Dynamics of nap sleep during a 40 hour period.

Following 1 baseline night, the sleep of 8 adult males in equally space 1 h naps during a 40 h period was examined. Ten additional subjects were sleep-deprived for 40 h with 1 h periods of exercise given in place of naps. One recovery night followed the 40 h period for both groups. Total sleep time and the amount of stage REM during the naps were negatively related to the circadian-temperature cycle. Stage REM frequently appeared within 10 min of stage 1 onset and the normal sequence of stages REM and 4 were altered, demonstrating that the organization of sleep within a nap is quite different from that in monophasic nocturnal sleep. Auto-correlation and cross-correlation analyses showed that the relation of sleep stages from hour to hour in normal continuous baseline sleep was altered in nap-to-nap comparison. The timing of REM onset may be controlled by a sleep-dependent ultradian clock; the clock may stop upon awakening and resume at the next sleep onset. Naps had recuperative value in terms of maintaining the normal amounts of sleep stages on the recovery night; recovery sleep for the exercise group showed typical sleep-loss effects.     

Minute-by-minute analysis of REM sleep timing in major depression

Sleep changes described in depressed patients may represent alterations in the timing of rapid-eye-movement (REM) sleep or sleep onset. We examined these variables in groups of healthy control subjects (n = 47), depressed outpatients (n = 98), and depressed inpatients (n = 41). Outpatient depressives had greater severity of clinical symptoms than inpatients using the Hamilton Rating Scale for Depression. The depressed inpatient group had a later mean sleep onset time than the other groups, and the depressed outpatient group had a wider range of good night times than control subjects. REM timing in each group was examined as a relative frequency distribution of REM sleep (FDRS) for each minute across the night. The FDRSs for the three groups were statistically compared using the parameters from a two-component model, which includes a deterministic sinusoidal function and a time series process for errors. The slope of the linear trend in the FDRS rhythm was smaller (less positive) for both depressed groups than for controls. The ultradian FDRS rhythm occurred at an earlier phase, relative to sleep onset, in the inpatient depressed group compared to the control group. The ultradian FDRS rhythm had a longer period in the outpatient group compared to the control and inpatient groups. When referenced to 24-hr clock time in an exploratory analysis, the depressed groups appeared to have less robust FDRS ultradian rhythms than controls, but they did not appear to have a systematic phase alteration compared to controls. Abnormalities of REM sleep timing in groups of depressed patients may reflect a disturbance of sleep initiation and generation, or difficulty in entrainment of REM, rather than a systematic phase alteration in REM sleep propensity.     

The first phase of nocturnal sleep in mentally retarded children

The first phase of sleep observed in 104 mentally retarded children (from 3 months to 8 years of age) was studied throughout nocturnal sleep, and the following results were obtained. In 4 out of 104 subjects, REM sleep onset was observed, and in the remaining 100 subjects NREM sleep onset was found at the first wakefulness-sleep transition of the night. Following awakenings (lasting 4 min or more) during the night, 170 (51.7%) out of a total of 329 samples were REM sleep onset, and 159 (48.3%) showed NREM sleep onset. The phases of sleep onset and those following awakenings evidenced no correlation between the frequency of NREM sleep onset and DQ or clinical EEG, whereas a positive correlation was found between the frequency of NREM sleep onset and age.     

Effects of sleep interruption on REM-NREM cycle in nocturnal human sleep

Forty-four normal male students, aged 18-23 years were studied. After adaptation and baseline night (BN), 3 or 4 consecutive nights were interrupted by a forced awakening (10-90 min) once a night (ENs). Subjects (Ss) were awakened after they had slept for the first sleep cycle plus 20 min of NREM sleep in the 2nd cycle. The REM latencies following return to sleep showed a bimodal distribution separated by 25-30 min. The ENs were divided into 2 clusters: SOREMP (sleep onset REM period) and non-SOREMP nights. After interruption, the 2nd and the 3rd REM durations increased on non-SOREMP nights compared to SOREMP nights. We plotted, separately for SOREMP and non-SOREMP nights, the fluctuation of REM episode probability (FRP) at successive points in time. We examined the correspondence of FRPs derived from the sleep-independent, the sleep-dependent, and the reset hypotheses, with FRP of intact BN. On both SOREMP and non-SOREMP nights, none of the 3 models corresponded with BN. Thus, we suggest that, for both SOREMP and non-SOREMP nights, intervening wakefulness cancels the pre-awakening REM rhythm, and a new REM rhythm starts with or without SOREMP. We discuss factors influencing the rate of SOREMP occurrence (SOREMP %), such as circadian effect, individual differences, length of interruption, and pre-awakening NREM duration.     

