consequences of self-generated actions. These mirror neu-
rons are components of numerous other circuits.
Supplementary Motor Area
Participates in the control of processes involved in the initiation of a selected action

plan, which often includes timing of movement onset. Associated circuits include
the basal ganglia and the dorsal cingulate.
Construct: Initiation
Processes involved in the initiation of a selected action plan; this may include tim-
ing of movement onset.
Circuits Involved
Basal Ganglia
The basal ganglia are a group of structures linked to the thalamus in the base of
the brain and involved in coordination of movement. The main components of the
basal ganglia are the striatum, consisting of both the dorsal striatum (caudate
nucleus and putamen) and the ventral striatum (nucleus accumbens and olfactory
tubercle), the globus pallidus, the ventral pallidum, the substantia nigra, and the
subthalamic nucleus.
Processes involved in the specification/parameterization of an action plan and
program based on integration of internal or external information, such as sensations
and urges and modeling of body dynamics. This process is continuously and itera-
tively refined via sensory information and reward-reinforced information. This cir-
cuit is also involved in processes involved in the inhibition of motor plans, either
before or after an action is initiated, and the sense that a motor plan has been suc-
cessfully completed. The inhibition subconstruct is commonly operationalized as
motor response inhibition and has conceptual overlaps with the inhibition/suppres-
sion subconstruct of the cognitive control construct within the cognitive sys-
tems domain.
Dorsal Cingulate
Also involved with the initiation of a selected action plan.
Construct: Execution
These are processes involved in the actualization and adaptation of action

implementation.
Circuits Involved
Efferent and Afferent Spinal and Peripheral Pathways
Afferent and efferent pathways are two types of nerves in the peripheral nervous
system. Afferent pathways bring information from the body to the central nervous
system, and efferent pathways bring information from the central nervous system to
the body.
Motor Cortex
The motor cortex is an area within the cerebral cortex of the brain that is involved in
the planning, control, and execution of voluntary movements. The motor cortex is
often divided into the primary motor cortex and the nonprimary motor cortex. The
primary motor cortex is critical for initiating motor movements.
Construct: Inhibition and Execution
Processes involved in the inhibition of motor plans, either before or after an action
is initiated, and the sense that a motor plan has been successfully completed. The
inhibition subconstruct is commonly operationalized as motor response inhibition
and has conceptual overlaps with the inhibition/suppression subconstruct of the
cognitive control construct within the cognitive systems domain.
Circuits Involved
Basal Ganglia
Previously described
Appendix I: Network Properties Breakdown of Ideational Apraxia 215
Supplementary Motor Area
Previously described
Posterior Cingulate Gyrus
A central node of the default mode network (DMN), it is a set of brain regions show-
ing strongly correlated neural activity and a reliable deactivation in activity during
many cognitive tasks.
Inferior Frontal Gyrus
The inferior frontal gyrus is a part of the articulatory network involved in motor
syllable programs. The articulatory network also contains the premotor cortex and
the anterior insula. These areas are interrelated but have specific functions in speech
comprehension and production. The articulatory network acts mostly when the
vocal tract moves to produce syllables. The inferior frontal gyrus contains the
Broca’s area, which is involved in language processing and speech production.
Dorsolateral Prefrontal Cortex
The dorsolateral prefrontal cortex has been found to be involved in superordinate

control functions for various cognitive tasks such as decision-making, novelty
detection, working memory, conflict management, mood regulation, theory of mind
processing, and timing.
Inferior Parietal Cortex
The inferior parietal lobe (IPL) is a key neural substrate underlying diverse mental
processes, from basic attention to language and social cognition, that define human
interactions.
Lateral Premotor Cortex
Contributes to the overall control of movement

