Static and Dynamic Connectivity Structure of White-Matter Functional Network across the Adult Lifespan

Abstract Background. The maturation and ageing of the human brain involve intricate biological processes that result in complex changes in brain structure and function. Although the effects of aging on functional connectivity within gray matter (GM) regions have been extensively studied, the investigation of white matter (WM) functional changes remains limited. Methods. In this study, our aim was to investigate age-related trajectory in WM functional dynamics using resting-state functional magnetic resonance imaging (rs-fMRI) data from a large lifespan sample of 494 individuals. First, GM and WM functional networks (FNs) were identified by k-means clustering. Next, we performed static and dynamic analysis of WM functional network connectivity (FNC) to explore age effect on WM-FNs. Furthermore, we investigated recurrent patterns of dynamic FNC. Finally, we conducted several validation analyses to ensure replicability. Results. We identified 9 reliable WM and 12 GM FNs. The findings revealed age-related effects on WM FNC strength and WM-GM FNC dynamics, primarily including linear positive and U-shaped age trajectories in static FNC strength, as well as linear negative and inverted U-shaped age trajectories in FNC temporal variability. Additionally, we identified three distinct brain states with significant age-related differences. The aforementioned findings were largely replicated in the validation analysis. Conclusion. High integration and low temporal variability in WN-GM FNC may reflect a less efficient network system in older adults. These findings enhance our understanding of brain aging processes and provide insights into the trajectory of WM functional dynamics during normal ageing.