Opposing effects of aging on large-scale brain systems for memory encoding and cognitive control

Abstract

Episodic memory declines with advancing age. Neuroimaging studies have associated such decline to age-related changes in general cognitive-control networks as well as to changes in process-specific encoding or retrieval networks. To assess the specific influence of aging on encoding and retrieval processes and associated brain systems, it is vital to dissociate encoding and retrieval from each other and from shared cognitive-control processes. We used multivariate partial-least-squares to analyze functional magnetic resonance imaging data from a large population-based sample (n = 292, 25-80 years). The participants performed a face-name paired-associates task and an active baseline task. The analysis revealed two significant network patterns. The first reflected a process-general encoding-retrieval network that included frontoparietal cortices and posterior hippocampus. The second pattern dissociated encoding and retrieval networks. The anterior hippocampus was differentially engaged during encoding. Brain scores, representing whole-brain integrated measures of how strongly an individual recruited a brain network, were correlated with cognitive performance and chronological age. The scores from the general cognitive-control network correlated negatively with episodic memory performance and positively with age. The encoding brain scores, which strongly reflected hippocampal functioning, correlated positively with episodic memory performance and negatively with age. Univariate analyses confirmed that bilateral hippocampus showed the most pronounced activity reduction in older age, and brain structure analyses found that the activity reduction partly related to hippocampus atrophy. Collectively, these findings suggest that age-related structural brain changes underlie age-related reductions in the efficient recruitment of a process-specific encoding network, which cascades into upregulated recruitment of a general cognitive-control network.

Figure 1.

Singular images, brain scores, and signal changes (for selected local maxima) for the two significant LVs. A, E, Singular images for LV1 and LV2, which display regions reliably contributing to the pattern identified in each LV. For LV1, red represents regions showing greater activity during encoding and retrieval relative to baseline, whereas green represents brain regions more active during baseline than during encoding and retrieval. B, F, Brain scores for LV1 and LV2, reflecting commonality and differentiation, respectively, for episodic encoding and retrieval. C, D, Signal changes in two regions contributing to LV1. Error bars indicate 1 SE. G, H, Signal changes in left and right PFC, highlighting the HERA model.

Figure 2.

Anatomical localization and signal changes for the posterior and anterior hippocampus identified by LV1 and LV2, respectively. A, Signal changes for the bilateral posterior hippocampus, which mimics the brain score pattern identified by LV1 (greater activity during both encoding and retrieval relative baseline). Error bars indicate 1 SE. B, Functional activations of the bilateral posterior (identified by LV1) and anterior (identified by LV2) hippocampus overlaid on the sample-specific template created by DARTEL (red, posterior hippocampus; green, anterior hippocampus). C, Signal changes for the bilateral anterior hippocampus, reflecting greater activation during encoding than during retrieval.

Figure 3.

Upregulated recruitment of the task-general network as a function of encoding-specific network integrity. Age- and performance-matched older adults were subdivided on basis of their engagement of the process-specific encoding network (LV2). The bar graph displays the corresponding engagement of the process-general network (LV1). Process-general network engagement, as reflected by brain scores, was highest for older adults with low engagement of the encoding network (old low), intermediate for elderly with higher encoding-network recruitment (old high), and lowest for younger adults.

Figure 4.

Age effects in relation to brain activity during encoding. The upper part displays brain activity for the main effect of encoding versus baseline (cortical renderings in the top corners). Main (blue) and age (red) effects of encoding in the hippocampus are shown on sagittal and coronal slices. The line graphs show differences in hippocampal activity (β values from the regression analysis) as a function of age. The age-related functional decline in the hippocampus accelerated with increasing age. Rectangles highlight participants in the oldest group (70–80 years) who had lowest hippocampal activation. At bottom, a plot of the hippocampal β-value distribution across all participants (n = 292). Dashed rectangle indicates participants with lowest hippocampal activation. L, left; r, right.

Figure 5.

Results from the multimodal BPM analysis overlaid on the sample-specific template. Circles indicate structural and functional age-related decline in bilateral anterior hippocampus. A, Regression analysis reflecting age-related functional differences. B, Regression analysis demonstrating age-related GM volume loss. C, Regression analysis indicating age-related functional changes after controlling for local GM loss. When controlling for GM loss, age-related functional decline was still apparent in bilateral hippocampus.