Effective connectivity of default mode network subsystems and automatic smoking behaviour among males

Background: The default mode network (DMN) is not a single system, but rather is composed of smaller and distinct functional subsystems that interact with each other. The functional relevance of these subsystems in tobacco use disorder (TUD) and the neurobiological features associated with smoking motivation are still unclear; thus, we sought to assess causal or direct connectivity alterations within 3 subsystems of the DMN among people with TUD.

Methods: We recruited male smokers and nonsmokers. We conducted resting-state functional magnetic resonance imaging (rs-fMRI) and collected ratings on smoking-related clinical scales. We applied dynamic causal modelling (DCM) to rs-fMRI to characterize changes of effective connectivity in TUD from 3 DMN subsystems, including the midline core network (i.e., the posterior cingulate cortex and the anterior medial prefrontal cortex [PCC-aMPFC] core DMN), the medial temporal subsystem (MTL-DMN), and the dorsal medial prefrontal cortex subsystem (dMPFC-DMN). We used leave-one-out cross-validation to investigate whether the neural response could predict smoking reasons, evaluated using the Russell Reason for Smoking Questionnaire).

Results: We recruited 88 smokers and 54 nonsmokers. Among people with TUD, the parahippocampal cortex (PHC) region showed enhanced self-connection, which was associated with the severity of TUD after nighttime withdrawal. Compared with nonsmokers, people with TUD displayed significant increased effective connectivity within the dMPFC-DMN, and decreased effective connectivity from the dMPFC-DMN to the PCC-aMPFC core DMN. Moreover, decreased effective connectivity from the lateral temporal cortex to the dMPFC could predict the smoking reason related to automatic behaviour.

Limitations: Although we found aberrance in causal connections in DMN subsystems among people with TUD, our cross-sectional study could not be used to investigate changes in effective connectivity over time and their relationship with clinical features.

Conclusion: This study emphasized the aberrant causal connections of different functional subsystems of the DMN in TUD and revealed the neural correlates of automatic smoking behaviours. These findings suggested DMN subsystem-derived indicators could be a potential biomarker for TUD and could be used to identify the heterogeneity in motivation for smoking behaviour.