Rapid Eye Movement Sleep Cycles Research Articles

Human Rapid Eye Movement Sleep Shows Local Increases in Low-Frequency Oscillations and Global Decreases in High-Frequency Oscillations Compared to Resting Wakefulness.

It is often assumed that during rapid eye movement (REM) sleep the cerebral cortex homogenously shows electroencephalogram (EEG) activity highly similar to wakefulness. However, to date no studies have compared neural oscillatory activity in human REM sleep to resting wakefulness with high spatial sampling. In the current study, we evaluated high-resolution topographical changes in neural oscillatory power between both early and late naturalistic REM sleep and resting wakefulness in adult humans. All-night recordings with 256-channel high-density EEG (hd-EEG) were collected in healthy volunteers (N = 12). Topographic analysis revealed that, compared to wake, both the first and last cycle of REM sleep were associated with increased low-frequency oscillations in local central and occipital regions. In contrast, high-frequency activity in both α and β bands (8–20 Hz) was globally decreased during both early and late REM sleep cycles compared to wakefulness. No significant differences in topographic power in any frequency band were observed between REM sleep cycles occurring early and late in the night. We replicated these findings in an independent dataset (N = 33). Together, our findings show that human REM sleep shows consistent topographical changes in oscillatory power across both early and late sleep cycles compared to resting wakefulness.

B-4. Neurophysiology of sleep in humans

Studies on EEG slowing in the progression of sleep since the discovery of electroencephalogram (EEG) in the 1920s, and identification of rapid eye movement (REM) sleep in the 1950s lead to the current principle that human sleep consists of REM and non-REM (NREM) sleep cycles. In this lecture, I will review sleep-wake homeostasis. Quantitative analysis of sleep EEG has revealed that delta EEG activity is enhanced according to the length of prior wakefulness, and achieved the recovery of the brain. This provides understanding on those clinical facts that disturbed sleep accelerates physical or mental disorders. I will also review a recent topic that deep NREM sleep with delta EEG activity is an active brain process, in which memory and skills acquired during wakefulness are consolidated and made to be ready for use. In addition, such delta EEG activity during sleep is more strongly induced in those cortical areas where intensive task is loaded during wakefulness. Finally, I will consider how the above processes are controlled by the network between the thalamus and the cortex, with special reference to its relation to conventional sleep EEG patterns such as K-complex, spindle or sleep delta waves.

Sleep–wake patterns, non-rapid eye movement, and rapid eye movement sleep cycles in teenage narcolepsy

BackgroundTo further characterize sleep disorders associated with narcolepsy, we assessed the sleep–wake patterns, rapid eye movement (REM), and non-REM (NREM) sleep cycles in Chinese teenagers with narcolepsy. MethodsA total of 14 Chinese type 1 narcoleptic patients (13.4 ± 2.6 years of age) and 14 healthy age- and sex-matched control subjects (13.6 ± 1.8 years of age) were recruited. Ambulatory 24-h polysomnography was recorded for two days, with test subjects adapting to the instruments on day one and the study data collection performed on day two. ResultsCompared with the controls, the narcoleptic patients showed a 1.5-fold increase in total sleep time over 24 h, characterized by enhanced slow-wave sleep and REM sleep. Frequent sleep–wake transitions were identified in nocturnal sleep with all sleep stages switching to wakefulness, with more awakenings and time spent in wakefulness after sleep onset. Despite eight cases of narcolepsy with sleep onset REM periods at night, the mean duration of NREM–REM sleep cycle episode and the ratio of REM/NREM sleep between patients and controls were not significantly different. ConclusionOur study identified hypersomnia in teenage narcolepsy despite excessive daytime sleepiness. Sleep fragmentation extended to all sleep stages, indicating impaired sleep–wake cycles and instability of sleep stages. The limited effects on NREM–REM sleep cycles suggest the relative conservation of ultradian regulation of sleep.

