Deficits in daytime performance due to sleep loss are experienced universally and associated with a significant social, financial, and human cost. Microsleeps, sleep attacks, and lapses in cognition increase with sleep loss as a function of state instability. Sleep deprivation studies repeatedly show a variable (negative) impact on mood, cognitive performance, and motor function due to an increasing sleep propensity and destabilization of the wake state. Specific neurocognitive domains including executive attention, working memory, and divergent higher cognitive functions are particularly vulnerable to sleep loss. In humans, functional metabolic and neurophysiological studies demonstrate that neural systems involved in executive function (i.e., prefrontal cortex) are more susceptible to sleep deprivation in some individuals than others. Recent chronic partial sleep deprivation experiments, which more closely replicate sleep loss in society, demonstrate that profound neurocognitive deficits accumulate over time in the face of subjective adaptation to the sensation of sleepiness. Sleep deprivation associated with disease-related sleep fragmentation (i.e., sleep apnea and restless legs syndrome) also results in neurocognitive performance decrements similar to those seen in sleep restriction studies. Performance deficits associated with sleep disorders are often viewed as a simple function of disease severity; however, recent experiments suggest that individual vulnerability to sleep loss may play a more critical role than previously thought.

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Neurocognitive Consequences of Sleep Deprivation

background Although sleep deprivation has been shown to impair neurobehavioral performance, few studies have measured its effects on medical errors. methods We conducted a prospective, randomized study comparing the rates of serious medical errors made by interns while they were working according to a traditional schedule with extended (24 hours or more) work shifts every other shift (an “every third night” call schedule) and while they were working according to an intervention schedule that eliminated extended work shifts and reduced the number of hours worked per week. Incidents were identified by means of a multidisciplinary, four-pronged approach that included direct, continuous observation. Two physicians who were unaware of the interns’ schedule assignments independently rated each incident. results During a total of 2203 patient-days involving 634 admissions, interns made 35.9 percent more serious medical errors during the traditional schedule than during the intervention schedule (136.0 vs. 100.1 per 1000 patient-days, P<0.001), including 56.6 percent more nonintercepted serious errors (P<0.001). The total rate of serious errors on the critical care units was 22.0 percent higher during the traditional schedule than during the intervention schedule (193.2 vs. 158.4 per 1000 patient-days, P<0.001). Interns made 20.8 percent more serious medication errors during the traditional schedule than during the intervention schedule (99.7 vs. 82.5 per 1000 patient-days, P = 0.03). Interns also made 5.6 times as many serious diagnostic errors during the traditional schedule as during the intervention schedule (18.6 vs. 3.3 per 1000 patientdays, P<0.001). conclusions Interns made substantially more serious medical errors when they worked frequent shifts of 24 hours or more than when they worked shorter shifts. Eliminating extended work shifts and reducing the number of hours interns work per week can reduce serious medical errors in the intensive care unit.

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Effect of reducing interns' work hours on serious medical errors in intensive care units.

Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to average 25 hours in adulthood, and to shorten with age. However, those observations were based on studies of humans exposed to light levels sufficient to confound circadian period estimation. Precise estimation of the periods of the endogenous circadian rhythms of melatonin, core body temperature, and cortisol in healthy young and older individuals living in carefully controlled lighting conditions has now revealed that the intrinsic period of the human circadian pacemaker averages 24.18 hours in both age groups, with a tight distribution consistent with other species. These findings have important implications for understanding the pathophysiology of disrupted sleep in older people.

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Stability, Precision, and Near-24-Hour Period of the Human Circadian Pacemaker

The role of the endogenous circadian pacemaker in the timing of the sleep-wake cycle and the regulation of the internal structure of sleep, including REM sleep, EEG slow-wave (0.75-4.5 Hz) and sleep spindle activity (12.75-15.0 Hz) was investigated. Eight men lived in an environment free of time cues for 33-36 d and were scheduled to a 28 hr rest-activity cycle so that sleep episodes (9.33 hr each) occurred at all phases of the endogenous circadian cycle and variations in wakefulness preceding sleep were minimized. The crest of the robust circadian rhythm of REM sleep, which was observed throughout the sleep episode, was positioned shortly after the minimum of the core body temperature rhythm. Furthermore, a sleep-dependent increase of REM sleep was present, which, interacting with the circadian modulation, resulted in highest values of REM sleep when the end of scheduled sleep episodes coincided with habitual wake-time. Slow-wave activity decreased and sleep spindle activity increased in the course of all sleep episodes. Slow-wave activity in non-REM sleep exhibited a low amplitude circadian modulation which did not parallel the circadian rhythm of sleep propensity. Sleep spindle activity showed a marked endogenous circadian rhythm; its crest coincident with the beginning of the habitual sleep episode. Analyses of the (nonadditive) interaction of the circadian and sleep-dependent components of sleep propensity and sleep structure revealed that the phase relation between the sleep-wake cycle and the circadian pacemaker during entrainment promotes the consolidation of sleep and wakefulness and facilitates the transitions between these vigilance states.

