LAUSR

The human circadian clock is synchronized to the outside world through regular ocular light exposure. Light does not need to be continuous to be an effective time cue. Light administered as a sequence of light flashes can be more effective than continuous light of the same illuminance. Exposure to a sequence of light flashes while awake is annoying, but such exposure can occur during sleep, without disrupting sleep, when the circadian system is most sensitive to light. As such, the purpose of this experiment was to determine the magnitude of circadian phase shift that could be obtained when exposing individuals to light flash sequences during sleep. Healthy young individuals (n=10) participated in a crossover study of two separate 16-d protocols, the order of which was randomized. The first 14 d were an at-home circadian phase/amplitude optimization period, followed by a 37-h in-laboratory stay during which participants had constant routines (CR) on two consecutive evenings. The onset of salivary melatonin determined during the CRs was used as a marker of circadian phase. Light was dim (< 5 lux) or dark between CRs, except for the light flashes (2-ms flashes, ~1500 lux, every 15 s for 1 h) that were administered via custom goggles while participants slept (starting 30 m after habitual bedtime). During the placebo condition, the goggles provided no light. The impact of the light on circadian phase (pre-post) and polysomnographically-measured sleep were assessed. As compared to the control condition (12±20 minutes), exposure to the flashes engendered substantial shifts (1.13±1.27 h, p< 0.01; d=1.02). There was considerable variability in response to the stimulus, with two individuals not displaying any phase changes, three having a modest phase change (< 1 hour), two having a moderate phase change (1-2 hours) and two having a large phase shift (>2 hours), one of whom shifted more than 6 hours. There were no significant differences in sleep on placebo or flash exposure nights. Exposure to a sequence of light flashes during sleep has the capacity to engender large changes in circadian timing without necessitating behavior changes during wake to receive phototherapy. Department of Defense (W81XWH-16-1-0223)