Sleep continuity and the REM-nonREM cycle in the rat under baseline conditions and after sleep deprivation

Wakefulness, nonrapid eye movement sleep (nonREMS) and REMS of rats were scored in 4-s epochs during the first 8 h of the 12-h light period of a baseline (BL) day and during recovery (REC) from 24-h sleep deprivation (SD). Vigilance state continuity was investigated by analyzing the distribution of state episodes. After SD, state continuity was enhanced. The reduced occurrence of short wake episodes resulted in a consolidation of sleep states. The distribution of the REM-nonREM cycle length showed a mode at 10-13 min for both BL and REC. The variability of the cycle length was reduced after SD. The mean cycle length was markedly influenced by the criteria of minimum REMS episode duration and maximal allowed REMS episode interruption.     

Sleep deprivation in the rat: VIII. High EEG amplitude sleep deprivation

The disk apparatus was used to deprive six rats of the portion of non-rapid eye movement (NREM) sleep with high electroencephalogram (EEG) amplitude (HS2). All HS2 deprived (HS2D) rats died or were sacrificed when death seemed imminent within 23 to 66 days. No anatomical cause of death was identified. All deprived rats showed a debilitated appearance, lesions on their tails and paws, and weight loss in spite of increased food intake. Energy expenditure (calculated from the caloric value of food, weight change, and wastes) increased to more than twice baseline values. With one exception, yoked control rats remained generally healthy. It was not clear whether the changes in HS2D rats resulted from the loss of HS2 or the general disruption of NREM sleep that accompanied this loss. Also, it was not possible to produce major HS2 loss without incurring some loss of paradoxical sleep (PS). Control studies indicated that the partial PS loss in HS2D rats could not, in and of itself, account for all the pathological effects. However, an interaction of HS2D and partial PS loss in producing pathological effects cannot be ruled out.     

Zolpidem and sleep deprivation: different effect on EEG power spectra

To study the role of GABA-ergic mechanisms in sleep regulation, the combined action of 40 h sleep deprivation and either 20 mg zolpidem or placebo on the sleep electroencephalogram (EEG) were investigated by quantitative EEG analysis in eight young men who participated in a positron emission tomography study. Compared with baseline, sleep deprivation increased low-frequency (1.25-7.0 Hz) EEG power in non-rapid eye movement (NREM) sleep in the placebo night. After administration of zolpidem, power in the 3.75-10.0 Hz range and 14. 25-16.0 Hz band was reduced. The largest decrease was observed in the theta band. Comparison with placebo revealed that zolpidem attenuated power in the entire 1.75-11.0 Hz range. The plasma concentration of zolpidem at 4.5 h after intake showed a positive correlation with the drug-induced difference in power from placebo in the 14.25-16.0 Hz band. Regional EEG analysis based on bipolar derivations along the antero-posterior axis disclosed, for NREM sleep, a drug-induced posterior shift of power in the frequency range of 7.75-9.75 Hz. Zolpidem did not affect rapid eye movemnt sleep spectra. We conclude that sleep deprivation and agonistic modulation of GABAA receptors have separate and additive effects on power spectra and that their effects are mediated by different neurophysiological mechanisms.     

Sleep extension in humans: sleep stages, EEG power spectra and body temperature

In eight male subjects the electroencephalogram (EEG) and core body temperature (Tcore) were recorded during long sleep episodes from 0000 to 1,500 hr. EEGs were visually scored and subjected to spectral analysis by fast Fourier transform. Slow-wave sleep [SWS, i.e. stages 3 + 4 of non-rapid eye movement (NREM) sleep and slow wave activity (SWA, mean EEG power density in the range of 0.75-4.5 Hz)] in NREM sleep attained highest values in the first 3 hr of sleep and lowest values in the morning hours when rapid eye movement (REM) sleep was at its maximum. Wakefulness was significantly enhanced in the last 3 hr of the recording period. Occasional NREM episodes containing SWS were observed in the late morning and early afternoon. However, no significant increase in SWS or SWA in the last 3 hr of the sleep episode over any of the preceding 3-hr intervals was present and SWA in this interval was significantly below the values observed at the beginning of sleep. The duration of NREM episodes varied significantly over the sleep episode. Analysis of the dynamics of SWA within NREM episodes revealed that SWA gradually rose during the episode. Consequently, SWA averaged per episode was positively correlated with episode duration. Tcore dropped in the initial part of sleep, rose during the morning hours and reached values in the afternoon that were higher than at the beginning of sleep. Thus the time course of Tcore dissociated from the time course of SWA. This indicates that SWA in NREM sleep is not directly related to the variation in core body temperature.     

