Are age differences in sleep due to phase differences in the output of the circadian timing system?

Our aim was to evaluate whether age-related changes in the phase of the output of the circadian timing system (CTS) can explain age differences in habitual bedtime/wake time and in sleep consolidation parameters. Analyses focused on a group of healthy elderly people (older than 70 years) with no sleep problems and with similar subjective sleep quality as a young control group. The 2-week sleep diary data and 24h laboratory temperature recordings were examined for 70 subjects (22 young men [YM], 19 old men [OM], 29 old women [OW]). Polysomnographic (PSG) sleep data recorded during temperature data acquisition were also available for 62 subjects. These analyses made use of our recently developed technique to demask temperature rhythm data. As expected, compared to the young subjects, older subjects showed earlier habitual bedtime and wake time, more disturbed sleep, and a tendency for an earlier minimum of the circadian temperature rhythm. Despite sleep consolidation differences, the groups showed very similar habitual phase-angle differences (interval between the time occurrence of the fitted temperature minimum and habitual wake time). Both elderly and young subjects woke up on average 3h after the temperature minimum. After controlling for the effects of age group, habitual bedtime and wake time were related to clock time phase of the circadian temperature rhythm, with an earlier phase associated with earlier habitual bedtime and wake time. None of the sleep consolidation parameters were linked to the temperature phase angle. In conclusion, sleep consolidation changes associated with healthy aging do not appear to be related to changes in the phase-angle difference between the output signal from the CTS and sleep.     

An arousing, musically enhanced bird song stimulus mediates circadian rhythm phase advances in dim light

A musically enhanced bird song stimulus presented in the early subjective night phase delays human circadian rhythms. This study determined the phase-shifting effects of the same stimulus in the early subjective day. Eleven subjects (ages 18-63 yr; mean +/- SD: 28.0 +/- 16.6 yr) completed two 4-day laboratory sessions in constant dim light (<20 lux). They received two consecutive presentations of either a 2-h musically enhanced bird song or control stimulus from 0600 to 0800 on the second and third mornings while awake. The 4-day sessions employing either the stimulus or control were counterbalanced. Core body temperature (CBT) was collected throughout the study, and salivary melatonin was obtained every 30 min from 1900 to 2330 on the baseline and poststimulus/postcontrol nights. Dim light melatonin onset and CBT minimum circadian phase before and after stimulus or control presentation was assessed. The musically enhanced bird song stimulus produced significantly larger phase advances of the circadian melatonin (mean +/- SD: 0.87 +/- 0.36 vs. 0.24 +/- 0.22 h) and CBT (1.08 +/- 0.50 vs. 0.43 +/- 0.37 h) rhythms than the control. The stimulus also decreased fatigue and total mood disturbance, suggesting arousing effects. This study shows that a musically enhanced bird song stimulus presented during the early subjective day phase advances circadian rhythms. However, it remains unclear whether the phase shifts are due directly to effects of the stimulus on the clock or are arousal- or dim light-mediated effects. This nonphotic stimulus mediates circadian resynchronization in either the phase advance or delay direction.     

Wrist activity monitoring in air crew members: a method for analyzing sleep quality following transmeridian and north-south flights

Home base recordings of motor activity during bedtime, and of subjective sleep parameters, were obtained from air crew members before and after the following routes with multiple flight segments: (1) south-north (SN) across 1 time zone; (2) west-east (WE) across 17 time zones; (3) east-west (EW) across 7 time zones. For the EW route, recordings were also obtained during layover. Only after return from the EW route was bedtime motor activity (measured by a wrist-worn ambulatory monitor) enhanced, was the percentage of bedtime immobility periods reduced, and were frequency and duration of self-assessed waking after sleep onset increased. The subjects rated their sleep as less quiet and felt less rested than during baseline. The various parameters gradually reverted toward baseline during the first 4 days at home. Although sleep showed only minor impairments during the EW route, the subjective jet-lag score was high during layover and after return to home base. Ambulatory activity monitoring is a useful method for assessing sleep quality after long-haul flights.     

