Autism, Viewpoint on the Brain Disorder

1 - Behavior and the brain
Autism is a serious developmental disability but
defined in terms of behaviors not clearly related to
dysfunction of any specific neurological system – or,
at the present time no defect within the brain is known
that can account for autistic behaviors. Brain damage
has been looked for in neuropathological
investigations, magnetic resonance imaging (MRI),
and positron emission tomography (PET). No visible
anomalies can be detected in the majority of cases,
but measurements of MRI scans have revealed
decreased size of the brainstem [1-3]. Measurements
of other brain areas have not yielded consistent
results, but await refinement in terms of age and
severity of cognitive function.

Visible abnormalities of the cerebellum, brainstem,
limbic system, temporal lobes, and corpus callosum
have been described [4-6]. But the same
abnormalities are also seen in other neuro-
developmental disorders [7]. Thus the accounts of
neuropathology in cases of autism are not specific to
autism.

Nowell et al. (1990) reported highly variable MRI
findings in 53 patients with autism and were not able
to determine any single pattern that could predict the
presence or severity of autism [8]. Nowell et al
emphasized that autism is a heterogeneous disorder
made up of many different subgroups with different
clinical features and they urged caution in
interpretation of MRI findings. Deb and Thompson
(1998) suggested that neuroimaging is useful mainly
to look for a medical disorder as the cause of autism
in individual cases [9].

Visible signs of brain impairment therefore reflect the
many causes of autistic disorder and represent the
most severe manifestations of their etiologies. None
is a consistent finding in children with autism. Table 5
lists some of the visible abnormalities found in brains
from people with autism.

There have been many theories advanced about
possible brain areas responsible for autistic
behaviors. Rimland (1964) discussed how damage of
the brainstem reticular formation might lead to autism
[10]. Ornitz and Ritvo (1968) proposed dysfunction
within the vestibular system [11]. Hauser et al (1975)
suggested temporal lobe involvement [12], and in the
same year I first urged consideration of the inferior
colliculus [13].

Damasio and Maurer (1978) argued that dysfunction
in the mesolimbic cortex, subcortical motor system,
and thalamic targets of the dopamine system could
account for behavior and motor disturbances in
autism [14]. Neuropsychological test results implicate
frontal lobe defects [15], and this has support from
functional imaging studies [16]. Zilbovicius et al
(1995) reported hypoperfusion of the frontal lobes in
children with autism under the age of six, and
proposed a delay in frontal lobe maturation [17].

Ritvo et al (1986) reported reduced Purkinje cell
counts in the cerebellum in children with autism [18].
Kemper and Bauman (1998) also reported reduced
Purkinje cell numbers in the brains of autistic
individuals they examined [19]. Courchesne et al
(1988) provided evidence for anomalies of the
cerebellar vermis [6].

Reduced size of the corpus callosum in cases of
autism has been reported [20, 21]. Tubers in the
temporal lobes of children with tuberous sclerosis and
autism also provide evidence for temporal lobe
dysfunction [22-24].

Bauman and Kemper (1985) reported abnormalities in
the amygdala, along with other subcortical nuclei, in
the brain of one case of autism [25]; later they
included the amygdala among the most consistently
involved areas in nine brains examined [4]. Disruption
of function in the amygdala and its connections has
currently gained widespread interest [26-31].

Thus just about every area in the brain has been
implicated as potentially responsible for the syndrome
of autism. However, explanations for how any of these
brain regions might become impaired are lacking.
This is no doubt the reason that genetic causes are
assumed to be important. But finding the locus of
genes on chromosomes does not solve the puzzle of
autism. The locus of autistic disorder is in the brain,
and how this is affected by genes and/or
environmental insults is what must be understood.

Visible signs of damage reported by Ritvo et al.
(1986), Courchesne et al (1988), Kemper and
Bauman (1998, 2002), and Bailey et al. (1998) involve
mainly subcortical sites and the cerebellum [4-6, 18,
19]. These are the same sites known to be affected
by factors that disrupt aerobic metabolism [32, 33].
Most susceptible to damage are brainstem nuclei of
the auditory system, especially the inferior colliculus
because this is the most metabolically active site in
the brain [34].

