Effects of calibrated blue-yellow (–S+[L+M], +S–[L+M]) changes in light on the human circadian clock [ Registered Report Stage 1 Protocol]

Exposure to light in the evening and at night can profoundly affect human circadian rhythms and sleep-wake physiology. These effects are mediated by a pathway connecting the layer of nerve cells in the back our eye – the retina – to the suprachiasmatic nucleus, the circadian pacemaker in the hypothalamus. Signals originating in the so-called intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin control this pathway to a large extent. However, there is converging evidence from animal (rodent and primate) and human studies that the cones in the retina may also contribute to light-mediated effects on circadian physiology, specifically along the blue-yellow dimension of colour vision, corresponding to the colour-opponent channel pitting signals from the S-cones against luminance (reflecting a joint L and M signal). Here, we will confirm that calibrated silent-substitution changes along this +S–(L+M) dimension affect the human circadian system in a direct test. In a repeated 32.5-hour within-subjects laboratory protocol, we will expose participants to calibrated lighting scenarios during the night. During this 1-h light exposure we will apply the following light scenarios: (1) constant background light (100 lux), holding the excitation of the L, M, S-cones and melanopsin constant, (2) intermittently flickering light (1 Hz; 30 seconds on, 30 seconds off) along the blue-dim (+S–[L+M]) with no change in melanopsin excitation, or (3) intermittently flickering light (1 Hz; 30 seconds on, 30 seconds off) along the yellow-bright (–S+[L+M]) dimension with no change in melanopsin excitation. Specifically, we hypothesize that (1) flickering changes induce greater circadian phase shifts than constant background light and (2) yellow-bright flickering changes induce stronger circadian phase shifts than blue-dim flickering changes. Additionally, we will also examine a set of ringfenced secondary analyses regarding acute melatonin suppression, subjective and objective sleepiness, visual comfort, psychomotor vigilance, sleep onset latency and slow-wave activity during sleep. Our work will directly inform the fundamental biological question which photoreceptors and mechanisms of colour vision in the retina influence circadian and sleep-wake physiology. Last, this will also enable the prediction of the physiological effects of light in real-life contexts such as the effects of artificial screen light in the evening.

Item: Stage 1 Registered Report protocol