Pathophysiology of Spasmodic Dysphonia: a TMS study

描述（由申请人提供）：人类生活中最有意义的方面之一是沟通。人类交流的主要方式是声音，因此声音的损害可能对一个人充分参与社会的能力产生破坏性后果。内收肌痉挛性发声障碍（AdSD）是一种局灶性肌张力障碍，会影响声带肌肉，严重损害说话能力。这种基于神经学的运动障碍没有诊断标志物，经常与其他声音障碍混淆。通常人们在被正确诊断之前几年，才知道没有长期有效的治疗方法。AdSD的误诊导致提供无效的治疗，如声音治疗，延长这种衰弱的沟通障碍，并导致不必要的医疗保健费用。越来越多的证据表明，患有其他类型的局灶性肌张力障碍的人皮质抑制减少，导致过度兴奋，这可能导致运动控制异常。经颅磁刺激（TMS）是一种安全、无创的工具，可以提供有关疾病神经生理基础的广泛信息。这已被广泛用于调查局灶性手肌张力障碍，大大提高了对这种疾病的理解，但尚未用于痉挛性发声障碍。响应PA 10-156的R21提案将在主要受SD、甲杓状软骨和TMS影响的肌肉中使用细线EMG电极，以测量健康人和SD患者中与喉皮质延髓控制相关的中枢传导潜伏期和皮质内兴奋和抑制。它也将很好地使用 已建立的技术，以收集相同的数据，在未受影响的皮质脊髓控制的手。设计图：将进行甲杓肌和第一骨间背侧肌皮质兴奋性的两组比较（健康与AdSD）。预期成果：它将完善在初步数据部分中描述的技术，以优化喉部TMS测量的程序;开始建立健康人兴奋性测量的标准;确定手部测量与喉肌的关系;并比较SD受试者与健康受试者的数据。影响力：本研究的结果将：（1）推进关于中枢神经系统病理生理学的知识在AdDS，（2）阐明潜在的神经生理学基础的障碍，如皮质内机制不同于健康，如果它是本地化的受影响的肌肉组织或弥漫性。（三） 它将完善技术，为其他调查的兴奋性在喉。长期目标：未来的工作可能会导致AdSD和其他疾病之间更明确的鉴别诊断和创新的循证干预措施的发展直接推进NIDCD的使命。 公共卫生相关性：这项建议将建立技术，以安全地测量皮质潜伏期和兴奋性的肌肉声带在喉。它将使用这些技术来确定哪些神经机制是错误的神经运动障碍，影响声带，痉挛性发声障碍，通过比较反应，在受影响的肌肉未受影响的肌肉在健康的人和那些与障碍。

DESCRIPTION (provided by applicant): One of the most meaningful aspects to human life is communication. The primary method of communication in humans is voice, thus impairment of the voice can have a devastating consequences in one's ability to fully participate in society. Adductor spasmodic Dysphonia (AdSD) is a type of focal dystonia that affects the muscles of the vocal cords and can severely impair the ability to speak. There is no diagnostic marker for this neurologic-based movement disorder and it is frequently confused with other voice disorders. Often people go years before being correctly diagnosed, only to learn that there are no long-term efficacious treatments available. Misdiagnosis of AdSD leads to provision of ineffective treatment such as voice therapy prolonging this debilitating communication disorder and resulting in unnecessary health care expenses. There is growing evidence that people with other types of focal dystonia have reduced cortical inhibition, leading to excessive excitation, which may contribute to the resultant abnormal motor control. Transcranial magnetic stimulation (TMS) is a safe, non-invasive tool that can provide extensive information about the neurophysiologic underpinnings in a disorder. This has been used extensively to investigate focal hand dystonia, greatly enhancing the understanding of that disorder, but has not been used in spasmodic dysphonia. This R21 proposal in response to PA 10-156 will use fine wire EMG electrodes in the muscle primarily affected by SD, the thyroarytenoid, and TMS to measure the central conduction latency and intracortical excitation and inhibition associated with the corticobulbar control of the larynx in healthy people and people with SD. It will also use well established techniques to collect the same data in the unaffected corticospinal control of the hand. Design: Two group comparison (healthy vs. AdSD) of the cortical excitability of the thyroarytenoid muscle and first dorsal interosseous muscle will be performed. Expected outcomes: It will refine techniques described in the preliminary data section to optimize procedures for TMS measurement in the larynx; begin to establish norms for the excitability measures in healthy people; determine the relationship of measures in the hand to the larynex; and compare data in subjects with SD to healthy. Impact: The results of this study will: (1) advance the knowledge regarding the central nervous system pathophysiology in AdDS, (2) elucidate potential neurophysiologic underpinnings of the disorder such as which intracortical mechanism differs from healthy and if it is localized to the affected musculature or pervasive. (3) It will refine techniques for other investigations of excitability in the larynx. Long term objecties: Future work may lead to a more definitive differential diagnosis between AdSD and other disorders and the development of innovative evidence-based interventions directly advancing the mission of NIDCD. PUBLIC HEALTH RELEVANCE: This proposal will establish techniques to safely measure the cortical latency and excitability of the muscles of the vocal cords in the larynx. It will use thos techniques to determine which neural mechanisms are faulty in a neurologic movement disorder that affects the vocal cords, spasmodic dysphonia, by comparing responses in the affected muscles to unaffected muscles in healthy people and those with the disorder.