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 myelinated visual and somatomotor areas. Additionally, SC-FC coupling displayed a broadly negative association with age and, depending on the region, varied across sexes and with cognitive scores. Specifically, males had higher coupling strength in right supramarginal gyrus and left cerebellar regions while females had higher coupling strength in right visual, right limbic and right cerebellar regions. Furthermore, increased SC-FC coupling in the right lingual gyrus was associated with worse cognitive scores. Finally, we found SC-FC coupling to be highly heritable, particularly in the visual, dorsal attention, and fronto-parietal networks, and, interestingly, more heritable than FC or SC alone. Taken together, these results suggest regional structure-function coupling in young adults decreases with age, varies across sexes in a non-systematic way, is somewhat associated with cognition and is highly heritable.

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

“…Although communication models are becoming increasingly common and have been used recently to study individual differences in phenotypes and traits [27], cognition [28], and for subject identification [29], there remain many open questions and frontiers. First, most studies focus on a select set of communication measures and do not compare the performance of those measures against other models.…”

“…Consider, for instance, the human lifespan. Although many studies have independently documented differences in structural [32][33][34] and functional connections [35,36] through development, maturation, and adulthood, how they evolve jointly in terms of communication models and at the level of brain regions is unknown [28,37].…”

Time-resolved structure-function coupling in brain networks

“…As a result, structurefunction coupling is also likely to fluctuate over multiple timescales. Indeed, multiple studies have reported evidence of dynamic structure-function relationships over the course of single recording sessions [30,31], and over more protracted periods, including early childhood and young adult neurodevelopment [8,35].…”