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、最成问题的形式之一。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。酒精滥用和攻击性之间的关系已被充分证明。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一复杂现象，并可能为旨在减少与酒精有关的暴力的可能性的治疗策略提供进展。因此，本应用程序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与慢性酒精滥用之间关系的神经相关性，以及(b)检查急性酒精摄入引起的人类攻击行为变化的神经相关性。具体来说，将进行两个实验。第一个实验将使用人类攻击行为的实验室模型（点减法攻击范式，或PSAP）用于功能磁共振成像，以研究酒精依赖者和匹配健康对照者之间潜在攻击行为的大脑网络差异。第二个实验将检验急性酒精摄入对非酒精依赖性社交饮酒者攻击行为的影响，使用PSAP和功能磁共振成像来确定与酒精诱导的人类攻击有关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，并利用多种反应选项程序，提供货币收入和激进的反应选项（由另一个人的货币减法形式的挑衅引起）。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。该程序已被用于功能磁共振成像（fMRI），考虑到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，在PSAP会话期间，将获得fMRI扫描以测量大脑区域激活。在实验1中，稳态数据将在使用模拟扫描仪获取的预扫描PSAP会话中获得。一旦攻击行为水平稳定，在fMRI扫描符合酒精依赖标准和健康匹配对照的个体时，将重复进行PSAP会话。在实验2中，在fMRI下进行的重复PSAP会话中，酒精和安慰剂将被急性给予非依赖性社交饮酒者，使用受试者内部平衡设计。公共卫生相关性：该项目旨在进一步科学理解介导酒精使用与人类攻击之间关系的神经生物学因素。具体来说，一个完善的人类攻击的实验室范例（PSAP）已经适应在功能MRI下使用。该程序将用于研究酒精依赖组与匹配健康对照组中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).