Dissecting Cortical Contributions to Risky Decision-Making

剖析皮质对风险决策的贡献

基本信息

批准号：
9926480
负责人：
Mike J F Robinson
金额：
$ 0.73万
依托单位：
WESLEYAN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2020-06-30
项目状态：
已结题

项目摘要

Project Summary/Abstract Wesleyan University Poor decision-making can lead to drug use and substance use disorder in both males and females, and is predictive of relapse vulnerability. Decision-making is a complex behavior that integrates moderating cortical influences with subcortical urges. When the decision process becomes unbalanced in favor of subcortical urges, it may lead to compulsive choice, the pursuit of risky options, and the development of drug addiction. Dysfunction of the prefrontal cortex is believed to bias this process in favor of those subcortical urges. In particular, recent findings suggest that cortical activity in areas such as the anterior insula (AIC) and orbitofrontal (OFC) cortex may influence decisions, possibly by moderating these urges. However, recent pharmacological and lesion studies of the OFC and AIC conflate decision- making processes and their outcomes, and fail to capture the role of these areas `in the moment'. In addition, there are large individual differences in risky decision-making including sex differences in the activity of the AIC and OFC. The long-term goal of this project is to understand how, and the timing with which, the AIC and OFC influence risky decision-making. Important to this project, our preliminary data using optogenetic techniques has revealed a more complex role for the AIC than previously appreciated, showing that brief inhibition prior to making a choice increases risk-preference, whereas inhibition following risky wins, but not risky losses, dramatically increases risk-aversion. This suggests that the AIC tracks only positive risky outcomes, and uses this information during the deliberation process to promote future safe choices. In contrast, our preliminary work also shows that brief inhibition of the OFC prior to making a choice reduces risk preference. This suggests that the OFC normally increases risky choice and plays an opposing role to that of the AIC. Building on these preliminary findings, the objective of this proposal is to 1) test the hypothesis that the role of the AIC is to attenuate risky choices and that it does so by tracking risky wins, 2) test the hypothesis that the OFC has the opposite effect on risky decision-making, by increasing risky choices, particularly when a choice is presented, and finally 3) that females are more risk-averse and will therefore be less sensitive to optogenetic manipulations that increase risk-seeking. This will be achieved using advanced behavioral task designs combined with the temporal specificity of optogenetics to specifically inhibit the OFC or AIC either immediately prior to choice or following particular risky reward outcomes. This research will advance our understanding of the role and precise timing with which cortical structures influence risky decision-making and how these functions are influenced by individual risk preferences and sex differences. This will provide foundational knowledge necessary to develop intervention strategies aimed at reducing risk-taking and drug use.

项目摘要/摘要卫斯理大学决策不良会导致男性和女性的药物使用和药物使用障碍，以及可以预测复发脆弱性。决策是一种复杂的行为，可以整合中调皮质下的皮质影响。当决策过程变得不平衡而支持皮质下的冲动，可能导致强迫选择，追求风险选择以及发展吸毒成瘾。据信，前额叶皮层功能障碍会偏向此过程，以支持这些过程皮质下的冲动。特别是，最近的发现表明，前部区域的皮质活动岛（AIC）和轨道额（OFC）皮质可能会影响决策，可能通过调节这些决定敦促。但是，OFC和AIC的最新药理和病变研究将决策混为一谈制定过程及其结果，并且无法捕捉到“当下”这些领域的作用。在此外，在风险决策中存在很大的个体差异，包括性别差异 AIC和OFC的活动。该项目的长期目标是了解如何以及与 AIC和OFC会影响风险的决策。对这个项目很重要，我们的初步数据使用光遗传技术已经揭示了AIC的作用比以前更复杂值得赞赏的，表明在做出选择之前的短暂抑制会增加风险优先级，而风险胜利后的抑制作用，但没有冒险损失，大大增加了风险的规避。这暗示着 AIC仅跟踪积极的风险结果，并在审议期间使用此信息促进未来安全选择的过程。相反，我们的初步工作也表明了短暂的抑制作用在做出选择之前，OFC降低了风险偏好。这表明OFC通常增加了风险选择，并对AIC发挥了反对作用。基于这些初步调查结果，该提议的目的是1）检验AIC的作用是减弱的假设风险选择，并且通过跟踪风险获胜来做到这一点，2）检验OFC具有的假设对风险决策的影响相反，通过增加冒险选择，尤其是当选择是呈现，最后3）女性更适合风险，因此对遗传操作会增加寻求风险的方式。这将使用先进的行为来实现任务设计结合了光遗传学的时间特异性，以特别抑制OFC或 AIC可以立即选择或遵循特定的风险奖励结果。这项研究会促进我们对皮质结构影响风险的角色和精确时机的理解决策以及这些功能如何受到个人风险偏好和性别的影响差异。这将为制定干预策略提供必要的基本知识旨在减少冒险和吸毒。