What we know: Neural circuits

Iker Spozio


Autism is described as a ‘disconnection’ syndrome, and researchers have been attempted to distinguish local circuits from long-range connections. However, the terms ‘local’ and ‘long-range’ are poorly defined, and mechanisms of disconnection are not clear in either case.

What we know

  1. Several long axon tracts, including interhemispheric, corticostriatal, frontotemporal and cerebellar connections, measured by magnetic resonance imaging or in autopsy material, are reduced in size in some but not all cases of autism.
  2. Connectivity differences can be detected as early as 6 months of age.
  3. The diameter of cortical mini-columns in human autopsy material is reduced in autism brains, and the packing density of the mini-columns is increased.
  4. Functional magnetic resonance imaging studies show decreased synchrony between frontal and parietal areas in adults with autism who are performing social, language and executive tasks.
  5. The temporoparietal junction and regions of the medial prefrontal cortex are hypoactive in individuals with autism who are experiencing socially relevant stimuli such as biological motion and theory-of-mind tasks.
  6. Individuals with autism show an increased variance of cortical responses to repeated sensory stimuli, although mean responses are not altered.
  7. The autism-risk genes TAOK2 and CNTNAP2 expressed in mice are associated with changes in axon outgrowth and connectivity.

What is next?

  1. Are the alterations in white matter detected by diffusor tensor imaging due to a decrease in the number of axons, to altered myelination of axons or to more complex interactions within axon bundles?
  2. Can methods for electrophysiological or optical recording from large populations of neurons with single-cell resolution reveal ‘neural signatures’ of internal states that are characteristic of autism?
  3. What computational or modeling approaches are needed to manage such large amounts of data?
  4. Can principles of circuit function, such as divisive normalization, be defined that might serve as biomarkers for autism?
  5. Is there a resting-state neural signature (for instance, neural correlates of social cognition) for autism that functional magnetic resonance imaging, electroencephalography or magnetoencephalography can detect?
  6. Are feedback connections, perhaps involving the basal ganglia and thalamus, altered in autism?
  7. What cellular mechanisms (for example, the excitatory/inhibitory balance) might account for local or long-range functional disconnection?
  8. Is the function of the mirror neuron system altered in individuals with autism?
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