Disorders of the circadian system and/or misalignment of the circadian pacemaker with the timing of sleep and waking can adversely affect sleep onset duration, sleep quality and sleep episode duration. The light-dark cycle is the primary environmental stimulus for entraining circadian rhythms in most species, including humans. Previous work on this grant has demonstrated that the responsiveness of the human circadian pacemaker to light is within the wide range of sensitivity observed in lower organisms. Complete characterization of the relationship between stimulus strength, duration and timing, and the topology of circadian phase resetting by light in humans is critical to understanding how the human circadian pacemaker responds to environmental light exposure. Based upon preliminary data and progress supported by the present grant, 4 hypotheses addressing characteristics of light stimuli relevant to their resetting effects on the human pacemaker are proposed: 1) the magnitude of resetting to a bright light stimulus will vary as a function of stimulus duration; 2) a single short pulse of bright light will exhibit significant resetting that will be dependent on the circadian phase at which the stimulus is applied; 3) intermittent bright light stimuli will yield resetting effects that are greater than would be predicted from a simple summation of light-on time during the stimulus and will be dependent upon the light intensity; and 4) strong type 0 resetting can only be achieved with light intensities much greater than those sufficient to yield near-saturating type 1 phase resetting. To test these hypotheses, a series of experiments are proposed that will allow direct measurement of circadian phase both before and after exposure to an array of different light stimuli. The results of theses studies will lead to the development of model-derived recommendations for evaluation of potential clinical light treatments. This work has important implications for the treatment of circadian rhythm disorders, such as delayed-sleep phase syndrome, advanced-sleep phase syndrome, shift-work dyssomnia and jet-lag. Careful analysis of the effects of a single short exposure to bright light or of interrupted bright light episodes have important implications for the practical application of bright light treatment for circadian rhythm sleep disorders, since repetitive uninterrupted exposure to bright light for many hours and days is often not feasible in a clinical or occupational setting.
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