Raio Candace M, Brignoni-Perez Edith, Goldman Rachel, Phelps Elizabeth A
Psychology Department, New York University, New York, NY 10003, USA.
Psychology Department, University of Puerto Rico, San Juan 00936, Puerto Rico.
Neurobiol Learn Mem. 2014 Jul;112:212-21. doi: 10.1016/j.nlm.2014.01.015. Epub 2014 Feb 4.
Extinction training is a form of inhibitory learning that allows an organism to associate a previously aversive cue with a new, safe outcome. Extinction does not erase a fear association, but instead creates a competing association that may or may not be retrieved when a cue is subsequently encountered. Characterizing the conditions under which extinction learning is expressed is important to enhancing the treatment of anxiety disorders that rely on extinction-based exposure therapy as a primary treatment technique. The ventromedial prefrontal cortex, which plays a critical role in the expression of extinction memory, has been shown to be functionally impaired after stress exposure. Further, recent work in rodents has demonstrated that exposure to stress leads to deficits in extinction retrieval, although this has yet to be tested in humans. To explore how stress might influence extinction retrieval in humans, participants underwent a differential aversive learning paradigm, in which one image was probabilistically paired with an aversive shock while the other image denoted safety. Extinction training directly followed, at which point reinforcement was omitted. A day later, participants returned to the lab and either completed an acute stress manipulation (i.e., cold pressor), or a control task, before undergoing an extinction retrieval test. Skin conductance responses and salivary cortisol concentrations were measured throughout each session as indices of fear arousal and neuroendocrine stress response, respectively. The efficacy of our stress induction was established by observing significant increases in cortisol for the stress condition only. We examined extinction retrieval by comparing conditioned responses during the last trial of extinction (day 1) with that of the first trial of re-extinction (day 2). Groups did not differ on initial fear acquisition or extinction, however, a day later participants in the stress group (n=27) demonstrated significantly lower extinction retrieval (i.e., greater fear recovery) than those in the control group (n=25). Our results suggest that acute stress impairs the retrieval of extinction learning and offers insight into why treatment strategies used in the clinic may be challenging to recruit in daily life where stress is pervasive.
消退训练是一种抑制性学习形式，它使生物体能够将先前令人厌恶的线索与新的、安全的结果联系起来。消退并不会消除恐惧关联，而是会建立一种竞争性关联，当随后遇到线索时，这种关联可能会被提取，也可能不会。确定消退学习得以表现的条件，对于加强焦虑症的治疗很重要，因为焦虑症的治疗主要依赖基于消退的暴露疗法。腹内侧前额叶皮层在消退记忆的表现中起关键作用，研究表明，应激暴露后该区域功能受损。此外，最近对啮齿动物的研究表明，暴露于应激会导致消退提取缺陷，不过这一点尚未在人类身上得到验证。为了探究应激如何影响人类的消退提取，参与者接受了一种差别厌恶学习范式，其中一幅图像以概率方式与厌恶电击配对，而另一幅图像表示安全。随后直接进行消退训练，此时不再给予强化。一天后，参与者回到实验室，在进行消退提取测试之前，要么完成一项急性应激操作（即冷水加压试验），要么完成一项对照任务。在每个阶段都测量皮肤电导反应和唾液皮质醇浓度，分别作为恐惧唤醒和神经内分泌应激反应的指标。仅通过观察应激条件下皮质醇的显著增加，确定了我们应激诱导的效果。我们通过比较消退（第1天）最后一次试验与再次消退（第2天）第一次试验期间的条件反应，来检验消退提取情况。两组在初始恐惧习得或消退方面没有差异，然而，一天后，应激组（n = 27）的参与者表现出的消退提取显著低于对照组（n = 25）（即恐惧恢复程度更高）。我们的研究结果表明，急性应激会损害消退学习的提取，并为临床上使用的治疗策略在压力普遍存在的日常生活中难以应用提供了见解。
