Alpha oscillations in pain neuromodulation: From resting rhythms to reactive networks
(2026) Neurotherapeutics — Vol. 23, n° 3, p. e00929 (2026)
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- Chronic pain remains a major clinical challenge. Pharmacological treatments, while central to current care, often provide only partial and unsatisfactory relief [1]. This therapeutic gap has fueled increasing interest in non-invasive brain stimulation approaches, particularly repetitive transcranial magnetic stimulation (rTMS) [1-3]. In this context, a central goal is to identify neurophysiological processes that mediate analgesia. Alpha oscillations are prominent candidates, with resting-state power and peak frequency consistently linked to pain sensitivity [4-6]. Yet, a key question persists: are alpha rhythms merely a marker of ongoing pain states, or are they mechanistically relevant targets for neuromodulation? In this issue of Neurotherapeutics [7], Chowdhury and colleagues advance this debate by moving beyond resting-state measures to perturbation-evoked alpha dynamics. Using combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) in a capsaicin-induced tonic pain model, they tracked event-related spectral perturbations (ERSP) and inter-trial coherence (ITC) before and after posterior insula-proximal rTMS. In this perspective, alpha oscillations are not static features of brain state, rather they are dynamic, perturbation-sensitive properties of neural systems. Chowdhury et al. [7] re port that posterior insula-proximal rTMS-shown to produce analgesia in their prior study [8], was associated with a more positive pre-to-post change in frontocentral alpha ERSP following active compared to sham stimulation, although within-session changes were not significant. This pattern reflects a difference-indifferences interaction rather than a clear increase after active rTMS, pointing to a relative modulation of evoked alpha power and suggesting that perturbation-evoked alpha responses may track aspects of the analgesic process. Bayesian analysis and a substantial interaction effect size support the interpretation that this modulation is meaningful. This interaction, however, does not fully disambiguate the underlying pattern: it could reflect a decline in the sham condition , a modest increase after active stimulation, or both. As such, the data do not establish whether the effect reflects true enhancement, sham-related decrease, or relative preservation of alpha reactivity. Unlike prior work from the same group [9], no significant reduction in frontocentral ERSP from baseline to the pre-rTMS assessment during ongoing capsaicin-induced pain was observed in this dataset, possibly because recordings did not capture peak pain. Consequently, the rTMS-related relative increase cannot be interpreted as a restoration of a suppressed alpha state, but rather as a state-dependent modulation whose relationship to ongoing pain intensity remains to be clarified. Importantly, this effect should be interpreted alongside the complementary though exploratory-ITC findings. At the group level, parietal-occipital alpha ITC did not show a significant rTMS-related modulation, a null result that may reflect insufficient power rather than a true absence of effect. Exploratory analyses nonetheless revealed that lower pre-rTMS ITC predicted greater analgesic response in the active condition, a finding consistent with prior work from the same group in patients with chronic pain [10]. This pattern raises the possibility that power-and phase-based measures of alpha reactivity capture DOI of original article: https://doi.
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Liberati, G. (2026). Alpha oscillations in pain neuromodulation: From resting rhythms to reactive networks. Neurotherapeutics, 23(3), e00929. https://doi.org/10.1016/j.neurot.2026.e00929 (Original work published 2026)