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.     

Challenging the sleep homeostat does not influence the thermoregulatory system in men: evidence from a nap vs. sleep-deprivation study

The purpose of our study was to understand the relationship between the components of the three-process model of sleepiness regulation (homeostatic, circadian, and sleep inertia) and the thermoregulatory system. This was achieved by comparing the impact of a 40-h sleep deprivation vs. a 40-h multiple nap paradigm (10 cycles with 150/75 min wakefulness/sleep episodes) on distal and proximal skin temperatures, core body temperature (CBT), melatonin secretion, subjective sleepiness, and nocturnal sleep EEG slow-wave activity in eight healthy young men in a "controlled posture" protocol. The main finding of the study was that accumulation of sleep pressure increased subjective sleepiness and slow-wave activity during the succeeding recovery night but did not influence the thermoregulatory system as measured by distal, proximal, and CBT. The circadian rhythm of sleepiness (and proximal temperature) was significantly correlated and phase locked with CBT, whereas distal temperature and melatonin secretion were phase advanced (by 113 +/- 28 and 130 +/- 30 min, respectively; both P < 0.005). This provides evidence for a primary role of distal vasodilatation in the circadian regulation of CBT and its relationship with sleepiness. Specific thermoregulatory changes occur at lights off and on. After lights off, skin temperatures increased and were most pronounced for distal; after lights on, the converse occurred. The decay in distal temperature (vasoconstriction) was significantly correlated with the disappearance of sleep inertia. These effects showed minor and nonsignificant circadian modulation. In summary, the thermoregulatory system seems to be independent of the sleep homeostat, but the circadian modulation of sleepiness and sleep inertia is clearly associated with thermoregulatory changes.     

Early rising or delayed bedtime: which is better for a short night's sleep?

The present study compares the effects on sleep and the subsequent period of wakefulness of delaying bedtime of 2 h or advancing rising time by 2 h in subjects clearly differentiated by morningness or eveningness in their circadian rhythms. Twelve young healthy good sleepers, six morning types (MT) and six evening types (ET), were selected. The data obtained from the second 24 h (night and day) with delayed bedtime (DB) and advanced rising time (AR) were compared with those obtained in the reference condition (R) with normal sleep schedules. Sleep was recorded polygraphically and rectal temperature was continuously monitored during the nights and during the day following the second night of each condition. Subjective estimations of alertness, performance tasks and urinary steroids were analysed. Early rising appeared to be more disturbing than a late bedtime. The second shortened night showed fewer characteristics of recovery sleep in AR than in DB. The decrease in self rated alertness was a function both of the type of condition (DB or AR) and of the morning-evening typology of the subject. The largest decrease was observed in AR and in the ET subjects. AR also resulted in the most pronounced decrease in performance tasks and in an increase in urinary 17 ketosteroids without changes in the 17 hydroxy-corticosteroids. The effects on rectal temperature were limited to short periods after bedtime in DB and rising time in AR.     

Daily Rhythms of Toxicity and Effectiveness of Anesthetics (MS222 and Eugenol) in Zebrafish (Danio Rerio)

Sleep inertia is a brief period of inferior task performance and/or disori-entation immediately after sudden awakening from sleep. Normally sleep inertia lasts <5 min and has no serious impact on conducting routine jobs. This preliminary study examined whether there are best and worst times to wake up stemming from circadian effects on sleep inertia. Since the process of falling asleep is strongly influenced by circadian time, the reverse process of awakening could be similarly affected. A group of nine subjects stayed awake for a 64-h continuous work period, except for 20-min sleep periods (naps) every 6 h. Another group of 10 subjects stayed awake for 64 h without any sleep. The differences between these two groups in performance degradation are expected to show sleep inertia on the background of sleep deprivation. Sleep inertia was measured with Baddeley's logical reasoning task, which started within 1 min of awakening and lasted for 5 min. There appeared to be no specific circadian time when sleep inertia is either maximal or minimal. An extreme form of sleep inertia was observed, when the process of waking up during the period of the circadian body temperature trough became so traumatic that it created “sleep (nap) aversion.” The findings lead to the conclusion that there are no advantages realized on sleep inertia by waking up from sleep at specific times of day.     

