Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
Department of Pharmacology & Toxicology and Department of Psychiatry, University of Toronto, 1 King's College Circle, Toronto, ON, Canada.
Neuropsychopharmacology. 2023 May;48(6):936-945. doi: 10.1038/s41386-023-01528-0. Epub 2023 Mar 3.
Nicotine dependence is a major predictor of relapse in people with Tobacco Use Disorder (TUD). Accordingly, therapies that reduce nicotine dependence may promote sustained abstinence from smoking. The insular cortex has been identified as a promising target in brain-based therapies for TUD, and has three major sub-regions (ventral anterior, dorsal anterior, and posterior) that serve distinct functional networks. How these subregions and associated networks contribute to nicotine dependence is not well understood, and therefore was the focus of this study. Sixty individuals (28 women; 18-45 years old), who smoked cigarettes daily, rated their level of nicotine dependence (on the Fagerström Test for Nicotine Dependence) and, after abstaining from smoking overnight (~12 h), underwent functional magnetic resonance imaging (fMRI) in a resting state. A subset of these participants (N = 48) also completing a cue-induced craving task during fMRI. Correlations between nicotine dependence and resting-state functional connectivity (RSFC) and cue-induced activation of the major insular sub-regions were evaluated. Nicotine dependence was negatively correlated with connectivity of the left and right dorsal, and left ventral anterior insula with regions within the superior parietal lobule (SPL), including the left precuneus. No relationship between posterior insula connectivity and nicotine dependence was found. Cue-induced activation in the left dorsal anterior insula was positively associated with nicotine dependence and negatively associated with RSFC of the same region with SPL, suggesting that craving-related responsivity in this subregion was greater among participants who were more dependent. These results may inform therapeutic approaches, such as brain stimulation, which may elicit differential clinical outcomes (e.g., dependence, craving) depending on the insular subnetwork that is targeted.
尼古丁依赖是导致烟草使用障碍（TUD）患者复吸的主要预测因素。因此，减少尼古丁依赖的治疗方法可能会促进吸烟的持续戒断。岛叶已被确定为 TUD 基于大脑的治疗的一个有前途的靶点，它有三个主要的亚区（腹侧前、背侧前和后），分别服务于不同的功能网络。这些亚区和相关网络如何促进尼古丁依赖尚不清楚，因此是本研究的重点。60 名（28 名女性；18-45 岁）每日吸烟的个体，对其尼古丁依赖程度（用尼古丁依赖测试量表（FTND）进行评估），并在一夜（约 12 小时）戒烟后，在静息状态下进行功能磁共振成像（fMRI）。这些参与者中的一部分（N=48）也在 fMRI 期间完成了线索诱发的渴求任务。评估了尼古丁依赖与静息状态功能连接（RSFC）和主要岛叶亚区线索诱导激活之间的相关性。尼古丁依赖与左、右侧背侧和左侧腹侧前岛叶与上顶叶区域（包括左楔前叶）的连接呈负相关。未发现后岛叶连接与尼古丁依赖之间存在关系。左背侧前岛叶的线索诱导激活与尼古丁依赖呈正相关，与同一区域与上顶叶的 RSFC 呈负相关，表明该亚区与渴求相关的反应性在依赖程度较高的参与者中更高。这些结果可能为治疗方法提供信息，例如脑刺激，这可能会根据目标的岛叶子网产生不同的临床结果（例如，依赖、渴求）。
