Abstract

Computational models and in vivo studies in rodents suggest that the emergence of gamma activity (40-140Hz) during memory encoding and retrieval is coupled to opposed phase states of the underlying hippocampal theta rhythm (4-9Hz). However, direct evidence for whether human hippocampal gamma-modulated oscillatory activity in memory processes is coupled to opposed phase states of the ongoing theta rhythm remains elusive. Here we recorded local field potentials (LFP) directly from the hippocampus of ten epileptic patients with depth-electrodes. We used a memory encoding and retrieval task whereby trial unique sequences of pictures depicting real-life episodes were presented and 24h later, participants were asked to recall them upon the appearance of the first picture of the encoded episodic sequence. We found theta-to-gamma cross-frequency coupling that was specific to the hippocampus during both the encoding and retrieval of episodic memories. We also revealed that gamma was coupled to opposing theta phases during both encoding and recall processes. Additionally, we observed that the degree of theta-gamma phase opposition between encoding and recall was associated with participants’ memory performance, so gamma power was modulated by theta phase for both remembered and forgotten trials, though only for remembered trials the dominant theta phase was different for encoding and recall trials. The current results offer direct empirical evidence in support of hippocampal theta-gamma phase opposition models in human long-term memory and provide fundamental insights into mechanistic predictions derived from computational and animal work, thereby contributing to establishing similarities and differences across species.