Human circadian pacemaker is sensitive to light throughout subjective day without evidence of transients

1997 ◽  
Vol 273 (5) ◽  
pp. R1800-R1809 ◽  
Author(s):  
Megan E. Jewett ◽  
David W. Rimmer ◽  
Jeanne F. Duffy ◽  
Elizabeth B. Klerman ◽  
Richard E. Kronauer ◽  
...  
Keyword(s):  
Steady State ◽  
Response Curve ◽  
Phase Response Curve ◽  
Light Exposure ◽  
Light Stimulus ◽  
Dead Zone ◽  
Bright Light ◽  
Temperature Minimum ◽  
Circadian Pacemaker ◽  
Dim Light

Fifty-six resetting trials were conducted across the subjective day in 43 young men using a three-cycle bright-light (∼10,000 lx) stimulus against a background of very dim light (10–15 lx). The phase-response curve (PRC) to these trials was assessed for the presence of a “dead zone” of photic insensitivity and was compared with another three-cycle PRC that had used a background of ∼150 lx. To assess possible transients after the light stimulus, the trials were divided into 43 steady-state trials, which occurred after several baseline days, and 13 consecutive trials, which occurred immediately after a previous resetting trial. We found that 1) bright light induces phase shifts throughout subjective day with no apparent dead zone; 2) there is no evidence of transients in constant routine assessments of the fitted temperature minimum 1–2 days after completion of the resetting stimulus; and 3) the timing of background room light modulates the resetting response to bright light. These data indicate that the human circadian pacemaker is sensitive to light at virtually all circadian phases, implying that the entire 24-h pattern of light exposure contributes to entrainment.

scholarly journals An Exploration of the Temporal Dynamics of Circadian Resetting Responses to Short- and Long-Duration Light Exposures: Cross-Species Consistencies and Differences

2019 ◽  
Vol 34 (5) ◽  
pp. 497-514 ◽  
Author(s):  
Richard E. Kronauer ◽  
Melissa A. St. Hilaire ◽  
Shadab A. Rahman ◽  
Charles A. Czeisler ◽  
Elizabeth B. Klerman
Keyword(s):  
Temporal Dynamics ◽  
Light Exposure ◽  
Light Stimulus ◽  
Dead Zone ◽  
Mammalian Species ◽  
Circadian System ◽  
Circadian Pacemaker ◽  
Long Duration ◽  
Light Duration ◽  
Multiple Species

Light is the most effective environmental stimulus for shifting the mammalian circadian pacemaker. Numerous studies have been conducted across multiple species to delineate wavelength, intensity, duration, and timing contributions to the response of the circadian pacemaker to light. Recent studies have revealed a surprising sensitivity of the human circadian pacemaker to short pulses of light. Such responses have challenged photon counting–based theories of the temporal dynamics of the mammalian circadian system to both short- and long-duration light stimuli. Here, we collate published light exposure data from multiple species, including gerbil, hamster, mouse, and human, to investigate these temporal dynamics and explore how the circadian system integrates light information at both short- and long-duration time scales to produce phase shifts. Based on our investigation of these data sets, we propose 3 new interpretations: (1) intensity and duration are independent factors of total phase shift magnitude, (2) the possibility of a linear/log temporal function of light duration that is universal for all intensities for durations less than approximately 12 min, and (3) a potential universal minimum light duration of ~0.7 sec that describes a “dead zone” of light stimulus. We show that these properties appear to be consistent across mammalian species. These interpretations, if confirmed by further experiments, have important practical implications in terms of understanding the underlying physiology and for the design of lighting regimens to reset the mammalian circadian pacemaker.

Dynamic resetting of the human circadian pacemaker by intermittent bright light

2000 ◽  
Vol 279 (5) ◽  
pp. R1574-R1579 ◽  
Author(s):  
David W. Rimmer ◽  
Diane B. Boivin ◽  
Theresa L. Shanahan ◽  
Richard E. Kronauer ◽  
Jeanne F. Duffy ◽  
...  
Keyword(s):  
Time Course ◽  
Light Exposure ◽  
Light Stimulus ◽  
Experimental Studies ◽  
Bright Light ◽  
Circadian Pacemaker ◽  
Stimulus Exposure ◽  
Enhanced Sensitivity ◽  
Lighting Conditions ◽  
Bright Light Exposure

