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

随着光遗传学刺激技术的进步，临床前研究已经证明， 额叶-纹状体神经回路的活动对大量饮酒和酒精有因果关系 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 酒精使用障碍（AUD）患者的治疗技术。的长期目标 我们的多学科研究团队是为了确定最佳参数， 侵入性经颅磁刺激可用于改善饮酒结果 （禁欲，大量饮酒天）在寻求AUD行为治疗的个体中。 在几项靶点鉴定研究和一项小型双盲临床试验的基础上， 我们的研究小组在接受治疗的AUD患者中进行了一项试验，在此我们提出了一项双盲 安慰剂对照、随机化研究，评价2种潜在TMS的相对疗效 AUD的治疗策略。具体而言，利用MUSC密集型的现有基础设施 门诊治疗计划，知情同意的受试者将随机接受真实的或假手术 TMS传递到腹内侧前额叶皮层（vmPFC）或背外侧前额叶皮层 （dlPFC）进行20次治疗（2次/天，10天），然后立即进行每日强化门诊治疗 心理治疗这个5年R 01提案的科学前提是，通过调节 调节酒精线索反应性（策略1，目标1，vmPFC）或执行控制的神经回路 （战略2，目标2，dlPFC）将有可能提高戒酒率， 4个月内大量饮酒。结合我们在大脑方面的专业知识 刺激（Hanlon），神经影像学（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 在MUSC是唯一适合发展这一研究的关键线。拟议会议的成果 Aims将为多中心临床试验提供循证基础， 为AUD患者开发新的基于神经回路的治疗方法的进展。

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.