Effects of a Two‐Hour Change in Bedtime on the Sleep of Healthy Seniors

Some of the sleep disruption seen in seniors (>65 yrs) may be due to alteration of the circadian pacemaker phase and/or its phase angle with bedtime. The purpose of this study was to determine the effects of 2 h changes in the timing of bedtime (both earlier and later) on the sleep of seniors. Ten healthy seniors (9 F, 1 M, age 70–82 yrs) were each studied individually during three 120 h sessions (each separated by >2 weeks) in a time‐isolation laboratory. On nights 1 and 2, bedtime and rise‐time occurred at the subjects' habitual times; on nights 3–5, bedtime was specified by the experiment, but rise‐time was at the subjects' discretion (without knowledge of clock time). Under the control condition, subjects went to bed at their habitual bedtime (HBT), under the earlier bedtime condition at (HBT?2 h), and under the later bedtime condition at (HBT+2 h). Sleep was polysomnnographically recorded and rectal temperature continuously monitored. Although total sleep time increased in the earlier compared to the later condition (p<0.01), sleep efficiency decreased and wake after sleep onset increased (p<0.01). Subjective ratings of sleep were also worse under the earlier (HBT?2 h) than under later (HBT+ 2 h) condition (p<0.05). Performance did not differ between the earlier and later conditions. The larger the phase angle between actual bedtime and circadian temperature minimum (Tmin), the longer the time spent in bed and total sleep time, and the worse the sleep efficiency and subjective sleep ratings. There were no effects related to the phase angle between Tmin and rise‐time. The relative benefits of longer vs. more efficient sleep in the elderly require further investigation.     

Chronobiological characterization of women with primary vasospastic syndrome: body heat loss capacity in relation to sleep initiation and phase of entrainment

Women with primary vasospastic syndrome (VS), but otherwise healthy, exhibit a functional disorder of vascular regulation (main symptom: cold extremities) and often suffer from difficulties initiating sleep (DIS). Diverse studies have shown a close association between distal vasodilatation before lights off and a rapid onset of sleep. Therefore, we hypothesized that DIS in women with VS could be due to a reduced heat loss capacity in the evening, i.e., subjects are physiologically not ready for sleep. The aim of the study was to elucidate whether women having both VS and DIS (WVD) or not (controls) show different circadian characteristics (e.g., phase delay of the circadian thermoregulatory system with respect to the sleep-wake cycle). Healthy young women (n = 9 WVD and n = 9 control) completed a 40-h constant routine protocol (adjusted to habitual bedtime) before and after an 8-h sleep episode. Skin temperatures [off-line calculated as distal-proximal skin temperature gradient (DPG)] and core body temperature (CBT; rectal) were continuously recorded. Half-hourly saliva samples were collected for melatonin assay and subjective sleepiness was assessed on the Karolinska Sleepiness Scale (KSS). Compared with control, WVD showed no differences in habitual bed times, but a 1-h circadian phase delay of dim light-melatonin onset (hours after lights on: WVD 14.6 +/- 0.3 h; control 13.5 +/- 0.2 h; P = 0.01). Similar phase shifts were observed in CBT, DPG, and KSS ratings. In conclusion, WVD exhibit a phase delay of the endogenous circadian system with respect to their habitual sleep-wake cycle, which could be a cause of DIS.     

Is sleep per se a zeitgeber in humans?

