EEG biomarkers for a precision-medicine approach to noninvasive brain stimulation for major depressive disorder

Abstract

Major depressive disorder (MDD) is a prevalent and disabling condition with high rates of treatment resistance. Non-invasive brain stimulation (NIBS), including transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), has emerged as a promising option for individuals unresponsive to pharmacotherapy. However, many patients still fail to achieve meaningful improvement, underscoring the need for reliable biomarkers of treatment response. Electroencephalography (EEG) and combined TMS-EEG are increasingly explored as predictive tools because they index cortical excitability, connectivity and neuroplasticity. In this systematic review, we synthesize evidence from 18 high-quality studies evaluating EEG and TMS-EEG biomarkers of NIBS outcomes in MDD. Resting-state EEG studies highlight the relevance of spectral power alterations, frontal alpha asymmetry and connectivity measures, whereas TMS-EEG work emphasizes TMS-evoked potentials, particularly N100 and N45 components, in forecasting clinical response. Although results are encouraging, methodological heterogeneity, modest sample sizes and divergent stimulation protocols limit immediate clinical implementation. Nonetheless, converging findings indicate that pre-treatment EEG and TMS-EEG assessments can support a precision-medicine approach by informing target selection and stimulation parameters. Systematic integration of these neurophysiological markers could enhance personalization of NIBS, increase response rates and advance the development of mechanism-based interventions for depression across diverse patient profiles and clinical settings worldwide.