Exercise enhances hippocampal-cortical ripple interactions in the human brain

Physical exercise acutely improves hippocampus-dependent memory. Whereas animal studies have offered cellular- and synaptic-level accounts of these effects, human neuroimaging studies show that exercise improves hippocampal-cortical connectivity at the macroscale level. However, the neurophysiological basis of exercise-induced effects on hippocampal-cortical circuits remains unknown. Experimental evidence supports that hippocampal sharp wave-ripples (SWR) play a critical role in learning and memory. Coupling between SWRs in the hippocampus and neocortex may reflect modulations in inter-regional connectivity required by mnemonic processes. Here, we examine the hypothesis that exercise modulates hippocampal-cortical ripple dynamics in the human brain. We performed intracranial recordings in epilepsy patients undergoing pre-surgical evaluation, during awake resting state, before and after an exercise session. Exercise increased ripple rate in the hippocampus. Exercise also enhanced the coupling and phase-synchrony between cortical ripples in the limbic and the default mode (DM) cortical networks and hippocampal SWRs. Further, higher heart rate during exercise, reflecting exercise intensity, was related to a subsequent increase in resting state ripples across specific cortical networks including the DMN. These results offer the first direct evidence that a single exercise session elicits changes in ripple events, a well-established neurophysiological marker of mnemonic processing. The characterization and anatomical distribution of the described modulation points to hippocampal ripples as a potential mechanism by which exercise elicits its reported short-term effects in cognition.