The Neural Substrates of Impaired Feedback Control in P*

描述(申请人提供)：帕金森氏病患者 在语音制作方面有各种困难。这些赤字可能 帕金森病患者(PD)使用感觉反馈的能力降低 控制运动；这一假说与研究表明PD具有 对音调频率或幅度变化的发声反应受损 (音量)听觉语音反馈。在本提案中，神经 寻找语音反馈控制中这些损害的基础。听觉 语言反馈控制将在帕金森病患者和正常受试者中进行检验 发声，同时听频率或幅度的扰动 (响度)他们讲话的听觉反馈中的音调。这些 扰动将引起音调扰动响应(PPR)；补偿性 音调频率或幅度的变化，这是正常的特征 受试者，但只是PD的最低限度的特征。这项研究的第一个目的是 更全面-描述PD和法线的PPR有何不同，以及音高 微扰参数造成了最明显的差异。这将是 通过在广泛的心理物理中检查PD和正常完成 测试他们的PPR。在确定了音高扰动最大的原因之后 明确诊断PD的PPR缺陷，研究的第二个目标将确定 PD和正常人参与PPR的神经系统。这将使用以下工具完成 对产生或被动听PPR的PD和正常人进行fMRI扫描。我们 将发现PPR后比未更改后更活跃的CNS区域 发声，但当受试者被动地听 正常和音调混乱的讲话。在找到中枢神经系统出现的区域之后 参与PPR，研究的第三个目标将是确定 他们的神经活动导致PPR。为了检验这一点，我们将归纳 帕金森病发声患者和正常人脑磁图的PPR研究 并用脑电记录不同脑区的顺序激活 在扰动之后但在PPR之前的大脑区域。更好 对言语反馈控制受损的神经基础的认识 PDS将阐明与帕金森病相关的言语障碍的病理生理学 并促进对这些疾病的治疗进行精细化的定向治疗。

DESCRIPTION (provided by applicant): Patients with Parkinson's disease (PD) have a variety of difficulties with speech production. These deficits may result from a reduced ability of PD patients (PDs) to use sensory feedback to control movement; a hypothesis consistent with studies showing that PDs have impaired vocal responses to changes in the pitch frequency or amplitude (volume) of auditory speech feedback. In the present proposal, the neural substrates of these impairments in speech feedback control are sought. Auditory feedback control of speech will be examined in PD and normal subjects vocalizing, while listening to perturbations of the frequency or amplitude (loudness) of the pitch in the auditory feedback of their speech. These perturbations will cause pitch-perturbation responses (PPRs); compensatory changes in pitch frequency or amplitude that are well characterized for normal subjects, but only minimally characterized for PDs. The study's first aim is to more fully-describe how PPRs of PDs and normals differ, and what pitch perturbation parameters cause the clearest differences. This will be accomplished by examining both PDs and normals in extensive psychophysical testing of their PPRs. After having determined what pitch perturbations most clearly diagnose the PPR deficits in PDs, the study's second aim will identify the neural systems involved in PPRs in PDs and normals. This will be done using fMRI scanning of PDs and normals producing or passively listening to PPRs. We will find CNS regions that are more active after PPRs than after unaltered vocalizations, but show no activity when the subject passively listens to a normal and pitch-perturbed speech. After finding areas of the CNS that appear involved in PPRs, the third aim of the study will be to determine the order of their neural activities resulting in a PPR. To examine this, we will induce PPRs in vocalizing PD and normal subjects, while using magnetoencephalography and electroencephalography to record the sequential activation of different brain regions following perturbation but preceding the PPR. Better understanding of the neural substrates of impaired speech feedback control in PDs will elucidate the pathophysiology of speech disorders associated with PD and promote refined targeting of treatments for those disorders.