Abstract: Fear reversal learning refers to the process in which fear reaction changes between safe and threatening stimuli after the reversal of reinforcement event. It is a novel learning process combining conditioned fear and reversal learning. It reflects the problem of flexibility in fear learning. It is important to flexibly readjust fear behavior when circumstances change. Failure to adapt to the changing environment may lead to anxiety-related mental disorders. Compared with normal people, patients with anxiety usually generalize safe stimuli as threatening stimuli. These irrational fear responses impede the extinction of fearful memory. Therefore, flexible and appropriate responses to threatening and safe signals play a critical role in the adaptive regulation of emotions.
Although the paradigm of fear reversal learning has been constantly developed and innovated in recent years, the basic experimental principle still involves the reversal of a safe stimulus into a threatening stimulus, and vice versa. In fact, related studies usually use physiological (such as skin electricity), behavioral (such as anxiety arousal or valence ratings), and fMRI indicators to measure the fear responses. Moreover, considering that fear reversal learning can effectively reflect the individual's cognitive flexibility, some researchers have used this paradigm to preliminarily explore the pathogenesis of anxiety-related mental disorders. The results show that not all anxiety-related mental disorders will damage the individual's ability of fear reversal learning, but the specific reasons should be discussed in detail in future research.
To date, fear extinction paradigms are the most common model to study the process of shifting from fear to safety. However, the regulation of fear in fear reversal learning requires more flexible and accurate responses. To be specific, the shift from fear and safety and from safety to fear occur simultaneously. Clarifying the relationship between fear reversal and fear extinction can provide new ideas for the diagnosis and treatment of anxiety disorders.
Studies have shown that fear reversal and fear extinction have different neural substrates. the ventromedial prefrontal cortex(vmPFC), the dorsal anterior cingulate cortex(dACC) and amygdala are their overlapping functional brain regions. However, the orbitofrontal cortex(OFC) is the unique functional brain area of fear reversal while hippocampus is that of fear extinction. In general, vmPFC, dACC, amygdala, and hippocampus play a key role in fear extinction. They affect each other and jointly regulate the extinction effect. And vmPFC, dACC, OFC, and amygdala, can be used as functional brain regions related to fear reversal. Specifically, vmPFC is sensitive to CS-. Yet dACC is sensitive to CS+. OFC, and some amygdala cells can quickly adjust emotions and behaviors according to external changes, while other amygdala cells continue to respond according to the initial reinforcement association. In other words, OFC and amygdala are activated to varying degrees in the process of fear reversal, which may be related to the mutual regulation between them.
According to the analysis of the existing research, there are three potential directions for future research. Firstly, future research should improve and innovate the research design. Secondly, it should explore whether there are other relevant brain regions based on the existing neural mechanisms of fear reversal learning. And hormone regulation affecting functional brain regions should also be discussed.

Key words: reversal learning, conditioned fear learning, fear reversal learning, fear extinction, the neural substrates

摘要： 恐惧反转学习指在安全和威胁刺激之间发生反转后,个体灵活地调整自身的恐惧反应,是一种适应性的恐惧调节手段。本文以条件性恐惧学习和反转学习为切入点,突出恐惧反转的特点,并从恐惧调节的角度厘清其与恐惧消退的关系,探讨两者神经机制的差异,继而揭示恐惧反转对焦虑障碍临床治疗方面的启示。未来研究可进行脑区发育、衰老与恐惧反转的发展性探索,扩展恐惧反转学习的神经回路以及尝试使用外源性激素干预恐惧反转学习。

关键词: 条件性恐惧学习, 反转学习, 恐惧反转学习, 恐惧消退, 神经机制