In humans, experimental studies of circadian resetting typically have been limited to lengthy episodes of exposure to continuous bright light. To evaluate the time course of the human endogenous circadian pacemaker's resetting response to brief episodes of intermittent bright light, we studied 16 subjects assigned to one of two intermittent lighting conditions in which the subjects were presented with intermittent episodes of bright-light exposure at 25- or 90-min intervals. The effective duration of bright-light exposure was 31% or 63% compared with a continuous 5-h bright-light stimulus. Exposure to intermittent bright light elicited almost as great a resetting response compared with 5 h of continuous bright light. We conclude that exposure to intermittent bright light produces robust phase shifts of the endogenous circadian pacemaker. Furthermore, these results demonstrate that humans, like other species, exhibit an enhanced sensitivity to the initial minutes of bright-light exposure.

scholarly journals Efficacy of a single sequence of intermittent bright light pulses for delaying circadian phase in humans

2004 ◽  
Vol 287 (1) ◽  
pp. E174-E181 ◽  
Author(s):  
Claude Gronfier ◽  
Kenneth P. Wright ◽  
Richard E. Kronauer ◽  
Megan E. Jewett ◽  
Charles A. Czeisler
Keyword(s):  
Phase Shift ◽  
Light Exposure ◽  
Core Body Temperature ◽  
Bright Light ◽  
Phase Delay ◽  
Continuous Exposure ◽  
Circadian Pacemaker ◽  
Light Pulses ◽  
Dim Light ◽  
Single Sequence

It has been shown in animal studies that exposure to brief pulses of bright light can phase shift the circadian pacemaker and that the resetting action of light is most efficient during the first minutes of light exposure. In humans, multiple consecutive days of exposure to brief bright light pulses have been shown to phase shift the circadian pacemaker. The aim of the present study was to determine whether a single sequence of brief bright light pulses administered during the early biological night would phase delay the human circadian pacemaker. Twenty-one healthy young subjects underwent a 6.5-h light exposure session in one of three randomly assigned conditions: 1) continuous bright light of ∼9,500 lux, 2) intermittent bright light (six 15-min bright light pulses of ∼9,500 lux separated by 60 min of very dim light of <1 lux), and 3) continuous very dim light of <1 lux. Twenty subjects were included in the analysis. Core body temperature (CBT) and melatonin were used as phase markers of the circadian pacemaker. Phase delays of CBT and melatonin rhythms in response to intermittent bright light pulses were comparable to those measured after continuous bright light exposure, even though the total exposure to the intermittent bright light represented only 23% of the 6.5-h continuous exposure. These results demonstrate that a single sequence of intermittent bright light pulses can phase delay the human circadian pacemaker and show that intermittent pulses have a greater resetting efficacy on a per minute basis than does continuous exposure.

Effects of a two-hour early awakening and of bright light exposure on plasma patterns of cortisol, melatonin, prolactin and testosterone in man

1992 ◽  
Vol 126 (3) ◽  
pp. 201-205 ◽  
Author(s):  
Y Touitou ◽  
O Benoit ◽  
J Foret ◽  
A Aguirre ◽  
A Bogdan ◽  
...  
Keyword(s):  
Light Exposure ◽  
Light Stimulus ◽  
Bright Light ◽  
Male Students ◽  
Plasma Testosterone ◽  
Melatonin Concentration ◽  
Sleep Schedule ◽  
Dim Light ◽  
Bright Light Exposure ◽  
Neuroendocrine Functions

Bright light is a synchronizing agent that entrains human circadian rhythms and modifies various endocrine and neuroendocrine functions. The aim of the present study was to determine whether and how the exposure to a bright light stimulus during the 2 h following a 2 h earlier awakening could modify the disturbance induced by the the sleep deprivation on the plasma pattens of hormones whose secretion is sensitive to light and/or sleep, namely melatonin, prolactin, cortisol and testosterone. Six healthy and synchronized (lights on: 07.00–23.00) male students (22.5±1.1 years) with normal psychological profiles volunteered for the study in winter. The protocol consisted of a baseline control night (customary sleep schedule) followed by three shortened nights with a rising at 05.00 and a 2 h exposure to either dim light (50 lux; one week) or bright light (2000 lux: other week). Our study showed a phase advance of the circadian rhythm of plasma cortisol without significant modifications of the hormone mean or peak concentration. Plasma melatonin concentration decreased following bright light exposure, whereas no obvious modifications of plasma testosterone or prolactin patterns could be observed in this protocol.

