Neural Correlates of Alcohol Effects on Aggressive Behavior

描述(由申请人提供)：攻击性是人类社会交往中最持久、最复杂和最有问题的形式之一。人类侵略的后果对公共卫生和刑事司法系统、社区、家庭和个人造成重大损失。酗酒和攻击性之间的关系已经有了很好的记录。通过整合脑成像、精神药理学和实验室行为科学的方法来研究这种关系，将进一步科学地理解这种复杂的现象，并可能为旨在降低与酒精有关的暴力事件的可能性的治疗策略提供依据。因此，这项应用的主要目标是利用功能磁共振成像(FMRI)来(A)检查调节人类攻击行为和慢性酒精滥用之间关系的神经关联，以及(B)检查急性饮酒引起的人类攻击行为变化的神经关联。具体地说，将进行两个实验。第一个实验将使用适用于功能磁共振成像的人类攻击行为的实验室模型(点减法攻击范式，简称PSAP)，以研究酒精依赖和匹配的健康对照组参与者之间攻击行为背后的大脑网络的差异。第二个实验将考察急性饮酒对非酒精依赖社交饮酒者攻击行为的影响，使用PSAP for fMRI来确定参与酒精诱导的人类攻击行为的关键大脑区域和网络。PSAP方法具有良好的可靠性和有效性，并利用多重反应选择程序，提供货币收益和积极反应选择(由归因于另一个人的货币减法形式的挑衅提示)。在数十项研究中，PSAP已被证明对急性药物效应(包括酒精)和临床群体(包括药物滥用者)的差异都很敏感。该程序已被改装用于功能磁共振成像，考虑了关键的视觉和时间变量，并能够识别在攻击行为中唯一活跃的大脑区域。因此，功能磁共振成像扫描将在PSAP会议期间获得，以测量大脑的区域激活。在实验1中，将在使用模拟扫描仪获取的预扫描PSAP会话中获取稳态数据。一旦攻击性行为水平稳定，将在fMRI扫描符合酒精依赖标准的人和健康匹配的对照组期间进行重复的PSAP治疗。在实验2中，酒精和安慰剂将在功能磁共振下进行的重复PSAP会议中，使用受试者内平衡设计，对非依赖型社交饮酒者进行敏锐的注射。公共卫生相关性：该项目寻求进一步科学地理解调节酒精使用和人类攻击性之间关系的神经生物学因素。具体地说，一个完善的人类攻击性实验室范式(PSAP)已被改编用于功能磁共振成像。这一程序将用于研究酒精依赖组与匹配的健康对照组之间攻击行为的神经相关性(实验1)，并研究酒精对攻击行为的急性影响(实验2)。

DESCRIPTION (provided by applicant): Aggression is one of most enduring, complex, and problematic forms of human social interaction. The consequences of human aggression extract a substantial toll on public health and criminal justice systems, communities, families, and individuals. The relationship between alcohol abuse and aggression has been well documented. Studying this relationship through the integration of methodologies in brain imaging, psychopharmacology, and laboratory behavioral science will further scientific understanding of this complex phenomenon, and may provide inroads for treatment strategies aimed at decreasing the probability of alcohol-related violence. Accordingly, the primary objectives of this application are to utilize functional magnetic resonance imaging (fMRI) to (a) examine neural correlates that mediate the relationship between human aggressive behavior and chronic alcohol abuse, and (b) examine the examine neural correlates of changes in human aggressive behavior produced by acute alcohol administration. Specifically, two experiments will be conducted. The first experiment will use a laboratory model of human aggressive behavior (the Point Subtraction Aggression Paradigm, or PSAP) adapted for use during fMRI, to study differences in brain networks underlying aggressive behavior among alcohol dependent and matched healthy control participants. The second experiment will examine the effects of acute alcohol administration on aggressive behavior in non-alcohol dependent social drinkers, using the PSAP for fMRI to determine critical brain regions and networks involved in alcohol-induced human aggression. The PSAP methodology has well established reliability and validity, and utilizes a multiple response option procedure offering monetary earning and aggressive response options (cued by provocations in the form of monetary subtractions attributed to another individual). Across dozens of studies, the PSAP has been demonstrated to be sensitive to both acute drug effects (including alcohol) and differences in clinical groups (including substance abusers). The procedure has been adapted for use during fMRI, accounting for critical visual and temporal variables, and is able to identify brain regions that are uniquely active during aggressive behavior. Consequently, fMRI scans will be acquired during PSAP sessions to measure regional brain activation. In experiment 1, steady-state data will be acquired in pre-scanning PSAP sessions acquired using a mock scanner. Once levels of aggressive behavior are stable, repeated PSAP sessions will be conducted during fMRI scanning individuals meeting criteria for alcohol dependence and healthy matched controls. In experiment 2, alcohol and placebo will be acutely administered to non-dependent social drinkers during repeated PSAP sessions conducted under fMRI, using a within-subject counterbalanced design. PUBLIC HEALTH RELEVANCE: This project seeks to further scientific understanding of the neurobiological factors that mediate the relationship between alcohol use and human aggression. Specifically, a well-established laboratory paradigm of human aggression (PSAP) has been adapted for use under functional MRI. This procedure will be used to study the neural correlates of aggression in alcohol-dependent vs. matched healthy control groups (Experiment 1), and to study the acute effects of alcohol on aggression (Experiment 2).