Effects of Acute Nicotine Abstinence on Cue-elicited Ventral Striatum/Nucleus Accumbens Activation in Female Cigarette Smokers: A Functional Magnetic Resonance Imaging Study

Abstract

To achieve greater understanding of the brain mechanisms underlying nicotine craving in female smokers, we examined the influence of nicotine non-abstinence vs. acute nicotine abstinence on cue-elicited activation of the ventral striatum. Eight female smokers underwent an event-related functional magnetic resonance imaging (fMRI) paradigm presenting randomized sequences of smoking-related and non-smoking related pictures. Participants were asked to indicate by a key press the gender of individuals in smoking-related and non-smoking related pictures (gender discrimination task), to maintain and evaluate attention to the pictures. There was a significant effect of smoking condition on reaction times (RT) for a gender discrimination task intended to assess and maintain attention to the photographs-suggesting a deprivation effect of acute nicotine abstinence and a statistical trend indicating greater RTs for smoking cues than neutral cues. BOLD contrast (smoking vs. non-smoking cues) was greater in the non-abstinent vs. acutely abstinent conditions in the ventral striatum including the nucleus accumbens (VS/NAc). Moreover, a significant positive correlation was observed between baseline cigarette craving prior to scanning and VS/NAc activation (r=0.84, p=0.009), but only in the non-abstinent condition. These results may either be explained by ceiling effects of nicotine withdrawal in the abstinent condition or, may indicate reduced relative activation (smoking vs. neutral contrast) in the VS/NAc in the abstinent vs. non-abstinent conditions in this group of female smokers.

Fig. 1

Illustration of predicted blood-oxygen-level-dependent signal during a smoking cue reactivity paradigm. S smoking-related picture, N non-smoking/neutral picture, the fixation cross is present during the 1 s inter-stimulus intervals

Fig. 2

Mixed-effects group analyses of smokers in smoking and abstinent conditions. a Smoking condition, b Abstinent condition. Image depicts statistical maps using clusters determined by Z>2.3 and a corrected cluster significance level of p<0.05

Fig. 3

Activation within ventral striatum/nucleus accumbens anatomical mask. Statistical map of non-abstinent condition compared with abstinent condition within pre-defined VS/NAc anatomical masks. Activation is shown in blue. Activation clusters (in blue) represent group within-subjects mixed-effects analyses comparing average activation to smoking vs. neutral cues between non-abstinent and abstinent conditions. Thresholds were set at z-statistic of 2.0, p=0.05 uncorrected

Fig. 4

Ventral striatum/nucleus accumbens relative signal change by hemisphere and condition. Mean COPE (smoking vs. neutral stimulus contrast) within the ventral striatum including the nucleus accumbens (VS/NAc) for right and left hemispheres and both conditions (smoking and abstinent). Error bars represent the standard error of the relative activation (expressed as % signal change) for each hemisphere. Relative activation values were calculated within an anatomically-defined VS/NAc mask created with FSLview software as described in the text

Fig. 5

Tobacco craving and withdrawal during scanning. Craving (a) and withdrawal (b) prior to and following fMRI scans. Collapsed means ± SEs for both trials are provided

Fig. 6

Correlation of global VS/NAc relative signal change and tobacco craving in non-abstinent condition. Scatter plot of total score on the Shiffman-Jarvik Craving Scale prior to picture presentation averaged across both scanning sessions on the x-axis and mean bi-hemispheric relative activation (% signal change) averaged across both smoking sessions for the VS including the nucleus accumbens (VS/NAc) on the y-axis and best-fit regression line illustrating the correlation