Abstract
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.
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Data availability
All self-report, toxicology, and summary fMRI data discussed in this manuscript, as well as the code used for statistical analyses, are publicly available from the Open Science Framework web site under project title, “Functional connectivity of the anterior insula during withdrawal from cigarette smoking” (https://osf.io/89ph5).
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Acknowledgements
The authors would like to thank Ms. Andrea Donis, Ms. Diana Paez, Ms. Citlaly Cahuantzi, Ms. Tinisha Sakhrani, and Mr. Hector Diaz, whose contribution to data collection helped make this work possible.
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All authors were involved in designing the study and contributed to writing the manuscript and have reviewed and approved the final version of this manuscript. DGG and MPD acquired the data. J-BP, DGG, and MPD were primarily responsible for data analysis. DGG, J-BP, and EDL drafted the manuscript. As principal investigator of the study, EDL is accountable for all aspects of the work, including its accuracy and integrity.
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Ghahremani, D.G., Pochon, JB., Perez Diaz, M. et al. Functional connectivity of the anterior insula during withdrawal from cigarette smoking. Neuropsychopharmacol. 46, 2083–2089 (2021). https://doi.org/10.1038/s41386-021-01036-z
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DOI: https://doi.org/10.1038/s41386-021-01036-z
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