biostudies-literatureAndersson PVetenskapsrådete70189https://www.ebi.ac.uk/biostudies/studies/S-EPMC11975615biostudies-literatureUnknown46(5)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.Human brain mappingAge Differences in Brain Functional Connectivity Underlying Proactive Interference in Working Memory.PMC119756152018-01609Persson JAndersson PSchrooten MGSfalseAge 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.2025-01-01T00:00:00Z2025 Apr2026-06-02T04:19:12.555Z2026-04-14T03:14:04.966ZS-EPMC119756154019523710.1002/hbm.70189