Within-subjects ultra-short sleep-wake protocol for characterising circadian variations in retinal function

• Published in: PloS one Vol. 20; no. 5; p. e0300405
• Main Authors: Heinrichs, Hannah Sophie, Spitschan, Manuel
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.05.2025; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Biology and Life Sciences; Circadian rhythm; Circadian Rhythm - physiology; Circadian rhythms; Contrast Sensitivity - physiology; Entrainment; Female; Humans; Hypothalamus; Hypotheses; Influence; Investigations; Irradiance; Light; Male; Medicine and Health Sciences; Melanopsin; Melatonin; Photic Stimulation; Photoreception; Photoreceptors; Physical Sciences; Physiological aspects; Physiology; Psychophysics; Pupil - physiology; Pupil size; Retina; Retina - physiology; Sleep; Sleep - physiology; Sleep and wakefulness; Sleep-wake cycle; Social Sciences; Stimuli; Study Protocol; Substitutes; Time of use; Variation; Visual effects; Visual perception; Wakefulness; Wakefulness - physiology; Young Adult; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0300405

Prior studies suggest that visual functions undergo time-of-day variations. Under naturalistic entrainment, diurnal changes in physiology may be driven by circadian and/or homeostatic processes, and repeated measurements at different times of day are thus not suitable to draw unambiguous conclusions about circadian effects on visual function. In this study, we disentangle circadian and homeostatic effects on variations of retinal function. We examine the earliest stages of image-forming (temporal contrast sensitivity of the post-receptoral channels) and non-image forming visual functions (pupillary light response) by employing a short forced-desynchrony multiple-naps protocol lasting 40 hours. Participants (n = 12, 50% female) will stay in a controlled time-isolating environment under dim-light conditions and adhere to an ultra-short sleep-wake cycle, alternating between 2h30m of wake time in dim light and hour of sleep in no light. During eleven intervals of wakefulness, participants will undergo psychophysical and pupillometric assessments with silent-substitution stimuli. We hypothesize that the sensitivity of retinal mechanisms undergoes circadian variations. This hypothesis will be investigated by separately determining psychophysical contrast thresholds to silent-substitution stimuli targeting the post-receptoral (consistency) pathways (isoluminant red-green, L–M; isoluminant blue-yellow, S; luminance, L+M+S). We will furthermore measure the pupillary light response to peripheral stimuli (annulus 10 ∘ –30 ∘ ) in comparison to the response to stimuli isolating or including melanopsin stimulation. All stimuli will be delivered at constant retinal irradiance using a Maxwellian view system or artificially restricting pupil size. Additionally, we will quantify and report effects of our test stimuli on the circadian system by comparing the dim light melatonin onset (DLMO) timing during two supplementary evening sessions, comparing dim-light conditions to such with experimental light exposure. Our work informs the fundamental biological mechanisms underlying the influence of light on the human circadian system. Based on our findings, current models about the sensitivity of the circadian system may need to be modified in order to account for the bidirectional influence of circadian function and photoreception.