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Increased interregional functional connectivity of anterior insula is associated with improved smoking cessation outcome

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Abstract

Damage to the insular cortex has been shown to disrupt smoking behavior. However, whether smoking cessation outcomes are associated with abnormal functions of insula and its subregions remains unclear. In this study, we investigated the relationship between insular functions (interregional functional connectivity and regional activity) and treatment outcomes of cigarette smoking. Thirty treatment-seeking smokers were recruited into the treatment study and underwent magnetic resonance imaging (MRI) scans immediately before and after the treatment. Sixteen participants remained abstinent from smoking (quitters), while 14 relapsed to smoking (relapers). Changes in resting-state functional connectivity and fractional amplitude of low frequency fluctuation (fALFF) across groups and visits were assessed using repeated measures ANCOVA. Significant interaction effects were detected: 1) between the left anterior insula and left precuneus; and 2) between the right anterior insula and left precuneus and medial frontal gyrus. Post-hoc region-of-interest analyses in brain areas showing interaction effects indicated significantly increased functional connectivity after treatment compared with before treatment in quitters but opposite longitudinal changes in relapsers. However, no significant effects in fALFF were observed. These novel findings suggest that increased interregional functional connectivity of the anterior insula is associated with improved smoking cessation outcome: individuals with increased functional connectivity of the anterior insula during the treatment would more likely quit smoking successfully. These insular circuits may serve as therapeutic targets for more efficacious treatment of nicotine addiction.

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References

  • Abdolahi, A., Williams, G. C., Benesch, C. G., Wang, H. Z., Spitzer, E. M., Scott, B. E., et al. (2015). Damage to the insula leads to decreased nicotine withdrawal during abstinence. Addiction (Abingdon, England), 110(12), 1994–2003.

    Google Scholar 

  • Addicott, M. A., Sweitzer, M. M., Froeliger, B., Rose, J. E., & McClernon, F. J. (2015). Increased functional connectivity in an insula-based network is associated with improved smoking cessation outcomes. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 40(11), 2648–2656.

    Google Scholar 

  • Bi, Y., Yuan, K., Guan, Y., Cheng, J., Zhang, Y., Li, Y., et al. (2017). Altered resting state functional connectivity of anterior insula in young smokers. Brain Imaging and Behavior, 11(1), 155–165.

    PubMed  Google Scholar 

  • Brody, A. L., Mandelkern, M. A., London, E. D., Childress, A. R., Lee, G. S., Bota, R. G., et al. (2002). Brain metabolic changes during cigarette craving. Archives of General Psychiatry, 59(12), 1162–1172.

    PubMed  Google Scholar 

  • Buhle, J. T., Silvers, J. A., Wager, T. D., Lopez, R., Onyemekwu, C., Kober, H., et al. (2014). Cognitive reappraisal of emotion: A meta-analysis of human neuroimaging studies. Cerebral cortex (New York, NY : 1991), 24(11), 2981–2990.

    Google Scholar 

  • Cahill, K., Stead, L. F., & Lancaster, T. (2010). Nicotine receptor partial agonists for smoking cessation. The Cochrane Database of Systematic Reviews, (12), CD006103.

  • Cauda, F., D'Agata, F., Sacco, K., Duca, S., Geminiani, G., & Vercelli, A. (2011). Functional connectivity of the insula in the resting brain. NeuroImage, 55(1), 8–23.

    PubMed  Google Scholar 

  • Chang, L. J., Yarkoni, T., Khaw, M. W., & Sanfey, A. G. (2013). Decoding the role of the insula in human cognition: Functional parcellation and large-scale reverse inference. Cerebral cortex (New York, NY : 1991), 23(3), 739–749.

    Google Scholar 

  • Chen, Z., Peto, R., Zhou, M., Iona, A., Smith, M., Yang, L., et al. (2015). Contrasting male and female trends in tobacco-attributed mortality in China: Evidence from successive nationwide prospective cohort studies. Lancet (London, England), 386(10002), 1447–1456.

    Google Scholar 

  • Craig, A. D. (2002). How do you feel? Interoception: The sense of the physiological condition of the body. Nature Reviews Neuroscience, 3(8), 655–666.

    CAS  PubMed  Google Scholar 

  • Deen, B., Pitskel, N. B., & Pelphrey, K. A. (2011). Three systems of insular functional connectivity identified with cluster analysis. Cerebral cortex (New York, NY : 1991), 21(7), 1498–1506.

    Google Scholar 

  • Dinur-Klein, L., Dannon, P., Hadar, A., Rosenberg, O., Roth, Y., Kotler, M., et al. (2014). Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: A prospective, randomized controlled trial. Biological Psychiatry, 76(9), 742–749.

