Structure-Function Interactions in the Hippocampus and Prefrontal Cortex Are Associated with Episodic Memory in Healthy Aging

Abstract

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 multiecho 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 underlie 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.

Keywords: aging; compensation; episodic.

Figure 1.

Diagram of analytic pipeline for image processing and analyses. 1, Cortical thickness and BOLD signal were extracted from the caudal and rostral middle frontal gyrus (cMFG and rMFG, respectively) with FreeSurfer. Anterior and posterior hippocampal volumes (antHC and postHC, respectively) and BOLD signal were extracted with ASHS. 2, BOLD was extracted from frontoparietal (FP) and extended default networks (DN), excluding parcels overlapping with the MFG. 3, Hippocampal and MFG BOLD signal were correlated with FPN-DN BOLD to create 8 × 165 matrices for each participant. 4, Partial least squares analyses were used to assess relationships between brain structure, memory performance, and functional connectivity.

Figure 2.

A, Age differences in memory performance: younger adults display better performance across list recall, associative, and source memory tasks. B, Age differences in brain structure: older adults display smaller postHC volume and less rMFG and cMFG thickness. C, Greater cMFG thickness predicted greater associative memory performance in older but not younger adults.

Figure 3.

LV1: MFG thickness, postHC volume, and episodic memory performance relate to greater RSFC in older adults. B-PLS analysis revealed an association between memory performance, brain structure, and resting-state connectivity (25.69% cross-block covariance; p < 0.01). The connectivity summary plot display results of parcel-level analyses recapitulated at the network level. Memory performance and brain structure did not significantly relate to this pattern in young adults.

Figure 4.

LV2: HC volume and all measures of episodic memory performance relate to pattern reduced RSFC in older adults. B-PLS analysis revealed an association between memory performance, brain structure, and resting-state connectivity (16.68% cross-block covariance; p < 0.05). All episodic memory processes and antHC and postHC volumes are related to this pattern in older adults; antHC and postHC volumes are inversely related to this pattern in young adults.