Entrainment of the human circadian pacemaker to longer-than-24-h days

Abstract

Entrainment of the circadian pacemaker to the light:dark cycle is necessary for rhythmic physiological functions to be appropriately timed over the 24-h day. Nonentrainment results in sleep, endocrine, and neurobehavioral impairments. Exposures to intermittent bright light pulses have been reported to phase shift the circadian pacemaker with great efficacy. Therefore, we tested the hypothesis that a modulated light exposure (MLE) with bright light pulses in the evening would entrain subjects to a light:dark cycle 1 h longer than their own circadian period (tau). Twelve subjects underwent a 65-day inpatient study. Individual subject's circadian period was determined in a forced desynchrony protocol. Subsequently, subjects were released into 30 longer-than-24-h days (daylength of tau + 1 h) in one of three light:dark conditions: (i) approximately 25 lux; (ii) approximately 100 lux; and (iii) MLE: approximately 25 lux followed by approximately 100 lux, plus two 45-min bright light pulses of approximately 9,500 lux near the end of scheduled wakefulness. We found that lighting levels of approximately 25 lux were insufficient to entrain all subjects tested. Exposure to approximately 100 lux was sufficient to entrain subjects, although at a significantly wider phase angle compared with baseline. Exposure to MLE was able to entrain the subjects to the imposed sleep-wake cycles but at a phase angle comparable to baseline. These results suggest that MLE can be used to entrain the circadian pacemaker to non-24-h days. The implications of these findings are important because they could be used to treat circadian misalignment associated with space flight and circadian rhythm sleep disorders such as shift-work disorder.