Real-time neurochemical encoding of reward- and punishment-prediction errors and associated subjective experiences in humans

人类奖励和惩罚预测错误及相关主观体验的实时神经化学编码

• 批准号: 10398038
• 负责人: Kenneth Tucker Kishida
• 金额: $ 34.52万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10398038
• 关键词: Affect; Amygdaloid structure; Animal Model; Behavior; Behavior Control; Behavioral; Brain; Brain region; Chemicals; Cocaine; Conscious; Corpus striatum structure; Data; Decision Making; Decision Theory; Desire for food; Development; Dopamine; Exposure to; Feedback; Feeling; Foundations; Functional Magnetic Resonance Imaging; Future; Gambling; Goals; Grant; Human; Individual; Intractable Epilepsy; Knowledge; Lead; Learning; Mathematics; Measurement; Measures; Neurobiology; Nicotine; Nucleus Accumbens; Operant Conditioning; Opioid; Outcome; Participant; Patient Self-Report; Peer Review; Persons; Play; Prefrontal Cortex; Procedures; Process; Psychological reinforcement; Publishing; Punishment; Reporting; Research; Rewards; Role; Serotonergic System; Serotonin; Signal Transduction; Specificity; Substance Use Disorder; Substance of Abuse; System; Technology; Temporal Lobe; Testing; Time; Work; classical conditioning; conditioning; design; dopamine system; drug of abuse; emotional experience; experience; experimental study; extracellular; financial incentive; human subject; insight; neurochemistry; novel; putamen; reward processing; temporal measurement; theories

SUMMARY: Drugs of abuse (like opiates, cocaine, and nicotine) are initially taken because people want to alter how they subjectively feel, but these substances have potentially longer lasting negative consequences on the human brain, because of neurobiological effects that can lead to substance use disorder. The dopamine and serotonin systems have been strongly implicated in these processes, but these systems have not been investigated in humans with the temporal resolution required to connect (1) how these rapid signals alter our behavior as human navigate the world, nor (2) how these neurochemical signals alter how we feel subjectively. Progress has been hindered by lack of technology that permits simultaneous, real-time, measurements of dopamine and serotonin release during conscious decision-making and experience in humans (and for the fact that non-human model organisms cannot report ‘how they feel’). This proposal capitalizes on recent advances in mathematized human decision theory and our group’s first-of- its-kind technological approach, which now allows simultaneous, col-localized, measurements of dopamine and serotonin release in the human brain with sub-second temporal resolution during conscious decision- making and experience. Here, we pursue two specific goals, which uniquely combines our validated, peer- reviewed, and published approach with probabilistic learning tasks that have been specifically designed to probe the interplay between opponent reward and punishment behavioral signals, rapid changes in dopamine and serotonin release, and moment-to-moment changes in how participants feel during sequences of experience. First (aim 1), we will test the hypothesis that sub-second changes in extracellular dopamine and serotonin encode monetary reward/appetitive prediction errors and monetary punishment/aversive prediction errors, respectively, as opponent signals in the human striatum during an instrumental learning task and a passive Pavlovian conditioning task. Second (aim 2), we will test the hypothesis that sub-second changes in extracellular dopamine and serotonin, together, direct moment-to-moment changes in how people feel. The experiments proposed will for the first time directly test the controversial “opponent hypothesis” for serotonin/dopamine function in learning and decision-making in humans; and, we will for the first time begin to expose what role rapid microfluctuations in dopamine and serotonin play in encoding positive and negative subjective feelings in humans. We expect that these first-of-their-kind data will provide new insight into how drugs of abuse may alter how people feel, the impact drugs of abuse may have on critical neurochemical learning systems in the human brain, and may lay a foundation for future work aimed at understanding how these neurochemical systems affect other human brain regions (including nucleus accumbens, prefrontal cortex, amygdala, and the temporal lobes) where access maybe afforded by new DBS procedures or intracranial mapping for refractory epilepsy.

摘要：最初服用滥用药物（例如阿片类药物，可卡因和尼古丁），因为人们想改变自己的感觉，但是由于神经生物学作用可能导致药物使用障碍，因此这些物质可能对人脑产生持久的负面影响。多巴胺和5-羟色胺系统已经在这些过程中强烈牵涉，但是在人类中尚未对这些系统进行调查，而连接所需的临时分辨率（1）这些迅速信号如何改变我们的行为，因为人类导航世界，也没有（2）这些神经化学信号如何改变我们的感受。在有意识的决策和人类经验期间，由于缺乏技术，实时的测量，对多巴胺和5-羟色胺释放的测量所阻碍了进步（而且由于非人类模型生物体无法报告“他们的感觉”）。 该提案利用了数学化的人类决策理论的最新进展以及我们小组的首个技术方法，该方法现在允许在人脑中同时进行多巴胺和血清蛋白在人脑中释放，并在有意识的决策和经验中临时解决。在这里，我们实现了两个具体的目标，这些目标将我们经过验证的，经过同行评审和已发表的方法与概率学习任务结合在一起，这些任务是专门设计的，这些任务是专门设计的，旨在探究选项奖励和惩罚行为信号之间的相互作用，多巴胺和血清素释放的快速变化，以及参与者在经验序列序列的过程中的瞬间变化。首先（AIM 1），我们将检验以下假设：在器乐学习任务和被动的Pavlovian条件任务期间，在人类纹状体中，分别用作人类纹状体中的选择信号，将细胞外多巴胺和5-羟色胺编码的货币奖励/食欲预测错误以及货币惩罚/厌恶预测错误。其次（AIM 2），我们将检验以下假设：细胞外多巴胺和5-羟色胺的下一步变化，共同直接在人们的感受中直接变化。提出的实验将首次直接检验有争议的“对手假设”，用于在人类学习和决策中的5-羟色胺/多巴胺功能；而且，我们将首次开始揭示多巴胺和5-羟色胺在编码人类积极和消极的主观感觉中的作用。 We expect that these first-of-their-kind data will provide new insight into how drugs of abuse may alter how people feel, the impact drugs of abuse may have on critical neurochemical learning systems in the human brain, and may lay a foundation for future work aimed at understanding how these neurochemical systems affect Other human brain regions (including nuclear accumbens, prefrontal cortex, amygdala, and the temporary lobes) where access may be afforded by new DBS用于难治性癫痫的程序或颅内映射。