Order matters: sleep spindles contribute to memory consolidation only when followed by rapid-eye-movement sleep

Abstract

Sleep is known to benefit memory consolidation, but little is known about the contribution of sleep stages within the sleep cycle. The sequential hypothesis proposes that memories are first replayed during non-rapid-eye-movement (NREM or N) sleep and then integrated into existing networks during rapid-eye-movement (REM or R) sleep, two successive critical steps for memory consolidation. However, it lacks experimental evidence as N always precedes R sleep in physiological conditions. We tested this sequential hypothesis in patients with central hypersomnolence disorder, including patients with narcolepsy who present the unique, anti-physiological peculiarity of frequently falling asleep in R sleep before entering N sleep. Patients performed a visual perceptual learning task before and after daytime naps stopped after one sleep cycle, starting in N or R sleep and followed by the other stage (i.e. N-R vs. R-N sleep sequence). We compared over-nap changes in performance, reflecting memory consolidation, depending on the sleep sequence during the nap. Thirty-six patients who slept for a total of 67 naps were included in the analysis. Results show that sleep spindles are associated with memory consolidation only when N is followed by R sleep, that is in physiologically ordered N-R naps, thus providing support to the sequential hypothesis in humans. In addition, we found a negative effect of rapid-eye-movements in R sleep on perceptual consolidation, highlighting the complex role of sleep stages in the balance to remember and to forget.

A model of autonomous interactions between hippocampus and neocortex driving sleep-dependent memory consolidation

“…We found that the hippocampus helps to build neocortical representations of the new environment during NREM sleep (as in Simulation 1) and the neocortex then reinstates the old environment during REM sleep, allowing careful integration of the new information into neocortex without overwriting the old. Our proposal is strongly consistent with studies suggesting that memory reactivation during SWS sets up subsequent integration into existing knowledge during REM (59, 60), and more generally with the idea that both NREM and REM sleep are critical for memory integration, with the ordering of the stages being consequential (61, 62).…”

A model of autonomous interactions between hippocampus and neocortex driving sleep-dependent memory consolidation

“…Our proposal is strongly consistent with studies suggesting REM is important for integrating new information with existing knowledge ( 66 ) and that this process is set up by prior memory reactivation during slow wave sleep ( 67 , 68 ). It is also consonant, more generally, with the idea that both NREM and REM sleep are critical for memory integration, with the ordering of the stages being consequential ( 69 , 70 ).…”

Cortical thickness and sub-cortical volumes in post-H1N1 narcolepsy type 1: A brain-wide MRI case-control study

“…[53] NT1 patients often have naps starting in REM-sleep and then continuing to non-REMsleep (NREM), and the study found that sleep spindles only were associated with memory consolidation when the naps started with NREM-sleep followed by REM-sleep. [53] However, studies have indicated that possible memory deficits in NT1 patients seem to be limited to specific memory functions and there have been some indications of alterations of procedural memory with less effective memory consolidation as well as impaired working memory. [54] Previous structural MRI studies of narcolepsy patients [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] have revealed conflicting results involving various brain regions.…”