Investigating the Neural Basis of Shame and Guilt in Veterans with Posttraumatic Stress Disorder

摘要 异常调节的恐惧和威胁感知被广泛认为是 创伤后应激障碍(PTSD)的生理过程因此，联想恐惧 学习模型主导了创伤后应激障碍神经科学的研究。然而，羞愧， 内疚和道德伤害，而不是恐惧，是个体的主要认知过程 患有创伤后应激障碍，通常是在军事战斗创伤后发生的。人们对此知之甚少 创伤后应激障碍如何影响与羞耻和内疚相关的大脑回路，部分原因是缺乏 动物模型。该提案的第一个目标是开发符合以下条件的实验范例 适用于研究创伤后应激障碍患者羞耻和内疚神经回路的功能磁共振成像环境。我们会 首先建立一个简短的小插曲资料库，突出与创伤相关的主要主题 羞愧和内疚。创造一个与创伤相关的刺激来研究羞耻和内疚将大大 提高我们和广大科学界的能力，调查 战斗创伤后创伤后应激障碍的羞耻和内疚的神经科学研究。三组患者(1) 有显著羞耻感和内疚症状的创伤后应激障碍患者；(2)无羞耻感或 负罪感，以及(3)战斗创伤暴露的对照组受试者将被呈现唤起 在fMRI环境中，羞愧和内疚以及匹配的中性小插曲。我们假设 羞耻感和负罪感突出的创伤后应激障碍组比其他组表现出更大的激活度 典型羞耻和内疚处理脑区的小组(自我参照)符合 更多的负面自我归因。此外，大脑的功能组织将是 以解剖学上不同的大脑区域之间的时间相关活动为特征的 从任务相关的fMRI活动中获得。我们预测患者自我报告的羞耻感或负罪感 患有创伤后应激障碍的人将与突出的自我功能大脑网络的中断有关 参考脑区。内疚和羞耻的行为测量将被用来研究 创伤后应激障碍调节大脑活动/组织与主观因素之间的联系 羞愧/内疚的经历。从拟议的研究中获得的知识将推动 创伤后应激障碍的神经生物学，以及未来更多的研究，有助于阐明 与涉及羞耻感和负罪感的神经目标接触。经颅磁刺激(TMS)， 经颅直流电刺激(TDC)和实时功能磁共振神经反馈是有潜力的 未来可以应用的干预措施，直接调节这些新发现的 目标。

ABSTRACT Abnormally regulated fear and threat perception are widely regarded as the core patho- physiological process in posttraumatic stress disorder (PTSD). As a result, associative fear learning models have dominated research on the neuroscience of PTSD. However, shame, guilt, and moral injury, rather than fear, are dominant cognitive processes among individuals with PTSD, which often develops following military combat trauma. Very little is known about how PTSD affects the brain circuits associated with shame and guilt, in part due to the lack of animal models. The first goal of this proposal is to develop experimental paradigms that are suitable to the fMRI setting for investigating shame and guilt neurocircuits in PTSD. We will begin by developing a library of short vignettes highlighting dominant themes of trauma-related shame and guilt. Creating a trauma-relevant stimulus set to study shame and guilt will greatly enhance our ability, and that of the broader scientific community, to investigate the neuroscience of shame and guilt in PTSD from combat trauma. Three groups (1) patients with PTSD having prominent shame and guilt symptoms, (2) patients with PTSD without shame or guilt, and (3) combat-trauma exposed control subjects will be presented vignettes evocative of shame and guilt along with matched neutral vignettes in the fMRI environment. We hypothesize that the shame and guilt prominent PTSD group will exhibit greater activation than the other groups in canonical shame and guilt processing brain regions (self-referential) consistent with greater negative self-attribution. In addition, the functional organization of the brain will be characterized from temporally correlated activity between anatomically distinct brain regions obtained from task-related fMRI activity. We predict that self-reported shame or guilt in patients with PTSD will be associated with a disruption of functional brain networks in prominent self- referential brain regions. Behavioral measures of guilt and shame will be used to study whether PTSD modulates the association between brain activity/organization and the subjective experience of shame/guilt. The knowledge gained from the proposed research will advance the neurobiology of PTSD, and in the future with more research, shed light on treatments that engage neural targets implicated in shame and guilt. Transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and real-time fMRI neurofeedback are potential interventions that could be applied in the future to directly modulate these newly discovered targets.