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

本研究申请是对#RFA-DA-06-004的响应。毒品和酒精滥用的核心是有害的 决策，尤指对社会影响作出反应的决策。这种决策缺陷是非常严重的 这让人想起了神经科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学模型- 把事情搞砸了。临床前和临床水平的证据表明，vmpc是一个关键的大脑。 药物滥用的地区，我们认为VMPC功能障碍和社会决策缺陷可能 描述滥用药物和酒精成瘾的人的特征。在这项研究应用中， 我们计划在神经科患者中进行研究，以充实神经生物学基础 社会决策，利用唯一的爱荷华州患者注册表，该注册表包含 数千名患者的神经心理学和神经解剖学数据。一个特别的重点是性别 不同之处。我们有耐人寻味的初步发现表明可能有一个重要的与性有关的 VMPC与社会决策之间的关系差异：在男性中，正确的VMPC可能 关键，而在女性中，左VMPC可能是关键的。这些实验将测试三个具体目标： (1)确定在社会决策方面是否存在与性别有关的VMPC功能不对称- 制作、使用最后通牒游戏、信任游戏、爱荷华州赌博任务和Ellsberg任务； (2)将与性别有关的功能不对称的研究扩展到其他已知的大脑结构 对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)探讨发展对VMPC与社会关系的影响。 决策和情绪处理，通过研究在生命早期遭受VMPC损害的患者。 这些实验将提供有关社会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明显相似之处非常明显 瘾君子(“对未来的近视”)。因此，我们的研究可以帮助精确定位神经功能障碍的来源 有助于做出以吸毒和酗酒为特征的糟糕决策。 与公共健康相关：这项研究将帮助我们了解大脑的不同部分是如何重要的 对于社会决策和情绪加工，这些大脑中是否存在性别差异-- 行为关系，以及这些关系如何发展。这项研究有助于为治疗和治疗提供信息 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患率。

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.