Quantifying Human Circadian Pacemaker Response to Brief, Extended, and Repeated Light Stimuli over the Phototopic Range

Kronauer, Richard E.; Forger, Daniel B.; Jewett, Megan E.

doi:10.1177/074873099129001073

Cited by 145 publications

(150 citation statements)

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“…Every evening, participants were asked to report their expected bedtimes and to download the light data from the Daysimeter to a laptop that was provided to each participant. Once the download was complete, a modified algorithm based on the model of human circadian entrainment by Kronauer et al (24) was used to program the most effective timing to apply circadian light, each night, using the active light mask. The Kronauer model consists of a phototransduction process (L) driving a limit cycle oscillator process (P).…”

Section: Methodsmentioning

confidence: 99%

Individually tailored light intervention through closed eyelids to promote circadian alignment and sleep health

Figueiro

2015

Sleep Health

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Background Light is most effective at changing the timing of the circadian clock when applied close to the core body temperature minimum. The present study investigated, in a home setting, if individually tailored light treatment using flashing blue light delivered through closed eyelids during the early part of the sleep period delayed circadian phase and sleep in a population of healthy older adults and in those suffering from early awakening insomnia. Methods Twenty-eight participants (9 early awakening insomniacs) completed an 8-week, within-subjects study. Twice, participants collected data during two baseline weeks and one intervention week. During the intervention week, participants wore a flashing blue (active) or a flashing red (control) light mask during sleep. Light was expected to delay circadian phase. Saliva samples for dim light melatonin onset (DLMO) were collected at the end of each baseline and intervention week. Wrist actigraphy and Daysimeter, a calibrated light and activity meter, data were collected during the entire study. Results Compared to baseline, flashing blue light, but not flashing red light, significantly (p<0.05) delayed DLMO. The mean ± standard deviation phase shift (minutes) was 0:06 ± 0:30 for the flashing red light and 0:34 ± 0:30 for the flashing blue light. Compared to Day 1, sleep start times were significantly delayed (by approximately 46 minutes) at Day 7 after the flashing blue light. The light intervention did not affect sleep efficiency. Conclusions The present study demonstrated the feasibility of using light through closed eyelids during sleep for promoting circadian alignment and sleep health.

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Section: Methodsmentioning

confidence: 99%

Individually tailored light intervention through closed eyelids to promote circadian alignment and sleep health

Figueiro

2015

Sleep Health

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“…Scheduled sleep occurred in total darkness. The timing, duration, intensity, and pattern of light exposure stimuli were based on the dynamic resetting model developed by Kronauer and colleagues (15)(16)(17). The model predicted a successful circadian entrainment to T ϭ ϩ 1 h for the MLE condition and failure to entrain to T ϭ ϩ 1 h for the 25-and 100-lux light conditions.…”

Section: Methodsmentioning

confidence: 99%

“…The mathematical model developed by Kronauer and colleagues (15)(16)(17) was used as a guide to the design of these experiments. The present results imply a higher sensitivity to 100 lux than could have been inferred from previous data.…”

Section: Entrainment or Masking?mentioning

confidence: 99%

“…1). Based on the mathematical model of the effect of light on the human circadian pacemaker developed by Kronauer and colleagues (15)(16)(17), we hypothesized that the resetting effect of the MLE would entrain the biological clock of subjects to a ϩ 1 h T-cycle, whereas the resetting effect of 25 and 100 lux would be insufficient to entrain the biological clock to a ϩ 1 h T-cycle.…”

