Neural mechanisms of decision-making under uncertainty in PTSD

描述(申请人提供)：创伤后应激障碍(PTSD)影响了相当大比例的人口，一般人口估计在6.4%到6.8%之间。到目前为止，还没有生物标记物来识别创伤后应激障碍的风险个体，现有的治疗方法也只有部分成功。了解创伤后应激障碍发生和维持的行为和神经机制对于告知和改进旨在提高患者生活质量的行为和药物治疗干预措施非常重要，理想情况下，首先是预防这种疾病。在创伤后应激障碍的背景下，MST创伤的一个方面被广泛忽视，那就是围绕着极其不利的环境的高度不确定性。例如，在战场上，士兵们意识到自己和他人面临的各种危险，但很少能够估计这些危险实现的可能性。与没有这种痛苦的情况下的相同结果相比，不利的结果与不确定性的痛苦相结合，可能与更有害的结果相关(例如，创伤后应激障碍症状更严重)。因此，个人应对不确定性的能力可能决定他们对极端有害事件的反应，以及他们在心理上适应这些事件的能力。同时，不确定性与有害结果的关联可能会增强个人对不确定性的厌恶。行为经济学分析表明，不确定性下的行为受到两个独立因素的影响：(1)风险态度，反映了收益或损失的概率与收益和损失的大小之间的权衡；(2)模棱两可的态度，反映了个人对丢失关于这些概率的信息的敏感性。神经经济学研究表明，风险和模棱两可的态度反映在内侧前额叶皮质(MPFC)、纹状体和杏仁核等区域的神经激活上，所有这些区域通常都与估值过程有关。有趣的是，这些相同的区域显示出创伤后应激障碍的结构和功能异常。在这项提案中，我们的目标是描述患有和不患有创伤后应激障碍的创伤幸存者和没有创伤经历的健康对照组在不确定性下的行为及其神经相关性。我们假设，患有创伤后应激障碍的个体会更厌恶模棱两可，而创伤对照组与非创伤暴露的对照组相比，不会那么厌恶模棱两可。我们进一步假设，在有创伤后应激障碍的个人中，估值领域的活动通常反映了对风险和模棱两可的态度，在出现模棱两可的损失的情况下，将停止这样做。我们计划使用功能磁共振成像和实验经济学行为方法相结合的方法来检验这些假设。

DESCRIPTION (provided by applicant): Posttraumatic stress disorder (PTSD) affects a significant proportion of the population, with general population estimates ranging from 6.4% to 6.8%. To-date there is no biological markers to identify individuals at risk for PTSD, and available treatments are only partially successful. Understanding the behavioral and neural mechanisms that underlie the development and maintenance of PTSD is important in order to inform and refine behavioral and pharmacotherapeutic interventions designed to improve patients' quality of life and, ideally, to prevent the disorder in the first place. One aspect of mst traumas that is widely ignored in the context of PTSD is the high levels of uncertainty surrounding highly adverse circumstances. In the battlefield, for example, soldiers are aware of the various dangers to themselves and others, but are seldom able to estimate the likelihood for the realization of those dangers. An adverse outcome combined with the distress of uncertainty is likely to be associated with more deleterious outcomes (e.g., greater severity of PTSD symptoms) than the same outcome in the absence of such distress. The individual's ability to cope with uncertainty may therefore determine their reaction to extreme harmful events, as well as their ability to psychologically adapt to such events. At the same time, the association of uncertainty with harmful outcomes may subsequently augment the individual's aversion for uncertainty. Behavioral economics analysis suggests that behavior under uncertainty is affected by the individual's weighting of two separate factors: (1) risk attitude, which reflects a trade-of between the probabilities of gains or losses, and the magnitude of those gains and losses~ and (2) ambiguity attitude, which reflects an individual's sensitivity to missing information about these probabilities. Neuroeconomics studies show that risk and ambiguity attitudes are reflected in the neural activation in regions of the medial prefrontal cortex (MPFC), the striatum and the amygdala, all areas that have been implicated in valuation processes in general. Intriguingly, these very same areas show structural and functional abnormalities in PTSD. In this proposal, we aim to characterize behavior under uncertainty and its neural correlates in trauma survivors with and without PTSD and healthy controls with no trauma experience. We hypothesize that individuals with PTSD will be more averse to ambiguity, and that trauma controls will be less averse to ambiguity compared to non-trauma-exposed controls. We further hypothesize that in individuals with PTSD activity in valuation areas, which normally reflects attitudes towards risk and ambiguity will cease to do so under conditions of ambiguous losses. We plan to test these hypotheses using a combination of functional MRI and experimental economics behavioral methods.