Sleep deprivation in the rat: III. Total sleep deprivation

Ten rats were subjected to total sleep deprivation (TSD) by the disk apparatus. All TSD rats died or were sacrificed when death seemed imminent within 11-32 days. No anatomical cause of death was identified. All TSD rats showed a debilitated appearance, lesions on their tails and paws, and weight loss in spite of increased food intake. Their yoked control (TSC) rats remained healthy. Since dehydration was ruled out and several measures indicated accelerated use rather than failure to absorb nutrients, the food-weight changes in TSD rats were attributed to increased energy expenditure (EE). The measurement of EE, based upon caloric value of food, weight, and wastes, indicated that all TSD rats increased EE, with mean levels reaching more than twice baseline values.     

Recovery sleep following different visual conditions during total sleep deprivation in man.

The findings of visual impairment during total sleep deprivation were used as a basis for a possible link between vision and sleep. It was proposed that the level of visual load imposed during sleep deprivation was an important variable, and would have a substantial effect upon recovery sleep. Six young male subjects underwent two conditions of 64 h of sleep deprivation on separate occasions. One condition incorporated a high visual load, and the other a low load. Exercise and sound were balanced. All night sleep EEGs were taken for two baseline nights, and also for two recovery nights following each condition. There was a significant increase of stage 4 on all recovery nights and a REM rebound on the second recovery night. SWS, particularly stage 4, TST and REM density, were significantly greater following the high load. Implications of these findings for sleep theories and for sleep deprivation research are discussed.     

Sleep deprivation in the rat: IV. Paradoxical sleep deprivation

Twelve rats were subjected to paradoxical sleep deprivation (PSD) by the disk apparatus. All PSD rats died or were sacrificed when death seemed imminent within 16-54 days. No anatomical cause of death was identified. All PSD rats showed a debilitated appearance, lesions on their tails and paws, and weight loss in spite of increased food intake. Their yoked control (PSC) rats remained healthy. Since dehydration was ruled out and several measures indicated normal or accelerated use of nutrients, the food-weight changes in PSD rats were attributed to increased energy expenditure (EE). The measurement of EE, based upon caloric value of food, weight, and wastes, indicated that all PSD rats increased EE, with mean levels reaching more than twice baseline values. All of these changes had been observed in rats deprived totally of sleep; the major difference was that they developed more slowly in PSD rats.     

Effects of pinealectomy on baseline sleep and response to sleep deprivation

STUDY OBJECTIVES: We have previously reported that older (24 mo.) Fischer rats manifest a diminished post-sleep deprivation increase in NREM and REM sleep. In order to examine whether this decline reflects an age-related change in pineal function, we are now reporting on baseline and recovery sleep parameters in pinealectomized 3-, 12-, and 24-month old rats following 24 hours of sleep deprivation using the disk-over-water method. DESIGN: Three independent age groups; within each group there were sequential measures of sleep under baseline conditions and during recovery from sleep deprivation. SETTING: The Sleep Research Laboratory at the University of Chicago PARTICIPANTS: 56 male Fisher (F344) rats INTERVENTIONS: 24 hours of total sleep deprivation using the disk-over-water method MEASUREMENTS: Sleep staging of EEG and EMG, and power spectral analysis of the EEG RESULTS: Pinealectomized (pinex) rats did not differ from sham-operated (sham) rats in total sleep, REM sleep, super-modal high-amplitude NREM sleep (HS2), a measure of NREM EEG delta power, or circadian rhythm amplitude. In the pinex rats, there was a modest (2.5%) age-independent increase in NREM sleep (p<0.02). The pinex rats of all ages failed to manifest the increase in NREM sleep during recovery seen in the sham-operated animals (p<0.04). CONCLUSIONS: We found no evidence that altered pineal function is responsible for age-related changes in baseline sleep in the rat. These data also suggest that, independent of age, normal pineal function may be relevant to the ability to generate increased NREM sleep in response to prior sleep deprivation.     

