Sleep spindles mediate hippocampal-neocortical coupling during long-duration ripples

Abstract

Sleep is pivotal for memory consolidation. According to two-stage accounts, memory traces are gradually translocated from hippocampus to neocortex during non-rapid-eye-movement (NREM) sleep. Mechanistically, this information transfer is thought to rely on interactions between thalamocortical spindles and hippocampal ripples. To test this hypothesis, we analyzed intracranial and scalp Electroencephalography sleep recordings from pre-surgical epilepsy patients. We first observed a concurrent spindle power increase in hippocampus (HIPP) and neocortex (NC) time-locked to individual hippocampal ripple events. Coherence analysis confirmed elevated levels of hippocampal-neocortical spindle coupling around ripples, with directionality analyses indicating an influence from NC to HIPP. Importantly, these hippocampal-neocortical dynamics were particularly pronounced during long-duration compared to short-duration ripples. Together, our findings reveal a potential mechanism underlying active consolidation, comprising a neocortical-hippocampal-neocortical reactivation loop initiated by the neocortex. This hippocampal-cortical dialogue is mediated by sleep spindles and is enhanced during long-duration hippocampal ripples.

Endogenous memory reactivation during sleep in humans is clocked by slow oscillation spindle complexes

“…That said, a recent iEEG study has shown that both hippocampal ripples and hippocampal-cortical interactions are most eminent when preceded by a cortical SOspindle complex 20 . To the extent that reactivation observed here is linked to hippocampal engagement, the timing of our effects (Fig.2 a-b) is consistent with accumulating evidence that the hippocampal-cortical dialogue is in fact initiated by cortex 20,21,[57][58][59] . One tentative interpretation of our results might thus be that cortical SO-spindle complexes trigger hippocampal memory reactivation while ensuring that the cortical target area is optimally tuned for synaptic plasticity 15,17,60 .…”

“…Lastly, hippocampal ripples are transient network oscillations and have been closely linked to reactivation/replay of learning experiences 18,19 . They have been shown to occur in the excitable troughs of the spindle, suggesting that spindles might facilitate information transfer from the hippocampus to neocortical target sites 20,21 . The efficacy of systems consolidation through memory reactivation might thus hinge on concurrent SO-spindle coupling, ensuring optimal conditions to ignite structural changes in cortical target sites 7,10,22,23 .…”

Stability of ripple events during task engagement in human hippocampus

“…Sleep data was recorded overnight, during which polysomnography (PSG) recordings were performed to allow sleep staging. Following prior methods (Iber and American Academy of Sleep Medicine., 2007;Staresina et al, 2015;Ngo et al, 2020), PSG data was classified into awake, rapid-eye movement (REM) and non-REM (NREM) sleep states. We recorded 736 minutes (12.27 hours) of PSG data where 203 minutes (27.6%)…”

“…After pre-processing steps, ripple events were identified in three general stages: i) time domain detection for identifying putative ripple events; ii) frequency domain assessment for accepting/rejecting ripple events; iii) electrode wise ripple count thresholding for inclusion/exclusion. Analytic criteria were based on prior human hippocampal ripples studies (Staresina et al, 2015;Helfrich et al, 2019;Jiang et al, 2019;Jiang et al, 2020;Ngo et al, 2020), as detailed below.…”

“…Most recently, it has been reported that ripple events occur in the human hippocampus during the performance of episodic memory tasks (Norman et al, 2019;Vaz et al, 2019). Interestingly, ripples were observed at rates equal or greater than that typically observed during NREM sleep (Jiang et al, 2020;Ngo et al, 2020). Furthermore, hippocampal ripple events were associated with neocortical reinstatement activities and successful memory retrieval (Norman et al, 2019;Vaz et al, 2019).…”