Effects of dextroamphetamine, caffeine and modafinil on psychomotor vigilance test performance after 44 h of continuous wakefulness

Prolonged sleep loss impairs alertness, vigilance and some higher-order cognitive and affective capacities. Some deficits can be temporarily reversed by stimulant medications including caffeine, dextroamphetamine, and modafinil. To date, only one study has directly compared the effectiveness of these three compounds and specified the doses at which all were equally effective in restoring alertness and vigilance following 64 h of wakefulness. The present study compared the effectiveness of these same three stimulants/doses following a less extreme period of sleep loss (i.e., 44 h). Fifty-three healthy adults received a single dose of modafinil 400 mg ( n  =   11), dextroamphetamine 20 mg ( n  =   16), caffeine 600 mg ( n  =   12), or placebo ( n  =   14) after 44 h of continuous wakefulness. After 61 h of being awake, participants obtained 12 h of recovery sleep. Psychomotor vigilance was assessed bi-hourly during waking and following recovery sleep. Relative to placebo, all three stimulants were equally effective in restoring psychomotor vigilance test speed and reducing lapses, although the duration of action was shortest for caffeine and longest for dextroamphetamine. At these doses, caffeine was associated with the highest percentage of subjectively reported side-effects while modafinil did not differ significantly from placebo. Subsequent recovery sleep was adversely affected in the dextroamphetamine group, but none of the stimulants had deleterious effects on postrecovery performance. Decisions regarding stimulant selection should be made with consideration of how factors such as duration of action, potential side-effects, and subsequent disruption of recovery sleep may interact with the demands of a particular operational environment.     

Effects of two nights sleep deprivation and two nights recovery sleep on response inhibition

This study examined the effects of two nights of total sleep deprivation (TSD) and two nights of recovery sleep on response inhibition. Thirty-eight young, healthy adults performed a Go-NoGo task at 14 : 00 after: (1) a normal night of sleep; (2) each of two consecutive nights of TSD; and (3) each of two consecutive nights of recovery sleep; they also performed the task at 05 : 00 during the first night of sleep deprivation. We hypothesized that TSD would lead to an impaired ability to withhold a response that would be reversed with recovery sleep. Subjects did experience a significant increase in false positive responses throughout all of TSD, errors of omission (i.e. missed 'go' targets) were not significant until after the second night of TSD. Both components (withholding a response and automatic responding) of the task returned to baseline levels after one night of recovery sleep. These data suggest that individuals experience difficulty in withholding an inappropriate response during TSD, even when they are able to attend to the incoming stimuli and respond accurately to appropriate stimuli.     

Age, performance and sleep deprivation

Young subjects are frequently involved in sleep-related accidents. They could be more affected than older drivers by sleep loss and therefore worsen their driving skills quicker, or have a different perception of their level of impairment. To test these hypotheses we studied variations of reaction time (RT), a fundamental prerequisite for safe performing, as measured by lapses, i.e. responses > or = 500 ms and self-assessment of performance and sleepiness after a night awake and after a night asleep in a balanced crossover design in young versus older healthy subjects. Ten young (20-25 years old) and 10 older volunteers (52-63 years old) were tested with and without 24 h of sleep deprivation. Without sleep deprivation, RTs were slower in older subjects than in the younger ones. However, after sleep deprivation, the RTs of young subjects increased while that of the older subjects remained almost unaffected. Sleepiness and self-perception of performance were equally affected in both age groups showing different perception of performance in the age groups. Our findings are discussed in terms of vulnerability to sleep-related accidents.     

Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study

Daytime performance changes were examined during chronic sleep restriction or augmentation and following subsequent recovery sleep. Sixty-six normal volunteers spent either 3 (n = 18), 5 (n= 16), 7 (n = 16), or 9 h (n = 16) daily time in bed (TIB) for 7 days (restriction/augmentation) followed by 3 days with 8 h daily TIB (recovery). In the 3-h group, speed (mean and fastest 10% of responses) on the psychomotor vigilance task (PVT) declined, and PVT lapses (reaction times greater than 500 ms) increased steadily across the 7 days of sleep restriction. In the 7- and 5-h groups speed initially declined, then appeared to stabilize at a reduced level; lapses were increased only in the 5-h group. In the 9-h group, speed and lapses remained at baseline levels. During recovery, PVT speed in the 7- and 5-h groups (and lapses in the 5-h group) remained at the stable, but reduced levels seen during the last days of the experimental phase, with no evidence of recovery. Speed and lapses in the 3-h group recovered rapidly following the first night of recovery sleep; however, recovery was incomplete with speed and lapses stabilizing at a level comparable with the 7- and 5-h groups. Performance in the 9-h group remained at baseline levels during the recovery phase. These results suggest that the brain adapts to chronic sleep restriction. In mild to moderate sleep restriction this adaptation is sufficient to stabilize performance, although at a reduced level. These adaptive changes are hypothesized to restrict brain operational capacity and to persist for several days after normal sleep duration is restored, delaying recovery.     

