Abnormal white matter tracts of insula in smokers

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 in the maintenance of nicotine addiction. However, it remains largely unclear about the white matter (WM) microstructural alterations of insula in nicotine addiction and whether the WM alterations of insula could predict smoking cessation outcomes. In this study, 58 male nicotine-dependent smokers and 34 matched male nonsmoking controls were recruited. After a 12-week smoking cessation treatment with varenicline, 38 smokers relapsed, and 20 did not relapse. Diffusion tensor imaging and probabilistic tractography were used to investigate the differences of WM tracts of insula between smokers and nonsmokers. Relative to nonsmokers, in the left hemisphere, smokers showed lower fractional anisotropy (FA) in the fiber tracts of anterior insula cortex-to-nucleus accumbens and posterior insula cortex-to-nucleus accumbens; in the right hemisphere, smokers showed higher FA, and lower axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) in the fiber tracts of anterior insula cortex-to-medial orbitofrontal cortex, posterior insula cortex-to-medial orbitofrontal cortex, and posterior insula cortex-to-nucleus accumbens. However, there were no differences of WM diffusion properties between relapsers and nonrelapsers. This study is the first using probabilistic tractography to exclusively clarify the precise roles of insular WM tracts in smokers, which may provide new insights into the underlying neurobiology of nicotine addiction.