Light is the most powerful stimulus for influencing the human circadian pacemaker and is therefore the preferential stimulus for investigation of the fundamental properties of the circadian timing system. Extensive research has already demonstrated that the timing, duration, wavelength, pattern and number of consecutive light exposures influence the efficacy of light to stimulate circadian, neuroendocrine and electrophysiological responses in humans. Surprisingly, despite evidence in lower mammals that these responses to light are desensitized by prior exposure to white light and may be enhanced by pre-adaptation to red light, the influence of photic history on the sensitivity of the human circadian timing system has received little attention. In preliminary studies, we showed that prior exposure to a moderate intensity cool white fluorescent light (4100K, 200 lux;64 uW/cm2) significantly attenuated melatonin suppression to the same light exposure, as compared to the response in the same individuals following pre-exposure to dim light (0.5 lux;0.16 uW/cm2). The proposed investigation is designed to test the hypotheses that 1) melatonin suppression by a single 12-h moderately bright light exposure (200 lux;64 uW/cm2) will be more strongly desensitized as the duration of prior light exposure to room light intensity (200 lux;64 uW/cm2) is increased from 1.75 hours to 14 hours;2) the acute effect of light exposure on subjective alertness, EOG- and EEC-derived measures of fatigue and cognitive performance will be more strongly attenuated as the duration of prior light exposure to room light is increased from 1.75 hours to 14 hours;and 3) melatonin suppression and arousal by light will be greater if preceded by exposure to 3.5 hours of white light (200 lux, 64 uW/cm2) followed by 3.5 hours of red light (620 nm;1.78 x 10e14 photons/cm2/s;57 uW/cm2), as compared to 7 hours continuous exposure to an equal photon density of white light (200 lux;1.78 x 10e14 photons/cm2/s;64 uW/cm2). We propose to test these hypotheses in a parallel, within-subjects, dim light history-controlled design to compare the effect of different durations of prior light history of moderately bright light (1.75h, 3.5h, 7h, and 14h) on changes in melatonin secretion and alertness, as compared to that following 3-day very dim background light intensities. The results of this project will further our fundamental understanding of photic history-related changes in the efficacy of light stimuli in modulating circadian regulation. Furthermore, this project will quantify the time scale of prior light history that would be able to affect the efficiacy of light therapy in the treatment of circadian rhythm disturbances and SAD, and in the use of light as a direct, non-pharmacological fatigue countermeasure for safety-sensitive industries where prolonged vigilance is required (e.g. medical/surgical residents, nurses, pilots, truck and train drivers, nuclear power plant operators) or for the excessive day-time sleepiness experienced commonly by many patients with primary sleep disorders.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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He, Janet
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Brigham and Women's Hospital
United States
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Sullivan, Jason P; O'Brien, Conor S; Barger, Laura K et al. (2017) Randomized, Prospective Study of the Impact of a Sleep Health Program on Firefighter Injury and Disability. Sleep 40:
Lane, Jacqueline M; Chang, Anne-Marie; Bjonnes, Andrew C et al. (2016) Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology. Diabetes 65:1741-51
Chang, Anne-Marie; Buch, Alison M; Bradstreet, Dayna S et al. (2011) Human diurnal preference and circadian rhythmicity are not associated with the CLOCK 3111C/T gene polymorphism. J Biol Rhythms 26:276-9
RĂ¼ger, Melanie; Scheer, Frank A J L (2009) Effects of circadian disruption on the cardiometabolic system. Rev Endocr Metab Disord 10:245-60