Duration Of Prior Wakefulness Research Articles

A sleep physiologist's view of the drowsy driver

Drowsy driving is dangerous because of the impairment of driving skills that it causes. Unfortunately, the conceptual basis that underlies much of the multi-disciplinary research on this topic is muddled. The same poorly defined terms, such as fatigue and sleepiness, are used differently by different disciplines and researchers. Some new definitions and concepts are proposed here which may be helpful, as least as a stimulus for discussion by others. Drowsiness, sleepiness and fatigue are distinguished. A new conceptual model of sleepiness is outlined, based on a mutually inhibitory interaction between a putative sleep drive and a wake drive. Sleepiness, defined as sleep propensity, is a function of the relative strengths, not the absolute strengths, of the sleep and wake drives. The measurement of sleepiness requires some new variables such as instantaneous sleep propensity, to be distinguished from either the situational or the average sleep propensity. A subject's instantaneous sleep propensity depends on many variables including his average sleep propensity in daily life, the time of day, the duration of prior wakefulness, the subject's posture, physical and mental activity at the time, and individual differences based on psychophysiological traits. The relationship between dozing at the wheel while driving and crashing the vehicle may not be as straightforward as it appears at first.

Circadian timed wakefulness at dawn opposes compensatory sleep responses after sleep deprivation in Octodon degus.

The circadian timing system in mammals is thought to promote wakefulness and oppose sleep drive that accumulates across the activity phase in diurnal and nocturnal species. Whether the circadian system actively opposes compensatory sleep responses in mammals with episodes of alertness consolidated at dawn and dusk is unknown. In the present study, an interaction between circadian timed arousal at dawn and compensatory sleep responses after sleep deprivation (SD) was examined in Octodon degus, a hystricomorph rodent with crepuscular episodes of wakefulness. Recovery sleep was compared after 6 hours and 12 hours of SD ending at either CT 21 or 12, just before the dawn, and just after the dusk crepuscular episodes of consolidated wakefulness, respectively. Total sleep time and NREM sleep after SD increased proportionally to the amount of sleep loss; however, compensatory sleep responses after SD were attenuated at CT 23, a circadian time when a crepuscular event of wakefulness occurs in this species. EEG slow-wave activity (SWA) and body temperature levels in the first two hours after 6 and 12 hours of SD ending at CT 12 were similar. However, both were significantly higher than after 12 hours of SD ending at CT 21, suggesting factors other than the amount of prior wake duration can influence SWA levels. This study provides evidence that the circadian arousal system opposes compensatory sleep responses at dawn by actively promoting wakefulness in this species.

Circadian and homeostatic influences on sleep in the squirrel monkey: sleep after sleep deprivation.

A series of sleep deprivation (SD) experiments were performed to examine the relative influence of circadian and homeostatic factors on the timing of sleep in squirrel monkeys free-running in constant illumination. All SDs started at the beginning of subjective night and lasted 0, 1/4, 1/2, 1, 1 1/4, or 1 1/2 circadian cycles. These six lengths represented three pairs: (0.1), (1/4, 1 1/4), (1/2, 1 1/2). Within each pair, SD ended at the same circadian phase but differed by one circadian cycle in duration. Both before and after SD, consolidated sleep (CS) episodes occurred predominantly during subjective night, even after long SDs ending at the beginning of subjective day. CS duration was strongly influenced by circadian phase but had no overall correlation with prior wake duration. Sleep loss incurred during SDs longer than 1/4 cycle was only partially recovered over the next two circadian cycles, though total sleep duration was closer to baseline levels after the second circadian cycle after SD. There was a trend toward a positive correlation between prior wake duration and the amount of NREM and delta activity measures during subjective day. Delta activity was not increased in the first 2 hours of CS after the SD. Relatively high levels of delta activity occurred immediately after the SD ended and again at the time of baseline CS onset. These data indicate that the amount of sleep and delta activity after SD in squirrel monkeys is weakly dependent on prior wake duration. Circadian factors appear to dominate homeostatic processes in determining the timing, duration and content of sleep in these diurnal primates.

