Non-rapid Eye Movement Sleep Slow-wave Activity Research Articles

Comparison of sleep deprivation and a low dose of ketamine on sleep and the electroencephalogram in Brown Norway rats.

Ketamine is known for its antidepressant effects, but the mechanism underlying this effect remains largely unclear. In contrast to most antidepressant drugs, the action of ketamine is rapid, suggesting a different mode of action. A rapid antidepressant effect is also observed following sleep deprivation (SD). In the present study, we aimed to evaluate the effect of a 6-h SD and acute ketamine treatment on vigilance states, locomotor activity, and electroencephalogram (EEG) power density spectra in Brown Norway rats under constant condition over 2 recording days. After SD and after the initial waking period induced by ketamine, both treatments induced a similar increase in non-rapid eye movement (NREM) sleep and EEG slow-wave activity (SWA) in NREM sleep. Rapid eye movement (REM) sleep was reduced immediately after both treatments but was recovered later only after the SD. The effects on the waking EEG differed between the treatments, with a faster theta peak during and after SD, and no change in the waking spectrum after ketamine. In conclusion, SD and ketamine both lead to an acute increment in NREM sleep SWA as well as in a reduction in REM sleep. The results suggest that selective suppression of REM sleep, combined with enhancement of SWA during NREM may be effective in the treatment of depression.

Reduced Regional NREM Sleep Slow-Wave Activity Is Associated With Cognitive Impairment in Parkinson Disease

Growing evidence implicates a distinct role of disturbed slow-wave sleep in neurodegenerative diseases. Reduced non-rapid eye movement (NREM) sleep slow-wave activity (SWA), a marker of slow-wave sleep intensity, has been linked with age-related cognitive impairment and Alzheimer disease pathology. However, it remains debated if SWA is associated with cognition in Parkinson disease (PD). Here, we investigated the relationship of regional SWA with cognitive performance in PD. In the present study, 140 non-demented PD patients underwent polysomnography and were administered the Montréal Cognitive Assessment (MoCA) to screen for cognitive impairment. We performed spectral analysis of frontal, central, and occipital sleep electroencephalography (EEG) derivations to measure SWA, and spectral power in other frequency bands, which we compared to cognition using linear mixed models. We found that worse MoCA performance was associated with reduced 1–4 Hz SWA in a region-dependent manner (F2, 687 =11.67, p < 0.001). This effect was driven by reduced regional SWA in the lower delta frequencies, with a strong association of worse MoCA performance with reduced 1–2 Hz SWA (F2, 687 =18.0, p < 0.001). The association of MoCA with 1–2 Hz SWA (and 1–4 Hz SWA) followed an antero-posterior gradient, with strongest, weaker, and absent associations over frontal (rho = 0.33, p < 0.001), central (rho = 0.28, p < 0.001), and occipital derivations, respectively. Our study shows that cognitive impairment in PD is associated with reduced NREM sleep SWA, predominantly in lower delta frequencies (1–2 Hz) and over frontal regions. This finding suggests a potential role of reduced frontal slow-wave sleep intensity in cognitive impairment in PD.

Sleep Disturbance Forecasts β-Amyloid Accumulation across Subsequent Years

Experimental sleep-wake disruption in rodents and humans causally modulates β-amyloid (Aβ) dynamics (e.g., [1-3]). This leads to the hypothesis that, beyond cross-sectional associations, impaired sleep structure and physiology could represent prospective biomarkers of the speed with which Aβ accumulates over time. Here, we test the hypothesis that initial baseline measures of non-rapid eye movement (NREM) sleep slow-wave activity (SWA) and sleep quality (efficiency) provide future forecasting sensitivity to the rate of Aβ accumulation over subsequent years. A cohort of clinically normal older adults was assessed using objective sleep polysomnography in combination with longitudinal tracking of Aβ accumulation with [11C]PiB positron emission tomography (PET) imaging. Both the proportion of NREM SWA below 1Hz and the measure of sleep efficiency predicted the speed (slope) of subsequent Aβ deposition over time, and these associations remained robust when taking into account additional cofactors of interest (e.g., age, sex, sleep apnea). Moreover, these measures were specific, such that no other macro- and microphysiological architecture metrics of sleep demonstrated such sensitivity. Our data support the proposal that objective sleep markers could be part of a set of biomarkers that statistically forecast the longitudinal trajectory of cortical Aβ deposition in the human brain. Sleep may therefore represent a potentially affordable, scalable, repeatable, and non-invasive tool for quantifying of Aβ pathological progression, prior to cognitive symptoms of Alzheimer's disease (AD).

Reduced non-rapid eye movement sleep is associated with tau pathology in early Alzheimer's disease.

