Structure-function interactions in hippocampus and prefrontal cortex are associated with episodic memory in healthy aging.

Aging comes with declines in episodic memory. Memory decline is accompanied by structural and functional alterations within key brain regions, including the hippocampus and lateral prefrontal cortex, as well as their affiliated default and frontoparietal control networks. Most studies have examined how structural or functional differences relate to memory independently. Here we implemented a multimodal, multivariate approach to investigate how interactions between individual differences in structural integrity and functional connectivity relate to episodic memory performance in healthy aging. In a sample of younger (N = 111, mean age = 22.11 years) and older (N = 78, mean age = 67.29 years) adults we analyzed structural MRI and multi-echo resting state fMRI data. Participants completed measures of list recall (free recall of words from a list), associative memory (cued recall of paired words) and source memory (cued recall of the trial type, or the sensory modality in which a word was presented). The findings revealed that greater structural integrity of the posterior hippocampus and middle frontal gyrus were linked with a pattern of increased within-network connectivity, which together were related to better associative and source memory in older adulthood. Critically, older adults displayed better memory performance in the context of decreased hippocampal volumes when structural differences were accompanied by functional reorganization. This functional reorganization was characterized by a pruning of connections between the hippocampus and the limbic and frontoparietal control networks. Our work provides insight into the neural mechanisms that underly age-related compensation, revealing that the functional architecture associated with better memory performance in healthy aging is tied to the structural integrity of the hippocampus and prefrontal cortex.Significance Statement Aging affects episodic memory and impacts the structure and function of the hippocampus and prefrontal cortex. In the present study we report how functional changes in network organization may compensate for age-related structural declines to support episodic memory. Our analyses revealed two potential mechanisms to maintain memory performance in older adulthood. First, greater structural integrity and enhanced within-network connectivity together were related to better episodic memory in older adults. Second, performance was maintained amid atrophy to the hippocampus when accompanied by a pattern of hypoconnectivity. Understanding how the healthy aging brain compensates for structural degeneration provides insight into disease progression, offering a unique perspective on the intersecting structural and functional trajectories that eventually converge to promote a shift from normative to non-normative aging.