Department of Applied Mathematics and Statistics, Colorado School of Mines, Golden, CO, USA.
Sleep for Science Research Laboratory, Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA.
J Biol Rhythms. 2017 Oct;32(5):485-498. doi: 10.1177/0748730417730488. Epub 2017 Sep 27.
The human circadian system regulates internal 24-h rhythmicity and plays an important role in many aspects of human health and behavior. To investigate properties of the human circadian pacemaker such as intrinsic period and light sensitivity, experimental researchers have developed forced desynchrony (FD) protocols in which manipulations of the light-dark (LD) cycle are used to desynchronize the intrinsic circadian rhythm from the rest-activity cycle. FD protocols have typically been based on exposure to long LD cycles, but recently, ultradian FD protocols with short LD cycles have been proposed as a new methodology for assessing intrinsic circadian period. However, the effects of ultradian FD protocol design, including light intensity or study duration, on estimates of intrinsic circadian period have not, to our knowledge, been systematically studied. To address this gap, we applied a light-sensitive, dynamic mathematical model of the human circadian pacemaker to simulate ultradian FD protocols and analyze the effects of protocol design on estimates of intrinsic circadian period. We found that optimal estimates were obtained using protocols with low light intensities, at least 10 d of exposure to ultradian cycling, and a 7-h LD cycle duration that facilitated uniform light exposure across all circadian phases. Our results establish a theoretical framework for ultradian FD protocols that can be used to provide insights into data obtained under existing protocols and to optimize protocols for future experiments.
人类的生物钟系统调节着内部 24 小时的节律性，在人类健康和行为的许多方面都起着重要作用。为了研究人类生物钟的固有周期和光敏感性等特性，实验研究人员开发了强制不同步（FD）方案，通过改变光-暗（LD）周期来使内在的生物钟节律与休息-活动周期不同步。FD 方案通常基于长 LD 周期的暴露，但最近，具有短 LD 周期的超短 FD 方案已被提议作为评估内在生物钟周期的新方法。然而，据我们所知，超短 FD 方案设计的影响，包括光强度或研究持续时间，对内在生物钟周期的估计的影响尚未得到系统研究。为了解决这一差距，我们应用了一个光敏感的、动态的人类生物钟数学模型来模拟超短 FD 方案，并分析方案设计对内在生物钟周期估计的影响。我们发现，使用低光强度的方案、至少 10 天的超短周期暴露和 7 小时的 LD 周期持续时间，可以获得最佳的估计，这有利于在所有生物钟相位均匀地暴露在光线下。我们的结果为超短 FD 方案建立了一个理论框架，可以用来深入了解现有方案下获得的数据，并为未来的实验优化方案。
