A MR-based study employed diffusion tensor imaging (DTI) and voxel based morphometry to assess microstructural integrity and morphology, respectively, of the corpus callosum in middle aged chronic smokers [82]. Contrary to expectations, smokers demonstrated higher fractional anisotropy (FA; higher FA values are considered to reflect greater microstructural integrity [83,84]) in the body and total corpus callosum than did NSC and no volume differences were observed between smokers and NSC in the corpus callosum. However, smokers with high levels of nicotine dependence (as reflected by scores on the Fagerstrom Test for Nicotine Dependence) had significantly lower FA values than both smokers with low levels of nicotine dependence and NSC. It is widely recognized from population-based studies, with middle-aged and older adults, that chronic smoking is associated with increased incidence of regional white matter (WM) signal hyperintensities on standard MR imaging (e.g., T2-weighted and FLAIR) [85–89]. WM hyperintensities are associated with decreased cerebral blood perfusion [90,91] and neurocognitive dysfunction [92,93]. Overall, the degree of smoking-related morphological changes observed appears to be contingent on the method and brain region under consideration.