Predictors of Coupling Between Structural and Functional Cortical Networks in Normal Aging

r r Abstract: Understanding how the mammalian neocortex creates cognition largely depends on knowl-edge about large-scale cortical organization. Accumulated evidence has illuminated cortical substrates of cognition across the lifespan, but how topological properties of cortical networks support structure-function relationships in normal aging remains an open question. Here we investigate the role of con-nections (i.e., short=long and direct=indirect) and node properties (i.e., centrality and modularity) in predicting functional-structural connectivity coupling in healthy elderly subjects. Connectivity net-works were derived from correlations of cortical thickness and cortical glucose consumption in resting state. Local-direct connections (i.e., nodes separated by less than 30 mm) and node modularity (i.e., a set of nodes highly interconnected within a topological community and sparsely interconnected with nodes from other modules) in the functional network were identified as the main determinants of cou-pling between cortical networks, suggesting that the structural network in aging is mainly constrained by functional topological properties involved in the segregation of information, likely due to aging-related deficits in functional integration. This hypothesis is supported by an enhanced connectivity between cortical regions of different resting-state networks involved in sensorimotor and memory functions in detrimental to associations between fronto-parietal regions supporting executive processes. Taken collectively, these findings open new avenues to identify aging-related failures in the anatomo-functional organization of the neocortical mantle, and might contribute to early detection of prevalent neurodegenerative conditions occurring in the late life. Hum Brain Mapp 35:2724–2740, 2014. VC 201