Maren Stephen
Department of Psychological and Brain Sciences, Institute for Neuroscience, Texas A&M University, College Station, TX, United States.
Front Syst Neurosci. 2022 Apr 19;16:888461. doi: 10.3389/fnsys.2022.888461. eCollection 2022.
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.
针对恐惧和焦虑症的治疗干预依赖于减少病理性恐惧记忆的行为方法。例如，了解到威胁预测性刺激不再与厌恶结果相关联是条件性恐惧反应消退的核心。不幸的是，恐惧记忆持久、长期存在且难以消退，尤其是在高压力水平下。“即时消退缺陷”就说明了这一点，其特征是在恐惧条件化后的数小时内尝试进行消退程序时，条件性恐惧的长期减少效果不佳。在此，我将回顾最近的研究工作，这些工作为恐惧消退抗性背后的神经机制提供了新的见解。新兴研究表明，蓝斑去甲肾上腺素调节对消退学习至关重要的杏仁核 - 前额叶皮层回路。这些数据表明，应激诱导的脑内神经调节系统激活以牺牲消退学习为代价使恐惧记忆产生偏差。在接受暴露疗法的患者中，减轻压力的行为和药物策略可能会改善治疗效果。
