Higher-order interaction of brain microstructural and functional connectome

ABSTRACT Despite a relatively fixed anatomical structure, the human brain can support rich cognitive functions, triggering particular interest in investigating structure-function relationships. Myelin is a vital brain microstructure marker, yet the individual microstructure-function relationship is poorly understood. Here, we explore the brain microstructure-function relationships using a higher-order framework. Global (network-level) higher-order microstructure-function relationships negatively correlate with male participants’ personality scores and decline with aging. Nodal (node-level) higher-order microstructure-function relationships are not aligned uniformly throughout the brain, being stronger in association cortices and lower in sensory cortices, showing gender differences. Notably, higher-order microstructure-function relationships are maintained from the whole-brain to local circuits, which uncovers a compelling and straightforward principle of brain structure-function interactions. Additionally, targeted artificial attacks can disrupt these higher-order relationships, and the main results are robust against several factors. Together, our results increase the collective knowledge of higher-order structure-function interactions that may underlie cognition, individual differences, and aging.