Smoking Progression and Nicotine-Enhanced Reward Sensitivity Predicted by Resting-State Functional Connectivity in Salience and Executive Control Networks.

Introduction: The neural underpinnings underlying individual differences in nicotine-enhanced reward sensitivity (NERS) and smoking progression are poorly understood. Thus, we investigated whether brain resting-state functional connectivity (rsFC.) during smoking abstinence predicts NERS and smoking progression in young light smokers. We hypothesized that high rsFC between brain areas with high densities of nicotinic receptors (insula, anterior cingulate cortex [ACC], hippocampus, thalamus) and areas involved in reward-seeking (nucleus accumbens [NAcc], prefrontal cortex [PFC]) would predict NERS and smoking progression.

Aims And Methods: Young light smokers (N = 64, age 18-24, M = 1.89 cigarettes/day) participated in the study. These individuals smoked between 5 and 35 cigarettes per week and lifetime use never exceeded 35 cigarettes per week. Their rsFC was assessed using functional magnetic resonance imaging after 14 hours of nicotine deprivation. Subjects also completed a probabilistic reward task after smoking a placebo on 1 day and a regular cigarette on another day.

Results: The probabilistic-reward-task assessed greater NERS was associated with greater rsFC between the right anterior PFC and right NAcc, but with reduced rsFC between the ACC and left inferior prefrontal gyrus and the insula and ACC. Decreased rsFC within the salience network (ACC and insula) predicted increased smoking progression across 18 months and greater NERS.

Conclusions: These findings provide the first evidence that differences in rsFCs in young light smokers are associated with nicotine-enhanced reward sensitivity and smoking progression.

Clinical Trial Registration: NCT02129387 (preregistered hypothesis: www.clinicaltrials.gov).

Implications: Weaker rsFC within the salience network predicted greater NERS and smoking progression. These findings suggest that salience network rsFC and drug-enhanced reward sensitivity may be useful tools and potential endophenotypes for reward sensitivity and drug-dependence research.