Neural Correlates of Alcohol Effects on Aggressive Behavior

描述（由申请人提供）：攻击性是人类社会互动中最持久、最复杂、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、家庭和个人造成了重大损害。酒精滥用和攻击性之间的关系已经得到了很好的证明。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，并可能为旨在降低酒精相关暴力概率的治疗策略提供进展。因此，本申请的主要目的是利用功能性磁共振成像（fMRI）来（a）检查介导人类攻击行为和慢性酒精滥用之间的关系的神经相关物，和（B）检查由急性酒精施用产生的人类攻击行为变化的神经相关物。具体而言，将进行两个实验。第一个实验将使用适用于fMRI的人类攻击行为实验室模型（点减法攻击范式，或PSAP），以研究酒精依赖和匹配的健康对照参与者之间攻击行为背后的大脑网络差异。第二个实验将研究急性酒精管理对非酒精依赖的社交饮酒者的攻击行为的影响，使用PSAP的功能磁共振成像来确定酒精诱导的人类攻击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，并利用多个响应选项程序提供货币收入和积极的响应选项（通过归因于另一个人的货币扣减形式的挑衅来提示）。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）的差异敏感。该程序已适用于功能磁共振成像，占关键的视觉和时间变量，并能够识别大脑区域，是唯一活跃的攻击行为。因此，将在PSAP会话期间采集fMRI扫描，以测量局部大脑激活。在实验1中，将在使用模拟扫描仪采集的预扫描PSAP会话中采集稳态数据。一旦攻击行为水平稳定，将在fMRI扫描符合酒精依赖标准的个体和健康匹配对照期间进行重复的PSAP会话。在实验2中，酒精和安慰剂将急性给药的非依赖性社交饮酒者在重复的PSAP会议下进行功能磁共振成像，使用受试者内的平衡设计。公共卫生相关性：该项目旨在进一步科学地了解调节酒精使用和人类攻击之间关系的神经生物学因素。具体来说，一种成熟的人类攻击性实验室范式（PSAP）已被改编用于功能性MRI。这个程序将被用来研究酒精依赖与匹配的健康对照组（实验1）的神经相关的侵略，并研究酒精对侵略的急性影响（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).