Disordered connectivity configuration of triple-network model and visual-network in tobacco use disorder

Tobacco use disorder (TUD) is recognized as a significant neurobehavioral disorder, associated with alterations in functional network connectivity (FNC) within and between the triple-network and visual-network.

We recruited 87 male TUD patients and 45 male healthy control (HC), collecting resting-state functional magnetic resonance imaging(rs-fMRI) and smoking-related clinical scales. Group independent component analysis (ICA) combined with a sliding window method and k-means clustering analysis was used to assess static and dynamic time-varying FNC within networks. Spectral dynamic causal modelling (Sp DCM) and Parametric empirical bayes (PEB) framework were used to explore the aberrant effective connectivity (EC) among these networks in TUD.

Compared to HC, TUD patients exhibited within-network hyperconnectivity in the middle temporal gyrus (MTG) of the salience network (SAL), medial prefrontal cortex (MPFC) of the default mode network (DMN), and superior frontal gyrus (SFG) of the higher-order visual-network (HVN), alongside hypoconnectivity in the superior parietal lobule (SPL) of the HVN and posterior cingulate cortex (PCC) of the primary visual-network (PVN). Statically, increased connectivity was observed between SAL and executive control network (ECN). Dynamically, hyperconnectivity between SAL and PVN was identified in State I. EC analysis revealed enhanced self-inhibition within SAL, increased excitatory drive from ECN to SAL and HVN, and decreased excitatory influence from PVN to HVN in TUD. Correlation analyses indicated that static SAL-ECN connectivity positively correlated with Russell Reasons for Smoking Questionnaire (RRSQ)IV-VII scores, while EC from ECN to HVN negatively correlated with Fagerstr¨om Test for Nicotine Dependence (FTND) scores and cigarettes per day.

This study reveals a novel, hierarchical dysregulated connectivity configuration involving the triple-network and visual-network in TUD, characterized by static hyperconnectivity, dynamic state-specific abnormalities, and a causal model of enhanced top-down control coupled with disrupted bottom-up processing. This study also provides new insights into the neurobiology of TUD in males, highlighting the need for future studies to investigate sex-specific effects. These findings advance the neurobiological understanding of TUD and emphasize potential network-based targets for neuromodulation therapies.