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

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder, characterized by impairments in social communication and restricted, repetitive behaviors. Neuroimaging studies have shown complex patterns and functional connectivity (FC) in ASD, with no clear consensus on brain-behavior relationships or shared patterns of FC with typically developing controls. Here, we used a dimensional approach to characterize two distinct clusters of FC patterns across both ASD participants and controls using k-means clustering. Using multivariate statistical analyses, a categorical approach was taken to characterize differences in FC between subtypes and between diagnostic groups. One subtype was defined by increased FC within resting-state networks and decreased FC across networks compared with 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, a dimensional analysis of FC patterns with behavioral measures of IQ, social responsiveness, and ASD severity showed unique brain-behavior 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 across ASD and controls, and that FC subtypes can reveal unique information about brain-behavior relationships. Author SummaryAutism spectrum disorder (ASD) is a neurodevelopmental disorder, with high variation in the types of severity of impairments in social communication and restricted, repetitive behaviors. 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 behavior in a group of participants consisting of individuals with and without ASD. One subtype was defined by increased FC within distinct networks of brain regions and decreased FC between networks compared with the other subtype. A separate FC pattern distinguished ASD from controls. The interaction between subtypes and diagnostic groups was not significant. Dimensional analyses of FC patterns with behavioral measures revealed unique information about brain-behavior relations in each subtype.