Neurophysiologic Correlates of Sensory Over-Responsivity in Tourette Syndrome

抽动秽语综合征感觉过度反应的神经生理学相关性

• 批准号: 10644333
• 负责人: David A Isaacs
• 金额: $ 17.66万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10644333
• 关键词: Academic Medical Centers; Accounting; Adolescence; Adolescent; Adult; Affect; Age; Aptitude; Attention deficit hyperactivity disorder; Auditory; Autonomic Dysfunction; Award; Awareness; Behavior; Behavioral; Biological Markers; Child; Childhood; Clinic; Clinical; Clinical Management; Clinical Research; Clinical Trials; Clinical Trials Design; Clinical and Translational Science Awards; Clothing; Data; Development; Development Plans; Diagnosis; Dimensions; Disease; Disease model; Distress; Educational Curriculum; Educational workshop; Electroencephalography; Emotional; Ensure; Environment; Event; Event-Related Potentials; Exhibits; Faculty; Fostering; Frequencies; Functional disorder; Funding; Future; General Population; Gilles de la Tourette syndrome; Goals; Grant; Heart Rate; Heterogeneity; Impairment; Individual; Industry; Institution; International; Investigation; Knowledge; Link; Longevity; Longitudinal Studies; Measurement; Mental disorders; Mentors; Methodology; Mission; Modeling; Monitor; Motor; Movement Disorders; National Institute of Neurological Disorders and Stroke; Nature; Neurobiology; Neurodevelopmental Disorder; Neurology; Noise; Patients; Perception; Pharmaceutical Preparations; Phenotype; Physiological Processes; Population; Practice Guidelines; Principal Investigator; Productivity; Psychophysiology; Quality of life; Reporting; Research; Research Personnel; Research Project Grants; Research Proposals; Research Support; Rest; Risk; Risk Marker; Sample Size; Sampling; Scalp structure; School-Age Population; Scientist; Secure; Sensory; Sensory Disorders; Sensory Manifestations; Severities; Signal Transduction; Site; Skin; Stimulus; Symptoms; Tactile; Techniques; Time; Training; Visit; age group; arm; base; candidate identification; candidate marker; career; career development; clinical development; clinical infrastructure; clinical risk; clinically significant; experience; follow-up; functional disability; heart rate variability; improved; indexing; insight; motor symptom; multimodality; neurophysiology; neuropsychiatric symptom; non-motor symptom; novel; patient oriented; premonitory sensory phenomena; professor; psychiatric symptom; recruit; response; sensory gating; sensory input; sensory stimulus; sex; study population; symposium

