Light is a primary synchronizer of the human circadian pacemaker, with the response to light dependent on the timing, number, intensity, duration, and pattern of exposures. The timing of a light stimulus relative to circadian phase has particularly important practical implications in a real-world therapeutic setting, because inappropriately timed light exposure can cause an opposite phase resetting response to that desired. In prior years of this grant, we quantified the relationship between the timing of white light exposure and its circadian resetting effect in Phase Response Curves (PRC). These PRCs have provided the basis for designing appropriately-timed lighting regimes to reset the circadian pacemaker in a range of therapeutic applications. Recent studies have demonstrated that novel photoreceptors with a peak sensitivity in the shorter (blue) wavelengths, rather than rods and cones, are primarily responsible for mediating non-image forming responses such as circadian phase resetting and melatonin suppression. This has dramatic implications for using light to treat circadian rhythm disorders and other conditions. Current lighting is designed for the visual photopic system (peak sensitivity 555 nm), making most current lighting inappropriate for optimizing circadian responses. The development of solid-state lighting will make it possible to easily alter the spectral composition of light, such that light spectra could be tailored to the desired biological effect. Given that solid- state lighting for home and occupational settings will be introduced widely over the next decade, it is vital that we understand the fundamental aspects of how this new technology can be used to benefit human health. We have proposed a study in which we will systematically assess the circadian phase-shifting, melatonin suppressing, and alertness-enhancing response to a monochromatic light stimulus, using a wavelength (460 nm) that has been shown to maximally stimulate the circadian system. We will assess the phase-dependent response to this optimal light source (Aim I). We will examine the relationship between the melatonin- suppressing effects of the stimulus and its acute alerting and performance-enhancing effects in order to determine whether these effects are phase-dependent (Aims II and III), and whether the alerting and performance-enhancing effects are correlated with the degree of melatonin suppression (Aim II). We will examine changes in the EEG frequency power distribution to determine whether acute responses to the stimulus differentially affect the EEG spectrum at different times of day (Aim III). The results of this work will build the foundation for the application of new solid-state lighting technology for the phototherapy treatment of delayed sleep phase disorder, advanced sleep phase disorder, shift-work sleep disorder, jet lag, seasonal affective disorder, """"""""sundowning"""""""" in Alzheimer's Disease, and age-related sleep maintenance insomnia.

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National Institute of Mental Health (NIMH)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Muehrer, Peter R
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Brigham and Women's Hospital
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