Multiscale heterogeneity of functional connectivity in autism

Atypical functional connectivity (FC) in autism is a common finding, but the results of individual studies are often inconsistent and sometimes contradictory. Classical reliance on case-control comparisons of group means that ignore the inter-individual heterogeneity in autism may be a key drive of this inconsistency. Here, we used normative modelling to examine FC heterogeneity at the level of pair-wise inter-regional connections, specific brain regions, and broader functional networks in 1,824 participants (796 autistic) aged 5-58 years recruited across 32 different sites. Connection-level heterogeneity was high in both groups, with no single connection deviating in more than 4% of participants. However, deviant connections tended to converge on common regions and networks in autistic individuals more than in controls. Autistic individuals showed significantly greater overlap for positive deviations (i.e., atypically increased FC) in transmodal systems and negative deviations (atypically decreased FC) in sensory-motor areas. FC deviation patterns across coarser levels correlated with social functioning symptoms and intellectual ability. This work suggests that clinical variability in autism may be associated with extreme heterogeneity in the specific functional connections, whereas commonalities may be driven by convergence of atypical FC increases in transmodal systems and atypical decreases in sensorimotor networks, pointing to an imbalance in the functional organization of the brain’s sensorimotor-association axis.