Association between executive function and left dorsolateral prefrontal TMS-evoked potentials in major depressive disorder

Executive dysfunction is common in major depressive disorder (MDD) and may persist after remission of mood symptoms, but objective neurophysiological markers linking prefrontal dysfunction to cognitive impairment remain limited. The left dorsolateral prefrontal cortex (DLPFC) is central to cognitive control and is a primary neuromodulation target in depression. We examined whether F3-recorded TMS-evoked potentials (TEPs) following left dorsolateral prefrontal cortex (DLPFC) stimulation were associated with executive impairment and symptom severity in MDD. Seventy-nine participants (49 with MDD and 30 healthy controls) underwent clinical assessment, multidomain executive-function testing, and single-pulse TMS–EEG targeting the left DLPFC. TEP amplitudes at F3 (P30, N45, P60, N100, and P180) and executive performance were compared between groups. Within the MDD group, correlations examined associations among TEPs, symptom severity, and executive-function measures. Hierarchical regression further tested the N100–CPT association after adjustment for depressive and anxiety symptoms, age, sex, and education. Compared with healthy controls, patients with MDD showed poorer processing speed, sustained attention, cognitive flexibility/task switching, and inhibitory control during emotional conflict. The MDD group also showed a significantly greater F3-recorded N100 magnitude, whereas the other TEP components did not differ. Within the MDD group, a more negative N100 amplitude was associated with poorer sustained-attention performance after FDR correction. This association remained significant after full clinical and demographic adjustment. MDD was associated with multidomain executive dysfunction and an altered F3-recorded TMS-evoked response following left DLPFC stimulation. The association between N100 magnitude and sustained attention supports the F3-recorded N100 as a candidate neurophysiological correlate of cognitive dysfunction in MDD, although its functional specificity and clinical utility require longitudinal validation.