Individualized TMS–EEG mapping reveals clinically relevant early prefrontal cortical activity in major depressive disorder

Objective To determine whether individualized TMS–EEG mapping improves assessment of early cortical responses in the dorsolateral prefrontal cortex (DLPFC) compared with conventional Beam F3 targeting and their association with depressive symptom severity. Methods Single-pulse TMS–EEG was performed in 30 patients with major depressive disorder (MDD) and 15 healthy controls. Individualized mapping identified DLPFC stimulation sites and intensities that minimized artifacts while eliciting robust early TMS-evoked potentials (>6 μV within 60 ms). Responses were compared with Beam F3 stimulation at 120% resting motor threshold. Early cortical activity was quantified using global mean field power (GMFP) and region-of-interest (ROI) area-under-the-curve (AUC) during the 10–30 ms post-stimulation interval. Results Individualized mapping produced distinct early cortical responses and significantly smaller early GMFP and ROI AUC responses (q < 0.001) compared to Beam F3 stimulation. Within the MDD group, lower GMFP AUC was associated with greater depression (PHQ-9: ρ = − 0.43, q = 0.046) and anxiety severity (GAD-7: ρ = − 0.58, q = 0.008). Lower ROI AUC was associated with greater depressive symptoms (PHQ-9: ρ = − 0.57, q = 0.008; QIDS-SR: ρ = − 0.48, q = 0.033) and anxiety severity (GAD-7: ρ = − 0.45, q = 0.040). No significant clinical associations were observed for Beam F3-derived measures. Conclusions Individualized TMS–EEG mapping identifies clinically relevant early DLPFC responses not detected using conventional Beam F3 targeting. Significance Individualized targeting improves the sensitivity of prefrontal TMS–EEG and may enhance detection of early cortical responses associated with depressive and anxiety severity.