Neural bases of alcohol-related decision-making

 描述（由申请人提供）：酒精使用障碍（AUD）造成数十亿美元的工作时间损失，犯罪和医疗并发症，以及无法估量的人类痛苦。所有成瘾性障碍的核心都是倾向于将醉酒的即时奖励置于所有其他未来奖励之上，例如家庭，职业发展和尊严。虽然这一领域的研究主要集中在冲动选择立即较小的金钱奖励，而不是较大的延迟金钱奖励，但在澳元中做出的实际选择模式是立即陶醉而不是其他较大的延迟奖励。要了解大脑的脆弱性，可能会导致个人冲动饮酒，需要评估大脑机制，这些机制涉及即时存在的酒精与其他奖励的相对价值。通过了解所涉及的大脑区域，它们在高危受试者中的功能，以及如何使用行为方法操纵这种大脑活动，我们可以更好地针对成瘾治疗。 目标1将证明，衡量酒精与金钱的选择是一个更好的预测酒精问题比更标准的“金钱与金钱”的选择。目标2将利用功能性磁共振成像（fMRI）来确定风险因素如何改变与即时酒精选择相关的大脑活动。目标3将确定在酒精相关的决策过程中，外部刺激（复发触发因素）如何影响局部大脑活动。目标4将确定区域大脑活动如何受到非药物事件的影响，这些事件有可能使选择偏离醉酒。特别是，目标4将通过展示未来方向可以改变成瘾行为的机制来为成瘾的临床治疗提供信息。 通过利用更精确的AUD选择模型，研究结果将使酒精研究领域更接近于揭示这种毁灭性疾病的大脑机制。在进行这些研究的过程中，主要研究者布兰登奥伯林博士将接受其导师大卫卡雷肯博士及其顾问委员会的广泛培训和指导。在印第安纳州大学医学院的高级课程和补充教育的帮助下，这种资助机制将支持他，并为他作为成瘾研究领域独立科学家的职业生涯做好准备。

 DESCRIPTION (provided by applicant): Alcohol use disorders (AUD) cost billions of dollars in lost work time, crime, and medical complications, in addition to incalculable human misery. At the heart of all addiction disorders is a tendency to prefer the immediate reward of intoxication over all other future rewards, such as family, career development, and dignity. While research in this area has focused on impulsive choices for immediate smaller money rewards, versus larger delayed money rewards, the actual choice pattern that is made in AUD is immediate intoxication versus other larger delayed rewards. Understanding the cerebral vulnerabilities that may lead individuals to impulsive drinking instead requires assessing the brain mechanisms involved in the relative value of immediately present alcohol versus other rewards that are remote in time. By understanding the brain areas involved, their function in at-risk subjects, and how such brain activity can be manipulated using behavioral methods, we can better target addiction treatment. Aim 1 will demonstrate that measuring alcohol versus money choice is a better predictor of alcohol problems than the more standard "money versus money" choice. Aim 2 will utilize functional magnetic resonance imaging (fMRI) to determine how risk factors alter brain activity related to immediate alcohol choice. Aim 3 will determine how regional brain activity is biased by external stimuli (relapse triggers) during alcohol-related decision making. Aim 4 will determine how regional brain activity is biased by non-drug events that have the potential to bias choice away from intoxication. Aim 4, in particular, will inform clinical treatment of addictions by showing the mechanisms by which future orientation can alter addictive behavior. By utilizing a more precise model of AUD choice, the findings will bring the field of alcohol research closer to uncovering the brain mechanisms of this devastating disorder. In the course of performing these studies, the Primary Investigator, Dr. Brandon Oberlin, will receive extensive training and guidance from his mentor, Dr. David Kareken, and his advisory committee. Augmented by advanced coursework and supplemental education at the Indiana University School of Medicine, this grant mechanism will support and prepare him for his career as an independent scientist in the field of addiction research.