Integration of brief light flashes varying in intensity and duration by the human circadian system

AbstractThe human circadian system is exquisitely sensitive to light, through a pathway connecting the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) to the hypothalamic suprachiasmatic nuclei (SCN). ipRGCs are characterised by a delayed off-time following cessation of light exposure; we exploited this unusual physiologic property and examined how a sequence of flashes of bright light differing in intensity or duration presented in the biological night could delay the human circadian clock in vivo in healthy young participants (n=54). To understand the mechanism underlying circadian photoreception, we probed temporal integration by manipulating flash intensity and duration independently. In a 34-hour in-laboratory between-subjects design, we examined variable-intensity (3, 30, 95, 300, 950, 3000, or 9500 photopic lux; n=28 participants) flashes at fixed duration (2 ms), and variable-duration (10 μs, 100 μs, 1 ms, 10 ms, 100 ms, 1 sec, 10 sec) flashes at fixed intensity (2000 photopic lux; n=31 participants). We measured the phase shift of dim-light melatonin onset on the subsequent evening, and acute melatonin suppression and alertness during the flash sequence. In the variable-intensity study, we find a clear sigmoidal dose-response relationship for flash intensity and the induced circadian phase shift. In the variable-duration study, we find no parametric relationship between flash duration and induced circadian phase shift, indicating a relative insensitivity of the circadian system to flashes varying in duration. As the intermittent periods of darkness in our stimulation paradigm supports the recovery of extrinsic rod-cone signalling into the ipRGCs, our results strongly suggest rod-cone contributions into circadian photoreception.

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Comment Concerning the Effects of Light Intensity on Melatonin Suppression in the Review “Light Modulation of Human Clocks, Wake, and Sleep” by A. Prayag et al.

Clocks & Sleep ◽

10.3390/clockssleep3010011 ◽

2021 ◽

Vol 3 (1) ◽

pp. 181-188

Author(s):

Peter Bracke ◽

Eowyn Van de Putte ◽

Wouter R. Ryckaert

Keyword(s):

Phase Shift ◽

Light Intensity ◽

Dose Response ◽

Light Modulation ◽

Response Curves ◽

Practical Applications ◽

Circadian Phase ◽

Melatonin Suppression ◽

Dose Response Curves ◽

Circadian Phase Shift

Dose-response curves for circadian phase shift and melatonin suppression in relation to white or monochromatic nighttime illumination can be scaled to melanopic weighed illumination for normally constricted pupils, which makes them easier to interpret and compare. This is helpful for a practical applications.

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Lateral geniculate lesions block circadian phase-shift responses to a benzodiazepine.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.85.14.5301 ◽

1988 ◽

Vol 85 (14) ◽

pp. 5301-5304 ◽

Cited By ~ 105

Author(s):

R. F. Johnson ◽

L. Smale ◽

R. Y. Moore ◽

L. P. Morin

Keyword(s):

Phase Shift ◽

Circadian Phase ◽

Lateral Geniculate ◽

Circadian Phase Shift

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Actigraphy-based parameter tuning process for adaptive notch filter and circadian phase shift estimation

Chronobiology International ◽

10.1080/07420528.2020.1805460 ◽

2020 ◽

Vol 37 (11) ◽

pp. 1552-1564

Author(s):

Jiawei Yin ◽

Agung Julius ◽

John T. Wen ◽

Meeko M. K. Oishi ◽

Lee K. Brown

Keyword(s):

Phase Shift ◽

Notch Filter ◽

Parameter Tuning ◽

Circadian Phase ◽

Adaptive Notch Filter ◽

Tuning Process ◽

Circadian Phase Shift

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

SLEEP ◽

10.1093/sleep/zsab072.155 ◽

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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0641 Predicting Circadian Phase Shift: Circadian Monitoring and Regulation System

SLEEP ◽

10.1093/sleep/zsy061.640 ◽

2018 ◽

Vol 41 (suppl_1) ◽

pp. A238-A238

Author(s):

M S Rea ◽

G Jones ◽

P Hovareshti ◽

D Tolani ◽

A Bierman ◽

...

