Abstract Physical exercise acutely improves hippocampal-based learning and memory in rodents and humans. While animal studies have mainly 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 for exercise-induced effects on human hippocampal-cortical circuits remains unknown. A growing body of evidence supports the critical role of hippocampal sharp wave-ripples (SWRs) in learning and memory. Moreover, recent studies suggest that the coupling between ripples in the hippocampus and neocortex reflect acute modulations in inter-regional connectivity required by mnemonic processes. Here, we examine the hypothesis that exercise modulates hippocampal SWR events and their coupling with ripples in other cortical areas. We performed intracranial recordings in neurosurgery patients during awake resting state, before and after one session of aerobic exercise. Exercise elicited an increase in ripple rate and duration in mesio-temporal areas (hippocampus, amygdala and parahippocampal gyrus). These changes in ripple features were also observed in the limbic and the default mode (DMN) networks. Furthermore, after exercise, we observed an increase in coupling and phase synchrony between ripples in these two networks and hippocampal SWRs. Our results elucidate the potential mechanisms by which aerobic exercise elicits its reported short-term effects in cognition. Further investigations are needed to explore how these exercise-induced acute modulations contribute to long-term changes in neural plasticity. Significance Statement Physical activity is a modifiable lifestyle factor that improves cognitive function and prevents age-related cognitive decline. Even one session of exercise can enhance hippocampal-based memory and learning. However, the neurophysiological mechanisms by which exercise acutely affects human cognition remain unknown. Using intracranial recordings in neurosurgical patients we show that the hippocampus and neocortex often synchronize their activities via high-frequency neural synchrony events known as ripples. After exercise, hippocampal and neocortical ripples were prolonged and emerged more frequently. Moreover, hippocampal and neocortical ripples exhibited increased coupling and phase synchrony. These effects were neocortical region-specific, favoring structures of the limbic and default mode networks. Ultimately, our results shed light on the mechanisms behind the preventive and therapeutic potential of exercise interventions.

Exercise modulates human hippocampal-cortical ripple dynamics