Assessing rod, cone, and melanopsin contributions to human pupil flicker responses.

PURPOSE 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.