Level of arousal and the ability to maintain wakefulness

The ability to maintain wakefulness under baseline and sleep deprivation conditions was examined in a group of 14 normal young adults. Subjects participated in both standard and manipulation Maintenance of Wakefulness tests after being awake for 7, 19, and 31 h. In the manipulation Maintenance of Wakefulness tests, subjects performed varying degrees of physical activity at the onset of stage 1 to allow them to preserve wakefulness. As expected, ability to maintain wakefulness declined as time awake increased. With amount of time awake held constant, wakefulness was enhanced most after standing and doing knee bends, less after standing, less after sitting up, and least after subjects were spoken to. The improvement in alertness after doing knee bends as compared to being spoken to was of the same relative magnitude as the decrease in alertness after one night of total sleep deprivation. As expected, heart rate also increased consistently as activity increased. Each subject had a negative correlation between their EEG sleep latencies and their minimum r-r interval during the manipulation, i.e. the higher the heart rate, the longer the latency. These data were interpreted as a demonstration of the impact of discrete phasic arousal on the ability to maintain wakefulness.     

Residual,differential neurobehavioral deficits linger after multiple recovery nights following chronic sleep restriction or acute total sleep deprivation

Study ObjectivesThe amount of recovery sleep needed to fully restore well-established neurobehavioral deficits from sleep loss remains unknown, as does whether the recovery pattern differs across measures after total sleep deprivation (TSD) and chronic sleep restriction (SR).MethodsIn total, 83 adults received two baseline nights (10–12-hour time in bed [TIB]) followed by five 4-hour TIB SR nights or 36-hour TSD and four recovery nights (R1–R4; 12-hour TIB). Neurobehavioral tests were completed every 2 hours during wakefulness and a Maintenance of Wakefulness Test measured physiological sleepiness. Polysomnography was collected on B2, R1, and R4 nights.ResultsTSD and SR produced significant deficits in cognitive performance, increases in self-reported sleepiness and fatigue, decreases in vigor, and increases in physiological sleepiness. Neurobehavioral recovery from SR occurred after R1 and was maintained for all measures except Psychomotor Vigilance Test (PVT) lapses and response speed, which failed to completely recover. Neurobehavioral recovery from TSD occurred after R1 and was maintained for all cognitive and self-reported measures, except for vigor. After TSD and SR, R1 recovery sleep was longer and of higher efficiency and better quality than R4 recovery sleep.ConclusionsPVT impairments from SR failed to reverse completely; by contrast, vigor did not recover after TSD; all other deficits were reversed after sleep loss. These results suggest that TSD and SR induce sustained, differential biological, physiological, and/or neural changes, which remarkably are not reversed with chronic, long-duration recovery sleep. Our findings have critical implications for the population at large and for military and health professionals.     

Sleepiness and its relation to the length, content, and continuity of sleep

SUMMARY  This review of experimental studies focuses on the disturbances of sleep that may occur in connection with irregular work hours and their relation to ensuing alertness. Three aspects of sleep are covered: the duration of sleep, the stages of sleep, and the continuity of sleep. A sleep curtailment as small as 2 h has clear negative effects on alertness. Sleep disturbed as frequently as every minute clearly affects alertness, but such procedures also affect the stages of sleep and decrease total sleep time. However, fragmentation rates of one per 10 minutes also induce sleepiness without affecting sleep content or duration. There is no clear evidence for slow-wave sleep (SWS) being more important than other stages, but designs may not have been sensitive enough. In connection with fragmentation studies it is suggested, however, that the effects are stronger if more SWS is lost. In summary, the review suggests that the relatively mild disturbances of sleep in shift work may contribute to reduced alertness although there are probably other, more potent, factors.     

