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: 10152471
• 负责人: Kenneth Tucker Kishida
• 金额: $ 34.53万
• 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/10152471
• 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; 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：滥用药物(如阿片剂、可卡因和尼古丁)最初是因为人们想要改变他们的主观感受，但这些物质可能会对人类大脑产生更持久的负面影响，因为神经生物学效应可能导致物质使用障碍。多巴胺和5-羟色胺系统与这些过程密切相关，但这些系统还没有以所需的时间分辨率在人类身上进行研究，以连接(1)这些快速信号如何改变人类在世界上导航时的行为，或(2)这些神经化学信号如何改变我们的主观感受。由于缺乏允许在人类有意识的决策和体验期间同时实时测量多巴胺和5-羟色胺释放的技术(以及非人类模式生物无法报告它们的感受)，这一进展受到了阻碍。 这一建议利用了数学化人类决策理论的最新进展和我们小组的首个此类技术方法，现在可以同时、共同定位地测量人类大脑中多巴胺和5-羟色胺的释放，在有意识的决策和体验过程中，时间分辨率为亚秒。在这里，我们追求两个特定的目标，这两个目标独特地结合了我们经过验证、同行评议和已发表的方法与概率学习任务，这些任务专门设计来探索对手奖惩行为信号之间的相互作用，多巴胺和5-羟色胺释放的快速变化，以及参与者在体验序列中感觉的时刻变化。首先(目标1)，我们将检验这一假设，即在工具性学习任务和被动巴甫洛夫条件反射任务中，细胞外多巴胺和5-羟色胺的亚秒变化分别编码货币奖励/食欲预测错误和货币惩罚/厌恶预测错误，作为人类纹状体中的对手信号。其次(目标2)，我们将检验这样一种假设，即细胞外多巴胺和5-羟色胺的亚秒级变化共同直接改变了人们的感受。提出的实验将首次直接测试备受争议的关于5-羟色胺/多巴胺在人类学习和决策中作用的“对手假说”；我们将首次开始揭示多巴胺和5-羟色胺的快速微波动在编码人类积极和消极主观感受方面所起的作用。我们预计，这些首创的数据将提供新的见解，了解滥用药物可能如何改变人们的感受，滥用药物可能对人脑关键神经化学学习系统的影响，并可能为未来的工作奠定基础，目的是了解这些神经化学系统如何影响人类其他大脑区域(包括伏隔核、前额叶、杏仁核和颞叶)，这些区域可能通过新的DBS程序或难治性癫痫的颅内标测提供通道。