Department of Pharmaceutical Sciences, Research Group Experimental Pharmacology, Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
Department of Experimental Clinical and Health Psychology, Universiteit Gent - C, Heymanslaan 10, 9000, Gent, Belgium.
Brain Stimul. 2021 Mar-Apr;14(2):250-260. doi: 10.1016/j.brs.2021.01.005. Epub 2021 Jan 14.
Trauma-based psychotherapy is a first line treatment for post-traumatic stress disorder (PTSD) but not all patients achieve long-term remission. Transcranial direct current stimulation (tDCS) received considerable attention as a neuromodulation method that may improve trauma-based psychotherapy.
We explored the effects of repeated anodal tDCS over the prefrontal cortex (PFC) on fear extinction in mice as a preclinical model for trauma-based psychotherapy.
We performed auditory fear conditioning with moderate or high shock intensity on C57BL6/J mice. Next, mice received anodal tDCS (0.2 mA, 20 min) or sham stimulation over the PFC twice daily for five consecutive days. Extinction training was performed by repeatedly exposing mice to the auditory cue the day after the last stimulation session. Early and late retention of extinction were evaluated one day and three weeks after extinction training respectively.
We observed no significant effect of tDCS on the acquisition or retention of fear extinction in mice subjected to fear conditioning with moderate intensity. However, when the intensity of fear conditioning was high, tDCS significantly lowered freezing during the acquisition of extinction, regardless of the extinction protocol. Moreover, when tDCS was combined with a strong extinction protocol, we also observed a significant improvement of early extinction recall. Finally, we found that tDCS reduced generalized fear induced by contextual cues when the intensity of conditioning is high and extinction training limited.
Our data provide a rationale to further explore anodal tDCS over the PFC as potential support for trauma-based psychotherapy for PTSD.
创伤为基础的心理疗法是创伤后应激障碍（PTSD）的一线治疗方法，但并非所有患者都能长期缓解。经颅直流电刺激（tDCS）作为一种神经调节方法受到了广泛关注，可能会改善创伤为基础的心理疗法。
我们探索了重复经颅直流电刺激（tDCS）对前额叶皮质（PFC）的影响，以作为创伤为基础的心理疗法的临床前模型中的恐惧消退。
我们使用中等或高强度的听觉恐惧条件作用对 C57BL6/J 小鼠进行了实验。接下来，小鼠接受了经颅直流电刺激（0.2 mA，20 分钟）或假刺激，每天两次，连续五天。在最后一次刺激后，通过反复暴露于听觉提示来进行消退训练。在消退训练后的一天和三周分别评估早期和晚期的消退保留。
我们观察到 tDCS 对中等强度恐惧条件作用的小鼠的获得或保留恐惧消退没有显著影响。然而，当恐惧条件作用的强度很高时，tDCS 显著降低了消退获得过程中的冻结，而与消退方案无关。此外，当 tDCS 与强烈的消退方案相结合时，我们还观察到早期消退回忆的显著改善。最后，我们发现，当条件作用的强度高且消退训练有限时，tDCS 会降低由情境线索引起的泛化恐惧。
我们的数据为进一步探索经颅直流电刺激（tDCS）对 PFC 的作用提供了依据，认为其可能为 PTSD 的创伤为基础的心理疗法提供支持。
