Individual differences in resting alpha band power and changes in theta band power during sustained pain are correlated with the pain-relieving efficacy of alpha HD-tACS on SM1.

High-definition transcranial alternating current stimulation (HD-tACS) targeting alpha rhythms (8-13 Hz) shows promise as a pain-relieving intervention, but individual responses vary widely. Understanding the neurobiological mechanism behind this variability is crucial for optimizing HD-tACS parameters to enhance its efficacy in pain relief. In a double-blind, within-subject, sham-controlled experimental study, 34 healthy participants were recruited. We investigated how individual differences in brain oscillations during rest and capsaicin-induced sustained pain states influence the efficacy of alpha HD-tACS. Participants underwent EEG assessments at rest and during capsaicin-induced sustained pain. They then received either sham or active HD-tACS on the sensorimotor cortex (SM1) or dorsolateral prefrontal cortex (DLPFC). We found significant reductions in delta and theta band power at the C4 electrode during sustained pain correlated with individual pain intensity. Additionally, stimulating the SM1 and DLPFC significantly relieved sustained pain. Resting alpha band power and changes in theta band power during sustained pain (the difference in theta band power between sustained pain and rest) at the C4 electrode were both significantly correlated with the pain-relieving efficacy of alpha HD-tACS on SM1. Notably, changes in theta band power mediated the relationship between resting alpha band power and pain-relieving efficacy. These results were not found with alpha HD-tACS on DLPFC. Our results suggest that the variations in theta band power during sustained pain may be crucial for understanding the variability in the efficacy of alpha HD-tACS targeting SM1. The factors influencing the efficacy of alpha HD-tACS on the DLPFC might be multifaceted.