    PubMed  Google Scholar 

  • Dosenbach, N. U., Fair, D. A., Miezin, F. M., Cohen, A. L., Wenger, K. K., Dosenbach, R. A., et al. (2007). Distinct brain networks for adaptive and stable task control in humans. Proceedings of the National Academy of Sciences of the United States of America, 104(26), 11073–11078.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Engelmann, J. M., Versace, F., Robinson, J. D., Minnix, J. A., Lam, C. Y., Cui, Y., et al. (2012). Neural substrates of smoking cue reactivity: A meta-analysis of fMRI studies. NeuroImage, 60(1), 252–262.

    PubMed  Google Scholar 

  • Fagerstrom, K. O., & Schneider, N. G. (1989). Measuring nicotine dependence: A review of the Fagerstrom tolerance questionnaire. Journal of Behavioral Medicine, 12(2), 159–182.

    CAS  PubMed  Google Scholar 

  • Hayashi, T., Ko, J. H., Strafella, A. P., & Dagher, A. (2013). Dorsolateral prefrontal and orbitofrontal cortex interactions during self-control of cigarette craving. Proceedings of the National Academy of Sciences of the United States of America, 110(11), 4422–4427.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Honey, C. J., Kotter, R., Breakspear, M., & Sporns, O. (2007). Network structure of cerebral cortex shapes functional connectivity on multiple time scales. Proceedings of the National Academy of Sciences of the United States of America, 104(24), 10240–10245.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Janes, A. C., Pizzagalli, D. A., Richardt, S., de, B. F. B., Chuzi, S., Pachas, G., et al. (2010). Brain reactivity to smoking cues prior to smoking cessation predicts ability to maintain tobacco abstinence. Biological Psychiatry, 67(8), 722–729.

    PubMed  PubMed Central  Google Scholar 

  • Kalivas, P. W., & Volkow, N. D. (2005). The neural basis of addiction: A pathology of motivation and choice. The American Journal of Psychiatry, 162(8), 1403–1413.

    PubMed  Google Scholar 

  • Kelly, C., Toro, R., Di Martino, A., Cox, C. L., Bellec, P., Castellanos, F. X., et al. (2012). A convergent functional architecture of the insula emerges across imaging modalities. NeuroImage, 61(4), 1129–1142.

    PubMed  PubMed Central  Google Scholar 

  • Kober, H., Mende-Siedlecki, P., Kross, E. F., Weber, J., Mischel, W., Hart, C. L., et al. (2010). Prefrontal-striatal pathway underlies cognitive regulation of craving. Proceedings of the National Academy of Sciences of the United States of America, 107(33), 14811–14816.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Larson-Prior, L. J., Zempel, J. M., Nolan, T. S., Prior, F. W., Snyder, A. Z., & Raichle, M. E. (2009). Cortical network functional connectivity in the descent to sleep. Proceedings of the National Academy of Sciences of the United States of America, 106(11), 4489–4494.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li, X., Hartwell, K. J., Borckardt, J., Prisciandaro, J. J., Saladin, M. E., Morgan, P. S., et al. (2013). Volitional reduction of anterior cingulate cortex activity produces decreased cue craving in smoking cessation: A preliminary real-time fMRI study. Addiction Biology, 18(4), 739–748.

    PubMed  Google Scholar 

  • Menon, V., & Uddin, L. Q. (2010). Saliency, switching, attention and control: A network model of insula function. Brain Structure & Function, 214(5–6), 655–667.

    Google Scholar 

  • Mesulam, M. M., & Mufson, E. J. (1982a). Insula of the old world monkey. I. Architectonics in the insulo-orbito-temporal component of the paralimbic brain. The Journal of Comparative Neurology, 212(1), 1–22.

    CAS  PubMed  Google Scholar 

  • Mesulam, M. M., & Mufson, E. J. (1982b). Insula of the old world monkey. III: Efferent cortical output and comments on function. The Journal of Comparative Neurology, 212(1), 38–52.

    CAS  PubMed  Google Scholar 

  • Naqvi, N. H., & Bechara, A. (2010). The insula and drug addiction: An interoceptive view of pleasure, urges, and decision-making. Brain Structure & Function, 214(5–6), 435–450.

    Google Scholar 

  • Naqvi, N. H., Rudrauf, D., Damasio, H., & Bechara, A. (2007). Damage to the insula disrupts addiction to cigarette smoking. Science (New York, N.Y.), 315(5811), 531–534.

    CAS  Google Scholar 

  • Naqvi NH, Gaznick N, Tranel D, Bechara A (2014). The insula: a critical neural substrate for craving and drug seeking under conflict and risk. Annals of the New York Academy of Sciences1316: 53–70.

  • Niaura, R., Jones, C., & Kirkpatrick, P. (2006). Varenicline. Nature Reviews Drug Discovery, 5(7), 537–538.

    CAS  PubMed  Google Scholar 

  • Picard, F., Sadaghiani, S., Leroy, C., Courvoisier, D. S., Maroy, R., & Bottlaender, M. (2013). High density of nicotinic receptors in the cingulo-insular network. NeuroImage, 79, 42–51.

