A Phase Response Curve to Single Bright Light Pulses in Human Subjects

Abstract

The circadian pacemaker is differentially sensitive to the resetting effects of retinal light exposure, depending upon the circadian phase at which the light exposure occurs. Previously reported human phase response curves (PRCs) to single bright light exposures have employed small sample sizes, and were often based on relatively imprecise estimates of circadian phase and phase resetting. In the present study, 21 healthy, entrained subjects underwent pre‐ and post‐stimulus constant routines (CRs) in dim light (∼2–7 lx) with maintained wakefulness in a semi‐recumbent posture. The 6.7 h bright light exposure stimulus consisted of alternating 6 min fixed gaze (∼10 000 lx) and free gaze (∼5000–9000 lx) exposures. Light exposures were scheduled across the circadian cycle in different subjects so as to derive a PRC. Plasma melatonin was used to determine the phase of the onset, offset, and midpoint of the melatonin profiles during the CRs. Phase shifts were calculated as the difference in phase between the pre‐ and post‐stimulus CRs. The resultant PRC of the midpoint of the melatonin rhythm revealed a characteristic type 1 PRC with a significant peak‐to‐trough amplitude of 5.02 h. Phase delays occurred when the light stimulus was centred prior to the critical phase at the core body temperature minimum, phase advances occurred when the light stimulus was centred after the critical phase, and no phase shift occurred at the critical phase. During the subjective day, no prolonged ‘dead zone’ of photic insensitivity was apparent. Phase shifts derived using the melatonin onsets showed larger magnitudes than those derived from the melatonin offsets. These data provide a comprehensive characterization of the human PRC under highly controlled laboratory conditions.

Chronotype and environmental light exposure in a student population

“…The timing of light exposure has a differential effect upon circadian phase: early light exposure advances the cycle whilst light late in the internal day delays circadian phase (Czeisler et al 1989; Khalsa et al 2003). In our student population, we found that longer time spent outside the later chronotype, which would suggest that our population was exposed to more phase delaying evening light than phase advancing morning light.…”

“…The timing of light exposure has a differential effect upon circadian phase: early light exposure advances the cycle whilst light late in the internal day delays circadian phase (Czeisler et al 1989; Khalsa et al 2003). Thus, exposure to bright artificial light in the evening before bedtime has been associated with a delay in circadian phase, as assessed by measures of subjective chronotype (Martin et al 2012; Vollmer et al 2012), subjective sleep timing (Koo et al 2016), salivary melatonin levels (Gordijn et al 1999; Benloucif et al 2008; Cajochen et al 2011) and core body temperature (Krauchi et al 1997).…”

What Keeps Us Awake?—the Role of Clocks and Hourglasses, Light, and Melatonin

“…Similarly in other situations, such as rapidly rotating shifts and the normal office environment, it is more appealing to time light exposures toward improving alertness without phase shifting (Horowitz and Tanigawa, 2002). However, given that there is no dead zone for phase shifting the circadian system in humans (Khalsa et al, 2003), it is not conceivable to enhance alertness with light without affecting circadian phase. Thus, a "compromise" circadian phase position for permanent night-shift work in which the sleepiest circadian time is delayed out of the night work period and into the first half of the day sleep episode would seem a feasible alternative (Smith et al, 2009).…”

“…In contrast to the intensity dose-response relationships of light and the circadian system and alertness, very little is known about the duration dependence of the circadian resetting responses to light. However, in analyses of the human phase-response curve ("response to light"), maximum phase shifts to 1 h of bright white light (~10,000 lux) were about 40% as effective as phase shifts measured in response to 6.5 h of white light (~10,000 lux), despite representing only 15% of the stimulus strength (1 h/6.5 h) (Khalsa et al, 2003). Exposure to intermittent light also seems to be highly effective at resetting the human circadian system.…”

Genetics of Human Sleep Behavioral Phenotypes

“…Furthermore, entrainment is known to shift the intrinsic clock, depending on the time of day the entrainment cue (zeitgeber) is given (Khalsa, Jewett, Cajochen, & Czeisler, 2003). In the case of FASP, the possible involvement of light, the most important and pervasive environmental cue, has to be considered (Munch & Bromundt, 2012).…”