Combination of Light and Melatonin Time Cues for Phase Advancing the Human Circadian Clock (original) (raw)
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Combination of Light and Melatonin Time Cues for Phase Advancing the Human Cirdadian Clock
Phase Advancing with Bright Light and Melatonin-Burke et al The mammalian master circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. 1,2 The SCN provides environmental and biological timing information to the rest of the body so that physiology and behavior are coordinated for optimal functioning relative to the time of day. The SCN receives input about environmental time through photic pathways via rod, cone, and melanopsin photoreceptors in the retina. 5,6 The SCN also receives input about behavioral and physiological states through non-photic pathways (e.g., serotonergic input from the raphe nucleus). 7-10 Misalignment between environmental time and internal biological timing (e.g., shift work, jet lag, circadian sleep-wakefulness disorders) can result in adverse psychological, neurobehavioral, and physiological consequences. 11-16 Photic and non-photic stimuli have both been used to phase shift the human circadian clock; however, there is limited information about how combinations of phase-shifting stimuli influence the timing of the circadian clock in humans. Findings from research in non-humans suggest the combination of photic and non-photic stimuli interact to increase or attenuate the magnitude of circadian phase shifts 17-21 and contribute to
The internal circadian clock and sleep-wake homeostasis regulate and organize human brain function, physiology and behavior so that wakefulness and its associated functions are optimal during the solar day and that sleep and its related functions are optimal at night. The maintenance of a normal phase relationship between the internal circadian clock, sleep-wake homeostasis and the light-dark cycle is crucial for nominal neurobehavioral and physiological function in humans. Here we show that the phase relationship between these factors -the phase angle of entrainment (ψ)-is strongly determined by the intrinsic period (τ) of the master circadian clock located in the suprachiasmatic nucleus of the hypothalamus and the strength of the circadian synchronizer. Melatonin was used as a marker of internal biological time and circadian period was estimated during a forced desynchrony protocol. We observed relationships between the phase angle of entrainment and intrinsic period after exposure to scheduled habitual wakefulness-sleep light-dark cycle conditions inside and outside of the laboratory. Individuals with shorter circadian periods initiated sleep and awakened at a later biological time than individuals with longer circadian periods. We also observed that light exposure history influenced the phase angle of entrainment such that phase angle was later following exposure to a moderate bright light (~450 lux)-dark wakefulness-sleep schedule for 5 days than exposure to a normal indoor daytime level of light (~150 lux)-dark wakefulness-sleep schedule for 2 days. These findings demonstrate that neurobiological and environmental factors interact to regulate the phase angle of entrainment in humans. This finding has important implications for understanding physiological organization by the brain's master circadian clock and may have implications for understanding mechanisms underlying circadian sleep disorders.
Temporal dynamics of late-night photic stimulation of the human circadian timing system
AJP: Regulatory, Integrative and Comparative Physiology, 2005
The light-dark cycle is the primary synchronizing factor that keeps the internal circadian pacemaker appropriately aligned with the environmental 24-h day. Although it is known that ocular light exposure can effectively shift the human circadian pacemaker and do so in an intensity-dependent manner, the curve that describes the relationship between light intensity and pacemaker response has not been fully characterized for light exposure in the late biological night. We exposed subjects to 3 consecutive days of 5 h of experimental light, centered 1.5 h after the timing of the fitted minimum of core body temperature, and show that such light can phase advance shift the human circadian pacemaker in an intensity-dependent manner, with a logistic model best describing the relationship between light intensity and phase shift. A similar sigmoidal relationship is also observed between light intensity and the suppression of plasma melatonin concentrations that occurs during the experimental ...
Journal of Biological Rhythms, 2005
The internal circadian clock and sleep-wake homeostasis regulate and organize human brain function, physiology and behavior so that wakefulness and its associated functions are optimal during the solar day and that sleep and its related functions are optimal at night. The maintenance of a normal phase relationship between the internal circadian clock, sleep-wake homeostasis and the light-dark cycle is crucial for nominal neurobehavioral and physiological function in humans. Here we show that the phase relationship between these factors -the phase angle of entrainment (ψ)-is strongly determined by the intrinsic period (τ) of the master circadian clock located in the suprachiasmatic nucleus of the hypothalamus and the strength of the circadian synchronizer. Melatonin was used as a marker of internal biological time and circadian period was estimated during a forced desynchrony protocol. We observed relationships between the phase angle of entrainment and intrinsic period after exposure to scheduled habitual wakefulness-sleep light-dark cycle conditions inside and outside of the laboratory. Individuals with shorter circadian periods initiated sleep and awakened at a later biological time than individuals with longer circadian periods. We also observed that light exposure history influenced the phase angle of entrainment such that phase angle was later following exposure to a moderate bright light (~450 lux)-dark wakefulness-sleep schedule for 5 days than exposure to a normal indoor daytime level of light (~150 lux)-dark wakefulness-sleep schedule for 2 days. These findings demonstrate that neurobiological and environmental factors interact to regulate the phase angle of entrainment in humans. This finding has important implications for understanding physiological organization by the brain's master circadian clock and may have implications for understanding mechanisms underlying circadian sleep disorders.