It is not clear whether shifting of sleep per se, without a concomitant change in the light-dark cycle, can induce a phase shift of the human circadian pacemaker. Two 9-day protocols (crossover, counterbalanced order) were completed by 4 men and 6 women (20-34 years) after adherence to a 2330 to 0800 h sleep episode at home for 2 weeks. Following a modified baseline constant routine (CR) protocol on day 2, they remained under continuous near-darkness (< 0.2 lux, including sleep) for 6 days. Four isocaloric meals were equally distributed during scheduled wakefulness, and their timing was held constant. Subjects remained supine inbed from 2100 to 0800 h on all days; sleep was fixed from 2330 to 0800 h in the control condition and was gradually advanced 20 min per day during the sleep advance condition until a 2-h difference had been attained. On day 9, a 25 to 27 h CR protocol (approximately 0.1 lux) was carried out. Phase markers were the evening decline time of the core body temperature (CBT) rhythm and salivary melatonin onset (3 pg/ml threshhold). In the fixed sleep condition, the phase drift over 7 days ranged from +1.62 to -2.56 h (for both CBT and melatonin rhythms, which drifted in parallel). The drifts were consistently advanced in the sleep advance schedule by +0.66 +/- 0.23 (SEM) h for CBT (p = 0.02) and by 0.27 +/- 0.14 h for melatonin rhythms (p = 0.09). However, this advance was small to medium according to effect size. Sleep per se may feed back onto the circadian pacemaker, but it appears to be a weak zeitgeber in humans.     

Predominance of distal skin temperature changes at sleep onset across menstrual and circadian phases

Menstrual cycle-associated changes in reproductive hormones affect body temperature in women. We aimed to characterize the interaction between the menstrual, circadian, and scheduled sleep-wake cycles on body temperature regulation. Eight females entered the laboratory during the midfollicular (MF) and midluteal (ML) phases of their menstrual cycle for an ultradian sleep-wake cycle procedure, consisting of 36 cycles of 60-minute wake episodes alternating with 60-minute nap opportunities, in constant bed-rest conditions. Core body temperature (CBT) and distal skin temperature (DT) were recorded and used to calculate a distal-core gradient (DCG). Melatonin, sleep, and subjective sleepiness were also recorded. The circadian variation of DT and DCG was not affected by menstrual phase. DT and DCG showed rapid, large nap episode-dependent increases, whereas CBT showed slower, smaller nap episode-dependent decreases. DCG values were significantly reduced for most of the wake episode in an overall 60-minute wake/60-minute nap cycle during ML compared to MF, but these differences were eliminated at the wake-to-nap lights-out transition. Nap episode-dependent decreases in CBT were further modulated as a function of both circadian and menstrual factors, with nap episode-dependent deceases occurring more prominently during the late afternoon/evening in ML, whereas nap episode-dependent DT and DCG increases were not significantly affected by menstrual phase but only circadian phase. Circadian rhythms of melatonin secretion, DT, and DCG were significantly phase-advanced relative to CBT and sleep propensity rhythms. This study explored how the thermoregulatory system is influenced by an interaction between circadian phase and vigilance state and how this is further modulated by the menstrual cycle. Current results agree with the thermophysiological cascade model of sleep and indicate that despite increased CBT during ML, heat loss mechanisms are maintained at a similar level during nap episodes, which may allow for comparable circadian sleep propensity rhythms between menstrual phases.     

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.     

