title: Using Flickering Light to Enhance Nonimage-Forming Visual Stimulation in Humans.
abstract: OBJECTIVE
  Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate nonimage-forming visual functions such as pupillary constriction and circadian photoentrainment. Optimizing daytime nonimage-forming photostimulation has health benefits. We aimed to enhance ipRGC excitation using flickering instead of steady light.
  
  
  METHODS
  Human subjects were tested with a three-dimensional matrix of flickering 463-nm stimuli: three photon counts (13.7, 14.7 and 15.7 log photons cm(-2)), three duty cycles (12%, 47%, and 93%) and seven flicker frequencies (0.1, 0.25, 0.5, 1, 2, 4, and 7 Hz). Steady-state pupil constrictions were measured.
  
  
  RESULTS
  Among stimuli containing 13.7 log photons cm-2, the one flickering at 2 Hz with a 12% duty cycle evoked the greatest pupil constriction of 48% ± 4%, 71% greater than that evoked by an equal-intensity (12.3 log photons cm(-2) s(-1)) continuous light. This frequency and duty cycle were also best for 14.7 log photons cm-2 stimuli, inducing a 58% ± 4% constriction which was 38% more than that caused by an equal-intensity (13.3 log photons cm(-2) s(-1)) constant light. For 15.7 log photons cm-2 stimuli, the 1-Hz, 47% duty cycle flicker was optimal although it evoked the same constriction as the best 14.7 log photons cm(-2) flicker.
  
  
  CONCLUSIONS
  Pupillary constriction depends on flicker frequency and duty cycle besides intensity. Among the stimuli tested, the one with the lowest photon count inducing a maximal response is 13.3 log photons cm(-2) s(-1) flickering at 2 Hz with 12% duty cycle. Our data could guide the design of healthier architectural lighting and better phototherapy devices for treating seasonal affective disorder and jet lag.
authors.affiliation: Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States 2Graduate Program in Macromolecular Science & Engineering, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Garen V
authors.initials: GV
authors.lastname: Vartanian
authors.affiliation: Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Xiwu
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States 3Department of Molecular, Cellular & Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States.
authors.forename: Kwoon Y
authors.initials: KY
authors.lastname: Wong
mesh_terms: D000328:Adult; D000818:Animals; D003623:Dark Adaptation / Q000502:physiology*; D055724:Electrophysiological Phenomena; D005260:Female; D006801:Humans; D008027:Light; D008297:Male; D051379:Mice; D010775:Photic Stimulation / Q000379:methods*; D011680:Pupil / Q000502:physiology* / Q000528:radiation effects; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D017299:Rod Opsins / Q000378:metabolism / Q000528:radiation effects*; D014785:Vision, Ocular / Q000502:physiology*; D055815:Young Adult
chemical_list: D017299:Rod Opsins