Measures of Brain Connectivity and Cognition by Sex in US Children.

Importance: The neurobiological underpinnings underlying sex differences in cognition during adolescence are largely unknown. Objective: To examine sex differences in brain circuitry and their association with cognitive performance in US children. Design, Setting, and Participants: This cross-sectional study analyzed behavioral and imaging data from 9- to 11-year-old children from the Adolescent Brain Cognitive Development (ABCD) study between August 2017 and November 2018. The ABCD study is an open-science, multisite study following up more than 11 800 youths into early adulthood for 10 years with annual laboratory-based assessments and biennial magnetic resonance imaging (MRI). The selection of ABCD study children for the current analysis was based on the availability of functional and structural MRI data sets in ABCD Brain Imaging Data Structure Community Collection format. Five hundred and sixty participants who had excessive level of head motion (>50% of time points with framewise displacement >0.5 mm) during resting-state functional MRI were excluded from the analyses. Data were analyzed between January and August 2022. Main Outcomes and Measures: The main outcomes were the sex differences in (A) global functional connectivity density at rest and (B) mean water diffusivity (MD) and (C) the correlation of these metrics with total cognitive scores. Results: A total of 8961 children (4604 boys and 4357 girls; mean [SD] age, 9.92 [0.62] years) were included in this analysis. Girls had higher functional connectivity density in default mode network hubs than boys, predominantly in the posterior cingulate cortex (Cohen d = -0.36), and lower MD and transverse diffusivity, predominantly in the superior corticostriatal white matter bundle (Cohen d = 0.3). Age-corrected fluid and total composite scores were higher for girls than for boys (Cohen d = -0.08 [fluid] and -0.04 [total]; P = 2.7 × 10-5). Although total mean (SD) brain volume (1260 [104] mL in boys and 1160 [95] mL in girls; t = 50; Cohen d = 1.0; df = 8738) and the proportion of white matter (d = 0.4) were larger for boys than for girls, the proportion of gray matter was larger for girls than for boys (d = -0.3; P = 2.2 × 10-16). Conclusions and Relevance: The findings of this cross-sectional study on sex differences in brain connectivity and cognition are relevant to the future creation of brain developmental trajectory charts to monitor for deviations associated with impairments in cognition or behavior, including those due to psychiatric or neurological disorders. They could also serve as a framework for studies investigating the differential contribution of biological vs social or cultural factors in the neurodevelopmental trajectories of girls and boys.