Recent findings have led to a growing appreciation of the role of the lateral prefrontal cortex (PFC) in episodic long-term memory (LTM). Here, the authors will review results from neuropsychological and neuroimaging studies of humans and present a framework to explain how different regions of the PFC contribute to successful LTM formation. Central to this framework is the idea that different regions within the PFC implement different control processes that augment memory by enhancing or attenuating memory for certain aspects of a particular item or event. Evidence reviewed here suggests that ventrolateral regions of the PFC contribute to the ability to select goal-relevant item information, and that this processing strengthens the representation of goal-relevant features of items during LTM encoding. Dorsolateral regions of the PFC may contribute to the ability to organize multiple pieces of information in working memory, thereby enhancing memory for associations among items in LTM. Thus, dorsolateral and ventrolateral regions of the PFC may implement different control processes that support LTM formation in a complementary fashion.

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.

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Objective Episodic memory impairments represent a core deficit in schizophrenia that severely limits patients’ functional outcome. This quantitative meta-analysis of functional imaging studies of episodic encoding and retrieval tests the prediction that these deficits are most consistently associated with dysfunction in the prefrontal cortex. Method Activation likelihood estimation (ALE) was used to perform a quantitative meta-analysis of functional imaging studies that contrasted patients with schizophrenia and healthy volunteers during episodic encoding and retrieval. From a pool of 36 potential studies, 18 whole-brain studies in standard space that included a healthy comparison sample and low-level baseline contrast were selected. Results As predicted, patients showed less prefrontal activation than comparison subjects in the frontal pole, dorsolateral and ventrolateral prefrontal cortex during encoding, and the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex during retrieval. The ventrolateral prefrontal cortex encoding deficits were not present in studies that provided patients with encoding strategies, but dorsolateral prefrontal cortex deficits remained and were not secondary to group performance differences. The only medial temporal lobe finding was relatively greater patient versus comparison subject activation in the parahippocampal gyrus during encoding and retrieval. Conclusions The finding of prominent prefrontal dysfunction suggests that cognitive control deficits strongly contribute to episodic memory impairment in schizophrenia. Memory rehabilitation approaches developed for patients with frontal lobe lesions and pharmacotherapy approaches designed to improve prefrontal cortex function may therefore hold special promise for remediating memory deficits in patients with schizophrenia.

Results from functional magnetic resonance imaging (fMRI) have strongly supported the idea that the ventrolateral prefrontal cortex (VLPFC) contributes to successful memory formation, but the role the dorsolateral prefrontal cortex (DLPFC) in memory encoding is more controversial. Some findings suggest that the DLPFC is recruited when one is processing relationships between items in working memory, and this processing specifically promotes subsequent memory for these relationships. However, previous studies could not rule out the possibility that DLPFC promotes memory during all elaborative encoding conditions and contributes to memory on all subsequent associative memory tests. To address this question directly, we used functional magnetic resonance imaging (fMRI) to examine activity during two encoding tasks which prompted participants to encode either relational or item-specific information. On relational trials, participants imagined pairs of items interacting, whereas on item-specific trials, participants imagined the items spatially separated and in different sizes. After scanning we examined memory for relational information and item-specific information. FMRI results showed that DLPFC activity specifically promoted memory for relational information during relational encoding and not memory for item-specific information during item-specific encoding. In contrast, activity in the VLPFC predicted memory for both relational and item-specific information. The present results are consistent with the idea that the DLPFC specifically contributes to successful memory formation through its role in building relationships amongst items.