This hypothesized shift in network dynamics during abstinence (Fig 7A) would result in one or more of the following observable changes in rsFC: 1) enhanced rsFC between insula and DMN, which would correlate with the severity of self-reported withdrawal symptoms and impaired task performance; 2) reduced rsFC between insula and the ECN; 3) enhanced rsFC within the DMN; 4) reduced rsFC within the ECN; (e.g., Cole et al., 2010; Kelly et al., 2011); and 5) a breakdown in negative coupling between the DMN and ECN (e.g., Cole et al., 2010). Conversely, acute nicotine administration (Fig 7B) may bias processing away from the DMN, resulting in enhanced rsFC within the ECN and between the ECN and insula. Such network dynamics may not only underlie the amelioration of withdrawal symptoms, but may also reflect an inherent property of nicotine to suppress DMN activity and enhance processing of extrinsic task-based stimuli. This latter view derives from the cognitive enhancing effects observed in nicotine-naïve populations (Heishman et al., 2010) as well as evidence that nicotine suppresses the DMN activity in non-smokers (Tanabe et al.,
