Neural mechanisms of decision-making under uncertainty in PTSD

描述（由申请人提供）：创伤后应激障碍（PTSD）影响了很大一部分人口，一般人口估计在6.4%到6.8%之间。到目前为止，还没有生物标志物来识别有PTSD风险的个体，现有的治疗方法也只是部分成功。了解创伤后应激障碍发展和维持的行为和神经机制对于告知和改进旨在改善患者生活质量的行为和药物治疗干预非常重要，理想情况下，首先要预防这种疾病。大多数创伤的一个方面在创伤后应激障碍的背景下被广泛忽视，那就是围绕着高度不利环境的高度不确定性。例如，在战场上，士兵们意识到对自己和他人的各种危险，但很少能够估计这些危险实现的可能性。与没有这种痛苦的相同结果相比，不良结果与不确定的痛苦相结合可能与更有害的结果（例如，创伤后应激障碍症状的更严重程度）相关。因此，个人应对不确定性的能力可能决定了他们对极端有害事件的反应，以及他们对这些事件的心理适应能力。同时，不确定性与有害结果的关联可能随后增加个体对不确定性的厌恶。行为经济学分析表明，不确定性下的行为受到个人对两个独立因素的权重的影响：(1)风险态度，它反映了收益或损失的概率之间的交易，以及这些收益和损失的大小；(2)模糊态度，它反映了个人对这些概率缺失信息的敏感性。神经经济学研究表明，风险和模糊态度反映在内侧前额叶皮层（MPFC）、纹状体和杏仁核区域的神经激活中，这些区域通常与评估过程有关。有趣的是，这些相同的区域在PTSD中表现出结构和功能异常。在这个提议中，我们的目的是表征不确定性下的行为及其神经相关性在创伤幸存者有和没有创伤经验的健康对照。我们假设患有创伤后应激障碍的个体会更厌恶歧义，而创伤控制组与非创伤控制组相比，对歧义的厌恶程度会更低。我们进一步假设，在患有PTSD的个体中，通常反映对风险和模糊性态度的评估区域的活动在模糊性损失的条件下将停止这样做。我们计划结合功能性核磁共振成像和实验经济学行为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.