Loss of REM sleep features across nighttime in REM sleep behavior disorder

ObjectivesMelatonin is a chronobiotic treatment which also alleviates rapid eye movement (REM) sleep behavior disorder (RBD). Because the mechanisms of this benefit are unclear, we evaluated the clock-dependent REM sleep characteristics in patients with RBD, whether idiopathic (iRBD) or associated with Parkinson's Disease (PD), and we compared findings with PD patients without RBD and with healthy subjects. MethodsAn overnight videopolysomnography was performed in ten iRBD patients, ten PD patients with RBD (PD + RBD+), ten PD patients without RBD (PD + RBD−), and ten controls. The rapid eye movement frequency per minute (REMs index), the tonic and phasic electromyographic (EMG) activity of the levator menti muscle, and the duration of each REM sleep episode were evaluated. A generalized linear model was applied in each group, with the REM sleep cycle (four ordinal levels) as the dependent variable, as a function of REMs index, REM sleep duration, and tonic and phasic EMG activity. ResultsFrom the first to the fourth sleep cycle, REM sleep duration progressively increased in controls only, REMs index increased in subjects without RBD but not in patients with RBD, whether idiopathic or associated with PD, whereas tonic and phasic EMG activity did not change. ConclusionsPatients with PD or iRBD lost the physiologic nocturnal increase in REM sleep duration, and patients with RBD (either with or without PD) lost the increase of REMs frequency across the night, suggesting an alteration in the circadian system in RBD. This supports the hypothesis of a direct effect of melatonin on RBD symptoms by its chronobiotic activity.

Acute exposure to evening blue‐enriched light impacts on human sleep

Light in the short wavelength range (blue light: 446-483nm) elicits direct effects on human melatonin secretion, alertness and cognitive performance via non-image-forming photoreceptors. However, the impact of blue-enriched polychromatic light on human sleep architecture and sleep electroencephalographic activity remains fairly unknown. In this study we investigated sleep structure and sleep electroencephalographic characteristics of 30 healthy young participants (16 men, 14 women; age range 20-31years) following 2h of evening light exposure to polychromatic light at 6500K, 2500K and 3000K. Sleep structure across the first three non-rapid eye movement non-rapid eye movement - rapid eye movement sleep cycles did not differ significantly with respect to the light conditions. All-night non-rapid eye movement sleep electroencephalographic power density indicated that exposure to light at 6500K resulted in a tendency for less frontal non-rapid eye movement electroencephalographic power density, compared to light at 2500K and 3000K. The dynamics of non-rapid eye movement electroencephalographic slow wave activity (2.0-4.0Hz), a functional index of homeostatic sleep pressure, were such that slow wave activity was reduced significantly during the first sleep cycle after light at 6500K compared to light at 2500K and 3000K, particularly in the frontal derivation. Our data suggest that exposure to blue-enriched polychromatic light at relatively low room light levels impacts upon homeostatic sleep regulation, as indexed by reduction in frontal slow wave activity during the first non-rapid eye movement episode.

“I Choked My Wife Again!”—A Case Report

“I Choked My Wife Again!”—A Case Report

Insufficient non-REM sleep intensity in narcolepsy-cataplexy.

To compare electroencephalogram (EEG) dynamics during nocturnal sleep in patients with narcolepsy-cataplexy and healthy controls. Fragmented nocturnal sleep is a prominent feature and contributes to excessive daytime sleepiness in narcolepsy-cataplexy. Only 3 studies have addressed changes in homeostatic sleep regulation as a possible mechanism underlying nocturnal sleep fragmentation in narcolepsy-cataplexy. Baseline sleep of 11 drug-naive patients with narcolepsy-cataplexy (19-37 years) and 11 matched controls (18-41 years) was polysomnographically recorded. The EEG was subjected to spectral analysis. None, baseline condition. All patients with narcolepsy-cataplexy but no control subjects showed a sleep-onset rapid eye movement (REM) episode. Non-REM (NREM)-REM sleep cycles were longer in patients with narcolepsy-cataplexy than in controls (P = 0.04). Mean slow-wave activity declined in both groups across the first 3 NREM sleep episodes (P<0.001). The rate of decline, however, appeared to be steeper in patients with narcolepsy-cataplexy (time constant: narcolepsy-cataplexy 51.1 +/- 23.8 minutes [mean +/- SEM], 95% confidence interval [CI]: 33.4-108.8 minutes) than in controls (169.4 +/- 81.5 minutes, 95% CI: 110.9-357.6 minutes) as concluded from nonoverlapping 95% confidence interval of the time constants. The steeper decline of SWA in narcolepsy-cataplexy compared to controls was related to an impaired build-up of slow-wave activity in the second cycle. Sleep in the second cycle was interrupted in patients with narcolepsy-cataplexy, when compared with controls, by an increased number (P = 0.01) and longer duration (P = 0.01) of short wake episodes. Insufficient NREM sleep intensity is associated with nonconsolidated nocturnal sleep in narcolepsy-cataplexy. The inability to consolidate sleep manifests itself when NREM sleep intensity has decayed below a certain level and is reflected in an altered time course of slow-wave activity across NREM sleep episodes.

