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）影响相当大比例的人口，一般人口估计为6.4%至6.8%。到目前为止，还没有生物学标记来识别PTSD风险个体，可用的治疗方法也只是部分成功。 了解PTSD发展和维持的行为和神经机制对于提供信息和完善旨在改善患者生活质量的行为和药物干预非常重要，理想情况下，首先要预防这种疾病。在PTSD的背景下被广泛忽视的mst创伤的一个方面是围绕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。一个不利的结果加上不确定性的痛苦，很可能与更有害的结果有关（例如，更严重的PTSD症状）比没有这种痛苦的相同结果。因此，个人科普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种事件的能力。与此同时，不确定性与有害结果的关联可能随后增加个人对不确定性的厌恶。行为经济学分析表明，在不确定性下的行为受到两个独立因素的影响：（1）风险态度，它反映了收益或损失的可能性之间的权衡，以及这些收益和损失的大小，以及（2）模糊态度，它反映了个体对缺失这些概率信息的敏感性。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，所有区域都与一般的评估过程有关。有趣的是，这些区域在PTSD中表现出结构和功能异常。在这个建议中，我们的目标是表征行为的不确定性和它的神经相关的创伤幸存者与创伤后应激障碍和健康对照组没有创伤的经验。我们假设，PTSD患者会更厌恶模糊性，而创伤对照组与非创伤对照组相比，对模糊性的厌恶程度更低。我们进一步假设，在个人与PTSD活动的估值领域，这通常反映了对风险和模糊性的态度将不再这样做的条件下，模糊的损失。我们计划使用功能性磁共振成像和实验经济学行为方法相结合来测试这些假设。

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.