Autism brains: More or less connected?
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction and communication, and restricted interests and repetitive behavior. Current empirical and theoretical accounts based on studies in adults posit that the underlying neurobiological disturbance causing ASD is brain under-connectivity. Remarkably, there have been no systematic attempts to characterize brain connectivity in children with ASD, work that is critical for understanding the etiology of this complex neurodevelopmental disorder. In this talk, I will present results of a series of studies designed primarily to characterize functional connectivity in children with ASD, at the whole-brain level as well as within key large-scale brain networks including those involved in reward processing, salience detection, and social cognitive function. And secondly, to investigate neural mechanisms that could explain the observed aberrant functional brain connectivity patterns, if any. In stark contrast to the prevalent under-connectivity theory of ASD, we observed a much more complex pattern of over- and under-connectivity across brain regions and networks in ASD children. Linking the connectivity results in ASD children to animal models of autism, using neurocomputational modeling, we found, that atypical local neural dynamics, particularly, an imbalance of excitation-inhibition, was causally associated with the observed aberrant connectivity patterns in ASD. Our findings suggest that the regional imbalance between excitation and inhibition is likely to play a critical role in altering brain connectivity, contributing to both over- and under-connectivity in childhood autism; thereby, providing unique mechanistic insights that have broader implications for early detection and treatment strategies.