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: 10340121
• 负责人: Kristina Simonyan
• 金额: $ 74.96万
• 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/10340121
• 关键词: Understanding; disorder; specific; neural; pathophysiology

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.

项目摘要 /摘要 喉烦躁不安（LD）和配音震颤（VT）是神经科语音障碍 生产。 LD的特征（即在说话期间发生，但不笑或哭泣）和 缺乏身体喉部异常表明LD可能是影响特定于任务控制的疾病 中枢神经系统（CNS）发声。同样，通常观察到VT没有任何清晰的外围 喉病因学也表明了中心的起源，但与在LD中受影响的喉部起源不同。总体目标 该项目是为了表征CNS病理生理学的常见和独特特征 神经语音障碍，LD和VT。语音行为是一个动态过程，包括初始震颤 持续的运动反馈波动的运动，声音发作和补偿性响应 发声。确定LD和VT中的特定功能障碍需要清楚地了解何时 发声过程以及中枢神经系统中的位置发生了异常活动。由于他们的时间差 解决方案，事先神经影像学研究无法解决何时异常中枢神经系统的问题 激活相对于特定的发声事件发生。结果，有关潜在病因的关键线索 在这些疾病中可能被错过了。在这里，我们提出了CNS的多模式脑成像评估 与LD和VT相关的异常。具体目的是检查：1）空间和时间中枢神经系统 言语和其他声音任务期间的病理生理学； 2）有关CNS病理生理学的感觉运动调节； 3）运动学习和CNS病理生理学。 LD和VT的未来治疗方法可以由 靶向该项目中确定的CNS病理生理机制。例如，这个项目将有所帮助 确定具有基于疾病特异性病理生理学的治疗潜力的神经靶标的 侵入性和非侵入性脑刺激。