Longitudinal investigation of TMS as a tool to improve alcohol treatment outcomes

随着光遗传刺激技术的进步，临床前研究表明 额叶-纹状体神经回路的活动对酗酒有因果影响 复职。然而，在临床上，我们还没有将这项研究转化为神经回路。 基于酒精使用障碍(AUD)患者的治疗技术。的长期目标是 我们的多学科研究团队将确定最佳参数，通过这些参数 侵入性theta爆发式刺激(TBS-一种模式形式或经颅磁刺激)可以 用于改善饮酒结果(禁酒、酗酒天数) 寻求行为疗法治疗澳元病的个人。建立在多个目标的基础上 AUD患者的识别研究和小型双盲临床试验 我们小组在这里提出了一项双盲、安慰剂对照、随机研究来评估 两种潜在的TBS治疗酒精使用障碍策略的相对疗效。具体来说， 使用MUSC强化门诊治疗计划的现有基础设施，同意 参与者将被随机接受真实或虚假的TBS，这些TBS被送到腹侧内侧 前额叶皮质(MPFC)，或背外侧前额叶皮质(DlPFC)，为期20次(2次/天，10次 天)，紧接在他们每天的强化门诊治疗之前。科学的 这项为期5年的R01提案的前提是，通过调节调节酒精的神经回路 线索-反应性(策略1，目标1，mPFC)或执行控制(策略2，目标2，dlPFC) 可能在4个月内提高戒酒率并减少重度饮酒天数 句号。凭借我们在脑刺激(Hanlon、神经成像)方面的综合科学专业知识 (沙赫特和汉龙)，酒精使用障碍研究(沙赫特，安东，书)，和临床实践 对于AUD患者(Book，Smith)，我们在MUSC的研究团队是唯一适合开发这一技术的 研究的关键路线。这些目标的结果将提供以证据为基础的基础 进行多点临床试验，并将加快开发基于 AUD患者的治疗。

With advances in optogenetic stimulation techniques, preclinical studies have demonstrated that activity in frontal-striatal neural circuits has a causal influence on heavy drinking and alcohol reinstatement. Clinically, however, we have not yet translated this research into a neural circuit based therapeutic technique for patients with alcohol use disorder (AUD). The long term goal of our multidisciplinary research team is to determine the optimal parameters through which non- invasive theta burst stimulation (TBS – a patterned form or transcranial magnetic stimulation) can be used to improve alcohol drinking outcomes (abstinence, heavy drinking days) among individuals seeking behavioral treatment for AUD. Building on a foundation of several target identification studies and a small double blinded clinical trial in treatment-engaged AUD patients by our group, here we propose a double-blind placebo controlled, randomized study to evaluate the relative efficacy of 2 potential TBS treatment strategies for alcohol use disorder. Specifically, using the existing infrastructure of the MUSC Intensive Outpatient treatment Program, consenting participants will be randomized to receive real or sham TBS delivered to the ventral medial prefrontal cortex (mPFC), or dorsolateral prefrontal cortex (dlPFC) for 20 sessions (2x/day, 10 days) immediately before their daily intensive outpatient therapy sessions. The scientific premise of this 5 year R01 proposal is that, by modulating the neural circuits that regulate alcohol cue-reactivity (Strategy 1, Aim 1, mPFC) or executive control (Strategy 2, Aim 2, dlPFC) it will be possible to increase alcohol abstinence rates and decrease heavy drinking days over a 4 month period. With our combined scientific expertise in brain stimulation (Hanlon, neuroimaging (Schacht and Hanlon), alcohol use disorder research (Schacht, Anton, Book), and clinical practice with AUD patients (Book, Smith) our research team at MUSC is uniquely suited to develop this critical line of research. The outcomes of these Aims will provide an evidence-based foundation for a multisite clinical trial and will hasten progress towards developing a new neural circuit based treatment for patients with AUD.