Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit.
Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit.
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压力下无情的恐惧：立即灭绝缺陷的神经回路和机制。
DOI：
10.3389/fnsys.2022.888461
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发表时间：
2022
影响因子：
3
通讯作者：
Maren, Stephen
中科院分区：
文献类型：
--
作者：
Maren, Stephen
关键词：
恐惧和焦虑障碍的治疗干预依赖于减少病理性恐惧记忆的行为方法。例如，了解到威胁预测刺激不再与令人厌恶的结果相关联，是消除条件恐惧反应的核心。不幸的是，恐惧记忆是持久的，持久的，并且不会消失，特别是在高水平的压力下。这是说明了“立即灭绝赤字”，其特征是一个穷人的长期减少条件反射恐惧时，灭绝程序试图在几个小时内的恐惧条件反射。在这里，我将回顾最近的工作，这些工作为抵抗恐惧消退的神经机制提供了新的见解。新的研究表明，蓝斑去甲肾上腺素调节杏仁核-前额叶皮层回路，这对消退学习至关重要。这些数据表明，压力诱导的大脑神经调节系统的激活偏向于恐惧记忆的代价是灭绝学习。行为和药理学策略，以减少压力的患者接受暴露治疗可能会改善治疗结果。
Therapeutic interventions for disorders of fear and anxiety rely on behavioral approaches that reduce pathological fear memories. For example, learning that threat-predictive stimuli are no longer associated with aversive outcomes is central to the extinction of conditioned fear responses. Unfortunately, fear memories are durable, long-lasting, and resistant to extinction, particularly under high levels of stress. This is illustrated by the “immediate extinction deficit,” which is characterized by a poor long-term reduction of conditioned fear when extinction procedures are attempted within hours of fear conditioning. Here, I will review recent work that has provided new insight into the neural mechanisms underlying resistance to fear extinction. Emerging studies reveal that locus coeruleus norepinephrine modulates amygdala-prefrontal cortical circuits that are critical for extinction learning. These data suggest that stress-induced activation of brain neuromodulatory systems biases fear memory at the expense of extinction learning. Behavioral and pharmacological strategies to reduce stress in patients undergoing exposure therapy might improve therapeutic outcomes.
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