Representation of visual sequences in the tuning and topology of neuronal activity in the human hippocampus

Time is a critical component of memory and yet how the hippocampus incorporates temporal information with the sensory contents of memories remains unclear. We hypothesized that the hippocampus can learn arbitrary sequences through rapid changes in the tuning and population geometry of individual neurons to mirror the sequence structure. We recorded single-unit activity from 134 neurons in the hippocampus of 17 patients with epilepsy while they viewed sequences of visual scenes that were presented repeatedly in the same order by looping from the end to start. As the sequence repeated, hippocampal neurons that were initially responsive to one scene in the sequence began responding to the other scenes proportional to their temporal proximity. The population vectors of spiking activity across recorded hippocampal neurons for each scene came to form a high-dimensional ring topology that encoded the circular structure of the sequence in a manner that preserved the serial order of the scenes. These effects were not observed when sequences were scrambled upon each repetition to destroy temporal structure, nor in brain regions outside of the hippocampus for both structured and random sequences. These findings suggest that temporal structure governs the representation of sensory stimuli in human hippocampal neurons.