Greater BOLD Variability is Associated With Poorer Cognitive Function in an Adult Lifespan Sample

Abstract

Moment-to-moment fluctuations in brain signal assessed by functional magnetic resonance imaging blood oxygenation level dependent (BOLD) variability is increasingly thought to represent important "signal" rather than measurement-related "noise." Efforts to characterize BOLD variability in healthy aging have yielded mixed outcomes, demonstrating both age-related increases and decreases in BOLD variability and both detrimental and beneficial associations. Utilizing BOLD mean-squared-successive-differences (MSSD) during a digit n-back working memory (WM) task in a sample of healthy adults (aged 20-94 years; n = 171), we examined effects of aging on whole-brain 1) BOLD variability during task (mean condition MSSD across 0-2-3-4 back conditions), 2) BOLD variability modulation to incrementally increasing WM difficulty (linear slope from 0-2-3-4 back), and 3) the association of age-related differences in variability with in- and out-of-scanner WM performance. Widespread cortical and subcortical regions evidenced increased mean variability with increasing age, with no regions evidencing age-related decrease in variability. Additionally, posterior cingulate/precuneus exhibited increased variability to WM difficulty. Notably, both age-related increases in BOLD variability were associated with significantly poorer WM performance in all but the oldest adults. These findings lend support to the growing corpus suggesting that brain-signal variability is altered in healthy aging; specifically, in this adult lifespan sample, BOLD-variability increased with age and was detrimental to cognitive performance.

Keywords: n-back; MSSD; aging; fMRI; working memory.