Although a growing literature highlights sex differences in autism spectrum disorder clinical presentation, less is known about female variants at the neural level. We investigated sex-related patterns of functional connectivity within and between functional networks in children and adolescents with autism spectrum disorders, compared to typically developing peers. Resting-state functional magnetic resonance imaging data for 141 children and adolescents (7–17 years) selected from an in-house sample and four sites contributing to the Autism Brain Imaging Database Exchange (ABIDE I and II) were submitted to group independent component analysis to generate resting-state functional networks. Functional connectivity was estimated by generating resting-state functional network correlation matrices, which were directly compared between males and females, and autism spectrum disorder and typically developing groups. Results revealed greater connectivity within the default mode network in typically developing girls as compared to typically developing boys, while no such sex effect was observed in the autism spectrum disorder group. Correlational analyses with clinical indices revealed a negative relationship between sensorimotor connectivity and history of early autism symptoms in girls, but not in boys with autism spectrum disorder. A lack of neurotypical sex differentiation in default mode network functional connectivity observed in boys and girls with autism spectrum disorder suggests that sex-related differences in network integration may be altered in autism spectrum disorder.
Lay summary
We investigated whether children and adolescents with autism spectrum disorders show sex-specific patterns of brain function (using functional magnetic resonance imaging) that are well documented in typically developing males and females. We found, unexpectedly, that boys and girls with autism do not differ in their brain functional connectivity, whereas typically developing boys and girls showed differences in a brain network involved in thinking about self and others (the default mode network). Results suggest that autism may be characterized by a lack of brain sex differentiation.
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