Enhanced Brain Structure–Function Coupling In the Frontoparietal Control Network of Chronic Tobacco Smokers
Abstract
Purpose
This cross-sectional study quantified structural–functional (SC-FC) coupling in chronic tobacco smokers versus non-smokers using multimodal MR imaging, testing whether smoking is associated with altered correspondence between white-matter architecture and resting-state functional connectivity.
Methods
A total of 102 participants (51 smokers, 51 non-smokers) were recruited for the study and underwent brain scans on a whole-body 3T MRI system. After data exclusion due to subject motion, incomplete scans, or overall poor data quality, 46 non-smokers (22 F) and 48 smokers (23 F) were included in the analysis. Diffusion tensor imaging (DTI) and resting-state fMRI data were processed with standard pipelines. Structural connectivity (SC) matrices were derived from MRtrix3 tractography with SIFT2 weighting and volume correction, and functional connectivity (FC) matrices were constructed in Nilearn. SC–FC coupling, corrected for inter-regional distance, was quantified for the whole brain and the seven Schaefer–Yeo canonical networks using Spearman correlations, averaged across network densities 10-30% to reduce bias from single-thresholding selection in sparse brain networks. Group differences were tested using clusterwise non-parametric permutation (n = 5000) analysis with family-wise error (FWE) correction.
Results
Smokers were older than non-smokers (48±12 vs. 41±13 years, p = 0.007), with no sex differences between groups. Smokers showed higher SC-FC coupling within the Control/frontoparietal control network (FCPN) compared to controls. Statistical significance was observed at 22-30% (FWE-corrected, p < 0.0001) thresholds with age, sex, and education level as covariates. No significant differences were found for the other networks or subcortical structures.
Conclusion
Enhanced SC-FC coupling in the FPCN of smokers indicates a closer alignment between executive-control white matter pathways and intrinsic functional dynamics. This pattern may reflect reduced neural flexibility, where attention and control processes become more rigidly shaped by underlying white‑matter pathways. Such rigidity could help explain the habitual, cue‑driven patterns of control often observed in tobacco addiction.