The Bases Of Normal And Disordered Laryngeal And Speech Systems

正常和紊乱的喉部和言语系统的基础

• 批准号: 7969589
• 负责人: Christy Leslie Ludlow
• 金额: $ 434.22万
• 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/7969589
• 关键词: Adolescence; Adult; Affect; Age; Anisotropy; Axon; Blinded; Brain; Brain Stem; Case Study; Cell Nucleus; Cerebellum; Cessation of life; Characteristics; Child; Childhood; Childhood Stuttering; Demyelinations; Development; Developmental Stuttering; Diffusion Magnetic Resonance Imaging; Disease; Etiology; Financial compensation; Frequencies; Functional disorder; Human; Inferior; Internal Capsule; Laboratories; Laryngeal Diseases; Laryngeal muscle structure; Larynx; Left; Lentiform nucleus structure; Michigan; Microglia; Microscopic; Minerals; Nerve Degeneration; Nervous System Trauma; Neuraxis; Neurologic; Nucleus solitarius; Olives - dietary; Onset of illness; Pathogenesis; Pathologic; Patients; Peripheral; Persons; Postdoctoral Fellow; Production; Proteins; Relative (related person); Reporting; Research; Respiration; Reticular Formation; Risk; Sampling; Secondary to; Spasm; Spastic Dysphonias; Speech; Speech Disorders; Structure; Structure of trigeminal nerve spinal tract nucleus; Stuttering; Substantia nigra structure; Symptoms; System; Time; Trauma; Tremor; Ubiquitin; Universities; Voice; Voice Disorders; alpha synuclein; axonal degeneration; base; early childhood; forest; locus ceruleus structure; macrophage; medical schools; motor control; nervous system disorder; neuroimaging; neuromechanism; neuropathology; neuroregulation; nucleus ambiguus; psychologic; stem; tau Proteins; white matter

In the last year we have completed studies aimed at determining the pathophysiology and neuropathology of the two idiopathic voice and speech disorders: spasmodic dysphonia, an adult onset voice disorder and stuttering, a developmental speech disorder. Both are speech specific disorders of unknown etiology. Spasmodic dysphonia (SD) is characterized by involuntary spasms in the laryngeal muscles only thought to occur during speech production. Recently, a post mortem study of one case of spasmodic dysphonia found axonal degeneration and demyelination in the genu of the internal capsule and clusters of mineral accumulations in the internal capsule, lentiform nucleus and cerebellum. This year we completed a study of the brainstem in two patients; the same case of SD stydued the previous year and another case of SD combined with voice tremor. The brian stem findings were contrasted e with four control post mortem brains from persons with similar ages as the two patients at time of death. Detailed microscopic examination revealed subtle pathologic changes in the brainstem of the SD patients in contrast with none being found in the controls. Small clusters of microglia/macrophages were observed in the reticular formation surrounding the solitary tract nucleus, spinal trigeminal nucleus, nucleus ambiguus, inferior olive, and pyramids, while mild neuronal degeneration and depigmentation were found in the substantia nigra and locus coeruleus. No abnormal protein accumulations (e.g., tau, ubiquitin, or alpha-synuclein) and no signs of demyelination or loss of axons were identified in the brainstem of either SD patients. These neuropathological changes in the brainstem nuclei in SD patients may represent a component of pathophysiological basis of this disorder or be secondary to the supramedullar abnormalities. The other idiopathic speech and voice disorder we have been studying is developmental stuttering (DS). No neuropathologic studies have been conducted in this disorder although recent neuroimaging studies have reported differences in the white matter in the superior longitudinal fasciculus and arcuate fasciculus in the left hemisphere in both children and adults with DS. We had the opportunity of contrasting findings in developmental stuttering cases with cases with adult-onset stuttering (AS) which typically occur following neurological and/or psychological trauma. The adult onset disorder is considered different from developmental stuttering (DS). The latter starts during early childhood with few if any new cases reported after adolescence. We reported on four cases of AS, two with and two without an apparent psychological trigger, none with previous symptoms of developmental stuttering and no evidence of neurological injury, and not conforming to previously reported characteristics of psychogenic stuttering. To determine whether these AS cases had similar speech and neuroanatomical characteristics to DS, blinded analyses of speech samples of the 4 AS cases and 14 DS cases compared type, frequency, and loci of disfluencies in sentences. Diffusion tensor imaging (DTI) was conducted to compare white matter tracts using fractional anisotropy (FA) in controls, AS and DS. The AS cases were more mildly affected but did not differ from DS in their speech characteristics. On DTI, the DS group had significantly increased FA relative to controls in the right superior longitudinal tract while the AS cases had similar increases in these regions compared to controls differ from some previous findings and suggest right white matter compensation by adulthood for previous left hemisphere deficits found in children. The results suggest that symptoms similar to developmental stuttering can begin in adulthood, with similar neuroanatomical differences from controls in both developmental and adult onset idiopathic stuttering. This raises the possibility that some persons are at risk of stuttering because of brain structure differences and may develop symptoms after childhood. During this last year the Section closed with the departure of Dr. Ludlow to James Madison University in late July. Each of the postdoctoral fellows relocated to establish new laboratories of their own at various universities including Michigan State University, Wake Forest University and Mount Sinai Medical School.

