Abstract
Restricted and repetitive behaviors (RRBs) are a defining clinical feature of autism spectrum disorders (ASD). RRBs are highly heterogeneous with variable expression of circumscribed interests (CI), insistence of sameness (IS) and repetitive motor actions (RM), which are major impediments to effective functioning in individuals with ASD; yet, the neurobiological basis of CI, IS and RM is unknown. Here we evaluate a unified functional brain circuit model of RRBs and test the hypothesis that CI and IS are associated with aberrant cognitive control circuit dynamics, whereas RM is associated with aberrant motor circuit dynamics. Using task-free fMRI data from 96 children, we first demonstrate that time-varying cross-network interactions in cognitive control circuit are significantly reduced and inflexible in children with ASD, and predict CI and IS symptoms, but not RM symptoms. Furthermore, we show that time-varying cross-network interactions in motor circuit are significantly greater in children with ASD, and predict RM symptoms, but not CI or IS symptoms. We confirmed these results using cross-validation analyses. Moreover, we show that brain-clinical symptom relations are not detected with time-averaged functional connectivity analysis. Our findings provide neurobiological support for the validity of RRB subtypes and identify dissociable brain circuit dynamics as a candidate biomarker for a key clinical feature of ASD.
Highlights
Restricted and repetitive behaviors (RRBs) are a defining clinical feature of autism spectrum disorders (ASD)
Using a systems neuroscience-based approach and dynamic functional circuits analysis we provide evidence that childhood ASD is characterized by aberrant dynamics of multiple functional brain circuits, and crucially, that cognitive (CI, insistence of sameness (IS)) and motoric (RM) RRB symptoms are associated with unique neurobiological signatures
Our findings demonstrate that dynamic properties of brain circuits can provide fundamental insights into mechanisms underlying heterogeneity of clinical symptoms in ASD
Summary
Restricted and repetitive behaviors (RRBs) are a defining clinical feature of autism spectrum disorders (ASD). RRBs are highly heterogeneous with variable expression of circumscribed interests (CI), insistence of sameness (IS) and repetitive motor actions (RM), which are major impediments to effective functioning in individuals with ASD; yet, the neurobiological basis of CI, IS and RM is unknown. We show that time-varying cross-network interactions in motor circuit are significantly greater in children with ASD, and predict RM symptoms, but not CI or IS symptoms. Uncovering the brain circuit mechanisms underlying these heterogeneous RRB symptoms/ subtypes is important for a more precise understanding of the neurobiology of ASD and for further validating the distinctiveness of these individual phenotypic constructs. We predicted that, compared to static functional circuits, dynamic functional circuits would better distinguish and predict distinct RRB clinical symptoms
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