Institute of Cognitive Neuroscience, Department of Cognitive Psychology, Ruhr-University Bochum, Bochum, Germany.
Department of Psychotherapy and Systems Neuroscience, Justus Liebig University Giessen, Giessen, Germany.
Neuropsychopharmacology. 2018 Jan;43(2):384-392. doi: 10.1038/npp.2017.227. Epub 2017 Sep 26.
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.
条件性恐惧的消除体现了暴露疗法中包含的一个关键机制。临床研究表明，在暴露治疗前应用应激激素皮质醇有助于提高暴露治疗的成功率，但背后的神经相关性仍不清楚。本研究将描述皮质醇对消退学习的情境和刺激依赖性影响，并在消退和新情境中进行测试。40 名健康男性参与了为期 3 天的恐惧条件反射实验，在情境 A 中进行恐惧获得（第 1 天），在情境 B 中进行消退训练（第 2 天），并在一周后（第 3 天）在情境 B 和新情境 C 中进行回忆。在消退训练前给予氢可的松（30mg）或安慰剂。血氧水平依赖反应和皮肤电反应（SCR）作为因变量。在消退训练开始时，皮质醇降低了条件性 SCR，减弱了杏仁核-海马复合体的激活，并增强了前旁海马回与腹内侧前额叶皮层（vmPFC）的功能连接。一周后，皮质醇组在消退情境中表现出对已消退刺激的海马激活和与 vmPFC 的连接增加，以及对未消退刺激的岛叶激活减少。然而，这种抑制性皮质醇效应并没有扩展到新情境。总之，皮质醇在消退开始时降低了恐惧回忆，并促进了消退记忆的巩固，这一证据体现在一周后抑制性激活模式上。应激激素对恐惧和消退记忆的杏仁核-海马体-vmPFC 网络产生了关键影响。然而，皮质醇并没有减弱消退的情境依赖性。
