Dorsolateral prefrontal cortex promotes long-term memory formation through its role in working memory organization

Abstract

Results from neuroimaging studies have shown that the dorsolateral prefrontal cortex (DLPFC) implements processes critical for organizing items in working memory (WM). Based on its role in WM, we hypothesized that the DLPFC should contribute to long-term memory (LTM) formation by strengthening associations among items that are organized in WM. We conducted an event-related functional magnetic resonance imaging (fMRI) study to test this hypothesis by investigating prefrontal activity during performance of two different WM tasks: on "rehearse" trials, participants actively maintained triplets of words during a brief delay, whereas on "reorder" trials, participants actively organized each triplet during the delay. After scanning, subjects performed an LTM test on words presented during both WM conditions. Behavioral results showed that WM processing in the reorder condition enhanced LTM by strengthening inter-item associations. fMRI results showed that DLPFC activity specifically during reorder trials was predictive of subsequent LTM. In contrast, activity in the posterior ventrolateral prefrontal cortex was predictive of LTM for words studied on both reorder and rehearse trials. These results support the view that the DLPFC contributes to LTM formation through its role in organization of information in WM.

Figure 1.

Plot of local maxima within the lateral PFC reported in 33 fMRI studies of LTM formation. Local maxima plotted in green are those associated with subsequent memory (remembered>forgotten). Local maxima plotted in red are those associated with subsequent forgetting (forgotten>remembered). Of the 116 local maxima associated with subsequent memory, only 10 fall within the DLPFC (BA 46 and 9) compared with 106 in the VLPFC (BA 6, 44, 45, and 47). In contrast, 10 of the 11 local maxima associated with subsequent forgetting fall within the DLPFC. L, Left; R, right.

Figure 2.

Example stimuli and task timing for WM trials.

Figure 3.

Subsequent LTM performance for words studied during reorder and rehearse trials. a, Proportion of remember (gray bars) and know (black bars) hits for words studied in reorder and rehearse conditions. Error bars depict the SEM across subjects, and the asterisk denotes a significant difference in remember rates between reorder and rehearse trials. b, Difference between observed and expected numbers of recollected triplets from each memory set. The mean difference between the observed number of trials for which all three words were successfully judged as remembered and the expected number of such trials given the overall hit rate is separately plotted for reorder and rehearse trials. A positive difference indicated that subsequent memory performance was benefited by enhanced inter-item associations. Error bars depict the SEM across subjects, and the asterisk denotes that the observed expected difference was statistically significant for reorder trials.

Figure 4.

Cortical regions showing greater delay-period activity on reorder than on rehearse trials. Bilateral regions in the DLPFC (BA 9 and 46) and VLPFC (BA 44, 45, and 47) were activated in this contrast. L, Left; R, right.

Figure 5.

Time course of activation in prefrontal ROIs. The activity in the reorder and rehearse task is plotted separately for the left DLPFC, left aVLPFC, and left pVLPFC. These results show that delay-period activity in the DLPFC and aVLPFC was correlated with subsequent LTM performance specifically during reorder trials. In contrast, delay-period activation in the pVLPFC was predictive of subsequent LTM on both rehearse and reorder trials. The error bars in the time courses reflect the SEM at each time point for the reorder and rehearse tasks for each ROI.