Beta EEG reflects sensory processing in active wakefulness and homeostatic sleep drive in quiet wakefulness

Markers of sleep drive (<10 Hz; slow‐wave activity and theta) have been identified in the course of slow‐wave sleep and wakefulness. So far, higher frequencies in the waking electroencephalogram have not been examined thoroughly as a function of sleep drive. Here, electroencephalogram dynamics were measured in epochs of active wake (wake characterized by high muscle tone) or quiet wake (wake characterized by low muscle tone). It was hypothesized that the higher beta oscillations (15–35 Hz, measured by local field potential and electroencephalography) represent fundamentally different processes in active wake and quiet wake. In active wake, sensory stimulation elevated beta activity in parallel with gamma (80–90 Hz) activity, indicative of cognitive processing. In quiet wake, beta activity paralleled slow‐wave activity (1–4 Hz) and theta (5–8 Hz) in tracking sleep need. Cerebral lactate concentration, a measure of cerebral glucose utilization, increased during active wake whereas it declined during quiet wake. Mathematical modelling of state‐dependent dynamics of cortical lactate concentration was more precisely predictive when quiet wake and active wake were included as two distinct substates rather than a uniform state of wakefulness. The extent to which lactate concentration declined in quiet wake and increased in active wake was proportionate to the amount of beta activity. These data distinguish quiet wake from active wake. Quiet wake, particularly when characterized by beta activity, is permissive to metabolic and electrophysiological changes that occur in slow‐wave sleep. These data urge further studies on state‐dependent beta oscillations across species.     

Modafinil, d-amphetamine and placebo during 64 hours of sustained mental work. II. Effects on two nights of recovery sleep

Polysomnograms were obtained from 37 volunteers, before (baseline) and after (two consecutive recovery nights) a 64-h sleep deprivation, with (d-amphetamine or modafinil) or without (placebo) alerting substances. The drugs were administered at 23.00 hours during the first sleep deprivation night (after 17.5 h of wakefulness), to determine whether decrements in cognitive performance would be prevented; at 05.30 hours during the second night of sleep deprivation (after 47.5 h of wakefulness), to see whether performance would be restored; and at 15.30 hours during the third day of continuous work, to study effects on recovery sleep. The second recovery night served to verify whether drug-induced sleep disturbances on the first recovery night would carry over to a second night of sleep. Recovery sleep for the placebo group was as expected: the debt in slow-wave sleep (SWS) and REM sleep was paid back during the first recovery night, the rebound in SWS occurring mainly during the first half of the night, and that of REM sleep being distributed evenly across REM sleep episodes. Recovery sleep for the amphetamine group was also consistent with previously published work: increased sleep latency and intrasleep wakefulness, decreased total sleep time and sleep efficiency, alterations in stage shifts, Stage 1, Stage 2 and SWS, and decreased REM sleep with a longer REM sleep latency. For this group, REM sleep rebound was observed only during the second recovery night. Results for the modafinil group exhibited decreased time in bed and sleep period time, suggesting a reduced requirement for recovery sleep than for the other two groups. This group showed fewer disturbances during the first recovery night than the amphetamine group. In particular, there was no REM sleep deficit, with longer REM sleep episodes and a shorter REM latency, and the REM sleep rebound was limited to the first REM sleep episode. The difference with the amphetamine group was also marked by less NREM sleep and Stage 2 and more SWS episodes. No REM sleep rebound occurred during the second recovery night, which barely differed from placebo. Hence, modafinil allowed for sleep to occur, displayed sleep patterns close to that of the placebo group, and decreased the need for a long recovery sleep usually taken to compensate for the lost sleep due to total sleep deprivation.     

Absence of penile erections during paradoxical sleep. Peculiar penile events during wakefulness and slow wave sleep in the armadillo

The electroencephalogram (EEG) together with electromyogram (EMG) of the ischiocavernosus, bulbocavernosus and levator penis muscles were chronically monitored across behavioral states of the armadillo Chaetophractus villosus. This animal has a very long penis, which exhibits remarkable phenomena during wakefulness (W), slow wave sleep (SWS) and paradoxical sleep (PS). During W it remains retracted within a skin receptacle. During SWS penile protrusion can be observed together with very complex movements. Protrusion is a non erectile event during which the penis remains out of its receptacle but without rigidity. Penile erections are observed only during SWS. Contrasting with other mammals, no erections occur during PS. During this phase the penile muscles share the atonia of the body musculature characteristic of that phase. Some reflections on mechanisms of those penile events are presented.     

