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

The hippocampus plays a critical role in the formation of memories and in the representation of time, yet the coding principles that connect these functions are poorly understood. We hypothesized that hippocampal neurons selective for specific visual stimuli adjust their tuning to encode sequence structure, smoothly combining sensory and temporal codes. In epilepsy patients who underwent intracranial EEG, we recorded neuronal activity from the hippocampus and control brain regions as they viewed looping sequences of visual scenes in structured (repeating) or random orders. The firing rates of hippocampal neurons to individual scenes were modulated by temporal distance from their preferred scene in structured sequences, increasing for nearby scenes and decreasing for distant scenes; this modulation was absent in random sequences and control regions. Analysis of population activity in local field potentials revealed that the looping sequence structure was embedded in a high-dimensional ring shape representing the serial order of the scenes. These findings show that human hippocampal neurons encode sequence structure in their representational geometry, extracting topological features of experience to add temporal continuity to sensory memories.