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：
10554431
负责人：
Brittany Liebenow
金额：
$ 5.27万
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/10554431
关键词：
Affect Alcohol dependence Area Behavior Behavior assessment Behavioral Behavioral Sciences Brain region Categories 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 Protocols documentation Psychological reinforcement Punishment Questionnaires Recording of previous events Research Research Domain Criteria Rewards Risk Risk Assessment Risk Behaviors Risk Taking Role Scientist Signal Transduction Specificity Stimulus Substance Use Disorder Symptoms Syndrome System Technology Testing Time Training World Health Organization addiction behavior influence behavior measurement clinical training 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，并遭受了伤害超越药物使用障碍和糖尿病。冲动性是赌博临床评估的重要特征临床综合征中的多巴胺替代药物可以诱导疾病和赌博障碍称为冲动控制障碍（ICD）。多巴胺激动剂疗法比其他多巴胺更负责替代选择，多巴胺激动剂的患者的几率大约大约三倍开发ICD。神经影像学研究已将纹状体视为多巴胺的罪魁祸首。异常，随着人类电化学的最新技术进步提供了临时特异性将下秒多巴胺波动与奖励学习差异相关的必要条件。 NIMH RDOC 构建“奖励学习”及其子结构，“奖励预测错误”和“概率和强化学习提供了一个框架来研究多巴胺波动的临时差异对应于ICD决策的差异。基于显示多巴胺能的初步数据 ICD中的信号传导与冲动性相对应，该建议将研究以下特定目的：（1）量化患者的冒险阈值和RPE的行为影响 ICD在多巴胺能药物上包括。（2）测量纹状体中的亚秒多巴胺波动在决策期间的风险中。方法将采用人类奖励学习任务和简单的人类电化学。培训将在神经科学的Wake Forest医学院和医疗计划是MD/PHD计划的一部分。申请人将接受人类的培训实现拟议目的所必需的电化学和行为科学方法。申请人还强调R编程中的分析培训。指导包括一个多学科团队神经外科和神经科学部门的个人。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手稿准备的反馈。拟议的目标有可能为治疗心理健康提供新的治疗靶标涉及奖励学习的疾病。