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.

项目摘要/摘要 帕金森病(PD)是一种日益普遍的进行性神经退行性疾病， 导致运动、言语和认知障碍症状，从而降低患者和患者的生活质量 家人。随着帕金森病患病率的增加，深部脑刺激(DBS)作为一种治疗手段的使用也在增加 当药物未能控制运动波动或药物副作用时的手术治疗选择 药物会限制它们的疗效。100多万美国帕金森氏症患者中有多达15%的人感觉到 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用的靶点 在经过适当选择的患者中，STN-DBS显示出可靠和持续的改善。另一方面 STN-DBS术后的手语运动结果是不可预测的，更多的患者经历了 比起那些注意到语言能力改善的人，语言能力的下降更明显。据估计，40%的STN-DBS患者 注意到语言的恶化和严重的下降，足以降低生活质量。此外，几乎没有人 已经有了有效的治疗方法来持续改善那些患有抑郁症的人的言语表现 说话有障碍。 为了优化和开发对帕金森病患者更好的治疗方法，有必要更好地 理解STN作为人类言语产生的当代机制模型在言语中的作用 省略STN。在这里，我们研究了80例接受双侧STN-DBS的PD患者和40例非手术PD患者 控制受试者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 两组通过功能性交流能力(即可理解性的客观测量和 用于量化沟通参与度的经过验证的调查工具)和工具性语言(即声学) 测量所有受试者在手术前、术后6个月和12个月停用PD药物以及 STN-DBS受试者在术后两个时间点用刺激开和关进行评估。直接 在DBS植入手术期间，将获得言语和肢体运动的神经元记录 定义特定于言语的STN神经生理学的任务。此外，我们还将进行回归分析 使用基线患者因素和术中生理学结果来确定导致 我们将记录并测试低频DBS在逆转DBS方面的可行性- 诱导性言语减少。 据我们所知，这类数据将是第一个在患者之前、期间和之后评估患者的数据 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 在STN-DBS之后。这样的知识将提供使用其他方法无法获得的机械性见解 技术，并将指导开发新的治疗帕金森病语言障碍的方法。