Ventral striatum/nucleus accumbens activation to smoking-related pictorial cues in smokers and nonsmokers: a functional magnetic resonance imaging study

Abstract

Background: Converging evidence from several theories of the development of incentive-sensitization to smoking-related environmental stimuli suggests that the ventral striatum plays an important role in the processing of smoking-related cue reactivity.

Methods: Twenty-six healthy right-handed volunteers (14 smokers and 12 nonsmoking controls) underwent functional magnetic resonance imaging (fMRI) during which neutral and smoking-related images were presented. Region of interest analyses were performed within the ventral striatum/nucleus accumbens (VS/NAc) for the contrast between smoking-related (SR) and nonsmoking related neutral (N) cues.

Results: Group activation for SR versus N cues was observed in smokers but not in nonsmokers in medial orbitofrontal cortex, superior frontal gyrus, anterior cingulate cortex, and posterior fusiform gyrus using whole-brain corrected Z thresholds and in the ventral VS/NAc using uncorrected Z-statistics (smokers Z = 3.2). Region of interest analysis of signal change within ventral VS/NAc demonstrated significantly greater activation to SR versus N cues in smokers than controls.

Conclusions: This is the first demonstration of greater VS/NAc activation in addicted smokers than nonsmokers presented with smoking-related cues using fMRI. Smokers, but not controls, demonstrated activation to SR versus N cues in a distributed reward signaling network consistent with cue reactivity studies of other drugs of abuse.

Figure 1

Mixed-effects group analysis in smokers. Group statistical map of three activation clusters within the mixed-effects group analysis of smokers only. Color of clusters corresponds to increasing Z-statistic from dark to light yellow. Structural image is a group-averaged T1 structural scan from all subjects in the study registered to standard space. (A) Clusters for lingual gyrus (LG), anterior cingulate gyrus (ACC), and orbitofrontal gyrus (OFC) are indicated with white arrows in sagittal slice (x = +12). (B) Bilateral ACC activation in axial slice (z = +2). (C) Bilateral ACC, OFC, and left superior frontal gyrus (SFG) activation in coronal slice (y = +42).

Figure 2

Region of interest analysis of ventral striatum in smokers. Voxel-wise region of interest analysis of ventral striatum in smokers (n = 9) in coronal (A) and axial views (B). Color of activation clusters corresponds to increasing Z-statistic from dark to light blue. Analysis was restricted to a bilateral anatomical mask of the ventral striatum (C) at an uncorrected Z-statistic threshold of 2.3.

Figure 3

Differences between smokers and nonsmokers in activation to smoking – neutral cues in ventral striatum. Scatter plot comparing smokers and nonsmokers in contrast of the parameter estimates (COPE) for smoking versus neutral picture cues. Region of interest analysis performed was within a bilateral mask of ventral striatum/nucleus accumbens (VS/NAc) (Figure 2).