Hierarchy of transcriptomic specialization across human cortex captured by myelin map topography

Hierarchy provides a unifying principle for the macroscale organization of anatomical and functional properties across primate cortex, yet the microscale bases of hierarchical specialization across human cortex are poorly understood. Anatomical hierarchy is conventionally informed by invasively measured laminar patterns of long-range cortico-cortical projections, creating the need for a principled proxy measure of hierarchy in humans. Moreover, cortex exhibits a transcriptional architecture characterized by distinct profiles of gene expression across areas, yet organizing principles for areal transcriptomic specialization remain unclear. We hypothesized that functional specialization of human cortical microcircuitry across areas involves hierarchical gradients of gene expression. Here we show that a noninvasive neuroimaging measure, the MRI-derived myelin map, indexes the anatomical hierarchy and closely resembles the dominant areal pattern of transcriptomic variation across the human cortex. We found strong hierarchical gradients in expression of genes related to cortical microcircuit function, which we validated with microanatomical data from monkey cortex, and in expression of genes related to neuropsychiatric disorders. These findings establish hierarchy as a general organizing principle, defining an axis shared by the transcriptomic and anatomical architectures of human cortex, and suggest that hierarchical gradients of microscale properties shape the macroscale specialization of cortical function.