BEYOND THE HIPPOCAMPUS: EXERCISE AMPLIFIES RIPPLE-MEDIATED AMYGDALA-CORTICAL COUPLING

The amygdala plays a central role in the consolidation of emotional memories; its function is influenced by acute physical exercise via system-level mechanisms. These mechanisms include BDNF signaling, sympathetic noradrenergic activation, hypothalamic-pituitary-adrenal-axis hormones associated with arousal, and ripple-locked interactions with mesial-temporal structures. Whereas moderate-intensity exercise has been reported to alter functional connectivity in the amygdala and other affect- and reward-related brain regions, the underlying neurophysiological basis remains poorly understood. Experimental evidence indicates that high-synchrony neural events, such as hippocampal sharp wave-ripples and analogous events in other brain areas, play a key role in learning and memory. Coupling between mesial-temporal and neocortical ripples may reflect transient modulations in inter-regional connectivity required for mnemonic processing. We tested the hypothesis that exercise modulates ripple dynamics along the amygdala-neocortical axis of the human brain. We performed intracranial recordings in epilepsy patients during awake resting state periods before and after a physical exercise session. Exercise induced an increase in ripple rate across mesial structures, including the hippocampus, amygdala and parahippocampal gyrus. Analysis of ripple activity across seven canonical cortical networks (visual, somato-motor, dorsal and ventral attention, limbic, fronto-parietal, and default-mode) revealed enhanced coupling and phase-synchrony between amygdala ripples and ripples in the limbic and the default-mode networks. Notably, amygdala-cortical ripple coupling was significantly stronger than hippocampal-cortical coupling. These findings suggest that exercise enhances mesial-neocortical communication, with a prominent contribution from the amygdala. Ripple-associated modulation of cortical networks points to a mechanism by which exercise may reorganize limbic-cortical communication relevant for memory, arousal, and stress regulation.