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Final Paper
A Neurodevelopmental Model of Autism
Developmental Neurobiology
HDP 3286
Dayna Morris
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A well accepted theory of autism is that of executive dysfunction which makes an explicit
link to deficits in frontal lobe functioning. However, there is emerging evidence suggestive of
impairments in more basic, low level neurological structures and processes which leads one to
question the directionality and development of neurological deficits. Since abnormalities in more
primitive and early developing structures would undoubtedly have a profound impact on most, if
not all, aspects of neurological development, is it reasonable to assume that executive
dysfunction is not the primary deficit in autism, but rather a by-product of more basic and
primary neurological abnormalities? This paper will review the evidence of both posterior/lowlevel and frontal/high-level deficits in autism and propose a model to describe the ways which
the former might contribute to the development of the latter.
Autism is the most extreme form of a spectrum of related disorders collectively referred
to as Pervasive Development Disorders (PDDs). PDDs are characterized by impairments in
social and communicative development in the presence of repetitive and inflexible behaviour
(APA, 1994). Individuals with autism are said to lack “theory of mind” and present with a
specific pattern of problems with attention, perception, behavioural and cognitive rigidity and
perseveration, and emotion regulation. Due to the nature of the behavioural features described,
autism is often regarded as a disorder characterized by deficits in executive functioning (e.g.,
Damasio & Maurer, 1978), particularly planning, shifting set, working memory, impulse control,
inhibition, as well as the initiating and monitoring of action.
Research has provided evidence of such executive dysfunction in autism using a variety
of standard neuropsychological measures (e.g., Wisconsin Card Sorting Task, Tower of Hanoi;
see Hill, 2004 for a review) on which individuals with autism often demonstrate greater
difficulty than matched controls when required to respond in a flexible way. However, results are
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inconsistent and vary with the tasks employed. In addition, the measures commonly used tap
multiple processes, rendering it difficult to determine the exact nature of the deficits. Although
there is much that remains unknown about the exact nature of executive functioning in autism,
the evidence suggests that deficits are specific rather than global.
Executive functions are typically associated with the frontal lobes and the prefrontal
cortex in particular, therefore, a frontal deficit model of autism has been proposed to account for
deficits in these processes (Damasio & Maurer, 1978). However, neurological evidence of
frontal abnormalities in the autistic brain has been inconsistent. Post-mortem studies of the
autistic brain (which are few in number; e.g., Bauman & Kemper, 1985; Salmond, de Haan,
Friston, Gadian, & Vargha-Khadem, 2003) and neuroimaging studies (e.g., Egaas, Courchesne,
& Saitoh, 1995) have found cellular abnormalities in the anterior cingulate and orbitofrontal
cortex (which are involved in executive functioning) as well as a number of limbic structures
(e.g., amygdala, hippocampus). Limbic abnormalities are taken as evidence of frontal deficits
given the strong connections between these regions. Consistent with the frontal deficit theory,
transient delayed postnatal maturation of the frontal lobes (Zilbovicus et al., 1995) and
serotinergic abnormalities in the prefrontal cortex (Chugani et al., 1997) have been reported.
Cortical abnormalities that have been noted include increased cortical thickness, high neuronal
density, and neuronal disorganization (Koenig, Tsatsanis, & Volkmar, 2001).
Evidence for the frontal deficit theory has also come from neuropsychological, actually
studies of patients and animals with either acquired damage to the frontal lobes or other disorders
that lead to executive dysfunction. For example, in a behavioural study of patients with focal
frontal or posterior lesions and controls matched for age, gender, education, and handedness,
Stuss et al. (2000) found that medial and dorsolateral frontal structures were important for
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performance on the Wisconsin Card Sorting Test. Since individuals with autism tend to
experience difficulty on this task, this was taken as evidence of abnormalities in these same
structures in the autistic brain. While valuable, these types of comparisons must be made with
some caution since acquired and developmental disorders are unlikely to be entirely similar.
