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. 2022 Mar 9;289(1970):20211943.
doi: 10.1098/rspb.2021.1943. Epub 2022 Mar 9.

Duration invariance and intensity dependence of the human circadian system phase shifting response to brief light flashes

Daniel S Joyce  1   2   3 , Manuel Spitschan  1   4   5 , Jamie M Zeitzer  1   2
Affiliations

Duration invariance and intensity dependence of the human circadian system phase shifting response to brief light flashes

Daniel S Joyce et al. Proc Biol Sci. .

Abstract

The melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are characterized by a delayed off-time following the cessation of light stimulation. Here, we exploited this unusual physiologic property to characterize the exquisite sensitivity of the human circadian system to flashed light. In a 34 h in-laboratory between-subjects design, we examined phase shifting in response to variable-intensity (3-9500 photopic lux) flashes at fixed duration (2 ms; n = 28 participants) and variable-duration (10 µs-10 s) flashes at fixed intensity (2000 photopic lux; n = 31 participants). Acute melatonin suppression, objective alertness and subjective sleepiness during the flash sequence were also assessed. We find a dose-response relationship between flash intensity and circadian phase shift, with an indication of a possible threshold-like behaviour. We find a slight parametric relationship between flash duration and circadian phase shift. Consistent with prior studies, we observe no dose-response relationship to either flash intensity or duration and the acute impact of light on melatonin suppression, objective alertness or subjective sleepiness. Our findings are consistent with circadian responses to a sequence of flashes being mediated by rod or cone photoreceptors via ipRGC integration.

Keywords: alertness; circadian; flash; light; melatonin; sleep.

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Conflict of interest statement

We declare we have no competing interests.

Figures

Figure 1.
Figure 1.
Circadian phase shifting protocol. (a) Schematic diagram of 16-day study protocol. During CP1 and CP2, saliva samples were collected and behavioural assessments (objective alertness, subjective sleepiness) were performed. MSP, mid-sleep point; LE, light exposure; CP, constant posture. (b) Schematic diagram of flash sequence over the 1 h light exposure phase. Flashes at fixed duration (2 ms) were separated by 15 s onset-to-onset and varied between 3 and 9500 lux. (c) Schematic diagram of flash sequence over the 1 h light exposure phase. Flashes at fixed intensity (approx. 2000 lux) were separated by 15 s onset-to-onset and varied between 10 µs and 10 s. Spectral properties of the stimulus were invariant of flash intensity and duration (electronic supplementary material, figure S2), and for variable-duration stimuli the total time-averaged radiance delivered was as expected, scaling linear with duration. (Online version in colour.)
Figure 2.
Figure 2.
Flashes of light shift circadian phase in an illuminance-dependent manner. Dose–response curve for circadian phase shifts across four orders of magnitude of photopic illuminance (2 ms flashes delivered every 15 s for 60 min) measured in an in-laboratory between-subjects design (n = 27). Individual, per-subject data points are shown as white circles. A four-parameter dose–response curve (black line) with 95% CI (shaded grey) fitted to these data is overlaid. There is no relationship between the timing of light exposure and the phase shift (b) or the residuals in the linear model (c). (Online version in colour.)
Figure 3.
Figure 3.
Dose–response relationship for circadian phase shifts across six orders of magnitude of flash duration (2000 lux flashes delivered every 15 s for 60 min) measured in an in-laboratory between-subjects design (n = 27). Individual, per-subject data points are shown as white circles, group mean ± s.d. estimates are shown as filled orange circles. Note, the control condition (filled dark grey circle) is arbitrarily plotted at 5 × 10−5 for visualization purposes only—there is no light in this condition so the duration would be 0. These data were unable to be fitted with a dose–response. There is no relationship between the timing of light exposure and the phase shift (b) or the residuals in the linear model (c). (Online version in colour.)
Figure 4.
Figure 4.
Flashes of light do not affect acute non-visual effects of light reliably. (a,c,e) Measurements of acute melatonin suppression, acute sleepiness and acute objective alertness in the variable-intensity protocol. (b,d,f) Measurements of acute melatonin suppression, acute sleepiness and acute objective alertness in the variable-duration protocol. Individual, per-subject data points are shown as white circles, mean ± s.d. estimates are shown as green (variable-intensity; left column) and orange (variable-duration; right column) circles. (Online version in colour.)
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References

    1. Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Markey SP. 1980. Light suppresses melatonin secretion in humans. Science 210, 1267-1269. (10.1126/science.7434030) - DOI - PubMed
    1. Thapan K, Arendt J, Skene DJ. 2001. An action spectrum for melatonin suppression: evidence for a novel non-rod, non-cone photoreceptor system in humans. J. Physiol. 535, 261-267. (10.1111/j.1469-7793.2001.t01-1-00261.x) - DOI - PMC - PubMed
    1. Prayag AS, Najjar RP, Gronfier C. 2019. Melatonin suppression is exquisitely sensitive to light and primarily driven by melanopsin in humans. J. Pineal Res. 66, e12562. (10.1111/jpi.12562) - DOI - PubMed
    1. Brainard GC, Lewy AJ, Menaker M, Fredrickson RH, Miller LS, Weleber RG, Cassone V, Hudson D. 1988. Dose-response relationship between light irradiance and the suppression of plasma melatonin in human volunteers. Brain Res. 454, 212-218. (10.1016/0006-8993(88)90820-7) - DOI - PubMed
    1. Zeitzer JM, Dijk D-J, Kronauer RE, Brown EN, Czeisler CA. 2000. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression. J. Physiol. 526, 695-702. (10.1111/j.1469-7793.2000.00695.x) - DOI - PMC - PubMed

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