Human behavior shows large interindividual variation in temporal organization. Extreme "larks" wake up when extreme "owls" fall asleep. These chronotypes are attributed to differences in the circadian clock, and in animals, the genetic basis of similar phenotypic differences is well established. To better understand the genetic basis of temporal organization in humans, the authors developed a questionnaire to document individual sleep times, self-reported light exposure, and self-assessed chronotype, considering work and free days separately. This report summarizes the results of 500 questionnaires completed in a pilot study. Individual sleep times show large differences between work and free days, except for extreme early types. During the workweek, late chronotypes accumulate considerable sleep debt, for which they compensate on free days by lengthening their sleep by several hours. For all chronotypes, the amount of time spent outdoors in broad daylight significantly affects the timing of sleep: Increased self-reported light exposure advances sleep. The timing of selfselected sleep is multifactorial, including genetic disposition, sleep debt accumulated on workdays, and light exposure. Thus, accurate assessment of genetic chronotypes has to incorporate all of these parameters. The dependence of human chronotype on light, that is, on the amplitude of the light:dark signal, follows the known characteristics of circadian systems in all other experimental organisms. Our results predict that the timing of sleep has changed during industrialization and that a majority of humans are sleep deprived during the workweek. The implications are far ranging concerning learning, memory, vigilance, performance, and quality of life.

SUMMARYIn the last three decades the two-process model of sleep regulation has served as a major conceptual framework in sleep research. It has been applied widely in studies on fatigue and performance and to dissect individual differences in sleep regulation. The model posits that a homeostatic process (Process S) interacts with a process controlled by the circadian pacemaker (Process C), with time-courses derived from physiological and behavioural variables. The model simulates successfully the timing and intensity of sleep in diverse experimental protocols. Electrophysiological recordings from the suprachiasmatic nuclei (SCN) suggest that S and C interact continuously. Oscillators outside the SCN that are linked to energy metabolism are evident in SCN-lesioned arrhythmic animals subjected to restricted feeding or methamphetamine administration, as well as in human subjects during internal desynchronization. In intact animals these peripheral oscillators may dissociate from the central pacemaker rhythm. A sleep/fast and wake/feed phase segregate antagonistic anabolic and catabolic metabolic processes in peripheral tissues. A deficiency of Process S was proposed to account for both depressive sleep disturbances and the antidepressant effect of sleep deprivation. The model supported the development of novel non-pharmacological treatment paradigms in psychiatry, based on manipulating circadian phase, sleep and light exposure. In conclusion, the model remains conceptually useful for promoting the integration of sleep and circadian rhythm research. Sleep appears to have not only a short-term, use-dependent function; it also serves to enforce rest and fasting, thereby supporting the optimization of metabolic processes at the appropriate phase of the 24-h cycle. IN TROD UCTI ONThe two-process model of sleep regulation was proposed more than three decades ago. It had a large impact on sleep research and is still a prevalent conceptual model. This is reflected by the persistently high number of citations per year of the original papers. AAB and SD published the original papers of the two process model (Borb ely, 1982;Daan et al., 1984), whereas AAB and AWJ related the model to sleep in depression and the antidepressant effect of sleep deprivation (Borb ely and Wirz-Justice, 1982).

Light can elicit acute physiological and alerting responses in humans, the magnitude of which depends on the timing, intensity, and duration of light exposure. Here, we report that the alerting response of light as well as its effects on thermoregulation and heart rate are also wavelength dependent. Exposure to 2 h of monochromatic light at 460 nm in the late evening induced a significantly greater melatonin suppression than occurred with 550-nm monochromatic light, concomitant with a significantly greater alerting response and increased core body temperature and heart rate ( approximately 2.8 x 10(13) photons/cm(2)/sec for each light treatment). Light diminished the distal-proximal skin temperature gradient, a measure of the degree of vasoconstriction, independent of wavelength. Nonclassical ocular photoreceptors with peak sensitivity around 460 nm have been found to regulate circadian rhythm function as measured by melatonin suppression and phase shifting. Our findings-that the sensitivity of the human alerting response to light and its thermoregulatory sequelae are blue-shifted relative to the three-cone visual photopic system-indicate an additional role for these novel photoreceptors in modifying human alertness, thermophysiology, and heart rate.