Immediate error correction process following sleep deprivation

Previous studies have suggested that one night of sleep deprivation decreases frontal lobe metabolic activity, particularly in the anterior cingulated cortex (ACC), resulting in decreased performance in various executive function tasks. This study thus attempted to address whether sleep deprivation impaired the executive function of error detection and error correction. Sixteen young healthy college students (seven women, nine men, with ages ranging from 18 to 23 years) participated in this study. Participants performed a modified letter flanker task and were instructed to make immediate error corrections on detecting performance errors. Event-related potentials (ERPs) during the flanker task were obtained using a within-subject, repeated-measure design. The error negativity or error-related negativity (Ne/ERN) and the error positivity (Pe) seen immediately after errors were analyzed. The results show that the amplitude of the Ne/ERN was reduced significantly following sleep deprivation. Reduction also occurred for error trials with subsequent correction, indicating that sleep deprivation influenced error correction ability. This study further demonstrated that the impairment in immediate error correction following sleep deprivation was confined to specific stimulus types, with both Ne/ERN and behavioral correction rates being reduced only for trials in which flanker stimuli were incongruent with the target stimulus, while the response to the target was compatible with that of the flanker stimuli following sleep deprivation. The results thus warrant future systematic investigation of the interaction between stimulus type and error correction following sleep deprivation.     

Odor identification accuracy declines following 24 h of sleep deprivation

Brain imaging studies demonstrate that sleep deprivation reduces glucose metabolism and blood flow in the prefrontal cortex, and such reductions are associated with impairments in cognitive functioning. Although some of the greatest metabolic declines occur within the orbitofrontal cortex, little is known about the effects of sleep loss on the types of processes mediated by this region, including emotion, motivation, feeding, and olfaction. The present study tested odor identification accuracy when individuals were well rested and again following 24 h of wakefulness. Relative to rested baseline performance, sleep-deprived individuals demonstrated a significant decline in the ability to identify specific odors on the Smell Identification Test. This decrement in olfactory functioning occurred concomitantly with slowed psychomotor speed and increased ratings of self-reported sleepiness. Performance on a task that required complex mental set shifting did not change significantly following sleep deprivation, suggesting that the decrements in odor identification could not be attributed to task difficulty. Finally, while there was no relationship between subjective sleepiness and odor identification at rested baseline, greater subjective sleepiness was associated with better odor identification ability following 24 h of sleep loss. Possible implications of these findings are discussed.     

The dynamics of neurobehavioural recovery following sleep loss

Rate of recovery of daytime performance and sleepiness following moderate and severe sleep deprivation (SD) was examined when recovery opportunity was either augmented or restricted. Thirty healthy non-smokers, aged 18-33 years, participated in one of three conditions: moderate SD with augmented (9-h) recovery opportunities, moderate SD with restricted (6-h) recovery opportunities, or severe SD with augmented recovery opportunities. Each participant attended the laboratory for 8-9 consecutive nights: an adaptation and baseline night (23:00-08:00 hours), one or two night(s) of wakefulness, and five consecutive recovery sleep opportunities (23:00-08:00 hours or 02:00-08:00 hours). On each experimental day, psychomotor vigilance performance (PVT) and subjective sleepiness (SSS) were assessed at two-hourly intervals, and MSLTs were performed at 1000 h. PSG data was collected for each sleep period. For all groups, PVT performance significantly deteriorated during the period of wakefulness, and sleepiness significantly increased. Significant differences were observed between the groups during the recovery phase. Following moderate SD, response speed, lapses and SSS returned to baseline after one 9-h sleep opportunity, while sleep latencies required two 9-h opportunities. When the recovery opportunity was restricted to six hours, neither PVT performance nor sleepiness recovered, but stabilised at below-baseline levels. Following severe SD, sleepiness recovered after one (SSS) or two (physiological) 9-h sleep opportunities, however PVT performance remained significantly below baseline for the entire recovery period. These results suggest that the mechanisms underlying the recovery process may be more complicated than previously thought, and that we may have underestimated the impact of sleep loss and/or the restorative value of subsequent sleep.     