The effects of caerulein on nocturnal, sleep

1. Caerulein, a decapeptide chemically related to cholecystokinin octapeptide, was examined polysoninographically for its effect on nocturnal sleep in healthy volunteers.

2. The subjects were 6 males (20–24 years of age). Either a placebo (saline) or caerulein 0.6 μg/kg was administered intramuscularly to volunteers at 23:00.

3. Polysomnograms were then recorded from 23:00 till 06:30.

4. Little variation in sleep period time, total sleep time, sleep efficiency index, sleep latency, or REM sleep latency in the drug night were found as compared to the control night values.

5. The percentage of REM stage sleep increased significantly (P < 0.01) on the drug administered night, whereas the change in the percentages of each of the other stages was not significant.

6. The REM density of the vertical eye movements tended to increase on the drug night, but the density of the horizontal eye movements showed no change.

7. There were no changes in the spontaneous GSRs in either vola or dorsum manus.

8. As caerulein shows alpha-1 adrenergic receptor blocker activity, it is suggested that caerulein may increase REM sleep by affecting the central noradrenergic neurons.     

REM sleep in depression is influenced by ethnicity

The influence of ethnicity on the manifestation of EEG sleep changes in depression was studied in 95 patients (21 African-Americans [AA], 17 Asians [AS], 37 Caucasians [C] and 20 Hispanics [H]) with unipolar major depression. Subjects were studied twice for 2 consecutive nights. On the second night of each 2-night session, placebo or scopolamine (1.5 microg/kg, IM, at 23.00 h) was administered. On the baseline (placebo) night, sleep architecture, sleep continuity and rapid eye movement (REM) sleep variables were generally comparable among the groups. However, REM sleep was less in AA and AS subjects than in C and H subjects. Furthermore, the distribution of REM sleep over the course of the night in AA and AS subjects differed significantly from that in the C and H groups. Although scopolamine significantly affected sleep continuity and REM sleep measures, no significant differential effects of scopolamine were observed. Because many antidepressants suppress REM sleep, the differences in baseline REM sleep observed might be related to the greater sensitivity of some ethnic-minority depressed patients to pharmacotherapy.     

REM sleep in primary depression: a computerized analysis.

REM sleep in 35 inpatients with primary depression was automatically analyzed for 7 consecutive nights during placebo administration. For the total night of sleep, as well as each individual REM period, the number of REMs, their total voltage integral over time, the sum of their durations and the average REM size were automatically calculated. Validity of these automated REM measures was established by significant correlations with manually scored REM measures. Changes in REM sleep across the night were also investigated. Similar to findings in normal subjects, REM time did not change from REM period to REM period. Average REM size increased significantly from REM period 2-3 and 3-4. Contrary to what is seen in normal subjects, REM frequency was high during the first REM period, significantly decreased from the first to second REM period and then remained constant. Finally, a significant inverse correlation between REM frequency for the first REM period and REM latency was noted. This pattern of REM sleep is interpreted as indicating a high pressure for phasic REM at the beginning of the night which is dissipated by the first REM period.     

