David R. Thorne

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 Walter Reed palm-held psychomotor vigilance test.

This field-portable reaction time test and analysis software run on devices using the Palm operating system. It is designed to emulate a test and commercial device widely used in sleep deprivation, shift work, fatigue, and stimulant drug research but provides additional capabilities. Experimental comparisons with the standard commercial device in a 40-hour total sleep deprivation study show it to be comparably sensitive to selected experimental variables. A Pocket PC-compatible version is under developement.

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.

Throughput: a simple performance index with desirable characteristics.

Throughput is a corrected response rate measure giving the number of successes per unit of discretionary time. It is a simple but general index applicable to psychomotor, behavioral, and cognitive tasks in which response times are measured. This measure has several attractive features: (1) It allows comparisons to be made across various tasks in which speed and accuracy are meaningful and measurable, independently of temporal differences in hardware, software, and procedures; (2) under conditions in which both speed and accuracy decline (or improve), throughput will be a more sensitive index of performance than either alone will be; and (3) in those tasks in which the speed—accuracy trade-off phenomenon operates, throughput will tend to be relatively less variable than either component alone will be. The measure allows both behavioral and information-processing interpretations of data and may be useful as a simple composite index, a measure of effectiveness or of cognitive consistency in studies investigating performance degradation or enhancement.Throughput is a corrected response rate measure giving the number of successes per unit of discretionary time. It is a simple but general index applicable to psychomotor, behavioral, and cognitive tasks in which response times are measured. This measure has several attractive features: (1) It allows comparisons to be made across various tasks in which speed and accuracy are meaningful and measurable, independently of temporal differences in hardware, software, and procedures; (2) under conditions in which both speed and accuracy decline (or improve), throughput will be a more sensitive index of performance than either alone will be; and (3) in those tasks in which the speed-accuracy trade-off phenomenon operates, throughput will tend to be relatively less variable than either component alone will be. The measure allows both behavioral and information-processing interpretations of data and may be useful as a simple composite index, a measure of effectiveness or of cognitive efficiency [corrected] in studies investigating performance degradation or enhancement.

Circadian variation in human performance evaluated by the walter reed performance assessment battery

As part of a two clock-time (0830 versus 2030) evaluation of administration-time dependent effects of dexedrine (5 mg) and triazolam (0.25 mg) on human cognitive performance, placebo (control) studies were conducted on 12 diurnally active (0700-2300) male adults (23-38 yrs) using a double-blind, randomized crossover design. Testing was conducted hourly during a series of sleepless 13-hr spans commencing in the morning or evening, using the Walter Reed computer controlled and scored multi-task cognitive performance assessment battery. For the placebo condition, Single and Group Cosinor analyses documented circadian rhythms in performance for most tasks (reaction time, logical reasoning, serial add/subtract and spatial orientation) both for individuals and the group. Overall, performance was worse overnight, when sleepiness was greatest, and best between 1830 and 2030. It was most variable around 0600-0700. The day-night variation in performance over all cognitive tests amounted to 21% of the 24-hr mean.

Sleep deprivation and impaired cognition possible role of brain catecholamines

To assess the role of brain catecholamines in cognitive decline associated with sleep deprivation, 40 healthy male volunteers were randomized to conditions of total sleep deprivation or 40.5 h of rest. Within each sleep condition, subjects were further randomized to treatment with a 2-day regimen of placebo or alpha-methyl-para-tyrosine (AMPT), a catecholamine synthesis inhibitor. Cognitive performance was measured repeatedly over time using a computerized performance assessment battery. Treatment with AMPT or treatment with sleep deprivation increased sleepiness without producing marked or consistent deterioration in performance. By contrast, subjects who received both treatments reported greater sleepiness than those receiving either treatment alone, and developed severe cognitive impairment on a variety of tasks. These findings, along with previous evidence that catecholamine-enhancing drugs improve performance in sleep-deprived individuals, support the view that decline in cognitive performance during sleep deprivation may be mediated by brain catecholamines.