Effects of deep brain stimulation (DBS) on laryngeal function and associated behaviors in Parkinson Disease

项目摘要/摘要 北美现在有近100万人患有帕金森氏症(PD)，这一数字是 预计到2030年将增加到近120万。随着神经调节技术的进步， 这些人中更多的人选择接受脑深部刺激(DBS)手术，以控制 这种疾病包括顽固性震颤、药物引起的运动障碍和帕金森病相关的肌张力障碍。两个人 控制这些症状最常见的DBS神经靶点是苍白球内段(Gpi)。 和丘脑底核(STN)。最近的荟萃分析表明，这两者之间具有相对的等价性 控制核心帕金森病症状的网站。到目前为止，还没有关于潜在影响的确凿证据 DBS到GPI或STN对喉部介导的发声、吞咽和咳嗽功能的影响，因此没有 指导在选择星展银行目标时是否应考虑这些结果。因此，目标是 此应用程序用于确定星展银行神经靶点(STN与GPI)的影响、靶点内的导联位置、 帕金森病患者的偏侧性，以及对声音、吞咽和咳嗽功能的刺激设置。喉头是一种 在这些功能中扮演重要角色，我们的中心假设是刺激传播到 内囊膝部的皮质球纤维对喉运动有不良影响 控制，导致发声、吞咽和咳嗽功能障碍。我们为此确定了三个具体目标 申请：1.)比较DBS前、后DBS和DBS时的喉部功能 对于STN和GPI目标，放置是双边的，而不是单边的。2.)比较喉部功能的变化 STN患者术后DBS前的自愿性和诱发性咳嗽任务，以及双侧DBS放置与单侧DBS放置时 和GPI目标。3.)比较喉部症状、程度和持续时间与呼吸道安全的关系 在吞咽过程中、术后DBS前和当DBS放置为双侧而不是单侧时，STN和 GPI目标。这些假说是在令人信服的已发表和未发表的初步研究的基础上提出的 数据。我们将通过招募正在考虑接受星展手术的PD患者来实现这些目标， 和年龄、病程和严重程度相似的对照队列，他们目前没有被考虑 星展银行的手术。我们将测量发声、吞咽和咳嗽的生理、功能和生活质量参数 手术前和手术后(对照组在等间隔的时间点)。可持续发展目标的实现 提议的目标意义重大，因为它将解决我们对星展成果的理解中存在的重大差距 与通信和呼吸道保护有关，这在发病率、死亡率和质量方面都很重要 帕金森病患者的生活质量。为星展银行手术团队提供额外指导的翻译潜力 在选择DBS目标和/或时是否应考虑发声、吞咽或咳嗽功能 偏侧性很高。最终，该项目正好符合研究团队要交付的总体目标 尽可能为帕金森病患者提供最好的护理。

Project Summary/Abstract Nearly one-million people in North America are now living with Parkinson’s disease (PD), and that number is projected to rise to nearly 1.2 million by 2030. With advancements in neuromodulatory technologies, increasingly more of these individuals elect to undergo deep brain stimulation (DBS) surgery in order to control symptoms of the disease, including refractory tremor, medication-induced dyskinesias, and PD-associated dystonia. The two most common DBS neural targets for controlling these symptoms are the globus pallidus internal segment (GPi) and the subthalamic nucleus (STN). Recent meta-analyses have shown relative equivalence between these two sites at controlling core PD symptoms. To date, there is not conclusive evidence regarding the potential impact of DBS to GPi or STN on laryngeal-mediated functions of voice, swallowing, and cough, and consequently no guidance on whether these outcomes should be considered when selecting DBS target. Therefore, the goal of this application is to determine the impact of DBS neural target (STN versus GPi), lead location within the target, laterality, and stimulation settings on voice, swallow and cough function in people with PD. The larynx is an important player in each of these functions, and our central hypothesis is that spread of stimulation to corticobulbar fibers in the genu of the internal capsule have deleterious effects on laryngeal motor control, resulting in voice, swallow, and cough dysfunction. We have identified three specific aims for this application: 1.) To compare laryngeal function during volitional voice tasks pre-post DBS, and when DBS placement is bilateral versus unilateral for STN and GPi targets. 2.) To compare laryngeal function during volitional and induced cough tasks pre-post DBS, and when DBS placement is bilateral versus unilateral for STN and GPi targets. 3.) To compare airway safety associated with laryngeal onset, degree, and duration of maximum closure during swallowing, pre-post DBS, and when DBS placement is bilateral versus unilateral for STN and GPi targets. These hypotheses were developed based on compelling published and unpublished preliminary data. We will accomplish these aims by enrolling people with PD who are being considered for DBS surgery, and a control cohort with similar age, disease duration and severity, who are not currently being considered for DBS surgery. We will measure physiologic, functional, and quality of life parameters of voice, swallow and cough pre- and post-surgically (and at equivalently spaced time-points for the control group.) The realization of the proposed aims is significant because it will address a substantial gap in our understanding of DBS outcomes related to communication and airway protection, which are important in terms of morbidity, mortality, and quality of life for patients with PD. The translational potential to provide additional guidance to DBS surgical teams regarding whether voice, swallow or cough functions should be considered with selecting DBS target and/or laterality is high. Ultimately, the project fits squarely within the overarching goal of the research team to deliver the best possible care to people with PD.