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

Researchers studied brain connection patterns in autistic boys and girls compared to typically developing children. They found that autistic children of both sexes had differences in how brain regions communicate, particularly in areas controlling attention and processing emotions. Interestingly, autistic boys and girls showed opposite patterns in some brain connections. Children with more severe autism symptoms had difficulty maintaining certain brain connection patterns that help with thinking and sensory processing.

This study examined brain connectivity patterns in 98 autistic individuals (49 female, 49 male) compared to 98 typically developing controls, matched for age, sex, and IQ. Using dynamic functional connectivity analysis, researchers found both shared and sex-specific differences in brain network patterns. Both autistic males and females showed reduced variability in frontal brain regions and altered connectivity between olfactory and motor areas. Notably, autistic individuals displayed sex-opposite patterns in connectivity between emotional processing regions (amygdala) and attention control areas.

Greater autism symptom severity was linked to reduced maintenance of high-connectivity brain states involving competition between frontal and sensory regions, suggesting potential targets for individualized interventions.

Findings support need for sex-sensitive assessment and intervention approaches in autism. Dynamic connectivity patterns may serve as biomarkers for treatment monitoring. Results suggest both universal and sex-specific neural targets for therapeutic interventions, particularly in emotional regulation and sensory processing domains.

Single study design without longitudinal follow-up. Limited to individuals with IQ ≥70, excluding those with intellectual disability. Sample size relatively modest for sex-specific analyses. Cross-sectional design cannot establish causality between brain patterns and autism symptoms.

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.