The human visual cortex response to melanopsin-directed stimulation is accompanied by a distinct perceptual experience
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Edited by Brian A. Wandell, Stanford University, Stanford, CA, and approved September 28, 2017 (received for review June 27, 2017)

Significance
Melanopsin-containing retinal cells detect bright light and contribute to reflex visual responses such as pupil constriction. Their role in conscious, cortical vision is less understood. Using functional MRI to measure brain activity, we find that melanopsin-directed stimulation reaches the visual cortex in people. Such stimulation also produces a distinct perceptual experience. Our results have clinical importance as melanopsin function may contribute to the discomfort that some people experience from bright light.
Abstract
The photopigment melanopsin supports reflexive visual functions in people, such as pupil constriction and circadian photoentrainment. What contribution melanopsin makes to conscious visual perception is less studied. We devised a stimulus that targeted melanopsin separately from the cones using pulsed (3-s) spectral modulations around a photopic background. Pupillometry confirmed that the melanopsin stimulus evokes a response different from that produced by cone stimulation. In each of four subjects, a functional MRI response in area V1 was found. This response scaled with melanopic contrast and was not easily explained by imprecision in the silencing of the cones. Twenty additional subjects then observed melanopsin pulses and provided a structured rating of the perceptual experience. Melanopsin stimulation was described as an unpleasant, blurry, minimal brightening that quickly faded. We conclude that isolated stimulation of melanopsin is likely associated with a response within the cortical visual pathway and with an evoked conscious percept.
Footnotes
- ↵1To whom correspondence should be addressed. Email: aguirreg{at}upenn.edu.
Author contributions: M.S., D.H.B., and G.K.A. conceived the project; M.S. and G.K.A. designed the fMRI experiments; J.R., D.H.B., and G.K.A. designed the perceptual experiment; M.S. and D.H.B. designed the spectral modulations; M.S., A.S.B., J.R., G.F., and G.K.A. collected fMRI data; G.F. collected pupillometry data; J.R. collected perceptual data; M.S., A.S.B., and G.F. analyzed fMRI data; M.S. and G.F. analyzed pupillometry data; G.K.A. implemented temporal models for the fMRI and pupillometry data; J.R., D.H.B., and G.K.A. analyzed perceptual data; M.S. analyzed the effects of biological variability upon photoreceptor contrast; G.K.A. created the figures; and M.S. and G.K.A. wrote the paper with contributions from A.S.B., J.R., G.F., and D.H.B.
Conflict of interest statement: G.K.A., D.H.B., and M.S. are listed as inventors on a patent application filed by the Trustees of the University of Pennsylvania on September 11, 2015 (US Patent Application No. 14/852,001, “Robust Targeting of Photosensitive Molecules”). The authors declare no other competing financial interests.
This article is a PNAS Direct Submission.
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