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.     

The pendulum technique for paradoxical sleep deprivation in rats

A new technique for paradoxical sleep (PS) deprivation in rats is presented. Animals are prevented from entering into PS by allowing them to sleep for only brief periods of time. This is accomplished by an apparatus which moves the animals' cages backwards and forwards like a pendulum. At the extremes of the motion postural imbalance is produced in the animals forcing them to walk downwards to the other side of their cages. A minimal amount of PS and a moderate amount of slow wave sleep (SWS) were detected during a deprivation period of 72 hrs. Following the deprivation treatment the recovery of sleep was monitored for 3 hrs; at the beginning of the light period for one group and at the beginning of the dark period for a second group. The sleep-waking patterns of two baseline groups were established at the time when the recovery sleep was examined in the deprivation groups. The deprivation treatment resulted in a significant increase in the amount of PS and a significant decrease in the amount of SWS. The extent of PS increase was similar in both deprivation groups, in spite of a large difference in the amount of SWS. The decrease of SWS mainly occurred during recovery sleep in the light. It was observed that sleep in the dark differs from sleep in the light in behavioural aspects.     

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.     

Pattern of desynchronized sleep during deprivation and recovery induced in the rat by changes in ambient temperature

The pattern of desynchronized sleep (DS) occurrence in the rat was studied during exposure to an ambient temperature (Ta) of 0 degrees C for 48 h and during a 12 h recovery period at laboratory Ta (23 degrees C) following the first and second 24 h of cold exposure. The exposure to low Ta induces a DS deprivation which is followed, during recovery, by a clear DS rebound. Both the decrease and the following increase in the amount of DS are due to changes in the frequency rather than in the duration of DS episodes. The frequency distribution of the intervals between the end of one DS episode and the beginning of the next (DS interval) has shown that two populations of DS intervals exist, i.e. short DS intervals (3 min). On the basis of this, two types of DS episodes have been identified: the 'single DS episode', which is both preceded and followed by a long DS interval, and the 'sequential DS episode', which is a DS episode occurring within a cluster or a sequence of DS episodes and is characteristically separated by short DS intervals. The occurrence of such sequential DS episodes in a 'DS cluster', allows a high amount of DS to occur without increasing the duration of the DS episode. DS clusters are repressed during cold exposure, when the DS drive is counteracted by the need to thermoregulate, and enhanced during recovery, when the DS drive is unrestrained. In contrast, the occurrence of single DS episodes is much less affected by such different experimental conditions.     

Relationships between affect, vigilance, and sleepiness following sleep deprivation

This pilot study examined the relationships between the effects of sleep deprivation on subjective and objective measures of sleepiness and affect, and psychomotor vigilance performance. Following an adaptation night in the laboratory, healthy young adults were randomly assigned to either a night of total sleep deprivation (SD group; n = 15) or to a night of normal sleep (non-SD group; n = 14) under controlled laboratory conditions. The following day, subjective reports of mood and sleepiness, objective sleepiness (Multiple Sleep Latency Test and spontaneous oscillations in pupil diameter, PUI), affective reactivity/regulation (pupil dilation responses to emotional pictures), and psychomotor vigilance performance (PVT) were measured. Sleep deprivation had a significant impact on all three domains (affect, sleepiness, and vigilance), with significant group differences for eight of the nine outcome measures. Exploratory factor analyses performed across the entire sample and within the SD group alone revealed that the outcomes clustered on three orthogonal dimensions reflecting the method of measurement: physiological measures of sleepiness and affective reactivity/regulation, subjective measures of sleepiness and mood, and vigilance performance. Sleepiness and affective responses to sleep deprivation were associated (although separately for objective and subjective measures). PVT performance was also independent of the sleepiness and affect outcomes. These findings suggest that objective and subjective measures represent distinct entities that should not be assumed to be equivalent. By including affective outcomes in experimental sleep deprivation research, the impact of sleep loss on affective function and their relationship to other neurobehavioral domains can be assessed.     

