Alteration of functional connectivity in autism spectrum disorder: effect of age and anatomical distance

Autism spectrum disorder (ASD) is associated with disruption of local- and long-range functional connectivity (FC). The direction of those changes in FC (increase or decrease), however, is inconsistent across studies. Further, age-dependent changes of distance-specific FC in ASD remain unclear. In this study, we used resting-state functional magnetic resonance imaging data from sixty-four typical controls (TC) and sixty-four patients with ASD, whom we further classified into child (<11 years), adolescent (11-18 years) and adult cohorts (>18 years). Functional connectivity (FC) analysis was conducted at voxel level. We employed a three-way analysis of covariance on FC to conduct statistical analyses. Results revealed that patients with ASD had lower FC than TC in cerebellum, fusiform gyrus, inferior occipital gyrus and posterior inferior temporal gyrus. Significant diagnosis-by-distance interaction was observed in ASD patients with reduced short-range and long-range FC in posterior cingulate cortex and medial prefrontal cortex. Importantly, we found significant diagnosis-by-age-by-distance interaction in orbitofrontal cortex with short-range FC being lower in autistic children, but -to a less extent- higher in autistic adults. Our findings suggest a major role of connection length in development changes of FC in ASD. We hope our study will facilitate deeper understanding of the neural mechanisms underlying ASD.