Nonphotic entrainment of the human circadian pacemaker

1998 ◽  
Vol 274 (4) ◽  
pp. R991-R996 ◽  
Author(s):  
Elizabeth B. Klerman ◽  
David W. Rimmer ◽  
Derk-Jan Dijk ◽  
Richard E. Kronauer ◽  
Joseph F. Rizzo ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Light Exposure ◽  
Core Body Temperature ◽  
Biological Clock ◽  
Bright Light ◽  
Circadian Pacemaker ◽  
Temperature Rhythms ◽  
Blind Individuals ◽  
Nonphotic Entrainment ◽  
Core Body

In organisms as diverse as single-celled algae and humans, light is the primary stimulus mediating entrainment of the circadian biological clock. Reports that some totally blind individuals appear entrained to the 24-h day have suggested that nonphotic stimuli may also be effective circadian synchronizers in humans, although the nonphotic stimuli are probably comparatively weak synchronizers, because the circadian rhythms of many totally blind individuals “free run” even when they maintain a 24-h activity-rest schedule. To investigate entrainment by nonphotic synchronizers, we studied the endogenous circadian melatonin and core body temperature rhythms of 15 totally blind subjects who lacked conscious light perception and exhibited no suppression of plasma melatonin in response to ocular bright-light exposure. Nine of these fifteen blind individuals were able to maintain synchronization to the 24-h day, albeit often at an atypical phase angle of entrainment. Nonphotic stimuli also synchronized the endogenous circadian rhythms of a totally blind individual to a non-24-h schedule while living in constant near darkness. We conclude that nonphotic stimuli can entrain the human circadian pacemaker in some individuals lacking ocular circadian photoreception.

scholarly journals 111 Artificial Light-Triggered Sleep Deprivation May Lead to Allodynia in Rodent Model

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A45-A46
Author(s):  
Skyler Kanegi ◽  
Armen Akopian
Keyword(s):  
Sleep Deprivation ◽  
Light Exposure ◽  
Light Stimulus ◽  
Continuous Light ◽  
Artificial Light ◽  
Light Cycle ◽  
Tissue Samples ◽  
Mechanical Threshold ◽  
Dim Light ◽  
Von Frey Filaments

Abstract Introduction The combination of artificial light and lack of exposure to natural light can delay the circadian clock, dysregulate the circadian cycle, and decrease alertness upon waking. This effect has been especially significant during the COVID-19 pandemic, where overexposure to artificial light at improper hours has contributed to increased rates of clinical insomnia. Artificial light may also contribute to concomitant neurological conditions such as primary headache, but the mechanisms by which light triggers sleep deprivation-induced headache are not well-understood. Methods To measure pain sensitivity, we habituated 13 wild-type male mice to von Frey filaments applied to the periorbital area until there was no response to 0.6g stimulus. We then applied 5 lux of continuous dim light to mice during their usual 12-hour dark cycle. The 12-hour light cycle remained unchanged with 200 lux continuous light. Three groups of mice experienced the dim light stimulus for one, three, or five consecutive days. Ambulation and rest activity were measured using SOF-812 Activity Monitor machines. After the experiment concluded, we waited 24 hours and measured mechanical threshold using von Frey filaments at 1, 3, 5, 8, and every 3 days subsequently until mice no longer responded to 0.6g stimulus. Results Artificial light triggered changes in circadian behavior including increased number of rest periods during 12-hour dark (dim light) cycle and shortened sleep duration during 12-hour light cycle. Following the artificial light stimulus, there was a significant decrease in mechanical threshold (P&lt;0.05), representing allodynia. The one-day group displayed one day of significant allodynia. The three-day group displayed three days of significant allodynia. The five-day group displayed five days of significant allodynia. Conclusion Artificial light may trigger circadian dysregulation, and the duration of artificial light exposure seemed to be directly correlated to the duration of allodynia up to one week after the stimulus was removed. We will repeat these experiments and analyze CNS and PNS tissue samples to understand the underlying physiological and biochemical bases of how artificial light triggers sleep deprivation-induced headache. This knowledge could increase our understanding of the pathophysiology and comorbidity of sleep deprivation and headache. Support (if any) Funding was received from the National Institute of Health (NS104200).

