Drug addiction is a public health crisis for which new treatments are urgently needed. In rare cases, regional brain damage can lead to addiction remission. These cases may be used to identify therapeutic targets for neuromodulation. We analyzed two cohorts of patients addicted to smoking at the time of focal brain damage (cohort 1 n = 67; cohort 2 n = 62). Lesion locations were mapped to a brain atlas and the brain network functionally connected to each lesion location was computed using human connectome data (n = 1,000). Associations with addiction remission were identified. Generalizability was assessed using an independent cohort of patients with focal brain damage and alcohol addiction risk scores (n = 186). Specificity was assessed through comparison to 37 other neuropsychological variables. Lesions disrupting smoking addiction occurred in many different brain locations but were characterized by a specific pattern of brain connectivity. This pattern involved positive connectivity to the dorsal cingulate, lateral prefrontal cortex, and insula and negative connectivity to the medial prefrontal and temporal cortex. This circuit was reproducible across independent lesion cohorts, associated with reduced alcohol addiction risk, and specific to addiction metrics. Hubs that best matched the connectivity profile for addiction remission were the paracingulate gyrus, left frontal operculum, and medial fronto-polar cortex. We conclude that brain lesions disrupting addiction map to a specific human brain circuit and that hubs in this circuit provide testable targets for therapeutic neuromodulation.

毒瘾是一场公共卫生危机，迫切需要新的治疗方法。在极少数情况下，区域性脑损伤可以导致毒瘾缓解。这些病例可用于确定神经调节的治疗靶点。我们分析了两组在局灶性脑损伤时吸烟成瘾的患者（队列 1 n  = 67；队列 2 n  = 62）。将病变位置映射到大脑图谱上，并使用人类连接组数据（n  = 1,000）计算功能连接到每个病变位置的大脑网络。确定了与成瘾缓解的关联。使用具有局灶性脑损伤和酒精成瘾风险评分的独立患者队列评估了普遍性（n = 186）。通过与其他 37 个神经心理学变量进行比较来评估特异性。破坏吸烟成瘾的损伤发生在许多不同的大脑位置，但其特征是大脑连接的特定模式。这种模式涉及到背侧扣带回、外侧前额叶皮层和岛叶的正连接以及与内侧前额叶和颞叶皮层的负连接。该回路在独立的病变群体中是可重复的，与酒精成瘾风险降低相关，并且特定于成瘾指标。最符合成瘾缓解连接特征的中枢是副扣带回、左额叶盖和内侧额极皮层。