Abstract

Hippocampal sharp-wave ripples (SWRs) are thought to play a key role in systems memory consolidation by broadcasting reactivated memory content to distributed cortical networks while we sleep. Elucidating how this hippocampal-cortical dialogue unfolds at the brain-wide level is therefore essential to understanding how sleep transforms new experiences into lasting memories. Here we combined simultaneous hippocampal intracranial EEG and 21-channel scalp EEG during overnight sleep to characterize the large-scale cortical impact of hippocampal ripple events. We found that individual hippocampal ripples elicited a decodable, phase-locked cortical response at the scalp level. This cortical response was followed by increases in cortico-cortical synchronization and network density in the spindle-band. Mediation analyses revealed a sequential pathway in which ripple magnitude predicted large-scale cortical connectivity through this intermediate cortical response and subsequent spindle activity. These findings demonstrate that hippocampal ripples trigger a two-step cascade, i.e., an early stereotyped cortical response followed by spindle-mediated network synchronization, consistent with the view that SWRs co-activate distributed cortical nodes and potentiate the cortical-cortical connections that support memory consolidation. By demonstrating that ripple-related cortical responses are decodable noninvasively, our results moreover suggest a new strategy for inferring hippocampal ripple activity from scalp electrophysiology. ### Competing Interest Statement The authors have declared no competing interest. Marie Skłodowska-Curie Postdoctoral Fellowship, SEP-210878699 European Research Council, 101001121