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， 大多数患者最终导致致残性非运动症状，包括明显的言语， 认知功能障碍这些损伤可以显著降低患者的生活质量， 家庭重要的是，很少有治疗方法可以有效地治疗这些非运动效应。此外，委员会认为， 多巴胺能药物和脑深部电刺激（DBS）等治疗通常有效 在改善PD患者的运动功能方面， 认知.在许多情况下，这些治疗甚至会使这些功能恶化。 前额叶皮层（PFC）是人类有效的语言和认知功能的关键。然而，在这方面， 关于人类PFC如何受到PD的影响，以及这些疾病特异性效应如何 导致言语和认知功能紊乱。为了弥补这些知识差距， 为PD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名选择接受 双侧丘脑底核（DBS）植入手术，以利用这一特殊机会， 在手术期间的语音和认知任务期间直接从PFC部位记录。此外，我们将 同时记录，因为它被称为是连接到PFC和调制的那些大脑 地区为了补充直接PFC和小脑的详细解剖和时间分辨率， 记录和这些皮层和皮层下区域之间的有效连接测量， 参与者还将接受详细的结构、功能和连接性MRI成像评估 问题研究将在手术前和手术后三个月进行扫描，以便PFC的所有区域， 大脑半球可以用语言和认知任务来评估。 此外，我们将在这些参与者的手术过程中收集PFC组织样本，以检查基因。 表情与多巴胺和胆碱能通路和语言相关的基因表达谱将 要量化。据我们所知，这一可行性数据将是第一个评估参与者的同类数据 在手术前、手术中和手术后对PD进行研究，目的是确定PFC的作用及其相互作用 在语言和认知功能上都有缺陷。这样的知识将提供机械的见解， 使用其他技术获得，并将指导新研究的发展，并希望最终 治疗PD患者的言语和认知障碍。

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.