Biology subjects

Aguirre, G. K.

Publications and source records attributed to Aguirre, G. K..

26 records · Page 2Linked to original sources

bioRxiv2020

Selective amplification of ipRGC signals accounts for interictal photophobia in migraine

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.

neuroscience↗

bioRxiv2020

A neural correlate of visual discomfort from flicker

The theory of "visual stress" holds that visual discomfort results from overactivation of the visual cortex. Despite general acceptance, there is a paucity of empirical data that confirm this relationship, particularly for discomfort from visual flicker. We examined the association between neural response and visual discomfort using flickering light of different temporal frequencies that separately targeted the magnocellular, parvocellular, and koniocellular post-receptoral pathways. Given prior work that has shown larger cortical responses to flickering light in people with migraine, we examined 10 headache free people and 10 migraineurs with visual aura. The stimulus was a uniform field, 50 degrees in diameter, that modulated with high-contrast flicker between 1.625 and 30 Hz. We asked subjects to rate their visual discomfort while we recorded steady state visually evoked potentials (ssVEP) from primary visual cortex. The peak temporal sensitivity ssVEP amplitude varied by post-receptoral pathway, and was consistent with the known properties of these visual channels. Notably, there was a direct, linear relationship between the amplitude of neural response to a stimulus and the degree of visual discomfort it evoked. No substantive differences between the migraine and control groups was found. These data link increased visual cortical activation with the experience of visual discomfort.

neuroscience↗

bioRxiv2018

A web-based, branching logic questionnaire for the automated classification of migraine

ObjectiveTo identify migraineurs and headache-free individuals with an online questionnaire and automated analysis algorithm.\n\nMethodsWe created a branching-logic, web-based questionnaire--the Penn Online Evaluation of Migraine (POEM)--to obtain standardized headache history from a previously studied cohort. Responses were analyzed with an automated algorithm to assign subjects to one of several categories based on ICHD-3 (beta) criteria. Following a pre-registered protocol, this result was compared to prior diagnostic classification by a neurologist following a direct interview.\n\nResultsOf 118 subjects contacted, 90 (76%) completed the questionnaire; of these 31 were headache-free, 29 migraine without aura (MwoA), and 30 migraine with aura (MwA). Mean age was 41 {+/-} 6 years and 76% were female. There were no significant demographic differences between groups. The median time to complete the questionnaire was 2.5 minutes. Sensitivity of the POEM tool was 42%, 59%, and 70%, and specificity was 100%, 84%, and 94% for headache-free, MwoA, and MwA, respectively. Sensitivity and specificity of the POEM tool for migraine overall (with or without aura), was 83% and 90%, respectively.\n\nConclusionsThe POEM web-based questionnaire, and associated analysis routines, identifies headache-free and migraine subjects with good specificity. It may be useful for classifying subjects for large-scale research studies.\n\nTrial Registration: https://osf.io/sq9ef

epidemiology↗

bioRxiv2018

Pulses of melanopsin-directed contrast produce highly reliable pupil responses that are insensitive to a change in background radiance

PurposeTo measure the pupil response to pulses of melanopsin-directed contrast, and compare this response to those evoked by cone-directed contrast and spectrally-narrowband stimuli.\n\nMethods3-second unipolar pulses were used to elicit pupil responses in human subjects across 3 sessions. Thirty subjects were studied in Session 1, and most returned for Sessions 2 and 3. The stimuli of primary interest were \"silent substitution\" cone- and melanopsin-directed modulations. Red and blue narrowband pulses delivered using the post-illumination pupil response (PIPR) paradigm were also studied. Sessions 1 and 2 were identical, while Session 3 involved modulations around higher radiance backgrounds. The pupil responses were fit by a model whose parameters described response amplitude and temporal shape.\n\nResultsGroup average pupil responses for all stimuli overlapped extensively across Sessions 1 and 2, indicating high reproducibility. Model fits indicate that the response to melanopsin-directed contrast is prolonged relative to that elicited by cone-directed contrast. The group average cone- and melanopsin-directed pupil responses from Session 3 were highly similar to those from Sessions 1 and 2, suggesting that these responses are insensitive to background radiance over the range studied. The increase in radiance enhanced persistent pupil constriction to blue light.\n\nConclusionsThe group average pupil response to stimuli designed through silent substitution provides a reliable probe of the function of a melanopsin-mediated system in humans. As disruption of the melanopsin system may relate to clinical pathology, the reproducibility of response suggests that silent substitution pupillometry can test if melanopsin signals differ between clinical groups.

