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; 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 帕金森氏病（PD）是一种越来越普遍的进行性神经退行性疾病 大多数患者最终导致致残的非运动症状，包括大量语音， 认知功能障碍。这些障碍可以大大降低患者及其的生活质量 家庭。重要的是，很少有可以有效治疗这些非运动作用的治疗方法。此外， 诸如多巴胺能药物和深脑刺激（DBS）等治疗通常是有效的 在改善PD患者的运动功能方面，通常无法改善语音和 认识。在许多情况下，这些治疗方法甚至会使这些功能恶化。 已知前额叶皮层（PFC）是有效人类言语和认知功能的关键。然而， 关于人类PFC如何受到PD的影响以及这些疾病特定的影响仍然存在许多问题 导致言语和认知功能中断。解决这些知识差距，以便 优化并为患有PD的人提供更好的治疗方法，有必要更好地了解 PFC在语音和认知中的作用。在这里，我们研究了20例选择接受的PD患者 双侧下丘脑核（STN）DBS植入手术，以利用这一特殊机会 手术期间的语音和认知任务中直接从PFC站点记录。此外，我们将 同时记录了STN，因为已知已连接到PFC并由这些大脑调节 地区。补充直接PFC和STN脑的详细解剖学和时间分辨率 记录和这些皮质和皮质下区域之间的有效连通性测量， 参与者还将通过详细的结构，功能和连接性MRI成像进行评估 研究。扫描将在手术前和三个月后进行，因此PFC的所有区域都在这两个区域中 可以通过语音和认知任务评估脑半球。 此外，我们将在手术期间收集这些参与者的PFC组织样品以检查基因 表达。与多巴胺和胆碱能途径和语言有关的基因表达剖面 被量化。据我们所知，这些可行性数据将是第一个评估参与者的此类数据 在手术之前，期间和之后使用PD，其目标是定义PFC及其相互作用的作用 具有语音和认知功能的STN。这样的知识将提供无法 可以使用其他技术获得，并将指导新研究的发展，并希望最终 PD中语音和认知受损的治疗方法。