Posttraumatic stress disorder can be viewed as a disorder of fear dysregulation. An abundance of research suggests that the prefrontal cortex is central to fear processing—that is, how fears are acquired and strategies to regulate or diminish fear responses. The current review covers foundational research on threat or fear acquisition and extinction in nonhuman animals, healthy humans, and patients with posttraumatic stress disorder, through the lens of the involvement of the prefrontal cortex in these processes. Research harnessing advances in technology to further probe the role of the prefrontal cortex in these processes, such as the use of optogenetics in rodents and brain stimulation in humans, will be highlighted, as well other fear regulation approaches that are relevant to the treatment of posttraumatic stress disorder and involve the prefrontal cortex, namely cognitive regulation and avoidance/active coping. Despite the large body of translational research, many questions remain unanswered and posttraumatic stress disorder remains difficult to treat. We conclude by outlining future research directions related to the role of the prefrontal cortex in fear processing and implications for the treatment of posttraumatic stress disorder.

创伤后应激障碍可以被视为一种恐惧失调症。大量研究表明，前额叶皮层是恐惧处理的核心——即恐惧是如何获得的以及调节或减少恐惧反应的策略。当前的综述涵盖了关于非人类动物、健康人类和创伤后应激障碍患者的威胁或恐惧获得和消退的基础研究，通过前额叶皮层参与这些过程的镜头。将重点介绍利用技术进步进一步探讨前额叶皮层在这些过程中的作用的研究，例如在啮齿动物中使用光遗传学和在人类中进行大脑刺激，以及其他与创伤后应激障碍治疗相关并涉及前额皮质的恐惧调节方法，即认知调节和回避/积极应对。尽管有大量的转化研究，但许多问题仍未得到解答，创伤后应激障碍仍然难以治疗。最后，我们概述了与前额叶皮层在恐惧处理中的作用以及对治疗创伤后应激障碍的影响相关的未来研究方向。