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

  • Chao WangEmail author
  • Zhujing Shen
  • Peiyu Huang
  • Wei Qian
  • Cheng Zhou
  • Kaicheng Li
  • Qingze Zeng
  • Xiao Luo
  • Quanquan Gu
  • Hualiang Yu
  • Yihong Yang
  • Minming ZhangEmail author
Original Research
  • 36 Downloads

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.

Keywords

Anterior insula Resting state functional connectivity Nicotine dependence Smoking cessation 

Notes

Funding information

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 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.CrossRefGoogle Scholar
  2. 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.CrossRefGoogle Scholar
  3. 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.CrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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
  6. Cahill, K., Stead, L. F., & Lancaster, T. (2010). Nicotine receptor partial agonists for smoking cessation. The Cochrane Database of Systematic Reviews, (12), CD006103.Google Scholar
  7. 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.CrossRefGoogle Scholar
  8. 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
  9. 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.CrossRefGoogle Scholar
  10. 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.CrossRefGoogle Scholar
  11. 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
  12. 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.CrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.CrossRefGoogle Scholar
  16. 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.CrossRefGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 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.CrossRefGoogle Scholar
  21. 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.CrossRefGoogle Scholar
  22. 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.CrossRefGoogle Scholar
  23. 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.CrossRefGoogle Scholar
  24. 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.CrossRefGoogle Scholar
  25. 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.CrossRefGoogle Scholar
  26. 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.CrossRefGoogle Scholar
  27. 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.CrossRefGoogle Scholar
  28. 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.CrossRefGoogle Scholar
  29. 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 Sciences 1316: 53–70.Google Scholar
  30. Niaura, R., Jones, C., & Kirkpatrick, P. (2006). Varenicline. Nature Reviews Drug Discovery, 5(7), 537–538.CrossRefGoogle Scholar
  31. 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.CrossRefGoogle Scholar
  32. 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.CrossRefGoogle Scholar
  33. 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.CrossRefGoogle Scholar
  34. 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.CrossRefGoogle Scholar
  35. Scott, D., & Hiroi, N. (2011). Deconstructing craving: Dissociable cortical control of cue reactivity in nicotine addiction. Biological Psychiatry, 69(11), 1052–1059.CrossRefGoogle Scholar
  36. 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.CrossRefGoogle Scholar
  37. 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.CrossRefGoogle Scholar
  38. 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.CrossRefGoogle Scholar
  39. 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.CrossRefGoogle Scholar
  40. Uddin, L. Q. (2015). Salience processing and insular cortical function and dysfunction. Nature Reviews Neuroscience, 16(1), 55–61.CrossRefGoogle Scholar
  41. 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.CrossRefGoogle Scholar
  42. 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.CrossRefGoogle Scholar
  43. 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
  44. 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.CrossRefGoogle Scholar
  45. 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.
  46. Zhang, D., & Raichle, M. E. (2010). Disease and the brain's dark energy. Nature Reviews Neurology, 6(1), 15–28.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Radiology, the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  2. 2.Department of Psychiatry, the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina
  3. 3.Neuroimaging Research Branch, National Institute on Drug AbuseNational Institutes of HealthBaltimoreUSA

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