Distinct Alteration Patterns of Resting-State Functional Connectivity of the Corticostriatal Circuits Effected by Cigarette Smoking in Mild Cognitive Impairment Patients and Cognitively Normal subjects

Abstract

\n To explore the interaction effects of smoking status (non-smoking vs. smoking) and disease (cognitively normal (CN) vs. MCI) based on resting-state functional connectivity (rsFC) of the corticostriatal circuits. We included 304 CN non-smokers, 44 CN smokers, 130 MCI non-smokers, and 33 MCI smokers. The seed-based rsFC of striatal subregions (caudate, putamen, and nucleus accumbens [NAc]) with the whole-brain voxel was calculated. Furthermore, we performed mixed effect analysis to explore the interaction effects between smoking status and disease. Significant interaction effects were detected between: (1) right caudate and left inferior parietal lobule (IPL); (2) right putamen and bilateral cuneus; (3) bilateral NAc and bilateral anterior cingulate cortex (ACC). The post-hoc analyses revealed that the CN smokers showed increased rsFC between right caudate and left IPL compared to non-smokers; while the MCI smokers demonstrated decreased rsFC between right putamen and cuneus, and increased rsFC between bilateral NAc and ACC compared to non-smokers. In MCI smokers, the rsFC value between left NAc and ACC was positively correlated with Semantic Verbal Fluency (SVF, r = 0.387, p = 0.026), and the rsFC value between right NAc and ACC was positively correlated with SVF (r = 0.390, p = 0.025), Wechsler memory scale-logical memory (WMS-LM) immediate recall (r = 0.378, p = 0.03), and WMS-LM delayed recall (r = 0.367, p = 0.036). Our findings suggest that chronic nicotine exposure may lead to functional connectivity alterations of corticostriatal circuits in MCI patients, and the pattern is different from CN smokers.