The Cellular Underpinnings of the Human Cortical Connectome

Abstract

The functional properties of the human brain arise, in part, from the vast assortment of cell types that pattern the cortex. The cortical sheet can be broadly divided into distinct networks, which are further embedded into processing streams, or gradients, that extend from unimodal systems through higher-order association territories. Here, using transcriptional data from the Allen Human Brain Atlas, we demonstrate that imputed cell type distributions are spatially coupled to the functional organization of cortex, as estimated through fMRI. Cortical cellular profiles follow the macro-scale organization of the functional gradients as well as the associated large-scale networks. Distinct cellular fingerprints were evident across networks, and a classifier trained on post-mortem cell-type distributions was able to predict the functional network allegiance of cortical tissue samples. These data indicate that the in vivo organization of the cortical sheet is reflected in the spatial variability of its cellular composition.

Embracing variability in the search for biological mechanisms of psychiatric illness

“…Noninvasive neuroimaging is limited in this respect, with most current techniques only able to probe brain structure and function at a spatial resolution of 1 mm 3 . Over the past decade, progress has been made in combining coarse-scale measures with complementary information that allow various annotations of the brain across different scales [106], such as data provided by transcriptomics [107][108][109][110][111][112], histology [113,114], and chemoarchitectonic mapping [115], among others [116,117]. The combination of techniques has already helped to characterize the molecular correlates of various clinical imaging phenotypes (reviewed in [112]), but a major challenge will involve integrating information across different spatial scales [118][119][120][121] to understand precisely how microscale processes may drive the macroscale morphological and functional changes observed in patient populations.…”