Prior spontaneous nocturnal waking duration and EEG during quiet sleep in infants: an automatic analysis approach

To ascertain the role of spontaneous nocturnal waking duration on the EEG dynamics during quiet sleep (QS) periods, we analysed the nocturnal polygraphic recordings of 12 infants aged 9–47 weeks old. Their sleep was characterised by two sleep episodes, separated by spontaneous waking and containing at least two QS-paradoxical sleep (PS) cycles each. Automatic analysis of the EEG activity recorded by the centro-occipital lead and reflecting the degree of synchronisation allowed us to compute a parameter whose values ranged from 0 (maximum of EEG synchronisation) to 10 (maximum of EEG de-synchronisation). Three indicators of the time course of the parameter value were computed during the first QS period of the sleep episode subsequent to nocturnal waking: (i) the parameter range (difference between the EEG parameter value at the QS onset and that at the trough-maximum of EEG synchronisation); (ii) the trough latency (time interval between QS onset and trough); and (iii) rate of synchronisation (range/trough latency). These three indicators were the dependent variables in a multiple regression model, where the independent variables were age and the logarithm of the duration of prior waking. The parameter range was correlated with the duration of prior waking. Both the trough latency and the rate of synchronisation were correlated with age only, respectively, positively and negatively. The marked decline in the rate of synchronisation throughout the first year of life could account for the failure to find a significant correlation between prior waking and the above indicator of the EEG dynamics. The relationship between the duration of prior waking and the parameter range in following sleep in infants supports the hypothesis of the early emergence of the homeostatic regulation of sleep.

Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness.

Both subjective and electroencephalographic arousal diminish as a function of the duration of prior wakefulness. Data reported here suggest that the major criteria for a neural sleep factor mediating the somnogenic effects of prolonged wakefulness are satisfied by adenosine, a neuromodulator whose extracellular concentration increases with brain metabolism and which, in vitro, inhibits basal forebrain cholinergic neurons. In vivo microdialysis measurements in freely behaving cats showed that adenosine extracellular concentrations in the basal forebrain cholinergic region increased during spontaneous wakefulness as contrasted with slow wave sleep; exhibited progressive increases during sustained, prolonged wakefulness; and declined slowly during recovery sleep. Furthermore, the sleep-wakefulness profile occurring after prolonged wakefulness was mimicked by increased extracellular adenosine induced by microdialysis perfusion of an adenosine transport inhibitor in the cholinergic basal forebrain but not by perfusion in a control noncholinergic region.

Social stress induces high intensity sleep in rats

We studied the effect of social stress on sleep electroencephalogram (EEG) in rats. Animals were subjected to a single social defeat by introducing them in the cage of an aggressive male conspecific for 1 h. The animals responded to the social conflict by a sharp increase in EEG slow-wave activity (SWA) during non-rapid eye movement sleep (NREM) afterwards. Since SWA has been identified as an indicator of sleep intensity, the results suggest that acute stressors may accelerate the build up of sleep debt. Sleep intensity may, thus, not only depend on the duration of prior wakefulness but also on the nature of the waking experience. The strong increase in SWA after social defeat indicates that sleep may function to offset the mental loads imposed on the nervous system during wakefulness.

Complex interaction of the sleep-wake cycle and circadian phase modulates mood in healthy subjects.

Several studies of healthy volunteers have revealed that subjective mood may vary with the duration of prior wakefulness and with the time of day. However, in these studies, the effects of extended wakefulness and circadian phase remained confounded, and the interaction of these 2 processes could not be assessed quantitatively. In the present study, a total of 24 healthy young subjects (16 men, 8 women) lived on a 30-hour sleep-wake schedule for 19 to 23 days or on a 28-hour sleep-wake schedule for 33 to 36 days; both schedules induced desynchrony between the subjects' sleep-wake cycle and their endogenous circadian pacemaker. Subjective mood was assessed by 2 types of visual analog scales, which were administered twice every 2 hours and every 20 minutes, respectively, during all scheduled wakefulness episodes. A circadian phase and an interval elapsed since awakening were attributed to each data point, and circadian and wake-dependent fluctuations of mood were assessed. A significant variation of mood with circadian phase was observed, but no reliable main effect of the duration of prior wakefulness was found. A statistically significant interaction of circadian and wake-dependent fluctuations was evident; when the analysis was restricted to specific circadian phases, mood improved, deteriorated, or remained stable with the duration of prior wakefulness. These results indicate that, in healthy young subjects, subjective mood is influenced by a complex and nonadditive interaction of circadian phase and duration of prior wakefulness. The nature of this interaction is such that moderate changes in the timing of the sleep-wake cycle may have profound effects on subsequent mood.

Adenosine inhibition of mesopontine cholinergic neurons: implications for EEG arousal.

