Changes in white matter functional networks across late adulthood

Abstract

IntroductionThe aging brain is characterized by decreases in not only neuronal density but also reductions in myelinated white matter (WM) fibers that provide the essential foundation for communication between cortical regions. Age-related degeneration of WM has been previously characterized by histopathology as well as T2 FLAIR and diffusion MRI. Recent studies have consistently shown that BOLD (blood oxygenation level dependent) effects in WM are robustly detectable, are modulated by neural activities, and thus represent a complementary window into the functional organization of the brain. However, there have been no previous systematic studies of whether or how WM BOLD signals vary with normal aging. We therefore performed a comprehensive quantification of WM BOLD signals across scales to evaluate their potential as indicators of functional changes that arise with aging.MethodsBy using spatial independent component analysis (ICA) of BOLD signals acquired in a resting state, WM voxels were grouped into spatially distinct functional units. The functional connectivities (FCs) within and among those units were measured and their relationships with aging were assessed. On a larger spatial scale, a graph was reconstructed based on the pair-wise connectivities among units, modeling the WM as a complex network and producing a set of graph-theoretical metrics.ResultsThe spectral powers that reflect the intensities of BOLD signals were found to be significantly affected by aging across more than half of the WM units. The functional connectivities (FCs) within and among those units were found to decrease significantly with aging. We observed a widespread reduction of graph-theoretical metrics, suggesting a decrease in the ability to exchange information between remote WM regions with aging.DiscussionOur findings converge to support the notion that WM BOLD signals in specific regions, and their interactions with other regions, have the potential to serve as imaging markers of aging.

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

“…Although the WM signal in resting-state has been gradually accepted and recognized by the field, there is a lack of research investigating how WM function and their interactions with GM change throughout the lifespan, which could provide new insights into the functional architecture basis for brain ageing. Using independent component analysis to group WM voxels into spatially distinct functional units, researchers have found that FCs within and among those units decrease significantly with aging (Li et al, 2023). Another recent study revealed three age effects on WM-GM FC pairs including a negative linear age effect, a positive linear age effect and an inverted-U-shaped age effect (Gao et al, 2023).…”