Department of Cognitive Psychology, Institute of Cognitive Neuroscience, Faculty of Psychology, Ruhr University Bochum, Germany.
Department of Cognitive Psychology, Institute of Cognitive Neuroscience, Faculty of Psychology, Ruhr University Bochum, Germany.
Psychoneuroendocrinology. 2022 Feb;136:105607. doi: 10.1016/j.psyneuen.2021.105607. Epub 2021 Nov 27.
While generalization of fear seems to be naturally acquired as frequently observed in fear-related disorders, extinction learning appears to be stimulus-specific. Thus, treatments aiming to generalize extinction learning comprise the chance to overcome stimulus-specificity and consequently reduce relapse. One suggested candidate is the timing-dependent administration of the stress hormone cortisol. In the present pre-registered, three-day fear conditioning study, we aimed to create a generalized extinction memory trace in 60 healthy men and women using multiple sizes of one conditioned stimulus (CS+G; generalized) during extinction training, whereas the other CS (CS+N; non-generalized) and the CS- were solely presented in their original sizes. Extinction training took place either after pharmacological administration of 20 mg cortisol or placebo. Following successful fear acquisition on day one, generalization effects during extinction training and retrieval were investigated in the comparison of CS+G and CS+N. Insula and dorsal anterior cingulate cortex (dACC) activation for CS+G as compared to CS+N extending to the second half of extinction training indicated prolonged fear processing during extinction training for the CS+G on day two. During retrieval on day three, an activation of the anterior hippocampus occurred for CS+N minus CS+G in the cortisol but not in the placebo group. Additionally, a more posterior hippocampal activation (compared to the other hippocampal activation) was observed for the contrast CS+G minus CS+N. In accordance with our hypotheses, amygdala and dACC responding during reinstatement test was reduced for the CS+G as compared to CS+N. However, cortisol did not modulate amygdala responding, but abolished the CS+G/CS+N differentiation in the dACC relative to placebo. Generalization and cortisol effects were not mirrored in skin conductance responses. In conclusion, extinction generalization processes appear to rely on prolonged fear processing still present in the second half of extinction training that in turn leads to reduced fear-related processing after reinstatement. Cortisol administration prior to extinction training, however, selectively reduced fear-related activation for standard extinction but did not further reduce fear-related activation for extinction generalization.
虽然恐惧的泛化似乎是自然获得的，如在与恐惧相关的障碍中经常观察到的那样，但消退学习似乎是刺激特异性的。因此，旨在泛化消退学习的治疗包括克服刺激特异性的机会，从而减少复发。一种被提议的候选药物是应激激素皮质醇的时程依赖性给药。在本预先注册的为期三天的恐惧条件反射研究中，我们旨在通过在消退训练期间使用多个大小的一个条件刺激 (CS+G; 广义) 来创建 60 名健康男性和女性的广义消退记忆痕迹，而其他 CS (CS+N; 非广义) 和 CS- 仅以其原始大小呈现。消退训练要么在 20mg 皮质醇或安慰剂给药后进行。在第一天成功获得恐惧后，在 CS+G 和 CS+N 的比较中研究了消退训练和检索期间的泛化效应。与 CS+N 相比，CS+G 在第二半消退训练期间的岛叶和背侧前扣带皮层 (dACC) 激活表明 CS+G 在第二天的消退训练中进行了延长的恐惧处理。在第三天的检索中，对于 CS+N 减去 CS+G，皮质醇组而非安慰剂组的前海马出现激活。此外，与其他海马激活相比，观察到更靠后的海马激活 (与其他海马激活相比) 用于对比 CS+G 减去 CS+N。与我们的假设一致，与 CS+N 相比，CS+G 再巩固测试中的杏仁核和 dACC 反应减少。然而，皮质醇并没有调节杏仁核反应，而是相对于安慰剂消除了 dACC 中 CS+G/CS+N 的分化。皮肤电反应没有反映出泛化和皮质醇的作用。总之，消退的泛化过程似乎依赖于仍然存在于消退训练的后半部分的延长的恐惧处理，这反过来又导致再巩固后减少与恐惧相关的处理。然而，在消退训练之前给予皮质醇选择性地降低了标准消退的与恐惧相关的激活，但没有进一步降低消退泛化的与恐惧相关的激活。
