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

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不好的 决策，特别是对社会影响的反应。这种决策缺陷是非常严重的。 这让人想起了神经系统受损患者的社会决策障碍， 腹内侧前额叶皮质（VMPC）。VMPC患者提供了一个社会决策的神经模型- 让事情变糟在临床前和临床水平都有证据表明VMPC是一个关键的大脑 我们认为，VMPC功能障碍和有缺陷的社会决策可能 描述滥用药物和酒精并上瘾的人的特征。在这个研究应用中， 我们计划在神经系统患者中进行研究，以充实神经生物学基础， 社会决策，利用独特的爱荷华州患者登记，其中包括 神经心理学和神经解剖学数据。一个特别的重点是性别问题 差异我们有有趣的初步发现表明，可能有一个重要的性相关的 VMPC和社会决策之间关系的差异：在男性中，正确的VMPC可能 在女性中，左VMPC可能是关键的。这些实验将测试三个具体目标： (1)为了确定VMPC在社会决策方面是否存在性别相关的功能不对称性， 制作，使用任务，如最后通牒游戏，信任游戏，爱荷华州赌博任务，和埃尔斯伯格任务; (2)将性别相关功能不对称的研究扩展到其他已知的大脑结构， 对于与决策有关的社会和情感过程至关重要，即杏仁核和岛叶 （3）探讨VMPC与社会功能之间的关系及其与发育的关系。 决策和情绪处理，通过研究在生命早期遭受VMPC损伤的患者。 这些实验将提供有关社会行为的神经生物学基础的重要新信息。 决策和情绪处理。与药物滥用的联系是直接的：决策 VMPC患者的缺陷与药物和酒精滥用者的缺陷有惊人的相似之处， 成瘾者（“近视未来”）。因此，我们的研究可以帮助确定神经功能障碍的来源， 导致不良决策，这是滥用药物和酒精的特征。 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是如何重要的 对于社会决策和情绪处理，这些大脑中是否存在性别差异- 行为关系，以及这些关系是如何发展的。这项研究可以帮助指导治疗， 预防药物和酒精滥用障碍，以及社会行为障碍、人格障碍， 以及焦虑和情绪障碍，所有这些都与药物和酒精滥用有很高的共病率。

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.