Regional structural-functional connectome coupling is heritable and associated with age, sex and cognitive scores in adults

ABSTRACT Large scale white matter brain connections quantified via the structural connectome (SC) act as the backbone for the flow of functional activation, which can be represented via the functional connectome (FC). Many studies have used statistical analysis or computational modeling techniques to relate SC and FC at a global, whole-brain level. However, relatively few studies have investigated the relationship between individual cortical and subcortical regions’ structural and functional connectivity profiles, here called SC-FC coupling, or how this SC-FC coupling may be heritable or related to age, sex and cognitive abilities. Here, we quantify regional SC-FC coupling in a large group of healthy young adults (22 to 37 years) using diffusion-weighted MRI and resting-state functional MRI data from the Human Connectome Project. We find that while regional SC-FC coupling strengths vary widely across cortical, subcortical and cerebellar regions, they were strongest in highly structurally connected visual and subcortical areas. Additionally, depending on the region, SC-FC coupling varied across sexes and with age and composite cognitive scores. Specifically, SC-FC coupling in the cerebellum tended to decrease with age while coupling in medial fronto-orbital areas tended to increase with age. Males had stronger coupling in many regions, particularly in the right orbito-frontal region and areas in the ventral attention and default mode networks, while females had higher coupling strength in right hippocampus. Furthermore, increased SC-FC coupling in the right insula and decreased coupling in bilateral middle cingulate and supplementary motor areas was associated with higher composite cognitive scores. Finally, we found SC-FC coupling to be highly heritable, particularly in higher order default mode, dorsal/ventral attention and fronto-parietal networks. Taken together, these results suggest regional structure-function coupling in young adults varies with age, is generally stronger in males, is associated with composite cognitive scores and is highly heritable.