Improved sleep continuity and increased slow wave sleep and REM latency during ziprasidone treatment: a randomized, controlled, crossover trial of 12 healthy male subjects

OBJECTIVE: Ziprasidone, an atypical antipsychotic, is a potent dopamine (D(2)) and serotonin (5-HT(2A/C)) receptor blocker, has agonistic properties at the 5-HT(1A) receptor, and blocks serotonin and norepinephrine reuptake. These transmitter systems are closely related to the regulation of sleep. METHOD: The aim of this double-blind, placebo-controlled, randomized, crossover study was to investigate the effects of ziprasidone on polysomnographic sleep structure and subjective sleep quality. Twelve healthy male subjects were randomly assigned to receive ziprasidone 40 mg or placebo for 2 sessions each composed of 2 consecutive nights (night 1, standard sleep conditions; night 2, acoustic stress) 5 days apart. Treatment was administered orally 2 hours before bedtime. The study was conducted from April 2004 to July 2004. RESULTS: Ziprasidone significantly increased total sleep time, sleep efficiency, percentage of sleep stage 2, and slow wave sleep; decreased the number of awakenings; and significantly affected tonic and phasic REM sleep parameters, i.e., it decreased percentage of REM and REM density and profoundly increased REM latency. CONCLUSION: Ziprasidone's effects on the sleep profile are somehow opposite to what is known about sleep of depressed patients (e.g., disturbances of sleep continuity, a reduciton of slow wave sleep, and a disinhibition of REM sleep). Its REM sleep-suppressing properties resemble those of most, although not all, antidepressants and may be clinically relevant. The drug also demonstrates sleep-consolidating properties under both standard routine and acoustic stress conditions. These effects are most likely related to ziprasidone's 5-HT(2C) antagonism, 5-HT(1A) agonism, and serotonin and norepinephrine reuptake inhibition.     

Sleepiness in sleepwalking and sleep terrors: a higher sleep pressure?

ObjectiveTo identify the determinants of excessive daytime sleepiness in adults with sleepwalking or sleep terrors (SW/ST).MethodsWe collected the charts of all consecutive adult patients admitted from 2012 to 2014 for SW/ST. They had completed the Paris Arousal Disorders Severity Scale and the Epworth Sleepiness Scale, and had undergone one (n = 34) or two consecutive (n = 124) nocturnal videopolysomnographies. The demographic, clinical, and sleep determinants of excessive daytime sleepiness (defined as an Epworth Sleepiness Scale score of greater than 10) were analyzed.ResultsAlmost half (46.8%) of the 158 adult patients with SW/ST reported excessive daytime sleepiness. They had shorter sleep onset latencies (in night 1 and night 2), shorter REM sleep latencies, longer total sleep time, and higher REM sleep percentages in night 2, but no greater clinical severity of the parasomnia than patients without sleepiness. The level of sleepiness correlated with the same measures (sleep onset latency on both nights, REM sleep onset latency, and total sleep time in night 2), plus the latency to N3. In the regression model, higher sleepiness was determined by shorter sleep onset latency on night 1, lower number of awakenings in N3 on night 1, and higher total sleep time on night 2.ConclusionDaytime sleepiness in patients with SW/ST is not the consequence of disturbed sleep but is associated with a specific polygraphic phenotype (rapid sleep onset, long sleep time, lower numbers of awakenings on N3) that is suggestive of a higher sleep pressure that may contribute to incomplete arousal from N3.     

Relationship between Delta, Sigma, Beta, and Gamma EEG bands at REM sleep onset and REM sleep end.