Human circadian rhythms: physiological and therapeutic relevance of light and melatonin
Annals of Clinical Biochemistry: International Journal of Laboratory Medicine, 2006
Ocular light plays a key role in human physiology by transmitting time of day information. The production of the pineal gland hormone melatonin is under the control of the light-dark cycle. Its profile of secretion defines biological night and it has been called the 'darkness hormone'. Light mediates a number of non-visual responses, such as phase shifting the internal circadian clock, increasing alertness, heart rate and pupil constriction. Both exogenous melatonin and light, if appropriately timed, can phase shift the human circadian system. These 'chronobiotic' effects of light and melatonin have been used successfully to alleviate and correct circadian rhythm disorders, such as those experienced following travel across time zones, in night shift work and in circadian sleep disorders. The effectiveness of melatonin and light are currently being optimized in terms of time of administration, light intensity, duration and wavelength, and melatonin dose and formulatio...
Light, circadian and circannual rhythms
Organisms use circadian and circannual rhythms in cells or cell complexes for time measurements, thus the term biological clocks. Properties and models of biological clocks are discussed. In mammals, the biological clock system perceives light signals via the retina. Signals are then led to the suprachiasmatic nucleus (SCN) of the brain, functioning as the central clock region. Via pathways – involving the pineal organ and its production of the 'sleep' hormone melatonin – the rhythmic signals from the SCN affect body cells, hormone balances etc. Light strongly affects the circadian rhythms and also circannual and seasonal phenomena. Light can trigger the SCN and cause phase shifts of the circadian rhythms. The rhythms can be used by organisms to measure day/night length and control processes that should start at specific times of the year (photoperiodic control). Health effects might be expected when the clock system has deficiencies. Clinical effects of malfunctioning circadian light perception and of defect functions of the circadian system are discussed. Rhythm disturbances can result, for example, in sleep disorders and in depressive syndromes, and are connected with forms of cancer etc. Therapeutic effects of light treatment are reported. So-called Seasonal Affective Disorders (SAD) are reported to be light dependent and light treatment successful in several cases. Light induced rhythm disturbances also occur due to shift-work or jet travels over time zones.
American journal of physiology. Regulatory, integrative and comparative physiology, 2014
Our previous study demonstrated that physical exercise under dim lights (<10 lux) accelerated reentrainment of the sleep-wake cycle but not the circadian melatonin rhythm to an 8-h phase-advanced sleep schedule, indicating differential effects of physical exercise on the human circadian system. The present study examined the effects of bright light (>5,000 lux) on exercise-induced acceleration of reentrainment because timed bright lights are known to reset the circadian pacemaker. Fifteen male subjects spent 12 days in temporal isolation. The sleep schedule was advanced from habitual sleep times by 8 h for 4 days, which was followed by a free-run session. In the shift session, bright lights were given during the waking time. Subjects in the exercise group performed 2-h bicycle running twice a day. Subjects in the control kept quiet. As a result, the sleep-wake cycle was fully entrained by the shift schedule in both groups. Bright light may strengthen the resetting potency of t...
Functional decoupling of melatonin suppression and circadian phase resetting in humans
The Journal of Physiology, 2018
Key points There is assumed to be a monotonic association between melatonin suppression and circadian phase resetting induced by light exposure. We tested the association between melatonin suppression and phase resetting in humans. Sixteen young healthy participants received nocturnal bright light (∼9500 lux) exposure of continuous or intermittent patterns, and different durations ranging from 12 min to 6.5 h. Intermittent exposure patterns showed significant phase shifts with disproportionately less melatonin suppression. Each and every bright light stimulus in an intermittent exposure pattern induced a similar degree of melatonin suppression, but did not appear to cause an equal magnitude of phase shift. These results suggest that phase shifts and melatonin suppression are functionally independent such that one cannot be used as a proxy measure of the other. Continuous experimental light exposures show that, in general, the conditions that produce greater melatonin suppression als...