Sustained Hippocampal Theta Oscillations Reflect Experience-Dependent Learning in Backward Temporal Order Memory Retrieval

Abstract

Navigating within our neighborhood or learning a set of concepts requires remembering the relationship between individual items that are presented sequentially. Theta activity in the mammalian hippocampus is related to the encoding and recall of relational structures. However, how theta oscillations are involved in retrieving temporal order information in opposing directionality (forward vs backward) has not been characterized. Here, using intracranial recordings from 10 human epileptic patients of both genders with hippocampal electrodes, we tested the patients with a temporal order memory task in which they learned the spatial relationship among individual items arranged along a circular track and were tested on both forward-cued and backward-cued retrieval conditions. We found that sustained high-power oscillatory events in the hippocampal theta (2–8 Hz) band, as quantified by P episode rate, were higher for the backward conditions during the later stage but not in the earlier stage. The theta P episode rate results are consistent with the behavioral memory performance and the theta phase to gamma power cross-frequency coupling. Control analyses on change in theta or gamma power and their peak frequencies, aperiodic activity, hemispheric differences, and P episode duration confirm that elevated theta rhythmic activity carry specific physiological information with respect to experience-dependent (episodic) learning. In contrast, we observed a stronger effect of forward than backward retrieval for the low gamma (30–70 Hz) P episode rate irrespective of stages. Our results revealed how theta oscillations are specifically implicated in the learning process for efficient retrieval of temporal order memories under opposing directionality.