Age-related changes in neural mechanisms of prospective memory

Abstract

The capability to remember and execute intentions in the future - termed prospective memory (PM) - may be of special significance for older adults to enable successful completion of important activities of daily living. Despite the importance of this cognitive function, mixed findings have been obtained regarding age-related decline in PM, and, currently, there is limited understanding of potential contributing mechanisms. In the current study, older (N=41) and younger adults (N=47) underwent task-functional MRI during performance of PM conditions that encouraged either spontaneous retrieval (Focal) or sustained attentional monitoring (Non-focal) to detect PM targets. Older adults exhibited a reduction in PM-related sustained activity within the anterior prefrontal cortex (aPFC) and associated dorsal frontoparietal cognitive control network, due to an increase in non-specific sustained activation in (no-PM) control blocks (i.e., an age-related compensatory shift). Transient PM-trial specific activity was observed in both age groups within a ventral parietal memory network that included the precuneus. However, within a left posterior inferior parietal node of this network, transient PM-related activity was selectively reduced in older adults during the non-focal condition. These age differences in sustained and transient brain activity statistically mediated age-related declines in PM performance, and were potentially linked via age-related changes in functional connectivity between the aPFC and precuneus. Together, they support an account consistent with the Dual Mechanisms of Control framework, in which age-related PM declines are due to neural mechanisms that support proactive cognitive control processes, such as sustained attentional monitoring, while leaving reactive control mechanisms relatively spared.

Keywords: Frontoparietal network; Parietal memory network; Proactive control; Prospective memory; Reactive control; Salience network; Sustained brain activity; Transient brain activity.

Figure 1.. Task paradigm.

Each scanning run consisted of three task blocks (~120 sec) alternating with four rest fixation blocks (30 sec); runs began and ended with rest blocks. In the OT condition, participants made semantic classification judgments on each trial. The instruction was to make a ‘yes’ response (button 1) if the target word (lower case) was in the same category as the preceding semantic category word (upper case), and a ‘no’ response (button 2) otherwise. In PM blocks, the instructions were identical, except that participants were asked to make an additional response (button 3, PM-target response) if a PM target occurred. In the Focal condition, the PM target was the word “table”. In the Nonfocal condition, it was the syllable “tor”.

Figure 2.. Behavioral performance.

(A) Percentage of correct PM responses and (B) PM costs (accuracy (bottom) and RT (top). Results shown for younger (YA; red) and older (OA; blue) in the Focal and Nonfocal conditions. Error bars indicate standard error of the mean. (* indicates significant effects)

Figure 3.

Sustained activation in the left anterior prefrontal cortex (aPFC) region of interest (anatomical location: −34, +56, +9; independently defined based on functional-anatomic criteria). Younger adults (YA) show sustained activity selectively in the PM Nonfocal condition, whereas in older adults (OA) sustained activity is non-selective (i.e., in both PM and OT control conditions). PM condition (PM-sus) = blue; OT control (OT-sus) = red. * indicates relevant significant effects

Figure 4.. Statistical mediation analyses.

A. Graphic depiction of analysis involving aPFC, in which the main effect of increasing age associated with reduced PM target accuracy was found to be statistically mediated by aPFC sustained activity during the OT control condition. B. Graphic depiction of analysis involving LIPL region of the PMN, in which the age x condition interaction in PM target accuracy (disproportionately lower for older adults in the Nonfocal condition) was found to be statistically mediated by transient PM target-related activity. Numbers indicate standardized path (regression) weights. Parentheses indicate the corrected standardized regression coefficient for the direct pathway, after accounting for the indirect effect.

Figure 5.. Transient brain response of ventral parietal memory network.

(A) LIPL: left inferior parietal lobe. RIPL: right inferior parietal lobe and PCU: precuneus (B) PM-pm: transient activation on PM trials (correct trials only); PM-ot: transient activation for ongoing (category decision) trials in the PM block (correct trials only); OT-ot: transient activation for ongoing trials during the OT control block (correct trials only). (C) Transient activation (PM-pm) in LIPL. Activation in terms of fMRI beta values (arbitrary units). (YA-young adult, OA- old adult; * indicates relevant significant effects)

Figure 6.. Brain-behavior correlation.

PM-related transient activity (mean activity over four regions in the ventral parietal memory network; x-axis, z-score normalized fMRI beta values) is significantly associated with PM target accuracy (y-axis, z-score normalized). Data from all participants included. OAF = older adults Focal PM; OANF = older adults Nonfocal PM; YAF = younger adults Focal PM; YANF = younger adults Nonfocal PM.

Figure 7.. Psychophysiological interaction (PPI) effect in Precuneus (PCU).

A. Overlap of a priori precuneus ROI node from the ventral parietal memory network (red), and the activation cluster resulted from the conjunction analysis of PPI effect (green; centered at +4,−68,+34), which detected consistent connectivity in all three PM task components independently (i.e. PM-sus, PM-pm, PM-ot). B. Plot of aPFC-precuneus PPI effect, broken down by age and component (error bars represent the standard error of the mean). OAF = older adults Focal PM; OANF = older adults Nonfocal PM; YAF = younger adults focalFocal PM; YANF = younger adults Nonfocal PM. PM-sus: PM sustained component; PM-pm: PM target trials; PM-ot: ongoing trials in PM block. Activation in terms of PPI beta values (arbitrary units).