Sex Similarities and Differences in Brain Dynamic Functional Connectivity Among Individuals With and Without Autism Spectrum Disorders

Given the historical underrepresentation of autistic females in neuroscience research, few neuroimaging studies have directly compared females and males with autism spectrum disorders (ASD) to explore both sex-independent and -specific neural features. This study employed a sliding-window approach to construct dynamic functional connectivity and investigated sex similarities and differences in modular variability (nodal level), edge variability (edge level), and state variability (brain state level) in brain connectomes among individuals with and without ASD. Ninety-eight autistic individuals (49 female, 49 male; full-scale IQ ≥ 70) and 98 typically developing individuals (TD; 49 female, 49 male), matched on sex, age, and full-scale IQ, were selected from the Autism Brain Imaging Data Exchange (ABIDE). Results showed that both autistic males and females exhibited reduced modular variability in the left middle frontal gyrus and diminished edge variability in the functional connectivity between the right olfactory cortex and the right paracentral lobule, compared to their TD peers. Notably, autistic individuals manifested a sex-opposite shift in the edge variability of functional connectivity between the left amygdala and the right anterior cingulate and paracingulate gyri. Furthermore, greater autistic symptom severity was associated with reduced maintenance of a high-connectivity brain state characterized by functional competition between the frontal cortex and sensory-perceptual or subcortical regions. These findings reveal both shared and sex-differentiated alterations in connectome dynamics in ASD, with the sex-specific patterns aligning with the gender incoherence model. Understanding these dynamic features may inform more individualized and sex-sensitive educational and social support for individuals with ASD.