Evaluating Robustness of Brain Stimulation Biomarkers for Depression: A Systematic Review of Magnetic Resonance Imaging and Electroencephalography Studies

Non-invasive brain stimulation (NIBS) treatments have gained considerable attention as a potential therapeutic intervention for psychiatric disorders. The identification of reliable biomarkers for predicting clinical response to NIBS has been a major focus of research in recent years. Neuroimaging techniques, such as electroencephalography (EEG) and (functional) magnetic resonance imaging (fMRI), have been used to identify potential biomarkers that could predict response to NIBS. However, identifying clinically actionable brain biomarkers requires robustness.In this systematic review, we aimed to summarize the current state of brain biomarker research for NIBS in depression, focusing only on well-powered studies (N≥88) and/or studies that aimed at independently replicating prior findings, either successfully or unsuccessfully. A total of 220 studies were initially identified, of which 18 MRI studies and 18 EEG studies adhered to the inclusion criteria, all focused on repetitive transcranial magnetic stimulation treatment in depression.After reviewing the included studies, we found the following MRI and EEG biomarkers to be most robust: 1) fMRI-based functional connectivity between the dorsolateral prefrontal cortex and subgenual anterior cingulate cortex, 2) fMRI-based network connectivity, 3) task-induced EEG frontal-midline theta, and 4) EEG individual alpha frequency.Future prospective studies should further investigate the clinical actionability of these specific EEG and MRI biomarkers to bring biomarkers closer to clinical reality.