Whole-brain functional connectivity predicted by indirect structural connections

Modern functional and diffusion magnetic resonance imaging (fMRI and dMRI) provide data from which macro-scale networks of functional and structural whole brain connectivity can be estimated. Although networks derived from these two modalities describe different properties of the human brain, they emerge from the same underlying brain organization, and functional communication is presumably mediated by structural connections. In this paper, we assess the structure-function relationship by evaluating how well functional connectivity can be predicted from structural graphs. Using high-resolution whole brain networks generated with varying density, we contrast the performance of several non-parametric link predictors that measure structural communication flow. While functional connectivity is not well predicted directly by structural connections, we show that superior predictions can be achieved by taking indirect structural pathways into account. In particular, we find that the length of the shortest structural path between brain regions is a good predictor of functional connectivity in sparse networks (density less than one percent), and that this improvement comes from integrating indirect pathways comprising up to three steps. Our results support the existence of important indirect relationships between structure and function, extending beyond the immediate direct structural connections that are typically investigated.