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

2003 ◽  
Vol 549 (3) ◽  
pp. 945-952 ◽  
Author(s):  
Sat Bir S. Khalsa ◽  
Megan E. Jewett ◽  
Christian Cajochen ◽  
Charles A. Czeisler
Keyword(s):  
Response Curve ◽  
Phase Response Curve ◽  
Human Subjects ◽  
Bright Light ◽  
Phase Response ◽  
Light Pulses

Contemporaneous melatonin administration modifies the circadian response to nocturnal bright light stimuli

1997 ◽  
Vol 272 (2) ◽  
pp. R482-R486 ◽  
Author(s):  
A. Cagnacci ◽  
R. Soldani ◽  
S. S. Yen
Keyword(s):  
Light Exposure ◽  
Light Stimulus ◽  
Core Body Temperature ◽  
Bright Light ◽  
Phase Shifts ◽  
Double Blind ◽  
Circadian Phase ◽  
Melatonin Administration ◽  
Baseline Evaluation ◽  
Light Stimuli

We investigated whether the contemporaneous administration of melatonin can modify circadian phase shifts induced by bright light stimuli. After a baseline evaluation, 10 women were exposed for three consecutive nights to a 4-h bright light stimulus (>3,000 lx) initiated at the time of the estimated core body temperature (BT(c)) nadir. Along with light, each woman orally received, randomly and in a double-blind fashion, placebo (n = 5) or melatonin (n = 5; 1 mg 30 min before and 0.75 mg 120 min after the start of light exposure). Daily rhythms were reevaluated at the end of treatment. Bright light phase advanced, by about 90-120 min, BT(c) (P < 0.01), cortisol (P < 0.05), and melatonin (P < 0.01) rhythms. Contemporaneous administration of melatonin antagonized the phase advances of the cortisol and BT(c) rhythms, as well as the melatonin peak and melatonin offset. The phase advance of the melatonin onset was instead enhanced (P < 0.05). Contemporaneous melatonin administration modifies the capability of light to induce circadian phase shifts.

Melatonin Rhythm Observed throughout a Three-Cycle Bright-Light Stimulus Designed to Reset the Human Circadian Pacemaker

1999 ◽  
Vol 14 (3) ◽  
pp. 237-253 ◽  
Author(s):  
Theresa L. Shanahan ◽  
Richard E. Kronauer ◽  
Jeanne F. Duffy ◽  
Gordon H. Williams ◽  
Charles A. Czeisler
Keyword(s):  
Light Stimulus ◽  
Bright Light ◽  
Circadian Pacemaker ◽  
Melatonin Rhythm

156 Evening Light-Induced Circadian Phase Shift in Preschool-Aged Children

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A63-A64
Author(s):  
Lauren Hartstein ◽  
Lameese Akacem ◽  
Cecilia Diniz Behn ◽  
Shelby Stowe ◽  
Kenneth Wright ◽  
...  
Keyword(s):  
Phase Shift ◽  
Light Exposure ◽  
Light Stimulus ◽  
Phase Delay ◽  
Healthy Children ◽  
Dependent Manner ◽  
Circadian Phase ◽  
Light Intensities ◽  
Dim Light ◽  
Dose Dependent

Abstract Introduction In adults, exposure to light at night delays the timing of the circadian clock in a dose-dependent manner with intensity. Although children’s melatonin levels are highly suppressed by evening bright light, the sensitivity of young children’s circadian timing to evening light is unknown. This research aimed to establish an illuminance response curve for phase delay in preschool children as a result of exposure to varying light intensities in the hour before bedtime. Methods Healthy children (n=36, 3.0 – 4.9 years, 39% males), participated in a 10-day protocol. For 7 days, children followed a strict parent-selected sleep schedule. On Days 8-10, an in-home dim-light assessment was performed. On Day 8, dim light melatonin onset (DLMO) was measured through saliva samples collected in 20-30-min intervals throughout the evening until 1-h past habitual bedtime. On Day 9, children were exposed to a white light stimulus (semi-randomly assigned from 5lx to 5000lx) for 1-h before their habitual bedtime, and saliva was collected before, during, and after the exposure. On Day 10, children provided saliva samples in the evening for 2.5-h past bedtime for a final DLMO assessment. Phase angle of entrainment (habitual bedtime – DLMObaseline) and circadian phase delay (DLMOfinal – DLMObaseline) were computed. Results Final DLMO (Day 10) shifted between -8 and 123 minutes (M = 56.1 +/- 33.6 min; negative value = phase advance, positive value = phase delay) compared with DLMO at baseline (Day 8). Raw phase shift did not demonstrate a dose-dependent relationship with light intensity. Rather, we observed a robust phase delay across all intensities. Conclusion These data suggest preschoolers’ circadian clocks are immensely sensitive to a large range of light intensities, which may be mechanistically influenced by less mature ophthalmologic features (e.g. clearer lenses, larger pupils). With young children’s ever-growing use of light-emitting devices and evening exposure to artificial lighting, as well as the prevalence of behavioral sleep problems, these findings may inform recommendations for parents on the effects of evening light exposure on sleep timing in early childhood. Support (if any) This research was supported with funds from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (R01-HD087707).

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