Melanopsin and cone signals in human visual processing

人类视觉处理中的黑视蛋白和视锥细胞信号

• 批准号: 8964828
• 负责人: Geoffrey Karl Aguirre
• 金额: $ 38.6万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8964828
• 关键词: Affect; Auras; Brain; Cells; Classic Migraine; Clinical; Color; Cone; Data; Detection; Disease; Esthesia; Eye; Frequencies; Functional Magnetic Resonance Imaging; Glare; Headache; Human; Individual; Individual Differences; Insula of Reil; Light; Link; Measures; Mediating; Migraine; Pain; Pathway interactions; Patients; Perception; Photic Stimulation; Photophobia; Photoreceptors; Problem Solving; Psychophysics; Pupil; Reporting; Retinal Cone; Retinal Ganglion Cells; Role; Signal Transduction; Site; Somatosensory Cortex; Source; Stimulus; Study Subject; Symptoms; Techniques; Testing; Time; Variant; Visual; Visual Cortex; Visual Discomfort; Visual Pathways; Visual Perception; Visual system structure; area striata; behavior measurement; behavioral study; constriction; digital; experience; habituation; human subject; irritation; luminance; melanopsin; nervous system disorder; neural correlate; novel; patient population; public health relevance; relating to nervous system; research study; response; somatosensory; visual process; visual processing

 DESCRIPTION (provided by applicant): A symptom of many ophthalmologic and neurologic disorders is photophobia: discomfort and pain from flickering and bright lights. More specifically, photophobia is a key symptom in patients with migraine, both during headache and also in the headache-free inter-ictal period. This clinical observation has been confirmed by systematic behavioral studies demonstrating lower discomfort thresholds for visual stimulation in such patients. There is also evidence that some forms of visual discomfort may be related to signals from intrinsically photosensitive retinal ganglion cells (ipRGCs) that contain the photopigment melanopsin. The three aims of this proposal will test the hypothesis that photophobia associated with migraine headache is related to altered responses to stimulation of melanopsin, as well as characterize the photoreceptor mechanisms that mediate the documented elevated neural response to light observed in migraine with aura. All three aims will employ a digital light integrator to produce spectral modulations that selectively and robustly stimulate individual photopigment classes. We will measure the effect of stimulation directed separately at melanopsin and the cone photoreceptors, as well as interactions between melanopsin and cone signals. Aim 1 will examine direct effects of melanopsin stimulation in healthy human subjects, using three distinct but complementary response measures: behavioral reports of visual discomfort and perception of brightness, fMRI and the pupillary light response. We will examine the specific role of melanopsin in behaviorally-assessed visual discomfort and brightness perception, measure sustained brain responses to direct melanopsin stimulation, and use the pupillary light response to assess individual differences in melanopsin responsivity as well as the stability of these differences over time. Aim 2 will also study healthy control subjects and characterize whether and how melanopsin signals interact with signals from cones, to regulate the response to cone-mediated light flicker. We will measure psychophysical thresholds for detection of cone-mediated flicker and assess how these are affected by changes in the melanopic component of an adapting background light, use fMRI to measure neural correlates of the psychophysical effects, and employ a novel paradigm that allows us to use the sluggish pupillary light response to test the hypothesis that melanopsin signals regulate the response to cone-mediated flicker at an early site along the visual pathways. Aim 3 will build on the results of Aims 1 and 2 to characterize the photoreceptor mechanism of the enhanced neural response to light observed in migraine with aura. We will also measure whether the migraineurs demonstrate systematic differences with controls in either the direct or interactive effects of melanopsin, and whether such differences are related to the enhanced light sensitivity of this patient population.

 描述（由申请人提供）：许多眼科和神经系统疾病的症状是畏光：闪烁和强光带来的不适和疼痛。 畏光是偏头痛患者的一个关键症状，无论是在头痛期间还是在无头痛发作间期，这一临床观察结果已被系统行为研究证实，表明此类患者对视觉刺激的不适阈值较低。某些形式的视觉不适可能与含有感光色素黑视蛋白的固有光敏视网膜神经节细胞（ipRGC）发出的信号有关。该提案的三个目标将检验与偏头痛相关的畏光是一种假设。与对黑视蛋白刺激的反应改变有关，以及表征光感受器机制，该机制介导在先兆偏头痛中观察到的对光的升高的神经反应。这三个目标都将采用数字光积分器来产生光谱调制，选择性地、强有力地刺激个体。我们将测量分别针对黑视蛋白和视锥细胞光感受器的刺激效果，以及黑视蛋白和视锥细胞信号之间的相互作用。 1 将使用三种不同但互补的反应措施来检查黑视蛋白刺激对健康人类受试者的直接影响：视觉不适和亮度感知的行为报告、功能磁共振成像和瞳孔光反应我们将检查黑视蛋白在行为评估中的具体作用。视觉不适和亮度感知，测量大脑对直接黑视蛋白刺激的持续反应，并使用瞳孔光反应来评估黑视蛋白反应性的个体差异以及稳定性目标 2 还将研究健康对照受试者，并表征黑视蛋白信号是否以及如何与视锥细胞信号相互作用，以调节对视锥细胞介导的闪烁的反应。评估这些如何受到适应性背景光的黑素成分变化的影响，使用功能磁共振成像来测量心理物理效应的神经相关性，并采用一种新的范式，使我们能够使用迟缓的瞳孔光响应来测试黑视蛋白信号调节视觉通路早期部位对视锥细胞介导的闪烁的反应的假设，目标 3 将建立在目标 1 和 2 的结果的基础上，以表征增强的神经对光响应的光感受器机制。我们还将测量偏头痛患者在黑视蛋白的直接作用或相互作用作用方面是否与对照组存在系统性差异，以及这些差异是否与该患者的光敏感性增强有关。人口。