Effects of ipsapirone, a 5-HT1A agonist, on sleep/wakefulness cycles: probable post-synaptic action

The effects of ipsapirone, a ligand of the 5-HT1A receptors and a new potential anxiolytic, on sleep/wakefulness regulation were examined in the rat. Injected i.p. at 1, 3 and 5 mg kg-1, this compound induced a dose-dependent reduction of paradoxical sleep for 2 to 4 hours, followed, at a dose of 5 mg kg-1, by a secondary rebound. The other states of vigilance were not modified, except at the latter dose where the amounts of wakefulness were enhanced initially and decreased secondarily, while those of SWS were enhanced from 2 to 4 hours post-treatment. The effects of ipsapirone (3 mg kg-1) persisted after infusion of the neurotoxin 5,7-dihydroxytryptamine into the dorsal raphe nucleus which induced the sub-total destruction of the serotoninergic system. Thus, the action of the 5-HT1A agonist ipsapirone on sleep/wakefulness cycles probably involves the stimulation of the post-synaptic 5-HT1A receptors.     

Effects of amphetamine and modafinil on the sleep/wake cycle during experimental hypersomnia induced by sleep deprivation in the cat

Modafinil is a newly discovered waking substance now being used in the treatment of hypersomnia and narcolepsy. We have shown previously in the cat that, unlike amphetamine, modafinil induces long-lasting wakefulness (W) without behavioral excitation and subsequent sleep rebound, and that its waking effect does not depend on endogenous catecholamines. To further characterize the awakening properties of modafinil and current psychostimulants in experimental models of hypersomnia, we examined the effect of oral administration of placebo, modafinil (5 mg kg-1) or amphetamine (1 mg kg-1) on the sleep/wake cycle and power spectral density (PSD) in cats after an 18-h water-tank sleep deprivation period. We found that the placebo had no effect on the dynamics of sleep recovery, while both modafinil and amphetamine induced suppression of cortical slow activity and a waking state lasting 6-8 h. After the amphetamine-induced waking period, both deep slow wave sleep (SWS2) and paradoxical sleep (PS) occurred in greater amounts than after placebo and the PSD during SWS was also increased. Thus, the cumulative time spent in W during a 48-h period was similar to that with placebo, indicating enhanced sleep rebound. In contrast, after the modafinil-induced W, the occurrence and evolution of SWS2 or PS, as well as the PSD during SWS, were similar to those seen with placebo during the same period, so that the total time spent in W in a 48-h period remained significantly higher than the control level, indicating no additional sleep rebound. These results indicate that modafinil is effective against somnolence and hypersomnia and does not produce a subsequent increase in sleep and suggest that the pharmacological profile of modafinil is different from that of amphetamine.     

Slow-wave sleep deprivation and waking function

SUMMARY  Slow-wave sleep (SWS) has been theorized to be an intense form of nonREM sleep, but selective deprivation of SWS or Stage 4 sleep has not been shown to cause greater decrements in alertness or performance, compared to deprivation or disruption of the other stages of sleep. The present experiment examined the effects of marked SWS deprivation (SD) for two nights, a control sleep disruption (CD) condition in which minutes of SWS were preserved, and a no sleep disruption (ND) condition. Daytime sleepiness was assessed with the multiple sleep latency test (MSLT) and performance was evaluated with the simulated assembly line task (SALT), neither of which was used in previous studies of SWS or Stage 4 sleep deprivation. In agreement with prior studies, two nights of SD did not cause greater daytime sleepiness than did CD, although sleepiness in both conditions was increased compared to the ND condition. In addition, neither SD nor CD caused declines in performance or mood. However, post hoc analysis suggests an interaction between SWS and sleep duration, such that sufficient SWS may tend to prevent adverse effects of mild sleep loss on waking function.     

Electrodermal lability as an indicator for subjective sleepiness during total sleep deprivation

The present study addresses the suitability of electrodermal lability as an indicator of individual vulnerability to the effects of total sleep deprivation. During two complete circadian cycles, the effects of 48h of total sleep deprivation on physiological measures (electrodermal activity and body temperature), subjective sleepiness (measured by visual analogue scale and tiredness symptom scale) and task performance (reaction time and errors in a go/no go task) were investigated. Analyses of variance with repeated measures revealed substantial decreases of the number of skin conductance responses, body temperature, and increases for subjective sleepiness, reaction time and error rates. For all changes, strong circadian oscillations could be observed as well. The electrodermal more labile subgroup reported higher subjective sleepiness compared with electrodermal more stable participants, but showed no differences in the time courses of body temperature and task performance. Therefore, electrodermal lability seems to be a specific indicator for the changes in subjective sleepiness due to total sleep deprivation and circadian oscillations, but not a suitable indicator for vulnerability to the effects of sleep deprivation per se.     

