Functional Brain Networks in Essential Tremor and Dystonic Tremor

特发性震颤和肌张力障碍性震颤的功能性大脑网络

• 批准号: 9262301
• 负责人: Aparna Wagle Shukla
• 金额: $ 17.56万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9262301
• 关键词: Advisory Committees; Affect; Age; Age-Years; Algorithms; Basal Ganglia; Basal Ganglia Diseases; Biological Assay; Biometry; Brain; Cerebellum; Clinical; Clinical Research; Communities; Custom; Data; Data Analyses; Deep Brain Stimulation; Development; Devices; Diagnosis; Diagnostic; Differential Diagnosis; Differentiation Antigens; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Dystonia; Environment; Essential Tremor; FDA approved; Florida; Fostering; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; Gait abnormality; General Population; Genetic; Goals; Guidelines; Healthcare Systems; Human; Image; Imaging Techniques; Impaired cognition; Intention Tremor; Journals; Judgment; Measures; Medical; Mentors; Methods; Motor Cortex; Movement Disorders; New York; Operative Surgical Procedures; Output; Parkinson Disease; Patients; Pattern; Pharmacological Treatment; Physiological; Physiology; Play; Prevalence; Progressive Disease; Protocols documentation; Research; Research Methodology; Research Personnel; Resources; Retirement; Role; Scanning; Severities; Social Impacts; Spasm; Specialist; Techniques; Therapeutic; Training Activity; Training Programs; Tremor; United States National Institutes of Health; Universities; Work; base; biomedical referral center; blood oxygen level dependent; brain abnormalities; clinical practice; diffusion weighted; disability; dopamine transporter; experience; falls; grasp; imaging modality; improved; individual patient; innovation; insight; lectures; member; nervous system disorder; new therapeutic target; novel; outcome forecast; premature; programs; public health relevance; single photon emission computed tomography; tractography

 DESCRIPTION (provided by applicant): Essential tremor (ET) is regarded as the most common movement disorder with an estimated prevalence of around 4% after the age of 40 years. Diagnosis of ET is ascertained on the basis of defined clinical criteria however there are concerns among movement disorder specialists that ET is over diagnosed in the community. ET is frequently confused with other neurological disorders associated with tremors for example Parkinson's disease. Since the FDA approved dopamine transporter SPECT (the DAT scan) imaging, differentiation of ET from Parkinson's disease has become easier and reliable. The other major differential diagnosis of ET is tremors associated with dystonia (dystonic tremor). Differentiation of ET from dystonic tremor based on the existing clinical methods is a major challenge. Although imaging methods may allow a better differentiation of ET and dystonic tremor, these methods cannot develop without a complete understanding on the pathophysiology of these two disorders. The pathophysiology of ET and dystonic tremor is broadly considered to have relation to abnormal brain networks. ET is primarily related to abnormal functioning of the cerebellum-motor cortex network and dystonic tremor traditionally is related to abnormal basal ganglia-motor cortex network. However recent studies suggest the cerebellum-motor cortex network may be important even in dystonic tremor. The primary goal of this K23 study is to characterize and compare these brain networks related to ET and dystonic tremor and advance our pathophysiological understanding. We will examine ET and dystonic tremor with a task based functional MRI protocol and diffusion weighted imaging. We will use a reliable grip force task to identify the amplitude of blood oxygenation level dependent (BOLD) activity and connectivity in these networks. We will use diffusion tractography to examine the connectivity patterns in these networks. Our central hypothesis is that the BOLD activity and the functional and structural connectivity in basal ganglia- motor cortex and cerebellum-motor cortex networks will reveal distinct patterns of abnormalities in ET and dystonic tremor. These critical insights into pathophysiological brain networks that underlie ET and dystonic tremor will be used to develop imaging based markers for differentiation of tremors in the clinical settings The candidate's long-term goal is to develop an independent and successful research program focused on the characterization of movement disorders physiology which can lay guidelines for better diagnosis and improve treatment opportunities for these disorders. To achieve this goal, the candidate has organized a training program involving advanced coursework in functional and structural imaging techniques, tremor physiology methods, biostatistics and clinical research methods. The primary mentor, Dr. David Vaillancourt is a well- established NIH funded researcher in functional and structural imaging techniques. He is an experienced mentor with a reputation for fostering the development of many young trainees into independent, NIH funded, investigators. In this application, he has assembled a team of renowned clinicians, biostatistician and experts in essential tremor, dystonia and imaging to serve as co-mentors and members on the advisory committee. University of Florida provides numerous training activities and resources, including regular seminars, lectures and journal clubs on clinical research, physiological techniques and relevant data analysis techniques. In summary, the candidate has chosen the right setting and environment to conduct a mentor guided research with advanced imaging techniques important for differentiation of ET and dystonic tremor and improved therapeutics in future.

