Age Differences in Brain Functional Connectivity Underlying Proactive Interference in Working Memory

Aging is typically accompanied by a decline in working memory (WM) capacity, even in the absence of pathology. Proficient WM requires cognitive control processes that can retain goal-relevant information for easy retrieval and resolve interference from irrelevant information. Aging has been associated with a reduced ability to resolve proactive interference (PI) in WM, leading to impaired retrieval of goal-relevant information. It remains unclear how age-related differences in the ability to resolve PI in WM are related to patterns of resting-state functional connectivity (rsFC) in the brain. Here, we investigated the association between PI in WM and rsFC cross-sectionally (n = 237) and 5 years longitudinally (n = 134) across the adult life span by employing both seed-based and data-driven approaches. Results revealed that the ability to resolve PI was associated with differential patterns of inferior frontal gyrus (IFG) rsFC in younger/middle-aged adults (25-60 years) and older adults (65-80 years) in two clusters centered in the vermis and caudate. Specifically, more PI was associated with stronger inferior frontal gyrus-vermis connectivity and weaker inferior frontal gyrus-caudate connectivity in older adults, while younger/middle-aged adults showed associations in the opposite directions with the identified clusters. Longitudinal analyses revealed that a reduced ability to control PI was associated with reduced inferior frontal gyrus-insula and inferior frontal gyrus-anterior cingulate cortex connectivity in older adults, while younger/middle-aged adults showed associations in the opposite direction with these clusters. Whole brain multivariate pattern analyses showed age-differential patterns of rsFC indicative of age-related structural decline and age-related compensation. The current results show that rsFC is associated with the ability to control PI in WM and that these associations are modulated by age.