A gradient of electrophysiological novelty responses along the human hippocampal long axis.

The hippocampus is implicated in novelty detection, thought to be important for regulating entry of information into long-term memory. Whether electrophysiological responses to novelty differ along the human hippocampal long axis is currently unknown. By recording from electrodes implanted longitudinally in the hippocampus of epilepsy patients, here we show a gradual increase of theta frequency oscillatory power from anterior to posterior in response to unexpected stimuli, superimposed on novelty responses common to all long axis portions. Intracranial event-related potentials (iERPs) were larger for unexpected vs. expected stimuli and demonstrated a polarity inversion between the hippocampal head (HH) and body (HB). We observed stronger theta coherence between HH and hippocampal tail (HT) than between HB and HT, similarly for expected and unexpected stimuli. This was accompanied by theta and alpha traveling waves with surprisingly variable direction of travel characterized by a [~]180{degrees} phase lag between hippocampal poles. Interestingly, this phase lag showed a pronounced phase offset between anterior and middle (HH-HB) hippocampal portions coinciding anatomically with a drop in theta coherence and the novelty iERP polarity inversion. Our findings indicate common response properties along the hippocampal long axis to unexpected stimuli, as well as a multifaceted, non-uniform engagement along the long axis for novelty processing.