EEG Biomarkers for a Precision-Medicine Approach to Noninvasive Brain Stimulation for Major Depressive Disorder

Major Depressive Disorder (MDD) is a prevalent and debilitating psychiatric condition with significant 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 pharmacological interventions. However, a substantial proportion of patients still fail to achieve meaningful clinical improvement, underscoring the need for reliable biomarkers to predict treatment response. Electroencephalography (EEG) and TMS-EEG have been increasingly explored as promising predictive tools due to their ability to assess cortical excitability, connectivity, and neuroplasticity. The evidence gathered from 18 high-quality studies highlights the relevance of EEG and TMS-EEG biomarkers in predicting outcomes of NIBS in MDD. Resting-state EEG studies emphasize the importance of spectral power alterations, alpha asymmetry, and connectivity patterns, while TMS-EEG studies underline the role of TMS-evoked potentials (TEPs), particularly the N100 and N45 components, in forecasting therapeutic response. While these findings suggest significant potential, methodological variability, small sample sizes, and differing stimulation protocols limit their immediate clinical translation. However, these biomarkers provide a solid foundation for implementing precision medicine. Prior EEG or TMS-EEG assessments can play a valuable role in guiding the personalization of NIBS treatment strategies. The systematic integration of these neurophysiological biomarkers into clinical practice could maximize therapeutic efficacy and reduce non-response rates, paving the way for more precise and effective interventions in depression treatment.