The Bases Of Normal And Disordered Laryngeal And Speech

正常和紊乱的喉部和言语的基础

• 批准号: 6990714
• 负责人: Christy Leslie Ludlow
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6990714
• 关键词: adolescence (12-20); brain stem; child (0-11); clinical research; communication disorders; disease /disorder prevention /control; disease /disorder proneness /risk; dystonia; family genetics; gene mutation; genetic disorder; genetic screening; human subject; immunocytochemistry; laryngoscopy; larynx disorder; larynx muscle; motor neurons; nervous system disorder; nervous system prosthesis; neuromuscular function; sensory feedback; speech disorders; swallowing; voice

Our goal is to improve the treatment and prevention of voice, speech and swallowing disorders. For this purpose, the Section conducts both research on the neural control of the larynx for voice, speech and swallowing as well as studies of the pathogenesis and pathophysiology of neurogenic idiopathic disorders. Clinical trials are being conducted to develop new treatments for spasmodic dysphonia and chronic pharyngeal dysphagia. Significant advances have been made during the last year in several areas. The laryngeal adductor response is a selective thyroarytenoid muscle spasm that occurs in response to stimulation of mechanoreceptors in the larynx. Previously we have found that when this reflex is elicited by electrical stimulation of afferents in the superior laryngeal nerve, responses are not normally suppressed in patients with spasmodic dysphonia, an idiopathic chronic focal dystonia affecting voice production. We have used an animal model to determine the brain stem regions that may be involved in eliciting this reflex. Fos immunohistochemistry was used to determine which neurons in the medulla fired when this reflex was elicited. With unilateral electrical stimulation of the internal branch of the superior laryngeal nerve, significant increases (p <0.003) occurred in the interstitial subnucleus, the ventrolateral subnucleus, the commissural subnucleus of the nucleus tractus solitarius, the lateral tegmental field of the reticular formation, the area postrema and the nucleus ambiguus. This pathway involved a subset of the same structures as those involved in cough and swallow. Neither the dorsal motor nucleus of the vagus, usually active for swallow, nor the nucleus retroambiguus, retrofacial nucleus, or the lateral reticular nucleus, usually active for cough, were active with elicitation of the laryngeal adductor response alone. Because many voice disorders have their onset with laryngitis, we have been investigating possible changes in brain stem function as a result of acute and chronic laryngeal inflammation. We have been using lipopolysaccharide injection into one vocal to induce an inflammatory reaction and examining c fos expression and cytokine expression (IL1 beta and TNF alpha) in the same regions previously identified with electrical stimulation of the laryngeal afferents (see above). Collaboration with another group is addressing whether these findings can be replicated using in situ hybridization. Because of the hypothesized role of sensory feedback in the generation of involuntary muscles spasms during speech in spasmodic dysphonia, we have been investigating normal human responses to air pressure indentation of the laryngeal mucosa using air puffs in humans. In the first study we presented 100 ms air puff stimuli to the laryngeal mucosa overlying the arytenoid cartilages on one side while recording from the thyroarytenoid and cricothyroid muscles. The earliest laryngeal muscle responses occurred between 80 and 125 ms after the air pressure onset in the thyroarytenoid muscles on both sides. Further in a second study, we recently determined that with repeated air puffs, muscles responses are normally suppressed when stimuli are presented at intervals of less than 1 second. Similar studies are planned in spasmodic dysphonia to determine if muscle responses to laryngeal stimulation are abnormal in these patients. For rehabilitation of laryngeal motor control disorders, improved understanding of the biomechanical actions of each of the laryngeal muscles is needed. We combined laryngeal imaging, to quantify vocal fold movement, with synchronized recordings of laryngeal muscles in normal speakers during different laryngeal tasks; sniff, cough and repetition of syllables involving a glottal fricative /h/ and a vowel. Cross-correlations between vocal fold position and level of muscle activity distinguished whether a muscle was active for vocal fold closing or opening. Only the posterior cricoarytenoid muscle related well with vocal fold motion; it had a high relationship with vocal fold opening during all three tasks. The cricothyroid muscle had an opening action only for sniff while the adductor muscles only related with closing during cough. Different combinations of muscles were used by different subjects on various tasks to accomplish vocal fold opening and closing. This motor equivalence across individuals and tasks in the use of the laryngeal muscles for vocal fold movement was most evident during speech. Dysphagia, a significant health problem, usually stems from central nervous system injury, leaving peripheral muscles intact and functional but without appropriate control. Last year, we used intra-muscular hooked wires to stimulate muscles in normal volunteers at rest and used videofluoroscopy to measure the extent of hyo-laryngeal anterior and superior movement when single muscles and different combinations were stimulated. Recently, a study of patients with chronic pharyngeal dysphagia was initiated to compare the effects of intra-muscular stimulation and surface stimulation on the frequency of aspiration during swallowing.

