Ocular motor control and MRI in hereditary ataxia

描述(由申请人提供)：这项资助申请详细说明了在丰富的学术环境中指导研究和教学培训的计划，该计划将为候选人提供进行独立研究的知识和技能，这些研究对基础视觉神经科学和临床神经眼科学都具有重要意义。应聘者是一名神经科医生，曾接触过眼球运动和前庭功能障碍以及结构神经成像技术。这一奖项将使候选人能够扩展她的研究技能，开发出更好的小脑疾病基本眼睛运动控制机制的模型，并将这些模型应用到临床有用的方案中，以了解小脑疾病患者经常遭受的致残复视和振荡视的机制。候选人将在两个互补的领域获得新的技能：1)开发眼运动学习的生理和数学模型，以及2)结构和功能磁共振的获取和分析，包括它们在控制系统建模中的应用。教学和研究部分将在David Zee博士的指导下进行，David Zee博士在小脑性共济失调综合征的临床、眼运动和控制系统特征方面拥有专业知识，并在眼运动系统的结构和功能磁共振成像方面拥有经验。在图像处理和脑成像算法方面具有专长的曾傑瑞·普林斯博士和在视觉和躯体运动功能的神经生理学和功能神经成像方面具有专长的Michael Kraut博士将作为主要合作者，并将监督培训计划的神经成像方面，包括改进用于结构和功能成像的高分辨率磁共振技术。威尔默眼科研究所的尼尔·米勒博士将帮助对英博士进行临床神经眼科方面的培训，并将强调她的研究的临床意义。研究部分将涉及开发一种可变形的多维概率脑图谱，该图谱将包括两个模型群体SCA2和SCA6的基因特征、临床表现、眼球运动功能测量和形态测量，这两个模型群体是具有互补眼球运动表型的遗传学定义的小脑性共济失调综合征。这个基于解剖学的模式将使我们能够阐明基本的眼球运动控制和眼球运动学习的模型，重点是凝视保持和屈光适应。我们将检验这一假设，即大脑结构和功能的异常是特定于基因型的，并与疾病的进展有关。了解眼球运动控制中的这些结构-功能关系对小脑疾病的各个方面都有重要的意义，从诊断到临床治疗到康复策略的发展，并可能适用于其他退行性疾病，在这些疾病中存在与眼球错位和异常眼球运动相关的视觉障碍。

DESCRIPTION (provided by applicant): This grant application details a plan for mentored research and didactic training in an enriched academic environment that will provide the candidate with the knowledge and skills to conduct independent research that has important implications for both basic visual neuroscience and clinical neuro-ophthalmology. The candidate is a neurologist with some prior exposure to eye movement and vestibular disorders and structural neuroimaging techniques. This award will enable the candidate to expand her research skills to develop better models of basic ocular motor control mechanisms in cerebellar disease and to implement these models into a clinically useful schema for understanding the mechanisms of the disabling diplopia and oscillopsia often suffered by patients with cerebellar disease. The candidate will acquire new skills in two complementary areas: 1) developing physiological and mathematical models of ocular motor learning, and 2) acquisition and analysis of structural and functional MRI, including their application to control systems modeling. The didactic and research components will be conducted under the mentorship of Dr. David Zee, who has expertise in clinical, ocular motor, and control-systems characterization of cerebellar ataxia syndromes as well as experience in structural and functional MR imaging of the ocular motor system. Dr. Jerry Prince, who has expertise in image processing and brain mapping algorithms, and Dr. Michael Kraut, who has expertise in neurophysiology and functional neuroimaging of visual and somatomotor function, will serve as primary collaborators and will supervise neuroimaging aspects of the training plan, including refinement of high resolution MR techniques for structural and functional imaging. Dr. Neil Miller at the Wilmer Eye Institute will help train Dr. Ying in clinical neuro-ophthalmology and will also emphasize the clinical implications of her research. The research component will involve development of a deformable multidimensional probabilistic brain atlas that will incorporate features of genotype, clinical presentation, functional measures of eye movements, and morphometry for two model populations, SCA2 and SCA6, which are genetically-defined cerebellar ataxia syndromes with complementary ocular motor phenotypes. This anatomically based schema will enable us to elucidate models of basic eye movement control and ocular motor learning, with an emphasis on gaze holding and on phoria adaptation. We will test the hypothesis that abnormalities of brain structure and function are genotype-specific and are associated with progression of disease. Understanding these structure-function relationships in the control of eye movements has important implications for every aspect of cerebellar disease, from diagnosis to clinical management to development of rehabilitative strategies, and may be applicable to other degenerative disease in which there are visual disturbances associated with ocular misalignment and abnormal eye movements.