WIC significantly correlated (peak r = 0.76) with the strength of rsFC in the precuneus, insula, caudate, putamen, middle cingulate gyrus, and precentral gyrus (P < 0.05 Table ​Table2D,2D, Fig. ​Fig.4).4). Table ​Table2D2D summarizes the results with the corresponding peak clusters. Figure 2 Comparing anterior cingulate cortex (ACC)-seeded resting-state functional connectivity (rsFC) in smokers during the abstinent condition to that of nonsmokers. Smokers showed greater rsFC in the precuneus, caudate, putamen, superior frontal gyrus, middle ... Figure 3 Areas of increased resting-state functional connectivity Inhibitors,research,lifescience,medical (rsFC) during withdrawal. To identify changes in

rsFC associated with nicotine withdrawal, paired t test was implemented between the anterior Inhibitors,research,lifescience,medical cingulate cortex (ACC)-seeded rsFC maps for the abstinent … Figure 4 Areas where resting-state functional connectivity (rsFC) in the abstinent state correlates with the intensity of Withdrawal-Induced Craving. Highly correlated areas (shown in red) included: the precuneus, Inhibitors,research,lifescience,medical insula, caudate, putamen, middle cingulate gyrus, … Discussion Addiction researchers have long hypothesized that PD is attributable to the development of neural adaptations. By employing a new survey measure of PD, (DiFranza et al. 2011) we were able to demonstrate

that the progressive development of PD is associated with decreasing FA in the ACb (r = −0.68), increasing density of white matter tracts between the ACb and white matter ZSTK474 approaching the precuneus (r = 0.75), and decreasing density of white matter tracts between the ACb and the frontal lobe (r = −0.86). (Huang et al. 2013) The density of tracts between the ACb Inhibitors,research,lifescience,medical and white matter approaching the precuneus also correlated with scores on the HONC and the FTND. (Huang et al. 2013) These observations suggested that neural adaptations in the ACC-precuneus circuit might play a key role in the development of PD. Despite the small sample

size, our results using two different methods (ICA and ACC-seed based rsFC analysis) were highly consistent. We found that 11 Inhibitors,research,lifescience,medical h into withdrawal, abstinent smokers showed increased rsFC in many pathways as compared to the satiated condition (Table ​(Table2B),2B), and that rsFC in smokers in withdrawal was greater than that of nonsmoking controls. Our analysis identified several pathways connecting Histamine H2 receptor to the ACC in which rsFC was significantly correlated with the intensity of WIC (Table ​(Table2D,2D, Fig. ​Fig.4).4). These included pathways involving the precuneus, insula, caudate, putamen, middle cingulate gyrus, right precentral gyrus, and left post central gyrus. While we studied correlates of withdrawal-induced craving in the absence of cues, others have studied correlates of cue-induced craving. Cue-induced craving has been shown to correlate with activity in the ACC, precuneus, precentral gyrus, and postcentral gyrus. (McClernon et al. 2005; Culbertson et al.