CONTRIBUTION OF CIRCADIAN PHYSIOLOGY AND SLEEP HOMEOSTASIS TO AGE-RELATED CHANGES IN HUMAN SLEEP

The circadian pacemaker and sleep homeostasis play pivotal roles in vigilance state control. It has been hypothesized that age-related changes in the human circadian pacemaker, as well as sleep homeostatic mechanisms, contribute to the hallmarks of age-related changes in sleep, that is, earlier wake time and reduced sleep consolidation. Assessments of circadian parameters in healthy young (～20–30 years old) and older people (～65–75 years old)—in the absence of the confounding effects of sleep, changes in posture, and light exposure—have demonstrated that an earlier wake time in older people is accompanied by about a 1h advance of the rhythms of core body temperature and melatonin. In addition, older people wake up at an earlier circadian phase of the body temperature and plasma melatonin rhythm. The amplitude of the endogenous circadian component of the core body temperature rhythm assessed during constant routine and forced desynchrony protocols is reduced by 20–30% in older people. Recent assessments of the intrinsic period of the human circadian pacemaker in the absence of the confounding effects of light revealed no age-related reduction of this parameter in both sighted and blind individuals. Wake maintenance and sleep initiation are not markedly affected by age except that sleep latencies are longer in older people when sleep initiation is attempted in the early morning. In contrast, major age-related reductions in the consolidation and duration of sleep occur at all circadian phases. Sleep of older people is particularly disrupted when scheduled on the rising limb of the temperature rhythm, indicating that the sleep of older people is more susceptible to arousal signals genernpated by the circadian pacemaker. Sleep-homeostatic mechanisms, as assayed by the sleep-deprivation–induced increase of EEG slow-wave activity (SWA), are operative in older people, although during both baseline sleep and recovery sleep SWA in older people remains at lower levels. The internal circadian phase advance of awakening, as well as the age-related reduction in sleep consolidation, appears related to an age-related reduction in the promotion of sleep by the circadian pacemaker during the biological night in combination with a reduced homeostatic pressure for sleep. Early morning light exposure associated with this advance of awakening in older people could reinforce the advanced circadian phase. Quantification of the interaction between sleep homeostasis and circadian rhythmicity contributes to understanding age-related changes in sleep timing and quality. (Chronobiology International, 17(3), 285–311, 2000)     

Contribution of circadian physiology and sleep homeostasis to age-related changes in human sleep

The circadian pacemaker and sleep homeostasis play pivotal roles in vigilance state control. It has been hypothesized that age-related changes in the human circadian pacemaker, as well as sleep homeostatic mechanisms, contribute to the hallmarks of age-related changes in sleep, that is, earlier wake time and reduced sleep consolidation. Assessments of circadian parameters in healthy young (∼20-30 years old) and older people (∼65-75 years old)—in the absence of the confounding effects of sleep, changes in posture, and light exposure—have demonstrated that an earlier wake time in older people is accompanied by about a 1h advance of the rhythms of core body temperature and melatonin. In addition, older people wake up at an earlier circadian phase of the body temperature and plasma melatonin rhythm. The amplitude of the endogenous circadian component of the core body temperature rhythm assessed during constant routine and forced desynchrony protocols is reduced by 20-30% in older people. Recent assessments of the intrinsic period of the human circadian pacemaker in the absence of the confounding effects of light revealed no age-related reduction of this parameter in both sighted and blind individuals. Wake maintenance and sleep initiation are not markedly affected by age except that sleep latencies are longer in older people when sleep initiation is attempted in the early morning. In contrast, major age-related reductions in the consolidation and duration of sleep occur at all circadian phases. Sleep of older people is particularly disrupted when scheduled on the rising limb of the temperature rhythm, indicating that the sleep of older people is more susceptible to arousal signals genernpated by the circadian pacemaker. Sleep-homeostatic mechanisms, as assayed by the sleep-deprivation-induced increase of EEG slow-wave activity (SWA), are operative in older people, although during both baseline sleep and recovery sleep SWA in older people remains at lower levels. The internal circadian phase advance of awakening, as well as the age-related reduction in sleep consolidation, appears related to an age-related reduction in the promotion of sleep by the circadian pacemaker during the biological night in combination with a reduced homeostatic pressure for sleep. Early morning light exposure associated with this advance of awakening in older people could reinforce the advanced circadian phase. Quantification of the interaction between sleep homeostasis and circadian rhythmicity contributes to understanding age-related changes in sleep timing and quality. (Chronobiology International, 17(3), 285-311, 2000)     

