Investigating the differential contributions of sex and brain size to gray matter asymmetry

Scientific reports of sex differences in brain asymmetry - the difference between the two hemispheres - are rather inconsistent. Some studies report no sex differences whatsoever, others reveal striking sex effects, with large discrepancies across studies in the magnitude, direction, and location of the observed effects. One reason for the lack of consistency in findings may be the confounding effects of brain size as male brains are usually larger than female brains. Thus, the goal of this study was to investigate the differential contributions of sex and brain size to asymmetry with a particular focus on gray matter. For this purpose, we applied a well-validated workflow for voxel-wise gray matter asymmetry analyses in a sample of 96 participants (48 males/48 females), in which a subsample of brains (24 males/24 females) were matched for size. By comparing outcomes based on three different contrasts - all males versus all females; all large brains versus all small brains; matched males versus matched females - we were able to disentangle the contributing effects of sex and brain size, to reveal true (size-independent) sex differences in gray matter asymmetry: Males show a significantly stronger rightward asymmetry than females within the cerebellum, specifically in lobules VII, VIII, and IX. This finding agrees closely with prior research suggesting sex differences in sensorimotor, cognitive and emotional function, which are all moderated by the respective cerebellar sections. No other significant sex effects on gray matter were detected across the remainder of the brain.