stanfield.qxp 24/6/08 04:44 Page 63
Understanding Brain Anatomy in Autism – Findings from Structural Neuroimaging
Other than the developmental time-course, a number of questions remain connected brain regions that are known to be involved in social cognition.
regarding the nature of the brain enlargement in autism. Studies differ as These include the fusiform face area, the superior temporal sulcus (STS) and
to whether they have found enlargements that are generalised across the the amygdala, which are covered below, and the frontal–thalamo–striatial
whole brain or confined to certain regions, and whether they affect grey networks, which are dealt with in a separate section.
42–44
The fusiform face
matter, white matter or both.
11,15–19
In addition, it is not known whether the area is located on the ventral surface of the temporal lobe and is known
extra brain volume reflects a quantitative difference from typical to play an important role in the processing of facial stimuli.
45
Although
development or a more profound qualitative difference in the process of differences in the amount of fusiform grey matter have been observed
brain development. Proposed mechanisms include an increase in glial cell between individuals with autism and controls, these are inconsistent,
proliferation, an abnormal myelin maturational process and the with both increases
46,47
and decreases
48,49
identified. However, a recent
development of smaller but more numerous cortical minicolumns (vertically
orientated groups of cortical cells thought to represent functional units).
20
The causes of brain enlargement in autism are also currently unknown,
The development of computed
although there is some evidence that genetic factors may be important. A
tomography in the early 1970s was a
recent study identified an association between enlargements of the cerebral
hemispheres and a low-activity variant of the promoter for the monoamine
major breakthrough in clinical brain
oxidase A gene (MAO-A) – an enzyme that breaks down catecholamines,
science as it allowed, for the first time,
including noradrenaline and serotonin – in individuals with autism.
21
Increases in catecholamines, which could be caused by reduced MAO-A
researchers to use a non-invasive
activity, have been associated with autism,
22
and this low-activity variant has
technique to gather in vivo information
also been associated with more severe autistic symptomatology.
23
regarding brain structure.
Dysconnectivity
Given the multifaceted nature of human behaviours, it is not surprising that post mortem study did find a reduction in neuronal number and size in
the brain functions that subserve them are not carried out by specific areas the fusiform face area,
50
and functional imaging studies have reported
of the brain in isolation, but rather require the temporally co-ordinated that people with autism show abnormal activation patterns in the
integration of multiple brain regions. The complex nature of the behaviours fusiform gyrus when viewing faces compared with unaffected
central to the autism phenotype brings into focus dysconnectivity between individuals.
51,52
The regions around the superior temporal sulcus are
distributed brain regions as a putative contributing factor. Electro- proposed to be involved in auditory perception as well as the initial
physiological
24
and functional MRI studies
25–29
have demonstrated analysis of more complex social stimuli derived from biological motion.
53
alterations in connectivity in the autistic brain during a variety of tasks, while There are several MRI studies of autism that have found reductions in
the strongest neuroanatomical evidence for dysconnectivity comes from MRI grey matter around the superior temporal sulcus.
49,54
Cortical thinning
studies of white matter. The corpus callosum is the largest white matter tract has also been found in this region, the degree of which was associated
in the human brain and connects homotopic areas of the contralateral with overall symptom severity.
55
In addition, anterior shifting of the
cerebral cortices. A reduction in the mid-sagittal area of the corpus callosum relative position of the superior temporal sulcus within the brain has been
was the first white matter abnormality to be identified in autism,
30
and has reported in autism (along with displacements of other major frontal and
been consistently replicated.
31
More recently, several DTI studies have temporal sulci).
56
reported reduced FA in the corpus callosum, which is consistent with the
volumetric findings and indicative of interhemispheric dysconnectivity.
32–34
The amygdala is a collection of nuclei that lie in the medial temporal lobe.
It is involved in many aspects of social cognition, including the mediation
In addition to reports of interhemispheric dysconnectivity, other patterns of of fear and arousal and the attribution of emotional valence to stimuli. It
reduced FA have been identified in autism, including in brain regions has been found to be increased in size in younger individuals with autism,
involved in social cognition such as the anterior cingulate, orbitofrontal but is normal or reduced in volume in adults.
31,57
This is particularly notable
cortex, superior temporal sulcus and areas approaching the amygdala and when considered in the light of findings that early amygdala damage has
fusiform gyrus.
35
Other DTI studies have found reductions in FA in the significant effects on social cognition, whereas later damage does not.
58
In
internal capsule,
34
superior temporal gyrus and temporal stem
36
and the addition, in children with autism a large amygdala has been associated
short association fibres of the prefrontal lobe.
37
The last of these studies also with increased anxiety levels,
59
whereas in adolescents and adults a small
found that people with autism have a fibre distribution skewed towards amygdala was found to be associated with social impairment.
60
These
long association fibres, and these fibres were also found to be longer than findings suggest that it is not just the initial enlargement of the amygdala,
in typically developing controls. Other neuroanatomical evidence of but also the extent of the volume reduction that affects the clinical severity
dysconnectivity comes indirectly from reports of disturbances to prefrontal of autism. As with the findings for the whole brain volume, it must be
cortical folding
38
and greater sulcal depth in autism,
39
both of which may be emphasised that longitudinal studies are required to definitively establish
related to changes in the underlying innervation of a region.
40
the temporal pattern of amygdala enlargement in autism. In addition to
the traditional network of social brain regions described above, recent
The Social Brain studies have suggested that there is a further system that is important in
Deficits in social cognition are well documented in autism and include social cognition: the mirror neuron system. Located in the inferior frontal
impairments in mentalising ability (attributing mental states to others) and and inferior parietal cortices, mirror neurons are activated both when an
the recognition of the emotional content of a variety of stimuli, particularly individual performs an action and when he or she views an action carried
facial expressions.
41
In typically developing individuals there are several out by another person.
61
This mental representation is proposed to be
EUROPEAN PSYCHIATRIC REVIEW 63
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