Dorsolateral prefrontal TMS-evoked N100 as a neurophysiological correlate of symptom change in adolescent depression

Major depressive disorder (MDD) is highly prevalent in adolescence. Up to 30% of patients insufficiently benefit from first-line treatments, underscoring the need for improved treatment strategies and better understanding of pathophysiology. In depression, an imbalance between cortical excitation and inhibition in the dorsolateral prefrontal cortex (DLPFC), assessed by the TMS-evoked N100 potential, is suggested as one of several contributing neurobiological mechanisms. While elevated N100 amplitudes have been observed in depressed adults and adolescents, its association with symptom change remains insufficiently investigated.

In a randomized controlled trial, N = 54 adolescents (38 girls, 16 boys) with MDD received six weeks of whole body vibration training (exercising on a vibrating plate that triggers involuntary muscle contractions through a neurological reflex) or light stretching as add-on treatments to treatment as usual. TMS-EEG was applied before and after the intervention to assess N100 amplitudes over the left and right DLPFC. Depressive symptoms were measured using the Children's Depression Rating Scale-Revised. Changes in N100 amplitudes were analyzed using repeated measures ANOVA. Multiple regression analyses with intervention group as predictor examined associations between changes in N100 amplitudes and depressive symptoms, including sex as moderator and a subsequent girls-only analysis.

Across both groups, N100 amplitudes significantly decreased from pre-to post-intervention. No differential effects between interventions were observed. Reductions in right-hemispheric N100 amplitudes were significantly associated with improvements in depressive symptoms. This association reached statistical significance in girls.

Our findings support the N100 as a candidate neurophysiological correlate of depressive symptom improvement.