Keeley Robin J, Hsu Li-Ming, Brynildsen Julia K, Lu Hanbing, Yang Yihong, Stein Elliot A
Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, 251 Bayview Blvd, Baltimore, MD, 21224, USA.
Department of Radiology and BRIC, University of North Carolina at Chapel Hill, 130 Mason Farm Rd, Chapel Hill, NC, 27599, USA.
Neuropsychopharmacology. 2020 May;45(6):1042-1049. doi: 10.1038/s41386-020-0635-x. Epub 2020 Feb 13.
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.
开发基于大脑的生物标志物以评估尼古丁依赖的严重程度和治疗效果，对于改善目前效果欠佳的治疗结果至关重要。对人类进行的横断面静息态功能连接（rsFC）研究发现，背侧前扣带回皮层和腹侧纹状体之间存在一个回路，该回路与尼古丁依赖严重程度的增加呈负相关，但不受急性尼古丁给药的影响，这表明其是成瘾的一种特质标志物。然而，这种特质回路失调是尼古丁依赖的易患因素还是其结果尚不清楚。我们使用具有纵向功能磁共振成像测量的尼古丁依赖大鼠模型，评估了前扣带回-纹状体rsFC与尼古丁依赖严重程度之间的关系。基于数据驱动的模块化大鼠内侧前额叶皮层（mPFC）分割，结合与纹状体的基于种子点的连接性分析，重现了在人类中观察到的扣带回-纹状体关系。此外，扣带回-纹状体脑回路与以戒断诱发强度为指标的尼古丁依赖严重程度之间的关系，完全由一个易患性岛叶-额叶皮层功能回路在统计学上进行调节。这些数据表明，所确定的跨物种前扣带回-纹状体回路与尼古丁依赖严重程度的关系在慢性尼古丁给药诱导的依赖后失调，并且可能受到基于岛叶的纹状体-额叶回路个体差异的影响，突出了该回路作为依赖严重程度生物标志物的潜力。
