Transcranial direct current stimulation (tDCS) has been studied as an adjunctive therapeutic option to alter maladaptive cortical excitability, activity, and connectivity associated with chronic substance use via the application of a weak direct current through the brain. The underlying mechanism of action remains ambiguous, however. We present a randomized, triple-blind, sham-controlled, clinical trial with two parallel arms conducted to determine the neural substrates of tDCS effects on drug craving using an fMRI drug cue reactivity paradigm. Sixty participants with methamphetamine use disorder were randomly assigned to two groups: 30 participants to active tDCS (5x7 cm2, 2 mA, for 20 minutes, anode/cathode over the F4/Fp1 in EEG 10-20 standard system) and 30 participants to the sham group. Neuroimaging data of a methamphetamine cue reactivity (MCR) task were collected immediately before and after stimulation with subjective craving assessed before, after, and during fMRI scans. There was a significant reduction in self-reported craving after stimulation (main effect of time) without any significant effect of group, time, or by group-time interaction. Our whole-brain analysis demonstrated that brain activation decreased in all parts of the brain in the second (post-stimulation) MCR imaging session after sham stimulation (habituation) but this uniform decrease did not occur throughout the brain in the active group. There were significant interactions between the group (active vs. sham) and time (after vs. before stimulation) in five main regions; medial frontal gyrus, anterior insula, inferior parietal lobule, precuneus, and inferior frontal gyrus with higher activations after active stimulation. We simulated computational head models for each individual. There was a significant effect of group in the relationship between level of current in the above-mentioned significant clusters and changes in task-modulated activation. We also found that brain regions with the highest electric fields in the prefrontal cortex showed a significant time by group interaction in task-modulated connectivity (psychophysiological interaction during MCR) in the frontoparietal network. In this two-parallel-arms triple-blind randomized control trial, we did not find any significant effect of the one session of active F4/Fp1 tDCS on drug craving self-report compared to sham stimulation. However, connectivity differences induced by active compared to sham stimulation suggested some potential mechanisms of tDCS to modulate neural response to drug cues among people with methamphetamine use disorder.

中文翻译：

---

经颅直流电刺激甲基苯丙胺用户fMRI药物提示反应性：一项随机临床试验。

经颅直流电刺激（tDCS）已作为辅助治疗选择进行了研究，可通过通过大脑施加较弱的直流电来改变与慢性物质使用相关的适应不良的皮质兴奋性，活动性和连通性。但是，基本的作用机制仍然是模棱两可的。我们提出了一项随机，三盲，假手术控制的临床试验，其中有两个平行臂，目的是使用功能磁共振成像药物提示反应性范式确定tDCS对药物渴望的神经底物。60名患有甲基苯丙胺使用障碍的参与者被随机分为两组：30名参与者参加活动tDCS（5x7 cm2，2 mA，持续20分钟，在EEG 10-20标准系统中通过F4 / Fp1阳极/阴极）和30名参与者参加假组。在刺激之前和之后立即收集甲基苯丙胺提示反应性（MCR）任务的神经影像学数据，并在fMRI扫描之前，之后和期间评估主观渴望。刺激后自我报告的渴望显着减少（时间的主要影响），而没有小组，时间或小组与时间的互动的显着影响。我们的全脑分析表明，在假刺激（适应）后的第二次（刺激后）MCR成像过程中，大脑所有部位的大脑激活均下降，但活动组的整个大脑并未出现这种均匀下降。在五个主要区域中，组（活动组与假组）和时间（刺激后组与刺激前组）之间存在显着的相互作用。额中内侧，前岛突，顶叶下小叶，前突，主动刺激后，额叶下部和下额回具有更高的激活率。我们为每个人模拟了计算头模型。在上述重要集群中的电流水平与任务调节激活的变化之间的关系中，组具有显着影响。我们还发现，额叶前额叶皮质中电场最高的大脑区域在任务调节的连通性（MCR期间的心理生理学相互作用）中通过小组互动表现出了明显的时间。在这项两臂三盲随机对照试验中，与假刺激相比，我们没有发现一疗程的活动F4 / Fp1 tDCS对渴望药物的自我报告有任何显着影响。然而，