WINCS and DBS

WINCS 和 DBS

• 批准号: 8274635
• 负责人: Kendall H. Lee
• 金额: $ 34.16万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-15 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8274635
• 关键词: Address; Adenosine; Animal Model; Animals; Area; Basal Ganglia; Biosensor; Brain; Brain region; Chemicals; Clinical; Complex; Data; Deep Brain Stimulation; Dependency; Devices; Disease; Distal; Dopamine; Electrochemistry; Electrodes; Enzymes; Family suidae; Functional Magnetic Resonance Imaging; Glutamates; Goals; Human; Image Analysis; Implant; Lesion; Link; Macaca mulatta; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mediating; Microelectrodes; Modality; Modeling; Monitor; Monkeys; Neurons; Neurotransmitters; Outcome; Output; Parkinson Disease; Pattern; Pharmacological Treatment; Protocols documentation; STN stimulation; Scanning; Signal Transduction; Site; Structure; Structure of subthalamic nucleus; Symptoms; System; Techniques; Technology; Therapeutic; Thinking; Time; Tyrosine Hydroxylase Inhibitor; Wireless Technology; base; carbon fiber; extracellular; implantation; improved; in vivo; insight; monitoring device; neurobiological mechanism; neurochemistry; neuropathology; neurosurgery; neurotransmitter release; novel; putamen; relating to nervous system; response; restoration; transmission process; transport inhibitor

DESCRIPTION (provided by applicant): Deep brain stimulation (DBS) within the basal ganglia complex is an effective neurosurgical approach for treating motoric symptoms of Parkinson's disease (PD). Elucidating DBS mechanisms for improving outcomes in PD and other targeted disorders has become a critical clinical goal in stereotactic and functional neurosurgery. We propose to address this issue by combining for the first time two powerful technologies, notably functional Magnetic Resonance Imaging (fMRI) and in vivo neurochemical monitoring to investigate DBS-mediated activation of basal ganglia network circuitry. For this purpose, we have developed an MRI-compatible wireless monitoring device to obtain chemically resolved neurotransmitter measurements at implanted microsensors in a large mammalian model (rhesus monkey). This device supports an array of electrochemical measurements that includes fast-scan cyclic voltammetry (FSCV) for real-time simultaneous in vivo monitoring of dopamine and adenosine release at carbon-fiber microelectrodes as well as fixed potential amperometry for monitoring of glutamate at enzyme-linked biosensors. Using electrophysiological targeting of the STN to implant appropriately scaled-down human DBS electrodes, our rhesus monkey model will enable us to employ fMRI to initially determine the major sites of activation in the basal ganglia during application of clinically-defined "therapeutic" (tDBS) versus "non-therapeutic" (nDBS) STN stimulation. We will then electrochemically monitor extracellular levels of glutamate, dopamine and adenosine release evoked by STN DBS in the brain areas identified by fMRI activation. Lastly, we propose to combine fMRI and FSCV recordings in the rhesus monkey to confirm a causal relationship between glutamate, dopamine and/or adenosine release and the fMRI-identified anatomical sites in the basal ganglia complex by determining the consequences of dopamine depletion and repletion mimicking advanced PD and pharmacological treatment of the disease, as well as adenosine depletion. The three Specific Aims are (1) identify using fMRI brain regions within the basal ganglia complex activated by STN DBS, (2) quantify glutamate, dopamine and adenosine release evoked by STN DBS of the brain region(s) identified by fMRI, and (3) correlate STN DBS-evoked glutamate, dopamine and adenosine release in the regions identified by fMRI with simultaneous fMRI before, during, and after pharmacological depletion and restoration of dopamine, and reductions in adenosine. We believe that the simultaneous combination of fMRI and electrochemistry offer a new and exciting approach that provides complementary anatomical mapping and neurochemical monitoring implicated in the therapeutic actions of STN DBS.

描述（由申请人提供）：基底神经节复合体内的深部脑刺激（DBS）是治疗帕金森病（PD）运动症状的有效神经外科方法。 阐明 DBS 改善 PD 和其他靶向疾病预后的机制已成为立体定向和功能神经外科的一个关键临床目标。 我们建议通过首次结合两种强大的技术来解决这个问题，特别是功能性磁共振成像（fMRI）和体内神经化学监测，以研究 DBS 介导的基底神经节网络电路的激活。 为此，我们开发了一种与 MRI 兼容的无线监测设备，用于在大型哺乳动物模型（恒河猴）中植入的微传感器上获得化学解析的神经递质测量结果。 该器件支持一系列电化学测量，包括用于实时同时体内监测碳纤维微电极上的多巴胺和腺苷释放的快速扫描循环伏安法 (FSCV)，以及用于监测酶联谷氨酸盐的固定电位安培法。生物传感器。 利用 STN 的电生理学靶向来植入适当缩小的人类 DBS 电极，我们的恒河猴模型将使我们能够利用功能磁共振成像来初步确定在应用临床定义的“治疗”（tDBS）期间基底神经节的主要激活位点与“非治疗性”(nDBS) STN 刺激相比。 然后，我们将通过电化学方式监测 STN DBS 在功能磁共振成像激活识别的大脑区域中引起的谷氨酸、多巴胺和腺苷释放的细胞外水平。 最后，我们建议将恒河猴的 fMRI 和 FSCV 记录结合起来，通过确定多巴胺消耗和补充模拟的后果来确认谷氨酸、多巴胺和/或腺苷释放与基底神经节复合体中 fMRI 识别的解剖部位之间的因果关系。先进的帕金森病和药物治疗，以及腺苷耗竭。 三个具体目标是 (1) 使用 fMRI 识别由 STN DBS 激活的基底神经节复合体内的大脑区域，(2) 量化由 fMRI 识别的大脑区域的 STN DBS 引起的谷氨酸、多巴胺和腺苷释放，以及（ 3) 将 fMRI 识别的区域中 STN DBS 诱发的谷氨酸、多巴胺和腺苷释放与之前、期间和期间的同步 fMRI 相关联在多巴胺的药理学耗尽和恢复以及腺苷减少之后。 我们相信，功能磁共振成像和电化学的同时结合提供了一种令人兴奋的新方法，可以提供与 STN DBS 治疗作用相关的补充解剖图和神经化学监测。