Pulses of Melanopsin-Directed Contrast Produce Highly Reproducible Pupil Responses That Are Insensitive to a Change in Background Radiance

McAdams, Harrison; Igdalova, Aleksandra; Spitschan, Manuel; Brainard, David H.; Aguirre, Geoffrey K.

doi:10.1167/iovs.18-25219

Cited by 7 publications

(10 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Figure 4a presents the mean, across-participant pupil responses observed in each of the three groups to the stimuli used in the experiment. The temporal profile of the pupil response to stimuli that target melanopsin, the cones, or their combination is in good agreement with prior reports 25 . There is also a clear increase in the amplitude of the pupil constriction produced by stimuli with increasing (100%, 200%, 400%) contrast.…”

Section: Migraine Groups Do Not Have Enhanced Pupil Responses Indicasupporting

confidence: 91%

“…While there is evidence that rod signals can modulate RGC firing at any light level 85 , the amplitude of these effects under photopic conditions is quite small relative to the cones. Further, our prior work indicates that rod signals do not make a measurable contribution to the pupil response at these background light levels 25 .…”

Section: The Neural Locus Of Amplificationmentioning

confidence: 86%

“…In previous work we have shown that carefully tailored modulations of the spectral content of light may be used to selectively target melanopsin or the cones. 24,25 Here, we examine the contribution of cone and melanopsin signals to visual discomfort, and to pupil responses, in people who have migraine with interictal photophobia.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Selective amplification of ipRGC signals accounts for interictal photophobia in migraine

McAdams

Kaiser

Igdalova

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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 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 also 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 amplification of integrated ipRGC signals for discomfort.This effect of migraine is selective for ratings of visual discomfort, in that an amplification 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 versus pupil response, our findings suggest a post-retinal alteration in processing of ipRGC signals for photophobia in migraine. SignificanceThe melanopsin-containing, intrinsically photosensitive retinal ganglion cells (ipRGCs) may contribute to photophobia in migraine. We measured visual discomfort and pupil responses to cone and melanopsin stimulation-the photoreceptor inputs to the ipRGCs-in people with and without migraine. We find that people with migraine do not differ from those without headaches in how cone and melanopsin signals are weighted and combined to produce visual discomfort.Instead, migraine is associated with an amplification of ipRGC signals for discomfort. This effect of migraine upon ipRGC signals is limited to photophobia, as we did not find an enhancement of pupil responses or a change in other behaviors linked to ipRGC function. Our findings suggest a post-retinal amplification of ipRGC signals for photophobia in migraine.

show abstract

Section: Migraine Groups Do Not Have Enhanced Pupil Responses Indicasupporting

confidence: 91%

Section: The Neural Locus Of Amplificationmentioning

confidence: 86%

See 1 more Smart Citation

Selective amplification of ipRGC signals accounts for interictal photophobia in migraine

McAdams

Kaiser

Igdalova

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Analyzing these relative changes minimized the influence of preexisting pupil sizes and the impact of dark-adapted responses. Another limitation of our study is that with the current pupil measurement protocol, we are not able to completely isolate the different photoreceptor contributions to the physiological pupil responses, as was recently shown by others (McAdams et al, 2018; Rukmini et al, 2019). However, a methodological comparison revealed comparable results for the PIPR and this different method, called silent substitution (Estevez and Spekreijse, 1982; Spitschan and Woelders, 2018; Tsujimura et al, 2010).…”

Section: Discussionmentioning

confidence: 90%

Living in Biological Darkness: Objective Sleepiness and the Pupillary Light Responses Are Affected by Different Metameric Lighting Conditions during Daytime

et al. 2019

View full text Add to dashboard Cite

Nighttime melatonin suppression is the most commonly used method to indirectly quantify acute nonvisual light effects. Since light is the principal zeitgeber in humans, there is a need to assess its strength during daytime as well. This is especially important since humans evolved under natural daylight but now often spend their time indoors under artificial light, resulting in a different quality and quantity of light. We tested whether the pupillary light response (PLR) could be used as a marker for nonvisual light effects during daytime. We also recorded the wake electroencephalogram to objectively determine changes in daytime sleepiness between different illuminance levels and/or spectral compositions of light. In total, 72 participants visited the laboratory 4 times for 3-h light exposures. All participants underwent a dim-light condition and either 3 metameric daytime light exposures with different spectral compositions of polychromatic white light (100 photopic lux, peak wavelengths at 435 nm or 480 nm, enriched with longer wavelengths of light) or 3 different illuminances (200, 600, and 1200 photopic lux) with 1 metameric lighting condition (peak wavelength at 435 nm or 480 nm; 24 participants each). The results show that the PLR was sensitive to both spectral differences between metameric lighting conditions and different illuminances in a dose-responsive manner, depending on melanopic irradiance. Objective sleepiness was significantly reduced, depending on melanopic irradiance, at low illuminance (100 lux) and showed fewer differences at higher illuminance. Since many people are exposed to such low illuminance for most of their day—living in biological darkness—our results imply that optimizing the light spectrum could be important to improve daytime alertness. Our results suggest the PLR as a noninvasive physiological marker for ambient light exposure effects during daytime. These findings may be applied to assess light-dependent zeitgeber strength and evaluate lighting improvements at workplaces, schools, hospitals, and homes.

show abstract

“…In previous work, we have shown that carefully tailored modulations of the spectral content of light may be used to selectively target melanopsin or the cones (24,25). Here, we examine the contribution of cone and melanopsin signals to visual discomfort, and to pupil responses, in people who have migraine…”

mentioning

confidence: 97%

Selective amplification of ipRGC signals accounts for interictal photophobia in migraine

McAdams

Kaiser

Igdalova

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Pulses of Melanopsin-Directed Contrast Produce Highly Reproducible Pupil Responses That Are Insensitive to a Change in Background Radiance

Cited by 7 publications

References 53 publications

Selective amplification of ipRGC signals accounts for interictal photophobia in migraine

Selective amplification of ipRGC signals accounts for interictal photophobia in migraine

Living in Biological Darkness: Objective Sleepiness and the Pupillary Light Responses Are Affected by Different Metameric Lighting Conditions during Daytime

Selective amplification of ipRGC signals accounts for interictal photophobia in migraine

Contact Info

Product

Resources

About