No evidence for blocking the return of fear by disrupting reconsolidation prior to extinction learning
No evidence for blocking the return of fear by disrupting reconsolidation prior to extinction learning
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DOI：
10.1016/j.cortex.2016.03.015
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发表时间：
2016-06-01
期刊：
影响因子：
3.6
通讯作者：
Stark, Rudolf
中科院分区：
文献类型：
--
作者：
Klucken, Tim;Kruse, Onno;Stark, Rudolf
消除恐惧是治疗焦虑症的一个核心模型。最初的研究报告说，在灭绝学习之前，条件刺激的单一呈现可以永久地阻止恐惧的回归。然而，只有少数研究探讨了这个问题，并不能总是复制的结果。在第一天，两个中性刺激与电刺激（UCS）配对，而第三个刺激（CS-）则不配对。24 h后，在消退学习前10 min，一个条件刺激（CS+（rem））和CS-被提醒一次，而另一个条件刺激（CS+（non-rem））在消退学习前不被提示。所有的刺激，在灭绝学习和两个再灭绝会议（24小时和6个月后灭绝学习）没有强化。在获得、消退和两次再消退过程中，研究了对CS+和CS-的血氧水平依赖性（BOLD）反应和皮肤电导反应（SCR）。关于SCR，结果表明，条件刺激的单一呈现并不能阻止再消退过程中恐惧的回归：与CS-相比，CS+（rem）和CS+（non-rem）之间没有差异，观察到CS+在再消退期间（消退学习后24小时和6个月）的恐惧恢复。关于BOLD反应，CS+（REM）和CS+（非REM）之间没有显着差异，发现在兴趣区（ROI）分析（杏仁核，腹内侧前额叶皮层）在灭绝学习和两个再灭绝会议。全脑分析显示，与CS+（rem）相比，在几个区域（例如，本研究结果表明，通过破坏再巩固来防止恐惧回归的效果似乎是一种比以前假设的更不稳定的现象。可能的边界条件和影响进行了讨论。(C)2016作者由爱思唯尔有限公司发布
Fear extinction is a central model for the treatment of anxiety disorders. Initial research has reported that the single presentation of a conditioned stimulus prior to extinction learning can permanently block the return of fear. However, only few studies have explored this issue and could not always replicate the findings.The present study examined human fear extinction using a four-day design. On the first day, two neutral stimuli were paired with electrical stimulation (UCS), while a third stimulus (CS-) was not. Twenty-four hours later, one conditioned stimulus (CS+(rem)) and the CS- were reminded once, 10 min before extinction learning, while the other conditioned stimulus (CS+(non-rem)) was not presented prior to extinction learning. All stimuli were presented during extinction learning and during two re-extinction sessions (24 h and 6-months after extinction learning) without reinforcement. Blood oxygen level-dependent (BOLD) responses and skin conductance responses (SCRs) to both CS+ and the CS- were explored during acquisition, extinction, and in both re-extinction sessions.Regarding SCRs, the results showed that a single presentation of a conditioned stimulus did not block the return of fear during re-extinction: Fear recovery during re-extinction (24 h and 6-months after extinction learning) was observed for both CS+ compared with the CS- with no difference between CS+(rem) and CS+(non-rem). Regarding BOLD-responses, no significant differences between CS+(rem) and CS+(non-rem) were found in region of interest (ROI)-analyses (amygdala, ventromedial prefrontal cortex) during extinction learning and both re-extinction sessions. Whole-brain analyses showed increased BOLD-responses to the CS+(non-rem) as compared to the CS+(rem) in several regions (e.g., middle frontal gyrus) during extinction learning and re-extinction (24 h after extinction learning).The present findings suggest that the effect of preventing the return of fear by disrupting reconsolidation seems to be a more labile phenomenon than previously assumed. Possible boundary conditions and implications are discussed. (C) 2016 The Authors. Published by Elsevier Ltd.