OBJECTIVE: The aim of the present study was to analyze in detail the relationship of two newly introduced measures, related to the Beta and Gamma EEG bands during REM sleep, with Delta and Sigma activity at REM sleep onset and REM sleep end, in order to understand their eventual role in the sleep modulation mechanism. METHODS: For this purpose, power spectra of 1 EEG channel (C4, referred to A1) were obtained by means of the fast Fourier transform and the power of the bands ranging 0.75-4.50 Hz (Delta), 4.75-7.75 (Theta), 8.00-12.25 (Alpha), 12.50-15.00 (Sigma), 15.25-24.75 (Beta), 25.00-34.75 (Gamma 1), and 35.00-44.75 (Gamma 2) was calculated for the whole period of analysis (7 h), in 10 healthy subjects. Additionally, two other time series were calculated: the ratio between Beta and Gamma2, and between Gamma1 and Gamma2 (Beta and Gamma ratios). For each subject, we extracted 3 epochs of 30 min corresponding to the 15 min preceding and the 15 min following the onset of the first 3 REM episodes. Data were then averaged in order to obtain group mean values and standard deviation. The same process was applied to the 30-min epochs around REM sleep end. RESULTS: The course of the Delta band around REM sleep onset was found to be characterized by a first phase of slow decline lasting from the beginning of our window up to a few seconds before REM onset; this phase was followed by a sudden, short decrease centered around REM onset, lasting for approximately 1.5-2 min. At the end of this phase, the Delta band reached its lowest values and remained stable up to the end of the time window. The Sigma band showed a similar course with stable values before and after REM sleep onset. The Beta and Gamma ratios also showed a 3-phase course; the first phase, in this case, was characterized by stable low values, from the beginning of our window up to approximately 5 min before REM onset. The following second phase was characterized by an increase which reached its maximum shortly after REM sleep onset (approximately 1 min). In the last phase, both Beta and Gamma ratios showed stable high values, up to the end of our time window. At REM sleep end, the Delta band only showed a very small gradual increase, the Sigma band presented a more evident gradual increase; on the contrary, both Beta and Gamma ratios showed a small gradual decrease. CONCLUSIONS: The results of the present study show a different time synchronization of the changes in the Delta band and in Beta and Gamma ratios, at around REM sleep onset, and seem to suggest that the oscillations of these parameters might be modulated by mechanisms more complex than a simple reciprocity. All these considerations point to the fact that REM sleep can be considered as a complex phenomenon and the analysis of high-frequency EEG bands and of our Beta and Gamma ratios represent an additional important element to include in the study of this sleep stage.     

Sleep onset and first cycle of sleep in human subjects: change with time of day.

The first cycle of sleep was studied in different situations: normal night sleep, naps, diurnal sleep after night shifts (3 x 8 shift workers). Results show two types of first cycle: some started with SWS (normal cycles), others with REM (sleep onset REM periods: SOREMPs). (1) Normal cycles: the length of SWS in the first cycle was positively correlated with prior wakefulness; conversely, the latency of SWS decreased as prior wakefulness increased; the decrease was due to the decrease in the length of the previous stage II or of the sleep onset latency (SOL). Length of sleep onset (SO) showed only few variations. The structure of the first cycle of shift workers' sleep probably reflects an important sleep loss. (2) SOREMPs occcurred during diurnal sleep. Some hypotheses about these cycles are discussed including REM 'pressures' (circadian, sleep loss) and inter-individual variations.     

Spontaneous sleep interruptions during extended nights. Relationships with NREM and REM sleep phases and effects on REM sleep regulation.

OBJECTIVES: There is no agreement in the literature as to whether sleep interruption causes rapid eye movement (REM) pressure to increase, and if so, whether this increase is expressed as shortened REM latency, increased REM density, or increased duration of REM sleep. The purpose of the present study was to examine the effect of different durations of spontaneous sleep interruptions on the regulation of REM sleep that occurs after return to sleep. METHODS: The occurrence of spontaneous periods of wakefulness and their effects on subsequent REM sleep periods were analysed in a total sample of 1189 sleep interruptions which occurred across 364 extended nights in 13 normal subjects. RESULTS: Compared with sleep interruptions that last less than 10 min, sleep interruptions that last longer than 10 min occur preferentially out of REM sleep. In both the short and long types of sleep interruptions, the duration of REM periods that ended in wakefulness were shorter than the duration of those that were not interrupted by wakefulness. REM densities of the REM periods that terminated in periods of wakefulness were higher than those of uninterrupted REM periods. The proportion of episodes of wakefulness following REM sleep that were long-lasting progressively increased over the course of the extended night period. The sleep episodes that followed the periods of wakefulness were characterised by a short REM latency. REM duration was increased in episodes that followed long sleep interruptions compared to those that followed short sleep interruptions. REM density did not appear to change significantly in the episodes that followed sleep interruption. CONCLUSIONS: REM sleep mechanisms appear to be the main force controlling sleep after a spontaneous sleep interruption, presumably because during the second half of the night, where more sleep interruptions occur, the pressure for non-rapid eye movement sleep is reduced and the circadian rhythm in REM sleep propensity reaches its peak. Processes promoting REM sleep at the end of the night are consistent with the Pittendrigh and Daan dual oscillator model of the circadian pacemaker.     

Effects of auditory stimulation during rapid eye movement sleep in healthy volunteers and depressed patients.

