Theta Phase Synchronization between the Human Hippocampus and Prefrontal Cortex Increases during Encoding of Unexpected Information: A Case Study

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.