Activity and Connectivity Differences Underlying Inhibitory Control Across the Adult Life Span

Abstract

Inhibitory control requires precise regulation of activity and connectivity within multiple brain networks. Previous studies have typically evaluated age-related changes in regional activity or changes in interregional interactions. Instead, we test the hypothesis that activity and connectivity make distinct, complementary contributions to performance across the life span and the maintenance of successful inhibitory control systems. A representative sample of healthy human adults in a large, population-based life span cohort performed an integrated Stop-Signal (SS)/No-Go task during functional magnetic resonance imaging (n = 119; age range, 18–88 years). Individual differences in inhibitory control were measured in terms of the SS reaction time (SSRT), using the blocked integration method. Linear models and independent components analysis revealed that individual differences in SSRT correlated with both activity and connectivity in a distributed inhibition network, comprising prefrontal, premotor, and motor regions. Importantly, this pattern was moderated by age, such that the association between inhibitory control and connectivity, but not activity, differed with age. Multivariate statistics and out-of-sample validation tests of multifactorial functional organization identified differential roles of activity and connectivity in determining an individual's SSRT across the life span. We propose that age-related differences in adaptive cognitive control are best characterized by the joint consideration of multifocal activity and connectivity within distributed brain networks. These insights may facilitate the development of new strategies to support cognitive ability in old age.SIGNIFICANCE STATEMENT The preservation of cognitive and motor control is crucial for maintaining well being across the life span. We show that such control is determined by both activity and connectivity within distributed brain networks. In a large, population-based cohort, we used a novel whole-brain multivariate approach to estimate the functional components of inhibitory control, in terms of their activity and connectivity. Both activity and connectivity in the inhibition network changed with age. But only the association between performance and connectivity, not activity, differed with age. The results suggest that adaptive control is best characterized by the joint consideration of multifocal activity and connectivity. These insights may facilitate the development of new strategies to maintain cognitive ability across the life span in health and disease.

Noradrenergic-dependent functions are associated with age-related locus coeruleus signal intensity differences

“…As the in vivo studies that formed the basis of these predictions for emotional reactivity 5 and inhibitory control 6,7 were fMRI studies conducted in younger adults, further research is needed to investigate how LC connectivity or reactivity is related to age-related changes in LC structural integrity. For example, a recent study using Cam-CAN data showed age-related differences in the relationship between NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-020-15410-w ARTICLE response inhibition performance and brain connectivity but not activity in a distributed inhibition network 49 , which raises the possibility of compensatory changes in response to age-related reductions in LC structural integrity.…”

“…For emotional regulation and reactivity, we used the negative regulation score (computed by subtracting the negative emotion rating from the negative watch condition from the negative regulate condition) and the negative reactivity score (computed by subtracting the neutral watch score from the negative watch score), respectively 53 . The stop signal response time (SSRT) measures response inhibition during a Stop-Signal/No-Go task and was used to represent inhibitory control 49 . To measure overall executive function, we used the time taken to complete the Hotel task, which tests the ability to plan and multitask 54,55 .…”

The effects of age on resting-state BOLD signal variability is explained by cardiovascular and cerebrovascular factors

“…This is particularly relevant to the research in neurocognitive aging, and may reduce selection bias, for example by permitting the inclusion of individuals with a wider range of hypertension, cardiovascular conditions or comorbidity. The use of RSFA as a mechanism to adjust for confounds in BOLD-fMRI, or as a predictor, will allow the development of better models of ageing and age-related disorders (Cabeza et al, 2018;Tsvetanov et al, 2018). Figure 1.…”

Dispersion of functional gradients across the lifespan

“…Ageing is consistently related to weakened within-network connectivity co-occurring with increased between-network connectivity (Geerligs 2015, Betzel 2014. Crucially, the coordination of within-and between-network connectivity supports the maintenance of general cognition (Tsvetanov et al, 2016) and performance in specific cognitive domains Tsvetanov et al, 2018) across the lifespan.…”