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

项目摘要/摘要 喉发音困难(LD)和发声震颤(VT)是损害言语的神经性嗓音障碍 制作。学习障碍的特征(即说话时有，但不笑或哭)和 缺少喉部生理异常提示LD可能是一种影响任务特异性控制的障碍 中枢神经系统(CNS)的发声作用。同样，室性心动过速经常在没有任何清晰外周的情况下被观察到 喉部病因学，也提示中枢性起源，但与LD的影响不同。的总目标是 本研究的目的是描述慢性阻塞性肺疾病患者中枢神经系统病理生理的共同和独特特征。 神经性嗓音障碍，LD和VT。言语行为是一个动态的过程，包括最初的声门 持续状态下感觉反馈波动的运动、发声和代偿反应 发声。识别LD和VT的特定功能障碍需要清楚地了解 发声的过程，以及中枢神经系统中发生异常活动的地方。由于他们糟糕的时代性 分辨率，以前的神经成像研究还不能解决中枢神经系统何时异常的问题 激活是相对于特定发音事件发生的。因此，关于潜在病因的关键线索 在这些障碍中很可能被遗漏了。在这里，我们提出了一种对中枢神经系统的多模式脑成像评估 与LD和VT相关的异常。具体目的是考察：1)时空中枢 语音和其他发声任务的病理生理学：2)中枢神经系统的感觉运动调节； 3)运动学习与中枢神经系统病理生理学。未来对LD和VT的治疗可以通过以下方式开发 针对本项目中确定的中枢神经系统病理生理机制。例如，这个项目将有助于 根据两种疾病的特定病理生理学，确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.