The Neural Substrates of Impaired Feedback Control in P*

描述（由申请人提供）：帕金森病（PD）患者 有各种各样的语言表达困难。这些缺陷可能 PD患者（PD）使用感觉反馈的能力降低， 控制运动;与研究一致的假设表明PD具有 对音高频率或振幅变化的声音反应受损 （音量）的听觉语音反馈。在目前的建议中，神经 寻找语音反馈控制中这些损害的根源。听觉 言语的反馈控制将在PD和正常受试者中进行检查 发声，同时聆听频率或振幅的扰动 在他们讲话的听觉反馈中的音高（响度）。这些 扰动将引起俯仰扰动响应（PPRs）;补偿 音高频率或振幅的变化，其特征在于正常 受试者，但仅对PD进行了最低限度的表征。这项研究的首要目标是 更全面地描述PD和法线的PPR如何不同，以及 扰动参数引起最明显的差异。这将是 通过检查PD和正常人在广泛的心理物理 测试他们的PPR。在确定了什么样的音高扰动最大之后， 明确诊断PD中的PPR缺陷，该研究的第二个目标将确定 帕金森病患者和正常人的PPR所涉及的神经系统。这将使用 功能磁共振成像扫描PD和正常人生产或被动地听PPR。我们 将发现在PPR后比未改变后更活跃的CNS区域 发声，但当受试者被动地听一个声音时， 正常和音调紊乱的语音。在发现中枢神经系统中出现 参与PPR，研究的第三个目的将是确定 导致PPR的神经活动为了检验这一点，我们将归纳 用脑磁图研究发声型PD和正常人的PPR 和脑电图来记录不同脑区的连续激活 在扰动之后但在PPR之前的大脑区域。更好 理解受损的言语反馈控制的神经基础， PD将阐明与PD相关的言语障碍的病理生理学 并促进针对这些疾病的精准治疗。

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.