Functional connectivity within and between n-back modulated regions: An adult lifespan PPI investigation

Working memory (WM) and its BOLD-related parametric modulation under load decrease with age. Functional connectivity (FC) generally increases with WM load; however, how aging impacts connectivity and whether this is load-dependent, region-dependent, or associated with cognitive performance is unclear. This study examines these questions in 170 healthy adults (Mage = 52.99 {+/-} 19.18) who completed fMRI scanning during an n-back task (0-, 2-, 3-, and 4-back). FC was estimated utilizing a modified generalized psychophysiological interaction approach with seeds from fronto-parietal (FP) and default mode (DM) regions that modulated to n-back difficulty. FC analyses focused on both connectivity during WM engagement (task vs control) and connectivity in response to increased WM load (linear slope across conditions). Each analysis utilized within- and between-region FC, predicted by age (linear or quadratic), and its associations with in- and out-of-scanner task performance. Engaging in WM either generally (task vs control) or as a function of difficulty strengthened integration within- and between-FP and DM regions. Notably, these task-sensitive functional connections were robust to the effects of age. Stronger negative FC between FP and DM regions was also associated with better WM performance in an age-dependent manner, occurring selectively in middle- and older-adults. These results suggest that FC is critical for engaging in cognitively demanding tasks, and its lack of sensitivity to healthy aging may provide a means to maintain cognition across the adult lifespan. Thus, this study highlights the contribution of maintenance in brain function to support working memory processing with aging. Impact StatementThe literature examining functional connectivity (FC) during working memory (WM) in healthy adults is mixed in both age effects and its relationship to performance. This study contributes to the literature by examining a large, adult lifespan sample, increased levels of WM load, and additional investigation of connections within and between fronto-parietal and default mode regions. Results revealed age-invariant strengthened FC during WM, suggesting that healthy aging may be resilient to FC changes. Additionally, negative FC between regions was associated with better WM performance in middle-aged and older adults, highlighting the important of FC maintenance to support successful WM ability.