In Alzheimer's disease (AD), deposition of insoluble amyloid-β (Aβ) is followed by intracellular aggregation of tau in the neocortex and subsequent neuronal cell loss, synaptic loss, brain atrophy, and cognitive impairment. By the time even the earliest clinical symptoms are detectable, Aβ accumulation is close to reaching its peak and neocortical tau pathology is frequently already present. The period in which AD pathology is accumulating in the absence of cognitive symptoms represents a clinically relevant time window for therapeutic intervention. Sleep is increasingly recognized as a potential marker for AD pathology and future risk of cognitive impairment. Previous studies in animal models and humans have associated decreased non-rapid eye movement (NREM) sleep slow wave activity (SWA) with Aβ deposition. In this study, we analyzed cognitive performance, brain imaging, and cerebrospinal fluid (CSF) AD biomarkers in participants enrolled in longitudinal studies of aging. In addition, we monitored their sleep using a single-channel electroencephalography (EEG) device worn on the forehead. After adjusting for multiple covariates such as age and sex, we found that NREM SWA showed an inverse relationship with AD pathology, particularly tauopathy, and that this association was most evident at the lowest frequencies of NREM SWA. Given that our study participants were predominantly cognitively normal, this suggested that changes in NREM SWA, especially at 1 to 2 Hz, might be able to discriminate tau pathology and cognitive impairment either before or at the earliest stages of symptomatic AD.

Cortical region-specific sleep homeostasis in mice: effects of time of day and waking experience.

Sleep–wake history, wake behaviors, lighting conditions, and circadian time influence sleep, but neither their relative contribution nor the underlying mechanisms are fully understood. The dynamics of electroencephalogram (EEG) slow-wave activity (SWA) during sleep can be described using the two-process model, whereby the parameters of homeostatic Process S are estimated using empirical EEG SWA (0.5–4 Hz) in nonrapid eye movement sleep (NREMS), and the 24 hr distribution of vigilance states. We hypothesized that the influence of extrinsic factors on sleep homeostasis, such as the time of day or wake behavior, would manifest in systematic deviations between empirical SWA and model predictions. To test this hypothesis, we performed parameter estimation and tested model predictions using NREMS SWA derived from continuous EEG recordings from the frontal and occipital cortex in mice. The animals showed prolonged wake periods, followed by consolidated sleep, both during the dark and light phases, and wakefulness primarily consisted of voluntary wheel running, learning a new motor skill or novel object exploration. Simulated SWA matched empirical levels well across conditions, and neither waking experience nor time of day had a significant influence on the fit between data and simulation. However, we consistently observed that Process S declined during sleep significantly faster in the frontal than in the occipital area of the neocortex. The striking resilience of the model to specific wake behaviors, lighting conditions, and time of day suggests that intrinsic factors underpinning the dynamics of Process S are robust to extrinsic influences, despite their major role in shaping the overall amount and distribution of vigilance states across 24 hr.

Homeostatic regulation of sleep in the white-crowned sparrow (Zonotrichia leucophrys gambelii)

BackgroundSleep is regulated by both a circadian and a homeostatic process. The homeostatic process reflects the duration of prior wakefulness: the longer one stays awake, the longer and/or more intense is subsequent sleep. In mammals, the best marker of the homeostatic sleep drive is slow wave activity (SWA), the electroencephalographic (EEG) power spectrum in the 0.5–4 Hz frequency range during non-rapid eye movement (NREM) sleep. In mammals, NREM sleep SWA is high at sleep onset, when sleep pressure is high, and decreases progressively to reach low levels in late sleep. Moreover, SWA increases further with sleep deprivation, when sleep also becomes less fragmented (the duration of sleep episodes increases, and the number of brief awakenings decreases). Although avian and mammalian sleep share several features, the evidence of a clear homeostatic response to sleep loss has been conflicting in the few avian species studied so far. The aim of the current study was therefore to ascertain whether established markers of sleep homeostasis in mammals are also present in the white-crowned sparrow (Zonotrichia leucophrys gambelii), a migratory songbird of the order Passeriformes. To accomplish this goal, we investigated amount of sleep, sleep time course, and measures of sleep intensity in 6 birds during baseline sleep and during recovery sleep following 6 hours of sleep deprivation.ResultsContinuous (24 hours) EEG and video recordings were used to measure baseline sleep and recovery sleep following short-term sleep deprivation. Sleep stages were scored visually based on 4-sec epochs. EEG power spectra (0.5–25 Hz) were calculated on consecutive 4-sec epochs. Four vigilance states were reliably distinguished based on behavior, visual inspection of the EEG, and spectral EEG analysis: Wakefulness (W), Drowsiness (D), slow wave sleep (SWS) and rapid-eye movement (REM) sleep. During baseline, SWA during D, SWS, and NREM sleep (defined as D and SWS combined) was highest at the beginning of the major sleep period and declined thereafter. Moreover, peak SWA in both SWS and NREM sleep increased significantly immediately following sleep deprivation relative to baseline.ConclusionAs in mammals, sleep deprivation in the white-crowned sparrow increases the intensity of sleep as measured by SWA.