Structural optimality and neurogenetic expression mediate functional dynamics in the human brain

The human brain exhibits a rich functional repertoire in terms of complex functional connectivity patterns during rest and tasks. However, how this is developed upon a fixed structural anatomy remains poorly understood. Here we investigated the hypothesis that resting state functional connectivity and the manner in which it changes during tasks related to a set of underlying structural connections that promote optimal communication in the brain. We used a game‐theoretic model to identify such optimal connections in the structural connectome of 50 healthy individuals and subsequently used the optimal structural connections to predict resting‐state functional connectivity with high accuracy. In contrast, we found that nonoptimal connections accurately predicted functional connectivity during a working memory task. We further found that this balance between optimal and nonoptimal connections between brain regions was associated with a specific gene expression linked to neurotransmission. This multimodal evidence shows for the first time that structure–function relationships in the human brain are related to how brain networks navigate information along different white matter connections as well as the brain's underlying genetic profile.