Contributions of white matter connectivity and BOLD modulation to cognitive aging: A lifespan structure-function association study

Abstract

The ability to flexibly modulate brain activation to increasing cognitive challenge decreases with aging. This age-related decrease in dynamic range of function of regional gray matter may be, in part, due to age-related degradation of regional white matter tracts. Here, a lifespan sample of 171 healthy adults (aged 20-94) underwent MRI scanning including diffusion-weighted imaging (for tractography) and functional imaging (a digit n-back task). We utilized structural equation modeling to test the hypothesis that age-related decrements in white matter microstructure are associated with altered BOLD modulation, and both in turn, are associated with scanner-task accuracy and executive function performance. Specified structural equation model evidenced good fit, demonstrating that increased age negatively affects n-back task accuracy and executive function performance in part due to both degraded white matter tract microstructure and reduced task-difficulty related BOLD modulation. We further demonstrated that poorer white matter microstructure integrity was associated with weakened BOLD modulation, particularly in regions showing positive modulation effects, as opposed to negative modulation effects. This structure-function association study provides further evidence that structural connectivity influences functional activation, and the two mechanisms in tandem are predictive of cognitive performance, both during the task, and for cognition measured outside the scanner environment.

Age-related degradation of optic radiation white matter predicts visual, but not verbal executive functions

“…This age-related cortical disconnection is suggested to contribute to cognitive dysfunction observed in aging, especially in relation to measures of fluid cognition such as processing speed and executive function (1)(2)(3)(4)(5). In support of this theory, age-related performance variations in these cognitive domains are shown to be mediated by age differences in white matter properties (5)(6)(7)(8)(9)(10)(11)(12)(13). This evidence collectively demonstrates that age-related degradation of white matter connectivity contributes to poorer cognitive functioning in aging; yet, empirical evidence has largely been limited to the study of major association white matter tracts that link heteromodal gray matter regions supporting higher-order cognitive functioning.…”

Individual differences in attentional lapses are associated with fiber‐specific white matter microstructure in healthy adults

“…Despite these interesting findings, the fMRI studies did not take into account the white matter tracts connecting these regions. Functional brain activations are likely to be subserved by the organization of the white matter fiber tracts that make up the connections of the network (Sharp et al, 2011;Webb et al, 2019). Therefore, investigating white matter organization is just as important as identifying gray matter regions involved in handling attention.…”

“…The brain's white matter includes pathways necessary for the transmission of regulatory signals required for attention (Sharp et al, 2011;Webb et al, 2019). In particular, the white matter pathways involved in top-down control linking visual sensory cortex to parietal and prefrontal attentional areas include the three segments of superior longitudinal fasciculus (Chica et al, 2018;Thiebaut de Schotten et al, 2011): SLF-I, SLF-II, and SLF-III.…”

fMRI-guided white matter connectivity in fluid and crystallized cognitive abilities in healthy adults

“…Previous studies that combined fMRI and DTI to examine age-related changes in cognition usually focused on one or two specific cognitive tasks such as episodic (Fjell et al, 2016) and working memory (Webb et al, 2019) that tend to decline with age. However, it is essential to examine both abilities that decline (fluid abilities) as well as remain stable (crystallized abilities) with age in order to explore the mechanism underlying aging that enables certain abilities to remain stable while others decline with older age.…”

“…In Cabeza et al (2004), decreased activation was reported in the occipital cortex and increased activation in the prefrontal and parietal cortices in older than younger adults in working memory, visual attention and episodic memory tasks. The decreased activation has been attributed to worse activation capacity with older age when the processes cannot activate as much as younger adults can, and increased activation has been attributed to lower efficiency in task processing, necessitating great resources to perform the same task as younger adults (Grady, 2008;Stern, 2012).Previous studies that combined fMRI and DTI to examine age-related changes in cognition usually focused on one or two specific cognitive tasks such as episodic (Fjell et al, 2016) and working memory (Webb et al, 2019) that tend to decline with age. However, it is essential to examine both abilities that decline (fluid abilities) as well as remain stable (crystallized abilities) with age in order to explore the mechanism underlying aging that enables certain abilities to remain stable while others decline with older age.…”