Selective amplification of ipRGC signals accounts for interictal photophobia in migraine

Abstract

<jats:p>Second only to headache, photophobia is the most debilitating symptom reported by people with migraine. While the melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to play a role, how cone and melanopsin signals are integrated in this pathway to produce visual discomfort is poorly understood. We studied 60 people: 20 without headache and 20 each with interictal photophobia from migraine with or without visual aura. Participants viewed pulses of spectral change that selectively targeted melanopsin, the cones, or both and rated the degree of visual discomfort produced by these stimuli while we recorded pupil responses. We examined the data within a model that describes how cone and melanopsin signals are weighted and combined at the level of the retina and how this combined signal is transformed into a rating of discomfort or pupil response. Our results indicate that people with migraine do not differ from headache-free controls in the manner in which melanopsin and cone signals are combined. Instead, people with migraine demonstrate an enhanced response to integrated ipRGC signals for discomfort. This effect of migraine is selective for ratings of visual discomfort, in that an enhancement of pupil responses was not seen in the migraine group, nor were group differences found in surveys of other behaviors putatively linked to ipRGC function (chronotype, seasonal sensitivity, presence of a photic sneeze reflex). By revealing a dissociation in the amplification of discomfort vs. pupil response, our findings suggest a postretinal alteration in processing of ipRGC signals for photophobia in migraine.</jats:p>

Enhanced reflexive eye closure is mediated by ipRGC signals and is specific to migraine with visual aura

“…We presented 4-second pulses of these stimuli while we recorded OO-EMG, and blinking in the contralateral eye via an infrared camera. The participants and stimuli presented here have been the subject of a prior paper on pupil responses and self-reported visual discomfort; 17 the current data were collected in the same experimental sessions.…”

“…Explicit report of visual discomfort in people with migraine and interictal photophobia appears to result from a selective amplification of ipRCG signals, after the integration of melanopsin and cone inputs. 17 Here we ask if the same findings are present for two implicit measures of visual discomfort: electromyography of the orbicularis oculi (OO-EMG) and blink frequency. These were recorded while participants observed spectral pulses that selectively targeted the cones and/or melanopsin (Figure 1b, 1c).…”

“…19 Recruited participants also completed the Visual Discomfort Score (VDS) survey; 20 our scoring has been previously described. 17 Candidate participants were required to meet all inclusion criteria for one of three groups: 3) Control: a) classification of mild non-migrainous headache or headache-free by the POEM, b) a response of "No" or "I don't know" to a question regarding a family history of migraine, c) a response of "No" to a question regarding a history of childhood motion sickness, d) VDS score of 7 or lower.…”

“…Exclusion criteria related to impaired vision, inability to collect usable pupillometry, head trauma, and seizure history have been previously described. 17 Participants were not excluded based on medication use and were allowed to continue to take their current medications during data collection.…”

A Quadratic Model Captures the Human V1 Response to Variations in Chromatic Direction and Contrast

“…These corrections were made to the modulation spectra at the maximum contrast used in each direction. Additional information about the correction procedure is provided in McAdams et al (2020). The order in which spectroradiometric measurements were taken during an experimental session was 1) five pre-correction measurements for each chromatic direction used in the session, 2) the corrections procedure, 3) five post-correction measurements per direction, and 4) five postexperiment measurements per direction.…”