Maria L. Thomas

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.

Neural basis of alertness and cognitive performance impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human regional brain activity.

The negative effects of sleep deprivation on alertness and cognitive performance suggest decreases in brain activity and function, primarily in the thalamus, a subcortical structure involved in alertness and attention, and in the prefrontal cortex, a region subserving alertness, attention, and higher‐order cognitive processes. To test this hypothesis, 17 normal subjects were scanned for quantifiable brain activity changes during 85 h of sleep deprivation using positron emission tomography (PET) and 18Fluorine‐2‐deoxyglucose (18FDG), a marker for regional cerebral metabolic rate for glucose (CMRglu) and neuronal synaptic activity. Subjects were scanned prior to and at 24‐h intervals during the sleep deprivation period, for a total of four scans per subject. During each 30 min 18FDG uptake, subjects performed a sleep deprivation‐sensitive Serial Addition/Subtraction task. Polysomnographic monitoring confirmed that subjects were awake. Twenty‐four hours of sleep deprivation, reported here, resulted in a significant decrease in global CMRglu, and significant decreases in absolute regional CMRglu in several cortical and subcortical structures. No areas of the brain evidenced a significant increase in absolute regional CMRglu. Significant decreases in relative regional CMRglu, reflecting regional brain reductions greater than the global decrease, occurred predominantly in the thalamus and prefrontal and posterior parietal cortices. Alertness and cognitive performance declined in association with these brain deactivations. This study provides evidence that short‐term sleep deprivation produces global decreases in brain activity, with larger reductions in activity in the distributed cortico‐thalamic network mediating attention and higher‐order cognitive processes, and is complementary to studies demonstrating deactivation of these cortical regions during NREM and REM sleep.

Caffeine reversal of sleep deprivation effects on alertness and mood

This study assessed the ability of high doses of caffeine to reverse changes in alertness and mood produced by prolonged sleep deprivation. Fifty healthy, nonsmoking males between the ages of 18 and 32 served as volunteers. Following 49 h without sleep, caffeine (0, 150, 300, or 600 mg/70 kg, PO) was administered in a double-blind fashion. Measures of alertness were obtained with sleep onset tests, the Stanford Sleepiness Scale (SSS), and Visual Analog Scales (VAS). Sleep deprivation decreased onset to sleep from a rested average of 19.9 min to 7 min. Following the highest dose of caffeine tested, sleep onset averaged just over 10 min; sleep onset for the placebo group averaged 5 min. Scores on the SSS increased from a rested mean of 1.6–4.8 after sleep deprivation. Caffeine reduced this score to near rested values. Caffeine reversed sleep deprivation-induced changes in three subscales of the POMS (vigor, fatigue, and confusion) and produced values close to fully rested conditions on several VAS. Serum caffeine concentrations peaked 90 min after ingestion and remained elevated for 12 h. This study showed that caffeine was able to produce significant alerting and long-lasting beneficial mood effects in individuals deprived of sleep for 48 h.

Comparative utility of instruments for monitoring sleepiness- related performance decrements in the operational environment

As both military and commercial operations increasingly become continuous, 24‐h‐per‐day enterprises, the likelihood of operator errors or inefficiencies caused by sleep loss and/or circadian desynchrony also increases. Avoidance of such incidents requires the timely application of appropriate interventions – which, in turn, depend on the ability to measure and monitor the performance capacity of individuals in the operational environment. Several factors determine the potential suitability of candidate measures, including their relative sensitivity, reliability, content validity, intrusiveness and cumbersomeness/fieldability. In the present study, the relative sensitivity (defined as the ratio of effect size to 95% confidence interval) of several measures to the effects of sleep loss was compared in a sleep restriction experiment, in which groups were allowed 3, 5, 7, or 9 h time in bed (TIB) across seven consecutive nights. Of the measures compared, the Psychomotor Vigilance Test was among the most sensitive to sleep restriction, was among the most reliable with no evidence of learning over repeated administrations, and possesses characteristics that make it among the most practical for use in the operational environment.

The effects of d-amphetamine on arousal, cognition, and mood after prolonged total sleep deprivation.

Thirty-six normal male subjects underwent total sleep deprivation for 48 hours, were then administered either placebo, 5, 10, or 20 mg of d-amphetamine, and sleep deprived for an additional 12 hours. Sleep deprivation produced a significant reduction in sleep latency, as well as marked decrements in cognitive performance and self-ratings reflecting vigor and fatigue. Amphetamine reversed these effects in a dose-related way but the pattern and persistence of the reversal varied across measures. After 20 mg, sleep latency normalized for several hours, but then declined. Behavioral effects tended to follow the pattern of sleep latency. On cognitive tasks, 20 mg produced a sustained return to normal performance in an attentional arithmetic task and a gradual improvement in a verbal reasoning task. The partial temporal dissociation among sleep latency, behavioral, and cognitive effects suggests that varying doses of amphetamine may have time-related differential neurochemical effects or that various dimensions of arousal and alertness may be differentially sensitive to amphetamine.