Interdependency between heart rate variability and sleep EEG: linear/non-linear?

Objective: To investigate whether the interdependency between heart rate variability (HRV) and sleep electroencephalogram (EEG) power spectra is linear or non-linear. Methods: Heart rate and sleep EEG signals were recorded in 8 healthy young men. Spectral analysis was applied to electrocardiogram and EEG sleep recordings. Synchronization likelihood was computed over the first 3 non-rapid eye movement–rapid eye movement sleep cycles between normalized high frequency of RR intervals (RRI) and all electroencephalographic frequency bands. Comparison to surrogate data of different types was used to attest statistical significance of the coupling between RRI and EEG power bands and its linear or non-linear character. Results: Synchronization likelihood values were statistically greater than univariate surrogate synchronization for all sleep bands both at the individual and the group levels. With reference to multivariate surrogates, synchronization values were statistically greater at the group level and, in a majority of cases, for individual comparison except for σ and β bands. Conclusions: While all electroencephalographic power bands are linked to normalized high frequency RRI band, this interdependency is non-linear for δ, θ and α bands. Significance: Non-linear description is required to capture the full interdependent dynamics of HRV and sleep EEG power bands.

Interdependency between heart rate variability and sleep EEG: linear/non-linear?

Objective : To investigate whether the interdependency between heart rate variability (HRV) and sleep electroencephalogram (EEG) power spectra is linear or non-linear. Methods : Heart rate and sleep EEG signals were recorded in 8 healthy young men. Spectral analysis was applied to electrocardiogram and EEG sleep recordings. Synchronization likelihood was computed over the first 3 non-rapid eye movement–rapid eye movement sleep cycles between normalized high frequency of RR intervals (RRI) and all electroencephalographic frequency bands. Comparison to surrogate data of different types was used to attest statistical significance of the coupling between RRI and EEG power bands and its linear or non-linear character. Results : Synchronization likelihood values were statistically greater than univariate surrogate synchronization for all sleep bands both at the individual and the group levels. With reference to multivariate surrogates, synchronization values were statistically greater at the group level and, in a majority of cases, for individual comparison except for σ and β bands. Conclusions : While all electroencephalographic power bands are linked to normalized high frequency RRI band, this interdependency is non-linear for δ , θ and α bands. Significance : Non-linear description is required to capture the full interdependent dynamics of HRV and sleep EEG power bands.

The sleep EEG's microstructure in depression: alterations of the phase relations between EEG rhythms during REM and NREM sleep

Objective: We investigated the microstructure of sleep electroencephalograms (EEGs) of 13 unmedicated depressive inpatients and 13 healthy controls matched in sex and age, hypothesizing that depressives depict an alteration of certain EEG oscillations across the night. Methods: We digitized the sleep EEGs with a sampling rate of 100 Hz (bipolar derivation C z–P z, 1440 single sweeps; 2048 data points each), calculated the time course of delta (1–3.5 Hz), theta (3.5–7.5 Hz), alpha (7.5–15 Hz), and beta (15–35 Hz) activity over the night, and determined the correlation coefficients of these different EEG rhythms separately for rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Results: For both groups we detected a clear difference between REM and NREM sleep cycles at certain frequency bands. The most impressive changes occurred for the delta/beta and theta/beta correlations, which change their signs between NREM (negatively correlated) and REM (positively correlated) sleep cycles. Following an analysis of variance model with repeated measurement design, a statistically significant group effect ( P=0.024) between depressives and controls was observable during NREM sleep for the delta/beta ( P=0.010) and theta/beta ( P=0.018) interactions. Conclusion: We detected alterations of certain sleep EEG oscillations during the NREM sleep cycle, where the delta/beta as well as the theta/beta activities were higher (negatively) compared to healthy controls. Together with previous investigations on the influence of antidepressants on the microstructure of sleep EEGs, this is another hint that the NREM sleep cycle plays a major role in depression.

Long-term vs. short-term processes regulating REM sleep.