 描述（由申请人提供）：特发性震颤（ET）被认为是最常见的运动障碍，估计40岁后的患病率约为4%。ET的诊断是根据定义的临床标准确定的，但是运动障碍专家担心ET在社区中被过度诊断。ET经常与其他与震颤相关的神经系统疾病相混淆，例如帕金森病。自从FDA批准多巴胺转运蛋白SPECT（DAT扫描）成像以来，ET与帕金森病的鉴别变得更加容易和可靠。ET的另一个主要鉴别诊断是与肌张力障碍相关的震颤（肌张力障碍性震颤）。根据现有的临床方法区分ET和张力障碍性震颤是一个重大挑战。虽然成像方法可以更好地区分ET和张力障碍性震颤，但如果没有对这两种疾病的病理生理学的完全理解，这些方法就无法发展。ET和张力障碍性震颤的病理生理学被广泛认为与异常的脑网络有关。ET主要与小脑-运动皮层网络功能异常有关，而张力障碍性震颤传统上与基底节-运动皮层网络异常有关。然而，最近的研究表明，小脑运动皮层网络可能是重要的，即使在张力障碍性震颤。这项K23研究的主要目标是表征和比较这些与ET和张力障碍性震颤相关的脑网络，并推进我们的病理生理学理解。我们将研究ET和肌张力障碍性震颤与任务为基础的功能性MRI协议和扩散加权成像。我们将使用一个可靠的握力任务，以确定这些网络中的血氧水平依赖（BOLD）活动和连接的幅度。我们将使用扩散纤维束成像来检查这些网络中的连接模式。我们的中心假设是，BOLD活动和基底神经节-运动皮层和小脑-运动皮层网络的功能和结构连接将揭示ET和张力障碍性震颤异常的不同模式。这些关键的洞察到病理生理大脑网络的基础ET和张力障碍性震颤将被用来开发基于成像的标记物在临床环境中的震颤的分化候选人的长期目标是开发一个独立的和成功的研究计划，专注于运动障碍生理学的表征，可以奠定更好的诊断和改善这些疾病的治疗机会的指导方针。为了实现这一目标，候选人组织了一个培训计划，涉及功能和结构成像技术，震颤生理学方法，生物统计学和临床研究方法的高级课程。主要的导师，博士大卫Vaillancourt是一个完善的国家卫生研究院资助的研究人员在功能和结构成像技术。他是一位经验丰富的导师，以促进许多年轻学员发展为独立的NIH资助的研究人员而闻名。在这项申请中，他组建了一个由著名的临床医生、生物统计学家和特发性震颤、肌张力障碍和成像专家组成的团队，担任咨询委员会的共同导师和成员。佛罗里达大学提供大量的培训活动和资源，包括定期的研讨会，讲座和关于临床研究，生理技术和相关数据分析技术的期刊俱乐部。总之，候选人选择了正确的设置和环境，以进行导师指导的研究，先进的成像技术对ET和张力障碍性震颤的区分以及未来改进的治疗方法很重要。