In 36 migraine patients, galcanezumab responders (≥50% MMD reduction) showed reduced resting-state functional connectivity between somatosensory, motor, insular, and visual cortices after 3 months, while non-responders showed no changes.
Brain rewiring in respondersAnti-CGRP therapy reduced cortical hyperexcitability in migraine responders—the first fMRI evidence of brain connectivity normalization from neuropeptide-targeted treatment
What the researchers found
Responders (19/36): ↓functional connectivity between somatosensory/motor cortex, insula, and visual areas. Non-responders (17/36): no changes. No baseline differences between groups. 3-month galcanezumab treatment.
Why it matters
This provides the first neuroimaging evidence of how anti-CGRP drugs change brain function. Reducing cortical hyperexcitability explains the clinical benefit and suggests CGRP blockade initiates neural recovery beyond just pain relief.
How the study worked
Prospective resting-state fMRI study. 36 patients (high-frequency EM or CM). Pre- and post-3-month galcanezumab. ROI-to-ROI connectivity analysis. Responder (≥50% MMD reduction) vs non-responder comparison.
What this study cannot tell us
Small sample (36). Cannot determine if brain changes cause or result from clinical improvement. 3-month follow-up is short. Galcanezumab only—other CGRP drugs may differ.
How to read the evidence
Prospective neuroimaging study with responder/non-responder comparison. Good mechanistic evidence but small sample.
When this study was published
Published in 2025.
The bigger picture
Migraine is increasingly understood as a brain connectivity disorder. This study shows anti-CGRP drugs can normalize cortical communication patterns, providing neurobiological evidence for disease modification rather than just symptom relief.
Questions still open
- Do brain connectivity changes persist after stopping CGRP therapy?
- Could baseline fMRI predict who will respond to anti-CGRP drugs?
- Do the connectivity changes progress with longer treatment?
Common questions
Do anti-CGRP drugs change the brain?
What does this mean for migraine treatment?
Read the original research
Peripherally acting anti-CGRP monoclonal antibodies attenuate cortical resting-state connectivity in migraine patients.
Cephalalgia : an international journal of headache, 45(2), 3331024241313377
Citation
Szabo, Edina; Bolo, Nicolas R; Borsook, David; Burstein, Rami; Ashina, Sait. (2025). Peripherally acting anti-CGRP monoclonal antibodies attenuate cortical resting-state connectivity in migraine patients.. Cephalalgia : an international journal of headache, 45(2), 3331024241313377. https://doi.org/10.1177/03331024241313377