Mapping Consistent, Reproducible, and Transcriptionally Relevant Connectome Hubs of the Human Brain

Abstract

Human brain connectomes include sets of densely connected regions, known as connectome hubs, which play a vital role in understanding global brain communication, cognitive processing, and brain disorders. However, the consistency and reproducibility of functional connectome hubs anatomical localization have not been established to date and the genetic signatures underlying robust connectome hubs remain unknown. Here, we conduct the first worldwide, harmonized meta-connectomic analysis by pooling resting-state functional MRI data of 5,212 healthy young adults across 61 independent cohorts. We identify highly consistent and reproducible functional connectome hubs in heteromodal and unimodal regions both across cohorts and across individuals. These connectome hubs show heterogeneous connectivity profiles and are critical for both intra- and inter-network communications. Using post-mortem gene expression data, we show that these connectome hubs have a spatiotemporally distinctive transcriptomic pattern dominated by genes involved in the neuropeptide signaling pathway, neurodevelopmental processes, and metabolic processes. These results highlight the robustness of macroscopic connectome hubs and their potential cellular and molecular underpinnings.