Severity of dependence modulates smokers' functional connectivity in the reward circuit: a preliminary study

Nicotine dependence is characterized as a neural circuit dysfunction, particularly with regard to the reward circuit. Although dependence severity moderates cue reactivity in the brain regions involved in reward processing, the direction of its influence remains controversial.

Investigating the functional organization of the reward circuit may provide complementary information. Here, we used resting-state functional connectivity (rsFC) to evaluate the integrity of the reward circuit in smokers with different severities of nicotine dependence.

Totals of 65 smokers and 37 non-smokers underwent resting-state functional magnetic resonance imaging (fMRI). The smokers were divided into low-dependent (FTND < 5, n = 26) and high-dependent smoker groups (FTND ≥ 5, n = 39) based on their nicotine-dependence severity (as measured by the Fagerström test for nicotine dependence [FTND]). The region of interest (ROI)-wise rsFC within the reward circuit was compared between smokers and non-smokers as well as between low-dependent and high-dependent smokers and then correlated with smokers' FTND scores.

Widespread rsFC attenuation was observed in the reward circuit of smokers compared with non-smokers. Compared with low-dependent smokers, high-dependent smokers showed greater rsFC between the right amygdala and the left nucleus accumbens (NAcc) as well as between the bilateral hippocampus. Furthermore, a positive correlation between the inter-hippocampus rsFC and the severity of nicotine dependence (FTND) was detected among all smokers (r = 0.416, p = 0.001).

Our results indicate a dysfunction of the reward circuit in nicotine-dependent individuals. Moreover, our study improves the understanding of the neuroplastic changes that occur during the development of nicotine dependence.