BackgroundTobacco use remains the most preventable cause of death; however, its effects on the brain, and particularly white matter, remain elusive. Previous diffusion tensor imaging (DTI) studies have failed to yield consistent findings, with some reporting elevated measures of fractional anisotropy (FA) and others reporting lowered FA. MethodsIn our study, we sought to elucidate the effects of tobacco on white matter by using enhanced imaging acquisition parameters and multiple analysis methods, including tract-based spatial statistics (TBSS) with crossing fiber measures and probabilistic tractography. ResultsOur TBSS results revealed that chronic cigarette smokers have decreased FA in corpus callosum and bilateral anterior internal capsule, as well as specific reduced anisotropy in the two major fiber directions in a crossing fiber model. Further, our tractography results indicated that smokers have decreased FA in tracts projecting to the frontal cortex from (1) nucleus accumbens, (2) habenula, and (3) motor cortex. We also observed that smokers have greater disruptions in those regions when they had recently smoked compared to when they abstained from smoking for 24h. Our results also support previous evidence showing hemispheric asymmetry, with greater damage to the left side compared to the right. ConclusionsThese findings provide more conclusive evidence of white matter disruptions caused by nicotine use. By better understanding the neural disruptions correlating with cigarette smoking we can elucidate the addictive course and explore targeted treatment regimens for nicotine dependence.