Brain asymmetry is globally different in males and females: exploring cortical volume, area, thickness, and mean curvature.

Brain asymmetry is a cornerstone in the development of higher-level cognition, but it is unclear whether and how it differs in males and females. Asymmetry has been investigated using the laterality index, which compares homologous regions as pairwise weighted differences between the left and the right hemisphere. However, if asymmetry differences between males and females are global instead of pairwise, involving proportions between multiple brain areas, novel methodological tools are needed to evaluate them. Here, we used the Amsterdam Open MRI collection to investigate sexual dimorphism in brain asymmetry by comparing laterality index with the distance index, which is a global measure of differences within and across hemispheres, and with the subtraction index, which compares pairwise raw values in the left and right hemisphere. Machine learning models, robustness tests, and group analyses of cortical volume, area, thickness, and mean curvature revealed that, of the three indices, distance index was the most successful biomarker of sexual dimorphism. These findings suggest that left-right asymmetry in males and females involves global coherence rather than pairwise contrasts. Further studies are needed to investigate the biological basis of local and global asymmetry based on growth patterns under genetic, hormonal, and environmental factors.