van 't Wout-Frank Mascha, Garnaat Sarah L, Faucher Christiana R, Arulpragasam Amanda R, Cole Julia E, Philip Noah S, Burwell Rebecca D
Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI, United States.
COBRE Center for Neuromodulation, Butler Hospital, Providence, RI, United States.
Front Hum Neurosci. 2023 Apr 24;17:1104614. doi: 10.3389/fnhum.2023.1104614. eCollection 2023.
Exposure-based psychotherapies for the treatment of anxiety- and fear-based disorders rely on "corrective" associative learning. Namely the repeated confrontation with feared stimuli in the absence of negative outcomes allows the formation of new, corrected associations of safety, indicating that such stimuli no longer need to be avoided. Unfortunately, exposure-facilitated corrective learning tends to be bound by context and often poorly generalizes. One brain structure, the prefrontal cortex, is implicated in context-guided behavior and may be a relevant target for improving generalization of safety learning. Here, we tested whether inhibition of the left prefrontal cortex causally impaired updating of context-bound associations specifically or, alternatively, impaired updating of learned associations irrespective of contextual changes. Additionally, we tested whether prefrontal inhibition during corrective learning influenced subsequent generalization of associations to a novel context.
In two separate experiments, participants received either 10 min of 2 mA cathodal transcranial direct current stimulation (tDCS) over EEG coordinate F3 (Experiment 1 = 9, Experiment 2 = 22) or sham stimulation (Experiment 1 = 10, Experiment 2 = 22) while previously learned associations were reversed in the same or a different context from initial learning. Next, to assess generalization of learning, participants were asked to indicate which of the previously seen images they preferred in a novel, never seen before context.
Results indicate that tDCS significantly impaired reversal irrespective of context in Experiment 2 only. When taking learning rate across trials into account, both experiments suggest that participants who received sham had the greatest learning rate when reversal occurred in a different context, as expected, whereas participants who received active tDCS in this condition had the lowest learning rate. However, active tDCS was associated with preferring the originally disadvantageous, but then neural stimulus after stimulus after reversal occurred in a different context in Experiment 1 only.
These results support a causal role for the left prefrontal cortex in the updating of avoidance-based associations and encourage further inquiry investigating the use of non-invasive brain stimulation on flexible updating of learned associations.
基于暴露的心理疗法用于治疗焦虑和恐惧相关障碍，依赖于“矫正性”联想学习。也就是说，在没有负面结果的情况下反复面对恐惧刺激，能够形成新的、经过矫正的安全联想，这表明此类刺激不再需要回避。不幸的是，暴露促进的矫正学习往往受情境限制，且通常泛化性较差。一种脑结构，即前额叶皮层，与情境引导行为有关，可能是改善安全学习泛化性的一个相关靶点。在此，我们测试了抑制左前额叶皮层是否会因果性地损害特定情境绑定联想的更新，或者相反，是否会损害习得联想的更新而与情境变化无关。此外，我们测试了在矫正学习期间前额叶抑制是否会影响联想随后向新情境的泛化。
在两个独立实验中，参与者在脑电图坐标F3处接受10分钟2毫安的阴极经颅直流电刺激（tDCS）（实验1 = 9人，实验2 = 22人）或假刺激（实验1 = 10人，实验2 = 22人），同时之前习得的联想在与初始学习相同或不同的情境中被反转。接下来，为了评估学习的泛化，要求参与者指出在一个全新的、从未见过的情境中他们更喜欢之前看到的哪些图像。
结果表明，仅在实验2中，tDCS无论情境如何都显著损害了联想反转。当考虑跨试验的学习率时，两个实验均表明，如预期的那样，接受假刺激的参与者在不同情境中发生联想反转时学习率最高，而在此条件下接受主动tDCS的参与者学习率最低。然而，仅在实验1中，主动tDCS与在不同情境中发生联想反转后更喜欢最初不利但后来中性的刺激相关。
这些结果支持左前额叶皮层在基于回避的联想更新中具有因果作用，并鼓励进一步研究非侵入性脑刺激在灵活更新习得联想方面的应用。
