Duration invariance and intensity dependence of the human circadian system phase shifting response to brief light flashes

The melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are characterized by a delayed off-time following the cessation of light stimulation. Here, we exploited this unusual physiologic property to characterize the exquisite sensitivity of the human circadian system to flashed light. In a 34 h in-laboratory between-subjects design, we examined phase shifting in response to variable-intensity (3-9500 photopic lux) flashes at fixed duration (2 ms; = 28 participants) and variable-duration (10 µs-10 s) flashes at fixed intensity (2000 photopic lux; = 31 participants). Acute melatonin suppression, objective alertness and subjective sleepiness during the flash sequence were also assessed. We find a dose-response relationship between flash intensity and circadian phase shift, with an indication of a possible threshold-like behaviour. We find a slight parametric relationship between flash duration and circadian phase shift. Consistent with prior studies, we observe no dose-response relationship to either flash intensity or duration and the acute impact of light on melatonin suppression, objective alertness or subjective sleepiness. Our findings are consistent with circadian responses to a sequence of flashes being mediated by rod or cone photoreceptors via ipRGC integration.