Selective REM sleep deprivation during daytime. II. Muscle atonia in non-REM sleep

One of the hallmarks of rapid eye movement (REM) sleep is muscle atonia. Here we report extended epochs of muscle atonia in non-REM sleep (MAN). Their extent and time course was studied in a protocol that included a baseline night, a daytime sleep episode with or without selective REM sleep deprivation, and a recovery night. The distribution of the latency to the first occurrence of MAN was bimodal with a first mode shortly after sleep onset and a second mode 40 min later. Within a non-REM sleep episode, MAN showed a U-shaped distribution with the highest values before and after REM sleep. Whereas MAN was at a constant level over consecutive 2-h intervals of nighttime sleep, MAN showed high initial values when sleep began in the morning. Selective daytime REM sleep deprivation caused an initial enhancement of MAN during recovery sleep. It is concluded that episodes of MAN may represent an REM sleep equivalent and that it may be a marker of homeostatic and circadian REM sleep regulating processes. MAN episodes may contribute to the compensation of an REM sleep deficit.     

Effects of selective sleep deprivation on ventilation during recovery sleep in normal humans.

To assess the effects of selective sleep loss on ventilation during recovery sleep, we deprived 10 healthy young adult humans of rapid-eye-movement (REM) sleep for 48 h and compared ventilation measured during the recovery night with that measured during the baseline night. At a later date we repeated the study using awakenings during non-rapid-eye-movement (NREM) sleep at the same frequency as in REM sleep deprivation. Neither intervention produced significant changes in average minute ventilation during presleep wakefulness, NREM sleep, or the first REM sleep period. By contrast, both interventions resulted in an increased frequency of breaths, in which ventilation was reduced below the range for tonic REM sleep, and in an increased number of longer episodes, in which ventilation was reduced during the first REM sleep period on the recovery night. The changes after REM sleep deprivation were largely due to an increase in the duration of the REM sleep period with an increase in the total phasic activity and, to a lesser extent, to changes in the relationship between ventilatory components and phasic eye movements. The changes in ventilation after partial NREM sleep deprivation were associated with more pronounced changes in the relationship between specific ventilatory components and eye movement density, whereas no change was observed in the composition of the first REM sleep period. These findings demonstrate that sleep deprivation leads to changes in ventilation during subsequent REM sleep.     

Sleep homeostasis and models of sleep regulation

According to the two-process model of sleep regulation, the timing and structure of sleep are determined by the interaction of a homeostatic and a circadian process. The original qualitative model was elaborated to quantitative versions that included the ultradian dynamics of sleep in relation to the non-REM-REM sleep cycle. The time course of EEG slow-wave activity, the major marker of non-REM sleep homeostasis, as well as daytime alertness were simulated successfully for a considerable number of experimental protocols. They include sleep after partial sleep deprivation and daytime napping, sleep in habitual short and long sleepers, and alertness in a forced desynchrony protocol or during an extended photoperiod. Simulations revealed that internal desynchronization can be obtained for different shapes of the thresholds. New developments include the analysis of the waking EEG to delineate homeostatic and circadian processes, studies of REM sleep homeostasis, and recent evidence for local, use-dependent sleep processes. Moreover, nonlinear interactions between homeostatic and circadian processes were identified. In the past two decades, models have contributed considerably to conceptualizing and analyzing the major processes underlying sleep regulation, and they are likely to play an important role in future advances in the field.     

