WINCS and DBS

WINCS 和 DBS

• 批准号: 8850909
• 负责人: Kendall H. Lee
• 金额: $ 34.13万
• 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 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8850909
• 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; microsensor; 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）：基底神经节复合物中的深脑刺激（DBS）是治疗帕金森氏病（PD）的有效神经外科手术方法。 阐明DBS机制改善PD和其他靶向疾病的结局已成为立体定向和功能性神经外科手术的关键临床目标。 我们建议通过首次合并两种强大的技术，尤其是功能性磁共振成像（fMRI）和体内神经化学监测来研究DBS介导的基础神经节网络电路激活。 为此，我们开发了一种与MRI兼容的无线监测设备，以在大型哺乳动物模型（Rhesus Monkey）中植入的微传感器上获得化学分辨的神经递质测量值。 该设备支持一系列的电化学测量值，包括快速扫描的环状伏安法（FSCV），用于实时同时在体内监测多巴胺和腺苷释放，碳纤维微电极上的腺苷释放，以及固定电位截肢测定术以及在乙酰糖中监测Enzyme-ememe-comememe-link的固定电位截止性。 使用STN的电生理靶向对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使用fMRI来确定在临床定义的“治疗性”（TDBS）与非刺激性（NDBS）（ndbs）（ndbs）的临床定义的“治疗”（TDB）期间，在临床定义的“治疗”（TDBS）应用过程中，基础神经节中的主要激活部位。 然后，我们将通过fMRI激活鉴定的大脑区域中STN DBS引起的谷氨酸，多巴胺和腺苷释放的细胞外谷氨酸，多巴胺和腺苷释放。 最后，我们建议将恒河猴中的fMRI和FSCV记录结合在一起，以确认谷氨酸，多巴胺和/或腺苷释放与/或腺苷释放之间的因果关系，以及fMRI-ISSIDED在基底神经节中的解剖位点，通过确定多巴胺消耗和repletion Mimickic contocical Mimickics Mimickics Mimickic and Pressication Mimicking and the and Adimicking Portocic and Pressication Mimickic and the and Adimickic and the and dy the the and p.d the and p.D的疾病。耗尽。 （1）使用STN DBS激活的基底神经节复合物中的FMRI大脑区域确定，（（2）量化谷氨酸，多巴胺和腺苷释放，由FMRI鉴定的STN DBS引起的STN DBS诱发，并通过FMRI鉴定的STN DBS释放，以及（3）通过释放的STN DBS-ESEN-EDENES iSADERIPIAN-DOPIRIENIPRIATION-DOPRI，DOPRI，DOPRI，DOPRIN和DOPRIN，dopamine inter anden和dopririention和dopri，并释放出DOPRIN和DOPRIN，并释放。在药理学耗竭和多巴胺的恢复期间，期间和之后同时进行fMRI，并减少腺苷。 我们认为，fMRI和电化学的同时组合提供了一种新的令人兴奋的方法，提供了互补的解剖学映射和神经化学监测，该方法与STN DBS的治疗作用有关。

项目成果

Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor.

• DOI: 10.1093/brain/aww145
• 发表时间: 2016-08
• 期刊: Brain : a journal of neurology
• 作者: Gibson WS;Jo HJ;Testini P;Cho S;Felmlee JP;Welker KM;Klassen BT;Min HK;Lee KH
• 通讯作者: Lee KH

A Diamond-Based Electrode for Detection of Neurochemicals in the Human Brain.

• DOI: 10.3389/fnhum.2016.00102
• 发表时间: 2016
• 期刊: Frontiers in human neuroscience
• 影响因子: 2.9
• 作者: Bennet KE;Tomshine JR;Min HK;Manciu FS;Marsh MP;Paek SB;Settell ML;Nicolai EN;Blaha CD;Kouzani AZ;Chang SY;Lee KH
• 通讯作者: Lee KH

Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens.

• DOI: 10.1016/j.neuroimage.2015.12.056
• 发表时间: 2016-03
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Ross EK;Kim JP;Settell ML;Han SR;Blaha CD;Min HK;Lee KH
• 通讯作者: Lee KH

WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions.

• DOI: 10.1038/srep46675
• 发表时间: 2017-04-28
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Lee KH;Lujan JL;Trevathan JK;Ross EK;Bartoletta JJ;Park HO;Paek SB;Nicolai EN;Lee JH;Min HK;Kimble CJ;Blaha CD;Bennet KE
• 通讯作者: Bennet KE

Centromedian-Parafascicular Complex Deep Brain Stimulation for Tourette Syndrome: A Retrospective Study.

中央正中-束旁复合深部脑刺激治疗抽动秽语综合征：一项回顾性研究。

• DOI: 10.1016/j.mayocp.2015.11.016
• 发表时间: 2016
• 期刊: Mayo Clinic proceedings
• 影响因子: 8.9
• 作者: Testini,Paola;Zhao,CongZ;Stead,Matt;Duffy,PenelopeS;Klassen,BryanT;Lee,KendallH
• 通讯作者: Lee,KendallH