Investigation and Treatment of Ocular Motor Disorders

描述（由申请人提供）：眼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测量和分析的可访问性，以及对其神经基质的广泛理解。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移动（共轭）。拟议的研究旨在控制眼球运动的几个基本方面，包括对视觉保持清晰和单一至关重要的特性。它也适用于这些基本属性之一，水平快速运动的共轭性，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从基础和临床研究中开发的用于控制眼球运动的当前模型来调查凝视异常：转化研究。这三个具体目标是在前一个资助期内完成的工作的基础上发展起来的：第一个项目涉及快速眼动（扫视）的开始和结束。要测试的第一个假设是，产生扫视开始的机制包括突然的，刻板的激活扫视产生的爆发神经元时，从他们的抑制被删除（抑制后反弹放电）。第二个假设是，扫视的结束是由小脑顶核从兴奋性到抑制性爆发神经元的转换决定的。第二个项目的目的是开发一个眼运动模型的疲劳现象，在MS。初步研究表明，内收运动的峰值速度下降相对于外展运动的峰值速度在重复扫视（疲劳测试）MS患者，但不是由对照组。第三个项目旨在更好地了解一种损害视力的后天性眼球震颤（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。 公共卫生相关性：这三个拟议项目将提供有关常见和视力障碍性眼球运动障碍的发病机制和治疗方法的新信息。眼球运动也将作为一种实验工具来研究全身性疲劳的机制，这种疲劳困扰着大多数MS患者。

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.