The light-dark cycle is the most important environmental synchronizer of circadian rhythms in most species. In fact, it has been shown that critically-timed light exposures can reset circadian phase. Animal studies have demonstrated that the magnitude and direction of these phase shifts are dependent on the intensity and the duration of the light exposure (described by a dose response curve [DRC]) as well as on the initial circadian phase of the light exposure (described by a phase response curve (PRC]). Based on our preliminary data, we hypothesize that: (1) scheduled exposure to bright light stimuli can reproducibly enhance the resetting of the human circadian pacemaker, such that steady state phase shifts can be achieved within three days; (2) the timing of exposure to darkness/sleep modulates the resetting effect of bright light on the human circadian system; (3) the resetting response to a three-cycle light-dark stimulus is dose dependent (as measured by the illuminance of the light stimulus); (4) the resetting response to a cyclic bright light stimulus is dependent on the initial circadian phase of light exposure; (5) exposure to bright light can be used therapeutically in the treatment of circadian sleep disorders. A series of experiments are proposed utilizing methodologies that allow direct measurement of circadian phase both before and after exposure to bright light. These experiments will accomplish 5 specific aims: (1) quantification of the extent to which exposure to bright light can facilitate the resetting of the human circadian pacemaker; (2) characterization of the manner in which darkness/sleep modulates the resetting effect of bright light stimuli; (3) establishment of a dose response curve for the resetting of the human circadian pacemaker by light; (4) determination of the phase response curve of the human circadian pacemaker to a cyclic stimulus of bright light and darkness, and; (5) evaluation of the therapeutic effectiveness of controlled exposure to light and darkness in the treatment of circadian sleep disorders. This work has important implications for the treatment of circadian rhythm sleep disorders such as Delayed Sleep Phase Syndrome, Shift Work Dyssomnia, and Rapid Time Zone Change (Jet-lag) Syndrome. The ability to rapidly reset circadian phase with bright light provides a means of correcting the misalignment of phase seen in these disorders. However, since individuals appear to vary in their sensitivity to light and since the efficacy of light seems to have a strong saturating response curve, careful quantification of these processes will be essential before practical therapies can be devised.
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