Sarrazin Verena, Overman Margot Juliëtte, Mezossy-Dona Luca, Browning Michael, O'Shea Jacinta
Wellcome Centre for Integrative Neuroimaging, University of Oxford, OX3 9DU, Oxford, United Kingdom.
Department of Psychiatry, Warneford Hospital, University of Oxford, OX3 7JX, Oxford, United Kingdom.
Transl Psychiatry. 2024 Dec 18;14(1):487. doi: 10.1038/s41398-024-03204-3.
Depression and anxiety are associated with deficits in adjusting learning behaviour to changing outcome contingencies. This is likely to drive and maintain symptoms, for instance, by perpetuating negative biases or a sense of uncontrollability. Normalising such deficits in adaptive learning might therefore be a novel treatment target for affective disorders. The aim of this experimental medicine study was to test whether prefrontal cortex transcranial direct current stimulation (tDCS) could normalise these aberrant learning processes in depressed mood. To test proof-of-concept, we combined tDCS with a decision-making paradigm that manipulates the volatility of reward and punishment associations. 85 participants with low mood received tDCS during (or before) the task. In two sessions participants received real or sham tDCS in counter-balanced order. Compared to healthy controls (n = 40), individuals with low mood showed significantly impaired adjustment of learning rates to the volatility of loss outcomes. Prefrontal tDCS applied during task performance normalised this deficit, by increasing the adjustment of loss learning rates. As predicted, prefrontal tDCS before task performance (control) had no effect. Thus, the effect was cognitive-state dependent. Our study shows, for the first time, that a candidate depression treatment, prefrontal tDCS, when paired with a task, can reverse deficits in adaptive learning from outcome contingencies in low mood. Thus, combining neurostimulation with a concurrent cognitive manipulation is a potential novel strategy to enhance the effect of tDCS in depression treatment.
抑郁和焦虑与在根据变化的结果偶发事件调整学习行为方面的缺陷有关。这可能会驱动并维持症状，例如，通过使负面偏差或不可控感持续存在。因此，使适应性学习中的此类缺陷正常化可能是情感障碍的一个新的治疗靶点。这项实验医学研究的目的是测试前额叶皮质经颅直流电刺激（tDCS）是否能使抑郁情绪下这些异常的学习过程正常化。为了测试概念验证，我们将tDCS与一种决策范式相结合，该范式可操纵奖励和惩罚关联的波动性。85名情绪低落的参与者在任务期间（或之前）接受了tDCS。在两个疗程中，参与者以平衡的顺序接受了真正的或伪tDCS。与健康对照组（n = 40）相比，情绪低落的个体在根据损失结果的波动性调整学习率方面表现出明显受损。在任务执行期间应用前额叶tDCS通过增加对损失学习率的调整使这种缺陷正常化。正如预测的那样，在任务执行前（对照组）应用前额叶tDCS没有效果。因此，这种效果依赖于认知状态。我们的研究首次表明，一种候选的抑郁症治疗方法，即前额叶tDCS，与一项任务相结合时，可以逆转情绪低落时从结果偶发事件中进行适应性学习的缺陷。因此，将神经刺激与同时进行的认知操作相结合是增强tDCS在抑郁症治疗中效果的一种潜在新策略。
