Understanding the Voice Control System in Parkinson's Disease

描述(由申请人提供)：本提案描述了一项为期3年的研究转化项目计划，以获得可在后续提交研究项目拨款(R01)时用作试点数据的数据。PI是一名语音科学家，曾接受过语音信号处理、情感韵律和韵律处理、声学建模和EEG/ERP技术方面的培训，目前在西北大学从事语音控制和运动性言语障碍领域的博士后工作。她现在将应用这些技能来模拟帕金森氏症(PD)声音控制的神经机制。环境：西北大学传播科学和疾病学系，这是一个研究密集型大学和系。作为一名博士后研究员，PI将被安置在她导师的实验室里，可以使用太空、设备和世界知名科学家的网络。研究：这项研究的长期目标是了解控制声音的神经机制，并将这些发现推广到患有神经性发声障碍的人。短期目标是确定帕金森病患者发声控制受损的神经基础，特别是通过测试传出复制机制的异常功能，对潜在的神经回路进行建模，并将结果与健康对照组和弥漫性皮质受损的临床组(“受损对照”)进行比较。该项目的具体目标是：1)确定传出复制在语音源识别和PD的错误检测/纠正中的作用，并对神经电路进行建模；2)确定音调扰动对意志F0调制的影响和 神经通路和脑电微态特征的差异。在这个实验中，帕金森氏症患者的发声和大脑活动(EEG/ERP，微态)将被检查时，他们的声音的听觉反馈给予微小的扰动，特别是为了检查控制系统的目的，其中预期的声音输出的传出副本与实际的感觉反馈进行比较。除了提出的复杂的神经学建模之外，这种行为-神经测量策略-包括动态因果建模、一致性分析和脑电微状态分析-是检查运动控制的一种新方法。此外，导致帕金森病语音障碍的语音控制的神经机制，包括前馈(快速和自动控制)和反馈控制(缓慢和依赖于感觉反馈)将使用一种高度创新的范例来定义，该范例要求受试者动态改变他们的音调以跟随(或阴影)或反对音调变化。我们在帕金森病患者中与年轻人相比的初步数据支持了我们的假设，并证明了进一步的实验。这些实验的结果将极大地促进我们对听觉反馈在帕金森病语音控制和发声障碍方面的理解。

DESCRIPTION (provided by applicant): This proposal describes a 3 year research translational project program to obtain data that can serve as pilot data in a subsequent submission for a research project grant (R01) by the early stage investigator. The PI is a speech scientist with training in speech signal processing, emotional prosody and prosodic processing, acoustic modeling, and EEG/ERP techniques and is currently working in the area of voice control and motor speech disorders as a postdoctoral fellow at Northwestern University. She will now apply these skills to modeling the neural mechanisms underlying voice control in Parkinson's disease (PD). Environment: The Communication Sciences and Disorders Department at Northwestern University, a research-intensive university and department. As a postdoctoral fellow, the PI will be housed in her mentor's laboratory and has access to space, equipment, and a network of world-renowned scientists. Research: The long-term goal of this research is to understand the neural mechanisms controlling the voice and to extend these findings to people with neurogenic disorders of voice production. The short-term objective is to identify the neurological substrates of impaired vocal control in PD, specifically by testing for abnormal function of the efference copy mechanisms, model the underlying neural circuitry, and compare the results with healthy controls and with a clinical group having diffuse cortical impairment ("impaired controls"). The Specific Aims of the project are: 1) Identify the role of efference copy during voice source identification and error detection/correction in PD and model the neural circuitry and 2) Identify effects of pitch perturbations on volitional F0 modulation and differences in the neural pathways and EEG microstate characteristics. In this experiment, the vocalizations and brain activity (EEG/ERP, microstates) of individuals with Parkinson's disease will be examined when given small perturbations to the auditory feedback of their voice, specifically for the purpose of examining the control system wherein an efference copy of the intended vocal output is compared with the actual sensory feedback. This behavioral-neurological measurement strategy in addition to the sophisticated neurological modeling proposed-including dynamic causal modeling, coherence analysis, and EEG microstate analysis-is a novel approach to examining motor control. Also, the neural mechanisms of voice control that contribute to the voice disorder in PD, including feed forward (fast and automatic control) and feedback control (slow and reliant on sensory feedback) will be defined using a highly innovative paradigm that requires subjects to dynamically change their voice pitch to follow (or shadow) or oppose a pitch shift. Our preliminary data in PD compared to young adults support our hypotheses and warrant further experimentation. The results of these experiments will significantly advance our understanding of auditory feedback on voice control and vocal impairments in PD.