Age-related changes in the circadian and homeostatic regulation of human sleep

The reduction of electroencephalographic (EEG) slow-wave activity (SWA) (EEG power density between 0.75-4.5 Hz) and spindle frequency activity, together with an increase in involuntary awakenings during sleep, represent the hallmarks of human sleep alterations with age. It has been assumed that this decrease in non-rapid eye movement (NREM) sleep consolidation reflects an age-related attenuation of the sleep homeostatic drive. To test this hypothesis, we measured sleep EEG characteristics (i.e., SWA, sleep spindles) in healthy older volunteers in response to high (sleep deprivation protocol) and low sleep pressure (nap protocol) conditions. Despite the fact that the older volunteers had impaired sleep consolidation and reduced SWA levels, their relative SWA response to both high and low sleep pressure conditions was similar to that of younger persons. Only in frontal brain regions did we find an age-related diminished SWA response to high sleep pressure. On the other hand, we have clear evidence that the circadian regulation of sleep during the 40 h nap protocol was changed such that the circadian arousal signal in the evening was weaker in the older study participants. More sleep occurred during the wake maintenance zone, and subjective sleepiness ratings in the late afternoon and evening were higher than in younger participants. In addition, we found a diminished melatonin secretion and a reduced circadian modulation of REM sleep and spindle frequency-the latter was phase-advanced relative to the circadian melatonin profile. Therefore, we favor the hypothesis that age-related changes in sleep are due to weaker circadian regulation of sleep and wakefulness. Our data suggest that manipulations of the circadian timing system, rather than the sleep homeostat, may offer a potential strategy to alleviate age-related decrements in sleep and daytime alertness levels.     

Timing and consolidation of human sleep, wakefulness, and performance by a symphony of oscillators

Daily rhythms in sleep and waking performance are generated by the interplay of multiple external and internal oscillators. These include the light-dark and social cycles, a circadian hypothalamic oscillator oscillating virtually independently of behavior, and a homeostatic oscillator driven primarily by sleep-wake behavior. Both internal oscillators contribute to variation in many aspects of sleep and wakefulness (e.g., sleep timing and duration, REM sleep, non-REM sleep, REM density, sleep spindles, slow-wave sleep, electroencephalographic oscillations during wakefulness and sleep, and performance parameters, including attention and memory). The relative contribution of the oscillators varies greatly between these variables. Sleep and performance cannot be predicted by either oscillator independently but critically depend on their phase relationship and amplitude. The homeostatic oscillator feeds back onto the central pacemaker or its outputs. Thus, the amplitude of observed circadian variation in sleep and performance depends on how long we have been asleep or awake. During entrainment to external 24-h cycles, the opposing interplay between circadian and homeostatic changes in sleep propensity consolidates sleep and wakefulness. Some physiological correlates and mediators of both the circadian process (e.g., melatonin and hypocretin rhythms) and the homeostat (e.g., EEG, slow-wave activity, and adenosine release) have been established, offering targets for the development of countermeasures for circadian sleep and performance disorders. Interindividual differences in sleep timing, duration, and morning or evening preference are associated with changes of circadian or sleep homeostatic processes or both. Molecular genetic correlates, including polymorphisms in clock genes, of some of these interindividual differences are emerging.     

Age-related reduction in the maximal capacity for sleep--implications for insomnia

Sleep changes markedly across the life span and complaints about insomnia are prevalent in older people [1]. Whether age-related alterations in sleep are due to modifications in social factors, circadian physiology, homeostatic drive, or the ability to sleep remains unresolved. We assessed habitual sleep duration at home and then quantified daytime sleep propensity, sleep duration, and sleep structure in an inpatient protocol that included extended sleep opportunities covering 2/3 of the circadian cycle (12 hr at night and 4 hr in the afternoon) for 3-7 days in 18 older and 35 younger healthy men and women. At baseline, older subjects had less daytime sleep propensity than did younger subjects. Total daily sleep duration, which was initially longer than habitual sleep duration, declined during the experiment to asymptotic values that were 1.5 hr shorter in older (7.4 +/- 0.4 SEM, hour) than in younger subjects (8.9 +/- 0.4). Rapid-eye-movement sleep and non-rapid-eye-movement sleep contributed about equally to this reduction. Thus, in the absence of social and circadian constraints, both daytime sleep propensity and the maximal capacity for sleep are reduced in older people. These data have important implications for understanding age-related insomnia.     

Control of REM sleep: an aspect of the regulation of physiological homeostasis.

