Zamorano, A. M.; Chen, C.; Millard, S. K.; Kleber, B.; Vuust, P.; Flor, H.; Graven-Nielsen, T.

Individual variability in pain perception raises fundamental questions about how biological and experiential factors shape pain processing. Cognitive-demanding motor training is a key driver of use-dependent brain plasticity and may contribute to differences in pain responses. Using musicians as a model of cognitive-motor expertise, we examined how such experience influences cortical dynamics and pain perception during experimentally induced prolonged musculoskeletal pain. Resting-state electroencephalography (EEG) was recorded in musicians and non-musicians before (Day 1) and during pain development (Days 3 and 8) following intramuscular nerve growth factor (NGF) administration. We parameterized periodic (alpha peak frequency, power, frontal asymmetry) and aperiodic (exponent, offset) components of the EEG signal to characterize intrinsic cortical activity. During pain development, non-musicians exhibited slowing of peak alpha frequency, a neural marker associated with ongoing pain. In contrast, musicians showed preserved alpha dynamics and greater left frontal asymmetry, reflecting resilient top-down pain regulation. Musicians also displayed higher aperiodic exponent across sessions, suggesting that musical training shapes the excitation-to-inhibition (E:I) balance potentially reflecting a shift toward greater inhibitory activity. Notably, across all participants, only aperiodic features improved the prediction of pain severity, with higher exponents and higher offsets associated with lower pain ratings. These findings demonstrate that cognitive-motor training shapes cortical dynamics during sustained pain, supporting more stable, resilient cortical responses to pain. Such training also contributes to inter-individual variability in pain processing. Moreover, this study identifies aperiodic EEG components as predictors of pain severity and resilience.