Normative Brain Size Variation and the Remodeling of Brain Shape in Humans

Abstract

Evolutionary and developmental increases in primate brain size have been accompanied by systematic shifts in the proportionality of different primate brain systems. However, it remains unknown if and how brain patterning varies across the more than 2-fold inter-individual variation in brain size that occurs amongst typically-developing humans. Using in vivo neuroimaging data from 2 independent cohorts totaling nearly 3000 individuals, we find that larger-brained humans show preferential areal expansion within specific fronto-parietal cortical networks (default mode, dorsal attentional) and related subcortical regions, at the expense of primary sensory/motor systems. This targeted areal expansion recapitulates cortical remodeling across evolution, manifests by early childhood and is linked to molecular signatures of heightened metabolic cost. Our results define a new organizing principle in human brain patterning which governs the highly-coordinated remodeling of human brain shape as a function of naturally-occurring variations in brain size.