AbstractThe human circadian system is exquisitely sensitive to light, through a pathway connecting the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) to the hypothalamic suprachiasmatic nuclei (SCN). ipRGCs are characterised by a delayed off-time following cessation of light exposure; we exploited this unusual physiologic property and examined how a sequence of flashes of bright light differing in intensity or duration presented in the biological night could delay the human circadian clock in vivo in healthy young participants (n=54). To understand the mechanism underlying circadian photoreception, we probed temporal integration by manipulating flash intensity and duration independently. In a 34-hour in-laboratory between-subjects design, we examined variable-intensity (3, 30, 95, 300, 950, 3000, or 9500 photopic lux; n=28 participants) flashes at fixed duration (2 ms), and variable-duration (10 μs, 100 μs, 1 ms, 10 ms, 100 ms, 1 sec, 10 sec) flashes at fixed intensity (2000 photopic lux; n=31 participants). We measured the phase shift of dim-light melatonin onset on the subsequent evening, and acute melatonin suppression and alertness during the flash sequence. In the variable-intensity study, we find a clear sigmoidal dose-response relationship for flash intensity and the induced circadian phase shift. In the variable-duration study, we find no parametric relationship between flash duration and induced circadian phase shift, indicating a relative insensitivity of the circadian system to flashes varying in duration. As the intermittent periods of darkness in our stimulation paradigm supports the recovery of extrinsic rod-cone signalling into the ipRGCs, our results strongly suggest rod-cone contributions into circadian photoreception.
Comment Concerning the Effects of Light Intensity on Melatonin Suppression in the Review “Light Modulation of Human Clocks, Wake, and Sleep” by A. Prayag et al.