title: Assessing rod, cone, and melanopsin contributions to human pupil flicker responses.
abstract: OBJECTIVE
  We determined the relative contributions of rods, cones, and melanopsin to pupil responses in humans using temporal sinusoidal stimulation for light levels spanning the low mesopic to photopic range.
  
  
  METHODS
  A four-primary Ganzfeld photostimulator controlled flicker stimulations at seven light levels (-2.7 to 2 log cd/m(2)) and five frequencies (0.5-8 Hz). Pupil diameter was measured using a high-resolution eye tracker. Three kinds of sinusoidal photoreceptor modulations were generated using silent substitution: rod modulation, cone modulation, and combined rod and cone modulation in phase (experiment 1) or cone phase shifted (experiment 2) from a fixed rod phase. The melanopsin excitation was computed for each condition. A vector sum model was used to estimate the relative contribution of rods, cones, and melanopsin to the pupil response.
  
  
  RESULTS
  From experiment 1, the pupil frequency response peaked at 1 Hz at two mesopic light levels for the three modulation conditions. Analyzing the rod-cone phase difference for the combined modulations (experiment 2) identified a V-shaped response amplitude with a minimum between 135° and 180°. The pupil response phases increased as cone modulation phase increased. The pupil amplitude increased with increasing light level for cone, and combined (in-phase rod and cone) modulation, but not for the rod modulation.
  
  
  CONCLUSIONS
  These results demonstrate that cone- and rod-pathway contributions are more predominant than melanopsin contribution to the phasic pupil response. The combined rod, cone, and melanopsin inputs to the phasic state of the pupil light reflex follow linear summation.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Barrionuevo
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Nicandro
authors.forename: J Jason
authors.initials: JJ
authors.lastname: McAnany
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Zele
authors.forename: Paul
authors.initials: P
authors.lastname: Gamlin
authors.forename: Dingcai
authors.initials: D
authors.lastname: Cao
mesh_terms: D000328:Adult; D055253:Color Vision / Q000502:physiology; D006801:Humans; D008027:Light; D010775:Photic Stimulation; D011680:Pupil / Q000528:radiation effects; D012025:Reflex, Pupillary / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D017299:Rod Opsins / Q000502:physiology*; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult; D000099210:Melanopsin
chemical_list: D017299:Rod Opsins; D000099210:Melanopsin
keywords: flicker; melanopsin; pupil light reflex; silent-substitution