Auditory and somesthesic forms of stimulation have substantially increased rapid eye movement (REM) sleep in cats. We investigated whether auditory stimulation, applied during REM sleep or outside REM sleep, would have similar effects in normal volunteers. We also administered auditory stimulation to depressed patients during REM sleep. Subjects were studied during 1 acclimatization night, 2 baseline nights, 4 consecutive nights with auditory stimulation, and 1 followup night without auditory stimulation. Normal volunteers were randomly divided into Group R, which received auditory stimulation during each REM sleep episode, and Group NR, which received auditory stimulation at the end of each REM sleep episode. Depressed patients (Group D) received auditory stimulation during each REM sleep period. Only Group R showed increased REM sleep time during the nights of auditory stimulation and throughout the followup night. This group also increased their sleep efficiency. Group NR showed reduced sleep efficiency due to an increase in both the duration and frequency of awakenings. Group D did not show increased REM sleep time, but did show shortened REM sleep episodes, increased REM sleep frequency, and increased duration of awakenings. Group D did not show clinical changes.     

Individual variations in response of human REM sleep to amitriptyline and haloperidol.

The effect of amitriptyline and haloperidol on REM sleep was investigated in healthy human adults, with special attention to individual variations in these drugs' effects. In addition, an investigation was made of the rebound elevation of REM sleep occurring on the following night of partial differential REM deprivation (PDRD), again with emphasis being placed on individual variations in that effect. The administration of amitriptyline in a single oral dose of 25 mg was followed by an inhibition of REM sleep in all subjects. The per cent decrease in REM sleep was found to have a significant negative correlation with the per cent increase in REM sleep following PDRD in individual subjects. The amount of REM sleep during the recovery night following the night of amitriptyline medication tended to correlate with the per cent increase in REM sleep following PDRD in individual subjects. Haloperidol in a single oral dose of 1.5 mg caused REM sleep to augment in some subjects but inhibit in others. A significant correlation was noted to exist between drug-induced change in REM sleep and the per cent increase in REM sleep following PDRD.     

Scopolamine-induced muscarinic supersensitivity in normal man: Changes in sleep

Scopolamine (6 μg/kg) was administered on 3 consecutive mornings to normal human subjects. Sleep recordings obtained at night (when the central anticholinergic effect of the morning scopolamine was no longer present) indicated a significant reduction in latency to REM-sleep onset on the nights following the second and third injections. This effect is opposite to the direct pharmacological action of nighttime administration of scopolamine (i.e., prolongation of REM latency). In addition, total sleep time and sleep efficiency were reduced, and sleep latency was increased. Furthermore, scopolamine pretreatment on 2 consecutive mornings also potentiated the REM-inducing effect of arecoline, a central muscarinic agonist. These data are consistent with the development of cholinergic supersensitivity following cholinergic blockade.     

Characteristics of rapid eye movement production during REM sleep in man: organization and rhythmicity

The purpose of this study was to verify statistically the existence of certain characteristics of rapid eye movement (REM) production during REM sleep: organization and rhythmicity. REM data were collected intermittently, over a period of 20 consecutive nights, from 6 normal adult subjects of both sexes. Results concerning the organization of REM production revealed the presence of 3 evolving slow trends: quadratic, linear and quasi-sinusoidal. The occurrence of a given trend type was not related to subject, night, time of night or length of REM sleep phase being analysed. Results of the analysis showed that it is possible for a series of REMs to contain one, two or more statistically significant rhythmic periods, or no significant rhythmic period. The rhythmic periods that were detected ranged from 1 to 21 min, and no predominant periods were present. As in the case of the slow trends, the occurrence of a given rhythmic period was not dependent on subject, night, time of night or length of the REM sleep phase.     

EEG sleep studies in patients with generalized anxiety disorder

Sleep polygraphic recordings were performed during 3 consecutive nights in 12 inpatients with generalized anxiety disorder (GAD) in comparison with age- and sex-matched groups of patients with major depressive disorder (MDD) and normal subjects. GAD patients differed significantly from those with MDD. A lower number of awakenings and stage shifts in night 1 and the mean of the 3 nights and a shorter rapid eye movement (REM) duration in night 1 but longer REM latency in the mean of the 3 nights were observed in GAD in comparison to MDD. GAD patients also showed a significantly longer sleep onset latency and shorter duration of total sleep time and Stage 2 than control subjects. Electroencephalographic sleep recordings, as well as other laboratory tests, may help the clinician to differentiate anxiety from depressive disorders.     