Rather than focusing on structural abnormalities, a number of neuroimaging studies (see
Koenig, Tsatsanis, & Volkmar, 2001 for a review) have found that individuals with autism
process information differently from normal controls on tests of executive functioning. For
example, employing functional MRI, Luna et al. (2002) found that individuals with autism
displayed significantly less task-related activity in the dorsolateral prefrontal cortex and posterior
cingulate cortex than typical controls on an occulomotor spatial working memory task. This body
of research may help to explain the lack of consistent evidence of abnormal frontal lobe
structures; rather than specific structural abnormalities, perhaps the deficits seen in autism result
from atypical connections with other brain structures resulting in inefficient information
processing pathways.
While there is support for the frontal deficit theory of autism, research has also suggested
more basic, low-level neurological impairments. Behavioural features in autism consistent with
this hypothesis include lack of facial expression, hypersensitivity to touch and sound, poor motor
coordination, abnormalities in eye movements, and sleep disturbances. These are all believed to
be associated with brain stem or cerebellar control (Rodier, 2000). Low level brain impairments
have also been suggested based on behavioural research on attention and inhibition. Whereas
certain aspects of attention and inhibition are predominantly under the control of frontal
structures, they are subserved by multiple systems in the human brain including more primitive
brain regions (e.g., superior colliculi). While certain attention and inhibition systems appear to be
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intact in individuals with autism, there is evidence to suggest that more primitive systems may
not be functioning appropriately. For instance, Bryson and colleagues (as cited in Bryson,
Landry, Czapinski, McConnell, Rombough, & Wainwright, 2004) found that, compared to
matched typical controls and children with Down Syndrome, children with autism had marked
difficulty disengaging their attention from a flashing light on a central screen when an equally
engaging peripheral stimulus was illuminated. They could shift their focus to the periphery as
long as the central screen was off, but could not do so when it remained flashing. The ability to
disengage attention is typically developed by three to four months of age, but prior to that,
performance is comparable to that of older children with autism (Johnson, Posner & Rothbart,
1991). This finding underscores how primitive this function is and provides support for the
implication of lower brain regions. It also highlights the basic nature of certain autistic
impairments, since the inability to disengage one’s attention likely has important implications for
survival and learning.
These behavioural indices of low level brain impairment in autism are actually quite
consistent with neurological evidence. As mentioned previously, relatively few
neuropathological studies have been performed on the brains of autistic subjects, yet the findings
consistently demonstrate? neuroanatomic abnormalities in the brain stem and cerebellum
(Bauman & Kemper, 1994). In terms of the cerebellum, a significant decrease in the number of
Purkinje cells has consistently been reported regardless of age, sex and intelligence (Bauman &
Kemper, 2003). There was a more variable decrease in granule cells. Rodier (2000) has reported
abnormalities in the brain stem of a woman with autism. Specifically, it was shorter than a
normal brain stem, as if a band of tissue had been removed at the junction of the pons and
medulla. As a result, the structures typically found at this location were affected; the superior
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olive (which is a relay station for auditory information) was absent and the facial nucleus (which
controls the muscles of facial expression) was significantly reduced in size. As compared to the
9,000 facial neurons found in a control brain, there were only about 400 in the autistic brain.
In summary, there appears to be evidence of both high level (frontal lobe) and low level
(brain stem and cerebellum) structural abnormalities in the autistic brain as well as indications of
atypical information processing pathways. Although there is considerably more research on
executive functioning and the frontal lobe, evidence of abnormalities in the cerebellum and brain
stem seems to be more consistent. Since low level structures and systems develop first in the
brain and are considered to be most resistant to change from experience (i.e., closed systems),
the question then arises: Could abnormalities in the brain stem and cerebellum impact on
executive functions believed to be primarily under the control of the prefrontal cortex?
A Neurodevelopmental? Model of Autism
The brain is a self-organizing system. According to Lewis (in press), self-organization
refers to “the process by which coherent wholes emerge and consolidate from interacting
constituents” (p. 11). Therefore, abnormal functioning in any of the brain’s constituent structures
or systems would be expected to impact on this process, resulting in a lack of or reduced
amounts of overall organization and coherence. Following this line of reasoning, it seems logical
to assume that abnormalities in the brain stem and cerebellum reported to exist in individuals
with autism could account for the development of frontal deficits and executive dysfunction
commonly associated with the disorder.