Unihemispheric sleep deprivation in bottlenose dolphins

SUMMARY  Unihemispheric and bihemispheric sleep deprivation were performed in bottlenose dolphins. One brain hemisphere was capable of being deprived of delta (0.5-3.0 Hz) sleep in the former condition. Here, an increase in sleep pressure was observed during sleep deprivation in the deprived hemisphere. In the recovery sleep, following unihemispheric sleep deprivation, there was a rebound of delta sleep only in the deprived hemisphere. Following bihemispheric sleep deprivation the animals exhibited an increase in delta sleep in both hemispheres.     

Impaired decision making following 49 h of sleep deprivation

Sleep deprivation reduces regional cerebral metabolism within the prefrontal cortex, the brain region most responsible for higher-order cognitive processes, including judgment and decision making. Accordingly, we hypothesized that two nights of sleep loss would impair decision making quality and lead to increased risk-taking behavior on the Iowa Gambling Task (IGT), which mimics real-world decision making under conditions of uncertainty. Thirty-four healthy participants completed the IGT at rested baseline and again following 49.5 h of sleep deprivation. At baseline, volunteers performed in a manner similar to that seen in most samples of healthy normal individuals, rapidly learning to avoid high-risk decks and selecting more frequently from advantageous low-risk decks as the game progressed. After sleep loss, however, volunteers showed a strikingly different pattern of performance. Relative to rested baseline, sleep-deprived individuals tended to choose more frequently from risky decks as the game progressed, a pattern similar to, though less severe than, previously published reports of patients with lesions to the ventromedial prefrontal cortex. Although risky decision making was not related to participant age when tested at rested baseline, age was negatively correlated with advantageous decision making on the IGT, when tested following sleep deprivation (i.e. older subjects made more risky choices). These findings suggest that cognitive functions known to be mediated by the ventromedial prefrontal cortex, including decision making under conditions of uncertainty, may be particularly vulnerable to sleep loss and that this vulnerability may become more pronounced with increased age.     

Effects of age on recovery of body weight following REM sleep deprivation of rats

Chronically enforced rapid eye (paradoxical) movement sleep deprivation (REM-SD) of rats leads to a host of pathologies, of which hyperphagia and loss of body weight are among the most readily observed. In recent years, the etiology of many REM-SD-associated pathologies have been elucidated, but one unexplored area is whether age affects outcomes. In this study, male Sprague-Dawley rats at 2, 6, and 12 months of age were REM sleep-deprived with the platform (flowerpot) method for 10-12 days. Two-month-old rats resided on 7-cm platforms, while 10-cm platforms were used for 6- and 12-month-old rats; rats on 15-cm platforms served as tank controls (TCs). Daily changes in food consumption (g/kg(0.67)) and body weight (g) during baseline, REM-SD or TCs, and post-experiment recovery in home cages were determined. Compared to TCs, REM-SD resulted in higher food intake and decreases in body weight. When returned to home cages, food intake rapidly declined to baseline levels. Of primary interest was that rates of body weight gain during recovery differed between the age groups. Two-month-old rats rapidly restored body weight to pre-REM-SD mass within 5 days; 6-month-old rats were extrapolated by linear regression to have taken about 10 days, and for 12-month-old rats, the estimate was about 35 days. The observation that restoration of body weight following its loss during REM-SD may be age-dependent is in general agreement with the literature on aging effects on how mammals respond to stress.     

Increased cerebral response during a divided attention task following sleep deprivation

We recently reported that the brain showed greater responsiveness to some cognitive demands following total sleep deprivation (TSD). Specifically, verbal learning led to increased cerebral activation following TSD while arithmetic resulted in decreased activation. Here we report data from a divided attention task that combined verbal learning and arithmetic. Thirteen normal control subjects performed the task while undergoing functional magnetic resonance imaging (FMRI) scans after a normal night of sleep and following 35 h TSD. Behaviourally, subjects showed only modest impairments following TSD. With respect to cerebral activation, the results showed (a) increased activation in the prefrontal cortex and parietal lobes, particularly in the right hemisphere, following TSD, (b) activation in left inferior frontal gyrus correlated with increased subjective sleepiness after TSD, and (c) activation in bilateral parietal lobes correlated with the extent of intact memory performance after TSD. Many of the brain regions showing a greater response after TSD compared with normal sleep are thought to be involved in control of attention. These data imply that the divided attention task required more attentional resources (specifically, performance monitoring and sustained attention) following TSD than after normal sleep. Other neuroimaging results may relate to the verbal learning and/or arithmetic demands of the task. This is the first study to examine divided attention performance after TSD with neuroimaging and supports our previous suggestion that the brain may be more plastic during cognitive performance following TSD than previously thought.     