Medial Prefrontal Cortex
The medial prefrontal cortex plays an important regulatory role in numerous cogni-
tive functions, including attention, inhibitory control, habit formation and working,
and spatial or long-term memory.
Things that are unclear are the following:
1. It is unclear whether a disruption of any of the component networks would pro-
duce the same outcome.
2. It is unclear as to just what combination of networks must be disrupted in order
to produce an ideational apraxia.
3. Can the same network disruption that produces ideational apraxia also produce
something else depending on where in the network configuration the disruption
occurs? This is not clear.
4. It is unclear whether multiple sets of networks that can be disrupted would pro-
duce the same outcome.
5. As each of the networks outlined above participates in other functional behaviors
and outcomes, it seems likely that disruptions of those networks would also pro-
duce comorbid conditions. This area of research is poorly investigated and
resultingly unclear. It seems logical to suggest that if the initiation networks are
dysfunctional, any downstream behavior or associated network would be
impacted.
Index
A D
Acquired apraxia, vi–viii, 1, 4, 5, 17, 18, 41, Developmental motor coordination disorder, 5
42, 45, 68, 72, 148, 149, 186 Diagnosis, vi, 1, 2, 5, 8, 9, 19, 30, 31, 33,
Apraxia, v, 35, 63, 79, 97, 111, 139, 161 41–43, 59, 82, 83, 87, 89, 99–105,
Apraxia of speech, viii, 1, 8, 17–19, 25, 59, 115, 125, 126, 131, 132, 142, 144,
63, 68, 98–100, 102, 103, 116, 117, 145, 147, 149, 184–186,
148, 149, 162, 163, 184, 186, 193, 188–191, 194–198
194, 198 Domain, 17, 28, 37, 42, 51, 64, 69, 71, 83,
Arcuate fasciculus (AF), 73, 112–114, 120 86–88, 94, 103, 108, 117, 121, 126,
128, 130, 131, 139–149, 164, 187,
190, 211, 213, 214
B Double duty neuron, 10, 11, 57
Basal ganglia, 7, 15, 32, 46, 56, 57, 59, 60, Dual pathway model, 118–120, 142
65–68, 72, 75, 84, 86, 87, 115, 121, Dyslexia, 106, 107, 115, 124, 132, 188,
122, 125–130, 142, 143, 184, 192, 193
213, 214 Dyspraxia, 2, 4–7, 21, 31, 80, 91, 94, 133, 163
Buccofacial apraxia, 11, 13, 15, 58
E
C Early motor networks, 79
Cerebellum, 12, 29, 43, 45, 66, 84, 86, 87, 91, Error prediction, 122–124
108, 122–125, 127, 128
Cerebral hemispheres, 4, 58, 73, 133
Child development, 86, 90, 92, 93, 131 F
Childhood apraxia of speech (CAS), 1, 4–6, 8, FOXP2/7q31.1 deletion, 30
9, 18, 19, 25, 29–31, 40, 41, 59–61,
67, 68, 71, 80, 84, 87, 97–109,
111–135, 141, 162, 163, 169, 183, G
184, 187, 188, 194–196 The gene APTX, 15, 28, 29
Conceptual apraxia, 11–13, 57, 71, 212, 213
Connectome, 35–37, 39–44, 53, 60, 61, 64, 82,
83, 86, 101, 114–118, 121, 189, 197 H
Constructional apraxia, 11, 13, 14, 58, 59 Hubs, 39, 51–54, 130
Cortico-subcortical networks, 67
© The Editor(s) (if applicable) and The Author(s), under exclusive license to 217
Springer Nature Switzerland AG 2023
218 Index
I Node, 36, 38, 39, 41, 43, 49–55, 64, 68, 115,
Ideational apraxia, 3, 9, 11–13, 19, 21, 32, 57, 189, 215
58, 71, 147, 211–216
Ideomotor apraxia, 3, 11, 12, 16, 19, 21, 32,
56, 57, 70, 212, 213 O
Oculomotor apraxia, 7, 11, 14, 15, 28, 29
L
Limb kinetic apraxia (LKA), 11, 212, 213 P
Pathognomonic sign, 85, 89, 93, 100, 120,
131, 132, 146–148
M Plasticity, vii, 39, 40, 45, 46, 56, 85, 161–171,
Math, 112, 115, 116, 187, 193 185, 193, 196
Motor coordination disorder, 21, 40, 88, 101 Praxis, 3, 7, 12, 20, 32, 46, 56, 71, 75, 76, 89,
Motor speech, 8, 17, 26, 103, 109, 111, 112, 148, 184, 186
118–119, 121–123, 164 Prediction error, 122, 123
Procedural memory, 125–128
Progressive apraxia of speech (PAOS), 26–28
N
Neural networks, v–vii, 1, 2, 6, 18, 20, 21, 25,
27, 35, 36, 38, 39, 42, 46, 47, R
51–52, 56, 59, 60, 64, 68, 72, 75, Research domain criteria (RDoC), 190,
76, 79–81, 85–87, 91, 97, 99, 109, 191, 211
111, 114, 115, 120, 142, 144, 146,
166, 168, 170, 183–186, 188, 189,
193, 197, 198 S
Neural node, 50, 51 Scaling, 39
Neural pathway, 42, 49, 56, 60, 64, 67, 68, 74, Sensory motor, 70, 80, 106, 119, 121, 122, 124
79, 83, 85, 86, 88, 90, 101, 116, Spelling, 18, 108, 118, 187, 188, 193
120, 126, 131, 144
Neurodevelopmental disorder, 1, 5, 9, 25, 28,
29, 31, 67, 80, 84, 87, 100, 188, 195 V
Neuropsychological assessment, 94, 107, Verbal apraxia, 11, 16, 58, 71, 73, 101, 184
139–149, 188 Verbal dyspraxia, 98, 99, 102
Neuropsychological testing, 79, 139, 142,
145, 197

