Measurement devices.
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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.
既往研究表明,视觉功能存在日间节律变化。在自然节律同步(naturalistic entrainment)条件下,生理的日间变化可能由昼夜节律(circadian)和/或稳态(homeostatic)过程驱动,因此在一天中不同时段重复测量,无法明确得出昼夜节律对视觉功能影响的结论。本研究旨在厘清昼夜节律与稳态过程对视网膜功能变化的独立影响。 本研究采用时长40小时的短时强制去同步多小睡实验方案,探究成像视觉(感受器后通路的时间对比敏感度)与非成像视觉功能(瞳孔光反射)的早期阶段。受试者共12名,男女各占50%,将在受控的时间隔离环境与弱光条件下,遵循超短睡眠-觉醒周期:即弱光下保持2小时30分钟清醒,随后在全黑环境中睡眠1小时,循环往复。在11个清醒时段内,受试者将接受基于静默替代刺激(silent-substitution stimuli)的心理物理学与瞳孔测量评估。 我们提出假设:视网膜机制的敏感度存在昼夜节律变化。本研究将通过分别测定针对不同感受器后(一致性)通路的静默替代刺激的心理物理学对比阈值,验证该假设,这些通路包括:等亮度红-绿通道(L–M)、等亮度蓝-黄通道(S)以及亮度通道(L+M+S)。此外,本研究还将测量外周刺激(10°–30°环形视野)引发的瞳孔光反射,并与仅激活或包含黑视蛋白(melanopsin)激活的刺激引发的反射进行对比。所有刺激均将通过马克斯韦尔视野系统(Maxwellian view system),以恒定的视网膜辐照度呈现,或通过人工限制瞳孔大小实现。 此外,本研究还将通过对比两次补充晚间实验中的弱光褪黑素起始(dim light melatonin onset, DLMO)时间,即分别对比弱光条件与实验性光照暴露条件下的DLMO,量化并报告测试刺激对昼夜节律系统的影响。本研究旨在阐明光线影响人类昼夜节律系统的核心生物学机制。基于本研究结果,当前关于昼夜节律系统敏感度的模型或需修正,以纳入昼夜节律功能与光感受之间的双向影响。




