Heterogeneity of white-matter organization in the human brain

. Here, we present a histological and imaging pipeline optimized for post-mortem human white-matter that shows the 3D trajectories of densely stained large (diameter greater than ~1 μm) projection axons. Applying our approach to multiple centimeter-scale WM regions in an adult human brain, we observed striking regional diversity in axonal organization. Specifically, we identified distinct architectural motifs ranging from loosely packed, multi-orientation meshworks (in most superficial white matter), to laminar lattice-like structures (near the basal ganglia), to tightly packed bundles of fibers (e.g. in the corpus callosum). We speculate that these patterns reflect local adaptations to spatial constraints, axonal density, and the diversity of axonal sources and targets, offering region-specific solutions to anatomical optimization problems. These findings offer new insights into the principles shaping brain connectivity and underscore the need for regionally detailed atlases of human white matter..