Functional connectivity correlates of sequence memory decline in healthy older adults

Episodic sequence memory is crucial for daily functioning and typically declines during aging. However, the neural mechanisms underlying this decline remain poorly understood. We examined the resting-state functional connectivity (FC) correlates of sequence memory in healthy older adults (OA), with a young adult (YA) group included for comparison. Thirty-eight OA (mean ± SD age: 69.9 ± 3.9 years; 24 women) and 20 YA (mean ± SD age: 24.2 ± 3.4 years; 14 women) completed a sequence memory task and resting-state functional magnetic resonance imaging (rsfMRI). Participants encoded sequences of greyscale pictures presented in colored frames and retrieved their sequential order. We compared the sequence memory performance (% correct) between age groups and examined associations between performance and seed-based FC patterns within each group, focusing on hippocampal and default mode network (DMN) regions. OA exhibited poorer sequence memory performance than YA. In OA, lower performance was associated with reduced FC between the left posterior hippocampus and DMN hubs, and the DMN and right posterior parietal cortex, suggesting that reduced intrinsic coupling within memory networks and between memory and attention networks contributes to sequence memory decline in aging. In YA, superior sequence memory performance correlated with higher FC between the left posterior hippocampus and right medial occipital cortex, indicating that hippocampal-perceptual integration benefits memory function. The FC in these networks did not differ between age groups, indicating a potential shift in memory-relevant connectivity in older adults rather than reduced network function per se. Our findings provide novel evidence of large-scale network correlates underlying sequence memory decline in old age and suggest qualitatively distinct connectivity patterns supporting sequence memory in young and older adults.