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: 9887437
• 负责人: Jeremy Greenlee
• 金额: $ 69.44万
• 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/9887437
• 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; 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; 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