Temporal integration of light flashes by the human circadian system
Raymond P. Najjar, Jamie M. Zeitzer
Raymond P. Najjar, Jamie M. Zeitzer
Published March 1, 2016; First 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 Medicine 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 1

CONSORT flow diagram showing enrollment, allocation, and analysis.

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CONSORT flow diagram showing enrollment, allocation, and analysis. Seven...
Seventy-seven participants were assessed for eligibility. Thirty-five participants were excluded from participation for either not meeting the criteria (n = 4) or declining to participate (n = 31). Forty-two participants participated in the study and were randomized to either a flash sequence or continuous light exposure protocol. Of the 34 participants who were allocated randomly to the different flash sequence light exposures, 3 failed to comply with the prelaboratory sleep schedule and were excluded and 31 were randomly assigned to different sequences of light flashes. Eight participants were allocated to the continuous light exposure. All 39 participants were analyzed. Melatonin suppression values in 3 participants from the flash allocated group were aberrant and had to be excluded.