The Effect of Activity on the Waking Temperature Rhythm in Humans

Nine healthy female subjects were studied when exposed to the natural light-dark cycle, but living for 17 “days” on a 27h day (9h sleep, 18h wake). Since the circadian endogenous oscillator cannot entrain to this imposed period, forced desynchronization between the sleep/activity cycle and the endogenous circadian temperature rhythm took place. This enabled the effects of activity on core temperature to be assessed at different endogenous circadian phases and at different stages of the sleep/activity cycle. Rectal temperature was measured at 6-minute intervals, and the activity of the nondominant wrist was summed at 1-minute intervals. Each waking span was divided into overlapping 3h sections, and each section was submitted to linear regression analysis between the rectal temperatures and the total activity in the previous 30 minutes. From this analysis were obtained the gradient (of the change in rectal temperature produced by a unit change in activity) and the intercept (the rectal temperature predicted when activity was zero). The gradients were subjected to a two-factor analysis of variance (ANOVA) (circadian phase/ time awake). There was no significant effect of time awake, but circadian phase was highly significant statistically. Post hoc tests (Newman-Keuls) indicated that gradients around the temperature peak were significantly less than those around its trough. The intercepts formed a sinusoid that, for the group, showed a mesor (±SE) of 36.97 (±0.12) and amplitude (95% confidence interval) of 0.22°C (0.12°C, 0.32°C). We conclude that this is a further method for removing masking effects from circadian temperature rhythm data in order to assess its endogenous component, a method that can be used when subjects are able to live normally. We suggest also that the decreased effect of activity on temperature when the endogenous circadian rhythm and activity are at their peak will reduce the possibility of hyperthermia.     

Prolonged mild hypoxia modifies human circadian core body temperature and may be associated with sleep disturbances

Fatigue is often reported after long-haul airplane flights. Hypobaric hypoxia, observed in pressurized cabins, may play a role in this phenomenon by altering circadian rhythms. In a controlled cross-over study, we assessed the effects of two levels of hypoxia, corresponding to cabin altitudes of 8000 and 12,000 ft, on the rhythm of core body temperature (CBT), a marker of circadian rhythmicity, and on subjective sleep. Twenty healthy young male volunteers were exposed for 8 h (08:00-16:00 h) in a hypobaric chamber to a cabin altitude of 8000 ft and, 4 weeks later, 12,000 ft. Each subject served as his own control. For each exposure, CBT was recorded by telemetry for two 24 h cycles (control and hypoxic exposure). After filtering out nonphysiological values, the individual CBT data were fitted with a five-order moving average before statistical group analysis. Sleep latency, sleep time, and sleep efficiency were studied by sleep logs completed every day in the morning. Our results show that the CBT rhythm expression was altered, mainly at 12,000 ft, with a significant increase of amplitude and a delay in the evening decline in CBT, associated with alterations of sleep latency. Mild hypoxia may therefore alter circadian structure and result in sleep disturbances. These results may explain in part the frequent complaints of prolonged post-flight fatigue after long flights, even when no time zones are crossed.     

Sleep restriction masks the influence of the circadian process on sleep propensity

