Connectome-wide mega-analysis reveals robust patterns of atypical functional connectivity in autism

Neuroimaging studies on functional connectivity (FC) in autism have been hampered by small sample sizes and inconsistent findings with regard to whether connectivity is increased or decreased in individuals with autism, whether these alterations affect focal systems or reflect a brain-wide dysfunction, and whether these are age- and/or sex-dependent. The study included resting-state fMRI and clinical data from the LEAP and the ABIDE I and II initiatives, of 1824 (796 with autism) participants with age range 5-58 years. Between-group differences in FC were assessed, and associations between FC and clinical symptom ratings were investigated through canonical correlation analysis. Autism was associated with a brain-wide pattern of hypo- and hyperconnectivity. Hypoconnectivity predominantly affected sensory and higher-order attentional networks and correlated with social impairments, restrictive and repetitive behavior (RRB), and sensory processing. Hyperconnectivity was observed primarily between the default mode network and the rest of the brain, and between cortical and subcortical systems. This pattern was strongly associated with social impairments and sensory processing. Interactions between diagnosis and age or sex were not statistically significant. The FC alterations observed in this study, which primarily involve hypoconnectivity of primary sensory and attention networks and hyperconnectivity of the DMN and subcortex with the rest of the brain, do not appear to be age or sex-dependent and correlate with clinical dimensions of social difficulties, RRBs, and alterations in sensory processing. These findings suggest that the observed connectivity alterations are stable, trait-like features of autism that are related to the three main symptom domains.