Oculomotor impairment during chronic partial sleep deprivation

OBJECTIVE The effects of chronic partial sleep (sleep deprivation) and extended sleep (sleep augmentation) followed by recovery sleep on oculomotor function were evaluated in normal subjects to explore the usefulness of oculomotor assessment for alertness monitoring in fitness-for-duty testing. METHODS Sixty-six commercial drivers (24-62 years, 50m/16f) participated in a 15 day study composed of 3 training days with 8h time in bed per night, 7 experimental days with subjects randomly assigned to either 3, 5, 7, or 9h time in bed, and 3 recovery nights with 8h time in bed. Data from 57 subjects were used. Saccadic velocity (SV), initial pupil diameter (IPD), latency to pupil constriction (CL), and amplitude of pupil constriction (CA) were assessed and correlated with the sleep latency test (SLT), the Stanford sleepiness scale (SSS), and simulated driving performance. RESULTS Regression analyses showed that SV slowed significantly in the 3 and 5h groups, IPD decreased significantly in the 9h group, and CL increased significantly in the 3h group. SLT and SSS significantly correlated with SV, IPD, CL, and driving accidents for the 3h group, and with CL for the 5h group. Analyses also showed a significant negative correlation between decreasing SV and increasing driving accidents in the 3h group and a significant negative correlation between IPD and driving accidents for the 7h group. CONCLUSIONS The results demonstrate a sensitivity primarily of SV to sleepiness, and a correlation of SV and IPD to impaired simulated driving performance, providing evidence for the potential utility of oculomotor indicators in the detection of excessive sleepiness and deterioration of complex motor performance with chronic partial sleep restriction. SIGNIFICANCE This paper shows a relationship between sleep deprivation and oculomotor measures, and suggests a potential utility for oculometrics in assessing operational performance readiness under sleep restricted conditions.

Effects of catecholamine depletion on alertness and mood in rested and sleep deprived normal volunteers

Alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, was used to evaluate the physiologic role of central nervous system catecholamines at modulating alertness and mood. Forty healthy males were randomized to one of four conditions: AMPT in a rested condition; AMPT plus 40.5 hours of total sleep deprivation; placebo plus sleep deprivation; or placebo in a rested condition. Repeated measures of alertness and mood revealed that treatment with AMPT or sleep deprivation increased sleepiness, and combined treatment produced greater sleepiness than either treatment alone. In contrast, although combined treatment with AMPT and sleep deprivation led to large increases in negative mood, neither treatment alone produced consistent mood changes. These findings are consistent with the view that sleep deprivation is associated with decreased functional catecholamine neurotransmission. Furthermore, mood effects following sleep deprivation plus AMPT suggest that catecholamines may be involved in mood changes during sleep deprivation.

The effects of L-dihydroxyphenylalanine on alertness and mood in α-methyl-para-tyrosine-treated healthy humans : further evidence for the role of catecholamines in arousal and anxiety

Treatment with α-methyl-para-tyrosine (AMPT), a catecholamine synthesis inhibitor, has been shown to produce pronounced increases in sleepiness and mild increases in negative mood and anxiety when administered to healthy male adults. The present study was conducted to ascertain whether these effects of AMPT are secondary to decreases in brain catecholamines or whether they represent nonspecific drug effects. Forty-one healthy males were randomized to one of four treatment groups. (1) Treatment with AMPT alone (AMPT/placebo); (2) treatment with AMPT plus L-dopa/carbidopa (AMPT plus L-dopa/carbidopa); (3) treatment with L-dopa/carbidopa alone (placebo plus L-dopa/carbidopa); or (4) treatment with placebo alone (placebo plus placebo). Repeated measures of alertness, mood, and anxiety were obtained over a three-day period of drug treatment and following drug discontinuation. As before, AMPT treatment led to increased sleepiness. In addition, AMPT treatment led to decreased calmness, increased tension and anger, and a trend for increased depression. Replacement of catecholamine stores with L-dopa reversed the effects of AMPT and was associated with a more rapid recovery from AMPTs effects. These findings indicate that AMPTs effects on alertness and anxiety are catecholamine-specific. Further, they provide additional evidence that catecholamines are involved in the regulation of normal states of arousal, and they are consistent with the view that brain catecholaminergic dysregulation is involved in pathological anxiety states.

Effects of Partial and Total Sleep Deprivation on Driving Performance

The National Highway Traffic Safety Administration estimates that from 1989 through 1993, driver drowsiness/fatigue was a contributing factor in 100,000 crashes annually on U.S. highways. A recent study examined the effects of progressive sleep deprivation on driving performance to assess the rate of crashes and the changes in driving performance resulting from sleepiness. Because it would be unsafe to study this under real driving conditions, the high-fidelity highway driving simulator was used. A variety of measures, including continuous electroencephalogram (EEG) monitoring, videotaping, and analyses of driving performance data and questionnaire data were used to determine the effects of sleep deprivation on the driving performance of six men and six women aged 26-35. Highway safety variables, including number of crashes and number of lane excursions, were unacceptably high on day three after 36 hours of no sleep and on day four after 60 hours without sleep. More subtle measures of highway safety, such as speed and lateral placement variance, were also linked to sleep deprivation. Although some trends appeared, none of the variables were significantly affected by partial sleep deprivation, perhaps because participants were young, very healthy, and nonmedicated and because they had no sleep debt at the start of the study. A preliminary neural net analysis using the data collected is underway. If patterns of driving performance can be identified, it will lend strong support for the development of a neural net in-vehicle-based system for detecting and warning drowsy drivers of potential danger.

Brain and Behavior Changes during Sleep Deprivation

Cognitive performance is critical to military and civilian operational success. Sleep deprivation produces deficits in alertness and general cognitive performance, especially performance requiring higher-order mental processes such as attention, memory, anticipation, planning, and decision making. To demonstrate the degradation on cognitive performance and its brain correlates during sleep deprivation, we have used positron emission tomography (PET), a brain imaging technique, and 2-[‘*F]fluoro-2deoxy-D-glucose (FDG), an index of regional cerebral glucose metabolic rate (rCMRglu) and brain activity. We report that 24 hours of sleep deprivation results in decreased alertness and cognitive performance, and in decreased rCMRglu, predominantly in prefrontal and posterior parietal cortices, and thalamus. Our results provide evidence that the impairments produced by sleep deprivation have a biological basis in reduced brain activity in regions subserving higher-order cognitive and alertness functions. These findings have relevance for educational and sleep management programs, as well as the use of countermeasures.