Title : PNeuroplasticity-driven cognitive intervention for opioid addiction: A randomized controlled trial
Abstract:
Purpose: Opioid use disorder (OUD) is distinguished by its high relapse rates and intricate neuropsychological mechanisms, with conventional therapies exhibiting limited efficacy. The present study aims to evaluate the effectiveness of a neuroplasticity-targeted cognitive intervention (NCI) in enhancing executive functioning, mitigating impulsivity, and preventing relapse, thereby contributing to the advancement of neuroscience-informed strategies in addiction psychiatry.
Method: A 12-week randomized, double-blind controlled trial was conducted at the Third Affiliated Hospital of Sun Yat-sen University. The study population comprised 120 participants (N=120) who had been diagnosed with OUD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and had undergone detoxification. These participants were randomly assigned to either the NCI group (n=60) or the cognitive behavioral therapy (CBT) group (n=60).The NCI protocol included:
- Adaptive cognitive training: Dynamic N-back and modified Iowa gambling tasks to strengthen prefrontal-striatal circuitry;
- Real-time fMRI neurofeedback: Targeting dlPFC-NAc functional connectivity to modulate reward-related neural activity;
- Virtual reality-based episodic future thinking: Simulating adverse consequences to improve decision-making.
- Outcomes included neuroimaging (resting/task fMRI), impulsivity (BIS-11), relapse rates, and social function at baseline, post-intervention, and 6-month follow-up.
Results:
- Neuroplasticity: NCI significantly enhanced dlPFC-NAc connectivity (Δ=0.32, p<0.001), correlating with reduced impulsivity (BIS-11↓38.7%, p<0.01).
- Cognitive Gains: NCI outperformed CBT in delayed discounting (2.1 vs. 0.8-fold improvement, p=0.007) and working memory accuracy (+19.3%, p<0.01).
- Relapse Reduction: NCI group exhibited lower 6-month relapse rates (31.7% vs. 56.4%; HR=0.52, 95%CI 0.32–0.85).
- Dose-Response: Neurofeedback duration inversely predicted NAc activation (r=-0.71, p=0.003), confirming intervention specificity.
Conclusion: This trial demonstrates that NCI induces sustained neurobehavioral improvements in OUD by augmenting prefrontal regulation and attenuating hyperactive reward processing.
Keywords: Opioid Addiction; Neuroplasticity; Cognitive Intervention; Real-Time Fmri Neural Feedback; Executive Function
