Pathophysiology of Spasmodic Dysphonia: a TMS study

描述(申请人提供)：人类生活中最有意义的方面之一就是交流。人类的主要交流方式是语音，因此，语音受损会对一个人充分参与社会的能力产生毁灭性的后果。内收肌痉挛发音障碍(ADSD)是一种局灶性肌张力障碍，影响声带肌肉，严重损害说话能力。这种以神经为基础的运动障碍没有诊断标记物，它经常与其他声音障碍混淆。通常，人们在被正确诊断之前需要数年时间，才知道没有长期有效的治疗方法可用。ADSD的误诊导致提供无效的治疗，如语音治疗，延长了这种使人衰弱的沟通障碍，并导致不必要的医疗费用。越来越多的证据表明，患有其他类型局灶性肌张力障碍的人皮质抑制减少，导致过度兴奋，这可能是导致运动控制异常的原因之一。经颅磁刺激(TMS)是一种安全、非侵入性的工具，可以提供有关疾病神经生理基础的广泛信息。它已被广泛用于研究局灶性手部肌张力障碍，极大地提高了对该疾病的了解，但尚未用于痉挛性发音障碍。这项针对PA 10-156的R21提案将在主要受SD影响的肌肉、甲颧骨和TMS中使用细丝EMG电极，以测量健康人和SD患者与皮质球控制喉部相关的中枢传导潜伏期和皮质内兴奋和抑制。它也会用得很好 建立了在未受影响的手部皮质脊髓控制中收集相同数据的技术。设计：两组(健康组和老年性痴呆组)的甲状旁肌和第一骨间背侧肌的皮质兴奋性比较。预期结果：它将改进初步数据部分中描述的技术，以优化喉部TMS测量的程序；开始为健康人的兴奋性测量建立标准；确定手中测量与喉部的关系；并将SD受试者的数据与健康人进行比较。影响：这项研究的结果将：(1)提高对ADS中枢神经系统病理生理学的认识，(2)阐明ADS的潜在神经生理学基础，如皮质内机制与健康的不同，以及它是否局限于受影响的肌肉系统或弥漫性。(3) 它将改进其他喉部兴奋性研究的技术。长期目标：未来的工作可能导致ADSD和其他疾病之间更明确的鉴别诊断，并开发创新的循证干预措施，直接推动NIDCD的使命。 公共卫生相关性：这项提案将建立安全地测量喉部声带肌肉的皮质潜伏期和兴奋性的技术。它将使用这些技术来确定影响声带的神经运动障碍的神经机制是错误的，通过比较健康人和有这种疾病的人受影响的肌肉对未受影响的肌肉的反应，痉挛性发音困难。

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.