Understanding disorder-specific neural pathophysiology in laryngeal dystonia and voice tremor

了解喉肌张力障碍和声音震颤的疾病特异性神经病理生理学

• 批准号: 10488253
• 负责人: Kristina Simonyan
• 金额: $ 74.3万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10488253
• 关键词: Acoustics; Address; Affect; Anesthetics; Behavioral; Behavioral trial; Brain; Brain imaging; Bupivacaine; Characteristics; Clinical; Clinical Management; Communication; Congenital neurologic anomalies; Crying; Deformity; Differential Diagnosis; Disease; Dysphonia; Dystonia; EEG-based imaging; Etiology; Event; Feedback; Financial compensation; Focal Dystonias; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Human; Impairment; Knowledge; Laryngeal Mucosa; Larynx; Learning; Magnetic Resonance Imaging; Magnetoencephalography; Mission; Modeling; Motor; Movement; Nature; Neuraxis; Neurologic Voice Disorder; Neuronal Plasticity; Patients; Peripheral; Persons; Phonation; Process; Production; Public Health; Research; Risk; Role; Spastic Dysphonias; Speech; Therapeutic; Tremor; United States National Institutes of Health; Voice; auditory feedback; base; behavioral response; clinical phenotype; disability; experimental study; functional disability; functional magnetic resonance imaging/electroencephalography; motor learning; multimodality; nervous system disorder; neural correlate; neuroimaging; next generation; noninvasive brain stimulation; novel strategies; reduce symptoms; relating to nervous system; response; screening; sensory feedback; sequence learning; somatosensory; temporal measurement

PROJECT SUMMARY / ABSTRACT Laryngeal dysphonia (LD) and Voice Tremor (VT) are neurological voice disorders that impair speech production. The characteristic feature of LD (i.e., occurring during speaking but not laughing or crying) and the lack of physical laryngeal abnormalities suggests that LD is likely a disorder affecting the task-specific control of phonation by the central nervous system (CNS). Similarly, VT is often observed without any clear peripheral laryngeal etiology, also suggesting a central origin but distinct from that affected in LD. The overall goal of this project is to characterize the common and distinct features of CNS pathophysiology in the neurological voice disorders, LD and VT. The act of speech is a dynamic process, including initial glottal movement, voice onset, and compensatory responses to sensory feedback fluctuations during sustained phonation. Identifying specific functional impairments in LD and VT requires a clear understanding of when in the process of phonation, as well as where in the CNS, aberrant activity occurs. Due to their poor temporal resolution, prior neuroimaging studies have not been able to address the question of when abnormal CNS activation occurs relative to specific phonation events. As a result, critical clues about the underlying etiologies in these disorders have likely been missed. Here, we propose a multimodal brain imaging assessment of CNS abnormalities associated with LD and VT. The specific aims are to examine: 1) Spatial and temporal CNS pathophysiology during speech and other vocal tasks; 2) Sensorimotor modulations on CNS pathophysiology; and 3) Motor learning and CNS pathophysiology. Future treatments for LD and VT can be developed by targeting CNS pathophysiological mechanisms identified in this project. For example, this project will help identify neural targets that have a therapeutic potential based on disorder-specific pathophysiology for both invasive and non-invasive brain stimulation.

项目概要/摘要 喉发声困难 (LD) 和声音震颤 (VT) 是损害言语的神经性发声障碍 生产。 LD 的典型特征（即发生在说话但不笑或哭时）和 缺乏喉部异常表明 LD 可能是一种影响任务特异性控制的疾病 中枢神经系统（CNS）的发声。同样，VT 通常在没有任何明确的外周血管的情况下观察到。 喉部病因，也表明有一个中心起源，但与 LD 中受影响的不同。总体目标为 该项目旨在描述中枢神经系统病理生理学的共同和独特特征 神经性声音障碍、LD 和 VT。言语行为是一个动态过程，包括初始声门 持续过程中的运动、发声和对感觉反馈波动的补偿反应 发声。识别 LD 和 VT 的特定功能障碍需要清楚地了解何时发生 发声过程以及中枢神经系统中发生异常活动的位置。由于他们的时间差 解决方案，之前的神经影像学研究未能解决中枢神经系统何时异常的问题 激活的发生与特定的发声事件相关。因此，关于潜在病因的关键线索 在这些疾病中，很可能被遗漏了。在这里，我们提出了中枢神经系统的多模式脑成像评估 与 LD 和 VT 相关的异常。具体目标是检查：1）空间和时间 CNS 言语和其他发声任务期间的病理生理学； 2）中枢神经系统病理生理学的感觉运动调节； 3) 运动学习和中枢神经系统病理生理学。 LD 和 VT 的未来治疗方法可以通过 针对本项目中确定的中枢神经系统病理生理机制。例如，该项目将帮助 根据疾病特异性病理生理学，识别具有治疗潜力的神经靶点 侵入性和非侵入性脑刺激。