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

项目摘要 DSM-V将赌博障碍归类为第一种行为成瘾。世界卫生组织 (WHO)将问题赌博确定为进一步研究的必要领域，其危害超过 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 在临床综合征中，多巴胺替代药物可诱发赌博障碍， 被称为冲动控制障碍（ICD）。多巴胺激动剂治疗比其他多巴胺 替代选择，多巴胺受体激动剂的患者经历大约三倍的几率， 发展ICD。神经影像学研究已经确定纹状体是多巴胺的罪魁祸首大脑区域 异常，随着人类电化学技术的最新进展，提供了时间特异性 将亚秒多巴胺波动与奖励学习的差异联系起来是必要的。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”提供了一个框架来研究多巴胺波动的时间差异 与ICD中决策的差异相对应。根据初步数据显示多巴胺能 信号在ICD中改变对应于冲动性，本提案将研究以下具体目标： (1)量化患者的冒险阈值和RPE对有以下病史患者的行为影响： ICD在服用和停用多巴胺能药物的情况下。(2)测量纹状体中的亚秒多巴胺波动 在风险下的决策。方法将采用人类奖励学习任务和同时的人类奖励学习任务。 电化学培训将在维克森林医学院的神经科学和 医学课程作为MD/PhD课程的一部分。申请人将接受培训， 电化学和行为科学的方法来实现提出的目标。申请人 还强调R编程的分析培训。指导包括一个多学科的团队 与神经外科和神经科学部门的人员进行了交流。该团队将为申请人提供 关于项目实施、数据收集和分析以及稿件准备的反馈。的 提出的目标有可能为精神健康的治疗提供新的治疗靶点 涉及奖励学习的疾病

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.