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。 正常人的喉部运动对言语和吞咽的影响 有喉部运动障碍的个体。研究针对的是 感觉输入在喉运动控制中的作用 语音发声、呼吸道保护和 吞下去。基础研究已经检查了喉部感觉 刺激诱导中脑导水管周围灰质(PAG)神经元活动， 已知的哺乳动物中参与发声的中脑区域。我们 测定Fos蛋白产物Fos表达的神经元数量 电刺激后PAG即刻早期基因c-Fos的表达 对实验性喉上神经内支的影响 并控制动物。广为人知的PAG的离散区域 在发声时，Fos的表达数量最多 实验动物的神经元。来审视感觉的作用 在喉部控制说话和吞咽的过程中，有两项研究 在正常志愿者中完成。喉内收肌反射，它可以 由刺激喉上神经(SLN)而引起 被认为在呼吸道保护中具有作用，在不同的时期进行了研究 正常志愿者的吞咽阶段。据推测，这是 当吞咽时，反射机制会特别活跃。 呼吸道保护具有重要的功能。刺激SLN是在 不同的时间：在燕子开始的时候；在燕子的时候；和 在吞咽完成后的3到5秒之间。出乎意料的是， 后一种反应，即出现在65到75毫秒之间的双边R2 在吞咽过程中抑制SLN刺激并持续3秒 吞下之后。相反，较早的R1响应未受影响 通过吞咽活动。这表明喉部保护性脑 在吞咽过程中，茎的机制继续活跃，而之后更多 感官刺激引起的中枢反应可能会受到抑制。这个 感觉在说话和屏息时的作用也是 在正常志愿者中进行了检查。在这两种意志控制中 任务、早期R1脑干反应的频率和幅度 与后来的R2双侧反应一样受到抑制。因此， 意志性喉部运动控制通常抑制保护性呼吸道 条件反射。 我们还继续我们对喉部感觉运动功能的研究 在患有运动控制障碍的个体中。在此之前我们演示了 喉部感觉-运动反射反应在 精确持续刺激的反射反应条件反射 正常志愿者的间歇时间。这种反射反应并不是类似的。 有内收肌痉挛发音困难的个体抑制。结果是 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发挥作用 痉挛性发音困难。以检查这是否为内收肌所特有 痉挛性发音困难，对另外两个患者组的研究 今年完成：外展肌痉挛发音困难患者，以及 有发声震颤的个体。在个体身上发现的异常 外展肌痉挛发音障碍与正常人相似 有内收肌痉挛发音困难，而有发声震颤的人 无喉感觉-运动反应条件反射异常。 因此，痉挛性发音困难的病理生理学被发现 不同于声带震颤。 该项目将被终止，取而代之的是对感觉功能的研究 在喉部疾病中。

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.