Temporal integration of light flashes by the human circadian system
Raymond P. Najjar, Jamie M. Zeitzer
Raymond P. Najjar, Jamie M. Zeitzer
Published February 8, 2016
Citation Information: J Clin Invest. 2016;126(3):938-947. https://doi.org/10.1172/JCI82306.
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Clinical Research and Public Health Neuroscience

Temporal integration of light flashes by the human circadian system

Abstract

BACKGROUND. Beyond image formation, the light that is detected by retinal photoreceptors influences subcortical functions, including circadian timing, sleep, and arousal. The physiology of nonimage-forming (NIF) photoresponses in humans is not well understood; therefore, the development of therapeutic interventions based on this physiology, such as bright light therapy to treat chronobiological disorders, remains challenging.

METHODS. Thirty-nine participants were exposed to 60 minutes of either continuous light (n = 8) or sequences of 2-millisecond light flashes (n = 31) with different interstimulus intervals (ISIs; ranging from 2.5 to 240 seconds). Melatonin phase shift and suppression, along with changes in alertness and sleepiness, were assessed.

RESULTS. We determined that the human circadian system integrates flash sequences in a nonlinear fashion with a linear rise to a peak response (ISI = 7.6 ± 0.53 seconds) and a power function decrease following the peak of responsivity. At peak ISI, flashes were at least 2-fold more effective in phase delaying the circadian system as compared with exposure to equiluminous continuous light 3,800 times the duration. Flashes did not change melatonin concentrations or alertness in an ISI-dependent manner.

CONCLUSION. We have demonstrated that intermittent light is more effective than continuous light at eliciting circadian changes. These findings cast light on the phenomenology of photic integration and suggest a dichotomous retinohypothalamic network leading to circadian phase shifting and other NIF photoresponses. Further clinical trials are required to judge the practicality of light flash protocols.

TRIAL REGISTRATION. Clinicaltrials.gov NCT01119365.

FUNDING. National Heart, Lung, and Blood Institute (1R01HL108441-01A1) and Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education, and Clinical Center.

Authors

Raymond P. Najjar, Jamie M. Zeitzer

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Figure 4

Effect of flashes and continuous light on melatonin suppression, objective alertness, and subjective sleepiness.

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Effect of flashes and continuous light on melatonin suppression, objecti...
There was no systematic ISI-dependent change in (A) melatonin suppression (n = 28), (B and C) objective alertness (n = 31), or (D) subjective sleepiness (n = 31). Continuous light significantly suppressed melatonin (W = 35, Z = 2.31, P = 0.016, Wilcoxon signed-rank test), reduced RT (t = 4.49, df = 7, P = 0.002, paired t test), and number of lapses (W = 34, Z = 2.18, P = 0.02, Wilcoxon signed-rank test) but did not decrease subjective sleepiness, as assessed by the SSS (W = 13.5, Z = 1.5, P = 0.19, Wilcoxon signed-rank test). (A–C) Average and (D) median changes induced by continuous light are represented as gray horizontal bars; yellow diamonds represent individual data. (D) Overlapping yellow diamonds are represented next to each other separated by a vertical red bar. Descending arrows or negative values indicate less melatonin suppression, faster RTs, fewer lapses, and decreased sleepiness.