What the structural-functional connectome reveals about brain aging: The key role of the fronto-striatal-thalamic circuit and the rejuvenating impact of physical activity

Physiological ageing affects brain structure and function impacting its morphology, connectivity and performance. However, at which extent brain-connectivity metrics reflect the age of an individual and whether treatments or lifestyle factors such as physical activity influence the age-connectivity match is still unclear. Here, we assessed the level of physical activity and collected brain images from healthy participants (N=155) ranging from 10 to 80 years to build functional (resting-state) and structural (tractography) connectivity matrices that were combined as connectivity descriptors. Connectivity descriptors were used to compute a maximum likelihood age estimator that was optimized by minimizing the mean absolute error. The connectivity-based estimated age, i.e. the brain-connectome age (BCA), was compared to the chronological age (ChA). Our results were threefold. First, we showed that ageing widely affects the structural-functional connectivity of multiple structures, such as the anterior part of the default mode network, basal ganglia, thalamus, insula, cingulum, hippocampus, parahippocampus, occipital cortex, fusiform, precuneus and temporal pole. Second, our analysis showed that the structure-function connectivity between basal ganglia and thalamus to orbitofrontal and frontal areas make a major contribution to age estimation. Third, we found that high levels of physical activity reduce BCA as compared to ChA, and vice versa, low levels increment it. In conclusion, the BCA model results highlight the impact of physical activity and the key role played by the connectivity between basal ganglia and thalamus to frontal areas on the process of healthy aging. Notably, the same methodology can be generally applied both to evaluate the impact of other factors and therapies on brain ageing, and to identify the structural-functional brain connectivity correlate of other biomarkers than ChA.