Events that violate predictions are thought to not only modulate activity within the hippocampus and PFC but also enhance communication between the two regions. Scalp and intracranial EEG studies have shown that oscillations in the theta frequency band are enhanced during processing of contextually unexpected information. Some theories suggest that the hippocampus and PFC interact during processing of unexpected events, and it is possible that theta oscillations may mediate these interactions. Here, we had the rare opportunity to conduct simultaneous electrophysiological recordings from the human hippocampus and PFC from two patients undergoing presurgical evaluation for pharmacoresistant epilepsy. Recordings were conducted during a task that involved encoding of contextually expected and unexpected visual stimuli. Across both patients, hippocampal–prefrontal theta phase synchronization was significantly higher during encoding of contextually unexpected study items, relative to contextually expected study items. Furthermore, the hippocampal–prefrontal theta phase synchronization was larger for contextually unexpected items that were later remembered compared with later forgotten items. Moreover, we did not find increased theta synchronization between the PFC and rhinal cortex, suggesting that the observed effects were specific to prefrontal–hippocampal interactions. Our findings are consistent with the idea that theta oscillations orchestrate communication between the hippocampus and PFC in support of enhanced encoding of contextually deviant information.

Functional magnetic resonance imaging was used to identify regions involved in working memory (WM) retrieval. Neural activation was examined in two WM tasks: an item recognition task, which can be mediated by a direct-access retrieval process, and a judgment of recency task that requires a serial search. Dissociations were found in the activation patterns in the hippocampus and in the left inferior frontal gyrus (LIFG) when the probe contained the most recently studied serial position (where a test probe can be matched to the contents of focal attention) compared to when it contained all other positions (where retrieval is required). The data implicate the hippocampus and the LIFG in retrieval from WM, complementing their established role in long-term memory. Results further suggest that the left posterior parietal cortex (LPPC) supports serial retrieval processes that are often required to recover temporal order information. Together, these data suggest that the LPPC, the LIFG, and the hippocampus collectively support WM retrieval. Critically, the reported findings support accounts that posit a distinction between representations maintained in and outside of focal attention, but are at odds with traditional dual-store models that assume distinct mechanisms for short- and long-term memory representations.

Although the general role of the medial-temporal lobe (MTL) in episodic memory is well established, controversy surrounds the precise division of labor between distinct MTL subregions. The perirhinal cortex (PrC) has been hypothesized to support nonassociative item encoding that contributes to later familiarity, whereas the hippocampus supports associative encoding that selectively contributes to later recollection. However, because previous paradigms have predominantly used recollection of the item context as a measure of associative encoding, it remains unclear whether recollection of different kinds of episodic detail depends on the same or different MTL encoding operations. In our current functional magnetic resonance imaging study, we devised a subsequent memory paradigm that assessed successful item encoding in addition to the encoding of two distinct episodic details: an item–color and an item–context detail. Hippocampal encoding activation was selectively enhanced during trials leading to successful recovery of either an item–color or item–context association. Moreover, the magnitude of hippocampal activation correlated with the number, and not the kind, of associated details successfully bound, providing strong evidence for a role of the hippocampus in domain-general associative encoding. By contrast, PrC encoding activation correlated with both nonassociative item encoding as well as associative item–color binding, but not with item–context binding. This pattern suggests that the PrC contributions to memory encoding may be domain-specific and limited to the binding of items with presented item-related features. Critically, together with a separately conducted behavioral study, these data raise the possibility that PrC encoding operations—in conjunction with hippocampal mechanisms—contribute to later recollection of presented item details.