2025/10/04 by Athanasia Metoki, Roselyne J. Chauvin, Evan M. Gordon +16 · 1 voice
Environmental Science · Neuroscience · #Health, Environment, Cognitive Aging #Stress Responses and Cortisol #Functional Brain Connectivity Studies
paper · doi:10.1016/j.dcn.2025.101624
Understanding sex differences in the adolescent brain is crucial, as they relate to sex-specific neurological and psychiatric conditions. Predicting sex from adolescent brain data may reveal how these differences influence neurodevelopment. Recently, attention has shifted toward socially-identified gender (distinct from sex assigned at birth) recognizing its explanatory power. This study evaluates whether resting-state functional connectivity (rsFC), cortical thickness, or cortical volume better predicts sex and sex/gender alignment (congruence between sex and gender) in preadolescents. Using Adolescent Brain Cognitive Development (ABCD) Study data and machine learning, rsFC predicted sex more accurately (85%) than cortical thickness (76%) and cortical volume (70%). Brain regions most predictive of sex belonged to association (default mode, dorsal attention, parietal memory) and visual networks. The rsFC classifier trained on sex/gender aligned youth classified more accurately unseen youth with sex/gender alignment ( n = 2,013) than unalignment ( n = 1,116). The female rsFC sex profile was positively associated with sex/gender alignment, while in males, there was a negative association. However, neither brain modality predicted sex/gender alignment. These findings suggest that while rsFC predicts sex in the adolescent brain more accurately, it does not directly capture sex/gender alignment, underscoring the need for further investigation into the neural underpinnings of gender. • Resting-state functional connectivity (rsFC) predicts sex with an accuracy of 85%, significantly outperforming cortical thickness and cortical volume, which achieve 76% and 70% respectively. • Key brain networks involved in predicting sex include association networks (default mode, dorsal attention, and parietal memory) and visual networks (visual and medial visual). • The rsFC sex classifier trained on sex/gender aligned youth was significantly more effective in classifying individuals with sex/gender alignment compared to individuals with sex/gender unalignment. • In females, the degree to which their brains’ rsFC matched a sex profile (female or male), was positively associated with the degree of sex/gender alignment. • rsFC, cortical thickness, and cortical volume did not predict sex/gender alignment, emphasizing the complexity of the relationship between sex, gender, and brain functional connectivity and neuroanatomy.