Connectional Hierarchy in Human Brain Revealed by Individual Variability of Functional Network Edges

The human cerebral cortex is connected by intricate inter-areal wiring at the macroscale. The cortical hierarchy from primary sensorimotor to higher-order association areas is a unifying organizational principle across various neurobiological properties; however, previous studies have not clarified whether the connections between cortical regions exhibit a similar hierarchical pattern. Here, we identify a connectional hierarchy indexed by inter-individual variability of functional connectivity edges, which continuously progresses along a hierarchical gradient from within-network connections to between-network edges connecting sensorimotor and association networks. We found that this connectional hierarchy of variability aligns with both hemodynamic and electromagnetic connectivity strength and is constrained by structural connectivity strength. Moreover, the patterning of connectional hierarchy is related to inter-regional similarity in transcriptional and neurotransmitter receptor profiles. Using the Neurosynth cognitive atlas and cortical vulnerability maps in 13 brain disorders, we found that the connectional hierarchy of variability is associated with similarity networks of cognitive relevance and that of disorder vulnerability. Finally, we found that the prominence of this hierarchical gradient of connectivity variability declines during youth. Together, our results reveal a novel hierarchal organizational principle at the connectional level that links multimodal and multiscale human connectomes to individual variability in functional connectivity.