Sleep deprivation and the physiological response to exercise under steady-state conditions in untrained subjects

Seven physically untrained subjects underwent 72 h total sleep deprivation, followed a baseline day. Daily, at 0400 and 1600 h, subjects pedalled on a bicycle ergometer under individually set work loads of 40, 60, and 80% VO2max. This was not a study oriented towards endurance but towards capacity, requiring steady-state measurement. From assessments of heart rate, VO2 and VCO2 were calculated: VO2max, gross mechanical efficiency, VO2 at a heart rate of 150, and respiratory quotient. To assess possible training effects, a control group underwent identical procedures except that they slept at night and had the morning measure delayed until 0830 h. A series of statistical models were applied to the data, which centered on quantifying the inherent underlying variability, to estimate the level any main effect had to reach to become significant. the analysis showed that the noise level was small enough for any real effect of importance to have been detected, with a reasonably large probability. No statistically significant effects were found for any of the parameters with respect to conditions, days, and time. The main significant outcome was with mechanical efficiency, which displayed greater variability during sleep deprivation. Both groups displayed similar trends in training effects. It was concluded that the physiological ability to do work of the type and duration used here was not adversely affected by 72 h of sleep loss.     

Interhemispheric sleep EEG asymmetry in the rat is enhanced by sleep deprivation

Vigilance state-related topographic variations of electroencephalographic (EEG) activity have been reported in humans and animals. To investigate their possible functional significance, the cortical EEG of the rat was recorded from frontal and parietal derivations in both hemispheres. Records were obtained for a 24-h baseline day, 6-h sleep deprivation (SD), and subsequent 18-h recovery. During the baseline 12-h light period, the main sleep period of the rat, low-frequency (<7.0 Hz) power in the non-rapid eye-movement (NREM) sleep EEG declined progressively. Left-hemispheric predominance of low-frequency power at the parietal derivations was observed at the beginning of the light period when sleep pressure is high due to preceding spontaneous waking. The left-hemispheric dominance changed to a right-hemispheric dominance in the course of the 12-h rest-phase when sleep pressure dissipated. During recovery from SD, both low-frequency power and parietal left-hemispheric predominance were enhanced. The increase in low-frequency power in NREM sleep observed after SD at the frontal site was larger than at the parietal site. However, frontally no interhemispheric differences were present. In REM sleep, power in the theta band (5.25-8.0 Hz) exhibited a right-hemispheric predominance. In contrast to NREM sleep, the hemispheric asymmetry showed no trend during baseline and was not affected by SD. Use-dependent local changes may underlie the regional differences in the low-frequency NREM sleep EEG within and between hemispheres. The different interhemispheric asymmetries in NREM and REM sleep suggest that the two sleep states may subserve different functions in the brain.     

Vascular resistance in the rat during baseline, chronic total sleep deprivation, and recovery from total sleep deprivation

