PFC circuits and systems in human intraoperative neurophysiology

PFC 电路和系统在人类术中神经生理学中的应用

• 批准号: 10490439
• 负责人: Jeremy Greenlee
• 金额: $ 12.32万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10490439
• 关键词: Address; Affect; Anatomy; Area; Basal Ganglia; Bilateral; Bradykinesia; Brain; Brain region; Cerebral hemisphere; Cognition; Cognitive; Cognitive deficits; Complement; DRD1 gene; Data; Deep Brain Stimulation; Development; Diffusion Magnetic Resonance Imaging; Disease; Dopamine; Electrophysiology (science); FOXP2 gene; Family; Foundations; Functional Magnetic Resonance Imaging; Gene Expression; Gene Expression Profile; Genes; Genetic; Goals; Human; Impaired cognition; Impairment; Knowledge; Language; Limb structure; Magnetic Resonance Imaging; Measurement; Measures; Medical; Microelectrodes; Molecular; Molecular Profiling; Motor; Neurodegenerative Disorders; Neurons; Operative Surgical Procedures; Outcome; Parkinson Disease; Participant; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Physiological; Physiology; Play; Prefrontal Cortex; Production; Quality of life; Refractory; Research; Resolution; Rest Tremor; Role; Scanning; Signal Pathway; Site; Specimen; Speech; Structure of subthalamic nucleus; Study Subject; Symptoms; Synaptic plasticity; System; Techniques; Tissue Sample; Transcript; alpha synuclein; awake; base; cholinergic; cognitive function; cognitive impairment in Parkinson' s; cognitive task; effective therapy; functional decline; gene therapy; imaging study; implantation; improved; insight; motor control; motor function improvement; neural model; neurophysiology; non-motor symptom; novel strategies; personalized medicine; relating to nervous system; side effect; temporal measurement; transcriptome sequencing

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.

抽象的 帕金森病 (PD) 是一种日益流行的进行性神经退行性疾病， 大多数患者最终会导致失能的非运动症状，包括重要的言语和 认知功能障碍。这些损害会极大地降低患者及其家属的生活质量 家庭。重要的是，很少有治疗方法可以有效治疗这些非运动效应。此外， 多巴胺能药物和深部脑刺激 (DBS) 等治疗方法通常有效 在改善帕金森病患者的运动功能方面，在改善言语和语言方面往往无效 认识。在许多情况下，这些治疗甚至会使这些功能恶化。 众所周知，前额皮质 (PFC) 是人类有效言语和认知功能的关键。然而， 关于人类 PFC 如何受到帕金森病的影响，以及这些疾病特异性的影响如何，仍然存在许多问题 导致言语和认知功能紊乱。为了解决这些知识差距并 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 名选择接受治疗的 PD 患者。 双侧丘脑底核 (STN) DBS 植入手术利用这一特殊机会 在手术期间的言语和认知任务期间直接从 PFC 部位进行记录。此外，我们将 同时从 STN 进行记录，因为已知它连接到 PFC 并由这些大脑进行调制 地区。补充直接 PFC 和 STN 大脑的详细解剖学和时间分辨率 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、功能和连接性 MRI 成像评估 研究。扫描将在手术前和手术后三个月进行，因此 PFC 的所有区域，包括 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采集PFC组织样本来检查基因 表达。与多巴胺和胆碱能途径以及语言相关的基因表达谱将 被量化。据我们所知，该可行性数据将是第一个评估参与者的可行性数据 手术前、手术中和手术后进行 PD，目的是确定 PFC 的作用及其相互作用 STN 的言语和认知功能。这些知识将提供机械的见解，而这是无法 使用其他技术获得并将指导新研究的发展，并希望最终 PD 言语和认知障碍的治疗。