Comprehensive large-scale analyses reveal association between brain structure and cognitive ability during adolescence

Abstract Significant changes occur in brain structure and cognition during adolescence. Investigating their association can provide insight into brain-based cognitive development, yet previous studies are limited by narrow measures, small samples, and lacking focus on age-dependence. Using a large cohort (n = 8534, age 9–15) with structural MRI and diffusion imaging, we derive 16 regional metrics and integrate them via morphometric similarity networks to characterize 16,563 brain features. We apply large-scale models to investigate their associations with seven cognitive subtests and general intelligence (g), as well as age-dependence. Brain areas most strongly associated with cognition also show the greatest age-dependence of the associations, primarily in the frontal, temporal, and occipital lobes. Stronger and more age-dependent associations with cognition are observed for structural MRI measures and global hub measures, compared with diffusion-derived metrics and local measures, respectively. Overall, our study provides a comprehensive and reliable characterization of adolescent brain structure-cognition associations.