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Dopamine's Role in Impulse Control and Reward Learning in Humans

多巴胺在人类冲动控制和奖励学习中的作用

基本信息

批准号：
10365933
负责人：
Brittany Liebenow
金额：
$ 5.18万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10365933
关键词：
Affect Alcohol dependence Area Behavior Behavioral Behavioral Sciences Brain region Characteristics Choice Behavior Clinical Clinical assessments Computers Conscious Corpus striatum structure DSM-V Data Data Analyses Data Collection Decision Making Deep Brain Stimulation Detection Diabetes Mellitus Disease Doctor of Philosophy Dopamine Dopamine Agonists Electrochemistry Electrodes Event Exhibits Feedback Future Gambling Human Impulse Control Disorders Impulsivity Individual Learning Major Depressive Disorder Manuscripts Measurement Measures Medical Mental disorders Mentorship Methods National Institute of Mental Health Neurosciences Operative Surgical Procedures Outcome Parkinson Disease Participant Patient Recruitments Patients Pharmaceutical Preparations Play Population Preparation Process Psychological reinforcement Punishment Questionnaires Recording of previous events Research Research Domain Criteria Rewards Risk Risk Behaviors Risk-Taking Role Scientist Signal Transduction Specificity Stimulus Substance Use Disorder Symptoms Syndrome System Technology Testing Time Training World Health Organization addiction base behavior influence behavior measurement design dopamine system dopaminergic neuron experience experimental study forest high risk implantation medical schools multidisciplinary neurochemistry neuroimaging neurosurgery new therapeutic target novel novel strategies programs prospective response reward processing trait

项目摘要

Project Summary The DSM-V categorized gambling disorder as the first behavioral addiction. The World Health Organization (WHO) identified problem gambling as a necessary area for further research, with a burden of harm surpassing substance use disorder and diabetes. Impulsivity is an important trait found on clinical assessment of gambling disorder, and gambling disorder can be induced by dopamine replacement medications in a clinical syndrome termed impulse control disorder (ICD). Dopamine agonist therapy is more responsible than other dopamine replacement options, with patients on dopamine agonists experiencing roughly three times greater odds of developing ICD. Neuroimaging studies have pinpointed the striatum as a culprit brain region for dopamine abnormalities, with recent technologic advances in human electrochemistry providing the temporal specificity necessary to correlate sub-second dopamine fluctuations to differences in reward learning. The NIMH RDoC construct ‘Reward Learning’ and its subconstructs, ‘Reward Prediction Error’ and ‘Probabilistic and Reinforcement Learning’ provide a framework to investigate temporal differences in dopamine fluctuations corresponding to differences in decision-making in ICD. Based on preliminary data showing dopaminergic signaling is altered in ICD corresponding to impulsivity, this proposal will investigate the following specific aims: (1) Quantify patients’ threshold for risk-taking and the behavioral influence of RPEs in patients with a history of ICD both on and off dopaminergic medications. (2) Measure sub-second dopamine fluctuations in the striatum during decision-making under risk. Methods will employ human reward learning tasks and simultaneous human electrochemistry. Training will take place at the Wake Forest School of Medicine in the Neuroscience and the Medical programs as a part of the MD/PhD program. The applicant will receive training in the human electrochemistry and behavioral science methods necessary to accomplish the proposed aims. The applicant also places an emphasis on analytical training in R programming. Mentorship includes a multidisciplinary team with individuals in the neurosurgery and neuroscience departments. This team will provide the applicant with feedback regarding project implementation, data collection and analysis, and manuscript preparation. The proposed aims have the potential to provide new therapeutic targets for the treatment of mental health disorders that involve reward learning.

项目概要 DSM-V 将赌博障碍列为第一种行为成瘾。世界卫生组织（世界卫生组织）将问题赌博确定为进一步研究的必要领域，其危害负担超过物质使用障碍和糖尿病。冲动是赌博临床评估中发现的一个重要特征临床综合征中的多巴胺替代药物可诱发障碍和赌博障碍称为冲动控制障碍（ICD）。多巴胺激动剂治疗比其他多巴胺更有效替代选择，使用多巴胺激动剂的患者经历大约三倍的几率开发 ICD。神经影像学研究已确定纹状体是多巴胺的罪魁祸首大脑区域异常，人体电化学的最新技术进步提供了时间特异性将亚秒级多巴胺波动与奖励学习的差异相关联是必要的。 NIMH RDoC 构建“奖励学习”及其子结构“奖励预测误差”和“概率和强化学习提供了一个研究多巴胺波动的时间差异的框架对应于 ICD 决策的差异。基于显示多巴胺能的初步数据 ICD 中的信号传导因冲动而改变，该提案将研究以下具体目标： (1) 量化患者的冒险阈值以及 RPE 对有以下病史的患者的行为影响： ICD 包括开启和关闭多巴胺能药物。 (2) 测量纹状体亚秒级多巴胺波动在面临风险的情况下进行决策。方法将采用人类奖励学习任务和同时人类电化学。培训将在维克森林医学院进行神经科学和医学课程是医学博士/博士课程的一部分。申请人将接受人类培训实现拟议目标所必需的电化学和行为科学方法。申请人还强调 R 编程的分析培训。指导包括多学科团队与神经外科和神经科学部门的人员合作。该团队将为申请人提供有关项目实施、数据收集和分析以及稿件准备的反馈。这拟议的目标有可能为心理健康的治疗提供新的治疗目标涉及奖励学习的疾病。