Abstract
Nicotine addiction is associated with dysregulated inhibitory control (IC), mediated by corticothalamic circuitry including the right inferior frontal gyrus (rIFG). Among sated smokers, worse IC task performance and greater IC-related rIFG activity have been shown to be associated with greater relapse vulnerability. The present study investigated the effects of smoking abstinence on associations between IC task performance, rIFG activation, and smoking behavior. Smokers (N = 26, 15 female) completed an IC task (Go/Go/No-go) during fMRI scanning followed by a laboratory-based smoking relapse analog task (SRT) on two visits: once when sated and once following 24 h of smoking abstinence. During the SRT, smokers were provided with monetary rewards for incrementally delaying smoking. A significant main effect of No-go accuracy on latency to smoke during the SRT was observed when collapsing across smoking states (abstinent vs. sated). Similarly, a significant main effect of IC-related activation in rIFG on SRT performance was observed across states. The main effect of state, however, was non-significant in both of these models. Furthermore, the interaction between smoking state and No-go accuracy on SRT performance was non-significant, indicating a similar relationship between IC and lapse vulnerability under both sated and abstinent conditions. The state X rIFG activation interaction on SRT performance was likewise non-significant. Post-hoc whole brain analyses indicated that abstinence resulted in greater IC-related activity in the right middle frontal gyrus (MFG) and insula. Activation during IC in these regions was significantly associated with decreased No-go accuracy. Moreover, greater abstinence induced activity in right MFG during IC was associated with smoking sooner on the SRT. These findings are bolstered by the extant literature on the effects of nicotine on executive function and also contribute novel insights on how individual differences in behavioral and neuroimaging measures of IC may influence relapse propensity independent of smoking state.
Highlights
Nicotine addiction is associated with dysregulated prefrontalmediated executive function including multiple forms of memory [1,2,3], reward processing [4,5,6,7], emotion-cognition interactions [8,9,10,11], and inhibitory control (IC) [12,13,14,15]
Except for somatic symptoms and arousal, all selfreported withdrawal symptoms were significantly higher under the Abstinent, as compared to the Sated condition
Bold p-values are significant at α = 0.05
Summary
Nicotine addiction is associated with dysregulated prefrontalmediated executive function including multiple forms of memory [1,2,3], reward processing [4,5,6,7], emotion-cognition interactions [8,9,10,11], and inhibitory control (IC) [12,13,14,15]. Inhibitory control is defined as the ability to withhold a prepotent response in favor of performing context-relevant, goal-directed behavior [16]. Numerous studies indicate that nicotine withdrawal induces deficits on performance of executive function tasks [20,21,22,23,24,25], including IC tasks [15]. Nicotine withdrawal-induced disruption of executive function may represent a significant factor underlying smoking maintenance and relapse [26]. The predictive relationship, between the mechanisms underlying withdrawal-induced cognitive deficits and relapse outcomes remain poorly understood. A better understanding of the factors and mechanisms undergirding relapse propensity may facilitate individually tailored treatments and improve their effectiveness
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