Sensory-to-Cognitive Systems Integration Is Associated With Clinical Severity in Autism Spectrum Disorder

Abstract Objective Impaired multisensory integration in autism spectrum disorder ( ASD) may arise from functional dysconnectivity among brain systems. Our study examines the functional connectivity integration between primary modal sensory regions and heteromodal processing cortex in ASD, and whether abnormalities in network integration relate to clinical severity. Method We studied a sample of 55 high-functioning ASDand 64 healthy controls (HC) male children and adolescents (total n = 119, age range 7-18). Stepwise functional connectivity analysis (SFC) was applied to resting state functionalmagnetic resonance images (rsfMRI) to characterize the connectivity paths that link primary sensory cortices to higher-order brain cognitive functional circuits and relate alterations in functional connectivity integration with three clinical scales: Social Communication Questionnaire, Social Responsiveness Scale, and Vineland Adaptive Behavior Scales. Results HC displayed typical functional connectivity transitions from primary sensory systemsto association areas, but the ASDgroup showed altered patterns of multimodal sensory integration to heteromodal systems. Specifically, compared to the HC group, the ASDgroup showed (1) hyper-connectivity in visual cortex at initial link step distances; (2) hyper-connectivity between sensory unimodalregions and regions of the default mode network; and (3) hypo-connectivity between sensory unimodalregions and areas of the fronto-parietal and attentional networks. These patterns of hyper- and hypo-connectivity were associated with increased clinical severity in ASD. Conclusion Network-wise reorganization in high-functioning ASDindividuals affects strategic regions of unimodal-to-heteromodal cortical integration predicting clinical severity. Additionally, SFC analysis appears to be a promising approach for studying the neural pathophysiology of multisensory integration deficits in ASD.