In this account, frontal deficits are not intended to be synonymous with structural
abnormality. Deficits may be conceptualized as atypical connections resulting in suboptimal
information processing, a view consistent with the functional imaging literature which has
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reported that individuals with autism use different brain regions from typical controls when
performing various executive functioning tasks (described above). This type of conceptualization
might also help to account for the lack of consistent evidence for damage/abnormality in specific
frontal and cortical structures since problems are seen to lie more in the connections between
structures than in the structures themselves (although structural abnormalities would also be
assumed given that their development is dependent on the nature of information received).
Additional evidence supportive of a progressive neurodevelopmental theory of autism is
the finding of increased brain weight (Bauman & Kemper, 1994) and irregularities in cortical
organization (Bailey et al., 1998). These findings seem to be suggestive of an aberration in the
normal mechanisms associated with brain development (e.g., neuronal migration, synaptic
pruning; Koenig, Tsatsanis, & Volkmar, 2001).
The fact that there is so much heterogeneity within the autistic population (not to mention
the autism spectrum) also suggests that a neurodevelopmental model of the disorder may be
useful. For instance, there may be a primary impairment common to individuals with autism
(which evidence suggests emerges prenatally, Rodier, 2000) that interacts with experience and
environmental inputs differentially to produce similar although somewhat different features of
the disorder. While certain core characteristics are expressed at an early age (e.g., lack of joint
attention) and are likely mediated by more primitive brain structures, others become more
noticeable when higher level processes associated with later developing structures (e.g., the
frontal cortex) do not emerge as expected. The fact that intensive early intervention for autism is
viewed as more successful than later intervention may lend support to this model? or perhaps it
could be called a theory, since it is indeed testable; the impact of lower-level deficits may be
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reduced through the intervention and resulting experiences, thus preventing abnormal
development of other brain regions, including the frontal and limbic structures.
In this theoretical model, abnormalities in the brain stem and cerebellum are viewed as
the origins (aside from genetic contributions) of other neurological deficits in autism. Although
neurological research in autism has failed to produce many consistent findings, there is strong
support for abnormalities in these structures (Bauman & Kemper, 2003; Rodier, 2000) which
Panksepp (1998) described as being “absolutely essential for spontaneous engagement with the
world” (p. 77). Therefore, it is assumed that such structural abnormalities would have a
profound impact on functioning and development.
Three mechanisms are proposed (as discussed in Lewis, in press) to account for the
developmental abnormalities that could result from brain stem dysfunction. They are: 1) nested
feedback loops and self-synchronization, 2) neuromodulation, and 3) vertical integration.
Nested Feedback Loops and Self-Synchronization. The brain stem and cerebellum are
influenced by higher cortical structures and in turn modify their functioning. By providing
appropriate feedback (both positive and negative) to various structures, different systems become
integrated, resulting in coordinated and efficient information processing. Abnormalities in brain
stem and cerebellar functioning could significantly interfere with the functioning of a particular
feedback loop, which would in turn impede the successful synchronization of multiple loops
necessary for coordinated action.
Neuromodulation. Specific cell bodies in the brain stem are responsible for the release of
dopamine, norepinephrine, acetylcholine, and serotonin to terminal sites in all limbic, striatal and
cortical areas including the amygdala and hippocampus (Izquierdo, 1997, as cited in Lewis, in
press) and prefrontal cortical systems (Lewis, in press). The effects of these neuromodulators are
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global, influencing activity throughout the brain by either stabilizing, augmenting or altering
patterns of neuron firing and for coordinating multiple areas to accomplish a particular action
(Lewis, in press). There is evidence that brain stem dopamine, acetylcholine, and norepinephrine
are involved in regulating the activation of prefrontal, orbitofrontal, insular, ACC, and other
systems involved in various cognitive and emotional functions (e.g., Fuster, 1996, as cited in
Lewis, in press). Lewis has also proposed that brain stem neuromodulator release (particularly of
acetylcholine) induces corticolimbic synchronization. Research suggests that such synchrony
reflects the coordination of neural components resulting in coherent psychological processes,
such as those necessary for learning (Lewis, in press). Irregularities in brain stem
neuromodulator release could therefore account for poorly coordinated systems and resultant
processing inefficiencies.
