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Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary almost twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 3000 individuals, we find that larger human brains show greater areal expansion in distributed frontoparietal cortical networks and related subcortical regions than in limbic, sensory, and motor systems. This areal redistribution recapitulates cortical remodeling across evolution, manifests by early childhood in humans, and is linked to multiple markers of heightened metabolic cost and neuronal connectivity. Thus, human brain shape is systematically coupled to naturally occurring variations in brain size through a scaling map that integrates spatiotemporally diverse aspects of neurobiology.

Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Sex-differentiated brain regions are hypothesized to reflect the experienced gender in GD and may play a role in sexual orientation development. Magnetic resonance brain images were acquired from 16 GD adolescents assigned female at birth (AFAB) not receiving hormone therapy, 17 cisgender girls, and 14 cisgender boys (ages 12-17 years) to examine three morphological and microstructural gray matter features in 76 brain regions: surface area (SA), cortical thickness (CT), and T1 relaxation time. Sexual orientation was represented by degree of androphilia-gynephilia and sexual attraction strength. Multivariate analyses found that cisgender boys had larger SA than cisgender girls and GD AFAB. Shorter T1, reflecting denser, macromolecule-rich tissue, correlated with older age and stronger gynephilia in cisgender boys and GD AFAB, and with stronger attractions in cisgender boys. Thus, cortical morphometry (mainly SA) was related to sex assigned at birth, but not experienced gender. Effects of experienced gender were found as similarities in correlation patterns in GD AFAB and cisgender boys in age and sexual orientation (mainly T1), indicating the need to consider developmental trajectories and sexual orientation in brain studies of GD.