Since REM sleep is characterized by a suspension of the hypothalamic integration of homeostatic regulations, it has been assumed that the duration of both REM sleep episodes and of the time interval between the end of one episode and the beginning of the following episode may be regulated according to sleep related processes and the homeostatic needs of the organism. A series of studies performed on the rat has shown that REM sleep episodes occur as two basic types: single REM sleep episodes, that are separated by intervals > 3 min and sequential episodes, that are separated by intervals < or = 3 min and appear in a cluster. Moreover, it has been observed that, in this species, a change in REM sleep occurrence is caused by a modification in the number of episodes and not in their duration. With respect to this, sleep deprivation and recovery are characterized by a decrease and an increase, respectively, in the number of sequential REM sleep episodes, but the number of single episodes tends to be kept constant. The central aspects of this kind of regulation have been examined biochemically in the preoptic-anterior hypothalamus, an area involved in the control of autonomic and sleep related processes. The results show that the accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) is impaired, in this region, during sleep deprivation and appears to return to the control levels, during the recovery, with a rate inversely related to the degree of the previous deprivation. Moreover, it has been observed that the systemic administration of DL-propranolol and LiCl reduces cAMP accumulation mainly in the preoptic-anterior hypothalamus; this condition is concomitant with a reduction in REM sleep occurrence.     

Young women with major depression live on higher homeostatic sleep pressure than healthy controls

There is mounting evidence for the involvement of the sleep-wake cycle and the circadian system in the pathogenesis of major depression. However, only a few studies so far focused on sleep and circadian rhythms under controlled experimental conditions. Thus, it remains unclear whether homeostatic sleep pressure or circadian rhythms, or both, are altered in depression. Here, the authors aimed at quantifying homeostatic and circadian sleep-wake regulatory mechanisms in young women suffering from major depressive disorder and healthy controls during a multiple nap paradigm under constant routine conditions. After an 8-h baseline night, 9 depressed women, 8 healthy young women, and 8 healthy older women underwent a 40-h multiple nap protocol (10 short sleep-wake cycles) followed by an 8-h recovery night. Polysomnographic recordings were done continuously, and subjective sleepiness was assessed. In order to measure circadian output, salivary melatonin samples were collected during scheduled wakefulness, and the circadian modulation of sleep spindles was analyzed with reference to the timing of melatonin secretion. Sleep parameters as well as non-rapid eye movement (NREM) sleep electroencephalographic (EEG) spectra were determined for collapsed left, central, and right frontal, central, parietal, and occipital derivations for the night and nap-sleep episodes in the frequency range .75-25 Hz. Young depressed women showed higher frontal EEG delta activity, as a marker of homeostatic sleep pressure, compared to healthy young and older women across both night sleep episodes together with significantly higher subjective sleepiness. Higher delta sleep EEG activity in the naps during the biological day were observed in young depressed women along with reduced nighttime melatonin secretion as compared to healthy young volunteers. The circadian modulation of sleep spindles between the biological night and day was virtually absent in healthy older women and partially impaired in young depressed women. These data provide strong evidence for higher homeostatic sleep pressure in young moderately depressed women, along with some indications for impairment of the strength of the endogenous circadian output signal involved in sleep-wake regulation. This finding may have important repercussions on the treatment of the illness as such that a selective suppression of EEG slow-wave activity could promote acute mood improvement.     

Restricted sleep regime in rhesus monkeys: differential effect of one night's sleep loss and selective REM deprivation.

The differential effect of either one night's total sleep deprivation (TSD) or of selective REM deprivation (REMD) was examined on post-deprivation daytime EEG patterns with respect to control, in the same group of rhesus monkeys. TSD resulted in significantly decreased wakefulness and increased amounts of NREM and REM on the first day following TSD. In contrast, highly significant REM elevation without alteration of other EEG states occurred for 3 days after REMD. Post-deprivation behavioural and photic-induced neural changes were minor. The results obtained after sleep deprivation in simians are comparable with similar findings in human subjects.     