Previous forced desynchrony studies have highlighted the close relationship between the circadian rhythms of core body temperature (CBT) and sleep propensity. In particular, these studies have shown that a "forbidden zone" for sleep exists on the rising limb of the CBT rhythm. In these previous studies, the length of the experimental day was either ultrashort (90 min), short (20 h), or long (28 h), and the ratio of sleep to wake was normal (i.e., 1:2). The aim of the current study was to examine the relative effects of the circadian and homeostatic processes on sleep propensity using a 28-h forced desynchrony protocol in which the ratio of sleep to wake was substantially lower than normal (i.e., 1:5). Twenty-seven healthy males lived in a time-isolation sleep laboratory for 11 consecutive days. Participants completed either a control (n = 13) or sleep restriction (n = 14) condition. In both conditions, the protocol consisted of 2 × 24-h baseline days followed by 8 × 28-h forced desynchrony days. On forced desynchrony days, the control group had 9.3 h in bed and 18.7 h of wake, and the sleep restriction group had 4.7 h in bed and 23.3 h of wake. For all participants, each 30-s epoch of time in bed was scored as sleep or wake based on standard polysomnography recordings, and was also assigned a circadian phase (360° = 24 h) based on a cosine equation fitted to continuously recorded CBT data. For each circadian phase (i.e., 72 × 5° bins), sleep propensity was calculated as the percentage of epochs spent in bed scored as sleep. For the control group, there was a clear circadian rhythm in sleep propensity, with a peak of 98.5% at 5° (~05:20 h), a trough of 64.9% at 245° (~21:20 h), and an average of 82.3%. In contrast, sleep propensity for the sleep restriction group was relatively high at all circadian phases, with an average of 96.7%. For this group, the highest sleep propensity (99.0%) occurred at 60° (~09:00 h), and the lowest sleep propensity (91.3%) occurred at 265° (~22:40 h). As has been shown previously, these current data indicate that with a normal sleep-to-wake ratio, the effect of the circadian process on sleep propensity is pronounced, such that a forbidden zone for sleep exists at a phase equivalent to evening time for a normally entrained individual. However, these current data also indicate that when the ratio of sleep to wake is substantially lower than normal, this circadian effect is masked. In particular, sleep propensity is very high at all circadian phases, including those that coincide with the forbidden zone for sleep. This finding suggests that if the homeostatic pressure for sleep is sufficiently high, then the circadian drive for wakefulness can be overridden. In future studies, it will be important to determine whether or not this masking effect occurs with less severe sleep restriction, e.g., with a sleep-to-wake ratio of 1:3.     

Performance, sleep and circadian phase during a week of simulated night work

The current study investigated changes in night-time performance, daytime sleep, and circadian phase during a week of simulated shift work. Fifteen young subjects participated in an adaptation and baseline night sleep, directly followed by seven night shifts. Subjects slept from approximately 0800 hr until they naturally awoke. Polysomnographic data was collected for each sleep period. Saliva samples were collected at half hourly intervals, from 2000 hr to bedtime. Each night, performance was tested at hourly intervals. Analysis indicated that there was a significant increase in mean performance across the week. In general, sleep was not negatively affected. Rather, sleep quality appeared to improve across the week. However, total sleep time (TST) for each day sleep was slightly reduced from baseline, resulting in a small cumulative sleep debt of 3.53 (SD = 5.62) hours. Finally, the melatonin profile shifted across the week, resulting in a mean phase delay of 5.5 hours. These findings indicate that when sleep loss is minimized and a circadian phase shift occurs, adaptation of performance can occur during several consecutive night shifts.     

Heart rate variability and body temperature during the sleep onset period

Heart rate variability (HRV) and body temperature during the sleep onset period was examined. The core body temperature and electrocardiogram were recorded continuously beginning 1 h before lights out (LO) until the end of the first rapid eye movement sleep (REM) in 14 young healthy subjects. HRV was calculated by the MemCalc method. The time course changes in body temperature and HRV was analyzed before and after sleep onset, and during the following eight consecutive phases: the 60 min before LO, the 30 min before LO, LO, first stage 2 (sleep onset), first slow wave sleep (SWS), stage 2 just before REM, start of REM, and end of REM. A clear decline was observed in the ratio of the low frequency (LF) to high frequency (HF) component of HRV (LF/HF), normalized LF (LF/(LF + HF)), and body temperature prior to sleep onset both in the time course of the sleep onset period and in the consecutive phases. The HF increased prior to sleep onset in the consecutive phases, while no clear increase was observed in the time course of sleep onset period. Changes in LF/(LF + HF) and LF/HF preceded SWS and REM. These results suggest the existence of a strong coupling between the cardiac autonomic nervous system and body temperature at the sleep onset period that may not be circadian effects. Furthermore, LF/(LF + HF) and LF/HF may possibly anticipate sleep and the onset of each sleep stage.