Three transcriptional axes underpin anatomy, development, and disorders of the human cortex

Abstract

AbstractThe Allen Human Brain Atlas (AHBA) has catalysed many discoveries linking macroscale brain organisation to microscale neurobiology, including the existence of a transcriptional axis stretching from sensorimotor to association cortices. However, the complex spatial structure of the human cortex likely includes multiple gradients of gene expression that have yet to be characterised. Here, we reveal two additional transcriptional axes that are anatomically differentiated and have distinct profiles of metabolic and immune function, cytoarchitecture, and developmental trajectory. Moreover, we validate the three transcriptional axes in external data, show they explain more than half of spatial variation across key anatomical and functional neuroimaging maps, and demonstrate they are dissociably aligned with maps of autism, depression, and schizophrenia from one of the largest case-control imaging datasets. Together, these results reveal how human brain anatomy, development, and disorders are patterned along multiple cortical axes underpinned by the intrinsic structure of gene transcription.