Topographic, cognitive, and neurobiological profiling of the interdependent structural and functional connectome in the human brain

The structural connectome (SC) is tightly coupled to the functional connectome (FC) in the human brain. Most previous related studies have modeled and analyzed SC or FC as isolated brain networks. However, challenges remain in modeling the interdependent structural-functional connectome and elucidating its cognitive implications and molecular underpinnings. Here, we present a multilayer connectome model composed of SC and FC components and further characterize their interacting topological properties. We found that the interdependent connectome is topographically heterogeneous, with the transmodal cortex exhibiting greater modular variability across layers. This spatial topography reflects cortical hierarchy and evolution and shows high test-retest reliability, reproducibility, and heritability. The interdependent connectome contributes to high-order cognitive processes and is associated with multiple neurotransmitter systems and transcriptional signatures of synaptic transmission. Our results provide insights into the nontrivial interdependencies of SC and FC, highlighting their cognitive significance and the molecular mechanisms underlying the connectome of connectomes.