Increased discharge activity of mesopontine cholinergic neurons participates in the production of electroencephalographic (EEG) arousal; such arousal diminishes as a function of the duration of prior wakefulness or of brain hyperthermia. Whole-cell and extracellular recordings in a brainstem slice show that mesopontine cholinergic neurons are under the tonic inhibitory control of endogenous adenosine, a neuromodulator released during brain metabolism. This inhibitory tone is mediated postsynaptically by an inwardly rectifying potassium conductance and by an inhibition of the hyperpolarization-activated current. These data provide a coupling mechanism linking neuronal control of EEG arousal with the effects of prior wakefulness, brain hyperthermia, and the use of the adenosine receptor blockers caffeine and theophylline.

Total sleep deprivation in the rat transiently abolishes the delta amplitude response to darkness: implications for the mechanism of the “negative delta rebound”

1. The homeostatic model of delta sleep has provided a useful framework for basic sleep research. This model is based on the relation of delta EEG to the duration of prior waking in man, a relation highlighted by the marked increase (rebound) in the delta EEG of nonrapid eye movement (NREM) sleep that follows total sleep deprivation (TSD). The generality of this model is severely challenged by the response to TSD in the rat. In the 12-h light period (LP) that immediately follows TSD, the rat shows a massive increase in REM sleep but only a modest increase in NREM delta EEG. Although this initial delta increase does not nearly compensate for the delta lost during deprivation, the rat then exhibits a depressed rate of delta production (the "negative delta rebound"). This robust and reproducible reaction worsens the delta deficit. 2. Using rats with chronic electrode implantations, we deprived them of all sleep for 24 h by handling them gently when they became inactive. We found that the negative delta rebound entails a transient, near-total failure of delta amplitude to increase normally in response to the onset of darkness. This loss of the rat's EEG response to darkness suggests a disruption of basic sleep physiology and raises the possibility that the negative rebound is also a pathological response. 3. We hypothesize that the negative rebound is maladaptive, and is caused by the massive increase in REM sleep that precedes it; this hypothesis can be tested experimentally.(ABSTRACT TRUNCATED AT 250 WORDS)

A model of human sleep homeostasis based on EEG slow-wave activity: Quantitative comparison of data and simulations

EEG slow-wave activity (SWA; spectral power in the 0.75–4.5 Hz band) is a function of the duration of prior waking and, thereby, an indicator of sleep homeostasis. We present a model that accounts for both the declining trend of SWA during sleep and for its variation within the successive nonrapid eye movement (non-REM) sleep episodes. The values of the model parameters were estimated by an optimization procedure in which empirical SWA of baseline nights (16 subjects, 26 nights) served as a reference. A sensitivity analysis revealed the model to be quite robust to small changes (±5%) of the parameter values. The estimated parameter values were used to simulate data sets from three different experimental protocols (sleep in the evening or sleep in the morning after prolonged waking, or extended sleep initiated at the habitual bedtime; n = 8 or 9). The timing of the REM trigger parameter was derived from the empirical data. A close fit was obtained between the simulated and empirical SWA data, and even the occasional late SWA peaks during extended sleep could be reproduced. Minor discrepancies suggest indirect or direct circadian influences on SWA. The simulations demonstrate that the concept of sleep homeostasis as proposed in the two-process model of sleep regulation can be refined to account in quantitative terms for empirical data and to predict the changes induced by the prolongation of waking or sleep.

Cortical and subcortical EEG in relation to sleep-wake behavior in mammalian species.

In humans and several other mammals, a quantitative EEG analysis has been used to study the regulation of sleep-wake behavior. In all mammalian species studied, cortical EEG recorded during non-REM sleep (NREMS) is characterized by the occurrence of spindles and high voltage, slow waves (0.5-4.0 Hz). Furthermore, slow-wave activity (SWA) is low at the beginning of a NREM episode and it rises in the course of a NREM episode. The rise rate and the maximal level of SWA are a monotonic function of the duration of prior wakefulness. During REMS, cortical EEG typically exists of low-voltage, mixed frequencies and, in some animals, a prominent theta rhythm is superimposed. Only after sleep deprivation in some species does cortical EEG within REMS change. Especially, the EEG activity during wakefulness depends considerably on the behavioral state, on the electrode location and on the species. On average, cortical EEG within wakefulness consists of low-voltage, mixed frequencies. The few studies done on subcortical EEG clearly show that the electrical activity differs highly between brain regions and between species. However, two recent studies, in which a spectral analysis of subcortical EEG was made, showed that, at least in humans and cats, the changes occurring in subcortical EEG associated with changes in sleep-wake behavior parallel the general characteristics of cortical EEG described above.