https://www.jneurosci.org/content/jneuro/15/5/3526.full.pdf

Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans

1 Non-image forming, irradiance-dependent responses mediated by the human eye include synchronisation of the circadian axis and suppression of pineal melatonin production The retinal photopigment(s) transducing these light responses in humans have not been characterised 2 Using the ability of light to suppress nocturnal melatonin production, we aimed to investigate its spectral sensitivity and produce an action spectrum Melatonin suppression was quantified in 22 volunteers in 215 light exposure trials using monochromatic light (30 min pulse administered at circadian time (CT) 16-18) of different wavelengths (lambda(max) 424, 456, 472, 496, 520 and 548 nm) and irradiances (07-650 microW cm(-2)) 3 At each wavelength, suppression of plasma melatonin increased with increasing irradiance Irradiance-response curves (IRCs) were fitted and the generated half-maximal responses (IR(50)) were corrected for lens filtering and used to construct an action spectrum 4 The resulting action spectrum showed unique short-wavelength sensitivity very different from the classical scotopic and photopic visual systems The lack of fit (r(2) or =073) Of these, the best fit was to the rhodopsin template with lambda(max) 459 nm (r(2) = 074) 5 Our data strongly support a primary role for a novel short-wavelength photopigment in light-induced melatonin suppression and provide the first direct evidence of a non-rod, non-cone photoreceptive system in humans

An action spectrum for melatonin suppression: evidence for a novel non‐rod, non‐cone photoreceptor system in humans

Human circadian rhythms were once thought to be insensitive to light, with synchronization to the 24-hour day accomplished either through social contacts or the sleep-wake schedule. Yet the demonstration of an intensity-dependent neuroendocrine response to bright light has led to renewed consideration of light as a possible synchronizer of the human circadian pacemaker. In a laboratory study, the output of the circadian pacemaker of an elderly woman was monitored before and after exposure to 4 hours of bright light for seven consecutive evenings, and before and after a control study in ordinary room light while her sleep-wake schedule and social contacts remained unchanged. The exposure to bright light in the evening induced a 6-hour delay shift of her circadian pacemaker, as indicated by recordings of body temperature and cortisol secretion. The unexpected magnitude, rapidity, and stability of the shift challenge existing concepts regarding circadian phase-resetting capacity in man and suggest that exposure to bright light can indeed reset the human circadian pacemaker, which controls daily variations in physiologic, behavioral, and cognitive function.

https://science.sciencemag.org/content/sci/233/4764/667.full.pdf

Bright light resets the human circadian pacemaker independent of the timing of the sleep-wake cycle.

Association of sleep-wake habits in older people with changes in output of circadian pacemaker

We studied 26 physicians in postgraduate medical training ("house staff") to objectively quantify their sleep, alertness, and psychomotor performance while working on call. This study provided precise data on the extent of sleep deprivation during a typical call night, the workload factors predictive of sleep loss, and the extent to which protected time for sleep within the call night can ameliorate sleep loss and consequent daytime sleepiness. We used ambulatory EEG recording equipment and a standardized computer-based performance test to monitor sleep and alertness over the course of a 36-hour call day. Comparisons were made between interns provided with 4 hours of protected time for sleep by a covering resident ("night-float") and interns without such coverage. As anticipated, we found evidence that hospital interns were severely sleep-deprived, to an extent even greater than prior behavioral observations have suggested. Interns in both conditions spent an average of less than 5 hours (295.4 minutes) in bed attempting to sleep and obtained an average of 3.67 hours (220.1 minutes) of sleep (range 37.4-358.4 minutes). Provision of the night-float for 4 hours did not significantly change total sleep time (TST) (212.8 minutes covered vs. 224.9 minutes uncovered), but sleep efficiency was significantly improved (86.5% vs. 70.3%; p = 0.001). Covered interns also obtained significantly more slow-wave sleep than the uncovered interns (65.4 minutes vs. 51.1 minutes; p = 0.05). However, measures of alertness and performance were not significantly different between the two groups and were only weakly related to TST. These data suggest that significant chronic sleep deprivation is relatively unaffected by sleep obtained in the hospital and that provision of protected time for sleep does not significantly improve TST. Language: en

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Objective assessment of sleep and alertness in medical house staff and the impact of protected time for sleep

A substantial and growing percentage of the U.S. work force now works on a rotating shift schedule. The repeated changes in sleep-wake, meal and work times inherent in such schedules conflict with the dictates of the internal biological clock and have adverse consequences for the health of the shiftworker population. An important consequence of this conflict is impaired performance, both on and off the job, as indexed by the increased incidence of motor vehicle accidents in shift workers. In this paper we report the results of a survey administered to rotating shift and straight day workers at a manufacturing plant in the eastern U.S. This survey documents an increased incidence of motor vehicle accidents or "near misses" in which sleepiness was implicated as a cause by the respondent. Complaints of poor sleep and increased sleepiness were also significantly more common in shiftworkers than day workers. Last, shiftworkers reported higher caffeine and alcohol consumption, and were more likely to use alcohol as a sleep aid. Although causal links cannot be established using these associative observations alone, previously reported experience with alteration of shift schedules, improvement of levels of alertness, and reduction in adverse performance outcomes corroborate the possibility of a causal link and suggest potential interventions.

G. S. Richardson

Papers

Bright light resets the human circadian pacemaker independent of the timing of the sleep-wake cycle.

Association of sleep-wake habits in older people with changes in output of circadian pacemaker

Objective assessment of sleep and alertness in medical house staff and the impact of protected time for sleep

Impaired driving performance in shiftworkers: the role of the circadian system in a multifactorial model