Increased integration and synergy in EEG- and fNIRS-based data in migraine patients after a three-month treatment with galcanezumab: relations with long-term clinical outcome

Galcanezumab is a well-tolerated monoclonal antibody developed for migraine prophylaxis. Although its action mechanisms are not fully understood, they may involve changes in cortical connectivity. This study explores galcanezumab-induced central changes by investigating metabolic-electrical brain interactions and network properties. We analyzed electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) during visual stimulation through connectivity and high-order interaction analyses using Partial information decomposition (PID). Furthermore, we explored the relationship between neurophysiological measures and long-term clinical effects. Fifteen patients underwent clinical and EEG/fNIRS recordings at baseline (B), 1 hour after the first galcanezumab administration (B'), and after 3 months of therapy (3M). Clinical outcomes were assessed after one year of treatment (1Y). Ten healthy controls underwent baseline EEG/fNIRS recordings. EEG and fNIRS signals were analyzed and harmonized. We computed global network properties including strength, global efficiency, clustering coefficient, and high-order interaction properties such as synergy and redundancy. For both EEG and fNIRS data, we found lower strength and clustering coefficients in patients than in controls at all time points [Formula: see text]. Global efficiency was reduced at B, and significantly increased in patients at 3M, reaching levels comparable to controls. PID on fNIRS data showed an overall increase in redundancy and synergy after treatment [Formula: see text]. Cluster analysis on EEG and fNIRS synergy matrices over time showed expansion of high-synergy channel clusters at 3M. Finally, for both EEG and fNIRS data, synergy and global efficiency at 3M correlated with clinical indicators at 1Y, including migraine-related disability and the number of acute medications/month [Formula: see text]. The results support central effects of galcanezumab associated with increased integration in functional and electrical brain connectivity, explaining its long-term efficacy and disease-modifying action.