Functional brain networks are uniquely associated with sex and gender in children

828 

Abstract Submission 

Elvisha Dhamala¹, Dani Bassett², B. T. Thomas Yeo³, Avram Holmes⁴

¹Feinstein Institutes for Medical Research, Glen Oaks, NY, ²UPenn, Philadelphia, PA, ³National University of Singapore, Singapore, Singapore, ⁴Department of Psychiatry, Brain Health Institute, Rutgers University, Piscataway, NJ

Elvisha Dhamala  
Feinstein Institutes for Medical Research
Glen Oaks, NY

Dani Bassett  
UPenn
Philadelphia, PA

B. T. Thomas Yeo  
National University of Singapore
Singapore, Singapore

Avram Holmes  
Department of Psychiatry, Brain Health Institute, Rutgers University
Piscataway, NJ

A fundamental aspect of our human experience is our sex and gender, how we perceive them, and how they are perceived by others. Sex and gender can explain our behavior and influence our health and disease throughout the lifespan. Women, people assigned female at birth, and sex/gender minorities have historically been excluded from biomedical research[1]. Consequently, this group of individuals is more likely to be underdiagnosed or misdiagnosed for common brain disorders (e.g., ADHD), and suffer adverse effects from treatment interventions (e.g., medications). An understanding of the functional brain correlates of sex and gender is essential for the study of brain disorders that exhibit sex differences.

Here, we used neuroimaging data from the Adolescent Brain Cognitive Development (ABCD) Study[2] (4757 children, 2351 females, 9-10 years old) at baseline, and self- and parent- reported gender data at the 1-year follow-up time point to quantify the functional correlates of sex and gender. First, we evaluated sex differences in self- and parent- reported gender data. Next, we use cross-validated linear ridge regression models[3] to establish associations between functional connectivity and sex and gender. Sex-independent (models trained on all individuals) and sex-specific (models trained specifically within each sex) approaches were used to quantify the functional correlates of gender. Finally, we evaluated whether shared or distinct functional networks were associated with sex and gender using the Haufe-transformed[4] feature weights extracted from the regression models.

Self- and parent- reported gender scores were more similar in children assigned female at birth (AFAB) than in children assigned male at birth (AMAB), and AMAB children exhibited greater sex congruence than AFAB children for both self- and parent- report scores (Fig. 1A).
Across all individuals, functional connectivity was significantly associated with sex, self-reported gender, and parent-reported gender (Fig. 1B). Within each sex, functional connectivity was not associated with self-reported gender, but was significantly associated with parent-reported gender in both AFAB and AMAB children (Fig. 1C).
For the sex-independent models, functional connections associated with sex largely overlapped with those associated with gender, suggesting that models trained to capture variability in gender are capturing variability related to sex, and vice versa (Fig. 2A). For the sex-specific models, functional connections associated with sex were distinct from the functional connections associated with gender in AFAB and AMAB children (Fig. 2A).
Functional correlates of sex were largely found in the somatomotor, visual, control and limbic networks, while the functional correlates of gender were more dispersed throughout the cortical networks (Fig. 2B). In AFAB children, functional correlates of gender largely involved connections within and between temporal parietal, limbic, dorsal/ventral attention, and somatomotor networks. In AMAB children, functional correlates of gender additionally included connections within and between default mode and visual networks.

Sex and gender differences in biology and behavior are tied to health outcomes throughout the lifespan. An understanding of the neurobiological underpinnings of sex and gender is crucial for the subsequent identification of how sex and gender influence health and illness and the development of sex-specific and gender-oriented diagnostic and prognostic tools. Here, we demonstrate that functional connectivity is associated with sex and parent-reported gender, and that sex and gender uniquely map onto functional brain networks in AFAB and AMAB children. As such, sex and gender must both be studied concurrently to fully capture the differences and similarities that exist between males and females, between boys and girls, and between other genders.

Social Neuroscience Other ¹

Early life, Adolescence, Aging ²

Normal Development

Computational Neuroscience

Development

DISORDERS

FUNCTIONAL MRI

Machine Learning

PEDIATRIC

Psychiatric

Psychiatric Disorders

Other - Sex differences