This article can be found at: http://www.ncbi.nlm.nih.gov/pubmed/18258309

sMRI

  • Pathological / abnormal regions in ASD: frontal lobes, amygdala and cerebellum
  • time course of brain development, not final product, is most disturbed in autism (so age is a salient factor, and we would want to assess if similar age = more similar brain)
  • Kanner’s asd features include: - impairments in reciprocal social interactions
  • abnormal development and use of language
  • repetitive and ritualized behaviors and a narrow range of interests

 

Behavior –> Regional Structural/ Functional Abnormality

These findings in the literature pertain to regional aberrancies associated with different behavioral types.  I would want to validate these associations in my work, or use them to quasi-validate my approach.  Broadly, these regions include the frontal lobe, the superior temporal cortex, the parietal cortex and the amygdala.

Language Function

  • Expressive language function: Broca’s area in the inferior frontal gyrus and portions of supplementary motor cortex
  • Receptive language function: Wernicke’s area,
  • Superior temporal sulcus (language processing and social attention)

Repetitive and Stereotyped Behaviors

  • share many similarities with abnormal actions of OCD
  • regions include orbitofrontal cortex, caudate nucleus
  • evidence for enlargement of the caudate nucleus: correlated with the presence of repetitive and ritualistic behaviors in adolescents and young adults?

Amygdala

  • boys with autism: appears to undergo an abnormal developmental time course (precocious enlargement that persists through late childhood)
  • 13%–16% abnormal enlargement of the amygdala in young children with autism (36–56 months of age)
  • amygdala enlargement is associated with more severe anxiety and worse social and communication skills
  • neurons in certain nuclei appear unusually small and more densely packed than in healthy control

Epilepsy (highly comorbid with OCD)

  • associated with pathology of cerebral cortex, amygdala, cerebellum, hippocampal formation

Brain Size

  • young children with autism (18 months to 4 years) have a 5%–10% abnormal enlargement in total brain volume, not clear if persists into adulthood
  • Herbert et al. postulated that abnormal brain enlargement in children with ASD is disproportionally accounted for by increased white matter, not gray matter, although gray matter is also increased too

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DTI

  • Reductions in FA in cerebral white matter, consistent reductions reported in and near the genu of the corpus callosum
  • DTI and volumetric study of the corpus callosum found a 14% reduction in corpus callosum size was associated with reduced FA in the genu and splenium
  • Most consistent increases in gray and white matter have been reported in the frontal lobes, but there is no consistent pattern

An informatics opportunity!

“A perusal of this literature emphasizes the need for the field of developmental neuropathology to establish a systematic approach to evaluating abnormal brain development”

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Morphometry

  • Abnormalities in cortical shape: sylvian fissure, superior temporal sulcus, intraparietal sulcus and inferior frontal gyrus
  • cortical thickness, increased over the entire cerebral cortex, most prominent in parietal and temporal regions
  • (postmortem) findings: irregular laminar patterns, esp anterior cingulate cortex, increased cortical thickness, high neuronal density, neurons preset in the molecular layer
  • abnormalities within the hippocampus, both in volume and shape

Why would neurons be in the molecular layer? or increased neurons in white matter?

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Microstructure of Cortex

  • Cortical layer III: reduced intercolumnar width of the minicolumns in dorsolateral prefrontal cortex or Brodmann’s area (BA) 9
  • 79% post-mortem studies show decreased density of Purkinje cells, particularly in the hemispheres, but these subjects also had comorbid seizure disorders, those medications are known to kill these cells
  • no postmortem evidence for abnormalities in the thalamus, basal ganglia

It would be worth looking up or assessing if there is abnormal (functional) connectivity with thalamus