Microstructural asymmetry in the human cortex

The human cerebral cortex shows hemispheric asymmetry, yet the microstructural basis of this asymmetry remains incompletely understood. Here, we probe layer-specific microstructural asymmetry using one post-mortem male brain. Overall, anterior and posterior regions show leftward and rightward asymmetry respectively, but this pattern varies across cortical layers. A similar anterior-posterior pattern is observed using in vivo Human Connectome Project (N = 1101) T1w/T2w microstructural data, with average cortical asymmetry showing the strongest similarity with post-mortem-based asymmetry of layer III. Moreover, microstructural asymmetry is found to be heritable, varies as a function of age and sex, and corresponds to intrinsic functional asymmetry. We also observe a differential association of language and markers of mental health with microstructural asymmetry patterns at the individual level, illustrating a functional divergence between inferior-superior and anterior-posterior microstructural axes, possibly anchored in development. Last, we could show concordant evidence with alternative in vivo microstructural measures: magnetization transfer (N = 286) and quantitative T1 (N = 50). Together, our study highlights microstructural asymmetry in the human cortex and its functional and behavioral relevance.