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Zeitzer, Jamie M., Sat Bir S. Khalsa, Diane B. Boivin, Jeanne F. Duffy, Theresa L. Shanahan, Richard E. Kronauer, and Charles A. Czeisler. Temporal dynamics of late-night photic stimulation of the human circadian timing system. Am J Physiol Regul Integr Comp Physiol 289: R839-R844, 2005. First published May 12, 2005; doi:10.1152/ajpregu.00232.2005.--The light-dark cycle is the primary synchronizing factor that keeps the internal circadian pacemaker appropriately aligned with the environmental 24-h day. Although it is known that ocular light exposure can effectively shift the human circadian pacemaker and do so in an intensity-dependent manner, the curve that describes the relationship between light intensity and pacemaker response has not been fully characterized for light exposure in the late biological night. We exposed subjects to 3 consecutive days of 5 h of experimental light, centered 1.5 h after the timing of the fitted minimum of core body temperature, and show that such light can phase advance shift the human circadian pacemaker in an intensity-dependent manner, with a logistic model best describing the relationship between light intensity and phase shift. A similar sigmoidal relationship is also observed between light intensity and the suppression of plasma melatonin concentrations that occurs during the experimental light exposure. As with a simpler, 1-day light exposure during the early biological night, our data indicate that the human circadian pacemaker is highly sensitive even to typical room light intensities during the late biological night, with ~ 100 lux evoking half of the effects observed with light 10 times as bright. light; phase shift; melatonin suppression

The model for human plasma melatonin diurnal variations was developed base on the application of Bayesian Monte Carlo Markov chain (BMCMC) methods. The model utilized BMCMC methods to correctly incorporate the effects of immunoassay errors on reported plasma melatonin levels. The reanalysis of immunoassay data permits the estimation of circadian and pharmacokinetics parameters of melatonin including posterior probability density and summary statistics.

The eyes of some totally blind persons may convey enough information about light and darkness to their brains to synchronize their internal circadian rhythms. A study of 11 blind patients who did not consciously perceive light and of six normal subjects found that three of the blind patients experienced decreases in plasma melatonin concentrations during exposure to bright light, as do sighted persons. The other eight blind patients did not experience changes in their plasma melatonin concentrations. Plasma concentrations of melatonin are found to be higher during nighttime than during the day, and are a way of synchronizing, or entraining, the circadian rhythm to the 24-hour day. Blind persons who do not perceive light may experience periods of severe insomnia because they do not receive the cues of light and dark to entrain their bodies to the 24-hour day.

Rimmer, David W., Diane B. Boivin, Theresa L. Shanahan, Richard E. Kronauer, Jeanne F. Duffy, and Charles A. Czeisler. Dynamic resetting of the human circadian pacemaker by intermittent bright light. Am J Physiol Regulatory Integrative Comp Physiol 279: R1574-R1579, 2000.--In humans, experimental studies of circadian resetting typically have been limited to lengthy episodes of exposure to continuous bright light. To evaluate the time course of the human endogenous circadian pacemaker's resetting response to brief episodes of intermittent bright light, we studied 16 subjects assigned to one of two intermittent lighting conditions in which the subjects were presented with intermittent episodes of bright-light exposure at 25- or 90-min intervals. The effective duration of bright-light exposure was 31% or 63% compared with a continuous 5-h bright-light stimulus. Exposure to intermittent bright light elicited almost as great a resetting response compared with 5 h of continuous bright light. We conclude that exposure to intermittent bright light produces robust phase shifts of the endogenous circadian pacemaker. Furthermore, these results demonstrate that humans, like other species, exhibit an enhanced sensitivity to the initial minutes of bright-light exposure. circadian rhythms; core body temperature; phototherapy

Background: The phase and amplitude of rhythms in physiology and behavior are generated by circadian oscillators and entrained to the 24-h day by exposure to the light-dark cycle and feedback from the sleep-wake cycle. The extent to which the phase and amplitude of multiple rhythms are similarly affected during altered timing of light exposure and the sleepwake cycle has not been fully characterized. Methodology/Principal Findings: We assessed the phase and amplitude of the rhythms of melatonin, core body temperature, cortisol, alertness, performance and sleep after a perturbation of entrainment by a gradual advance of the sleep-wake schedule (10 h in 5 days) and associated light-dark cycle in 14 healthy men. The light-dark cycle consisted either of moderate intensity 'room' light (∼90-150 lux) or moderate light supplemented with bright light (∼10,000 lux) for 5 to 8 hours following sleep. After the advance of the sleep-wake schedule in moderate light, no significant advance of the melatonin rhythm was observed whereas, after bright light supplementation the phase advance was 8.1 h (SEM 0.7 h). Individual differences in phase shifts correlated across variables. The amplitude of the melatonin rhythm assessed under constant conditions was reduced after moderate light by 54% (17-94%) and after bright light by 52% (range 12-84%), as compared to the amplitude at baseline in the presence of a sleep-wake cycle. Individual differences in amplitude reduction of the melatonin rhythm correlated with the amplitude of body temperature, cortisol and alertness. Conclusions/Significance: Alterations in the timing of the sleep-wake cycle and associated bright or moderate light exposure can lead to changes in phase and reduction of circadian amplitude which are consistent across multiple variables but differ between individuals. These data have implications for our understanding of circadian organization and the negative health outcomes associated with shift-work, jet-lag and exposure to artificial light. [ABSTRACT FROM AUTHOR]