Abstract The human neocortex consists of tangentially organized layers with unique cytoarchitectural properties. These layers show spatial variations in thickness and cytoarchitecture across the neocortex, which is thought to support brain function through enabling targeted corticocortical connections. Here, leveraging maps of the six cortical layers in 3D human brain histology, we aimed to quantitatively characterize the systematic covariation of laminar structure in the cortex and its functional consequences. After correcting for the effect of cortical curvature, we identified a spatial pattern of changes in laminar thickness covariance from lateral frontal to posterior occipital regions, which differentiated the dominance of infra- versus supragranular layer thickness. Corresponding to the laminar regularities of cortical connections along cortical hierarchy, the infragranular-dominant pattern of laminar thickness was associated with higher hierarchical positions of regions, mapped based on resting-state effective connectivity in humans and tract-tracing of structural connections in macaques. Moreover, we show that regions with comparable laminar thickness patterns correspond to inter-regional structural covariance, maturational coupling, and transcriptomic patterning, indicating developmental relevance. In sum, here we characterize the association between organization of laminar thickness and processing hierarchy, anchored in ontogeny. As such, we illustrate how laminar organization may provide a foundational principle ultimately supporting human cognitive functioning.

The spatial arrangement of laminar thickness profiles in the human cortex scaffolds processing hierarchy