Night-to-night variability in sleep in cystic fibrosis

OBJECTIVES: The impact of night-to-night variability (NNV) on polysomnography (PSG) has been reported mainly in normal subjects, the elderly and patients with obstructive sleep apnea with focus on changes in the apnea/hypopnea index, rather than measures of nocturnal oxygenation. There is very limited data on NNV in patients with cystic fibrosis (CF). The goal of this study was to assess for first-night effect and reliability of PSG measurements on nocturnal oxygenation and respiratory disturbance in CF. METHODS: A prospective observational study was performed in patients with CF who consented to PSG on two consecutive nights. Paired t-tests and intra-class correlation coefficients (ICCs) were calculated for repeated measures of sleep stage time, sleep efficiency, arousal indices, measures of nocturnal oxygenation, and respiratory events in all sleep stages. RESULTS: Thirty-one patients with CF were studied, aged 27+/-8 (mean+/-1 SD) years and forced expiratory volume in 1 s (FEV(1)) of 37+/-11% of predicted. Relative to the first-night PSG, on the second PSG, we observed the following: shorter latency to rapid eye movement (REM) sleep (P<0.001), increased sleep efficiency (P<0.01), decreased wake after sleep onset (WASO) time (P<0.01), decreased percentage of non-REM time with oxyhemoglobin saturation by pulse oximetry (SpO(2))< or =90% (P<0.05), decreased number of central apneas per hour (P<0.05) and reduced respiratory rate in stage 2 sleep on night 2 (P<0.05). Despite these changes, the ICCs between night 1 and night 2 showed good repeatability/reliability for measures of nocturnal oxygenation and indices of respiratory disturbance, including the percentage of total sleep time with SpO(2)< or =90% (ICC=0.85) and apnea-hypopnea index (ICC=0.75). Likewise, the ICCs were extremely high for respiratory rate in stage 2 (ICC=0.94), slow wave sleep (ICC=0.97), and REM sleep (ICC=0.96).CONCLUSION: Although a first-night effect is seen with sleep efficiency, REM latency, and WASO, a single-night PSG in patients with CF yields reliable information on nocturnal oxygenation and respiratory disturbance.     

Electroencephalographic sleep findings in depressed outpatients

We compared the electroencephalographic (EEG) sleep characteristics of 20 outpatients with those of 20 age-matched inpatients with major primary depressive disorders. Both groups showed similar patterns of sleep disturbance: reduced rapid eye movement (REM) sleep latencies, sleep efficiencies, and slow wave sleep. While the inpatients had greater REM activity in the first REM period than did the outpatients, both groups showed evidence of greater REM sleep time and REM activity during the first half of the night than do normals. The outpatients demonstrated a level of adaptation in that more REM sleep time and activity were present on night 2 than on night 1.     

Temporal EEG dynamics of non-REM sleep episodes in humans

The process of the human non-rapid eye movement (non-REM) sleep period has not been clarified. Time-based analysis on sleep EEG may provide an explanation. We focused on chronological aspects of initiation and termination of non-REM episodes, using spectral analysis of sleep EEG. The subjects were healthy male volunteers (n14 Hz) and longer in lower frequency ranges (<14 Hz). There were significant differences in the rise and decay latencies between low and high sigma ranges, indicating that the whole frequency ranges were clearly separated at the middle of the sigma range (14 Hz). The rise and decay latencies were significantly different in lower frequency ranges. The clock time of the night significantly affected only the rise latencies of the delta (0.78-3.9 Hz), alpha (8.2-11.7 Hz) and low sigma (12.1-13.7 Hz) ranges. In conclusion, initiation and termination of non-REM sleep was represented by higher frequency ranges, whereas further evolution and devolution of non-REM sleep was represented by lower frequency ranges, and only the evolution process was affected by the clock time of the night.