Early Non-rapid Eye Movement Sleep Research Articles

Conscious experiences and high-density EEG patterns predicting subjective sleep depth

What accounts for feeling deeply asleep? Standard sleep recordings only incompletely reflect subjective aspects of sleep and some individuals with so-called sleep misperception frequently feel awake although sleep recordings indicate clear-cut sleep. To identify the determinants of sleep perception, we performed 787 awakenings in 20 good sleepers and 10 individuals with sleep misperception and interviewed them about their subjective sleep depth while they underwent high-density EEG sleep recordings. Surprisingly, in good sleepers, sleep was subjectively lightest in the first 2h of non-rapid eye movement (NREM) sleep, generally considered the deepest sleep, and deepest in rapid eye movement (REM) sleep. Compared to good sleepers, sleep misperceptors felt more frequently awake during sleep and reported lighter REM sleep. At the EEG level, spatially widespread high-frequency power was inversely related to subjective sleep depth in NREM sleep in both groups and in REM sleep in misperceptors. Subjective sleep depth positively correlated with dream-like qualities of reports of mental activity. These findings challenge the widely held notion that slow wave sleep best accounts for feeling deeply asleep. Instead, they indicate that subjective sleep depth is inversely related to a neurophysiological process that predominates in early NREM sleep, becomes quiescent in REM sleep, and is reflected in high-frequency EEG activity. In sleep misperceptors, this process is more frequently active, more spatially widespread, and abnormally persists into REM sleep. These findings help identify the neuromodulatory systems involved in subjective sleep depth and are relevant for studies aiming to improve subjective sleep quality.

Sleep microstructure in Parkinson's disease: cycling alternating pattern (CAP) as a sensitive marker of early NREM sleep instability

BackgroundSleep disorders are frequent in Parkinson's disease (PD). Apart from the occurrence of REM behavior disorders, in the early phase of the disease standard sleep macrostructure evaluation was inconclusive. ObjectiveWe analyzed non-rapid eye movement (NREM) sleep microstructure (CAP) in a group of PD patients to provide an objective measure of sleep disruption. MethodsWe recruited 31 PD patients [mean age 59.5 ± 12.4 years; mean Hoehn-Yahr (H-Y) stage: 3.4 ± 1.8] and 34 age-matched non-parkinsonian subjects (mean age 61.5 ± 15.2 years) as a control group. All patients underwent full-night laboratory polysomnography (PSG). Conventional sleep macro/microstructure analysis was performed. Patients were then divided into two groups: group 1 (H-Y stage ≤ 2) and group 2 (H-Y stage ≥ 3). ResultsIn group 2 PD patients compared to controls, alterations of both sleep macrostructure and microstructure were found. The PD subgroup with milder disease (group 1) presented sleep macrostructure, movements and respiratory parameters not significantly different from controls, although their CAP rate was significantly higher and the proportion of the A1 phase of CAP was reduced (p = 0.03). Multivariate logistic regression showed that disease duration, disease severity, and arousal index emerged as independent predictive factors for CAP rate ≥55% and the A1 phase of CAP ≤40% (p < 0.05). ConclusionThe main result of our study consists in the disclosure of altered NREM sleep microstructure in PD even at an early stage of the disease, suggesting an early alteration of the central pathways involved in the NREM sleep building-up and stability.

Boosting Slow Oscillatory Activity Using tDCS during Early Nocturnal Slow Wave Sleep Does Not Improve Memory Consolidation in Healthy Older Adults.

Previous studies have demonstrated an enhancement of hippocampal-dependent declarative memory consolidation, associated slow wave sleep (SWS) and slow wave activity (SWA) after weak slow oscillatory stimulation (so-tDCS) during early non-rapid eye movement sleep (NREM) in young adults. Recent studies in older individuals could not confirm these findings. However, it remained unclear if this difference was due to variations in study protocol or to the age group under study. Here, we asked if so-tDCS promotes neurophysiological events and associated sleep-dependent memory in the visuo-spatial domain in older adults, using a stimulation protocol that closely resembled the one employed in young adults. In a randomized, placebo-controlled single-blind (participant) crossover study so-tDCS (0.75 Hz; max. current density 0.522 mA/cm(2)) vs. sham stimulation was applied over the frontal cortex of 21 healthy older subjects. Impact of stimulation on frequency band activity (linear mixed models), two declarative and one procedural memory tasks (repeated measures ANOVA) and percentage of sleep stages (comparison of means) was assessed. so-tDCS, as compared to sham, increased SWA and spindle activity immediately following stimulation, accompanied by significantly impaired visuo-spatial memory consolidation. Furthermore, verbal and procedural memory remained unchanged, while percentage of NREM sleep stage 4 was decreased over the entire night (uncorrected). so-tDCS increased SWA and spindle activity in older adults, events previously associated with stimulation-induced improved consolidation of declarative memories in young subjects. However, consolidation of visuo-spatial (primary outcome) and verbal memories was not beneficially modulated, possibly due to decline in SWS over the entire night that may have prevented and even reversed immediate beneficial effects of so-tDCS on SWA.

