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 侵入性经颅磁刺激可用于改善饮酒结果 (禁酒，酗酒日)在寻求行为治疗的澳元病患者中。 建立在几项目标识别研究和一项小型双盲临床研究的基础上 在本组进行的AUD患者的治疗试验中，我们提出了一种双盲法 评价2种潜在TMS相对疗效的安慰剂对照随机研究 AUD的治疗策略。具体地说，利用MUSC集约型的现有基础设施 门诊治疗计划，同意的参与者将随机接受真实或虚假的治疗 TMS传递到腹侧内侧前额叶皮质(VmPFC)，或背外侧前额叶皮质 (DLPFC)，为期20次(2次/天，10天)，紧接在他们的日常强化门诊之前 心理治疗。这个5年R01提案的科学前提是，通过调节 调节酒精线索反应性的神经回路(策略1，目标1，vmPFC)或执行控制 (战略2，目标2，dlPFC)将有可能提高戒酒率并降低 连续4个月大量饮酒。凭借我们在大脑方面的综合科学专业知识 刺激(Hanlon、神经成像(Schacht和Hanlon)、酒精使用障碍研究 (Schacht，Anton，Book)和AUD患者的临床实践(Book，Smith)我们的研究团队 MUSC是唯一适合发展这一关键研究领域的机构。建议的结果： AIMS将为多点临床试验提供循证基础，并将加快 为AUD患者开发一种基于神经回路的新治疗方法的进展。

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 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 performed by our group, here we propose a double-blind placebo controlled, randomized study to evaluate the relative efficacy of 2 potential TMS treatment strategies for AUD. Specifically, using the existing infrastructure of the MUSC Intensive Outpatient Treatment Program, consenting participants will be randomized to receive real or sham TMS delivered to the ventral medial prefrontal cortex (vmPFC), 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, vmPFC) 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 the proposed 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.