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


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.


Anterior insula Resting state functional connectivity Nicotine dependence Smoking cessation 


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.


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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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