Coordination of Human Hippocampal Sharpwave Ripples during NREM Sleep with Cortical Theta Bursts, Spindles, Downstates, and Upstates

In rodents, waking firing patterns replay in NREM sleep during hippocampal sharpwave ripples (HC-SWRs), correlated with neocortical graphoelements (NC-GEs). NC-GEs include theta bursts, spindles, downstates, and upstates. In humans, consolidation during sleep is correlated with scalp-recorded spindles and downstates/upstates, but HC-SWRs cannot be recorded noninvasively. Here we show in humans of both sexes that HC-SWRs are highly correlated with NC-GEs during NREM, with significantly more related HC-SWRs/NC-GEs for downstates or upstates than theta bursts or spindles, in N2 than N3, in posterior than anterior HC, in frontal than occipital cortex, and ipsilaterally than contralaterally. The preferences interacted (e.g., frontal spindles co-occurred frequently with posterior HC-SWRs in N2). These preferred GEs, stages, and locations for HC-SWR/NC-GE interactions may index selective consolidation activity, although that was not tested in this study. SWR recorded in different HC regions seldom co-occurred, and were related to GE in different cortical areas, showingthat HC-NC interact in multiple transient, widespread but discrete, networks. NC-GEs tend to occur with consistent temporal relationships to HC-SW Rs, and to each other. Cortical theta bursts usually precede HC-SWRs, where they may help define cortical input triggering HC-SWR firing. HC-SWRs often follow cortical downstate onsets, surrounded by locally decreased broadband power, suggesting a mechanism synchronizing cortical, thalamic, and hippocampal activities. Widespread cortical upstates and spindles follow HC-SWRs, consistent with the hypothesized contribution by hippocampal firing during HC-SW Rs to cortical firing-patterns during upstates and spindles. Overall, our results describe how hippocampal and cortical oscillations are coordinated in humans during events that are critical for memory consolidation in rodents.