Rats subjected to total sleep deprivation (TSD) by the disk-over-water method exhibit an elevated temperature set point, increased energy expenditure (EE), and increased circulating norepinephrine--all of which should militate for an increase in body temperature. Instead, after a small rise early in TSD, intraperitoneal temperature (T(ip)) fell progressively, indicating a reduced ability to retain body heat. To evaluate whether vasoconstrictor defenses against heat loss in the regions of major heat dissipation in the rat (hindpaws and tail) were impaired, peripheral vascular resistance (PVR) was calculated from aortic blood pressure (BP) and blood flow (BF) (BP and BF were continuously recorded at the aortic-iliac junction). TSD rats and their yoked control (TSC) rats were subjected to TSD for 10 to 22 days. As in earlier studies, TSD rats showed excessive heat loss indicated by a falling T(ip) (after an initial rise) while EE was elevated. Temperature set point was presumably raised throughout deprivation as shown previously. Although a small decline in PVR early in deprivation could have increased heat loss, there was no evidence of a massive vasodilation in the region examined which could, in itself, account for the progressive inability to retain heat over the course of TSD. In fact, PVR was near baseline levels during the latter half of TSD. Nevertheless, there was evidence of impaired vasoconstrictive defenses in TSD rats inasmuch as they showed significantly lower PVR than TSC rats during most of the deprivation period in spite of indications that they were farther below set point. It is not yet clear whether this impairment was a major determinant of the heat loss in TSD rats. A rapid PVR rebound during recovery suggested a release from a TSD-linked blockage of vasomotor compensation for excessive heat loss.     

Effects of paradoxical sleep deprivation in the rabbit

The effects of nonpharmacologically-induced deprivation of paradoxical sleep for a 24 hour period were studied in rabbits. Response characteristics commonly associated with the deprivation procedure in other species were observed, as well as features apparently peculiar to the rabbit. Like other mammals, rabbits: (1) show increased attempts to experience PS during the deprivation procedure relative to the baseline occurrence of PS; (2) become increasingly difficult to arouse from PS as the deprivation period progresses; (3) show increased amounts of PS (rebound) in post-deprivation recordings relative to baseline; and (4) compensate for only one-third of the PS deficit incurred during deprivation. Rabbits' response to PS deprivation differs from other mammals in the following ways: (1) the deprivation procedure is truly selective, significantly affecting only amounts of PS and not total sleep time or other sleep stages; (2) the rebound response is restricted to the light phase of the light-dark cycle on the first recovery day; and (3) as indexed by eye movement density, phasic activity during PS is not enhanced during the recovery period. Given that the crucial factor in the PS deprivation-compensation phenomenon is thought to be the deprivation and subsequent enhanced occurrence of phasic events, and considering that events within the oculomotor system have been emphasized in this regard, the results of this investigation suggest the existence of species differences regarding the nature and form of the compensatory response to PS deprivation.     

Changes in the waking EEG as a consequence of sleep and sleep deprivation.

Electroencephalographic (EEG) activity was monopolarly recorded during resting wakefulness in 10 volunteers under the following conditions: at night before going to sleep, at night before total sleep deprivation, in the morning after waking, in the morning after sleep deprivation and at night after having slept during the day. Absolute and relative power and inter- and intrahemispheric correlation were established. After diurnal and nocturnal sleep as compared to sleep deprivation, we obtained the following significant results: interhemispheric correlations were higher; intrahemispheric correlations were lower; absolute power of alpha 2, beta 1 and beta 2 was lower; and relative power of alpha 2 and beta 2 was lower. EEG changes as a consequence of sleep or lack of sleep are dependent on prior sleep and/or wakefulness and not on circadian phase. EEG activity during wakefulness is a sensitive parameter and a useful tool to assess the consequences of sleep on brain functional organization.     

Prolonged effects of 24-h total sleep deprivation on sleep and sleep EEG in the rat

Long-term effects of 24-h sleep deprivation (SD) on sleep and sleep EEG were analyzed in male rats during 4 recovery days (Rec). An increase of total sleep time and non-rapid eye-movement (NREM) sleep was present during Rec 1-4, and of REM sleep in Rec 1 and in the dark periods of Rec 2 and 3. After the initial increase of slow-wave activity (SWA, mean EEG power density in the 0.75-4.0 Hz range) in NREM sleep, SWA declined below baseline until Rec 3. Sleep continuity was increased in Rec 1. The persistent effects of SD which are probably due to homeostatic and circadian facets of sleep regulation, must be taken into account in the design of SD studies.     

