Human visual cortex is organized along two genetically opposed hierarchical gradients with unique developmental and evolutionary origins

Human visual cortex is organized with striking consistency across individuals. While recent findings demonstrate an unexpected coupling between functional and cytoarchitectonic regions relative to the folding of human visual cortex, a unifying principle linking these anatomical and functional features of the cortex remains elusive. To fill this gap in knowledge, we combined independent and ground truth measurements of cytoarchitectonic regions and genetic tissue characterization within human occipitotemporal cortex. Using a data-driven approach, we examined whether differential gene expression among cytoarchitectonic areas could contribute to the arealization of occipitotemporal cortex into a hierarchy based on transcriptomics. This approach revealed two opposing gene expression gradients: one that contains a series of genes with expression magnitudes that ascend from posterior (e.g., areas human occipital [hOc]1, hOc2, hOc3, etc.) to anterior cytoarchitectonic areas (e.g., areas fusiform gyrus [FG]1–FG4) and another that contains a separate series of genes that show a descending gradient from posterior to anterior areas. Using data from the living human brain, we show that each of these gradients correlates strongly with variations in measures related to either thickness or myelination of cortex, respectively. We further reveal that these genetic gradients emerge along unique trajectories in human development: the ascending gradient is present at 10–12 gestational weeks, while the descending gradient emerges later (19–24 gestational weeks). Interestingly, it is not until early childhood (before 5 years of age) that the two expression gradients achieve their adult-like mean expression values. Additional analyses in nonhuman primates (NHPs) reveal that homologous genes do not generate the same ascending and descending expression gradients as in humans. We discuss these findings relative to previously proposed hierarchies based on functional and cytoarchitectonic features of visual cortex. Altogether, these findings bridge macroscopic features of human cytoarchitectonic areas in visual cortex with microscopic features of cellular organization and genetic expression, which, despite the complexity of this multiscale correspondence, can be described by a sparse subset (approximately 200) of genes. These findings help pinpoint the genes contributing to healthy cortical development and explicate the cortical biology distinguishing humans from other primates, as well as establishing essential groundwork for understanding future work linking genetic mutations with the function and development of the human brain.