Assessing molecular, cellular and transcriptomic bases of laminar perfusion and cytoarchitecture coupling in the human cortex

Abstract

Understanding how cellular architecture shapes cortical function requires mesoscopic approaches that resolve structure-function relationships in vivo. Here we introduce the cerebral blood flow (CBF) – cell-body staining intensity (CSI) similarity index (CCSI), a quantitative measure of laminar perfusion-cytoarchitecture coupling derived from whole-brain 1-mm isotropic 7 T arterial spin labeling and cell-body staining intensity profiles from the BigBrain atlas. Across 30 participants, CCSI revealed reproducible, region-specific alignment between laminar perfusion and cellular density distributions. CCSI was selectively associated with mitochondrial respiratory capacity per mitochondrion and colocalized with capillary endothelial and end-state oligodendrocyte populations. Gene ontology enrichment converged on metabolic regulation, neurovascular organization, and mitochondrial homeostasis. A parallel control analysis using quantitative T1 yielded no significant associations, supporting the specificity of these findings. At the systems level, CCSI improved structure-function gradient correspondence in higher-hierarchy association cortices. These results support CCSI as a reproducible, non-invasive mesoscopic index linking cortical perfusion, microstructure, and metabolism. The biological basis of laminar perfusion– cytoarchitecture coupling in the human cortex has remained unclear. Here, the authors introduce CCSI, a non-invasive index linking this coupling to metabolism and functional organization.