Circadian control of the sleep–wake cycle

It is beyond doubt that the timing of sleep is under control of the circadian pacemaker. Humans are a diurnal species; they sleep mostly at night, and they do so at approximately 24-h intervals. If they do not adhere to this general pattern, for instance when working night shifts or when travelling across time zones, they experience the stubborn influence of their circadian clock. In recent years much has been discovered about the organisation of the circadian clock. New photoreceptor cells in the retina have been found to influence the input to the clock, and much of the molecular machinery of the clock has been unravelled. It is now known that the circadian rhythm of sleep and wakefulness is only loosely coupled to the circadian rhythm of the pacemaker. New theories have been proposed for the functions of sleep and the sites at which those functions are executed. In spite of this rapid increase in knowledge of the circadian clock and of sleep regulatory processes, much remains to be discovered concerning the precise interaction between the biological clock and sleep timing. This is particularly unfortunate in view of the 24-h demands of our society for 7 days a week. Too little is known about the negative consequences of the societal pressures on well-being and performance.

Comparison of the Munich Chronotype Questionnaire with the Horne-Östberg’s Morningness-Eveningness Score

We report on results from an Internet survey of sleeping habits in a Dutch population using the Munich Chronotype Questionnaire (MCTQ), supplemented with the Horne-Östberg Morningness-Eveningness Questionnaire (MEQ). The MCTQ was completed by 5,055 responders, of which 2,481 also completed the MEQ. MEQ score correlated well with the MCTQ assessment of time of mid-sleep on free days (MSF; r = -0.73) and on workdays (MSW; r = -0.61). MEQ was more strongly correlated with MSF (50% of sleep time) than with sleep onset (0%), rise time (100%), or with any other percentile (10 to 40, 60% to 90%) of sleep on free days. The study shows that chronotype (based on MSF as measured by the MCTQ) strongly correlates with morningness-eveningness (as measured by the MEQ). However, the MCTQ collects additional detailed information on sleep-wake behavior under natural conditions.

Nasal versus Temporal Illumination of the Human Retina: Effects on Core Body Temperature, Melatonin, and Circadian Phase

The mammalian retina contains both visual and circadian photoreceptors. In humans, nocturnal stimulation of the latter receptors leads to melatonin suppression, which might cause reduced nighttime sleepiness. Melatonin suppression is maximal when the nasal part of the retina is illuminated. Whether circadian phase shifting in humans is due to the same photoreceptors is not known. The authors explore whether phase shifts and melatonin suppression depend on the same retinal area. Twelve healthy subjects participated in a within-subjects design and received all of 3 light conditions—1) 10 lux of dim light on the whole retina, 2) 100 lux of ocular light on the nasal part of the retina, and 3) 100 lux of ocular light on the temporal part of the retina—on separate nights in random order. In all 3 conditions, pupils were dilated before and during light exposure. The protocol consisted of an adaptation night followed by a 23-h period of sustained wakefulness, during which a 4-h light pulse was presented at a time when maximal phase delays were expected. Nasal illumination resulted in an immediate suppression of melatonin but had no effect on subjective sleepiness or core body temperature (CBT). Nasal illumination delayed the subsequent melatonin rhythm by 78 min, which is significantly (p = 0.016) more than the delay drift in the dim-light condition (38 min), but had no detectable phase-shifting effect on the CBT rhythm. Temporal illumination suppressed melatonin less than the nasal illumination and had no effect on subjective sleepiness and CBT. Temporal illumination delayed neither the melatonin rhythm nor the CBT rhythm. The data show that the suppression of melatonin does not necessarily result in a reduction of subjective sleepiness and an elevation of CBT. In addition, 100 lux of bright white light is strong enough to affect the photoreceptors responsible for the suppression of melatonin but not strong enough to have a significant effect on sleepiness and CBT. This may be due to the larger variability of the latter variables.

Acute and Phase-Shifting Effects of Ocular and Extraocular Light in Human Circadian Physiology

Light can influence physiology and performance of humans in two distinct ways. It can acutely change the level of physiological and behavioral parameters, and it can induce a phase shift in the circadian oscillators underlying variations in these levels. Until recently, both effects were thought to require retinal light perception. This view was challenged previously, where significant phase shifts in core body temperature and melatonin were shown using an extraocular stimulus. Their study employed popliteal skin illumination and exclusively considered phase-shifting effects. In this paper, the authors explore both acute effects and phase-shifting effects of ocular as well as extraocular light. Twelve healthy males participated in a within-subject design and received all of three light conditions—(1) dim ocular light/no light to the knee, (2) dim ocular light/bright extraocular light to the knee, and (3) bright ocular light/no light to the knee—on separate nights in random order. The protocol consisted of an adaptation night followed by a 26-h period of sustained wakefulness, during which a 4-h light pulse was presented at a time when maximal phase delays were expected. The authors found neither immediate nor phase-shifting effects of extraocular light exposure on melatonin, core body temperature (CBT), or sleepiness. Ocular bright-light exposure reduced the nocturnal circadian drop in CBT, suppressed melatonin, and reduced sleepiness significantly. In addition, the 4-h ocular light pulse delayed the CBT rhythm by –55 min compared to the drift of the CBT rhythm in dim light. The melatonin rhythm shifted by –113 min, which differed significantly fromthe drift in the melatonin rhythm in the dim-light condition (–26 min). The failure to find immediate or phase-shifting effects in response to extraocular light in a within-subjects design in which effects of ocular bright light are confirmed strengthens the doubts raised by other labs of the impact of extraocular light on the human circadian system.

Time-of-day-dependent effects of bright light exposure on human psychophysiology: comparison of daytime and nighttime exposure

Bright light can influence human psychophysiology instantaneously by inducing endocrine (suppression of melatonin, increasing cortisol levels), other physiological changes (enhancement of core body temperature), and psychological changes (reduction of sleepiness, increase of alertness). Its broad range of action is reflected in the wide field of applications, ranging from optimizing a work environment to treating depressed patients. For optimally applying bright light and understanding its mechanism, it is crucial to know whether its effects depend on the time of day. In this paper, we report the effects of bright light given at two different times of day on psychological and physiological parameters. Twenty-four subjects participated in two experiments (n = 12 each). All subjects were nonsmoking, healthy young males (18–30 yr). In both experiments, subjects were exposed to either bright light (5,000 lux) or dim light <10 lux (control condition) either between 12:00 P.M. and 4:00 P.M. (experiment A) or between midnight and 4:00 A.M. (experiment B). Hourly measurements included salivary cortisol concentrations, electrocardiogram, sleepiness (Karolinska Sleepiness Scale), fatigue, and energy ratings (Visual Analog Scale). Core body temperature was measured continuously throughout the experiments. Bright light had a time-dependent effect on heart rate and core body temperature; i.e., bright light exposure at night, but not in daytime, increased heart rate and enhanced core body temperature. It had no significant effect at all on cortisol. The effect of bright light on the psychological variables was time independent, since nighttime and daytime bright light reduced sleepiness and fatigue significantly and similarly.