In cats, rats, and mice, the amount of rapid eye movement sleep (REMS) lost during a sleep deprivation (SD) predicts the subsequent REMS rebound during recovery sleep. This suggests that REMS is homeostatically regulated and that a need or pressure for REMS accumulates in its absence, i.e. during both wakefulness and non-rapid eye movement sleep (NREMS). Conversely, it has been proposed that REMS pressure accumulates exclusively during NREMS [Benington and Heller, Am. J. Physiol. 266 (1994) R1992; Prog. Neurobiol. 44 (1994b) 433]. This hypothesis is based on the analysis of the duration of successive NREMS and REMS episodes and of electroencephalogram (EEG) events preceding REMS. Pre-REMS events (PREs) do not always result in sustained REMS and can thus be regarded as REMS attempts that increase as NREMS progresses. It is assumed that two processes regulating REMS can resolve the apparent contradiction between these two concepts: a 'long-term' process that homeostatically regulates the daily REMS amount and a 'short-term' process that regulates the NREM--REMS cycle. These issues were addressed in two SD experiments in rats. The two SDs varied in length (12 and 24 h) and resulted in very similar compensatory changes in NREMS but evoked very different changes for all REMS parameters studied. The large REMS increase observed after 24-h SD was accompanied by a reduction in unsuccessful PREs and an increase in sustained REMS episodes, together resulting in a threefold increase in the success-rate to enter REMS. Changes in success-rate matched those of a theoretically derived long-term REMS pressure. The SD induced changes in sleep architecture could be reproduced by assuming that the increased long-term REMS pressure interacts with the short-term process by increasing the probability to enter and remain in REMS.

Nocturnal melatonin patterns in children.

Time patterns in nocturnal concentrations of circulating melatonin of children are quantified in 8 girls and 8 boys, 8.7-16.8 yr of age, classified by Tanner pubertal stage. Between 1900 and 0700 h, each provided blood samples at 30-min intervals for melatonin RIA. Associations with gender, body mass index, and chronological and pubertal age determined by multiple linear regression and ANOVA reveal that the area under the curve of 12-h melatonin concentrations was affected by pubertal rather than chronological age, an effect to which data collected during darkness contributed the most. Each data series was also analyzed by a least squares spectrum at frequencies of 1-20 cycles/day. Ultradian changes with periods of 3.4 and 1.5 h, putatively associated with rapid eye movement sleep cycles, characterize nocturnal melatonin in boys and girls.

Ultradian Rhythms in Hydromineral Hormones

The maintenance of hydromineral homeostasis depends on the coordinated action of arginine vasopressin (AVP), atrial natriuretic peptide (ANP), the renin-angiotensin-aldosterone system and other recently identified endocrine or paracrine hormones. Several reports have pointed out the changes in urinary excretion and osmolality during the sleep-wake cycle and the rapid eye movement (REM)-non(N)REM sleep cycles. No such changes occur for ANP levels which have a flat profile over 24 h. The pulsatile fluctuations of AVP are described as random. The ultradian rhythm of plasma renin activity (PRA) depends on the regularity of the REM-NREM sleep cycles and the nocturnal curves reflect all disturbances in the internal sleep structure. A study with a shift in the normal sleep time clearly demonstrated that both PRA and aldosterone oscillations are sleep-stage dependent. These hormones could account for the ultradian variations in renal function. The nocturnal oscillations in sympathovagal balance may play an additional role. It is suggested that a central generator synchronizes endocrine, renal, autonomic and sleep processes.

Relationship between muscle tone changes, sawtooth waves and rapid eye movements during sleep

‘Sawtoothed’ waves occur during rapid eye movement (REM) sleep, but their source as well as their function is not known. We studied the onset of sawtooth waves (STW) in relation to the onset of muscle tone reduction (MTR) and to REM during 20 polysomnographic recordings in 11 normal volunteers. Seventy-seven (85%) of a total of 91 REM sleep cycles were used for further analysis, because within a 1000 s interval they showed a relatively stereotyped sequence of events: a generalized body movement, followed by MTR, then the appearance of STW, and ending with the first REM. The first STW often occurred during the electrographic stage II period prior to the beginning of the REM, by which time muscle tone was either already at or close to the tone level of the REM sleep period in all subjects. The overall mean onset time of MTR was 267 s (range 89–660 s), STW was 378 s (range 169–779), and REM was 448 s (range 265–849); their differences were highly significant (F = 27.1, df 2,20, P < 0.001). Our data suggest that a predictable sequence of muscle tone reduction, then STW, and then REM, precedes the generally accepted onset of the REM sleep period, and may have implications for the redesignation of physiologic REM sleep onset.

Renin as a biological marker of the NREM-REM sleep cycle: effect of REM sleep suppression.