Keyword(s):

Phase Shift ◽

Regulation System ◽

Circadian Phase ◽

Circadian Phase Shift

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Stimulation of BIT induces a circadian phase shift of locomotor activity in rats

Brain Research ◽

10.1016/s0006-8993(03)02655-6 ◽

2003 ◽

Vol 976 (2) ◽

pp. 194-201 ◽

Cited By ~ 9

Author(s):

Yasukazu Nakahata ◽

Nobuaki Okumura ◽

Hiroto Otani ◽

Juri Hamada ◽

Tadahiro Numakawa ◽

...

Keyword(s):

Locomotor Activity ◽

Phase Shift ◽

Circadian Phase ◽

Circadian Phase Shift ◽

Stimulation Of

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Daytime naps in darkness phase shift the human circadian rhythms of melatonin and thyrotropin secretion

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.278.2.r373 ◽

2000 ◽

Vol 278 (2) ◽

pp. R373-R382 ◽

Cited By ~ 35

Author(s):

Orfeu M. Buxton ◽

Mireille L'Hermite-Balériaux ◽

Fred W. Turek ◽

Eve van Cauter

Keyword(s):

Circadian Rhythms ◽

Phase Shift ◽

Light Exposure ◽

Caloric Intake ◽

Stimulus Exposure ◽

Blood Samples ◽

Circadian Misalignment ◽

Circadian Phase ◽

Before And After ◽

Dim Light

To systematically determine the effects of daytime exposure to sleep in darkness on human circadian phase, four groups of subjects participated in 4-day studies involving either no nap (control), a morning nap (0900–1500), an afternoon nap (1400–2000), or an evening nap (1900–0100) in darkness. Except during the scheduled sleep/dark periods, subjects remained awake under constant conditions, i.e., constant dim light exposure (36 lx), recumbence, and caloric intake. Blood samples were collected at 20-min intervals for 64 h to determine the onsets of nocturnal melatonin and thyrotropin secretion as markers of circadian phase before and after stimulus exposure. Sleep was polygraphically recorded. Exposure to sleep and darkness in the morning resulted in phase delays, whereas exposure in the evening resulted in phase advances relative to controls. Afternoon naps did not change circadian phase. These findings indicate that human circadian phase is dependent on the timing of darkness and/or sleep exposure and that strategies to treat circadian misalignment should consider not only the timing and intensity of light, but also the timing of darkness and/or sleep.

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Dose–response effects of light therapy on sleepiness and circadian phase shift in shift workers: a meta-analysis and moderator analysis

Scientific Reports ◽

10.1038/s41598-021-89321-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Calvin Lam ◽

Min-Huey Chung

Keyword(s):

Phase Shift ◽

Meta Analysis ◽

Experimental Studies ◽

Light Therapy ◽

Shift Workers ◽

Random Effects Models ◽

Circadian Phase ◽

Medium Intensity ◽

Circadian Phase Shift ◽

Effect Of Light

AbstractLight therapy has been considered to be effective in mitigating sleepiness and regulating circadian phase shift in shift workers. However, the effective treatment dose of light therapy remains undetermined. We performed a meta-analysis of randomized experimental studies to determine the effect of light therapy doses on sleepiness and circadian phase shift in shift workers. An article search was performed in 10 electronic databases from inception to June 2020. Two raters independently screened and extracted data and reached consensus. Twenty-one eligible studies were included. Analyses were performed using random-effects models. Light therapy exerted significantly small to medium effects on sleepiness and large treatment effects on circadian phase shift. Moderator analyses performed with subgroup and metaregression analyses revealed that medium-intensity light therapy for a shorter duration more effectively reduced sleepiness at night, whereas higher-intensity light therapy more effectively induced phase shifting, but the required treatment duration remained inconclusive. This study provides evidence regarding the effect of light therapy in reducing sleepiness and shifting circadian phase in shift workers. Exposure to medium-intensity light for a short duration at night reduced sleepiness, whereas exposure to high-intensity light improved sleep by shifting their circadian phase.

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