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行为成瘾。世界卫生组织 (世卫组织)将问题赌博确定为进一步研究的必要领域，其危害负担超过了 物质使用障碍和糖尿病。冲动是赌博临床评估中的一个重要特征 在临床综合征中，多巴胺替代药物可引起精神障碍和赌博障碍 称为冲动控制障碍(ICD)。多巴胺激动剂治疗比其他多巴胺更负责任 替代选择，服用多巴胺激动剂的患者经历大约三倍于 发展中的ICD。神经成像研究已明确指出纹状体是多巴胺的罪魁祸首。 异常，人类电化学的最新技术进步提供了时间特异性 有必要将亚秒多巴胺波动与奖赏学习的差异联系起来。NIMH RDOC 构建“奖赏学习”及其子结构“奖赏预测误差”和“概率与” 强化学习为研究多巴胺波动的时间差异提供了一个框架 与ICD决策的差异相对应。基于初步数据显示多巴胺能 ICD中的信号会因冲动而改变，本提案将调查以下具体目标： (1)量化患者的冒险阈值和RPEs对患者行为的影响 ICD包括开和停用的多巴胺能药物。(2)测量纹状体中的亚秒多巴胺波动 在有风险的决策过程中。方法将使用人类奖励学习任务和同时人类 电化学学。培训将在维克森林医学院进行神经科学和 医学计划作为医学博士计划的一部分。申请人将接受人力资源方面的培训 实现所提出的目标所必需的电化学和行为科学方法。申请人 还强调了R编程中的分析培训。导师制包括一个多学科团队 神经外科和神经科学系的个人。该团队将为申请者提供 关于项目实施、数据收集和分析以及手稿准备的反馈。这个 提出的目标有可能为精神健康的治疗提供新的治疗靶点。 涉及奖励性学习的障碍。

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.