Alcohol use disorder (AUD) is a highly prevalent, often refractory, medical illness. The symptoms of AUD are driven by dysfunction in several neurocircuits centered on the nucleus accumbens (NAc). Case reports and animal studies suggest NAc-DBS may be an effective harm-reduction treatment in severe AUD. Six patients with severe, refractory AUD underwent NAc-DBS. Safety metrics and clinical outcomes were recorded. Positron emission tomography (FDG-PET) was used to measure glucose metabolism in the NAc at baseline and 6 months. Functional magnetic resonance imaging (fMRI) was used to characterize postoperative changes in NAc functional connectivity to the rest of the brain, as well as NAc and dorsal striatal reactivity to alcoholic visual cues. This study was registered with ClinicalTrials.gov, NCT03660124. All patients experienced a reduction in craving. There was a significant reduction in alcohol consumption, alcohol-related compulsivity, and anxiety at 12 months. There was no significant change in depression. FDG-PET analysis demonstrated reduced NAc metabolism by 6 months, which correlated with improvements in compulsive drinking behaviors. Clinical improvement correlated with reduced functional connectivity between the NAc and the visual association cortex. Active DBS was associated with reduced activation of the dorsal striatum during passive viewing of alcohol-containing pictures. NAc-DBS is feasible and safe in patients with severe, otherwise refractory AUD. It is associated with a reduction in cravings and addictive behavior. A potential mechanism underlying this process is a down-regulation of the NAc, a disruption of its functional connectivity to the visual association cortex, and interference of cue-elicited dorsal striatum reactivity. Trial Registration NCT03660124 (www.clinicaltrials.gov).

酒精使用障碍 (AUD) 是一种非常普遍且通常难以治愈的医学疾病。AUD 的症状是由以伏隔核 (NAc) 为中心的多个神经回路功能障碍引起的。病例报告和动物研究表明，NAc-DBS 可能是严重 AUD 的有效减害治疗方法。6 名患有严重、难治性 AUD 的患者接受了 NAc-DBS。记录了安全指标和临床结果。正电子发射断层扫描 (FDG-PET) 用于测量基线和 6 个月时 NAc 中的葡萄糖代谢。功能性磁共振成像 (fMRI) 用于表征 NAc 与大脑其余部分功能连接的术后变化，以及 NAc 和背侧纹状体对酒精视觉提示的反应性。本研究已在 ClinicalTrials.gov 注册，NCT03660124。所有患者的渴望都减少了。在 12 个月时，饮酒、与酒精有关的强迫症和焦虑显着减少。抑郁症没有显着变化。FDG-PET 分析表明 NAc 代谢减少了 6 个月，这与强迫性饮酒行为的改善相关。临床改善与 NAc 和视觉联合皮层之间的功能连接性降低相关。主动 DBS 与被动观看含酒精图片期间背侧纹状体的激活减少有关。NAc-DBS 对于严重的、难治性 AUD 患者是可行且安全的。它与渴望和成瘾行为的减少有关。这一过程的潜在机制是 NAc 的下调，其与视觉联合皮层的功能连接中断，以及提示引起的背侧纹状体反应性的干扰。试验注册 NCT03660124 (www.clinicaltrials.gov)。