Based on the above, we hypothesize that nicotine withdrawal can enhance and nicotine administration suppress, DMN functioning. Additionally, maladaptive interactions between DMN and TPN may provide a systems-level mechanistic account regarding deficits in sustained attention, performance monitoring and inhibitory control following acute abstinence from addictive drugs (Heishman et al., 1994; Garavan and Stout, 2005; Garavan and Hester, 2007; Verdejo-García et al., 2008). Specifically, nicotine may enhance performance via a shift in activity from a network subserving internally oriented, to one or more networks mediating externally oriented information processing. Such enhancing effects likely are more evident in populations experiencing state- (e.g., abstinent drug users, sleep deprived or fatigued participants) or trait-related (e.g., ADHD, chronic pain) dysfunctions in externally oriented information processing (Newhouse et al., 2004). However, the question remains: what are the neural substrates mediating such dynamic activity switching between large-scale brain networks, and is there a role for nicotine in such a process?