Reaction of sleepiness indicators to partial sleep deprivation,time of day and time on task in a driving simulator – the DROWSI project

Studies of driving and sleepiness indicators have mainly focused on prior sleep reduction. The present study sought to identify sleepiness indicators responsive to several potential regulators of sleepiness: sleep loss, time of day (TOD) and time on task (TOT) during simulator driving. Thirteen subjects drove a high‐fidelity moving base simulator in six 1‐h sessions across a 24‐h period, after normal sleep duration (8 h) and after partial sleep deprivation (PSD; 4 h). The results showed clear main effects of TOD (night) and TOT but not for PSD, although the latter strongly interacted with TOD. The most sensitive variable was subjective sleepiness, the standard deviation of lateral position (SDLAT) and measures of eye closure [duration, speed (slow), amplitude (low)]. Measures of electroencephalography and line crossings (LCs) showed only modest responses. For most variables individual differences vastly exceeded those of the fixed effects, except for subjective sleepiness and SDLAT. In a multiple regression analysis, SDLAT, amplitude/peak eye‐lid closing velocity and blink duration predicted subjective sleepiness bouts with a sensitivity and specificity of about 70%, but were mutually redundant. The prediction of LCs gave considerably weaker, but similar results. In summary, SDLAT and eye closure variables could be candidates for use in sleepiness‐monitoring devices. However, individual differences are considerable and there is need for research on how to identify and predict individual differences in susceptibility to sleepiness.     

Strong rebound of wakefulness follows prostaglandin D2- or adenosine A2a receptor agonist-induced sleep

We studied the effect of sleep excess on the sleep-wakefulness pattern of rats. Subarachnoid infusion of prostaglandin D2 or the adenosine A2a receptor agonist CGS21680 effectively induced slow wave sleep (SWS) for the first 12 h of the night-time period, whereas they did not induce sleep during the following 24 h of infusion. An increase in the amount of wakefulness was seen during the last 12 h of prostaglandin D2 infusion. The amounts of wakefulness strongly increased during the following 36-h recovery period. Rebound wakefulness was extraordinarily strong after the cessation of CGS21680 infusion, reaching almost complete insomnia during the night-time. Treatment of animals with prostaglandin D2 overnight, following by treatment with CGS21680 on the next night, resulted in the strongest induction of wakefulness rebound. During the rebound period, the amount of wakefulness reached up to 50 min per hour in the daytime. Rebound of wakefulness depended on the amounts of preceding SWS induced by infusion of prostaglandin D2 for 6 or 12 h and of CGS21680 for 12 h. The larger the amount of SWS, the larger the amount of the following rebound of wakefulness. Rebounds of wakefulness occurred as a result of decrease in SWS amounts, whereas paradoxical sleep amounts did not change. Desensitization of adenosine A2a receptors and accumulation of prostaglandin E2 may be involved in the production of strong wakefulness rebound following relatively long treatments (more than 12 h) with prostaglandin D2 or CGS21680.     

Effect of dopaminergic substances on sleep/wakefulness in saline- and MPTP-treated mice

Sleep/wakefulness (S/W) disorders are frequent in Parkinson's disease (PD). The underlying causes have yet to be elucidated but dopaminergic neurodegenerative lesions seem to contribute to appearance of the disorders and anti-Parkinsonian medication is known to accentuate S/W problems. Hence, we reasoned that studying the acute effect of dopaminergic compounds on S/W in an animal model of PD might improve our knowledge of S/W regulation in the context of partial dopaminergic depletion. To this end, we tested the effect of levodopa (l-dopa), pergolide (a mixed D(2)/D(1) agonist) and lisuride (a D(2) agonist) on S/W recordings in MPTP-treated mice, in comparison with controls. Our results showed that dopaminergic compounds modify S/W amounts in both control and MPTP mice. Wakefulness amounts are greater in MPTP mice after l-dopa (50 mg kg(-1)) and lisuride (1 mg kg(-1)) injections compared with control mice. Moreover, the paradoxical sleep latency was significantly longer in MPTP mice after high-dose l-dopa administration. Our observations suggest that the actions of both l-dopa and lisuride on S/W differ slightly in MPTP mice relative to controls. Hence, MPTP-induced partial DA depletion may modulate the effect of dopaminergic compounds on S/W regulation.     

