Research advances in neuronavigated target localization for repetitive transcranial magnetic stimulation in depression: from standardization to individualized neuromodulation

Depression is a highly disabling mental disorder imposing a substantial burden on global public health. Repetitive Transcranial Magnetic Stimulation (rTMS), as a non-invasive physical treatment modality, demonstrates favorable efficacy and safety in treating depression. However, significant inter-individual variability in treatment response exists, with the reliability of target localization being a key factor influencing efficacy. Traditional non-neuronavigated localization methods (e.g., 5-cm rule, Beam F3 method), while operationally convenient, suffer from limited reliability due to failure to account for individual variations in brain anatomy (e.g., cortical folding) and functional connectivity patterns. In recent years, driven by advances in magnetic resonance imaging (MRI) technology and individualized treatment paradigms, neuronavigated localization methods based on clinical symptom subtypes and patient-specific brain structural/functional connectivity profiles have significantly enhanced localization reliability and personalization, offering novel approaches to overcome efficacy variability. This review systematically summarizes the mechanisms of action and standard treatment protocols of rTMS for depression, with a primary focus on research advances in target localization methodologies. It encompasses the principles, clinical applications, efficacy comparisons, and optimized integration of both non-neuronavigated and neuronavigated techniques across different populations (adolescents, elderly) and symptom subtypes. By critically analyzing current research achievements and challenges, this review aims to provide clinicians with theoretical foundations and practical references for optimizing rTMS treatment protocols, enhancing response rates, and advancing individualized neuronavigated protocols.