帕金森氏病言语运动障碍的神经机制研究

Although 89% of individuals with Parkinson's disease (PD) are associated with motor speech disorders, the effective treatment techniques are quite limited. This is primarily attributable to the fact that neural mechanisms underlying the sensorimotor control of vocal production in individuals with PD are poorly understood. Successful execution of speech motor behavior relies on the coordination of sensory system (feedforward, auditory and somatosensory feedback) and motor system. It has been demonstrated that, however, individuals with PD fail to perceive the self-produced sound from auditory feedback. Moreover, they are also associated with the dysfunction of feedforward function and somatosensory feedback due to the impairment of the basal ganglia. Thus, we propose that there is an overreliance of auditory feedback in individuals with PD such that their audio-vocal system is highly sensitive to the changes in auditory feedback, which in turn leads to the abnormal sensorimotor control of vocal production. Using the acoustic and neurophysiological techniques that involve in the altered auditory feedback protocol, this project plans to investigate the neurophysiological mechanisms underlying auditory feedback control of vocal production in individuals with PD and they use auditory feedback to distinguish self-produced vocalizations from the external sounds at the cortical level. Our work will be of great help for the development of auditory-feeback-based new techniques to treat the motor speech disorders caused by PD.

大约90%帕金森氏病患者都患有不同程度的言语障碍，但是目前仍缺乏对之有效的治疗手段，这主要是由于帕金森氏病的言语运动调控神经机制尚未得到阐释。言语运动的调控，依赖于前馈、听觉反馈和本体感觉反馈等感觉系统与发声运动系统的共同协调。研究表明，帕金森氏病患者由于基底节病变导致前馈功能和本体感觉反馈功能出现障碍，对听觉反馈依赖增大，但患者也无法正确感知来自听觉反馈的声音。据此，我们提出帕金森氏病患者由于过度依赖听觉反馈，令其听觉感知系统对反馈信息过度敏感，导致中枢神经系统难以对发声运动进行准确调控。本项目拟利用基于听觉反馈扰动的生物声学和脑电/事件相关电位技术，研究帕金森氏病患者利用听觉反馈对发声运动进行调控的神经生理学机制，揭示听觉反馈在帕金森氏病患者区分自我发声和外界声音过程中的作用机制，为以听觉反馈为核心治疗帕金森氏病患者言语障碍的康复新技术研究奠定理论基础。

本项目利用基于听觉反馈扰动的心理声学和脑电/事件相关电位技术，结合静息态磁共振技术，对PD言语运动调控障碍的神经机制进行了一系列研究，在以下4个方面取得了重要成果：1）PD言语运动调控障碍的皮层处理机制。PD患者调控言语运动时，额叶、颞叶和顶叶等大脑区域的皮层活动强度显著高于正常人，说明PD言语运动调控障碍是感觉系统和运动系统整合异常的结果。颞叶癫痫患者虽然同样存在言语运动调控障碍，但是其大脑活动模式与PD患者相反，说明两者的言语运动调控机制存在显著区别。2）PD运动障碍的前馈和反馈基础。PD前馈障碍导致内在计划无法正常执行，使得站立和行走时的足底压力分布出现异常。但是视觉-听觉综合提示训练能够有效地改善足底压力分布和躯体运动功能障碍，说明反馈的加强能够弥补前馈障碍引起的运动功能损伤。3）注意力和工作记忆对言语运动调控的作用机制。注意力的提高和工作记忆能力的改善能够显著提高大脑处理言语反馈偏差的神经编码效率，促进听觉系统和运动系统之间的整合。这说明言语运动存在一个自上而下的认知处理机制，从而为通过认知功能的改善来治疗PD等神经系统疾病导致的言语运动调控障碍提供了新的思路。4）言语运动调控个体差异的神经基础。听觉和运动区域的局部一致性特性能够预测个体言语运动调控的行为学表现和皮层活动特征，并且女性生理周期变化引起的性激素水平能够对言语运动调控产生抑制性效应，为阐释言语运动调控个体差异的神经网络机制和神经化学机制提供了新依据。本项目执行期间，在NeuroImage、Human Brain Mapping等国际知名期刊上发表SCI论文9篇，另发表中文论文3篇。综上所述，本项目各项研究内容均顺利完成，实现了预期的目标，并在言语运动调控的认知神经机制及其个人差异的神经基础方面取得了突破。这不仅推动了PD言语运动调控障碍神经机制的进展，而且为实现PD言语障碍的精准康复奠定了基础。