Circadian and sleep/wake dependent aspects of subjective alertness and cognitive performance.

Circadian and sleep/wake dependent processes underlying variations in subjective alertness and cognitive performance were assessed in a constant routine protocol and in a protocol in which the sleep/wake cycle was uncoupled from the output of the endogenous circadian pacemaker. In the latter protocol, the contribution of a sleep/wake dependent process and a circadian process to alertness and performance were separated by folding the data at either the period of the sleep/wake cycle or at the period of the endogenous circadian body temperature rhythm. This analysis revealed that prior wakefulness within a range of 0-18 h significantly reduced alertness and performance and that the circadian rhythm of core body temperature paralleled the circadian rhythm of alertness and performance. During the first 16 h of the constant routine protocol, which coincided with the subjects' habitual period of wakefulness, alertness and performance remained at a stable level. The latter finding was explained by assuming that during our usual waking day the circadian system counteracts the detrimental effects of increasing duration of prior wakefulness.

Acute Deprivation of the Terminal 3.5 Hours of Sleep Does Not Increase Delta (0–3-Hz) Electroencephalograms in Recovery Sleep

Sleep electroencephalograms (EEG) and electrooculograms were recorded in nine young adult males on a baseline night, a night in which they were deprived of an average of 3 hr 27 min of sleep by early awakening, and on a recovery night. Records were analyzed by visual sleep stage scoring and period-amplitude analysis; the results of both were tabulated by successive nonrapid eye movement periods (NREMPs) and rapid eye movement (REM) periods. Neither visually scored delta nor REM measures were affected by this substitution of waking for sleep. Although there was a significant increase in the 0-3-Hz time/epoch on the recovery night, this finding was not confirmed in the accompanying report. These results, taken in association with data from previous studies, are consistent with the hypothesis that, in an acute experiment, visually scored delta and computer-measured 0-3-Hz EEGs increase above the baseline levels only if there has been loss of stage 3/4 EEG (or of sleep) from the first two NREMPs. The findings here are inconsistent with older reports and indicate that further parametric data are required to construct a quantitative model of the relation of sleep EEG waveforms to the duration of prior waking.

Time course of EEG power density during long sleep in humans

In nine subjects sleep was recorded under base-line conditions with a habitual bedtime (prior wakefulness 16 h; lights off at 2300 h) and during recovery from sleep deprivation with a phase-advanced bedtime (prior wakefulness 36 h; lights off at 1900 h). The duration of phase-advanced recovery sleep was greater than 12 h in all subjects. Spectral analysis of the sleep electroencephalogram (EEG) revealed that slow-wave activity (SWA; 0.75-4.5 Hz) in non-rapid-eye-movement (NREM) sleep was significantly enhanced during the first two NREM-REM sleep cycles of displaced recovery sleep. The sleep stages 3 and 4 (slow-wave sleep) and SWA decreased monotonically over the first three and four NREM-REM cycles of, respectively, base-line and recovery sleep. The time course of SWA in base-line and recovery sleep could be adequately described by an exponentially declining function with a horizontal asymptote. The results are in accordance with the two-process model of sleep regulation in which it is assumed that SWA rises as a function of the duration of prior wakefulness and decreases exponentially as a function of prior sleep. We conclude that the present data do not provide evidence for a 12.5-h sleep-dependent rhythm of deep NREM sleep.

EEG power density during nap sleep: reflection of an hourglass measuring the duration of prior wakefulness.

The relation between the duration of prior wakefulness and EEG power density during sleep in humans was assessed by means of a study of naps. The duration of prior wakefulness was varied from 2 to 20 hr by scheduling naps at 1000 hr, 1200 hr, 1400 hr, 1600 hr, 1800 hr, 2000 hr, and 0400 hr. In contrast to sleep latencies, which exhibited a minimum in the afternoon, EEG power densities in the delta and theta frequencies were a monotonic function of the duration of prior wakefulness. The data support the hypothesis that EEG power density during non-rapid eye movement sleep is only determined by the prior history of sleep and wakefulness and is not determined by clock-like mechanisms.

