A phase response curve to single bright light pulses in human subjects

• Published in: The Journal of physiology Vol. 549; no. 3; pp. 945 - 952
• Main Authors: Khalsa, Sat Bir S., Jewett, Megan E., Cajochen, Christian, Czeisler, Charles A.
• Format: Journal Article
• Language: English
• Published: Legacy CDMS The Physiological Society 15.06.2003; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Adult; Body Temperature; Circadian Rhythm - radiation effects; Female; Humans; Life Sciences (General); Male; Melatonin - blood; Melatonin - urine; Original; Photic Stimulation; Photoperiod; Support, U.s. Gov't, Non-P.h.s; Human; Support, Non-U.s. Gov't; Clinical Trial; Support, U.s. Gov't, P.h.s; Non-Nasa Center; Male; Circadian Rhythm/radiation Effects; Photoperiod; Randomized Controlled Trial; Body Temperature; Melatonin/blood/urine; Nasa Program Biomedical Research And Countermeasures; Nasa Discipline Regulatory Physiology; Adult; Female; Photic Stimulation; NASA Program Biomedical Research and Countermeasures; NASA Discipline Regulatory Physiology; Non-NASA Center
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2003.040477

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.