Ocular motor control and MRI in hereditary ataxia

遗传性共济失调的眼部运动控制和 MRI

• 批准号: 7685395
• 负责人: SARAH H YING
• 金额: $ 17.57万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7685395
• 关键词: Algorithms; Anatomy; Applications Grants; Area; Atlases; Atrophic; Award; Biological Models; Brain; Brain Mapping; Cerebellar Ataxia; Cerebellar Diseases; Cerebellum; Characteristics; Clinical; Clinical Management; Databases; Degenerative Disorder; Development; Diagnosis; Diplopia; Disease; Disease Progression; Employee Strikes; Environment; Exhibits; Exposure to; Eye; Eye Movements; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Genotype; Goals; Individual; Inherited Spinocerebellar Degenerations; Institutes; Knowledge; LY6E gene; Lobular; Magnetic Resonance Imaging; Measurement; Measures; Mentors; Mentorship; Methodology; Modeling; Neurologist; Ophthalmology; Pathogenesis; Patients; Pattern; Performance; Phenotype; Physiological; Population; Prediction of Response to Therapy; Process; Rehabilitation therapy; Research; Resolution; Severities; Strabismus; Structure; Structure-Activity Relationship; Syndrome; System; Techniques; Testing; Training; Visual; base; clinical phenotype; disability; disease diagnosis; experience; gaze; image processing; in vivo; mathematical model; morphometry; motor control; motor deficit; motor learning; neuroimaging; neurophysiology; novel; oculomotor; outcome forecast; skills; tool; visual image movement; visual neuroscience

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.

描述（由申请人提供）：该拨款申请详细介绍了在丰富的学术环境中进行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，这对基础视觉神经科学和临床神经眼科都有重要影响。候选人是一位神经科医生，之前接触过眼球运动和前庭疾病以及结构神经影像技术。该奖项将使候选人能够扩展她的研究技能，开发更好的小脑疾病基本眼运动控制机制模型，并将这些模型应用到临床上有用的模式中，以了解小脑疾病患者经常遭受的致残性复视和振动视的机制。候选人将获得两个互补领域的新技能：1）开发眼部运动学习的生理和数学模型，2）结构和功能 MRI 的采集和分析，包括其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，他拥有小脑共济失调综合征的临床、眼运动和控制系统特征方面的专业知识，以及眼运动系统的结构和功能 MR 成像方面的经验。杰里·普林斯博士（Jerry Prince）拥有图像处理和大脑映射算法方面的专业知识，迈克尔·克劳特（Michael Kraut）博士拥有神经生理学以及视觉和躯体运动功能的功能性神经影像方面的专业知识，他们将作为主要合作者，监督培训计划的神经影像方面，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·米勒博士将帮助培训应博士的临床神经眼科知识，并将强调她的研究的临床意义。该研究部分将涉及开发可变形的多维概率脑图谱，该图谱将结合两个模型群体 SCA2 和 SCA6 的基因型特征、临床表现、眼球运动功能测量和形态测量，SCA2 和 SCA6 是基因定义的小脑共济失调综合征，具有互补的眼运动表型。这种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部运动学习的模型，重点是注视保持和隐斜视适应。我们将检验以下假设：大脑结构和功能的异常具有基因型特异性，并且与疾病进展相关。了解眼球运动控制中的这些结构-功能关系对于小脑疾病的各个方面都具有重要意义，从诊断到临床管理再到康复策略的制定，并且可能适用于其他退行性疾病，其中存在与眼部错位和异常眼球运动相关的视觉障碍。