Neurotransmitter-related functional connectivity changes in serotonin and dopamine systems after mindfulness in medication overuse headache

Background/Hypothesis Mindfulness practice has gained attention in managing chronic migraine with medication overuse headache (CM-MOH), showing clinical improvements and functional connectivity reorganization. However, the relationship between these effects and the underlying neurotransmitter systems remains unexplored. Methods Thirty-four CM-MOH patients were divided into treatment as usual (TaU, N = 17) and mindfulness-added-to-TaU (TaU + MIND, N = 17) groups. Participants underwent resting-state fMRI scans before treatment and after one year. We adopted the neurotransmitter-related functional connectivity framework to investigate longitudinal functional changes associated with the distribution of serotonin, dopamine, and norepinephrine systems by comparing TaU + MIND with TaU groups. Results When compared with TaU, TaU + MIND patients longitudinally showed increased serotonin-enriched functional connectivity in the caudate and accumbens nuclei, and increased dopamine-enriched functional connectivity in the right insular cortex. Conclusion/Interpretation These regions are involved in emotional, cognitive, and sensory modulation of pain and addiction. Our findings suggest the impact of mindfulness practice on serotonin and dopamine systems with potential beneficial effects in chronic pain management.