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

项目总结/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、言语和认知功能障碍症状，降低患者的生活质量， 家庭随着PD患病率的增加，脑深部电刺激（DBS）作为一种治疗方法的使用也在增加。 当药物无法控制运动波动或副作用时， 药物限制了它们的功效。在100多万美国PD患者中， 成为DBS的候选人 丘脑底核（DBS）是DBS和肢体运动结局最常见的靶点 STN-DBS在适当选择的患者中显示出可靠和一致的改善。另 STN-DBS后手部语言运动的结果是不可预测的， 比那些注意到说话改善的人更糟糕。估计40%的STN-DBS患者 注意到恶化的语言和下降显着足以降低生活质量。此外，少数 存在有效的治疗方法来为那些患有 语言障碍 为了优化和开发更好的治疗PD患者，有必要更好地 理解作为当代人类言语产生的机械模型， 省略。我们研究了80例接受双侧STN-DBS的PD患者，其中沿着有40例非手术PD 控制主题，以解决现有的关键知识差距。我们将记录下 两组通过功能性沟通能力（即可理解性的客观测量和 经验证的调查工具，用于量化沟通参与）和工具性语音（即声学） 测量术前、术后6个月和12个月，所有受试者均停用PD药物， 在两个术后时间点，在刺激开启和关闭的情况下对STN-DBS受试者进行评价。直接 在DBS植入手术期间，将在言语和肢体运动期间获得神经元记录 任务来定义语言特异性神经生理学。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发现来确定导致 我们将记录语音结果，并测试低频DBS逆转DBS的可行性- 诱发性言语衰退。 据我们所知，这些数据将是第一个在术前、术中和术后对患者进行评估的数据。 手术的目的是直接确定语音中的作用和预测语音结果 在STN-DBS之后。这些知识将提供使用其他方法无法获得的机械见解。 技术，并将指导发展新的治疗受损的语言在PD。

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.