Higher pre-treatment evoked alpha-band oscillatory brain dynamics predict chronic pain reduction of non-invasive brain stimulation of non-motor targets

Repetitive transcranial magnetic stimulation (rTMS) of non-motor cortical targets, including the left dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and posterosuperior insula (PSI), has been proposed as a treatment for chronic pain with variable clinical outcomes. Pre-treatment local cortical dynamics were hypothesized to serve as markers of chronic pain reduction. In this secondary analysis of a large clinical trial comparing different rTMS targets for pain relief, it was examined whether pre-treatment evoked cortical responses measured by electroencephalography after TMS of DLPFC, ACC, or PSI were associated with at least 30 percent reduction in pain intensity scored on a visual analogue scale. Forty-five patients with chronic pain received 12 sessions over eight weeks of 10 Hz rTMS to DLPFC, ACC or PSI. Cortical reactivity was quantified using global and local mean field power, and oscillatory dynamics were assessed using event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) in the alpha-band (8-12 Hz). Responders (20 of 45, 44%) compared with non-responders showed higher pre-treatment alpha-band ERSP and ITC over the stimulated cortical targets (both P<0.05), and higher alpha-band ERSP and ITC values were negatively correlated with the percentage change in pain intensity (both P < 0.05). These results suggest that elevated pre-treatment TMS-evoked alpha-band oscillatory activity may indicate a higher probability of pain reduction to non-motor rTMS in chronic pain. This supports the development of enrichment strategies using cortical neurophysiology-based markers in neuromodulation trials aimed at individualized, precision-oriented treatments.