Synopsis

This study investigated the activation of brain regions to visual smoking cues in smokers before and after cessation treatment using an event-related design fMRI. The result demonstrated that smokers will have good tolerance to smoking-related stimuli after using varenicline. This may explain why the curative effect of varenicline is better than NRT which has been related to an increased the brain response. The results provide further evidence for medication choice of clinicians for smoking cessation.

Abstract

Purpose: Smoking is an addictive disease that can easily relapse. Even if the physiological addiction has been lifted, smoking-related cues may induce psychological addiction and thus cause relapse. Smokers’ brain reactivity to smoking-related cues may play an important role in smoking addiction and the maintenance of smoking cessation status. Several previous studies have examined smokers’ brain response to smoking-related images in different status, such as in nicotine abstinence status and in resting status after cessation^1,2. However, little is known about the changes in brain responses caused by smoking cessation treatment. Therefore we performed the current study aiming to evaluate the differences in patterns of spontaneous brain activity before and after smoking cessation treatment by using varenicline, a nicotinic receptor blocker.

Methods: Data were collected using a MAGNETOM Prisma 3T MR scanner with a 64-channel head coil from a total of 23 smokers (18 males and 5 females). They aged mean 23-40 years, with the mean (standard deviation, SD) age as 30.7 (4.2) years, when the study was performed. We used an event-related design functional magnetic resonance imaging (fMRI) to quantify the responses of subjects to three different types of images, namely smoking-related images, neutral images and mosaic images(Figure 1). The latter two were used as controls to reveal the response directly related to smoking cues. The scan parameters were as follow: TR/TE=3000/30 ms; total slices=33; slice thickness=3.5 mm; flip angle=90°; in-plane voxel size=3.5×3.5×3.5 mm3; Measurements=201; total acquisition time=10:11 min. Images were displayed in random order and subjects were asked to click on a response key when they saw the images. All subjects were scanned immediately before and 1 month after varenicline treatment. The data were processed using SPM12 which included bias correction, tissue classification, and data registration. One-sample T-test was performed to compare brain activation stimulated by different types of images with no task status separately, before and after cessation treatment (p<0.01 was considered significant).

Results: We found that neutral images activated the least brain area, while the other two kinds of images both led to obvious activation regions. However, only the activation area of smoking-related images was significantly reduced after smoking cessation, especially in areas of grey matter of cerebellum, superior occipital gyrus, insula, superior temporal gyrus, posterior cingulate, anterior cingulate and thalamus (Table 1-3; Figure 2).

Discussion: Previous findings suggest that brain reactivity of smokers to smoking-related images was increased in emotional processing regions which including the frontal and anterior cingulate cortex^3,4, visuospatial processing regions which including parietal and occipital cortices^5,6. This is consistent with our findings. Previous research has found that brain activation stimulated by smoking-related images increased obviously in abstinence status induced by nicotine replacement therapy (NRT)². Prefrontal, anterior and posterior cingulate, temporal, parietal cortex, and caudate nucleus were all more pronounced activation than pre-quit state. Those regions are known to be responsible for the action planning, habit learning, and craving and activation enhancement of these areas could increase relapse vulnerability^7-12. Such impact of NRT treatment is reasonable because NRT is a kind of harm reduction treatment, but not fundamentally addiction treatment. On the other hands, as a nicotinic receptor blocker, varenicline can significantly reduce smokers’ euphoric feeling from smoking, therefore facilitate smoking cessation. Our fMRI results also show that brain activity in areas in charge of habit learning, action planning and craving from smokers treated with varenicline to smoking cues was reduced, in contrast to the impact of NRT treatment. Such reduction is very important from the maintenance of smoking cessation status, may explain why smoking cessation efficacy of varenicline is significantly higher than that of NRT^13-16. We used mosaic images as another control to compare brain’s response to smoking and non-smoking related cues before and after treatment. The brain activation by mosaic images is obvious than neutral images and that might be related to the unclarity and meaningless of the images which stimulate the brain to explore and analyze. But this activation did not change significantly before and after smoking cessation, that was same as neutral image group.

Conclusions: These data suggest that compare to control groups, smoking-related images can obviously activate brain areas involved in action planning, habit learning, and craving processing. Using varenicline can reduce smokers’ response to smoking stimuli, which relate to its pharmacological mechanism and contribute to better therapeutic effect of smoking cessation.

Acknowledgements

References

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