After-Effects of Entrainment on Human Circadian Period

直到最近，人们才普遍认为人类昼夜节律起搏器的固有周期为25小时。然而，使用基于实验室的“强迫desperdy”协议，其中控制了光和活动对昼夜节律周期评估的混杂影响，我们发现昼夜节律系统的固有周期接近24小时（平均24.18小时）。 类似地，我们已经发现，生活在社会中的无光感（NPL）盲人具有褪黑激素的昼夜节律，其以平均约24.5小时的周期自由运行。 虽然这些数据也表明，固有的昼夜节律周期比以前认为的更接近24小时，但盲人和视力正常的受试者之间的差异表明，昼夜节律起搏器可能受到不明因素的影响。 一个可能的因素是在非夹带的盲人个体中不存在夹带到24小时光-暗循环的后效，因此，在从夹带释放时观察到的盲人个体可能具有比有视力的受试者更长的昼夜节律周期。 类似地，由于光同步器和非光同步器的后效的差异，社会中被非光时间线索夹带的盲人受试者在从夹带释放时可能不同于有视力和非夹带的盲人受试者。 我们建议通过评估盲人在野外和强制性despery条件下的昼夜节律，并将其与已经和将要研究的健康视力受试者进行比较，来研究夹带的后效作用。具体地说，我们将检验以下假设：1）NPL受试者的褪黑激素和温度节律的内源性昼夜节律周期显著长于有视力的受试者; 2）在非光时间线索不均匀分布的野外条件下观察到的NPL受试者的昼夜节律周期显著长于在受控的强迫性睡眠条件下评估时的昼夜节律周期; 3）那些被卷入社会但对光不敏感的NPL受试者将平均具有比那些不被卷入社会的NPL受试者显著更短的昼夜节律周期。 这项工作具有重要的意义，了解如何内在的周期与先前的夹带和夹带的后效的作用。 它将有助于确定非光同步器的夹带限制，并将评估这种时间线索治疗盲人和视力正常人群昼夜节律睡眠-觉醒障碍的疗效。

Until recently, it was widely believed that the intrinsic period of the human circadian pacemaker was 25 h. However, using a 'forced desynchrony' laboratory-based protocol in which the confounding effects of light and activity on circadian period assessment are controlled, we have found that the intrinsic period of the circadian system is close to 24 h (average 24.18 h). Similarly, we have found that blind individuals without light perception (NPL) living in society have circadian rhythms of melatonin which free-run with a period averaging approximately 24.5 h. While these data also suggest that the intrinsic circadian period is closer to 24 h than previously thought, the discrepancy between blind and sighted subjects suggests that the circadian pacemaker may be affected by unidentified factors. One likely factor is the absence of after- effects of entrainment to the 24 h light-dark cycle in non- entrained blind individuals, who may thus have a longer circadian period than sighted subjects observed upon release from entrainment. Similarly, blind subjects entrained by non-photic time cues in society may differ from sighted and non-entrained blind subjects upon release from entrainment due to differences in after-effects of photic- and non-photic synchronizers. We propose to investigate the role of after-effects of entrainment by assessing the circadian period of blind individuals under field and forced desynchrony conditions and comparing them to healthy sighted subjects who have been and will be studied. Specifically we will test the hypotheses that: 1) the endogenous circadian period of the melatonin and temperature rhythms is significantly longer in NPL subjects than sighted subjects; 2) the circadian period of NPL subjects observed in field conditions in which non-photic time cues are non-uniformly distributed is significantly longer than when assessed under controlled forced desynchrony conditions; 3) those NPL subjects who are entrained in society but who are insensitive to light will have, on average, a significantly shorter circadian period than those NPL subjects who are not entrained in society. This work has significant implications for understanding how intrinsic period relates to prior entrainment and the role of after-effects of entrainment. It will help define the limits of entrainment for non-photic synchronizers and will evaluate the efficacy of such time cues to treat circadian rhythm sleep-wake disorders in both the blind and sighted populations.