Functional connectivity-based subtypes of individuals with and without autism spectrum disorder

Abstract Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder, characterized by impairments in social communication and restricted, repetitive behaviours. Neuroimaging studies have shown complex patterns of functional connectivity (FC) in ASD, with no clear consensus on brain-behaviour relationships or shared patterns of FC with typically developing controls. Here, we used k-means clustering and multivariate statistical analyses to characterize distinct FC patterns and FC-behaviour relationships in participants with and without ASD. Two FC subtypes were identified by the clustering analysis. One subtype was defined by increased FC within resting-state networks and decreased FC across networks compared to the other subtype. A separate FC pattern distinguished ASD from controls, particularly within default mode, cingulo-opercular, sensorimotor, and occipital networks. There was no significant interaction between subtypes and diagnostic groups. Finally, analysis of FC patterns with behavioural measures of IQ, social responsiveness and ASD severity showed unique brain-behaviour relations in each subtype, and a continuum of brain-behavior relations from ASD to controls within one subtype. These results demonstrate that distinct clusters of FC patterns exist in both ASD and controls, and that FC subtypes can reveal unique information about brain-behaviour relationships. Author Summary Autism spectrum disorder (ASD) is a neurodevelopmental disorder, with high variation in the types of severity of impairments in social communication and restricted, repetitive behaviours. Neuroimaging studies have shown complex patterns of communication between brain regions, or functional connectivity (FC), in ASD. Here, we defined two distinct FC patterns and relationships between FC and behaviour in participants with and without ASD. One subtype was defined by increased FC within distinct networks of brain regions, and decreased FC between networks compared to the other subtype. A separate FC pattern distinguished ASD from controls. The interaction between subtypes and diagnostic groups was not significant. Analysis of FC patterns with behavioural measures revealed unique information about brain-behaviour relations in each subtype.