Encoding, Consolidation, Retrieval and Intervention of Conditioned Fear Extinction Memory

doi:10.16719/j.cnki.1671-6981.20240405

Abstract

Abstract: Exposure interventions based on the principles of extinction are effective methods for the treatment of anxiety disorders, but some patients still have problems such as spontaneous recovery, renewal, and reinstatement of fear. Therefore, how to promote and maintain fear extinction has been the key and difficulty of this field. Fear extinction refers to the formation of a new extinction memory established by presenting the conditioned stimulus (CS) repeatedly without the unconditioned stimulus (US). Good extinction learning is manifested not only in successful extinction, but also in retention of learned safety responses during subsequent extinction recall. This suggests that we need to explore the neural basis of extinction memory encoding, consolidation, and retrieval stages separately. The purpose of this paper is to discuss the effective intervention methods at each stage on the basis of systematically expounding the neural mechanism of memory extinction, and to provide some guidance for clinical treatment.
The Basolateral amygdala (BLA), infralimbic (IL) region of the prefrontal cortex, hippocampus, and the Dopamine (DA) system of the Ventral Tegmental Area (VTA) play distinct roles in the extinction of Pavlovian conditioned fear. (1) Successful extinction coding depends on the formation of "extinction memory neurons" in the BLA and the DA activity caused by anticipation errors. Furthermore, we suggest that the formation of "extinction memory neurons" in the BLA is regulated by DA caused by anticipation errors, but the neural circuit of this regulatory process is currently unclear. (2) The consolidation of extinction memory is mainly dependent on infralimbic-centered neural circuits, including the BLA, hippocampus, and DA system. The BLA mainly transmits the CS+-no US conditioned connection, the hippocampus inputs extinction memory context information, and DA is a key regulator of IL spontaneous activity. (3) The success of retrieval in extinction memory depends on whether the fear circuit or the extinction circuit is activated. There is another case of successful extinction recall: when CS+ is presented alone, it evokes fear memory but is immediately inhibited, that is, the retrieval stopping model, indicating that the individual consciously prevents negative thought intrusion. The two retrieval circuits do not conflict, and the prefrontal cortex is the center that provides inhibition.
According to the neural mechanism of extinction memory, we explore the intervention methods for different stages. Enhancing anticipatory errors during extinction learning and oral administration of DCS before extinction learning can enhance extinction memory encoding. To enhance extinction memory consolidation, neuromodulation, and L-DOPA after extinction learning are considered to be effective approaches. In addition, it can also be combined with proper exercise, and good sleep. In conclusion, although there are some methods of intervening in memory extinction, it is still necessary to explore diverse methods to maximize the optimization of clinical treatment.
The following aspects should be considered in future research. (1) Extinction memory traces weaken over time and are impaired in non-extinction contexts, suggesting that we need to deepen extinction memory traces and promote extinction generalization in the future. (2) Future research needs to continue to expand the neural mechanism of extinction memory at each stage, including enriching the neural mechanism of memory coding, exploring the regulation mechanism of the dopamine system, and the effect of prefrontal activity during sleep on consolidation. (3) Interfering with extinction memory retrieval is a new direction to enhance fear, such as the use of neuromodulation, positive emotion induction, and repetition strategies.

Key words: conditioned fear, extinction memory, encoding, consolidation, retrieval, intervention

摘要： 促进和保持条件性恐惧消退是改善暴露疗法的关键。恐惧消退并没有消除原来的恐惧记忆,而是形成新的消退记忆与其竞争。良好的消退记忆需要成功的编码、巩固与提取,杏仁核、前额叶、海马以及中脑多巴胺系统在其不同阶段具有不同作用。增大预期错误、口服认知增强剂、神经调控、口服左旋多巴胺等方法能够有效干预消退记忆编码和巩固。未来研究还需扩充各阶段神经机制,探讨如何增强消退记忆稳定性以及干预消退记忆提取。

关键词: 条件性恐惧, 消退记忆, 编码, 巩固, 提取, 干预

Huang Yixia, Wang Jinxia, Lei Yi. Encoding, Consolidation, Retrieval and Intervention of Conditioned Fear Extinction Memory[J]. Journal of Psychological Science, 2024, 47(4): 803-811.

黄益霞, 王金霞, 雷怡. 条件性恐惧消退记忆的编码、巩固、提取及其干预^*[J]. 心理科学, 2024, 47(4): 803-811.

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