Drug Abuse, Social Decision-Making, and Sex-Related Functional Brain Asymmetry

描述（由申请人提供）：本研究申请是对#RFA-DA-06-004的回应。毒品和酒精滥用的核心是错误的决策，尤其是对社会影响的反应。这种决策缺陷与腹内侧前额叶皮层（VMPC）损伤的神经系统患者的社会决策障碍非常相似。VMPC患者提供了社会决策出错的神经学模型。临床前和临床水平的证据表明，VMPC是药物滥用的关键脑区，我们认为VMPC功能障碍和社会决策缺陷可能是滥用药物和酒精成瘾的个体的特征。在这项研究申请中，我们计划在神经系统患者中进行研究，以充实社会决策的神经生物学基础，利用独特的爱荷华患者登记处，其中包含数千名患者的神经心理学和神经解剖学数据。特别关注的是性别差异。我们有一些有趣的初步发现，表明在VMPC和社会决策之间的关系中可能存在重要的性别差异：在男性中，右侧的VMPC可能是关键的，而在女性中，左侧的VMPC可能是关键的。实验将测试三个具体目标：(1)通过最后通牒游戏、信任游戏、爱荷华赌博任务和埃尔斯伯格任务等任务，确定在社会决策方面，VMPC是否存在与性别相关的功能不对称；(2)将性别相关功能不对称的研究扩展到其他已知对决策相关的社会和情感过程至关重要的大脑结构，即杏仁核和岛叶皮层；(3)通过对早期VMPC损伤患者的研究，探讨VMPC与社会决策和情绪加工之间的关系。这些实验将为社会决策和情绪处理的神经生物学基础提供重要的新信息。与药物滥用的联系是直接的：VMPC患者的决策缺陷与吸毒和酗酒者和成瘾者有着惊人的相似之处（“未来的近视”）。因此，我们的研究可以帮助查明神经功能障碍的来源，这些神经功能障碍导致了以药物和酒精滥用为特征的不良决策。公共卫生相关性：这项研究将帮助我们了解大脑的各个部分对社会决策和情绪处理是如何重要的，这些大脑-行为关系是否存在性别差异，以及这些关系是如何发展的。这项研究可以帮助治疗和预防药物和酒精滥用障碍，以及社会行为障碍、人格障碍、焦虑和情绪障碍，所有这些都与药物和酒精滥用有很高的合并症。

DESCRIPTION (provided by applicant): This research application is in response to #RFA-DA-06-004. At the heart of drug and alcohol abuse is bad decision-making, especially in response to social influences. This decision-making defect is highly reminiscent of the social decision-making impairments that characterize neurological patients with damage to ventromedial prefrontal cortex (VMPC). The VMPC patients provide a neurological model of social decision- making gone awry. There is evidence at both preclinical and clinical levels that the VMPC is a key brain region in drug abuse, and we propose that VMPC dysfunction and defective social decision-making may characterize individuals who abuse and become addicted to drugs and alcohol. In this research application, we plan to conduct studies in neurological patients in order to flesh out the neurobiological underpinnings of social decision-making, taking advantage of the unique Iowa Patient Registry that contains neuropsychological and neuroanatomical data for thousands of patients. A particular focus is on gender differences. We have intriguing preliminary findings suggesting that there might be an important sex-related difference in the relationship between the VMPC and social decision-making: in men, the right VMPC might be critical, whereas in women, the left VMPC might be critical. The experiments will test three specific aims: (1) To determine whether there is sex-related functional asymmetry of the VMPC in regard to social decision- making, using tasks such as the Ultimatum Game, Trust Game, Iowa Gambling Task, and Ellsberg Tasks; (2) To extend the investigation of sex-related functional asymmetry to other brain structures known to be critical for social and affective processes related to decision-making, namely, the amygdala and the insular cortex; (3) To investigate developmental influences on the relationship between the VMPC and social- decision making and emotional processing, by studying patients who incurred VMPC damage early in life. The experiments will furnish important new information about the neurobiological underpinnings of social decision-making and emotional processing. The link with substance abuse is direct: the decision-making deficits in VMPC patients have striking similarities with those evident in drug and alcohol abusers and addicts ("myopia for the future"). Thus, our research could help pinpoint sources of neural dysfunction that contribute to bad decision-making of the type that characterizes drug and alcohol abuse. Public health relevance: This research will help us understand how various parts of the brain are important for social decision-making and emotional processing, whether there are gender differences in these brain- behavior relationships, and how these relationships develop. The research could help inform treatment and prevention of drug and alcohol abuse disorders, as well as social conduct disorders, personality disorders, and anxiety and mood disorders, all of which have high comorbidity with drug and alcohol abuse.