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

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语音障碍 生产LD的特征（即，在说话时发生，但不是笑或哭）， 没有物理性喉部异常提示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）的发音。类似地，VT经常在没有任何明确的外周血管的情况下观察到。 喉病因学，也提示中枢起源，但与LD的受累不同。的总目标 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， 神经性语音障碍，LD和VT。言语行为是一个动态的过程，包括初始声门 运动、发声和对感觉反馈波动的代偿反应 发声识别LD和VT中的特定功能障碍需要清楚地了解何时 发声的过程，以及中枢神经系统中异常活动发生的位置。由于他们的时间差， 解决，以前的神经影像学研究还没有能够解决的问题，当异常的中枢神经系统 激活相对于特定发声事件发生。因此，关于潜在病因的关键线索 在这些疾病中很可能被忽略了。在这里，我们提出了一个多模式脑成像评估中枢神经系统 与LD和VT相关的异常。具体的目的是检查：1）空间和时间CNS 2）感觉运动对中枢神经系统病理生理的调节; （3）运动学习与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以下方式开发： 针对本项目中确定的CNS病理生理机制。例如，该项目将有助于 基于疾病特异性病理生理学，鉴定具有治疗潜力的神经靶点， 侵入性和非侵入性脑刺激。

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.