The spatial organization of the chronnectome associates with cortical hierarchy and transcriptional profiles in the human brain

Abstract

The chronnectome of the human brain represents dynamic connectivity patterns of brain networks among interacting regions, but its organization principle and related transcriptional signatures remain unclear. Using task-free fMRI data from the Human Connectome Project (681 participants) and microarray-based gene expression data from the Allen Institute for Brain Science (1791 brain tissue samples from six donors), we conduct a transcriptome-chronnectome association study to investigate the spatial configurations of dynamic brain networks and their linkages with transcriptional profiles. We first classify the dynamic brain networks into four categories of nodes according to their time-varying characteristics in global connectivity and modular switching: the primary sensorimotor regions with large global variations, the paralimbic/limbic regions with frequent modular switching, the frontoparietal cortex with both high global and modular dynamics, and the sensorimotor association cortex with limited dynamics. Such a spatial layout reflects the cortical functional hierarchy, microarchitecture, and primary connectivity gradient spanning from primary to transmodal areas, and the cognitive spectrum from perception to abstract processing. Importantly, the partial least squares regression analysis reveals that the transcriptional profiles could explain 28% of the variation in this spatial layout of network dynamics. The top-related genes in the transcriptional profiles are enriched for potassium ion channel complex and activity and mitochondrial part of the cellular component. These findings highlight the hierarchically spatial arrangement of dynamic brain networks and their coupling with the variation in transcriptional signatures, which provides indispensable implications for the organizational principle and cellular and molecular functions of spontaneous network dynamics.