Vertical Integration. Vertical integration refers to the bidirectional relationship between
higher (e.g., cortical) and lower level (e.g., brain stem and cerebellum) neuroanatomical
structures (Tucker, Derryberry & Luu, 2000). Whereas lower level structures are viewed as
having an upward arousing and recruiting influence, higher structures are involved in the
regulation of these lower systems. It is the coordination of these arousing and regulating
functions that allows an organism to behave in an adaptive and flexible manner (Tucker,
Derryberry, & Luu, 200). Based on this model, one would expect that if the arousing and
recruiting functions were not working appropriately, there would be a negative impact on higher
order processes.
Now that we have addressed possible neurological mechanisms for change resulting from
brain stem and cerebellar dysfunction, what follows is more of a psychobiological overview of
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specific brain stem and cerebellar functions and their implications for behavioural features of
autism.
Arousal/Motivation/Attention. The brain stem houses a number of structures that are
believed to be responsible for arousal/motivation/attention which is often atypical in individuals
with autism (e.g., extremely lethargic or hyperactive). Damage to the periaqueductal gray or its
surrounding reticular tissues results in sluggishness or coma if the damage is extensive
(Panksepp, 1998). Conversely, it may be possible that other abnormalities could lead to overarousal and hyperactivity. If unable to regulate levels of arousal, activity level, sleep, and
attentional focus could be impacted on. Attention is a particularly important cognitive function
since it determines the nature of information that enters the system. If overly focused, the
organism could miss out on important aspects of the environment. Similarly, much information
would be overlooked if over-aroused and lacking focus. While it is true that higher cortical
functions are responsible for regulating arousal and attention, this type of control may not be
adequately developed if levels of arousal are at extremely high or low levels.
Emotion. The brain stem also plays an important role in emotion. Although the limbic
structures are typically associated with this role, they require the participation of lower structures
to activate emotional behaviour (Lewis, in press). This activation originates in the medial
reticular networks of the lower brain stem and also the hypothalamus on the ventral part of the
upper brain stem (Panksepp, 1998). Since this basic information serves as input to limbic and
other structures, it is likely that emotional expression and regulation would be affected by
disruptions to the brain stem due to the atypical nature of the information being passed along
and/or abnormalities in the limbic structures resulting from faulty communication with the brain
stem. Such limbic abnormalities, particularly in the hippocampus, subiculum, entorhinal cortex,
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amygdala, mammilary body, anterior cingulate and septum, have been reported (Bauman &
Kemper, 1985). Given the close ties between the limbic system and cortical functions,
particularly for attention, memory, and other executive processes, it seems reasonable to assume
that abnormalities in limbic structures would limit effective communication with the frontal
cortex and thereby interfere with its development and organization. It is also worth emphasizing
the tremendous impact that emotion has on many aspects of learning and behaviour given that it
can motivate systems into action or depress them. Therefore, abnormal emotion systems could
impact on numerous aspects of development.
Sensorimotor Processing. Sensory, motor and basic evaluative processes take place in the
brain stem and cerebellum. Collectively, these structures are important for touch sensation as
well as hearing, vision, balance, taste and the control of certain facial muscles. In addition,
Panksepp (1998) has suggested that the ability to represent oneself in the environment may also
be the result of brain stem functions, particularly the superior colliculus. Dysfunction of such
basic perceptual and motor processing would undoubtedly have a considerable impact on the
development of the organism. Misinterpretation and/or inability to effectively process certain
types of information (e.g., faces) and inappropriate and possibly maladaptive responses to
environmental and social stimuli would have a significant impact on an individual’s experiences.
Fundamental sense of self may not develop perhaps resulting in lack of theory of mind
commonly attributed to frontal functions.
