The development of brain-based biomarkers to assess nicotine dependence severity and treatment efficacy are essential to improve the current marginally effective treatment outcomes. Cross-sectional resting state functional connectivity (rsFC) studies in humans identified a circuit between the dorsal anterior cingulate cortex and the ventral striatum that negatively correlated with increased nicotine dependence severity but was unaffected by acute nicotine administration, suggesting a trait marker of addiction. However, whether this trait circuit dysregulation is predispositional to or resultant from nicotine dependence is unclear. Using a rat model of nicotine dependence with longitudinal fMRI measurements, we assessed the relationship between ACC-striatal rsFC and nicotine dependence severity. Data-driven modularity-based parcellation of the rat medial prefrontal cortex (mPFC) combined with seed-based connectivity analysis with the striatum recapitulated the cingulate-striatum relationship observed in humans. Furthermore, the relationship between cingulate-striatal brain circuits and nicotine dependence severity as indexed by the intensity of precipitated withdrawal, was fully statistically moderated by a predispositional insular-frontal cortical functional circuit. These data suggest that the identified trans-species ACC-striatal circuit relationship with nicotine dependence severity is dysregulated following chronic nicotine administration-induced dependence and may be biased by individual differences in predispositional insula-based striatal-frontal circuits, highlighting the circuit's potential as a biomarker of dependence severity.

中文翻译：

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岛叶回路的内在差异调节了尼古丁依赖性与扣带回纹状体连接强度之间的负相关性。


开发基于大脑的生物标志物来评估尼古丁依赖的严重程度和治疗效果对于改善目前勉强有效的治疗结果至关重要。人类横断面静息态功能连接（rsFC）研究发现，背侧前扣带皮层和腹侧纹状体之间存在一条回路，该回路与尼古丁依赖性严重程度的增加呈负相关，但不受急性尼古丁给药的影响，这表明这是成瘾的特征标记。然而，这种特征回路失调是否是尼古丁依赖的倾向或结果尚不清楚。使用尼古丁依赖大鼠模型和纵向功能磁共振成像测量，我们评估了 ACC-纹状体 rsFC 与尼古丁依赖严重程度之间的关系。数据驱动的基于模块化的大鼠内侧前额叶皮层 (mPFC) 分区与基于种子的纹状体连接分析相结合，重现了在人类中观察到的扣带回-纹状体关系。此外，扣带回纹状体脑回路与尼古丁依赖严重程度之间的关系（以突然戒断的强度为指标）在统计学上完全受到易感岛叶皮质功能回路的调节。这些数据表明，已确定的跨物种 ACC-纹状体环路与尼古丁依赖严重程度的关系在长期尼古丁给药诱导的依赖后失调，并且可能因基于岛叶的易感性纹状体-额叶环路的个体差异而产生偏差，突出了该环路作为尼古丁依赖的潜力。依赖性严重程度的生物标志物。