Investigation and Treatment of Ocular Motor Disorders

描述（由申请人提供）：眼球运动现在被广泛用作神经科学的实验工具，包括记忆和意志的研究。眼球运动的流行源于其易于测量和分析，以及对其神经基础的广泛理解。临床医生主要依靠凝视控制的基本方面来指导他们的诊断，例如大脑如何使眼睛一起运动（共轭）。这项研究的目标是控制眼球运动的几个基本方面，包括对保持视觉清晰和单一至关重要的特性。它还应用了这些基本性质之一，即水平快速运动的共轭性，来开发一个简单的模型来研究多发性硬化症（MS）中常见的疲劳症状。研究策略将是通过应用和测试目前的眼动控制模型来研究凝视异常，这些模型是从基础研究和临床研究中发展出来的：转化研究。这三个具体目标是从之前的资助期内完成的工作中发展而来的：第一个项目涉及快速眼球运动（扫视）的开始和结束。要验证的第一个假设是，产生眼跳开始的机制包括当抑制被解除时，产生眼跳的突发神经元的突然、刻板激活（抑制后反弹放电）。第二个假设是，扫视的结束是由小脑顶状核从兴奋性神经元转换为抑制性爆发神经元决定的。第二个项目旨在为多发性硬化症患者的疲劳现象建立眼运动模型。初步研究表明，在重复性扫视（疲劳测试）中，多发性硬化症患者的内收运动的峰值速度相对于外展运动的峰值速度下降，而对照组则没有。第三个项目旨在更好地了解一种损害视力的获得性眼球震颤（眼腭震颤）。这些振荡的当前模型将使用在先前资助期间完成的美金刚与加巴喷丁治疗试验的详细结果进行测试。

DESCRIPTION (provided by applicant): Eye movements are now widely used as experimental tools in the neurosciences, including studies of memory and volition. The popularity of eye movements derives from their accessibility for measurement and analysis, combined with a broad understanding of their neural substrate. Clinicians mainly depend on basic aspects of gaze control to guide their diagnosis, such as how the brain makes the eyes move together (conjugacy). The proposed research takes aim at several of these basic aspects of the control of eye movements, including properties that are critical for vision to remain clear and single. It also applies one of these basic properties, the conjugacy of horizontal fast movements, to develop a simple model to study the common complaint of fatigue in multiple sclerosis (MS). The research strategy will be to investigate gaze abnormalities by applying and testing current models for the control of eye movements that have been developed from both basic and clinical studies: translational research. The three specific aims grow from work accomplished during the prior funding period: The first project concerns the beginning and ending of rapid eye movements (saccades). The first hypothesis to be tested is that the mechanism generating the beginning of saccades consists of a sudden, stereotyped activation of saccade-generating burst neurons when inhibition is removed from them (post-inhibitory rebound discharge). A second hypothesis is that the ending of saccades is determined by when the cerebellar fastigial nucleus switches firing from excitatory to inhibitory burst neurons. The second project aims to develop an ocular motor model for the phenomenon of fatigue in MS. Preliminary studies indicate that the peak velocity of adducting movements declines relative to the peak velocity of abducting movements during repetitive saccades (a fatigue test) made by MS patients but not by control subjects. The third project aims to better understand a form of acquired nystagmus (oculopalatal tremor) that impairs vision. A current model for these oscillations will be tested using detailed findings from a treatment trial of memantine versus gabapentin completed during the prior funding period. PUBLIC HEALTH RELEVANCE: Taken together, the three proposed projects will provide new information concerning the pathogenesis and treatment of common and visually disabling disorders of eye movements. Eye movements will also be put to work as an experimental tool to investigate the mechanism of generalized fatigue, which afflicts most patients with MS.