An fMRI study of cigarette smokers performing an inhibitory control task: neural correlates of nicotine withdrawal

In nicotine-dependent smokers, withdrawal may be associated with a blunted physiological response in brain networks that support self-control, a hypothesis that may explain high relapse rates. To test this hypothesis, a functional magnetic resonance imaging (fMRI) study was conducted. A Go/No-Go task that challenged ability to inhibit a prepotent response on demand was administered to 13 nicotine-dependent smokers during two fMRI sessions performed on separate days. Participants abstained from smoking for 12 hours prior to both sessions, but were administered a nicotine replacement therapy (NRT) patch before one session and a placebo patch prior to the other. The order in which each patch was administered was counterbalanced across subjects. A measure of affect (Positive and Negative Affective Schedule) was administered prior to both sessions to assess nicotine withdrawal. Participants endorsed significantly greater negative affect after being administered placebo (placebo > NRT; p < 0.01), but indices of Go/No-Go performance were similar across both sessions. Smokers exhibited significant event-related fMRI response during correct inhibition trials in prefrontal brain regions thought to be critically related to inhibitory control only following administration of NRT (p < .005, cst > 300 ml). In nicotine-dependent smokers undergoing withdrawal, greater recruitment of prefrontal cortex following administration of NRT is associated with an improvement in negative affect, but no change in ability to inhibit a prepotent response on demand. This evidence suggests that withdrawal from nicotine is not associated with further blunting of physiological response in the prefrontal cortex of smokers during response inhibition.