Age-related alterations in functional connectivity along the longitudinal axis of the hippocampus and its subfields

Abstract

Aging causes hippocampal circuit alterations that differentially affect hippocampal subfields and are associated with age-related memory decline. Additionally, functional organization along the longitudinal axis of the hippocampus has revealed distinctions between anterior and posterior (A-P) connectivity. Here, we examined the functional connectivity (FC) differences between young and older adults at high-resolution within the medial temporal lobe network (entorhinal, perirhinal, and parahippocampal cortices), allowing us to explore how hippocampal subfield connectivity across the longitudinal axis of the hippocampus changes with age. Overall, we found reliably greater connectivity for younger adults than older adults between the hippocampus and PHC and PRC. This drop in functional connectivity was more pronounced in the anterior regions of the hippocampus than the posterior ones, consistent for each of the hippocampal subfields. Further, intra-hippocampal connectivity also reflected an age-related decrease in functional connectivity within the anterior hippocampus in older adults that was offset by an increase in posterior hippocampal functional connectivity. Interestingly, the anterior-posterior shift in older adults between hippocampus and PHC was predictive of lure discrimination performance on the MST, suggesting that this shift may reflect a compensation mechanism that preserves memory performance. While age-related dysfunction within the hippocampal subfields has been well-documented, these results suggest that the age-related A-P shift in hippocampal connectivity may also contribute significantly to memory decline in older adults.