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: 10641756
• 负责人: Jeremy Greenlee
• 金额: $ 60.82万
• 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/10641756
• 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; Patient Selection; 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; 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 帕金森氏病（PD）是一种越来越普遍的进行性神经退行性疾病， 导致残疾运动，言语和认知症状，以降低患者及其的生活质量 家庭。随着PD的患病率的增加，使用深脑刺激（DBS）作为一个 当药物无法控制运动波动或副作用时，手术治疗选项 药物限制了它们的功效。感觉到超过100万美国PD患者中多达15％ 成为DBS的候选人。 丘脑下核（STN）是用于DB和肢体运动结果的最常见靶标 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之后的手语音运动结果是不可预测的，并且患者更多 语音恶化比注意到言语改善的言语。估计有40％的STN-DBS患者 通知使言语恶化，并且下降足以降低生活质量。此外，很少 存在有效的治疗方法，可以为患有的人提供持续的语音表现 言语受损。 为了优化和为患有PD的人提供更好的治疗方法，有必要更好 了解STN在语音中的作用作为人类语音生产的当代机械模型 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个非手术PD 控制对象解决现有的关键知识差距。我们将记录语音表现 两组都通过功能沟通能力（即，可理解的客观衡量和 经过验证的调查工具，用于量化沟通参与）和仪器语音（即声学） 手术前的手术前措施6个月和12个月，所有受试者都没有PD药物，并与 在两个术后时间点上刺激并关闭刺激的STN-DBS受试者。直接的 在语音和肢体运动期间，在DBS植入手术期间将获得神经元记录 定义语音特异性STN神经生理学的任务。此外，我们将执行回归分析 使用基线患者因素和术中生理学发现来识别导致的因素 语音结果我们将记录并测试低频DBS在逆转DBS时的可行性 - 诱导的言语下降。 据我们所知，这些数据将是第一个在之前，期间和之后评估患者的数据 手术的目标是直接定义STN在语音中的作用和预测语音结果的目标 STN-DBS之后。这种知识将提供无法使用其他的机械见解 技术并将指导PD中言语受损的新疗法的开发。

项目成果

Human subthalamic nucleus neurons differentially encode speech and limb movement.

人类底丘脑核神经元对言语和肢体运动进行差异编码。

• DOI: 10.3389/fnhum.2023.962909
• 发表时间: 2023
• 期刊: FRONTIERS IN HUMAN NEUROSCIENCE
• 影响因子: 2.9
• 作者: Johari, Karim;Kelley, Ryan M.;Tjaden, Kris;Patterson, Charity G.;Rohl, Andrea H.;Berger, Joel I.;Corcos, Daniel M.;Greenlee, Jeremy D. W.
• 通讯作者: Greenlee, Jeremy D. W.