    CAS  PubMed  Google Scholar 

  • Power, J. D., Barnes, K. A., Snyder, A. Z., Schlaggar, B. L., & Petersen, S. E. (2012). Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. NeuroImage, 59(3), 2142–2154.

    Google Scholar 

  • Power, J. D., Mitra, A., Laumann TO, Snyder, A. Z., Schlaggar, B. L., & Petersen, S. E. (2014). Methods to detect, characterize, and remove motion artifact in resting state fMRI. NeuroImage, 84, 320–341.

    PubMed  Google Scholar 

  • Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001). A default mode of brain function. Proceedings of the National Academy of Sciences of the United States of America, 98(2), 676–682.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Scott, D., & Hiroi, N. (2011). Deconstructing craving: Dissociable cortical control of cue reactivity in nicotine addiction. Biological Psychiatry, 69(11), 1052–1059.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., et al. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. The Journal of neuroscience : the official journal of the Society for Neuroscience, 27(9), 2349–2356.

    CAS  Google Scholar 

  • Sridharan, D., Levitin, D. J., & Menon, V. (2008). A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks. Proceedings of the National Academy of Sciences of the United States of America, 105(34), 12569–12574.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stoeckel, L. E., Chai, X. J., Zhang, J., Whitfield-Gabrieli, S., & Evins, A. E. (2016). Lower gray matter density and functional connectivity in the anterior insula in smokers compared with never smokers. Addiction Biology, 21(4), 972–981.

    PubMed  Google Scholar 

  • Sutherland, M. T., McHugh, M. J., Pariyadath, V., & Stein, E. A. (2012). Resting state functional connectivity in addiction: Lessons learned and a road ahead. NeuroImage, 62(4), 2281–2295.

    PubMed  PubMed Central  Google Scholar 

  • Uddin, L. Q. (2015). Salience processing and insular cortical function and dysfunction. Nature Reviews Neuroscience, 16(1), 55–61.

    CAS  PubMed  Google Scholar 

  • Wang, C., Shen, Z., Huang, P., Yu, H., Qian, W., Guan, X., et al. (2017). Altered spontaneous brain activity in chronic smokers revealed by fractional ramplitude of low-frequency fluctuation analysis: A preliminary study. Scientific Reports, 7(1), 328.

    PubMed  PubMed Central  Google Scholar 

  • Wang, C., Huang, P., Shen, Z., Qian, W., Li, K., Luo, X., et al. (2019). Gray matter volumes of insular subregions are not correlated with smoking cessation outcomes but negatively correlated with nicotine dependence severity in chronic smokers. Neuroscience Letters, 696, 7–12.

    CAS  PubMed  Google Scholar 

  • Whitney, C., Kirk, M., O'Sullivan, J., Lambon Ralph, M. A., & Jefferies, E. (2011). The neural organization of semantic control: TMS evidence for a distributed network in left inferior frontal and posterior middle temporal gyrus. Cerebral cortex (New York, NY : 1991), 21(5), 1066–1075.

    Google Scholar 

  • Wu, G., Yang, S., Zhu, L., & Lin, F. (2015). Altered spontaneous brain activity in heavy smokers revealed by regional homogeneity. Psychopharmacology, 232(14), 2481–2489.

    CAS  PubMed  Google Scholar 

  • Yan, C. G., Wang, X. D., Zuo, X. N., Zang, Y. F. (2016). DPABI: Data Processing & Analysis for (Resting-State) Brain Imaging. Neuroinformatics 14, 339–351. https://doi.org/10.1007/s12021-016-9299-4.

  • Zhang, D., & Raichle, M. E. (2010). Disease and the brain's dark energy. Nature Reviews Neurology, 6(1), 15–28.

    PubMed  Google Scholar 

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Funding

This research was supported by Zhejiang Provincial Natural Science Foundation of China under Grant No. LQ18H180001, Zhejiang Medicine and Health Science and Technology Program under Grant nos.2017KY080 and 2018KY418, National Natural Science Foundation of China under Grant nos. 81,171,310 and 81,701,647. YY was supported by the Intramural Research Program of the National Institute on Drug Abuse, the National Institutes of Health.

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Authors and Affiliations

  1. Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Chao Wang, Zhujing Shen, Peiyu Huang, Wei Qian, Cheng Zhou, Kaicheng Li, Qingze Zeng, Xiao Luo, Quanquan Gu & Minming Zhang

  2. Department of Psychiatry, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    Hualiang Yu

  3. Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA

    Yihong Yang

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  1. Chao Wang
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  2. Zhujing Shen
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Correspondence to Chao Wang or Minming Zhang.

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Wang, C., Shen, Z., Huang, P. et al. Increased interregional functional connectivity of anterior insula is associated with improved smoking cessation outcome. Brain Imaging and Behavior 14, 408–415 (2020). https://doi.org/10.1007/s11682-019-00197-2

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