Recovery sleep and performance following sleep deprivation with dextroamphetamine

Twelve subjects were studied to determine the after-effects of using three 10-mg doses of dextroamphetamine to sustain alertness during sleep deprivation. Sleep architecture during recovery sleep was evaluated by comparing post-deprivation sleep beginning 15 h after the last dextroamphetamine dose to post-deprivation sleep after placebo. Performance and mood recovery were assessed by comparing volunteers who received dextroamphetamine first (during sleep deprivation) to those who received placebo first. Stages 1 and 2 sleep, movement time, REM latency, and sleep latency increased on the night after sleep deprivation with dextroamphetamine vs. placebo. Stage 4 was unaffected. Comparisons to baseline revealed more stage 1 during baseline than during either post-deprivation sleep period and more stage 2 during baseline than during sleep following placebo. Stage 4 sleep was lower during baseline than it was after either dose, and REM sleep was lower during baseline and after dextroamphetamine than after placebo. Sleep onset was slowest on the baseline night. Next-day performance and mood were not different as a function of whether subjects received dextroamphetamine or placebo during deprivation. These data suggest dextroamphetamine alters post-deprivation sleep architecture when used to sustain alertness during acute sleep loss, but next-day performance and subjective mood ratings are not substantially affected. A recovery sleep period of only 8 h appears to be adequate to regain baseline performance levels after short-term sleep deprivation.     

Topography of EEG dynamics after sleep deprivation in mice

Several recent results show that sleep and sleep regulation are not only global phenomena encompassing the entire brain, but have local features. It is well established that slow-wave activity [SWA; mean electroencephalographic (EEG) power density in the 0.75-4.0 Hz band] in non-rapid eye movement (NREM) sleep is a function of the prior history of sleep and wakefulness. SWA is thought to reflect the homeostatic component of the two-process model of sleep regulation. According to this model, originally formulated for the rat and later extended to human sleep, the timing and structure of sleep are determined by the interaction of a homeostatic Process S and a circadian process. Our aim was to investigate the dynamics of SWA in the EEG of two brain regions (frontal and occipital cortex) after sleep deprivation (SD) in two of the mice strains most often used in gene targeting. C57BL/6J (n = 9) and 129/Ola (n = 8) were recorded during a 24-h baseline day, 6-h SD, and 18-h recovery. Both derivations showed a significant increase in SWA in NREM sleep after SD in both strains. In the first hour of recovery, SWA was enhanced more in the frontal derivation than in the occipital derivation and showed a faster decline. This difference resulted in a lower value for the time constant for the decrease of SWA in the frontal derivation (frontal: 10.9 +/- 2.1 and 6.8 +/- 0.9 h in Ola and C57, respectively; occipital: 16.6 +/- 2.1 and 14.1 +/- 1.5 h; P < 0.02; for each of the strains; paired t-test). Neither time constant differed significantly between the strains. The subdivision of SWA into a slower and faster band (0.75-2.5 Hz and 2.75-4.0 Hz) further highlighted regional differences in the effect of SD. The lower frequency band had a higher initial value in the frontal derivation than in the occipital derivation in both strains. Moreover, in the higher frequency band a prominent reversal took place so that power in the frontal derivation fell below the occipital values in both strains. Thus our results indicate that there may be differences in the brain in the effects of SD on SWA in mice, suggesting regional differences in the dynamics of the homeostatic component of sleep regulation. The data support the hypothesis that sleep has local, use- or waking-dependent features that are reflected in the EEG, as has been shown for humans and the laboratory rat.     

Interhemispheric asymmetry of human sleep EEG in response to selective slow-wave sleep deprivation

Recent evidence suggests that the human sleep electroencephalogram (EEG) shows regional differences over both the sagittal and coronal planes. In the present study, in a group of 10 right-handers, the authors investigated the presence of hemispheric asymmetries in the homeostatic regulation of human sleep EEG power during and after selective slow-wave sleep (SWS) deprivation. The SWS deprivation was slightly more effective over the right hemisphere, but the left hemisphere showed a markedly larger increase of EEG power in the 1.00-24.75 Hz range during recovery-night non-REM sleep, and a larger increase of EEG power during both deprivation-night and recovery-night REM sleep. These results support the greater need for sleep recuperative processes of the left hemisphere, suggesting that local sleep regulation processes may also act during REM sleep.     

