White matter microstructure and hemispheric asymmetry alterations in adults who smoke: a connectome-based analysis

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 (WM) microstructure and the architecture of structural brain networks in adults.

We used diffusion tensor imaging to compare fractional anisotropy between participants who smoke (n = 122) and non-smoking control participants (n = 55) to detect WM 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 WM connections that may serve as biomarkers for distinguishing individuals who smoke from those who do not.

Participants who smoke showed widespread WM 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.

Nicotine dependence is associated with extensive alterations in WM 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.

This study enhances our understanding of how nicotine dependence reshapes WM networks, potentially impairing communication within circuits sustaining addictive behaviors, and provide insights into how smoking alters brain structure and connectivity.