Photically evoked potentials in the visual cortex following paradoxical sleep deprivation in rats

Immediately following 72 hr of paradoxical sleep (PS) deprivation, the P3-N3 amplitude of the photically evoked response in the visual cortex was measured in waking rats. PS deprivation was achieved instrumentally by one of three different techniques: the classical platform, the multiple platform, or the pendulum technique. For each of the techniques a control condition was run additionally. The PS deprivation effect consisted of a decrement in the P3-N3 amplitude, which was interpreted as indicating an increase in tonic arousal having a depressing influence on cortical excitability. Concomitantly, a relatively large technique effect occurred, in which the difference between the two platform techniques on the one hand, and the pendulum technique on the other, was most apparent. The same factors did not influence behavioural activity taking place during the presentation of photic stimulation, but did during the preceding 5 min adaptation period. Although the present findings are in contrast with previous reports in animals, they may not be inconsistent with the basic idea of the neural excitability hypothesis of PS.     

The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects

The aim of this study was to compare the effects of total sleep deprivation (TSD), rapid eye movement (REM) sleep and slow wave sleep (SWS) interruption and sleep recovery on mechanical and thermal pain sensitivity in healthy adults. Nine healthy male volunteers (age 26--43 years) were randomly assigned in this double blind and crossover study to undergo either REM sleep or SWS interruption. Periods of 6 consecutive laboratory nights separated by at least 2 weeks were designed as follows: N1 Adaptation night; N2 Baseline night; N3 Total sleep deprivation (40 h); N4 and N5 SWS or REM sleep interruption; N6 Recovery. Sleep was recorded and scored using standard methods. Tolerance thresholds to mechanical and thermal pain were assessed using an electronic pressure dolorimeter and a thermode operating on a Peltier principle. Relative to baseline levels, TSD decreased significantly mechanical pain thresholds (-8%). Both REM sleep and SWS interruption tended to decrease mechanical pain thresholds. Recovery sleep, after SWS interruption produced a significant increase in mechanical pain thresholds (+ 15%). Recovery sleep after REM sleep interruption did not significantly increase mechanical pain thresholds. No significant differences in thermal pain thresholds were detected between and within periods. In conclusion this experimental study in healthy adult volunteers has demonstrated an hyperalgesic effect related to 40 h TSD and an analgesic effect related to SWS recovery. The analgesic effect of SWS recovery is apparently greater than the analgesia induced by level I (World Health Organization) analgesic compounds in mechanical pain experiments in healthy volunteers.     

Inter- and intra-individual variability in performance near the circadian nadir during sleep deprivation

The study purpose was to assess inter- and intra-individual variability in neurobehavioral function near the circadian nadir during sleep deprivation and conduct exploratory factor analyses to assess relationships among alertness and performance measures during sleep deprivation. Twenty-five healthy individuals (16 females) aged 18-25 years participated. Participants were sleep deprived for two nights under controlled laboratory conditions using a modified constant routine procedure. A comprehensive battery of neurobehavioral performance tests, subjective sleepiness (SSS), and objective alertness (MWT) were assessed. Seventeen of the 22 neurobehavioral measures were impaired by sleep deprivation (all P < 0.01). The use of multiple neurobehavioral performance measures revealed impairments for all individuals during sleep deprivation. However, sleep deprivation effects were task dependent within and between individuals. Gender contributed minimally to inter-individual variability in performance. Exploratory factor analysis reduced the 22 measures to seven independent factors. Our findings indicate that no individual was especially vulnerable or resistant to the performance impairing effects of sleep deprivation. Instead, inter- and intra-individual variability in performance during sleep deprivation was task dependent. The finding that subjective sleepiness and objective alertness were not related to any performance measure during sleep deprivation suggests that these measures may assess independent brain functions.     

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.