Increased EEG spectral power density during sleep following short-term sleep deprivation in pigeons (Columba livia): evidence for avian sleep homeostasis

Birds provide a unique opportunity to evaluate current theories for the function of sleep. Like mammalian sleep, avian sleep is composed of two states, slow-wave sleep (SWS) and rapid eye-movement (REM) sleep that apparently evolved independently in mammals and birds. Despite this resemblance, however, it has been unclear whether avian SWS shows a compensatory response to sleep loss (i.e., homeostatic regulation), a fundamental aspect of mammalian sleep potentially linked to the function of SWS. Here, we prevented pigeons (Columba livia) from taking their normal naps during the last 8 h of the day. Although time spent in SWS did not change significantly following short-term sleep deprivation, electroencephalogram (EEG) slow-wave activity (SWA; i.e., 0.78-2.34 Hz power density) during SWS increased significantly during the first 3 h of the recovery night when compared with the undisturbed night, and progressively declined thereafter in a manner comparable to that observed in similarly sleep-deprived mammals. SWA was also elevated during REM sleep on the recovery night, a response that might reflect increased SWS pressure and the concomitant 'spill-over' of SWS-related EEG activity into short episodes of REM sleep. As in rodents, power density during SWS also increased in higher frequencies (9-25 Hz) in response to short-term sleep deprivation. Finally, time spent in REM sleep increased following sleep deprivation. The mammalian-like increase in EEG spectral power density across both low and high frequencies, and the increase in time spent in REM sleep following sleep deprivation suggest that some aspects of avian and mammalian sleep are regulated in a similar manner.     

Sleep deprivation in the rat: XIII. The effect of hypothyroidism on sleep deprivation symptoms

Previous studies of rats subjected to total sleep deprivation by the disk-over-water method had shown a large increase in energy expenditure (EE) and an initial increase followed by a later decrease in body temperature (Tb). It had been proposed that the increase in Tb resulted from regulation toward a higher temperature or setpoint, that the later decline in Tb resulted from excessive heat loss, and that the increase in EE supported both of these thermoregulatory changes. To evaluate this proposed role of the increase in EE, we examined whether blunting the EE rise in sleep-deprived rats by making them hypothyroid attenuated and/or shortened the initial increase in Tb and accelerated the later decline in Tb. Rats made hypothyroid by propylthiouracil administration (TxD rats) were totally sleep deprived and compared to hypothyroid yoked control (TxC) rats and to previously studied, untreated, totally sleep-deprived (TSD) rats. Neither TxD nor TxC rats showed large increases in EE like those of TSD rats. TxD rats did not initially increase Tb, as TSD rats had. Presumably, TSD rats had been able to support an initially elevated Tb, in spite of excessive heat loss, by large increases in EE, although even these increases were eventually insufficient. TxD rats showed much earlier and greater declines in Tb than TxC and TSD rats, eventually becoming severely hypothermic. These results support the interpretation that the large increase in EE previously seen in TSD rats had been compensatory for deprivation-induced thermoregulatory deficits. TxD rats survived an average of 17.1 days, which was not significantly different from survival time in TSD rats. However, there were differences in mortal processes between the two groups. TxD rats died or were sacrificed after chronic, severe hypothermia without observable signs of other morbid pathology. TSD rats had not shown similarly low Tb until just prior to death, but had shown signs of severe pathology, including severely debilitated appearance, disheveled fur, and severe lesions on their tails and on the plantar surfaces of their paws. These signs were diminished or absent in TxD rats, possibly due to blunted EE, lower Tb, or other effects of hypothyroidism. Because the skin changes seen in TSD rats were minimal in TxD rats, they could not have been responsible for the excessive heat loss.