Many people spend an increasing amount of time in front of computer screens equipped with light-emitting diodes (LED) with a short wavelength (blue range). Thus we investigated the repercussions on melatonin (a marker of the circadian clock), alertness, and cognitive performance levels in 13 young male volunteers under controlled laboratory conditions in a balanced crossover design. A 5-h evening exposure to a white LED-backlit screen with more than twice as much 464 nm light emission {irradiance of 0,241 Watt/(steradian × m(2)) [W/(sr × m(2))], 2.1 × 10(13) photons/(cm(2) × s), in the wavelength range of 454 and 474 nm} than a white non-LED-backlit screen [irradiance of 0,099 W/(sr × m(2)), 0.7 × 10(13) photons/(cm(2) × s), in the wavelength range of 454 and 474 nm] elicited a significant suppression of the evening rise in endogenous melatonin and subjective as well as objective sleepiness, as indexed by a reduced incidence of slow eye movements and EEG low-frequency activity (1-7 Hz) in frontal brain regions. Concomitantly, sustained attention, as determined by the GO/NOGO task; working memory/attention, as assessed by "explicit timing"; and declarative memory performance in a word-learning paradigm were significantly enhanced in the LED-backlit screen compared with the non-LED condition. Screen quality and visual comfort were rated the same in both screen conditions, whereas the non-LED screen tended to be considered brighter. Our data indicate that the spectral profile of light emitted by computer screens impacts on circadian physiology, alertness, and cognitive performance levels. The challenge will be to design a computer screen with a spectral profile that can be individually programmed to add timed, essential light information to the circadian system in humans.

Seven healthy men were studied in a 34-h constant routine protocol to investigate whether the daily rhythm of heat production and heat loss has an endogenous circadian component. Under these unmasking conditions (constant bed rest, no sleep allowed, regular food and fluid intake), a significant circadian rhythm could be demonstrated for heat production, heart rate, and skin temperatures but not for the respiratory quotient. Heat production and heart rate were phase locked with a maximum at 1100-1200 h. Proximal skin temperatures (infraclavicular region, thigh, and forehead) followed the same circadian rhythm as rectal temperature, whereas distal skin temperatures (hands and feet) were opposite in phase. These physiological circadian rhythm parameters, as well as biochemical parameters (urinary sodium, potassium, urea, and urine flow), were phase advanced by 25-180 min with respect to the circadian rhythm in rectal temperature. Our findings under unmasking conditions show that the circadian variation in rectal temperature is a consequence of endogenous circadian rhythms in both heat production and heat loss.

The circadian rhythm of pineal melatonin is the best marker of internal time under low ambient light levels. The endogenous melatonin rhythm exhibits a close association with the endogenous circadian component of the sleep propensity rhythm. This has led to the idea that melatonin is an internal sleep "facilitator" in humans, and therefore useful in the treatment of insomnia and the readjustment of circadian rhythms. There is evidence that administration of melatonin is able: (i) to induce sleep when the homeostatic drive to sleep is insufficient; (ii) to inhibit the drive for wakefulness emanating from the circadian pacemaker; and (iii) induce phase shifts in the circadian clock such that the circadian phase of increased sleep propensity occurs at a new, desired time. Therefore, exogenous melatonin can act as soporific agent, a chronohypnotic, and/or a chronobiotic. We describe the role of melatonin in the regulation of sleep, and the use of exogenous melatonin to treat sleep or circadian rhythm disorders.

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Thermoregulatory processes have long been implicated in initiation of human sleep. The purpose of this study was to evaluate the role of heat loss in sleep initiation, under the controlled conditions of a constant-routine protocol modified to permit nocturnal sleep. Heat loss was indirectly measured by means of the distal-to-proximal skin temperature gradient (DPG). A stepwise regression analysis revealed that the DPG was the best predictor variable for sleep-onset latency (compared with core body temperature or its rate of change, heart rate, melatonin onset, and subjective sleepiness ratings). This study provides evidence that selective vasodilation of distal skin regions (and hence heat loss) promotes the rapid onset of sleep.