title: 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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01119365.
  
  
  BACKGROUND
  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
authors: RP
authors: Najjar
authors: Jamie M
authors: JM
authors: Zeitzer
mesh_terms: D000328:Adult; D002940:Circadian Rhythm / Q000528:radiation effects*; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000097:blood*; D010775:Photic Stimulation; D014796:Visual Perception; D014851:Wakefulness / Q000528:radiation effects; D055815:Young Adult
chemical_list: D008550:Melatonin