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: 9334595
• 负责人: Geoffrey Karl Aguirre
• 金额: $ 40万
• 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/9334595
• 关键词: Affect; Auras; Behavioral; 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; Ophthalmology; Pain; Pathway interactions; Patients; Perception; Photic Stimulation; Photophobia; Photoreceptors; Photosensitivity; 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; disabling symptom; experience; experimental study; habituation; human subject; irritation; luminance; melanopsin; nervous system disorder; neural correlate; novel; patient population; public health relevance; relating to nervous system; response; somatosensory; visual processing; visual threshold; Affect; Auras; Behavioral; 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; Ophthalmology; Pain; Pathway interactions; Patients; Perception; Photic Stimulation; Photophobia; Photoreceptors; Photosensitivity; 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; disabling symptom; experience; experimental study; habituation; human subject; irritation; luminance; melanopsin; nervous system disorder; neural correlate; novel; patient population; public health relevance; relating to nervous system; response; somatosensory; visual processing; visual threshold

 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（由适用提供）：许多眼科和神经系统疾病的症状是恐惧症：闪烁和明亮的灯光引起的不适和疼痛。更具体地说， 恐惧症是偏头痛患者的关键症状，无论是在标题期间还是在无标题的间歇期。通过系统的行为研究证实了这一临床观察结果，证明了此类患者视觉刺激的不适阈值较低。也有证据表明，某些形式的视觉不适可能与含有光化黑色素蛋白的内在光敏残留神经节细胞（IPRGC）的信号有关。该提案的三个目的将检验以下假设：与偏头痛标头相关的恐惧症与对刺激黑色素蛋白的反应的改变有关，并表征了介导已记录的对偏头痛的中性反应的光感受器机制。所有三个目标都将采用数字光积分来产生光谱调制，从而有选择，稳健地刺激单个光谱类别。我们将测量在黑色素蛋白和锥形感受器上分别定向的刺激的效果，以及黑色素蛋白和锥形信号之间的相互作用。 AIM 1将使用三种不同但互补的反应措施来检查黑色素蛋白刺激在健康的人类受试者中的直接影响：视觉不适和亮度，fMRI和瞳孔光反应的行为报道。我们将研究黑色素蛋白在行为评估的视觉不适和亮度感知中的特定作用，测量对直接黑色素蛋白刺激的持续大脑反应，并使用瞳孔光反应来评估黑色素蛋白反应的个体差异以及随时间差异的稳定性。 AIM 2还将研究健康的对照受试者，并表征黑色素信号与锥体信号是否与信号相互作用，以调节对锥体介导的光闪烁的响应。我们将测量心理物理阈值，以检测锥形介导的闪烁，并评估它们如何受到适应背景光的黑色素成分的变化的影响，使用fMRI测量心理物理效应的中性相关性，并采用新颖的范式，并使用一种使我们能够使用Slugg pubillary pubillary pubillary Signers sighopsisesiss sighopsisesions sighopsisesions sighopsissipers signe sigepied signe sigepins，在沿着视觉途径的早期站点。 AIM 3将基于目标1和2的结果，以表征具有AURA在偏头痛中观察到的光的中性反应增强的光感受器机制。我们还将衡量偏头痛是否在黑色素蛋白的直接或交互作用中表现出与对照的系统差异，以及这种差异是否与该患者人群的光敏度增强有关。