Hexadirectional Modulation of High-Frequency Electrophysiological Activity in the Human Anterior Medial Temporal Lobe...

Grid cells are one of the core building blocks of spatial navigation [1]. Single-cell recordings of grid cells in the rodent entorhinal cortex revealed hexagonal coding of the local environment during spatial navigation [1]. Grid-like activity has also been identified in human single-cell recordings during virtual navigation [2]. Human fMRI studies further provide evidence that grid-like signals are also accessible on a macroscopic level [3-7]. Studies in both non-human primates [8] and humans [9, 10] suggest that grid-like coding in the entorhinal cortex generalizes beyond spatial navigation during locomotion, providing evidence for grid-like mapping of visual space during visual exploration-akin to the grid cell positional code in rodents during spatial navigation. However, electrophysiological correlates of the grid code in humans remain unknown. Here, we provide evidence for grid-like, hexadirectional coding of visual space by human high-frequency activity, based on two independent datasets: non-invasive magnetoencephalography (MEG) in healthy subjects and entorhinal intracranial electroencephalography (EEG) recordings in an epileptic patient. Both datasets consistently show a hexadirectional modulation of broadband high-frequency activity (60-120 Hz). Our findings provide first evidence for a grid-like MEG signal, indicating that the human entorhinal cortex codes visual space in a grid-like manner [8-10], and support the view that grid coding generalizes beyond environmental mapping during locomotion [4-6, 11]. Due to their millisecond accuracy, MEG recordings allow linking of grid-like activity to epochs during relevant behavior, thereby opening up the possibility for new MEG-based investigations of grid coding at high temporal resolution.