Sleep initiation and initial sleep intensity: interactions of homeostatic and circadian mechanisms

Sleep initiation and sleep intensity in humans show a dissimilar time course. The propensity of sleep initiation (PSI), as measured by the multiple sleep latency test, remains at a relatively constant level throughout the habitual period of waking or exhibits a midafternoon peak. When waking is extended into the sleep period, PSI rises rapidly within a few hours. In contrast, sleep intensity, as measured by electroencephalographic slow-wave activity during naps, shows a gradual increase during the period of habitual waking. In the two-process model of sleep regulation, it corresponds to the rising limb of the homeostatic Process S. We propose that PSI is determined by the difference between Process S and the threshold H defining sleep onset, which is modulated by the circadian process C. In contrast to a previous version of the model, the parameters of H (amplitude, phase, skewness) differ from those of threshold L, which defines sleep termination. The present model is able to simulate the time course of PSI under baseline conditions as well as following recovery sleep after extended sleep deprivation. The simulations suggest that during the regular period of waking, a circadian process counteracts the increasing sleep propensity induced by a homeostatic process. Data obtained in the rat indicate that during the circadian period of predominant waking, a circadian process prevents a major intrusion of sleep.     

Partial sleep deprivation reduces phase advances to light in humans

Partial sleep deprivation is increasingly common in modern society. This study examined for the first time if partial sleep deprivation alters circadian phase shifts to bright light in humans. Thirteen young healthy subjects participated in a repeated-measures counterbalanced design with 2 conditions. Each condition had baseline sleep, a dim-light circadian phase assessment, a 3-day phase-advancing protocol with morning bright light, then another phase assessment. In one condition (no sleep deprivation), subjects had an 8-h sleep opportunity per night during the advancing protocol. In the other condition (partial sleep deprivation), subjects were kept awake for 4 h in near darkness (<0.25 lux), immediately followed by a 4-h sleep opportunity per night during the advancing protocol. The morning bright light stimulus was four 30-min pulses of bright light (~5000 lux), separated by 30-min intervals of room light. The light always began at the same circadian phase, 8 h after the baseline dim-light melatonin onset (DLMO). The average phase advance without sleep deprivation was 1.8 ± 0.6 (SD) h, which reduced to 1.4 ± 0.6 h with partial sleep deprivation (p < 0.05). Ten of the 13 subjects showed reductions in phase advances with partial sleep deprivation, ranging from 0.2 to 1.2 h. These results indicate that short-term partial sleep deprivation can moderately reduce circadian phase shifts to bright light in humans. This may have significant implications for the sleep-deprived general population and for the bright light treatment of circadian rhythm sleep disorders such as delayed sleep phase disorder.     

A world record in marathon tennis: sleep deprivation and performance

We studied the effects of marked sleep deprivation on the EEG patterns and performance of a physically fit man (age 26) on the occasion of the world record continuous marathon tennis play (147 hours, 20 minutes). Before and immediately after the marathon, the sleep patterns of the player were recorded in our laboratory. After playing for 40 and 80 hours and within 24 hours, the performance changes were evaluated each hour. Amounts of the different sleep stages during the first recovery night compared with those of the baseline indicate an increase of 56% for total sleep time, 54% for stages 1 and 2, 154% for stages 3 and 4 and 20% for REM sleep. During the second recovery night, only REM sleep showed an increase. Activity index showed a marked decrease after 80 hours of sleep deprivation compared with that after 40 hours and was dramatically worsened during nighttime. The number of faults and pauses was also increased after 80 hours, suggesting a clear performance deterioration. Our results confirmed the effects of sleep deprivation on the recovery and performance deterioration.     

The influence of prior wakefulness on REM sleep

Data from studies of naps and of shifted sleep were used to determine the relationship between two measures of rapid eye movement (REM) sleep (percentage of REM in the first 2 hr of sleep and REM latency) and prior wakefulness. For each sample, we calculated the difference between the observed value and that predicted by a cosine function that estimated the circadian rhythm of REM sleep propensity. The difference values were found to correlate reliably with hours and log hours of prior wakefulness. We conclude that while REM sleep is regulated in part by an endogenous circadian oscillator, it is also influenced by the duration of prior wakefulness.     

