Default mode network deactivation to smoking cue relative to food cue predicts treatment outcome in nicotine use disorder

Abstract

Identifying predictors of treatment outcome for nicotine use disorders (NUDs) may help improve efficacy of established treatments, like varenicline. Brain reactivity to drug stimuli predicts relapse risk in nicotine and other substance use disorders in some studies. Activity in the default mode network (DMN) is affected by drug cues and other palatable cues, but its clinical significance is unclear. In this study, 143 individuals with NUD (male n = 91, ages 18-55 years) received a functional magnetic resonance imaging scan during a visual cue task during which they were presented with a series of smoking-related or food-related video clips prior to randomization to treatment with varenicline (n = 80) or placebo. Group independent components analysis was utilized to isolate the DMN, and temporal sorting was used to calculate the difference between the DMN blood-oxygen-level dependent signal during smoke cues and that during food cues for each individual. Food cues were associated with greater deactivation compared with smoke cues in the DMN. In correcting for baseline smoking and other clinical variables, which have been shown to be related to treatment outcome in previous work, a less positive Smoke - Food difference score predicted greater smoking at 6 and 12 weeks when both treatment groups were combined (P = 0.005, β = -0.766). An exploratory analysis of executive control and salience networks demonstrated that a more positive Smoke - Food difference score for executive control network predicted a more robust response to varenicline relative to placebo. These findings provide further support to theories that brain reactivity to palatable cues, and in particular in DMN, may have a direct clinical relevance in NUD.

Keywords: default mode network; functional MRI; nicotine use disorder; smoking; treatment outcome; varenicline.

Figure 1

a. This figure shows the DMN component with each axial slice marked with a number representing the MNI z coordinate. Red indicates voxels which are more positively associated with the component (positive Z scores), and blue indicates voxels which are more negatively associated with this component (negative Z scores). b. This boxplot presents the results for the betas for the strength of the association of the DMN component with the smoke cues and the food cues separately. The upper and lower quartiles are represented by the box, and the median is represented by a black line within the box. The T bars extend to 1.5 times the height of the box or, if no case had a value in that range, to the minimum or maximum values. Circles represent outliers.

Figure 1

a. This figure shows the DMN component with each axial slice marked with a number representing the MNI z coordinate. Red indicates voxels which are more positively associated with the component (positive Z scores), and blue indicates voxels which are more negatively associated with this component (negative Z scores). b. This boxplot presents the results for the betas for the strength of the association of the DMN component with the smoke cues and the food cues separately. The upper and lower quartiles are represented by the box, and the median is represented by a black line within the box. The T bars extend to 1.5 times the height of the box or, if no case had a value in that range, to the minimum or maximum values. Circles represent outliers.

Figure 2

This figure demonstrates a simple scatter plot showing the relationship between the beta for the strength of the association of the DMN component with the smoke versus food cues (Smoke - Food) and total number of cigarettes smoked in the 28 days prior to the week 6 visit (NumCig at 6 weeks).