Neural Response to Theta-Burst Stimulation Predicts Long-Term Relapse in Patients With Alcohol Use Disorder: A Pilot...

Area of Science:

• Neuroscience
• Addiction Medicine
• Neuromodulation

Background:

• Alcohol use disorder (AUD) is associated with high relapse rates, often triggered by alcohol-related cues.
• Prefrontal-subcortical network dysregulation is implicated in cue-induced cravings and relapse in AUD.
• Non-invasive brain stimulation techniques are being explored to modulate neural circuits involved in addiction.

Purpose of the Study:

• To investigate the neurobiological effects of inhibitory continuous theta-burst stimulation (cTBS) targeting the right dorsolateral prefrontal cortex (rDLPFC) in patients with AUD.
• To assess the impact of rDLPFC-cTBS on neural responses to alcohol cues using fMRI.
• To evaluate the efficacy of rDLPFC-cTBS in reducing relapse rates over a 12-month follow-up period.

Main Methods:

• A randomized, double-blind, sham-controlled trial involving 28 AUD patients.
• Participants received 10 sessions of either active rDLPFC-cTBS or sham stimulation.
• fMRI scans were conducted pre- and post-intervention to measure brain activity in response to alcohol cues.
• Relapse was monitored for 12 months post-intervention.

Main Results:

• The active cTBS group showed a significantly lower risk of relapse compared to the sham group (HR = 0.210).
• Active cTBS prevented cue-induced hyperactivity in the right superior frontal gyrus, indicating network stabilization.
• A machine learning model accurately predicted long-term relapse based on intervention-induced neural activity changes (78.7% accuracy, AUC = 0.903).
• Increased post-intervention reactivity in the left medial prefrontal cortex was the strongest predictor of relapse.

Conclusions:

• rDLPFC-cTBS effectively modulates craving-related neural circuits in AUD patients.
• Dynamic neural responses to treatment serve as a potent biomarker for predicting long-term relapse.
• These findings support the development of personalized addiction medicine strategies using neuromodulation.