The effects of neural modulation on phonatory function in laryngeal dystonia

项目摘要 本申请将为主要研究者Teresa金伯利博士提供受保护的时间， 支持（1）加快建立指导初级调查员的成功记录;（2）提供研究 培训参与以病人为本的沟通障碍研究的学员;（3）加强 评估语音生产的培训;（4）推进金伯利博士正在进行的翻译 喉肌张力障碍的研究肌张力障碍是一组破坏性的神经运动障碍 可以影响身体的任何部位没有治愈或改善疾病的治疗方法， 该疾病的病理生理学仍然是未知的。最常见的肌张力障碍影响 声带肌肉是喉内收肌张力障碍（AdLD）。患有AdLD的人患有窒息性 由于甲状杓肌（TA）的不自主痉挛引起的声音和言语中断。很长的- 该奖项的长期目标是阐明喉肌张力障碍的病理生理学， 敏感的测试和新的干预措施来治疗这种疾病。该项目建立在博士。 金伯利的尖端工作，开发一种新颖有效的经颅磁刺激（TMS） 评估喉运动皮质区的皮质兴奋性的方法。最近的调查结果表明， 显示了一种非典型的大脑激活模式， AdLD。假设是针对左喉运动的5天抑制性rTMS方案 与TA肌肉相关的区域将增加皮质内抑制并改善发声 在AdLD患者中发挥作用。AdLD患者将参加一项随机、双盲、 假对照的初步试验主要的测试将包括发音功能的评估 (Aim 1）和TMS测量的神经生理学（目的2）。与积极回应有关的因素 还将探讨干预措施（目标3）。该项目为学员提供了一个独特的机会， 在皮质延髓神经生理学交叉点的临床和转化研究中， 侵入性神经调节和嗓音障碍的临床评估。丰富的资源在 马萨诸塞州总医院、MGH健康康复研究所和斯波尔丁康复中心 医院提供了一个优秀的科学环境，以培养下一代的研究人员， 沟通障碍研究的跨学科方法。该项目有可能 通过扩大治疗选择，改善生活质量， 减轻了患有这种疾病的人的医疗负担。从建议中获得的知识 这项研究将扩展到未来的研究，以优化神经调节干预，探索rTMS作为一种 目前治疗的辅助治疗，并确定rTMS是否可以转换为其他声音 疾病或类型的局灶性肌张力障碍。

Project Summary This application will provide the Principal Investigator, Dr. Teresa Kimberley, with protected time and support to (1) accelerate a successful record of mentoring junior investigators; (2) provide research training to mentees engaged in patient-oriented communication disorder research; (3) enhance training in assessing voice production and; (4) advance the translation of Dr. Kimberley's ongoing research on laryngeal dystonia. Dystonia is a group of devastating neurological movement disorders that can affect any body region. There is no cure or disease-modifying treatment and the pathophysiology of the disorder remains largely unknown. The most common dystonia affecting the vocal fold muscles is adductor laryngeal dystonia (AdLD). People with AdLD suffer from a strangled voice and speech interruption due to involuntary spasms of the thyroarytenoid (TA) muscles. The long- term goal of this award is to elucidate the pathophysiology of laryngeal dystonia and to develop sensitive testing and novel interventions to treat the disease. The proposed project builds upon Dr. Kimberley's cutting-edge work of developing a novel and valid transcranial magnetic stimulation (TMS) methodology to assess the cortical excitability of the laryngeal motor cortical area. Recent findings have shown an atypical pattern of brain activation and decreased intracortical inhibition in people with AdLD. The hypothesis is that a 5-day inhibitory rTMS protocol targeted to the left laryngeal motor area associated with the TA muscles will increase intracortical inhibition and improve phonatory function in people with AdLD. Individuals with AdLD will participate in a randomized, double-blinded, sham-controlled, preliminary trial. The primary tests will include assessments of phonatory function (Aim 1) and TMS-measured neurophysiology (Aim 2). Factors associated with positive response to the intervention will also be explored (Aim 3). This project offers a unique opportunity for mentees to train in clinical and translational research that is at the intersection of corticobulbar neurophysiology, non- invasive neuromodulation, and clinical assessment of voice disorders. The rich resources at Massachusetts General Hospital, MGH Institute of Health Professions, and Spaulding Rehabilitation Hospital provide an outstanding scientific environment to train the next generation of researchers in an interdisciplinary approach to communication disorders research. This project has the potential to positively impact people with AdLD by expanding treatment options, improving quality of life and reducing healthcare burden for people with this disorder. The knowledge gained from the proposed study will extend to future research to optimize neuromodulatory interventions, explore rTMS as an adjunct therapy to current treatments, and to determine if rTMS can be translated to other voice disorders or types of focal dystonia.