Sex Differences in Alterations of Brain Functional Network in Tobacco Use Disorder

Introduction: Many studies have found sex differences in alterations of brain function in cigarette-smoking adults from the perspective of functional activity or connectivity. However, no studies have systematically found different alteration patterns in brain functional topology of cigarette-smoking men and women from three perspectives: nodal and network efficiency and modular connections. Aims and Methods: Fifty-six tobacco use disorder (TUD) participants (25 women) and 66 non-TUD participants (28 women) underwent a resting-state functional magnetic resonance imaging scan. The whole-brain functional networks were constructed, and a two-way analysis of covariance with false discovery rate correction (q < 0.05) was performed to investigate whether men and women TUD participants had different alterations in the topological features at global, modular, and nodal levels. Results: Compared to non-TUD participants, men but not women TUD participants showed significantly lower global efficiency (lower intermodular connections between the visual and executive control and between the visual and subcortical modules did not pass the correction) and significantly lower nodal global efficiency in the right superior occipital gyrus, bilateral fusiform gyrus, the right pallidum, right putamen, the bilateral paracentral lobule, the postcentral gyrus, and lower nodal local efficiency in the left paracentral lobule. Conclusions: Men and women TUD participants have different topological properties of brain functional network, which may contribute to our understanding of neural mechanisms underlying sex differences in TUD. Implications: Compared to non-TUD participants, we found men but not women TUD participants with significantly lower network metrics at global, modular, and nodal levels, which could improve our understanding of neural mechanisms underlying sex differences in TUD and lay a solid foundation for future sex-based TUD prevention and treatment.