DATA-DRIVEN INVESTIGATION OF STRUCTURE-FUNCTION ASSOCIATION IN HEALTHY AGING BRAIN

Abstract

The age-related functional reorganization is a long-standing theory in the aging literature due to the evidence showing hyperactivity in multiple brain regions in older adults. However, the underlying neural mechanism is still far from clear. By integrating structural information into the analysis, the structure-function interaction can be particularly interesting to look at since previous studies suggested unique information embedded in the structurefunction coupling that is more sensitive to age-related alteration than structural or functional information alone. Thus, current study aims to characterize the aging brain by examining the structure-function association. Specifically, we used a multiple linear regression model to quantify the region-wise coupling strength between functional connectivity (FC) and structural connectivity (SC). Multiple complex network measures were also computed and included in the model to account for the potential indirect structural supporting on FC. By fitting the model to the large-scale(428 participants) multimodal aging dataset from the Cam- CAN project, we observed regional variability in SC-FC coupling strength that is related to the functional specialization across cortices, with regions specialized in transmodal information processing being more SC-FC uncoupled than unimodal regions. Moreover, our results demonstrated several clusters of brain regions showing prominent age-related SC-FC uncoupling, suggesting a gradual divergence between brain structure and function with advancing age. Further investigation on the underlying interplay between SC and FC pointed to several networks and brain regions as the potential source of age-related SC-FC uncoupling, including the visual network, salience network and prefrontal regions. Together, these findings help elucidate the interaction between SC and FC in the aging brain. Moreover, our results also proposed several brain regions and networks that might be particularly involved in age-related functional reorganization. Key words: aging brain, structure-function interaction, brain networks, functional reorganization.