Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

TLDR

Human brain hemispheres differ functionally and structurally, yet the influence of sex, handedness, age, and genetics on asymmetry remains controversial. This study presents the largest harmonized multi‑site meta‑analysis of subcortical brain asymmetries. The authors assessed volumetric asymmetry of seven subcortical structures in 15,847 MRI scans from 52 worldwide datasets. Sex differences were found in globus pallidus and putamen asymmetry, heritability analyses showed genetic influence on these and on hippocampus and thalamus, handedness had no effect, putamen asymmetry varied with age, and genetic drivers of asymmetry may impact cognition and psychiatric disorder susceptibility.

Abstract

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.