Local structure-function relationships in human brain networks across the human lifespan

Abstract

The human connectome is the set of physical pathways linking brain regions to one another. Empirical and in silico studies have demonstrated that the structure of this network helps shape patterns of functional coupling between brain regions. To better understand this link between structure and function, a growing number of studies have derived geometric, dynamic, and topological predictors from structural connectivity in order to make predictions about correlation structure. These studies, however, have typically focused on global (whole-brain) predictions using a restricted set of predictors. Here, we investigate a wide range of predictors and shift focus onto predictions of local (regional) patterns of functional coupling. We show that, globally, no individual predictor performs well and, that even the best predictors are largely driven by their ability to predict functional coupling between directly connected regions. We then use the same predictors to make predictions of local coupling and find marked improvement. Notably, the most predictable local FC is linked to sensorimotor regions, which are best predicted by measures based on topological similarity, mean first passage times of random walkers, and the brains embedding in Euclidean space. We then show that by combining the predictive power of more than one predictor using multi-linear models, we can further improve local predictions. Finally, we investigate how global and local structure-function coupling differences across the human lifespan. We find that, globally, the magnitude of coupling decreases with biological age, which is paralleled by an increase in the number of multi-step pathways. We also show that, locally, structure-function coupling is preserved in higher order cognitive systems, but preferentially decreases with age in sensorimotor systems. Our results illuminate the heterogeneous landscape of structure-function coupling across the cerebral cortex and help clarify its differences with age.