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.

Neural Variability in the Prefrontal Cortex as a Reflection of Neural Flexibility and Stability in Patients With Parkinson Disease

“…These studies have generally reported that BOLD variability is negatively related to age (lower in healthy controls) 15,16 and positively related to task performance. 12,18 However, a careful look reveals that these patterns of change in BOLD variability differ between brain regions and task requirements. For example, healthy controls presented greater BOLD variability in superior frontal and inferior temporal gyri 15 and lower BOLD variability in supplementary motor areas and inferior frontal gyrus.…”

Moment-to-moment fluctuations of hemodynamic responses in posterior default mode networks differentially predict level of attentional lapses in adolescents with Attention-Deficit/Hyperactivity Disorder

“…Higher IIVRT has in general been recognized as a marker of poorer brain health (61) and to predict all-cause mortality in adults (62). Further, moment-to-moment fluctuations of brain signaling also has been suggested as an important parameter of brain health (36, 52). This not only emphasizes the general importance of better understanding the neural mechanisms that give rise to IIVRT, it underscores the need to characterize how dysfunction in this neurobiology yields the typically high IIVRT found in most patients with ADHD.…”

“…We hoped to extend prior findings of IIVRT-related neurobiology primarily learned from attention paradigms by examining a moderate-sized adolescent non-ADHD and ADHD sample who performed a Go/NoGo fMRI task (35). We predicted that Go/NoGo task hemodynamic response amplitude variability in both anterior and posterior DMN hub regions would predict higher ADHD IIVRT (24, 36, 37). Secondary expectations included that mean amplitude would predict similarly as previous Go/NoGo fMRI studies higher IIVRT in pre-motor systems (31, 38) and temporal lobe cortex (2, 23).…”

“…Accordingly, the goals of this study were a) to concurrently evaluate task-elicited responsiveness and variability within all the brain’s major neural systems to determine which are linked to high IIVRT and are dysfunctional in ADHD, while retaining a specific focus on DMN as the leading candidate neural system, and b) to extend prior findings of IIVRT-related neurobiology learned primarily from attention paradigms by examining a moderate-sized adolescent non-ADHD and ADHD sample who performed a Go/NoGo fMRI task (35). We predicted that Go/NoGo task hemodynamic response amplitude variability in both anterior and posterior DMN hub regions would predict higher ADHD IIVRT (24, 36, 37). Secondary expectations included that mean amplitude would predict similarly as previous Go/NoGo fMRI studies higher IIVRT in pre-motor systems (31, 38) and temporal lobe cortex (2, 23).…”

Slow fluctuations in ongoing brain activity decrease in amplitude with ageing yet their impact on task-related evoked responses is dissociable from behaviour

“…In fact, age differences in BOLD SD might be explained by changes in cardiovascular and cerebrovascular factors that affect the link between neuronal activity and changes in blood flow (Tsvetanov et al, 2020). Moreover, BOLD MSSD, a measure of how much the BOLD signal changes across successive observations, is more often increased rather than decreased in older adults (Boylan et al, 2021;Nomi et al, 2017;Samanez-Larkin et al, 2010), highlighting the fact that agerelated changes in signal dynamics can result in more or less "signal variability" depending on the used metric. In fact, the relationship between the non-invasive measures of brain signal variability used in human neuroscience and neuronal noise is not trivial.…”