Dopaminergic activity and release during DBS implantation in humans

DBS 植入人体期间的多巴胺能活性和释放

• 批准号: 7361595
• 负责人: P Read Montague
• 金额: $ 16.81万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7361595
• 关键词: Active Learning; Acute; Bilateral; Biocompatible; Brain; Chronic; Cognition; Computer Simulation; Decision Making; Deep Brain Stimulation; Development; Disease; Dopamine; Electrodes; Functional Imaging; Human; Learning; Measurement; Mental disorders; Parkinson Disease; Pathology; Patients; Phase; Range; Rate; Side; Signal Transduction; Staging; Structure; Substantia nigra structure; Thinking; addiction; conditioning; dopamine system; dopaminergic neuron; extracellular; human subject; implantation; innovation; insight; research study

DESCRIPTION (provided by applicant): The convergence of 4 separate innovations has exposed the possibility of gaining unprecedented insights into the function of dopamine systems in humans. The many aspects of cognition, learning, decision-making, and action selection that depend on intact dopaminergic function make this opportunity important, timely, and exciting. The four innovations are (1) the invention, implantation, and successful chronic use of deep brain stimulation electrodes (DBS) in late stage Parkinson's patients, (2) the development of computational models of dopaminergic function that have now been validated at the level of single unit activity in dopamine neurons, dopamine release at target structures, and functional imaging experiments (fMRI) in human subjects, (3) the demonstration that learning signals thought to be encoded by dopamine delivery can be tracked in Parkinson's patients using fMRI and simple conditioning and decision-making tasks, and (4) the development of biocompatible electrodes capable of making sub-second measurements of extracellular dopamine during learning and decision-making tasks. This project will yield unprecedented insight into the function of dopamine systems in the human brain and should prove invaluable to a range of problems involving dopaminergic function including addiction and various forms of mental illness. The primary physical deficit in Parkinson's disease (PD) is the loss of 80-90% of dopamine neurons and so this proposal seeks to use the acute phase of DBS electrode implantation to gain new insights into exactly the pathology that tragically afflicts sufferers of the disease.

描述（由申请人提供）：4种独立创新的融合已经暴露了对人类多巴胺系统功能的前所未有的见解的可能性。认知，学习，决策和行动选择的许多方面取决于完整的多巴胺能功能，使这个机会变得重要，及时和令人兴奋。四项创新是（1）在晚期帕金森氏病患者中的发明，植入和成功地长期使用深脑刺激电极（DB），（2）多巴胺能功能的计算模型的发展，这些模型现已在多巴胺神经元中在单位单位活动水平上验证，在多巴胺神经元中，多巴胺释放，多巴胺在人类多巴胺中释放（三个）主题（三个），以及FMRIMIT（FMR），FMR（FMR）（FMR）（FMR）（FMR）（FMR）。可以使用fMRI，简单的调理和决策任务在帕金森患者中跟踪多巴胺传递编码的学习信号，以及（4）生物相容性电极的发展，能够在学习和决策任务期间对细胞外多巴胺进行次要测量。该项目将对人脑中多巴胺系统的功能进行前所未有的见解，并将证明对涉及多巴胺能功能（包括成瘾和各种精神疾病）的一系列问题证明是无价的。帕金森氏病（PD）的主要身体缺陷是多巴胺神经元的80-90％的损失，因此该提案试图利用DBS电极植入的急性期来获得对疾病患者悲惨病理的正当病理的新见解。