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

药物滥用、社会决策和与性别相关的大脑功能不对称

• 批准号: 7192900
• 负责人: Daniel T. Tranel
• 金额: $ 34.57万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7192900
• 关键词: brain; clinical research; decision making; drug abuse; sex

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.

描述（由申请人提供）：本研究申请是对 #RFA-DA-06-004 的回应。吸毒和酗酒的核心是错误的决策，尤其是在应对社会影响时。这种决策缺陷很容易让人联想到腹内侧前额叶皮层（VMPC）受损的神经系统患者的社会决策障碍。 VMPC 患者提供了一个社会决策出错的神经学模型。临床前和临床水平都有证据表明 VMPC 是药物滥用的关键大脑区域，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并成瘾的个体的特征。在这项研究应用中，我们计划利用包含数千名患者的神经心理学和神经解剖学数据的独特的爱荷华州患者登记处，对神经系统患者进行研究，以充实社会决策的神经生物学基础。特别关注的是性别差异。我们有有趣的初步研究结果表明，VMPC 和社会决策之间的关系可能存在重要的性别相关差异：在男性中，右侧 VMPC 可能至关重要，而在女性中，左侧 VMPC 可能至关重要。实验将测试三个具体目标：（1）使用最后通牒博弈、信任博弈、爱荷华赌博任务和埃尔斯伯格任务等任务，确定 VMPC 在社会决策方面是否存在与性别相关的功能不对称性。 ; (2) 将与性别相关的功能不对称性的研究扩展到已知对决策相关的社会和情感过程至关重要的其他大脑结构，即杏仁核和岛叶皮质； (3) 通过研究生命早期遭受 VMPC 损伤的患者，探讨发育对 VMPC 与社会决策和情绪处理之间关系的影响。这些实验将提供有关社会决策和情绪处理的神经生物学基础的重要新信息。与药物滥用的联系是直接的：VMPC 患者的决策缺陷与吸毒者、酗酒者和成瘾者（“未来近视”）的决策缺陷有着惊人的相似之处。因此，我们的研究可以帮助查明神经功能障碍的根源，这些神经功能障碍会导致药物和酒精滥用类型的错误决策。公共健康相关性：这项研究将帮助我们了解大脑的各个部分对于社会决策和情绪处理的重要性，这些大脑行为关系是否存在性别差异，以及这些关系如何发展。该研究可以帮助为药物和酒精滥用障碍以及社会行为障碍、人格障碍、焦虑和情绪障碍的治疗和预防提供信息，所有这些障碍都与药物和酒精滥用有很高的共病率。