We have previously described that, in normal man, the nocturnal oscillations of plasma renin activity (PRA) exactly reflect the rapid eye movement (REM)-non(N)REM sleep cycles, with increasing PRA levels during NREM sleep and decreasing levels during REM sleep. This study was carried out to determine whether REM sleep suppression affects nocturnal renin profiles and to define which sleep stage is essential for renin release. In a first experimental series, REM sleep was suppressed by using clomipramine, a tricyclic antidepressant. Seven healthy young men were studied once during a night when a placebo was given and once during a night following a single dose of 50 mg clomipramine. Blood was collected every 10 min from 23.00 hours to 07.00 hours. PRA was measured by radio-immunoassay and the nocturnal profiles were analysed using the pulse detection program ULTRA. Clomipramine suppressed REM sleep in all subjects but one, but did not affect the number of SWS episodes nor their duration. Similar PRA profiles were observed in both experimental conditions. Neither the mean levels, nor the number and the amplitude of the oscillations were modified and the normal relationship between slow wave sleep and increasing PRA levels was preserved. In a second experimental series, REM sleep was prevented by rapidly awakening the subjects as soon as they fell into REM sleep. The four subjects studied attempted several times to go into REM sleep, but only when PRA levels were decreasing. The interruption of REM sleep by short waking periods did not disturb PRA for which the oscillations remained unaffected. Again, the relationship between SWS and increasing PRA levels was preserved. These results provide evidence that mechanisms increasing slow-wave activity are principally involved in increasing PRA levels and that replacing REM sleep by waking periods and light sleep does not modify nocturnal PRA oscillations.

Quantitative analysis of the effects of slow wave sleep deprivation during the first 3 h of sleep on subsequent EEG power density.

The relation between EEG power density during slow wave sleep (SWS) deprivation and power density during subsequent sleep was investigated. Nine young male adults slept in the laboratory for 3 consecutive nights. Spectral analysis of the EEG on the 2nd (baseline) night revealed an exponential decline in mean EEG power density (0.25-15.0 Hz) over successive nonrapid eye movement--rapid eye movement sleep cycles. During the first 3 h of the 3rd night the subjects were deprived of SWS by means of acoustic stimuli, which did not induce wakefulness. During SWS deprivation an attenuation of EEG power densities was observed in the delta frequencies, as well as in the theta band. In the hours of sleep following SWS deprivation both the power densities in the frequency range from 1 to 7 Hz and the amount of SWS were enhanced, relative to the same period of the baseline night. Both the amount of EEG energy accumulating subsequent to SWS deprivation and its time course could be predicted accurately from the EEG energy deficit caused by SWS deprivation. The data show that the level of integral EEG power density during a certain period after sleep onset depends on the amount of EEG energy accumulated during the preceding sleep rather than on the time elapsed since sleep onset. In terms of the two-process model of sleep regulation (Borbély 1982; Daan et al. 1984) this finding indicates that EEG power density reflects the rate of decay of the regulating variable, S, rather than S itself, as was originally postulated.

Rapid eye movement sleep cycle, clock time and sleep onset

The phase of the REM sleep rhythm was studied in 10 normal subjects each of whom was sleep studied for 4 consecutive nights. For analysis, each night of sleep was aligned according to clock time and each minute was scored as REM or non-REM. With these data, REM probability was found as a function of clock time. Fractional harmonic analysis indicates a 90 min periodicity. The REM probability curve shows peaks occurring at 1:30 a.m., 3:15 a.m., 4:30 a.m., 5:45 a.m. and 7:00 a.m. Statistical measures comparing the time of REM sleep across subjects suggests that subjects tend to have REM sleep at the same time of the night as each other. The influence of elapsed time after sleep onset on REM sleep is also reestablished. Results indicate that the time of REM sleep is determined by both clock time and time of sleep onset, suggesting two clocks, one sleep dependent and the other related to the basic rest activity cycle (BRAC), which are responsible for driving REM sleep. Furthermore, the similarity of REM times across subjects indicates the possible existence of an extra-personae REM driving force linked to clock time and possibly the BRAC.

Relation of Sleep Onset to Rapid Eye Movement Sleep

ALTHOUGH most investigators conceptualize rapid eye movement (REM) sleep as one of two distinct kinds of sleep,^1,2a body of opinion persists which holds that the REM sleep cycle may be part of a more general rhythm continuing during both waking and sleeping.^3-10Kleitman has discussed a "basic rest-activity cycle," reflected in the two alternating kinds of sleep, which may also be operative during waking.^3,4Globus has reported data on daytime naps which suggests that REM sleep tends to occur at the same clock times each day^5,6and Globus and Gardner have conceptualized REM "sleep" as a time-locked ultradian rhythm superimposed as a ripple on the slower moving circadian rhythm of waking and sleeping.⁷Similarly, Friedman and Fisher have suggested that "the concept of a sleep dream cycle be amended to that of a 24 hour continuous cycle of drive accumula