Structural-functional decoupling in tobacco use disorder: Linking network dysfunction to molecular signatures.

Area of Science:

• Neuroscience
• Psychiatry
• Brain Imaging

Background:

• Structural-functional coupling (SFC) is sensitive to mental disorder abnormalities.
• Specific SFC alterations in tobacco use disorder (TUD) and their neurobiological basis are not well understood.

Purpose of the Study:

• To investigate SFC differences between individuals with TUD and healthy controls (HCs).
• To explore the diagnostic and predictive potential of aberrant SFC patterns in TUD.
• To examine the relationship between altered SFC, neurotransmitter distribution, and gene expression.

Main Methods:

• Structural and functional MRI data were acquired from 111 male TUD patients and 92 male HCs.
• Node-level SFC differences were quantified, and machine learning models were applied for TUD prediction.
• Correlations between altered SFC, neurotransmitter spatial distribution, and gene expression were analyzed.

Main Results:

• TUD subjects showed weakened coupling in executive control, default mode, salience, and sensorimotor networks, with enhanced basal ganglia coupling.
• Extra trees classification models effectively diagnosed and predicted TUD.
• Abnormal coupling patterns correlated significantly with the spatial distribution of specific neurotransmitters and gene expression profiles.

Conclusions:

• TUD is characterized by a decoupling pattern across key brain networks and hyperconnectivity in the basal ganglia.
• These SFC alterations offer potential for effective TUD diagnosis and intervention.
• Findings reveal neurobiological underpinnings of TUD, linking connectivity anomalies to neurotransmitter and genetic factors.