Adaptation of circadian responses to light treatment

Brigham And Women'S Hospital, Boston MA

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Abstract

DESCRIPTION (provided by applicant): Light is the most powerful stimulus to the circadian pacemaker. For this reason light is the preferential stimulus in the investigation of the fundamental properties of the circadian timing system and in the treatment of circadian misalignment (e.g. shift-work and jet lag). Extensive research has already demonstrated that the timing, intensity, duration, wavelength, and number of consecutive light exposures influence the efficacy of light treatment. Surprisingly, although animal experimental research demonstrated that the preceding photic history affects the resetting response to a light stimulus, such effects in humans have received little attention. In our preliminary data, we demonstrate that a photic history of exposure to a low light intensity (0.16 mu W/cm2 ; approximately 0.5 lux) significantly increased the melatonin-suppressive effect of a subsequent light stimulus in comparison to a moderate intensity photic history (64 mu W/cm2; approximately 200 lux). The proposed investigation is designed to test the hypotheses that 1) the phase delay of the human circadian pacemaker, 2) the suppression of melatonin plasma concentrations, and 3) the acute effect on alertness, as measured by subjective ratings, EEG activation, decreased incidence of slow eye movements, and improved neurobehavioral performance, as induced by a single 6.5-h moderately bright light exposure (64 mu W/cm2; approximately 200 lux) will be greater if it occurs following very dim light exposure (0.16 mu W/cm2; approximately 0.5 lux) than it will be following ordinary indoor room light exposure (16 mu W/cm2; approximately 50 lux). We propose to test the hypotheses in a non-light-controlled, crossover, within-subjects design to compare the effect of a standardized light exposure1 on changes in circadian phase, melatonin secretion and alertness between two 10-day background light intensities. Melatonin and core body temperature analysis will be performed to assess phase shifts and nocturnal melatonin suppression. Quantitative analysis of waking EEG, EOG and cognitive functioning will be performed to assess changes in alertness. The results of this project should further our fundamental understanding of photic history-related changes in the efficacy of light stimuli in modulating circadian regulation. Furthermore, this project may reveal a new method to potentiate light therapy in the treatment of circadian rhythm disturbances.