neuroscience↗

bioRxiv2018

The entrance pupil of the human eye

The pupil aperture of the iris is subject to refraction by the cornea, and thus an outside observer sees a virtual image: the \"entrance pupil\" of the eye. When viewed off-axis, the entrance pupil has an elliptical form. The precise appearance of the entrance pupil is the consequence of the anatomical and optical properties of the eye, and the relative positions of the eye and the observer. This paper presents a ray-traced, exact model eye that provides the parameters of the entrance pupil ellipse for an observer at an arbitrary location. The model is able to reproduce empirical measurements of the shape of the entrance pupil with good accuracy. I demonstrate that accurate specification of the entrance pupil of a stationary eye requires modeling of corneal refraction, the misalignment of the visual and optical axes, and the non-circularity of the pupil aperture. The model, including a three-dimensional ray-tracing function through quadric surfaces, is implemented in open-source MATLAB code.

neuroscience↗

bioRxiv2018

Individual differences in response precision correlate with adaptation bias

The internal representation of stimuli is imperfect and subject to bias. Noise introduced at initial encoding and during maintenance degrades the precision of representation. Stimulus estimation is also biased away from recently encountered stimuli, a phenomenon known as adaptation. Within a Bayesian framework, greater biases are predicted to result from poor precision. We tested for this effect in individual difference measures. 202 subjects contributed data through an on-line experiment (https://cfn.upenn.edu/iadapt). During separate face and color blocks, subjects performed three different tasks: an immediate stimulus-match (15 trials), a 5 seconds delayed match (30 trials), and 5 seconds of adaptation followed by a delayed match (30 trials). The stimulus spaces were circular and subjects entered their responses using a color/face wheel. Bias and precision of responses were extracted by fitting a mixture of von Mises distributions to account for random guesses. Two blocks of each measure were obtained, allowing for tests of measure reliability. We found that reliable differences between individuals in precision were as great as those between tasks or materials. The adaptation manipulation induced the expected bias in responses (colors: 7.8{degrees}; faces: 5.0{degrees}), and the magnitude of this bias reliably and substantially varied between subjects. Across subjects, there was a negative correlation between mean precision and bias (color:{rho} = -0.26; faces:{rho} = -0.13). This relationship was replicated in a new experiment with 192 subjects (color:{rho} = -0.22; faces:{rho} = -0.19). This result is consistent with a Bayesian observer model, in which individual differences in the precision of perceptual representation influences the magnitude of adaptation bias.

neuroscience↗

bioRxiv2018

Adaptation decorrelates shape representations

Perception and neural responses are modulated by sensory history. Visual adaptation, an example of such an effect, has been hypothesized to improve stimulus discrimination by decorrelating responses across a set of neural units. While a central theoretical model, behavioral and neural evidence for this theory is limited and inconclusive. Here, we use a parametric 3D shape-space to test whether adaptation decorrelates shape representations in humans. In a behavioral experiment with 20 subjects, we find that adaptation to a shape class improves discrimination of subsequently presented stimuli with similar features. In a BOLD fMRI experiment with 10 subjects we observe that adaptation to a shape class decorrelates the multivariate representations of subsequently presented stimuli with similar features in object-selective cortex. These results support the long-standing proposal that adaptation improves perceptual discrimination and decorrelates neural representations, offering insights into potential underlying mechanisms.

neuroscience↗

bioRxiv2017

The Human Visual Cortex Response To Melanopsin-Directed Stimulation Is Accompanied By A Distinct Perceptual Experience

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. Pupil-lometry confirmed that the melanopsin stimulus drives a retinal mechanism distinct from luminance. 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.

neuroscience↗