Functional connectivity of the anterior insula during withdrawal from cigarette smoking

Currently available therapies for smoking cessation have limited efficacy, and potential treatments that target specific brain regions are under evaluation, with a focus on the insula. The ventral and dorsal anterior subregions of the insula serve distinct functional networks, yet our understanding of how these subregions contribute to smoking behavior is unclear. Resting-state functional connectivity (RSFC) provides a window into network-level function associated with smoking-related internal states. The goal of this study was to determine potentially distinct relationships of ventral and dorsal anterior insula RSFC with cigarette withdrawal after brief abstinence from smoking. Forty-seven participants (24 women; 18-45 years old), who smoked cigarettes daily and were abstinent from smoking overnight (~12 h), provided self-reports of withdrawal and underwent resting-state fMRI before and after smoking the first cigarette of the day. Correlations between withdrawal and RSFC were computed separately for ventral and dorsal anterior insula seed regions in whole-brain voxel-wise analyses. Withdrawal was positively correlated with RSFC of the right ventral anterior insula and dorsal anterior cingulate cortex (dACC) before but not after smoking. The correlation was mainly due to a composite effect of craving and physical symptoms of withdrawal. These results suggest a role of right ventral anterior insula-dACC connectivity in the internal states that maintain smoking behavior (e.g., withdrawal) and present a specific neural target for brain-based therapies seeking to attenuate withdrawal symptoms in the critical early stages of smoking cessation.