At this time, I would like to elaborate on the role of the cerebellum in the development of
autism. It has traditionally been believed that the cerebellum is involved in coordinating
voluntary movements and controlling motor tone, posture and gait. Abnormalities in this
structure were posited to account for observed lack of motor coordination and awkward gait in
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autism (Allen, Muller, & Courchesne, 2004). There is, however, increasing support for the
notion that the cerebellum is also implicated in diverse higher cognitive functions, such as
language, memory, visuospatial skills, executive functions (e.g., working memory, planning, setshifting), thought modulation, and emotional regulation of behaviour (see Paquier & Marien,
2005 for a review). Courchesne and Allen (1997) proposed that the cerebellum plays a special
role in detecting signals in temporal sequences which allows it to predict, on the basis of prior
learning, what is about to happen and initiates preparatory actions. They posited that the
cerebellum performs this function for all systems with which it maintains connections.
Impairments in this system result in the suboptimal performance of other neural systems.
Courchesne and Allen further hypothesized that repetitive behaviours may develop in an attempt
to compensate for the inability to prepare for change. This may explain social difficulties such as
understanding the consequences of one’s actions, following conversations, and the like.
The cerebellum is believed to exert these effects through a highly organized neuronal
circuitry consisting of afferent cortico-ponto-cerebellar and efferent cerebello-thalamo-cortical
pathways linking the cerebellum with reticular, autonomic, and limbic structures, as well as with
associative and paralimbic areas of the cerebral hemispheres (Middleton & Strick, 2000). The
cerebellum is viewed as modulating rather than generating cognitive processes. According to
Schmahmann (as cited in Paquier & Marien, 2005), “the cerebellum modulates behaviours, and
serves as an oscillation dampener maintaining function steadily around a homeostatic baseline
and smoothing out performance in all domains [p.66]…. When the cerebellar component of the
distributed neural circuit is lost or disrupted, the oscillation dampener is removed. Mental
processes are imperfectly conceived, erratically monitored, and poorly performed [p.67].” This
research suggests that the cerebellar abnormalities consistently reported in autism would likely
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have a profound impact on the development of various neural networks and their related
processes. Not surprisingly, many of the processes the cerebellum has been linked with are
impaired in individuals with autism (e.g., absent or delayed language, executive functioning,
emotion regulation).
Conclusions
Autism is a complex and puzzling disorder characterized by impairments in
communication, socialization and behaviour that significantly interfere with day-to-day
functioning. The features are complex and have typically been associated with executive
dysfunction resulting from frontal lobe deficits. While there is support for this contention,
evidence suggests that more basic neurological deficits exist. This paper has reviewed the
evidence for both high (cortical) and low (brain stem and cerebellum) level impairments and
proposed that frontal deficits (expressed as executive dysfunction) are a by-product of
abnormalities in more primitive brain stem processes. Given the pervasive nature of impairments
in autism it seems logical to assume that a core neurological deficit exists which impacts on
most, if not all areas of development. This type of approach also seems to make sense in light of
what is known about neurological systems and brain development such that later developing
processes associated with higher level brain regions are dependent upon information from more
primitive systems associated with low level structures such as the brain stem and cerebellum.
While there are many factors to consider in the development of autism (particularly
genetic factors which are beyond the scope of this paper), it is believed that the proposed
neurodevelopmental model of autism raises important questions that will need to be addressed in
future research.
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Comments:
This was an absolutely fabulous paper. The integration of hard and detailed
knowledge, complex and clear analysis, insightful interpretation of data, progressive
argument, and especially creative and well-grounded modeling make it easily the best
paper I have read by any student in this area! My only question is: is this
neurodevelopmental model yours?! It is such a great model—so obvious after reading it,
which is what a great model should be—that I’d imagine it would have occurred to other
theorists. Of course, if you picked up aspects of it from others, that does not take away
from the quality of the paper. However, if it is a very original synthesis, I think it is
certainly publishable. And you should pursue this. Let me know...
Grade: A+ !!! (too bad there’s nothing higher)
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