Role of Subthalamic nucleus in Speech and Movement among people with Parkinson’s as Revealed by Intraoperative Recordings and Deep Brain Stimulation

术中记录和深部脑刺激揭示丘脑底核在帕金森病患者言语和运动中的作用

• 批准号: 10438534
• 负责人: Jeremy Greenlee
• 金额: $ 61.48万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10438534
• 关键词: Acoustics; Acute; Address; Aftercare; American; Articulation; Behavior; Bilateral; Brain; Characteristics; Cohort Studies; Communication; Control Groups; Data; Deep Brain Stimulation; Deterioration; Development; Disease; Disease Progression; Exhibits; Failure; Family; Frequencies; Future; Goals; Impairment; Knowledge; Limb structure; Literature; Measures; Microelectrodes; Motor; Movement; Neurobehavioral Manifestations; Neurodegenerative Disorders; Neurons; Operative Surgical Procedures; Outcome; Outcome Study; Parkinson Disease; Participant; Patients; Performance; Persons; Pharmaceutical Preparations; Physiology; Pilot Projects; Postoperative Period; Predictive Factor; Prevalence; Production; Protocols documentation; Quality of life; Regression Analysis; Reporting; Research; Respiratory physiology; Role; STN stimulation; Source; Speech; Structure of subthalamic nucleus; Surveys; Techniques; Testing; Therapeutic Effect; Time; awake; base; disorder control; disparity reduction; effective therapy; experience; feasibility testing; human model; implantation; improved; insight; motor control; motor symptom; neural model; neurophysiology; preoperative counseling; prospective; reduce symptoms; respiratory; side effect; tool; treatment optimization; treatment strategy

PROJECT SUMMARY / ABSTRACT Parkinson's disease (PD) is an increasingly prevalent progressive neurodegenerative disorder that leads to disabling motor, speech, and cognitive symptoms that reduce quality of life for patients and their families. As the prevalence of PD increases, so too does the use of deep brain stimulation (DBS) as a surgical treatment option when medications fail to control motor fluctuations or side effects from medications limit their efficacy. As many as 15% of the more than 1 million American PD patients are felt to be candidates for DBS. The subthalamic nucleus (STN) is the most common target utilized for DBS and limb motor outcomes after STN-DBS show reliable and consistent improvement in properly selected patients. On the other hand speech motor outcomes after STN-DBS are unpredictable and more patients experience deterioration of speech than those that notice improved speech. An estimated 40% of STN-DBS patients notice worsened speech and with declines significant enough to reduce quality of life. Furthermore, few effective treatments exist to provide sustained improvement in speech performance for those with impaired speech. In order to optimize and develop better treatments for those living with PD, it is necessary to better understand the role of STN in speech as contemporary mechanistic models of human speech production omit STN. Here we study 80 PD patients undergoing bilateral STN-DBS along with 40 non-surgical PD control subjects to address existing critical knowledge gaps. We will document speech performance of both groups through functional communication ability (i.e. objective measures of intelligibility and a validated survey tool for quantifying communication participation) and instrumental speech (i.e. acoustic) measures pre-surgery, 6- and 12-months post-surgery with all subjects off PD medications and with the STN-DBS subjects evaluated with stimulation ON & OFF at both post-operative timepoints. Direct neuronal recordings will be obtained during DBS implantation surgery during both speech and limb motor tasks to define speech-specific STN neurophysiology. In addition, we will perform regression analyses using baseline patient factors and intraoperative physiology findings to identify factors leading to the speech outcomes we will document, and test the feasibility of low frequency DBS in reversing DBS- induced speech declines. To our knowledge, this data will be the first of its kind to evaluate patients before, during, and after surgery with the goals of both directly defining the role of STN in speech and predicting speech outcome after STN-DBS. Such knowledge will provide mechanistic insights that cannot be obtained using other techniques and will guide development of new treatments of impaired speech in PD.

项目概要/摘要 帕金森病 (PD) 是一种日益流行的进行性神经退行性疾病， 导致运动、言语和认知功能障碍，从而降低患者及其生活质量 家庭。随着 PD 患病率的增加，深部脑刺激 (DBS) 作为治疗方法的使用也随之增加。 当药物无法控制运动波动或副作用时，可选择手术治疗 药物限制了它们的功效。美国超过100万PD患者中多达15%有这种感觉 成为星展银行的候选人。 丘脑底核 (STN) 是 DBS 和肢体运动结果最常见的目标 STN-DBS 在正确选择的患者中显示出可靠且一致的改善。另一方面 STN-DBS 后的手部言语运动结果是不可预测的，更多患者会经历 与那些注意到言语改善的人相比，言语恶化。估计有 40% 的 STN-DBS 患者 注意到言语恶化，并且下降严重到足以降低生活质量。此外，很少有 存在有效的治疗方法可以持续改善患有此症的人的言语表现 言语障碍。 为了优化和开发针对帕金森病患者的更好的治疗方法，有必要更好地 理解 STN 在语音中的作用，作为人类语音产生的当代机械模型 省略 STN。在这里，我们研究了 80 名接受双侧 STN-DBS 的 PD 患者以及 40 名非手术 PD 患者 控制科目以解决现有的关键知识差距。我们将记录以下人员的演讲表现 两组都通过功能性沟通能力（即可理解性的客观衡量标准和 经验证的调查工具，用于量化沟通参与）和器乐演讲（即声学） 测量术前、术后 6 个月和 12 个月，所有受试者均停止使用 PD 药物并使用 STN-DBS 受试者在术后两个时间点均通过刺激开启和关闭进行评估。直接的 DBS 植入手术期间将获得言语和肢体运动期间的神经元记录 定义语音特定 STN 神经生理学的任务。此外，我们将进行回归分析 使用基线患者因素和术中生理学发现来识别导致手术的因素 我们将记录演讲结果，并测试低频 DBS 在逆转 DBS 中的可行性 诱发言语能力下降。 据我们所知，该数据将是第一个用于评估患者之前、期间和之后的数据 手术的目的是直接确定 STN 在言语中的作用并预测言语结果 STN-DBS 后。这些知识将提供使用其他方法无法获得的机械见解 技术并将指导帕金森言语障碍新疗法的开发。