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confidence: 99%

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

Gronfier

Wright

Kronauer

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

181

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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 ( ). 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 ؉ 1 h) in one of three light:dark conditions: (i) Ϸ25 lux; (ii) Ϸ100 lux; and (iii) MLE: Ϸ25 lux followed by Ϸ100 lux, plus two 45-min bright light pulses of Ϸ9,500 lux near the end of scheduled wakefulness. We found that lighting levels of Ϸ25 lux were insufficient to entrain all subjects tested. Exposure to Ϸ100 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 shiftwork disorder.light ͉ melatonin ͉ phase angle of entrainment ͉ phase response curve ͉ sleep Entrainment of a circadian rhythm by a zeitgeber fulfills biological purpose in providing a very distinct phase relationship between the periodicity of the organism and that of the environment.J. Aschoff (1) T o be of functional significance for the organism, circadian rhythms must be entrained to the 24-h day. For nearly all species studied, the light:dark cycle is the most powerful circadian synchronizer. The resetting capacity of light depends on its intensity, timing, duration, temporal pattern, and spectral composition (2-7). In totally blind people, the circadian timekeeping system often loses synchrony with the earth's 24-h light:dark cycle (8). Well described in animals (9-11) and only recently confirmed in humans (12), entrainment of the circadian system depends on (i) its intrinsic period ( ), (ii) the light:dark cycle to which it is exposed (T; T-cycle), and (iii) the strength of the entraining stimulus (zeitgeber, from German for "time giver"). The generally accepted nonparametric model of circadian entrainment predicts immediate phase shifting in response to light, according to a phase response curve (PRC) (3, 9, 13). In humans, for whom the intrinsic period is on average Ϸ24.2 h (14), entrainment to the solar day of earth (T ϭ 24 h) requires that the biological clock be ''reset'' by on average of Ϸ0.2 h per day in th...

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“…We anticipated that the administration of morning light treatment within the first half-hour of the patient’s habitual wake time could maximize the effectiveness of the light treatment, because any advance shifts in circadian phase would be larger (see Instructions to Subjects, Table 1). In this respect, our specific instructions to patients were predicted [based on (Kronauer, Forger et al, 1999; 2000; St Hilaire, Klerman et al, 2007)] to enhance response rates relative to our previous protocol, in which a wider range of morning times for light treatment was allowed.…”

Section: Introductionmentioning

confidence: 99%

Are short (blue) wavelengths necessary for light treatment of seasonal affective disorder?

Anderson

Hilaire

Auger

et al. 2016

Chronobiology International

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Despite widely published speculation regarding a potential potency advantage of short-wavelength (blue-appearing) light for Seasonal Affective Disorder (SAD) treatment, there have been few systematic studies. Those comparing short-wavelength to broad-wavelength (white) light under actual clinical conditions suggest equivalent effectiveness. This multicenter, parallel-group design trial was undertaken to compare the effects of light therapy on SAD using blue (~465nm) versus blue-free (595–612nm) LED lights. Fifty-six medication-free subjects aged 21–64 years who met DSM-IV-TR criteria for recurrent major depression with winter-type seasonal pattern were enrolled in this blinded study at 5 participating centers between January and March 2012. Thirty-five subjects met criteria for randomization to 30 minutes of either blue (~465nm) or blue-free (595–612nm) daily morning light therapy. Twenty-nine subjects completed the study; three subjects withdrew due to treatment-related adverse events, including migraines, and three withdrew for non-study-related reasons. The primary effectiveness variable was depression score (SIGH-ADS) after six weeks of daily light treatment. Secondary effectiveness variables included Quality of Life and suicidality ratings. Using an intent-to-treat analysis, mean depression scores were different at baseline for the blue group (29±5 vs. 26±5, p=0.05 blue vs. blue-free, respectively), and initial score was used as a covariate. Baseline scores were not significantly different between treatment groups among those who completed the study, and no significant differences in depression scores were observed after 6 weeks (mean ± s.d. scores at 6 weeks: 5.6±6.1 vs. 4.5±5.3, p=0.74, blue vs. blue-free, respectively). In addition, the proportion of subjects who met remission criteria, defined as a depression score ≤8, was not significantly different between the two groups (p=0.41); among the 29 subjects who completed the study, 76% of subjects experienced remission by the end of the trial, which coincided with the beginning of spring. Quality of Life and suicidality ratings were also significantly improved from pre- to post-treatment, with no significant difference between treatments. No subject experienced worsening or non-improved symptoms over the 6-week trial. The main finding of this study is that subjects treated with blue light did not improve more than subjects treated with blue-free light; both showed substantial improvement on multiple measures. Failure to find differences may have resulted from methodological constraints, including a small sample size. Recruitment began mid-winter during an unusually mild season, and the trial was terminated earlier than planned by the study sponsor due to a failure to detect difference. However, if confirmed in a larger randomized sample, these results suggest that blue wavelengths are not necessary for successful SAD treatment.

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Quantifying Human Circadian Pacemaker Response to Brief, Extended, and Repeated Light Stimuli over the Phototopic Range

Cited by 145 publications

References 19 publications

Individually tailored light intervention through closed eyelids to promote circadian alignment and sleep health

Individually tailored light intervention through closed eyelids to promote circadian alignment and sleep health

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

Are short (blue) wavelengths necessary for light treatment of seasonal affective disorder?

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