Prospective open-label trial of personalised connectivity-guided transcranial magnetic stimulation therapy for migraine

Migraine is a leading cause of disability worldwide, affecting hundreds of millions of individuals. Repetitive transcranial magnetic stimulation (rTMS) offers a non-invasive therapeutic option, yet long-term effects remain unclear. We investigated whether rTMS treatment effects could be extended by personalising stimulation targets based on connectivity between the pregenual cingulate cortex (PGC) and dorsolateral prefrontal cortex (DLPFC)-a neural pathway implicated in migraine pathophysiology. Twenty-one patients completed all treatments and assessments. Clinical data were analysed using repeated-measures one-way ANOVAs (Baseline, Post, Follow-up), with comparisons being and Bonferroni correction (2-tailed). Personalised rTMS had a large effect on headache frequency (estimated difference, 4.42, p = 0.004, 95% CI, 1.30–7.54, Cohen’s d, 0.81) and intensity (estimated difference, 2.54, p < 0.001, 95% CI, 0.97–4.10, Cohen d = 0.92), at Follow-up. After treatment, 11/21 (52.38%) patients were classified as responders. The response rate was maintained at 52.38% at Follow-up. Changes in DLPFC-PGC connectivity were able to classify responders from non-responders (AUC, 0.80, p = 0.020, sensitivity, 72.70%, specificity, 80%). In this study, personalised rTMS treatment demonstrated a large and long-term effect for migraineurs. These novel findings need to be directly compared with conventional group-average targeting strategies in future controlled trials. Chinese Clinical Trials Registry (ChiCTR2400094055).