White Matter Microstructure and Hemispheric Asymmetry Alterations in Adults Who Smoke: A Connectome-Based Analysis

Introduction Cigarette smoking poses a pervasive health risk increasingly recognized for its impact on the nervous system, yet its effects on brain structure and organization remain incompletely understood. This study examined how smoking addiction influences white matter microstructure and the architecture of structural brain networks in adults. Methods We used diffusion tensor imaging to compare fractional anisotropy between participants who smoke (n = 122) and non-smoking control participants (n = 55) to detect white matter abnormalities. Whole-brain structural connectomes were constructed, with connections categorized by fiber length. Network features quantified included degree centrality and hemispheric asymmetry. Adaptive Best-Subset Selection method was applied to identify white matter connections that may serve as biomarkers for distinguishing individuals who smoke from those who do not. Results Participants who smoke showed widespread white matter alterations in pathways related to reward valuation, habit formation, and craving, along with abnormalities in both short- and medium-range connections. Reduced rightward asymmetry in the cuneus indicated lateralized structural changes possibly linked to cue processing in nicotine dependence. Discriminative connections involved orbitofrontal, sensorimotor, and visual regions, underscoring how smoking reshapes brain networks supporting reward valuation, motor control, and cue reactivity. Conclusions Nicotine dependence is associated with extensive alterations in white matter microstructure and network organization, including reduced hemispheric asymmetry. These findings suggest that smoking affects structural connectivity in circuits involved in emotional regulation and reward-related memory.