Integration of brief light flashes varying in intensity and duration by the human circadian system

The melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are characterised by a delayed off-time following light offset. Here, we exploited this unusual physiologic property to characterise the exquisite sensitivity of the human circadian system to flashed light. In a 34-hour in-laboratory between-subjects design, we examined variable-intensity (3-9500 photopic lux; n=28 participants) full-field flashes at fixed duration (2 ms), and variable-duration (10 μ s-10 s) full-field flashes at fixed intensity (2000 photopic lux; n=31 participants) delivered using eye masks. We measured the circadian phase shift of the dim-light melatonin onset (DLMO) on the subsequent evening, acute melatonin suppression, objective alertness, and subjective sleepiness during the flash sequence. We find a clear dose-response relationship between flash intensity and the induced circadian phase shift, with an approximate increase of 10 minutes of phase delay for each ten-fold increase in photopic illuminance, but no parametric relationship between flash duration and induced circadian phase shift.