Human Hippocampal Theta-Gamma Phase-Amplitude Coupling Signals the Distance to Remembered Goals
In mammals, flexible navigation is believed to rely on a cognitive map of known locations supported by the hippocampus and surrounding medial temporal lobe structures. Hippocampal place cells typically exhibit spatial firing fields within a given environment. Moreover, their firing is modulated by the movement-related theta rhythm such that "theta sweeps" of place cell activity encode the trajectory towards a hidden reward location during goal-directed navigation. Here, we attempted to detect signatures of theta sweeps in the human hippocampal local field potential (LFP) recorded with intracranial EEG. Specifically, we hypothesised that sequences of locations along a planned trajectory encoded by distinct cell assemblies are associated with gamma activity at successive theta phases. To test this hypothesis, we asked N=9 patients with epilepsy to perform a spatial navigation task in desktop virtual reality while we recorded LFP signals from depth electrode contacts implanted across the medial temporal lobe. Consistent with our predictions, we found an increase in hippocampal theta-gamma phase-amplitude coupling, a decrease in gamma power, and theta phase precession of gamma activity as hidden goal locations were approached and the sequence of locations remaining to be traversed became shorter. This suggests that goal-directed hippocampal theta sweeps during navigation are reflected in LFP theta-gamma phase-amplitude coupling, and that these neural mechanisms of model-based planning are conserved across species.