# Brain functional connectivity, but not neuroanatomy, captures the interrelationship between sex and gender in preadolescents

## TL;DR

This study finds that brain connectivity patterns better predict biological sex in preadolescents than brain structure, but neither captures gender alignment.

## Contribution

The study shows that functional connectivity, not neuroanatomy, is more effective for predicting sex and gender alignment in preadolescents.

## Key findings

- rsFC predicted sex with 85% accuracy, outperforming cortical thickness and volume.
- Brain regions in association and visual networks were most predictive of sex.
- rsFC did not predict sex/gender alignment, highlighting a gap in understanding gender's neural basis.

## Abstract

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 = 2013) than unalignment (n = 1116). 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.

•rsFC predicts sex with 85% accuracy, significantly better than cortical thickness at 76% and cortical volume at 70%.•Key sex prediction brain networks include association (default mode, dorsal attention, parietal memory) and visual networks.•The rsFC sex classifier trained on sex/gender aligned individuals classified aligned more effectively than unaligned ones.•In females, the degree of sex/gender alignment correlates with how closely their brain matches a sex profile.•Sex/gender alignment was not predicted by rsFC, cortical thickness, or cortical volume.

rsFC predicts sex with 85% accuracy, significantly better than cortical thickness at 76% and cortical volume at 70%.

Key sex prediction brain networks include association (default mode, dorsal attention, parietal memory) and visual networks.

The rsFC sex classifier trained on sex/gender aligned individuals classified aligned more effectively than unaligned ones.

In females, the degree of sex/gender alignment correlates with how closely their brain matches a sex profile.

Sex/gender alignment was not predicted by rsFC, cortical thickness, or cortical volume.