REM sleep latency during nocturnal sleep in mentally retarded infants

REM sleep latency observed in 61 mentally retarted infants (4–13 months of age) was studied throughout nocturnal sleep. Mentally retarded infants revealed a J distribution of short (less than 8 min) and long (more than 8 min) REM sleep latencies. This feature of distribution was similar to that obtained by other authors from normal infants under 3 months of age. REM sleep latency did not depend on the duration of prior wakefulness. Long REM sleep latencies were no more often preceded by long episodes of wakefulness than were short REM sleep latencies. No correlation was found between REM sleep latency and age, developmental quotient or daytime clinical EEG abnormalities.

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.

Differential effects of prior wakefulness and circadian phase on nap sleep

Studies of experimentally altered human sleep-wake cycles have shown that rapid eye movement (REM) sleep propensity exhibits a circadian periodicity, while slow wave sleep (SWS) is primarily responsive to the duration of prior wakefulness. What is not known is the extent to which REM sleep continues to show a circadian pattern under intense sleep pressure, and the extent to which SWS remains responsive to prior wakefulness at opposite phases of the circadian cycle. These questions were addressed by permitting healthy young adults a 2 h nap opportunity at opposite phases of the circadian cycle and with varying amounts of prior wakefulness, during a 54 h trial in a laboratory environment free of time cues. Three groups slept near the circadian peak (15.00 h) in the diurnal activity cycle, preceded by either 6, 30, or 54 h of prior wakefulness. Two other groups had naps near the circadian trough (03.00 h), midway between the peak naps and preceded by either 18 or 42 h of wakefulness. Comparisons both between and within groups revealed that latencies to sleep onset and to SWS decreased, while stage 4 sleep increased markedly in response to prior wakefulness up to 30 h, without any effect from the circadian placement of the nap. REM sleep propensity, as measured by the number of naps with REM and the amount of REM sleep among those naps that contained REM, was affected only by the circadian phase of the nap, with trough naps containing significantly less REM. Thus, no amount of sleep pressure changed the circadian phase-dependent expression of REM, and SWS remained wake-responsive at both phases of the diurnal cycle.

REM latency: Development in the first year of life

The development of REM latency in the first year of life was investigated in two groups of 10 infants each. While 10 infants were normal, the other 10 underwent continuous feeding for various gastrointestinal diseases. Each infant was continuously recorded polygraphically for 24 h. While younger infants (less than or equal to 3 months) manifested predominantly shorter REM latencies (less than or equal to 8 min), older infants (4-13 months) produced a mixed distribution of short and long REM latencies. The total distribution of the REM latencies appears to be bimodal with latencies either shorter than 8 min or longer than 16 min. It is only in the group of older infants that the temporal distribution of REM latencies constitutes a diurnal rhythm, with the longest latencies in the interval between 12:00 and 16:00 and the shortest between 4:00 and 8:00. In the group of older infants, REM latency also depends on the duration of prior wakefulness. Long REM latencies are significantly more often preceded by long episodes of wakefulness than are short REM latencies. The different feeding conditions had only a minor effect on REM latency.

Sleep deprivation: Effect on sleep stages and EEG power density in man

Sleep was analysed in 8 young adult subjects during two baseline nights and two recovery nights following 40.5 h sleep deprivation. Sleep stages were scored from the polygraph records according to conventional criteria. In addition, the EEG records of the entire nights were subjected to spectral analysis to compute the frequency distribution of the power density in the 0.25–25 Hz range for 0.5 Hz or 1.0 Hz bins. In the first recovery night, the power density in the delta band was significantly higher than baseline for total sleep time as well as for sleep stages 2, 3 and 4, 4 and REM. These changes were not restricted to the delta band, but extended to higher frequency bands. Minor, but significant, effects of sleep deprivation were seen in the power density distribution of the second recovery night. In the baseline nights, a progressive reduction of power density in the delta/theta range was present for successive non-REM-REM sleep cycles for total sleep time and stages 2, 3 and 4, and 4. The results show that effects of sleep deprivation as well as trends within the sleep periods are readily apparent from spectral analysis, but are inadequately reflected by conventional sleep scoring. When the power density values were integrated over the entire frequency range (0.75–25 Hz) for each non-REM-REM sleep cycle, an exponential decline from cycle 1 to cycle 3 was suggested. The present findings support the hypothesis that the EEG power density in the low frequency range is an indicator of a progressively declining process during sleep whose initial value is determined by the duration of prior waking.