Neural Underpinnings of Cortisol Effects on Fear Extinction
Neural Underpinnings of Cortisol Effects on Fear Extinction
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DOI：
10.1038/npp.2017.227
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发表时间：
2018
影响因子：
7.6
通讯作者：
C. Merz;T. C. Hamacher-Dang;R. Stark;O. Wolf;A. Hermann
中科院分区：
文献类型：
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作者：
C. Merz;T. C. Hamacher-Dang;R. Stark;O. Wolf;A. Hermann
消除条件性恐惧体现了暴露疗法中的一个关键机制。临床研究表明，在暴露前应用应激激素皮质醇有助于暴露成功，但潜在的神经相关性仍然未知。背景和刺激依赖性皮质醇对消退学习的影响将在这项研究中的特点和测试的灭绝和在一个新的背景下。40名健康男性参加了为期3天的恐惧条件反射实验，在情境A中进行恐惧习得（第1天），在情境B中进行消除训练（第2天），在情境B和一周后的新情境C中进行回忆（第3天）。在消退训练前给予氢化可的松（30 mg）或安慰剂。血氧水平依赖性反应和皮肤电导反应（SCR）作为依赖性措施。在消退训练开始时，皮质醇减少了条件性SCR，减少了杏仁核-海马复合体的激活，并增强了前海马旁回与腹内侧前额叶皮层（vmPFC）的功能连接。一周后，皮质醇组表现出增加海马激活和连接到vmPFC对一个熄灭的刺激和减少对一个非熄灭的刺激在灭绝的情况下，海马激活。然而，这种抑制性皮质醇效应并没有延伸到新的环境中。两者合计，皮质醇减少恐惧回忆在开始的灭绝和促进巩固的灭绝记忆证明了一个抑制激活模式一周后。应激激素对杏仁核-海马体-vmPFC网络产生了重要影响，这些网络是恐惧和灭绝记忆的基础。然而，皮质醇并没有减弱灭绝的背景依赖性。
Extinction of conditioned fear embodies a crucial mechanism incorporated in exposure therapy. Clinical studies demonstrated that application of the stress hormone cortisol before exposure sessions facilitates exposure success, but the underlying neural correlates remain unknown. Context-and stimulus-dependent cortisol effects on extinction learning will be characterized in this study and tested in the extinction and in a new context. Forty healthy men participated in a 3-day fear conditioning experiment with fear acquisition in context A (day 1), extinction training in context B (day 2), and recall in context B and a new context C one week later (day 3). Hydrocortisone (30 mg) or placebo was given before extinction training. Blood-oxygen-level-dependent responses and skin conductance responses (SCRs) served as dependent measures. At the beginning of extinction training, cortisol reduced conditioned SCRs, diminished activation of the amygdala–hippocampal complex, and enhanced functional connectivity of the anterior parahippocampal gyrus with the ventromedial prefrontal cortex (vmPFC). After one week, the cortisol group showed increased hippocampal activation and connectivity to the vmPFC toward an extinguished stimulus and reduced insula activation toward a nonextinguished stimulus in the extinction context. However, this inhibitory cortisol effect did not extend to the new context. Taken together, cortisol reduced fear recall at the beginning of extinction and facilitated the consolidation of the extinction memory as evidenced by an inhibitory activation pattern one week later. The stress hormone exerted a critical impact on the amygdala–hippocampus–vmPFC network underlying fear and extinction memories. However, cortisol did not attenuate the context dependency of extinction.