A salutogenic signature of the placebo effect in brain oscillations: A systematic review and meta-analysis

Ortega-Márquez J.; Gonzalez-Gonzalez L.F.; Sosa W.; Pacheco-Barrios K.; Fregni F. · Progress in Neuro-Psychopharmacology and Biological Psychiatry (2025) · DOI: 10.1016/j.pnpbp.2025.111518

Resumen

Background: The placebo effect is increasingly recognized in rehabilitation, yet its mechanisms remain poorly understood. Brain oscillations offer a non-invasive, time-sensitive and dynamic measure of neural activity, making them ideal for capturing the dynamic changes linked to placebo responses. This study explores oscillatory activity as a biomarker of the placebo effect's neural basis. Methodology: A systematic literature review up to September 2024 searched PubMed, Embase, and Cochrane databases for randomized controlled and cross-over trials reporting brain oscillations in resting state from placebo-controlled neurorehabilitation trials in healthy and subjects with neurological disorders. The analysis included a semi-quantitative (albatross plots), and quantitative meta-analysis (Hedge's g), focusing on the effect sizes of power differences between placebo and active groups. Results: We included 63 studies with 180 healthy subjects and 1758 neurological disorder patients. In healthy subjects, placebo showed an increase in alpha power compared to no intervention (g = 0.45, 95 % CI [0.09; 0.8]). In patients, sham interventions elevated alpha power in frontal (g = 0.08, 95 % CI [0.07; 0.08]), central (g = 0.55, 95 % CI [0.47; 0.65]), and parietal areas (g = 0.28, 95 % CI [0.18; 0.44]), as well as beta (g = 1.31, 95 % CI [1.06; 1.63]) and theta central (g = 0.58, 95 % CI [0.46; 0.72]). These effects were non-significant when compared to active interventions. Conclusion: Alpha oscillations in fronto-central regions are the primary biomarkers of the placebo effect, with beta and theta oscillations also indicative, especially in patients with neurological disorders. These effects were reversed when compared to active interventions, suggesting that active rehabilitation also encompass the placebo effect. Intriguingly, these placebo effects vary based on baseline brain activity, highlighting a tendency towards more stable, salutogenic rhythms in different populations.

Instituciones: Universidad San Ignacio de Loyola