Sleep tendency during extended wakefulness: insights into adolescent sleep regulation and behavior

Sleep tendency (latency to sleep onset) was examined during extended waking in prepubertal and mature adolescents to determine whether sleep pressure is lower near bedtime in the latter group. Participants were nine prepubertal (pubertal stage Tanner 1, mean age 11.1 years, SD+/-1.3 years, five males) and 11 pubertally mature adolescents (Tanner 5, 13.9+/-1.2 years, three males). They spent 10 nights at home on an identical fixed 10-h sleep schedule followed by a 36-h constant routine with sleep latency tests at 2-h intervals using standard polysomnography. Saliva was collected to assess dim-light melatonin onset (DLMO) phase. DLMO was earlier in the Tanner 1 (mean clock time=20:33 hours, SD=49 min) than Tanner 5 group (21:29 hours+/-42 min). Sleep latency compared at a 'critical period' spanning 12.5 (20:30 hours clock time) to 18.5 h (02:30 hours) after waking did not differ at 20:30 hours, but was shorter for the Tanner 1 group at 22:30 hours (Tanner 1=9.2+/-6.3 min; Tanner 5=15.7+/-5.8 min), 00:30 hours (Tanner 1=3.6+/-1.7 min; Tanner 5=9.0+/-6.4 min), and 02:30 hours (Tanner 1=2.0+/-1.7 min; Tanner 5=4.3+/-3.2 min; trend). These differences were apparent controlling for circadian phase by partial correlation. Sleep tendency after 14.5, 16.5, and 18.5 h awake was lower in mature versus prepubertal adolescents, supporting our hypothesis that a developmental change of intrinsic sleep-wake regulation may provide physiologically mediated 'permission' for later bedtimes in older adolescents.     

Dose-dependent effects of the 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness in the rat

SUMMARY  Sleep and wakefulness were studied in rats following administration of a selective 5-HT_1A agonist (8-OH-DPAT), a non-selective 5-HT_1A antagonist [(-) pindolol] and a combination of 8-OH-DPAT and (—) pindolol.
8-OH-DPAT (1.0–4.0 μg) injected into the dorsal raphe nucleus increased slow-wave sleep and decreased wakefulness. Administration of the 5-HT_1A agonist by subcutaneous route induced biphasic effects such that low doses (0.010 mg kg^-1) decreased wakefulness and increased slow-wave sleep while higher doses (0.375 mg kg^-1) induced opposite effects. REM sleep was suppressed and REM latency was increased, what could be tentatively ascribed to a non-specific effect (hypothermia). (-) Pindolol (1.0–4.0 mg kg^-1) induced an initial increase of wakefulness and a decrease of NREM sleep and REM sleep. Thereafter, NREM sleep showed a marked increase while REM sleep remained depressed. Pretreat-ment with (—) pindolol reversed the effects of both small and large doses of 8-OH-DPAT on slow-wave sleep and wakefulness.
The opposite effects, observed on the waking EEG after activation of either serotonin autoreceptors or postsynaptic 5-HT_1A receptors with adequate doses of 8-OH-DPAT, tend to indicate an active role for the 5-HT_1A receptor in the control of the waking state.     

