Sex heterogeneity of inter-individual functional hierarchical organization similarity in autism spectrum disorder based on the joint embedding analysis.

This brain imaging study looked at how different brain regions connect and communicate in autistic boys and girls compared to non-autistic children. The researchers found that brain connectivity patterns are different between autistic boys and girls, particularly in areas responsible for attention, social thinking, and self-awareness. Importantly, these brain differences could predict social difficulties in autistic boys but not girls, suggesting that autism may affect male and female brains differently.

This neuroimaging study examined sex differences in brain functional connectivity patterns in autism spectrum disorder using resting-state fMRI data from 349 individuals with ASD and 459 neurotypical controls. Researchers used joint embedding analysis to map inter-individual functional hierarchical organization similarity across brain networks. The study found significant diagnosis-by-sex interaction effects in five key brain networks: default mode, frontal-parietal, subcortical, dorsal attention, and undefined networks. Notably, functional connectivity patterns predicted social interaction impairments in males with ASD but not females, suggesting distinct neurobiological profiles between sexes in autism.

These findings highlight the importance of considering sex differences in autism research and potentially in clinical assessment and intervention approaches.

Results suggest autism assessment and intervention approaches may need to consider sex differences in brain connectivity patterns. Males and females with autism may require different neurobiological markers for predicting social difficulties. These findings support developing sex-specific clinical tools and highlight the importance of including more females in autism research.

Sample size imbalance with fewer females than males in both ASD and control groups. Cross-sectional design limits causal inferences. Methodology details and effect sizes not provided in abstract. Generalizability may be limited by sample characteristics from single database.

Autism spectrum disorder (ASD) has been reported to exhibit altered functional connectivity in the brain. While extant research has predominantly examined male samples, sex differences of functional organization in ASD remains poorly characterized. This study aimed to explore the sex heterogeneity of the inter-individual functional hierarchical organization similarity in ASD. Resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange database, including 284 males/65 females with ASD and 340 male/119 female neurotypical controls (NCs) were used in this study.

A joint embedding method was used to embed the functional connectomes of individuals into a common connectivity space and the inter-individual functional hierarchical organization similarity was further calculated within each group. Two-way analysis of variance (ANOVA) was used to explore sex heterogeneity in the functional hierarchical organization similarity in ASD. Significant diagnosis-by-sex interaction effects on the functional hierarchical organization similarity were observed in the default mode network, frontal-parietal network, subcortical network, dorsal attention network, and undefined network. The predictive analysis of symptom severity showed that the functional hierarchical organization similarity of brain regions with significant diagnosis-by-sex interaction effects can predict the social interaction impairments in males with ASD, whereas this relationship was not detected in females with ASD.

These findings emphasize the sex heterogeneity of functional hierarchical organization in ASD and underscore the necessity of considering sex differences in future studies of ASD.