PFC circuits and systems in human intraoperative neurophysiology

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，在 大多数患者最终会导致包括重要言语在内的非运动症状的残疾，并且 认知功能障碍。这些损伤会显著降低患者和他们的生活质量 家人。重要的是，几乎没有治疗方法可以有效地治疗这些非运动效应。此外， 多巴胺能药物和脑深部刺激(DBS)等通常有效的治疗方法 在改善帕金森病患者的运动功能方面，往往在改善言语和 认知力。在许多情况下，这些治疗甚至会恶化这些功能。 前额叶皮质(PFC)被认为是人类有效言语和认知功能的关键。然而， 关于帕金森病是如何影响人类PFC的，以及这些疾病特异性的影响如何，仍然存在许多问题 会导致言语和认知功能障碍。为了弥补这些知识差距，为了 为帕金森病患者优化和开发更好的治疗方法，有必要更好地了解 PFC在言语和认知中的作用。在这里，我们研究了20名PD患者，他们选择接受 双侧丘脑底核(STN)DBS植入手术利用这一特殊机会 在手术中的言语和认知任务中，直接从PFC站点记录。此外，我们还将 同时从STN记录，因为已知它连接到PFC并由这些大脑调制 地区。以补充直接PFC和STN脑的详细解剖和时间分辨率 这些皮质和皮质下区域之间的记录和有效的连接措施， 参与者还将接受详细的结构、功能和连通性MRI成像评估 学习。扫描将在手术前和术后三个月进行，因此PFC的所有区域，在 大脑半球可以通过言语和认知任务进行评估。 此外，我们将在这些参与者的手术过程中收集PFC组织样本，以检测基因 表情。与多巴胺和胆碱能通路及语言意志相关的基因表达谱 被量化。据我们所知，这一可行性数据将是第一次对参与者进行评估 手术前、术中和术后的PD，目的是确定PFC的作用及其相互作用 在言语和认知功能上有STN。这样的知识将提供机械的洞察力，而不是 使用其他技术获得，并将指导新研究的发展，希望最终 帕金森病患者言语和认知障碍的治疗。

Abstract Parkinson's disease (PD) is an increasingly prevalent progressive neurodegenerative disorder that in most patients eventually leads to disabling non-motor symptoms including significant speech, and cognitive dysfunction. These impairments can dramatically reduce quality of life for patients and their families. Importantly, few treatments exist that can effectively treat these non-motor effects. Furthermore, treatments like dopaminergic medications and deep brain stimulation (DBS) that are generally effective at improving the motor function of people with PD, are very often ineffective at improving speech and cognition. In many cases, these treatments can even worsen those functions. Prefrontal cortex (PFC) is known to be key to effective human speech and cognitive function. However, many questions remain about how human PFC is affected by PD, and how these disease-specific effects result in disrupted speech and cognitive function. To address these knowledge gaps and in order to optimize and develop better treatments for those living with PD, it is necessary to better understand the role of PFC in speech and cognition. Here we study 20 PD patients who have chosen to undergo bilateral subthalamic nucleus (STN) DBS implantation surgery to leverage this special opportunity to directly record from PFC sites during speech and cognitive tasks during surgery. In addition, we will simultaneously record from STN, as it is known to be connected to PFC and modulated by those brain regions. To complement the detailed anatomical and temporal resolution of direct PFC and STN brain recordings and effective connectivity measures between these cortical and subcortical regions, participants will also be assessed with detailed structural, functional, and connectivity MRI imaging studies. Scans will be obtained before and three months after surgery so all areas of PFC, in both cerebral hemispheres can be assessed with speech and cognitive tasks. In addition, we will collect PFC tissue samples in these participants during their surgery to examine gene expression. Gene expression profiles related to dopamine and cholinergic pathways and language will be quantified. To our knowledge, this feasibility data will be the first of its kind to evaluate participants with PD before, during, and after surgery with the goals of defining the role of PFC and its interactions with STN in speech and cognitive function. Such knowledge will provide mechanistic insights that cannot be obtained using other techniques and will guide development of new studies and hopefully eventually treatments of impaired speech and cognition in PD.