我们的目标是改善语音，言语和吞咽障碍的治疗和预防。为此，本节既进行了有关语音，语音和吞咽的喉神经控制的研究，又要研究神经发生特发性疾病的发病机理和病理生理学的研究。正在进行临床试验，以开发新的痉挛性吞咽困难和慢性咽吞咽困难的治疗方法。去年在多个领域取得了重大进展。 喉内收肌反应是一种选择性的甲状腺素肌肉痉挛，是为了响应喉中的机械感受器而发生的。以前，我们已经发现，当这种反射是通过上喉神经中传入的电刺激引起的时，通常不会抑制反应在痉挛性吞咽困难的患者中，这是一种特发性慢性局灶性肌张力障碍，影响语音产生。我们已经使用动物模型来确定可能引起这种反射的脑干区域。 FOS免疫组织化学用于确定延髓中的哪些神经元在引起这种反射时发射的。在上部喉神经的内部分支的单侧电刺激中，在间核下核，腹侧下核，肠细胞核下核的腹侧下核，小核肠细胞核的腹膜下核的显着增加（p <0.003），是网状形式的后期侧向核心肠系膜。该途径涉及与咳嗽和吞咽相同的结构的子集。通常用于燕子的背侧运动核，通常活跃的燕子核，逆然核，通常用于咳嗽的侧面网状核，它们仅伴有喉内加合物反应而活跃。 由于许多语音疾病患有喉炎的发作，因此我们一直在研究由于急性和慢性喉部炎症的导致脑干功能的可能变化。我们一直在一种声音中使用脂多糖注射来诱发炎症反应，并检查C FOS表达和细胞因子表达（IL1β和TNF Alpha）在先前用电刺激的喉部传入的相同区域中（见上文）。与另一个小组的合作是解决这些发现是否可以使用原位杂交复制。 由于感觉反馈在痉挛性吞咽困难期间的言语中有假设的作用在产生非自愿肌肉痉挛中，我们一直在研究人类使用空气泡芙的喉粘膜空压压痕的正常反应。在第一项研究中，我们向喉粘膜提出了100毫秒的空气泡芙刺激，一侧将芳香的软骨上覆盖，同时从甲状腺甲状腺素和甲状腺素肌肉记录下。最早的喉部肌肉反应发生在两侧甲状腺甲状腺素肌肉中的气压开始后的80至125毫秒之间。进一步在第二项研究中，我们最近确定，随着反复的空气泡芙，当刺激以小于1秒的间隔表示时，通常会抑制肌肉反应。计划在痉挛性吞咽困难中进行类似的研究，以确定这些患者对喉刺激的反应是否异常。 为了修复喉运动控制障碍，需要提高对每种喉肌的生物力学作用的了解。我们将喉成像结合在一起，以量化声带运动，并在不同的喉部任务中正常扬声器中喉肌的同步记录；音节的嗅探，咳嗽和重复，涉及发光摩擦 / h /和元音。声带位置和肌肉活动水平之间的互相关区分了肌肉是有效的人声折叠还是打开。只有后cricarytenoid肌肉与人声褶皱运动良好相关；在所有三个任务中，它与声带开口有很高的关系。环甲状腺肌肉仅针对嗅探进行开幕式动作，而内收肌只与咳嗽期间关闭有关。不同受试者在各种任务上使用了不同的肌肉组合来完成声带的开口和闭合。在语音期间，喉部肌肉使用喉部肌肉的这种运动等效性在语音折叠运动中最为明显。 吞咽困难，这是一个重大的健康问题，通常源自中枢神经系统损伤，使周围肌肉完好无损，但没有适当的控制。去年，我们使用肌肉内钩线在休息时刺激正常志愿者的肌肉，并使用视频荧光镜检查刺激了单个肌肉和不同组合时，测量了汉脑前和较高运动的程度。最近，开始对慢性咽吞咽困难的患者进行研究，以比较肌肉内刺激和表面刺激对吞咽过程中抽吸频率的影响。