Background: Although most cigarette smokers want to quit, current cessation therapies have limited effectiveness. Preventing relapse is limited by insufficient understanding of the neural pathways that are triggered during relapse. With recent advances in functional connectivity analysis, functional magnetic resonance imaging (fMRI) studies offer the ability to better neural functional connectivity during relapse. This study is the first to explore functional connectivity with smoking being immediately possible. We hope allowing participants to smoke in the scanner allows for more accurate simulation of true relapse settings.
Methods: Participants (n=50) abstained from smoking for 24 hours. These abstinent smokers underwent a brain fMRI while viewing a series of smoking-related and neutral photos. A colored photo border indicated to participants if they could smoke. Halfway through the images, the participants smoked a cigarette in the MRI scanner using a MRI compatible device. After smoking, the participants continued this picture viewing task. Psychophysiological Interaction (PPI) analysis was performed to analyze functional connectivity. This analysis correlated neural activity to map which regions of the brain fired together. By coupling PPI analysis with our cigarette picture viewing task, we determined which brain regions fired together when nicotine deprived smokers viewed cigarette stimuli and how these neural pathways changed after smoking.
Results: During cigarette relapse, there were Smoking Possible x Cue Type interactions in functional connectivity between the anterior cingulate cortex and superior medial gyrus in the post-smoke block, the nucleus accumbens and the right superior orbital gyrus in the pre-smoke block, and the caudate and left middle temporal gyrus, bilateral superior temporal gyrus, right inferior temporal gyrus, left inferior parietal lobe, and cerebellum in the pre-smoke block (p<.005, volume > 756 mm^3). These Smoking Possible x Cue Type interactions showed that the degree of connectivity between the listed brain regions changed with smoking being possible and with the type of picture presented (cigarette vs neutral). Prior to smoking, these brain regions were more functionally connected while viewing neutral pictures. After smoking, these brain regions were more functionally connected while viewing cigarette-related pictures.
Conclusions: During pre-smoking blocks, the possibility of smoking altered traditional cue reactivity. In the post-smoking block, traditional cue-reactivity was seen. Being presented with an opportunity to smoke seems to dysregulate neural reward systems, the function of which is restored by smoking. Notably, this reward dysregulation is seen in neural connections between the caudate nucleus and five connected regions- left middle temporal gyrus, bilateral superior temporal gyrus, right inferior temporal gyrus, left inferior parietal lobe, and cerebellum.