Sex-Based Differences in Cortical and Subcortical Development in 436 Individuals Aged 4-54 Years

Abstract

Sex-based differences in brain development have long been established in ex vivo studies. Recent in vivo studies using magnetic resonance imaging (MRI) have offered considerable insight into sex-based variations in brain maturation. However, reports of sex-based differences in cortical volumes and thickness are inconsistent. We examined brain maturation in a cross-sectional, single-site cohort of 436 individuals (201 [46%] males) aged 4-54 years (median = 16 years). Cortical thickness, cortical surface area, subcortical surface area, volumes of the cerebral cortex, white matter (WM), cortical and subcortical gray matter (GM), including the thalamic subnuclei, basal ganglia, and hippocampi were calculated using automatic segmentation pipelines. Subcortical structures demonstrated distinct curvilinear trajectories from the cortex, in both volumetric maturation and surface-area expansion in relation to age. Surface-area analysis indicated that dorsal regions of the thalamus, globus pallidus and striatum, regions demonstrating structural connectivity with frontoparietal cortices, exhibited extensive expansion with age, and were inversely related to changes seen in cortical maturation, which contracted with age. Furthermore, surface-area expansion was more robust in males in comparison to females. Age- and sex-related maturational changes may reflect alterations in dendritic and synaptic architecture known to occur during development from early childhood through to mid-adulthood.

Keywords: MRI; basal ganglia; brain; cortex; thalamus.

Figure 1

Trajectories of TCV, GM and WM volumes in males (blue lines) and females (red lines) aged 4–54 years.

Figure 2

Vertex-based cortical thickness analysis (corrected P map): corrected P values for cortical brain regions demonstrating significant quadratic age effects (inverted), representing a slow decrease in cortical thickness values in childhood followed by a steady decline in values until the 3rd and 4th decades and leveling out at the 5th decade, controlling for sex and corrected for multiple comparisons (P < 0.05). The color bar indicates corrected P values for significant peaks at the cluster (left; light blue–dark blue) and vertex-levels (right; red– orange).

Figure 3

Cortical (left), thalamic (middle) and striatal (right) surface area: association with age. Left: vertex-based surface analysis of corrected P values of age-related regional contractions in cortical surface area. Middle and right: corrected P values of age-related subcortical surface area expansion. All analyses were adjusted for sex and corrected for multiple comparisons (P < 0.05). The color bar indicates corrected P values for significant peaks at the vertex level (left) as well as at the cluster level (right).