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Gaffney GR et al. (1989)
Forebrain structure in infantile
autism.
Hashimoto T et al. (1993)
Brainstem involvement in
high functioning autistic
children.
Hashimoto T et al. (1995)
Development of the
brainstem and cerebellum in
autistic patients.
Kemper TL, Bauman ML
(2002) Neuropathology of
infantile autism.
Bailey A et al. (1998) A
clinicopathological study of
autism.
Courchesne E et al. (1988)
Hypoplasia of cerebellar
vermal lobules VI and VII in
autism.
Schaefer GB et al. (1996)
Hypoplasia of the cerebellar
vermis in neurogenetic
syndromes.
Nowell MA et al. (1990) Varied
MR appearance of autism:
fifty-three pediatric patients
having the full autistic
syndrome.
Deb S, Thompson B (1998)
Neuroimaging in autism.
Rimland B (1964) Infantile
Autism: the syndrome and its
implications for a neural
theory of. behavior.
Ornitz EM, Ritvo ER (1968)
Neurophysiologic
mechanisms underlying
perceptual inconstancy in
autistic and schizophrenic
children.
Hauser SL et al. (1975)
Pneumographic findings in
the infantile autism
syndrome. A correlation with
temporal lobe disease.
Simon N (1975) Echolalic
speech in childhood autism,
consideration of possible
underlying loci of brain
damage.
Damasio AR, Maurer RG
(1978) A neurological model
for childhood autism.
Rumsey JM, Hamburger SD.
(1988) Neuropsychological
findings in high-functioning
men with infantile autism,
residual state.
Baron-Cohen S et al. (1994)
Recognition of mental state
terms. Clinical findings in
children with autism and a
functional neuroimaging
study of normal adults.
Zilbovicius M et al.(1995).
Delayed maturation of the
frontal cortex in childhood
autism.
Ritvo ER et al. (1986) Lower
Purkinje cell counts in the
cerebella of four autistic
subjects: initial findings of the
UCLA-NSAC Autopsy
Research Report.
Kemper TL, Bauman M
(1998). Neuropathology of
infantile autism.
Egaas B et al (1995)
Reduced size of corpus
callosum in autism.
Piven J et al. (1997) An MRI
study of the corpus callosum
in autism.
Bolton PF, Griffiths PD (1997)
Association of tuberous
sclerosis of temporal lobes
with autism and atypical
autism.
Asano E et al. (2001) Autism
in tuberous sclerosis
complex is related to both
cortical and subcortical
dysfunction.
Bolton PF et al. (2002) Neuro-
epileptic determinants of
autism spectrum disorders in
tuberous sclerosis complex.
Bauman M, Kemper TL
(1985) Histoanatomic
observations of the brain in
early infantile autism.
Fotheringham JB (1991).
Autism: its primary
psychological and
neurological deficit.
Hoon AH Jr, Reiss AL. (1992)
The mesial-temporal lobe
and autism: case report and
review.
Bachevalier J. (1994) Medial
temporal lobe structures and
autism: a review of clinical
and experimental findings
Abell Fet al. (1999) The
neuroanatomy of autism: a
voxel-based whole brain
analysis of structural scans.
Baron-Cohen S et al. (2000)
The amygdala theory of
autism.
Howard MA et al.(2000).
Convergent neuroanatomical
and behavioural evidence of
an amygdala hypothesis of
autism.
Myers RE (1972) Two
patterns of perinatal brain
damage and their conditions
of occurrence.
Cavanagh JB, Nolan CC
(1993) The neurotoxicity of
alpha-chlorohydrin in rats and
mice: II. Lesion topography
and factors in selective
vulnerability in acute energy
deprivation syndromes.
Sokoloff L (1981) Localization
of functional activity in the
central nervous system by
measurement of glucose
utilization with radioactive
deoxyglucose.