Repetitive Transcranial Magnetic Stimulation in Alcohol Dependence: A Randomized, Double-Blind, Sham-Controlled Proof-of-Concept Trial Targeting the Medial Prefrontal and Anterior Cingulate Cortices
Repetitive Transcranial Magnetic Stimulation in Alcohol Dependence: A Randomized, Double-Blind, Sham-Controlled Proof-of-Concept Trial Targeting the Medial Prefrontal and Anterior Cingulate Cortices
复制标题
重复经颅磁刺激治疗酒精依赖：一项针对内侧前额叶和前扣带回皮质的随机、双盲、假刺激对照概念验证试验
DOI：
10.1016/j.biopsych.2021.11.020
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发表时间：
2022-05-30
影响因子：
10.6
通讯作者：
Zangen, Abraham
中科院分区：
文献类型：
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作者：
Harel, Maayan;Perini, Irene;Zangen, Abraham
背景：酒精成瘾与沉重的疾病负担相关，且治疗选择有限。在一项概念验证研究中，我们采用深部重复经颅磁刺激（dTMS）来作用于与酒精成瘾病理生理学相关的神经回路。我们评估了临床结果，并利用功能磁共振成像探索了相关的神经特征。
方法：这是一项双盲、随机、假刺激对照试验。共有51名近期戒酒且寻求治疗的（中重度）酒精使用障碍患者被随机分配接受假刺激或主动dTMS治疗，使用H7线圈靶向中线前额叶皮质区域，包括内侧前额叶皮质和前扣带回皮质。治疗包括在3周内进行15次治疗，随后在3个月的随访期内进行5次治疗。每次治疗以10赫兹的频率发放100串，每串30个脉冲。预先设定的主要结局是通过时间线追溯访谈得出的重度饮酒天数百分比的降低情况。次要分析包括对渴望程度的自我报告、尿液中的乙基葡萄糖醛酸苷以及脑成像指标。
结果：主动治疗组在治疗后的渴望程度以及随访期间的重度饮酒天数百分比均显著低于假刺激对照组（重度饮酒天数百分比分别为2.9±0.8% 与10.6±1.9%，p = 0.037）。主动dTMS与背侧前扣带回皮质与尾状核之间静息态功能连接的降低，以及内侧前额叶皮质与膝下前扣带回皮质之间连接的降低相关。
结论：我们为将dTMS靶向中线前额叶皮质结构作为酒精成瘾的一种治疗方法提供了初步的概念验证。这些数据有力地支持了开展全面验证性多中心试验的合理性。dTMS的治疗益处似乎与脑网络活动的持续变化相关。
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.