NORMAL PHYSIOLOGY, PATHOPHYSIOLOGY, AND TREATMENT OF VOICE DISORDERS

工作总结： 本课题的目的是研究神经生理学控制 正常人的语言和吞咽的喉部运动， 患有喉部运动障碍的人。 研究涉及 感觉输入在喉运动控制中的作用 活动，如发声讲话，气道保护和 吞咽 基础研究已经检查了喉感觉是否 刺激诱导中脑导水管周围灰质（PAG）中的神经元活动， 哺乳动物中与发声有关的中脑区域。 我们 确定了表达Fos的神经元数量，Fos的蛋白产物是 电刺激后PAG内即刻早期基因c-Fos 实验性喉上级神经内分支的解剖学研究 和对照动物。 已知涉及的PAG的离散区域 在发声中，发现有最多的Fos表达 实验动物的神经元。来检验感觉的作用 在语音和吞咽的喉部控制期间， 在正常志愿者中完成。 喉内收肌反射， 通过刺激上级喉神经（SLN）引起， 被认为在气道保护中起作用，在不同的时间段进行了研究。 正常志愿者的吞咽阶段。 据推测， 反射机制在吞咽期间将特别活跃， 气道保护具有功能重要性。 SLN被刺激， 不同时间：吞咽开始时;吞咽期间;以及 在吞咽完成后3到5秒之间。 没想到的是， 后一种反应，即双侧发生在65 - 75 ms之间的R2 在吞咽期间SLN刺激被抑制3秒后， 吞咽后。 相反，早期的R1反应不受影响 通过吞咽活动。 这表明喉部保护性大脑 在吞咽过程中，茎机制继续活跃， 可抑制由感觉刺激引起的中枢反应。 的 在讲话和屏住呼吸时，感觉的作用也是 在正常志愿者中进行检查。 在这两种意志控制中 任务，早期R1脑干反应的频率和振幅 与后来的R2双侧反应一样受到抑制。 因此 自主性喉运动控制通常抑制保护性气道 反射 我们也继续我们的研究喉感觉运动功能 在运动控制障碍的个体中。 之前我们展示了 喉部感觉运动反射反应在 反射反应条件反射，持续刺激， 在正常志愿者中。 这种反射反应与 内收肌痉挛性发音障碍患者的发音受到抑制。 结果 表明正常感觉运动反应的减少 抑制机制可能在内收肌的病理生理学中起作用 痉挛性发音困难 为了检验这是否是内收肌特有的 痉挛性发音困难，对另外两组患者的研究， 今年完成的：患有痉挛性外展肌发声困难的人士，以及 有声带震颤的人 在个体中发现的异常 外展肌痉挛性发声障碍与 内收肌痉挛性发声困难，而声音震颤的人 没有喉感觉运动反应条件反射异常。 因此，痉挛性发声障碍的病理生理学被发现， 与声带震颤不同 这个项目将被终止，取而代之的是感觉功能的研究 喉部疾病

Summary of Work: The purpose of this project is to examine the neurophysiological control of laryngeal movement for speech and swallowing in normal individuals and individuals with laryngeal movement disorders. Studies addressed the role of sensory input in laryngeal motor control for volitional activities such as phonation for speech, airway protection and swallowing. Basic studies have examined whether laryngeal sensory stimulation induced neuronal activity in the periaqueductal gray (PAG), a midbrain region known to be involved in vocalization in mammals. We determined the number of neurons expressing Fos, the protein product of the immediate early gene c-Fos in the PAG after electrical stimulation of the internal branch of the superior laryngeal nerve in experimental and control animals. Discrete areas of the PAG well known to be involved in vocalization were found to have the greatest numbers of Fos-expressing neurons in the experimental animals. To examine the role of sensation during laryngeal control for speech and swallow, two studies were completed in normal volunteers. The laryngeal adductor reflex, which can be elicited by stimulation of the superior laryngeal nerve (SLN) and is thought to have a role in airway protection, was studied during different phases of swallowing in normal volunteers. It was hypothesized that this reflex mechanism would be particularly active during the swallow when airway protection has functional importance. The SLN was stimulated at different times: on initiation of the swallow; during the swallow; and between 3 and 5 seconds after completion of the swallow. Unexpectedly, the later response, the R2 which occurs bilaterally between 65 and 75 ms after SLN stimulation was suppressed during the swallow and for 3 seconds after swallowing. In contrast, the earlier R1 response was unaffected by swallowing activity. This suggests that laryngeal protective brain stem mechanisms continue to be active during swallowing while later more central responses elicited by sensory stimulation may be suppressed. The role of sensation during speech and while holding one's breath was also examined in normal volunteers. During both of these volitional control tasks, the frequency and amplitude of the early R1 brainstem response were suppressed as were the later R2 bilateral responses. Thus volitional laryngeal motor control usually suppresses protective airway reflexes. We have also continued our studies of laryngeal sensory-motor functioning in individuals with motor control disorders. Previously we demonstrated that laryngeal sensori-motor reflex responses are suppressed during reflex response conditioning with continued stimulation at precise intervals in normal volunteers. Such reflex responses were not similarly suppressed in individuals with adductor spasmodic dysphonia. The results suggested that a reduction in the normal sensori-motor response suppression mechanisms may play a role in the pathophysiology of adductor spasmodic dysphonia. To examine whether this was specific to adductor spasmodic dysphonia, studies on two additional patient groups were completed this year: persons with abductor spasmodic dysphonia, and individuals with vocal tremor. The abnormalities found in individuals with abductor spasmodic dysphonia were similar to those found in persons with adductor spasmodic dysphonia, while individuals with vocal tremor did not have laryngeal sensori-motor response conditioning abnormalities. Thus the pathophysiology involved in spasmodic dysphonia was found to differ from that involved in vocal tremor. This project will be terminated and replaced by study of sensory function in laryngeal disorders.