INVESTIGATION AND TREATMENT OF OCULAR MOTOR DISORDERS

拟议研究的长期目标是：(1)更多地了解损害日常活动所需视力的人类眼球运动障碍，以及(2)评估恢复清晰视力的治疗措施。研究策略是将可靠的眼球运动测量与患者做出自然行为的视觉抱怨联系起来；使用正常和异常眼球运动的测量来测试生物学上可信的数学模型；以及通过对照试验评估眼球运动障碍的新疗法。根据先前的研究，有五个具体的目标：第一个项目包括测试获得性摆式眼球震颤的模型。确定大视线移动和亮度变化的影响将用于测试控制系统和神经网络模型。第二个项目旨在确定头部旋转之前的眼球运动是否会在突然头部旋转时改善前庭-眼睛反射的增益。这种“启动”效应可能会发生在各种先前的眼球运动中，但不会发生在凝视保持机制(神经积分器)缺陷的患者身上。第三个项目的目的是测试赫林定律是否适用于分离凝视转移过程中的扫视脉冲(即相等的脉冲大小)。研究对象为正常受试者和核间性眼肌麻痹患者。第四个项目包括对考虑眼跳振荡的模型进行测试。使用一种新的实验技术在正常受试者和患者中诱导眼跳振荡，系统地研究小脑和脑干病变的影响。第五个项目是对东莨菪碱和加巴喷丁治疗获得性眼球震颤的对照评估。已有研究表明，加巴喷丁可抑制摆动性眼球震颤，但共济失调等副作用限制了患者的耐受量。对于眼腭震颤的患者，东莨菪碱可能会更有效。总而言之，这些项目将证明一系列破坏清晰视力的常见眼球运动障碍的发病机制和治疗方面的新信息。

The long-term objectives of the proposed research are: (1) to learn more about human ocular motor disorders that impair the vision necessary for everyday activities, and (2) to appraise therapeutic measures to restore clear vision. The research strategies are to relate reliable measurements of eye movements to visual complaints of patients doing natural behaviors; and to use measurements of normal and abnormal eye movements to test mathematical models that are biologically plausible; and evaluate new treatments of disorders of ocular motility using controlled trials. There are five specific aims, which grow out of prior studies: The first project comprises tests of models for acquired pendular nystagmus. Determination of the effects of large gaze shifts and luminance changes will be used to test control systems and neural network models. The second project aims to determine whether eye movements prior to head rotation improve the gain of the vestibulo-ocular reflex, during sudden head turns. This "priming" effect may occur with a variety of prior eye movements but not in patients with a deficient gaze-holding mechanism (neural integrator). The third project aims to test whether Hering's law applies to saccadic pulses (i.e., equal pulse size) during disjunctive gaze shifts. Normal subjects and patients with internuclear ophthalmoplegia will be studied. The fourth project comprises tests of models that account for saccadic oscillations. Using a new experimental technique to induce saccadic oscillations in normal subjects and patients, the effects of cerebellar and brainstem lesions will be systematically investigated. The fifth project is a controlled evaluation of scopolamine and gabapentin as treatment for acquired forms of nystagmus. It has been shown that gabapentin suppresses pendular nystagmus, but side-effects such as ataxia limit the dosage tolerated. Scopolamine may prove more effective in patients with oculopalatel tremor. In sum, these projects will prove new information on the pathogenesis and treatment of a range of common disorders of eye movements that disrupt clear vision.