An Anatomical Substrate for Integration among Functional Networks in Human Cortex

The human brain shows several characteristics of an efficient communication network architecture, including short communication paths and the existence of modules interlinked by a small set of highly connected regions. Studies of structural networks comprising macroscopic white matter projections have shown that these putative hubs are densely interconnected, giving rise to a spatially distributed and topologically central collective called the "rich club." In parallel, studies of intrinsic brain activity have consistently revealed distinct functional communities or resting-state networks (RSNs), indicative of specialized processing and segregation of neuronal information. However, the pattern of structural connectivity interconnecting these functional RSNs and how such inter-RSN structural connections might bring about functional integration between RSNs remain largely unknown. Combining high-resolution diffusion weighted imaging with resting-state fMRI, we present novel evidence suggesting that the rich club structure plays a central role in cross-linking macroscopic RSNs of the human brain. Rich club hub nodes were present in all functional networks, accounted for a large proportion of "connector nodes," and were found to coincide with regions in which multiple networks overlap. In addition, a large proportion of all inter-RSN connections were found to involve rich club nodes, and these connections participated in a disproportionate number of communication paths linking nodes in different RSNs. Our findings suggest that the brain's rich club serves as a macroscopic anatomical substrate to cross-link functional networks and thus plays an important role in the integration of information between segregated functional domains of the human cortex.