The impact of sleep timing and bright light exposure on attentional impairment during night work

The prevalence of hazardous incidents induced by attentional impairment during night work and ensuing commute times is attributable to circadian misalignment and increased sleep pressure. In a 10-day shift work simulation protocol (4 day shifts and 3 night shifts), the efficacies of 2 countermeasures against nighttime (2300 to 0700 h) attentional impairment were compared: (1) Morning Sleep (0800 to 1600 h; n = 18) in conjunction with a phase-delaying light exposure (2300 to 0300 h), and (2) Evening Sleep (1400 to 2200 h; n = 17) in conjunction with a phase-advancing light exposure (0300 to 0700 h). Analysis of the dim light salivary melatonin onset indicated a modest but significant circadian realignment in both sleep groups (evening sleep: 2.27 +/- 0.6 h phase advance, p < 0.01; morning sleep: 4.98 +/- 0.43 h phase delay, p < 0.01). Daytime sleep efficiency and total sleep time did not differ between them or from their respective baseline sleep (2200 to 0600 h; p > 0.05). However, on the final night shift, the evening sleep subjects had 37% fewer episodes of attentional impairment (long response times: 22 +/- 4 vs. 35 +/- 4; p = 0.02) and quicker responses (p < 0.01) on the Psychomotor Vigilance Task than their morning sleep counterparts. Their response speed recovered to near daytime levels (p = 0.47), whereas those of the morning sleep subjects continued to be slower than their daytime levels (p = 0.008). It is concluded that partial circadian realignment to night work in combination with reduced homeostatic pressure contributed to the greater efficacy of a schedule of Evening Sleep with a phase-advancing light exposure as a countermeasure against attentional impairment, over a schedule of Morning Sleep with a phase-delaying light exposure. These results have important implications for managing patients with shift work disorder.     

A compromise phase position for permanent night shift workers: circadian phase after two night shifts with scheduled sleep and light/dark exposure

Night shift work is associated with a myriad of health and safety risks. Phase-shifting the circadian clock such that it is more aligned with night work and day sleep is one way to attenuate these risks. However, workers will not be satisfied with complete adaptation to night work if it leaves them misaligned during days off. Therefore, the goal of this set of studies is to produce a compromise phase position in which individuals working night shifts delay their circadian clocks to a position that is more compatible with nighttime work and daytime sleep yet is not incompatible with late nighttime sleep on days off. This is the first in the set of studies describing the magnitude of circadian phase delays that occurs on progressively later days within a series of night shifts interspersed with days off. The series will be ended on various days in order to take a "snapshot" of circadian phase. In this set of studies, subjects sleep from 23:00 to 7:00 h for three weeks. Following this baseline period, there is a series of night shifts (23:00 to 07:00 h) and days off. Experimental subjects receive five 15 min intermittent bright light pulses (approximately 3500 lux; approximately 1100 microW/cm2) once per hour during the night shifts, wear sunglasses that attenuate all visible wavelengths--especially short wavelengths ("blue-blockers")--while traveling home after the shifts, and sleep in the dark (08:30-15:30 h) after each night shift. Control subjects remain in typical dim room light (<50 lux) throughout the night shift, wear sunglasses that do not attenuate as much light, and sleep whenever they want after the night shifts. Circadian phase is determined from the circadian rhythm of melatonin collected during a dim light phase assessment at the beginning and end of each study. The sleepiest time of day, approximated by the body temperature minimum (Tmin), is estimated by adding 7 h to the dim light melatonin onset. In this first study, circadian phase was measured after two night shifts and day sleep periods. The Tmin of the experimental subjects (n=11) was 04:24+/-0.8 h (mean+/-SD) at baseline and 7:36+/-1.4 h after the night shifts. Thus, after two night shifts, the Tmin had not yet delayed into the daytime sleep period, which began at 08:30 h. The Tmin of the control subjects (n=12) was 04:00+/-1.2 h at baseline and drifted to 4:36+/-1.4 h after the night shifts. Thus, two night shifts with a practical pattern of intermittent bright light, the wearing of sunglasses on the way home from night shifts, and a regular sleep period early in the daytime, phase delayed the circadian clock toward the desired compromise phase position for permanent night shift workers. Additional night shifts with bright light pulses and daytime sleep in the dark are expected to displace the sleepiest time of day into the daytime sleep period, improving both nighttime alertness and daytime sleep but not precluding adequate sleep on days off.     