Lempel-Ziv complexity of cortical activity during sleep and waking in rats.

Understanding the dynamics of brain activity manifested in the EEG, local field potentials (LFP), and neuronal spiking is essential for explaining their underlying mechanisms and physiological significance. Much has been learned about sleep regulation using conventional EEG power spectrum, coherence, and period-amplitude analyses, which focus primarily on frequency and amplitude characteristics of the signals and on their spatio-temporal synchronicity. However, little is known about the effects of ongoing brain state or preceding sleep-wake history on the nonlinear dynamics of brain activity. Recent advances in developing novel mathematical approaches for investigating temporal structure of brain activity based on such measures, as Lempel-Ziv complexity (LZC) can provide insights that go beyond those obtained with conventional techniques of signal analysis. Here, we used extensive data sets obtained in spontaneously awake and sleeping adult male laboratory rats, as well as during and after sleep deprivation, to perform a detailed analysis of cortical LFP and neuronal activity with LZC approach. We found that activated brain states—waking and rapid eye movement (REM) sleep are characterized by higher LZC compared with non-rapid eye movement (NREM) sleep. Notably, LZC values derived from the LFP were especially low during early NREM sleep after sleep deprivation and toward the middle of individual NREM sleep episodes. We conclude that LZC is an important and yet largely unexplored measure with a high potential for investigating neurophysiological mechanisms of brain activity in health and disease.

Oscillating Square Wave Transcranial Direct Current Stimulation (tDCS) Delivered During Slow Wave Sleep Does Not Improve Declarative Memory More Than Sham: A Randomized Sham Controlled Crossover Study.

A 2006 trial in healthy medical students found that anodal slow oscillating tDCS delivered bi-frontally during slow wave sleep had an enhancing effect in declarative, but not procedural memory. Although there have been supporting animal studies, and similar findings in pathological groups, this study has not been replicated, or refuted, in the intervening years. We therefore tested these earlier results for replication using similar methods with the exception of current waveform (square in our study, nearly sinusoidal in the original). Our objective was to test the findings of a 2006 trial suggesting bi-frontal anodal tDCS during slow wave sleep enhances declarative memory. Twelve students (mean age 25, 9 women) free of medical problems underwent two testing conditions (active, sham) in a randomized counterbalanced fashion. Active stimulation consisted of oscillating square wave tDCS delivered during early Non-Rapid Eye Movement (NREM) sleep. The sham condition consisted of setting-up the tDCS device and electrodes, but not turning it on during sleep. tDCS was delivered bi-frontally with anodes placed at F3/F4, and cathodes placed at mastoids. Current density was 0.517 mA/cm(2), and oscillated between zero and maximal current at a frequency of 0.75 Hz. Stimulation occurred during five-five minute blocks with 1-min inter-block intervals (25 min total stimulation). The primary outcomes were both declarative memory consolidation measured by a paired word association test (PWA), and non-declarative memory, measured by a non-dominant finger-tapping test (FTT). We also recorded and analyzed sleep EEG. There was no difference in the number of paired word associations remembered before compared to after sleep [(active = 3.1 ± 3.0 SD more associations) (sham = 3.8 ± 3.1 SD more associations)]. Finger tapping improved, (non-significantly) following active stimulation [(3.6 ± 2.7 SD correctly typed sequences) compared to sham stimulation (2.3 ± 2.2 SD correctly typed sequences)]. In this study, we failed to find improvements in declarative or performance memory and could not replicate an earlier study using nearly identical settings. Specifically we failed to find a beneficial effect on either overnight declarative or non-declarative memory consolidation via square-wave oscillating tDCS intervention applied bi-frontally during early NREM sleep. It is unclear if the morphology of the tDCS pulse is critical in any memory related improvements.

