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

J Neurosci. 2019 Oct 30;39(44):8744-8761. doi: 10.1523/JNEUROSCI.2857-18.2019. Epub 2019 Sep 18.


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, showing that HC-NC interact in multiple transient, widespread but discrete, networks. NC-GEs tend to occur with consistent temporal relationships to HC-SWRs, 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-SWRs 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.SIGNIFICANCE STATEMENT Hippocampal sharpwave ripples, essential for memory consolidation, mark when hippocampal neurons replay waking firing patterns. In rodents, cortical sleep waves coordinate the transfer of temporary hippocampal to permanent cortical memories, but their relationship with human hippocampal sharpwave ripples remains unclear. We show that human hippocampal sharpwave ripples co-occur with all varieties of cortical sleep waves, in all cortical regions, and in all stages of NREM sleep, but with overall preferences for each of these. We found that sharpwave ripples in different parts of the hippocampus usually occurred independently of each other, and preferentially interacted with different cortical areas. We found that sharpwave ripples typically occur after certain types of cortical waves, and before others, suggesting how the cortico-hippocampo-cortical interaction may be organized in time and space.

Keywords: electrophysiology; hippocampus; human; memory; neocortex; sleep.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Cerebral Cortex / physiology*
  • Hippocampus / physiology*
  • Humans
  • Middle Aged
  • Neural Pathways / physiology
  • Sleep / physiology*
  • Theta Rhythm*
  • Young Adult