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核心病理学， 创伤后应激障碍（PTSD）的生理过程。因此，联想恐惧 学习模型已经主导了创伤后应激障碍的神经科学研究。然而，羞耻， 内疚和道德伤害，而不是恐惧，是个体的主要认知过程 创伤后应激障碍，通常在军事战斗创伤后发展。很少有人知道 PTSD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实验范式， 适合于研究PTSD中羞耻和内疚神经回路的功能磁共振成像设置。我们将 开始，开发一个简短的小插曲图书馆，突出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， 提高我们的能力，以及更广泛的科学界，调查 创伤后应激障碍的羞耻和内疚的神经科学。三组（1）患者 PTSD患者有明显的羞耻和内疚症状，（2）PTSD患者没有羞耻感， 内疚，和（3）战斗创伤暴露的对照组将呈现小插曲唤起的 沿着羞愧和内疚，以及功能磁共振成像环境中的中性小插曲。我们假设 感到羞耻和内疚的PTSD患者会比其他人表现出更强的活性 在典型的羞耻和内疚处理大脑区域（自我指涉）的群体符合 消极的自我归因。此外，大脑的功能组织将 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 从任务相关的功能磁共振成像活动中获得。我们预测病人自我报告的羞耻感或内疚感 创伤后应激障碍将与突出自我的功能性大脑网络中断有关， 参照脑区内疚和羞耻的行为措施将被用来研究是否 PTSD调节大脑活动/组织与主观 羞耻/内疚的体验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，并在未来与更多的研究，揭示了治疗， 与羞愧和内疚有关的神经目标经颅磁刺激（TMS）， 经颅直流电刺激（tDCS）和实时fMRI神经反馈是潜在的 这些干预措施可以在未来应用于直接调节这些新发现的 目标的

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.