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 项独立创新的融合揭示了获得对人类多巴胺系统功能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都依赖于完整的多巴胺能功能，这使得这个机会变得重要、及时和令人兴奋。这四项创新是（1）深部脑刺激电极（DBS）的发明、植入和在晚期帕金森病患者中的成功长期使用，（2）多巴胺能功能计算模型的开发，该模型现已在以下水平得到验证：多巴胺神经元的单个单元活动、目标结构的多巴胺释放以及人类受试者的功能成像实验 (fMRI)，(3) 证明被认为由多巴胺传递编码的学习信号可以在帕金森氏症患者使用功能磁共振成像和简单的调理和决策任务，以及（4）开发生物相容性电极，能够在学习和决策任务期间对细胞外多巴胺进行亚秒级测量。该项目将对人脑中多巴胺系统的功能产生前所未有的洞察力，并且对于解决一系列涉及多巴胺能功能的问题（包括成瘾和各种形式的精神疾病）具有无价的价值。帕金森病 (PD) 的主要身体缺陷是 80-90% 的多巴胺神经元丧失，因此该提案旨在利用 DBS 电极植入的急性期来准确了解困扰该疾病患者的病理学过程。