Theta-gamma phase-phase coupling during working memory maintenance in the human hippocampus.

The theta-gamma neural coding theory suggests that multiple items are represented in working memory (WM) by a superposition of gamma cycles on theta oscillations. To enable a stable, non-interfering representation of multiple items, such a theta-gamma neural code may be reflected by phase-phase coupling, i.e., a precise locking of gamma subcycles to specific theta phases. Recent data have indicated that the hippocampus critically contributes to multi-item working memory. Therefore, we investigated phase-phase coupling patterns in the hippocampus based on intracranial EEG recordings in presurgical epilepsy patients performing a variant of the serial Sternberg WM task. In accordance with predictions of the theta-gamma coding theory, we observed increased phase-phase coupling between theta and beta/gamma activity during working memory maintenance compared to inter-trial intervals. These phase-phase coupling patterns were apparent during maintenance of two and four items, but not during maintenance of a single item, where prominent lower coupling ratios occurred. Furthermore, we observed that load-dependent changes of coupling factors correlated with individual WM capacities. Our data demonstrate that multi-item WM is associated with changes in hippocampal phase-phase coupling between theta and beta/gamma activity.