Resilience to persistent pain is characterized by stable periodic and increased aperiodic cortical activity

Zamorano, Anna M.; Chen, Chuwen; Millard, Samantha K.; Kleber, Boris; Vuust, Peter; Flor, Herta; Graven-Nielsen, Thomas · 2026 · Crossref

DOI: 10.64898/2026.04.28.721303

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Summary

This study investigates how long-term cognitive-motor training, specifically musical expertise, influences cortical dynamics and resilience to persistent musculoskeletal pain. Individual variability in pain perception is shaped by biological and experiential factors, yet the neural mechanisms underlying resilience remain unclear. Using musicians as a model of use-dependent brain plasticity, the researchers examined whether prior motor experience stabilizes cortical activity during sustained pain. The study focused on both periodic (oscillatory) and aperiodic (non-oscillatory) components of resting-state electroencephalography (EEG), hypothesizing that musicians would exhibit more stable neural markers and greater resilience compared to non-musicians. The experimental design involved 39 participants: 19 musicians with extensive training and 20 non-musicians. Prolonged muscle pain was induced via intramuscular injection of nerve growth factor (NGF) into the right first dorsal interosseous muscle. Resting-state EEG was recorded on Day 1 (baseline, pre-injection), Day 3, and Day 8 (during pain development). The researchers parameterized periodic features, including peak alpha frequency (PAF), alpha power, and frontal alpha asymmetry (FAA), as well as aperiodic features, specifically the spectral exponent and offset, which reflect the excitation-inhibition balance and population firing rates, respectively. Statistical analyses included repeated-measures ANOVAs to compare groups over time and hierarchical regressions to determine if baseline EEG features predicted pain severity. The results revealed distinct neural signatures of resilience in musicians. Non-musicians exhibited a significant slowing of PAF during pain development, a marker associated with ongoing pain and reduced top-down regulation. In contrast, musicians maintained stable PAF dynamics. Musicians also displayed increased left frontal alpha asymmetry by Day 8, reflecting approach-related motivational states and adaptive coping, whereas non-musicians showed no such change. Regarding aperiodic activity, musicians consistently exhibited higher spectral exponents than non-musicians across all sessions, suggesting a training-induced shift toward greater inhibitory control. Crucially, baseline periodic EEG features did not predict pain severity. However, baseline aperiodic features significantly predicted pain outcomes: higher exponents and higher offsets were associated with lower pain ratings on Day 3 and for the week’s worst pain. Hierarchical regression confirmed that adding aperiodic components significantly improved the prediction of pain severity, explaining approximately 24% of the variance in Day 3 pain. These findings demonstrate that cognitive-motor training shapes cortical dynamics to support resilience against persistent pain. The stability of oscillatory rhythms and the adaptive frontal asymmetry in musicians suggest that long-term training preserves top-down regulatory processes. Furthermore, the study identifies aperiodic EEG components as robust predictors of pain severity, challenging the reliance on oscillatory markers alone. The association between higher baseline aperiodic exponents/offsets and lower pain suggests that a cortical state characterized by specific excitation-inhibition balances may confer protection against pain intensity. This work highlights the role of experience-dependent plasticity in modulating pain processing and establishes aperiodic EEG features as valuable biomarkers for individual differences in pain resilience.

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