On the ability to self-monitor cognitive performance during sleep deprivation: a calibration study

SUMMARY  The antagonistic effects of extensive sleep deprivation (SD) on human cognitive performance are well documented. However, one aspect of human performance that has not been investigated with respect to its susceptibility to SD is the 'metacognitive' ability to self-monitor overt performance. In the present study, 16 male subjects participated in an experiment requiring sustained cognitive work during a three day period. One of the cognitive tasks required the mental addition of rapidly presented numbers. On each trial, subjects reported the sum and then provided a subjective confidence rating to indicate the degree of certainty in their response. As expected, performance on the sequential addition task deteriorated with increasing fatigue and returned to baseline following a recovery sleep. However, calibration analyses, which quantify a number of properties of the relationship between subjective and overt performance, revealed that the correlation between confidence and performance (calibration), the ability to differentiate correct from incorrect judgments (resolution), and validity of subjective 'certainty', were all unaffected by SD. Hence, in the absence of external feedback from the environment, people have access to fairly reliable internal feedback about their performance during periods of sustained and vigilant cognitive activity.     

Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the epworth sleepiness scale: failure of the MSLT as a gold standard

Excessive daytime sleepiness (EDS) is an important symptom that needs to be quantified, but there is confusion over the best way to do this. Three of the most commonly used tests: the multiple sleep latency test (MSLT), the maintenance of wakefulness test (MWT) and the Epworth sleepiness scale (ESS) give results that are significantly correlated in a statistical sense, but are not closely related. The purpose of this investigation was to help clarify this problem. Previously published data from several investigations were used to calculate the reference range of normal values for each test, defined by the mean+/-2 SD or by the 2.5 and 97.5 percentiles. The 'rule of thumb' that many people rely on to interpret MSLT results is shown here to be misleading. Previously published results from each test were also available for narcoleptic patients who were drug-free at the time and who by definition had EDS. This enabled the sensitivity and specificity of the three tests to be compared for the first time, in their ability to distinguish the EDS of narcolepsy from the daytime sleepiness of normal subjects. The receiver operator characteristic curves clearly showed that the ESS is the most discriminating test, the MWT is next best and the MSLT the least discriminating test of daytime sleepiness. The MSLT can no longer be considered the gold standard for such tests.     

Electrodermal activity during total sleep deprivation and its relationship with other activation and performance measures

The present study analyses the variations of the skin resistance level (SRL) during 48 h of total sleep deprivation (TSD) and its relationship to body temperature, self-informed sleepiness in the Stanford Sleepiness Scale (SSS), and reaction time (RT). All of the variables were evaluated every 2 h except for the SSS, which was evaluated every hour. A total of 30 healthy subjects (15 men and 15 women) from 18 to 24 years old participated in the experiment. Analyses of variance (ANOVAs) with TSD days and time-of-day as factors showed a substantial increase of SRL, SSS, and RT, and a decrease in body temperature marked by strong circadian oscillations. The interaction between day by time-of-day was only significant for RT. Furthermore, Pearson's correlations showed that the increase of SRL is associated to the decrease in temperature (mean r=-0.511), the increase of SSS (mean r=0.509), and the deterioration of RT (mean r=0.425). The results support previous TSD reports and demonstrate the sensitivity of SRL to TSD. The non-invasive character of SRL, its simplicity, and its relationships with other activation parameters, widely validated by previous literature, convert SRL into an interesting and useful measure in this field.     

The effect of sleep loss on next day effort

The study had two primary objectives. The first was to determine whether sleep loss results in a preference for tasks demanding minimal effort. The second was to evaluate the quality of performance when participants, under conditions of sleep loss, have control over task demands. In experiment 1, using a repeated-measures design, 50 undergraduate college students were evaluated, following one night of no sleep loss and one night of sleep loss. The Math Effort Task (MET) presented addition problems via computer. Participants were able to select additions at one of five levels of difficulty. Less-demanding problems were selected and more additions were solved correctly when the participants were subject to sleep loss. In experiment 2, 58 undergraduate college students were randomly assigned to a no sleep deprivation or a sleep deprivation condition. Sleep-deprived participants selected less-demanding problems on the MET. Percentage correct on the MET was equivalent for both the non-sleep-deprived and sleep-deprived groups. On a task selection question, the sleep-deprived participants also selected significantly less-demanding non-academic tasks. Increased sleepiness, fatigue, and reaction time were associated with the selection of less difficult tasks. Both groups of participants reported equivalent effort expenditures; sleep-deprived participants did not perceive a reduction in effort. These studies demonstrate that sleep loss results in the choice of low-effort behavior that helps maintain accurate responding.