Modulation of evoked alpha oscillatory activity in the frontocentral region during analgesia by non-invasive brain stimulation

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) to the posterior superior insula (PSI) can produce analgesia, although the underlying mechanisms require further exploration. While alpha oscillations have been implicated in rTMS-induced plasticity, research has largely focused on resting-state metrics, whereas alterations in perturbation-evoked alpha activity remain unknown. OBJECTIVE: To examine the effect of PSI rTMS on perturbation-evoked alpha activity within a capsaicin-induced tonic pain model. METHODS: Twenty healthy adults (10 females) completed two randomised, counterbalanced rTMS sessions (active, sham). Capsaicin was applied to the forearm for 90 min and pain intensity recorded at 5 min intervals on a numerical rating scale. Left PSI rTMS (10 Hz, 100 pulses/train, 15 trains) was delivered ∼50 min after capsaicin application. Evoked electroencephalographic responses to primary motor cortex (M1) TMS were assessed at baseline, during capsaicin-induced pain pre-rTMS, and post-rTMS. The frontocentral event-related spectral perturbation (ERSP) and parietal-occipital inter-trial coherence (ITC) were extracted. RESULTS: Baseline-normalised frontocentral ERSP showed a more positive pre-to-post change in M1-TMS-evoked alpha power following active rTMS relative to sham (p = 0.013), though no significant effect on ITC was observed. Exploratory analysis showed that lower pre-rTMS ITC predicted a greater reduction in pain with active rTMS (r = 0.68, p < 0.001). CONCLUSIONS: PSI-rTMS modulates evoked alpha oscillatory power in frontocentral regions, advancing our understanding of the mechanisms underlying rTMS-induced analgesia. Evoked frontocentral alpha power may index a change in pain state, whereas exploratory findings suggest that alpha-band parietal-occipital ITC may predict individual differences in the rTMS analgesic response, though larger studies are needed to confirm these findings.