Information processing during sleep and stress‐related sleep vulnerability

Previous studies showed enhanced attention and decreased inhibitory processes during early non-rapid eye movement sleep in primary insomnia patients, as measured by event-related potentials. The current study aims to examine information processing during sleep in non-insomniac individuals with high vulnerability (HV) to stress-related sleep disturbances. Twenty-seven non-insomniac individuals were recruited, 14 with low vulnerability and 13 with HV. After passing a screening interview and polysomnographic recording, subjects came to the sleep laboratory for 2 nights (a baseline night and a stress-inducing night) for event-related potentials recordings. The HV group demonstrated shorter P2 latency during the first 5 min of stage 2 sleep and higher P900 amplitudes under the stress condition during slow-wave sleep, which indicates an increased level of inhibitory processes. In addition, they had shorter N1 latencies during slow-wave sleep that could indicate an elevated level of attention processing during deep sleep. Unlike patients with chronic insomnia, individuals with high sleep vulnerability to stress show a compensatory process that may prevent external stimulation from interfering with their sleep. This may be one of the factors preventing their acute sleep disturbances from becoming chronic problems.

Breakdown in cortical effective connectivity during midazolam-induced loss of consciousness

By employing transcranial magnetic stimulation (TMS) in combination with high-density electroencephalography (EEG), we recently reported that cortical effective connectivity is disrupted during early non-rapid eye movement (NREM) sleep. This is a time when subjects, if awakened, may report little or no conscious content. We hypothesized that a similar breakdown of cortical effective connectivity may underlie loss of consciousness (LOC) induced by pharmacologic agents. Here, we tested this hypothesis by comparing EEG responses to TMS during wakefulness and LOC induced by the benzodiazepine midazolam. Unlike spontaneous sleep states, a subject's level of vigilance can be monitored repeatedly during pharmacological LOC. We found that, unlike during wakefulness, wherein TMS triggered responses in multiple cortical areas lasting for >300 ms, during midazolam-induced LOC, TMS-evoked activity was local and of shorter duration. Furthermore, a measure of the propagation of evoked cortical currents (significant current scattering, SCS) could reliably discriminate between consciousness and LOC. These results resemble those observed in early NREM sleep and suggest that a breakdown of cortical effective connectivity may be a common feature of conditions characterized by LOC. Moreover, these results suggest that it might be possible to use TMS-EEG to assess consciousness during anesthesia and in pathological conditions, such as coma, vegetative state, and minimally conscious state.

Corticospinal excitability and sleep: a motor threshold assessment by transcranial magnetic stimulation after awakenings from REM and NREM sleep.

Transcranial magnetic stimulation (TMS) is a recently established technique in the neurosciences that allows the non-invasive assessment, among other parameters, of the excitability of motor cortex. Up to now, its application to sleep research has been very scarce and because of technical problems it provided contrasting results. In fact delivering one single suprathreshold magnetic stimulus easily awakes subjects, or lightens their sleep. For this reason, in the present study we assessed motor thresholds (MTs) upon rapid eye movement (REM) and non-rapid eye movement (NREM) sleep awakenings, both in the first and in the last part of the night. Taking into account that a full re-establishment of wake regional brain activity patterns upon awakening from sleep needs up to 20-30 min, it is possible to make inferences about the neurophysiological characteristics of the different sleep stages by analyzing the variables of interest immediately after provoked awakenings. Ten female volunteers slept in the lab for four consecutive nights. During the first night the MTs were collected, following a standardized procedure: 5 min before lights off, upon stage 2 awakening (second NREM period), upon REM sleep awakening (second REM period), upon the final morning awakening (always from stage 2). Results showed that MTs increased linearly from presleep wakefulness to REM sleep awakenings, and from the latter to stage 2 awakenings. There was also a time-of-night effect on MTs upon awakening from stage 2, indicating that MTs decreased from the first to the second part of the night. The increase in corticospinal excitability across the night, which parallels the fulfillment of sleep need, is consistent with the linear decrease of auditory arousal thresholds during the night. The maximal reduction of corticospinal excitability during early NREM sleep can be related to the hyperpolarization of thalamocortical neurons, and is in line with the decreased metabolic activity of motor cortices during this sleep stage. On the contrary, the increase of MTs upon REM sleep awakenings should reflect peripheral factors. We conclude that our findings legitimate the introduction of the TMS technique as a new proper tool in sleep research.