Preoptic hypothalamic warming suppresses laryngeal dilator activity during sleep

Upper airway dilator activity during sleep appears to be diminished under conditions of enhanced sleep propensity, such as after sleep deprivation, leading to worsening of obstructive sleep apnea (OSA). Non-rapid eye movement (NREM) sleep propensity originates in sleep-active neurons of the preoptic area (POA) of the hypothalamus and is facilitated by activation of POA warm-sensitive neurons (WSNs). We hypothesized that activation of WSNs by local POA warming would inhibit activity of the posterior cricoarytenoid (PCA) muscle, an airway dilator, during NREM sleep. In chronically prepared unrestrained cats, the PCA exhibited inspiratory bursts in approximate synchrony with inspiratory diaphragmatic activity during waking, NREM, and REM. Integrated inspiratory PCA activity (IA), peak activity (PA), and the lead time (LT) of the onset of inspiratory activity in PCA relative to diaphragm were significantly reduced in NREM sleep and further reduced during REM sleep compared with waking. Mild bilateral local POA warming (0.5-1.2 degrees C) significantly reduced IA, PA, and LT during NREM sleep compared with a prewarming NREM baseline. In some animals, effects of POA warming on PCA activity were found during waking or REM. Because POA WSN activity is increased during spontaneous NREM sleep and regulates sleep propensity, we hypothesize that this activation contributes to reduction of airway dilator activity in patients with OSA.     

Sleep processes exert a predominant influence on the 24-h profile of heart rate variability

Adverse cardiovascular events are known to exhibit 24-h variations with a peak incidence in the morning hours and a nonuniform distribution during the night. The authors examined whether these 24-h variations could be related to circadian or sleep-related changes in heart rate (HR) and in HR variability (HRV). To differentiate the effect of circadian and sleep-related influences, independent of posture and of meal ingestion, seven normal subjects were studied over 24 h, once with nocturnal sleep from 2300 to 0700 h and once after a night of sleep deprivation followed by 8 h of daytime sleep from 0700 to 1500 h. The subjects were submitted to constant conditions (continuous enteral nutrition and bed rest). HRV was calculated every 5 min using two indexes: the standard deviation of normal R-R intervals (SDNN) and the ratio of low-frequency to low-frequency plus high-frequency power. Sleep processes exerted a predominant influence on the 24-h profiles of HR and HRV, with lowest HRV levels during slow wave sleep, high levels during REM sleep and intrasleep awakenings, and abrupt increases in HR at each transition from deeper sleep to lighter sleep or awakenings. The circadian influence was smaller, except for SDNN, which displayed a nocturnal increase of 140% whether the subjects slept or not. This study demonstrates that 24-h variations in HR and HRV are little influenced by the circadian clock andare mainly sleep-stage dependent. The results suggest an important role for exogenous factors in the morning increase in cardiovascular events. During sleep, the sudden rises in HR at each transition from deeper sleep to lighter sleep or awakenings might precipitate the adverse cardiac events.     

Mood, alertness, and performance in response to sleep deprivation and recovery sleep in experienced shiftworkers versus non-shiftworkers