在去年，我们完成了旨在确定两种特发性声音和语音障碍的病理生理学和神经病理学的研究：痉挛性吞咽困难，一种成人发作的声音障碍和口吃，一种发育性语音障碍。 两者都是未知病因的言语特定疾病。 痉挛性吞咽困难（SD）的特征是喉部肌肉中仅被认为在言语生产过程中发生的非自愿痉挛。最近，一项对痉挛性吞咽困难的病例的验尸研究发现，内部胶囊内部胶囊和矿物质堆积的簇中的轴突变性和脱髓鞘在内胶囊，垒式核和小脑中的矿物质簇。 今年，我们完成了两名患者的脑干研究。同样的SD案例造型了上一年，SD的另一个案例与配音震颤相结合。 Brian Stem的发现与E的四个对照后尸体大脑相比，与两名患者相似的人的死亡人数与死亡时相似。详细的显微镜检查显示，与对照中未发现SD患者脑干的细微病理变化。在围绕孤立的区核，脊柱三叉神经核，Ambiguus核，下橄榄和金字塔的围绕的网状形成中观察到小胶质细胞/巨噬细胞的小簇，而在尼格拉和locus coerules中则发现了轻度神经元的变性和脱位。在任何一名SD患者的脑干中均未鉴定出异常的蛋白质积累（例如Tau，泛素或α-核蛋白），并且在任何SD患者的脑干中均未鉴定出脱髓鞘或轴突丧失的迹象。 SD患者脑干核中的这些神经病理学变化可能代表了该疾病的病理生理基础的组成部分，或者是superullailar异常的继发性。 我们一直在研究的其他特发性语音和语音障碍是发育口吃（DS）。 尽管最近的神经影像学研究报道了上纵向上筋膜上的白质的差异，但在这种疾病中没有进行神经病理学研究，但在儿童和成人DS的左半球中，左半球的白质差异。 我们有机会将发育口吃病例的发现与成人口吃（AS）进行对比，这些病例通常发生在神经系统和/或心理创伤之后。 成人发作障碍被认为与发育口吃不同（DS）不同。 后者在童年时期开始，青少年后报告的新病例很少。我们报告了四例AS，两例，两例没有明显的心理触发因素，没有先前的发育口吃症状，也没有神经损伤的证据，并且不符合先前报道的心理口吃的特征。为了确定这些AS病例是否具有与DS相似的语音和神经解剖学特征，对4个病例的语音样本进行了盲目的分析和14例DS病例，比较了句子中的类型，频率和基因座。进行扩散张量成像（DTI），以比较使用对照组中的分数各向异性（FA），AS和DS。 AS病例受到更轻微的影响，但与DS的语音特征没有差异。在DTI上，与对照组相比，这些区域的DS组相对于对照组的FA显着增加，而AS病例在这些区域中的增加与以前的发现不同，并暗示了儿童以前的左半球缺陷时的右白质补偿。结果表明，类似于发育口吃类似的症状可以从成年开始，在发育和成人发作特发性口吃中，与对照组的神经解剖学差异相似。这增加了某些人因大脑结构差异而有口吃的风险，并且可能会在儿童时期出现症状。 去年，该部分在7月下旬卢德洛（Ludlow）博士到詹姆斯·麦迪逊大学（James Madison University）的离开后关闭。 每位博士后研究员都搬迁，以在包括密歇根州立大学，威克森林大学和西奈山医学院在内的各种大学建立自己的新实验室。

项目成果

Brainstem pathology in spasmodic dysphonia.

• DOI: 10.1002/lary.20677
• 发表时间: 2010-01
• 期刊: LARYNGOSCOPE
• 影响因子: 2.6
• 作者: Simonyan, Kristina;Ludlow, Christy L.;Vortmeyer, Alexander O.
• 通讯作者: Vortmeyer, Alexander O.

Common neural substrates support speech and non-speech vocal tract gestures.

• DOI: 10.1016/j.neuroimage.2009.03.032
• 发表时间: 2009-08-01
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Chang SE;Kenney MK;Loucks TM;Poletto CJ;Ludlow CL
• 通讯作者: Ludlow CL

Recommendations of the Neurolaryngology Study Group on laryngeal electromyography.

• DOI: 10.1016/j.otohns.2009.01.026
• 发表时间: 2009-06
• 期刊: OTOLARYNGOLOGY-HEAD AND NECK SURGERY
• 影响因子: 3.4
• 作者: Blitzer, Andrew;Crumley, Roger L.;Dailey, Seth H.;Ford, Charles N.;Floeter, Mary Kay;Hillel, Allen D.;Hoffmann, Henry T.;Ludlow, Christy L.;Merati, Albert;Munin, Michael C.;Robinson, Lawrence R.;Rosen, Clark;Saxon, Keith G.;Sulica, Lucian;Thibeault, Susan L.;Titze, Ingo;Woo, Peak;Woodson, Gayle E.
• 通讯作者: Woodson, Gayle E.

Brain activation abnormalities during speech and non-speech in stuttering speakers.

• DOI: 10.1016/j.neuroimage.2009.01.066
• 发表时间: 2009-05-15
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Chang SE;Kenney MK;Loucks TM;Ludlow CL
• 通讯作者: Ludlow CL