Longitudinal Sex-at-Birth and Age Analyses of Cortical Structure in the ABCD Study

Abstract

While the brain continues to develop during adolescence, such development may depend on sex-at-birth. However, the elucidation of such differences may be hindered by analytical decisions (e.g., covariate selection to address brain-size differences) and the typical reporting of cross-sectional data. To further evaluate adolescent cortical development, we analyzed data from the Adolescent Brain Cognitive Development Study, whose cohort of 11,000+ youth participants with biannual neuroimaging data collection can facilitate understanding neuroanatomical change during a critical developmental window. Doubly considering individual differences within the context of group-level effects, we analyzed regional changes in cortical thickness, sulcal depth, surface area, and volume between two timepoints (∼2 years apart) in 9- to 12-year-olds assigned male or female sex-at-birth. First, we conducted linear mixed-effect models to gauge how controlling for intracranial volume, whole-brain volume (WBV), or a summary metric (e.g., mean cortical thickness) influenced interpretations of age-dependent cortical change. Next, we evaluated the relative changes in thickness and surface area as a function of sex-at-birth and age. Here, we showed that WBV (thickness, sulcal depth, volume) and total cortical surface area were more optimal covariates; controlling for different covariates would have substantially altered our interpretations of overall and sex-at-birth-specific neuroanatomical development. Furthermore, we provided evidence to suggest that aggregate change in how cortical thickness is changing relative to surface area is generally comparable across those assigned male or female sex-at-birth, with corresponding change happening at slightly older ages in those assigned male sex-at-birth. Overall, these results help elucidate neuroanatomical developmental trajectories in early adolescence.