Abnormal Insula White Matter Fiber Tracts in Nicotine Addiction

Abstract

Nicotine addiction is characterized as a neural circuit dysfunction, particularly with regard to the alterations in central reward pathways. The insula, a cortical region that is thought to play a central role in this reward circuitry, has been implicated as an important role in the maintenance of nicotine addiction. However, it remains largely unclear about the differences in white-matter diffusion properties of insula circuits between nicotine-dependent smokers and nonsmokers. Moreover, few studies have examined whether smoking relapse is related to white-matter diffusion properties of insula circuits. Here, a total of 58 smokers and 34 nonsmokers were enrolled. After a 12-week smoking cessation treatment, 38 smokers relapsed, 20 did not relapse. Diffusion tensor imaging and probabilistic tractography was used to investigate the white-matter tracts of insula circuits in this study. Relative to nonsmokers, in the left hemisphere, smokers showed lower fractional anisotropy (FA) in the anterior insula cortex-to-nucleus accumbens and posterior insula cortex-to-nucleus accumbens fiber tracts, suggesting decreased white-matter integrity in these insula tracts; in the right hemisphere, smokers showed higher FA, and lower axial (AD), radial (RD), and mean diffusivity (MD) in the anterior insula cortex-to-medial orbitofrontal cortex, posterior insula cortex-to-medial orbitofrontal cortex, and posterior insula cortex-to-nucleus accumbens fiber tracts, suggesting excessive myelination and axonal loss in these insula tracts. However, there were no differences of FA, AD, MD and RD values between relapsers and nonrelapsers. These altered insula microstructural connectivity could interfere with the normal neural circuitry of reward processing. The present study clarifies the precise roles of insula white-matter microstructures in nicotine addiction, which provides new insights into the underlying neurobiology of nicotine addiction. Funding: This research was supported by Zhejiang Provincial Natural Science Foundation of China under Grant No. LQ18H180001, Zhejiang Medicine Health Science and Technology Program under Grant nos.2017KY080 and 2018KY418, National Natural Science Foundation of China under Grant nos. 81171310 and 81701647. YY was supported by the Intramural Research Program of the National Institute on Drug Abuse, the National Institutes of Health. Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: All the procedures were reviewed and approved by the Institutional Review Boards of the Second Affiliated Hospital of Zhejiang University School of Medicine, and all the procedures were carried out in accordance with the approved guidelines.