Optimizing Light Flash Sequence Duration to Shift Human Circadian Phase

SIMPLE SUMMARY: Information about light exposure patterns is integrated across time and space in retinal circuits before being passed to downstream hypothalamic targets, including the circadian pacemaker in the suprachiasmatic nuclei. In multiple mammalian species, these circuits can integrate brief flashes of light such that the effective impact on the circadian pacemaker is greater than that of continuous light of similar intensity. Using a series of 16-d studies combining outpatient behavioral manipulation and in-laboratory intensive physiologic monitoring, we examined the impact of different durations of light flash sequences on the timing of the human circadian pacemaker. We find that 15 min of light flashes engenders a similar effect on the timing of the human circadian pacemaker as light flashes given for 3.5 h. Our study indicates that the impact of a sequence of light flashes occurs within the first 15 min of exposure, and the retinohypothalamic circuit responsible for shifting the timing of the circadian pacemaker is refractory to further stimulation. These data are important for both the understanding of retinohypothalamic circuitry and the design of robust light interventions meant to change circadian timing during sleep, as would be used in the treatment of circadian rhythm sleep disorders. ABSTRACT: Unlike light input for forming images, non-image-forming retinal pathways are optimized to convey information about the total light environment, integrating this information over time and space. In a variety of species, discontinuous light sequences (flashes) can be effective stimuli, notably impacting circadian entrainment. In this study, we examined the extent to which this temporal integration can occur. A group of healthy, young (n = 20) individuals took part in a series of 16-day protocols in which we examined the impact of different lengths of light flash sequences on circadian timing. We find a significant phase change of −0.70 h in response to flashes that did not differ by duration; a 15-min sequence could engender as much change in circadian timing as 3.5-h sequences. Acute suppression of melatonin was also observed during short (15-min) exposures, but not in exposures over one hour in length. Our data are consistent with the theory that responses to light flashes are mediated by the extrinsic, rod/cone pathway, and saturate the response of this pathway within 15 min. Further excitation leads to no greater change in circadian timing and an inability to acutely suppress melatonin, indicating that this pathway may be in a refractory state following this brief light stimulation.