Background

Alcohol addiction is associated with a high disease burden, and treatment options are limited. In a proof-of-concept study, we used deep repetitive transcranial magnetic stimulation (dTMS) to target circuitry associated with the pathophysiology of alcohol addiction. We evaluated clinical outcomes and explored associated neural signatures using functional magnetic resonance imaging.

Methods

This was a double-blind, randomized, sham-controlled trial. A total of 51 recently abstinent treatment-seeking patients with alcohol use disorder (moderate to severe) were randomized to sham or active dTMS, using an H7 coil targeting midline frontocortical areas, including the medial prefrontal and anterior cingulate cortices. Treatment included 15 sessions over 3 weeks, followed by five sessions over 3 months of follow-up. Each session delivered 100 trains of 30 pulses at 10 Hz. The primary predefined outcome was reduction in percentage of heavy drinking days, obtained using timeline follow-back interviews. Secondary analyses included self-reports of craving, ethyl glucuronide in urine, and brain imaging measures.

Results

Both craving after treatment and percentage of heavy drinking days during follow-up were significantly lower in the active versus sham control group (percentage of heavy drinking days = 2.9 ± 0.8% vs. 10.6 ± 1.9%, p = .037). Active dTMS was associated with decreased resting-state functional connectivity of the dorsal anterior cingulate cortex with the caudate nucleus and decreased connectivity of the medial prefrontal cortex to the subgenual anterior cingulate cortex.

Conclusions

We provide initial proof-of-concept for dTMS targeting midline frontocortical structures as a treatment for alcohol addiction. These data strongly support a rationale for a full-scale confirmatory multicenter trial. Therapeutic benefits of dTMS appear to be associated with persistent changes in brain network activity.

中文翻译：

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酒精依赖中的重复经颅磁刺激：针对内侧前额叶和前扣带皮层的随机、双盲、假控制概念验证试验

背景

酒精成瘾与高疾病负担有关，治疗选择有限。在一项概念验证研究中，我们使用深度重复经颅磁刺激 (dTMS) 来靶向与酒精成瘾的病理生理学相关的电路。我们使用功能性磁共振成像评估了临床结果并探索了相关的神经特征。

方法

这是一项双盲、随机、假对照试验。共有 51 名最近戒断寻求治疗的酒精使用障碍（中度至重度）患者被随机分配到假或主动 dTMS，使用针对中线额叶皮质区域的 H7 线圈，包括内侧前额叶和前扣带皮层。治疗包括在 3 周内进行 15 次治疗，然后在 3 个月的随访中进行 5 次治疗。每个会话以 10 Hz 发送 100 列 30 个脉冲。主要的预定义结果是减少大量饮酒天数的百分比，这是使用时间线跟踪访谈获得的。次要分析包括渴望的自我报告、尿液中的乙基葡糖苷酸和脑成像测量。

结果

与假对照组相比，治疗后的渴望和随访期间重度饮酒天数的百分比显着降低（重度饮酒天数百分比 = 2.9 ± 0.8% 对 10.6 ± 1.9%，p  = .037）。活动 dTMS 与背侧前扣带皮层与尾状核的静息状态功能连接性降低以及内侧前额叶皮层与膝下前扣带皮层的连接性降低有关。

结论

我们为针对中线额叶皮质结构的 dTMS 提供初步概念验证，以治疗酒精成瘾。这些数据有力地支持了全面验证性多中心试验的基本原理。dTMS 的治疗益处似乎与大脑网络活动的持续变化有关。