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

TL;DR

Personalized rTMS targeting brain connectivity significantly reduced migraine symptoms long-term in a clinical trial.

Contribution

Demonstrates that personalizing rTMS targets based on individual brain connectivity improves migraine treatment outcomes.

Findings

Personalized rTMS reduced headache frequency and intensity with large effect sizes at follow-up.

52.38% of patients were responders, with sustained response rates at follow-up.

Changes in DLPFC-PGC connectivity could distinguish responders from non-responders with high accuracy.

Abstract

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).

The online version contains supplementary material available at 10.1186/s10194-026-02273-7.

Figures