Functional Alterations in Gray Matter Networks Mediated by White Matter During the Aging Process

Extensive research has been carried out to investigate changes in various gray matter (GM) regions during the aging process using resting-state functional MRI. However, the impact of aging on the functional connectivity (FC) between white matter (WM) and GM, particularly white matter-gray matter functional connectivity (WM-GM FC), remains largely unknown. This study proposes a novel method for constructing functional networks that integrate both WM and GM.

By utilizing data from a lifespan cohort of 439 healthy adults, we devised a covariance-based approach to establish a gray matter-white matter-gray matter (GM-WM-GM) mediated network. The FC between GM and WM was quantified using the Johns Hopkins University International Consortium of Brain Mapping-Diffusion Tensor Imaging-81 WM atlas in combination with the Automated Anatomical Labeling atlas. First, the WM-GM FC was calculated via Pearson correlation coefficients between WM and GM regions, followed by the standardization of the resulting matrix. The GM-WM-GM FC was then constructed using the covariance matrix. Furthermore, topological properties were calculated for GM-WM-GM networks. Finally, the age effect of GM-WM-GM and its topology were explored.

Our findings reveal a significant age-related decline in intranetwork connectivity and global network efficiency, while internetwork connectivity followed an inverted U-shaped pattern, suggesting functional dedifferentiation in the aging brain. Despite relatively stable local efficiency, the observed reduction in global efficiency indicates a weakening of long-range neural connections. Additionally, a decrease in network modularity further supports this trend.

These results offer novel insights into the age-associated reorganization of brain networks, enhancing our understanding of the neural mechanisms underlying normal aging.