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Neural Network Model: Applications and Implications

Apraxia: The Neural

ISBN 978-3-031-24104-8 ISBN 978-3-031-24105-5 (eBook)

Would the idea of cognitive reserve be an important consideration in adult

1 Apraxia, Dyspraxia, and Motor Coordination Disorders:

5 I t Is Not Only Apraxia �������������������������������������������������������������������������� 63

8 Neural Network Components of Childhood Apraxia of Speech

Mechanisms of Neural Plasticity ������������������������������������������������������������ 167

Appendix I: Network Properties Breakdown of Ideational Apraxia�������� 211

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 1

History and Current State of the Study of Apraxia

Definitional Definitions and Confounds in Apraxia Research

Faglioni, 1999). This definition represents a good example of a highly “confined”

This led to the following definition: “Childhood Apraxia of Speech (CAS) is a

Hypothetical Neural Mechanisms of Apraxia

Logically, apraxia is likely not a movement disorder with a solitary neurological or

Double-Duty Neurons and Apraxia

information is unified. Research demonstrates that, at least in monkeys, performing

Recognized Apraxia Conditions

According to Liepmann (Liepmann & Mass, 1907), patients with limb-kinetic

Ideomotor apraxia (IMA) is a disorder characterized by deficits in properly per-

Conceptual apraxia is the cousin of ideational apraxia. They both correspond to a

Historically, ideational apraxia was defined as a disturbance in the conceptual orga-

gesture discrimination and matching tasks. Ideational apraxia is regularly confused

Buccofacial apraxia (also called facial-oral apraxia) is characterized by the inabil-

Constructional apraxia is defined as an inability or difficulty to build, assemble, or

Fig. 1.1 Severe

In Cogan-type ocular motor apraxia, there is a defect in side-to-side (horizontal)

Ataxia-oculomotor apraxia type 1 (AOA1) in most instances has an onset of symp-

Ataxia-Oculomotor Apraxia Type 2 (AOA2)

Orofacial apraxia (Gross & Grossman, Update on Apraxia, 2008) is characterized

Verbal apraxia is mainly described as an inability to respond properly to verbal

Other Apraxia Conditions

Verbal–Motor Dissociation Apraxia

lesions represents a disturbance distinct from elementary motor or sensory

Acquired Apraxia of Speech (AOS)

