Sexual dimorphism and laterality in neurostructural development from late childhood to early adulthood: A cross-sectional voxel based morphometry study

Intro: Adolescence is a sensitive period for social, emotional, risk, and reward behavior and is an onset period for serious psychiatric disorders. Changes in behavior in adolescence may be mediated by the rapid changes in brain structure observed during this time period. While adolescent structural development has been extensively analyzed, less is known about the developmental effects of sex or lateralized differences. Understanding how the brain typically develops during these critical periods may give insight into when structural deviations occur that result in psychopathology. Methods: Structural Magnetic Resonance Imaging (MRI) scans were obtained from samples of children (age 9-11, n=344), adolescents (age 13-14, n=271), and adults (age 22-25, n=56) using the same scanner and acquisition sequences. Gray and white matter densities and volumes were assessed using voxel-based morphometry, as were ventricular volumes, total tissue volumes, and average tissue densities. Asymmetry indices were created by comparing the left and right hemispheres of each individual’s brain maps. Age, sex, an age and sex interaction, age2, and an age2 and sex interaction were examined in a simultaneous multiple regression for each brain metric. Results: Gray matter density and volume declined with age, while white matter increased. Males had greater total volumes while females had greater white matter densities. After correcting for total tissue volume, local sex differences were largely greater in females. Laterality analyses suggested that medial brain structures developed earlier in the right hemisphere. Conclusions: Our findings suggest structural changes occur throughout adolescence and likely continue past early adulthood in frontal structures, primarily in white matter. Changes in density appear to precede volumetric changes. Males had larger global, not local, brain volumes. Total gray matter volume and average white matter densities changed faster in females. Lateralized differences in developmental timing offer a new line of investigation in adolescent approach and avoidance behavior.