Eye Movement Slow Wave Sleep Research Articles

Heart Rate Variability During Rapid Eye Movement Sleep is Associated with Reduced Negative Memory Bias.

Emotional memories change over time, but the mechanisms supporting this change are not well understood. Sleep has been identified as one mechanism that supports memory consolidation, with sleep selectively benefitting negative emotional consolidation at the expense of neutral memories, with specific oscillatory events linked to this process. In contrast, the consolidation of neutral and positive memories, compared to negative memories, has been associated with increased vagally-mediated vagal heart rate variability (HRV) during wakefulness. However, how HRV during sleep contributes to emotional memory consolidation remains unexplored. We investigated how sleep oscillations and vagal contributions during sleep contribute to the consolidation of neutral and negative memories. Using a double-blind, placebo-controlled, within-subject, cross-over design, we examined the impact of pharmacological vagal suppression using zolpidem on overnight emotional memory consolidation. Thirty-two participants encoded neutral and negative pictures in the morning, followed by picture recognition tests before and after a night of sleep. Zolpidem or placebo was administered in the evening before overnight sleep, and participants were monitored with electroencephalography and electrocardiography. In the placebo condition, greater overnight improvement for neutral pictures was associated with higher vagal HRV in both Non-Rapid Eye Movement Slow Wave Sleep (NREM SWS) and REM. Additionally, the emotional memory tradeoff (i.e., difference between consolidation of neutral versus negative memories) was associated with higher vagal HRV during REM, but in this case, neutral memories were remembered better than negative memories, indicating a potential role for REM vagal HRV in promoting a positive memory bias overnight. Zolpidem, on the other hand, reduced vagal HRV during SWS, increased NREM sigma power, and eliminated the positive memory bias. Lastly, we used a stepwise linear mixed effects regression to determine how NREM sigma power and vagal HRV during REM independently explained the variance in the emotional memory tradeoff effect. We found that the addition of vagal HRV in combination with sleep significantly improved the model's fit. Overall, our results suggest that sleep brain oscillations and vagal signals synergistically interact in the overnight consolidation of emotional memories, with REM vagal HRV critically contributing to the positive memory bias.

Intersection between sleep and neurovascular coupling as the driving pathophysiology of Alzheimer’s disease

Alzheimer’s disease (AD) is the commonest cause of dementia. There are tremendous personal and systemic costs associated with the disease. Although there has been significant progress in understanding the disease process, the precise pathophysiologic mechanism remains elusive. The amyloid hypothesis is the leading theory with impaired clearance of the amyloid beta (Aβ) believed to be the underpinning disease process. However, what triggers and propagates the accumulation of Aβ remains unclear. We propose that the impairment of neurovascular coupling triggers a cascade that ultimately leads to impaired Aβ clearance. With aging there is a generalized decline in cerebral blood flow and impairment of cerebrovascular reactivity. With impairment of this neurovascular coupling, the normal bulk clearance of cerebrospinal fluid and interstitial fluid (ISF) becomes hindered. We postulate that this clearance process occurs during non-rapid eye movement slow wave sleep, driven by the tight neurovascular coupling, via a pump-like action. The impairment of ISF clearance results in change in the interstitial microenvironment from accumulation of metabolites, reactive oxygen species, metal ions and results in decreased pH. The changes in the microenvironment promotes the accumulation and aggregation of Aβ, heralding the disease process.

A single-dose, randomized, double-blind, double dummy, placebo and positive-controlled, five-way cross-over study to assess the pharmacodynamic effects of lorediplon in a phase advance model of insomnia in healthy Caucasian adult male subjects.

A 5-h phase advance model of insomnia was used to evaluate the efficacy of lorediplon, a new non-benzodiazepine hypnotic. Thirty-five male, healthy subjects were included in a five-way randomized cross-over study. During each of the periods, sleep was recorded, and residual effects were measured. All subjects received lorediplon 1, 5, and 10 mg, placebo, and zolpidem 10 mg (i.e., active control). Polysomnographic evaluation revealed that lorediplon (5 and 10 mg) significantly decreased wake after sleep onset (WASO) and increased total sleep time. Analysis by quarters of the night showed a progressive increasing effectiveness of lorediplon 10 mg across the first three quarters. Lorediplon increased non-rapid eye movement slow wave sleep and stage N2 sleep in the second and third quarters. The magnitude of these effects was dose related, with minimal effects seen with 1 mg. No residual effects were observed 13 h post dose. Lorediplon demonstrated a dose-dependent improvement in sleep, whereas zolpidem showed a more sustained WASO effect. No next-day hangover effects were observed. These sleep effects are also consistent with the pharmacokinetic profile of lorediplon. These results warrant clinical trials in patients with insomnia.

Ritanserin, A 5-HT2 Receptor Blocker, as Add-on Treatment in Narcolepsy

In a double-blind placebo-controlled trial, ritanserin (a 5-HT2 receptor blocker) 5 mg/day or placebo was added to the usual medication in 28 patients with narcolepsy during 4 wk. The effect was assessed by means of polysomnography, daily and weekly subjective evaluations, and Multiple sleep latency tests (MSLT). During the night ritanserin increased the amount of nonrapid eye movement slow wave sleep and reduced wakefulness after sleep onset. It improved the feeling of being refreshed in the morning after awakening and reduced subjective daytime sleepiness. The drug did not significantly influence sleep latency in the MSLT.