Previous studies have shown increased sleepiness and mood changes in shiftworkers, which may be due to sleep deprivation or circadian disruption. Few studies, however, have compared responses of experienced shiftworkers and non-shiftworkers to sleep deprivation in an identical laboratory setting. The aim of this laboratory study, therefore, was to compare long-term shiftworkers and non-shiftworkers and to investigate the effects of one night of total sleep deprivation (30.5 h of continuous wakefulness) and recovery sleep on psychomotor vigilance, self-rated alertness, and mood. Eleven experienced male shiftworkers (shiftwork ≥5 yrs) were matched with 14 non-shiftworkers for age (mean ± SD: 35.7 ± 7.2 and 32.5 ± 6.2 yrs, respectively) and body mass index (BMI) (28.7 ± 3.8 and 26.6 ± 3.4 kg/m(2), respectively). After keeping a 7-d self-selected sleep/wake cycle (7.5/8 h nocturnal sleep), both groups entered a laboratory session consisting of a night of adaptation sleep and a baseline sleep (each 7.5/8 h), a sleep deprivation night, and recovery sleep (4-h nap plus 7.5/8 h nighttime sleep). Subjective alertness and mood were assessed with the Karolinska Sleepiness Scale (KSS) and 9-digit rating scales, and vigilance was measured by the visual psychomotor vigilance test (PVT). A mixed-model regression analysis was carried out on data collected every hour during the sleep deprivation night and on all days (except for the adaptation day), at .25, 4.25, 5.25, 11.5, 12.5, and 13.5 h after habitual wake-up time. Despite similar circadian phase (melatonin onset), demographics, food intake, body posture, and environmental light, shiftworkers felt significantly more alert, more cheerful, more elated, and calmer than non-shiftworkers throughout the laboratory study. In addition, shiftworkers showed a faster median reaction time (RT) compared to non-shiftworkers, although four other PVT parameters did not differ between the groups. As expected, both groups showed a decrease in subjective alertness and PVT performance during and following the sleep deprivation night. Subjective sleepiness and most aspects of PVT performance returned to baseline levels after a nap and recovery sleep. The mechanisms underlying the observed differences between shiftworkers and non-shiftworkers require further study, but may be related to the absence of shiftwork the week prior to and during the laboratory study as well as selection into and out of shiftwork.     

The levels of urinary epinephrine during daytime REM sleep deprivation.

Urinary excretion of epinephrine during REM sleep deprivation in the daytime was examined in an attempt to determine whether epinephrine excretion during sleep is related to the structure of disturbed sleep. Six healthy males were subjected to two experimental conditions: 1) day sleep without interruption, as a control condition, and 2) day sleep with REM sleep deprivation. Under both conditions, epinephrine excretion levels of five of the subjects were found to be distributed along a basal regression line, expressing the relationship of epinephrine excretion and percent of waking time, as calculated in a previous study. The epinephrine levels of the one remaining subject exceeded the values predicted by the regression line. His sleep structure was not only distorted under REM deprivation conditions but also under control conditions as well. These results suggest that the basal regression line is useful for observing the existence of sleep disturbance; indeed, a subject with epinephrine excretion levels much higher than those predicted by the regression line was found to have spontaneously disturbed sleep. More study is needed to clarify the relationship between high epinephrine levels and disturbed sleep.     

Age‐related Changes in the Circadian and Homeostatic Regulation of Human Sleep

The reduction of electroencephalographic (EEG) slow‐wave activity (SWA) (EEG power density between 0.75–4.5 Hz) and spindle frequency activity, together with an increase in involuntary awakenings during sleep, represent the hallmarks of human sleep alterations with age. It has been assumed that this decrease in non‐rapid eye movement (NREM) sleep consolidation reflects an age‐related attenuation of the sleep homeostatic drive. To test this hypothesis, we measured sleep EEG characteristics (i.e., SWA, sleep spindles) in healthy older volunteers in response to high (sleep deprivation protocol) and low sleep pressure (nap protocol) conditions. Despite the fact that the older volunteers had impaired sleep consolidation and reduced SWA levels, their relative SWA response to both high and low sleep pressure conditions was similar to that of younger persons. Only in frontal brain regions did we find an age‐related diminished SWA response to high sleep pressure. On the other hand, we have clear evidence that the circadian regulation of sleep during the 40 h nap protocol was changed such that the circadian arousal signal in the evening was weaker in the older study participants. More sleep occurred during the wake maintenance zone, and subjective sleepiness ratings in the late afternoon and evening were higher than in younger participants. In addition, we found a diminished melatonin secretion and a reduced circadian modulation of REM sleep and spindle frequency—the latter was phase‐advanced relative to the circadian melatonin profile. Therefore, we favor the hypothesis that age‐related changes in sleep are due to weaker circadian regulation of sleep and wakefulness. Our data suggest that manipulations of the circadian timing system, rather than the sleep homeostat, may offer a potential strategy to alleviate age‐related decrements in sleep and daytime alertness levels.