Newer Models of Speech Production

to a code amenable to a motor system tend to obscure the understanding of acquired

Childhood Apraxia of Speech

Childhood apraxia of speech (CAS) is a speech disorder, of presumed organic etiol-

Neuropsychological Models of Apraxia

Dual-component models of apraxic conditions have been proposed. Heilman and

Dual-Stream Models and Types of Apraxia

Apraxia can be caused by congenital or idiopathic means, by trauma such as stroke,

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 25

Genetically Based Apraxia

Non-stroke-Related Progressive Apraxia of Speech

Apraxia Associated with Neurodevelopmental Disorders

Looking at white matter implications of neurodegenerative disease can provide a

Childhood Apraxia of Speech (CAS)

Chromosomal deletions and truncating mutations in SETBP1 are associated with

Microdeletions of BCL11A have been reported in association with CAS, dysarthria,

 ANSL1 or 17q21.31 Microdeletion Koolen-De Vries

ELKS/ERC1 and 12p13.33 Deletion

The 16p11.2 is a relatively common deletion of about 1 in 5000 individuals. It can

Corticobasal Degeneration (CBD)

Ideomotor apraxia occurs in corticobasal degeneration (CBD), a neurodegenerative

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 35

The Connectome and Neural Networks

1 Apraxia, Dyspraxia, and Motor Coordination Disorders:

5 I t Is Not Only Apraxia �� 63

8 Neural Network Components of Childhood Apraxia of Speech

Mechanisms of Neural Plasticity �� 167

Appendix I: Network Properties Breakdown of Ideational Apraxia�� 211

History and Current State of the Study of Apraxia

Definitional Definitions and Confounds in Apraxia Research

Hypothetical Neural Mechanisms of Apraxia

Double-Duty Neurons and Apraxia

Recognized Apraxia Conditions

Ataxia-Oculomotor Apraxia Type 2 (AOA2)

Other Apraxia Conditions

Verbal–Motor Dissociation Apraxia

Acquired Apraxia of Speech (AOS)

Newer Models of Speech Production

Childhood Apraxia of Speech

Neuropsychological Models of Apraxia

Dual-Stream Models and Types of Apraxia

Genetically Based Apraxia

Non-stroke-Related Progressive Apraxia of Speech

Apraxia Associated with Neurodevelopmental Disorders

Childhood Apraxia of Speech (CAS)

ANSL1 or 17q21.31 Microdeletion Koolen-De Vries

ELKS/ERC1 and 12p13.33 Deletion

Corticobasal Degeneration (CBD)

The Connectome and Neural Networks

The Importance of Understanding the Connectome

Networks and Connectomics

Challenges to Understanding the Connectome

The Relationship of Connectome to Clinical Diagnosis

Neural Response to the Disruption of Pathway Function

The Neural Networks of Apraxia

Apraxia and Neural Pathways

What Is the Neural Population Level?

I ntegrating Neural Populations into a Coherent

Brain connectivity: description of structural or functional connectivity

Module: a group of nodes that maintain a large number of

ow the Neural Substrate Enables Integration of Distributed

What Is the Interface of Network Structure and Praxis?

eural Pathways and Structures Implicated

Oral Motor and Verbal Apraxia

Childhood Apraxia of Speech

he Structural Beginnings of Brain-Based Behavioral

The Development of Networks

The Cerebral Cortex and Basal Ganglia

eural Pathways Are Recruited for Multiple

Disruption of Early Domains Are Not Just Domain Specific

Limb-Kinetic Apraxia and Associated Conditions

Ideomotor Apraxia and Associated Conditions

Conceptual Apraxia and Associated Conditions

Ideational Apraxia and Related Conditions

Oral Motor and Verbal Apraxia and Related Conditions

Apraxic Conditions Rarely Occur in Isolation

White Matter Degeneration Following Injury

Neural Network Damage Models