Project Summary / Abstract Candidate: David Isaacs, MD, MPH is Assistant Professor in the Department of Neurology at Vanderbilt University Medical Center. During his faculty tenure, he has demonstrated enthusiasm and aptitude for patient- centered research, with emphasis on non-motor aspects of movement disorders. Notable early career highlights include founding Vanderbilt’s Adult Tourette Syndrome (TS) Clinic and co-directing Vanderbilt’s Tourette Association of America (TAA) Center of Excellence; securing multiple extra- and intra-mural grants, including the TAA Young Investigator Award to support research into sensory phenomena in TS; and serving as site principal investigator for industry-sponsored clinical trials in TS. He seeks to become a leading researcher in neurophysiologic mechanisms of non-motor symptoms in TS and other movement disorders. Research Project: TS affects 0.5-0.8% of school-aged children, one-third of whom suffer bothersome tics into adulthood. Tics are the defining feature of TS, but sensory symptoms are widespread. In particular, over 50% of children and 80% of adults with TS report sensory over-responsivity (SOR), defined as heightened awareness of and behavioral reactivity to sensory stimuli. SOR is an integral facet of the TS phenotype, but significant knowledge gaps surround its clinical significance and neurobiological underpinnings. This proposal seeks to clarify the mechanistic bases of SOR in TS (Aims 1 and 2) and to determine whether SOR is a risk marker for more severe clinical course in TS (Aim 3). To achieve Aims 1 and 2, Dr. Isaacs will use quantitative electroencephalography (EEG) and multi-modal autonomic measurement to assess neurophysiologic response to auditory and tactile stimuli in adults with TS. To achieve Aim 3, he will use validated rating scales to assess motor, sensory, and psychiatric symptoms in adolescents with TS at two time points: baseline and 2 years. Study results will deepen insight into TS pathophysiology and identify risk markers for more severe TS course. Career Development Plan and Goals: With guidance from his Scientific Steering Committee, Dr. Isaacs has created a curriculum incorporating formal coursework, workshops, conferences, and individualized training with mentors and collaborators to adequately prepare himself for independent research in the neurophysiologic basis of non-motor aspects of movement disorders. His short-term career goals are to develop proficiency in 1) measurement of sensory and neuropsychiatric symptoms; 2) event-related potentials and quantitative EEG methodology; and 3) psychophysiological techniques complementary to EEG. Environment: Vanderbilt University Medical Center is an optimal academic environment for nurturing Dr. Isaacs’ maturation into a fully-fledged independent researcher. The institution has an exceptional track record for fostering productive, independently funded, and internationally renowned clinician-scientists. The primary mission of Vanderbilt’s Clinical and Translational Science Award is provision of infrastructure for clinical research excellence, with an entire arm devoted to training and career development.

项目总结/摘要 候选人：大卫艾萨克斯，医学博士，公共卫生硕士是助理教授在神经学系在范德比尔特 大学医学中心。在他的教师任期内，他表现出热情和耐心的能力- 以运动障碍为中心的研究，重点是运动障碍的非运动方面。早期职业生涯 他的亮点包括成立了范德比尔特的成人图雷特综合征（TS）诊所，并共同指导了范德比尔特的 美国妥瑞症协会（TAA）卓越中心;获得多个额外和校内赠款， 包括TAA青年研究者奖，以支持TS中感觉现象的研究; 作为TS行业申办临床试验的研究中心主要研究者。他想成为一个领导者。 研究TS和其他运动障碍的非运动症状的神经生理机制。 研究项目：TS影响0.5-0.8%的学龄儿童，其中三分之一的人患有令人烦恼的抽搐， 成年抽搐是TS的定义特征，但感觉症状很普遍。特别是，超过50% 的儿童和80%的TS成人报告感觉过度反应（SOR），定义为 对感官刺激的意识和行为反应。SOR是TS表型的一个组成部分，但 围绕其临床意义和神经生物学基础的重大知识缺口。这项建议 试图澄清TS（目标1和2）中SOR的机械基础，并确定SOR是否是一种风险 TS中更严重临床病程的标志物（目的3）。为了实现目标1和2，艾萨克斯博士将使用定量 脑电图（EEG）和多模式自主神经测量，以评估神经生理反应 对成年TS患者的听觉和触觉刺激。为了实现目标3，他将使用经过验证的评级量表来评估 运动，感觉和精神症状的青少年TS在两个时间点：基线和2年。 研究结果将加深对TS病理生理学的了解，并确定更严重TS过程的风险标志物。 职业发展计划和目标：在科学指导委员会的指导下，Isaacs博士 创建了一个课程，包括正式的课程，研讨会，会议和个性化的培训， 导师和合作者充分准备自己在神经生理学的独立研究 运动障碍的非运动方面的基础。他的短期职业目标是熟练掌握1） 感觉和神经精神症状的测量; 2）事件相关电位和定量EEG 方法学; 3）与EEG互补的心理生理学技术。 环境：范德比尔特大学医学中心是培养博士的最佳学术环境。 艾萨克斯成长为一名成熟的独立研究员。该机构有着出色的业绩记录 培养生产力，独立资助，国际知名的临床科学家。主 范德比尔特临床和转化科学奖的使命是为临床 研究卓越，整个手臂致力于培训和职业发展。