THREE-AXIS OCULAR MOTOR CONTROL BY THE CEREBELLUM

本职业发展计划的目标是为眼运动神经眼科的职业生涯提供必要的教育和研究培训，重点是小脑在眼球运动的三轴（水平、垂直和扭转）控制中的作用。该研究计划包括实验和建模方法的结合，并在人类小脑患者和非人类灵长类动物中进行平行研究。额外的培训内容包括统计和数据分析方面的正式指导，眼运动系统的控制系统方法，神经建模技术的指导，以及临床神经眼科学和斜视方面的额外指导。虽然小脑对水平和垂直眼运动的控制已经有了很多了解，但对小脑对扭转运动的控制的研究却非常有限。本实验利用三轴技术的最新进展来研究前庭小脑，特别是絮状体，对眼扭转的贡献。使用三轴磁搜索线圈技术，记录人类小脑患者和灵长类动物手术前后的絮体病变。实验将探讨在视觉（追逐和光动力学）和前庭（低频率和高频）刺激引起的眼球运动中三轴眼速的控制。静态扭转和双目对准的控制也将被研究。后续的实验将关注小脑对线性VOR的贡献以及其他小脑区域病变对三轴眼动行为的影响。这些实验应该能更好地理解前庭小脑病变的病理生理，以及小脑中视觉和眼动信号的三轴表示。他们也补充了其他最近的研究处理扭转控制的外围机制。最后，它们可能会使我们更深入地了解小脑在补偿眼运动系统其他部位病变中的作用，例如上斜斜斜视和其他斜视原因。这可能会导致更好的治疗这些疾病。

The goal of this career development proposal is to provide the educational and research training necessary for a career in ocular motor neuro-ophthalmology, with an emphasis on the role of the cerebellum in the three-axis (horizontal, vertical, and torsional) control of eye movements. The research plan involves a combination of experimental and modeling approaches with parallel studies in human cerebellar patients and non-human primates. Additional training components include formal instruction in statistics and data analysis, control system approaches to the ocular motor system, mentoring in neural modeling techniques, and additional instruction in clinical neuro-ophthalmology and strabismus. Although much has been learned about the cerebellar control of horizontal and vertical eye movements, studies of the cerebellar control of torsion are much more limited. The experiments in this proposal take advantage of recent advances in three-axis techniques to investigate the vestibulocerebellar, and particularly the floccular, contribution to eye torsion. Using a three-axis magnetic search coil technique, recordings will be made in human cerebellar patients and in primates before and after surgical floccular lesions. Experiments will address the control of three-axis eye velocity during eye movements evoked by visual (pursuit and optokinetic) and vestibular (low- and high-frequency) stimulation. The control of static torsion and binocular alignment will also be investigated. Later experiments will focus on the cerebellar contribution to the linear VOR and on the effects of lesions in other cerebellar regions on three-axis eye movement behavior. These experiments should provide a greater understanding of the pathophysiology of vestibulocerebellar lesions, as well the three-axis representation of visual and eye movement signals in the cerebellum. They also complement other recent studies dealing with peripheral mechanisms of torsion control. Finally, they may lead to a greater insight into the role of the cerebellum in compensating for lesions elsewhere in the ocular motor system, such as superior oblique pareses and other causes of strabismus. This might lead to better treatment for these disorders.