P300 is enhanced in responders to vagus nerve stimulation for treatment of major depressive disorder.

Background: Vagus nerve stimulation (VNS) is a new therapy option for treatment of otherwise therapy-refractory major depressive disorder. However, the mechanism of central nervous action is poorly understood. Electroencephalographic (EEG) studies may be of interest since chronic peripheral current application to the vagus nerve may exert lasting neurophysiologically detectable effects on central electrical activity. In an exploratory study, we investigated the effects of VNS on auditory event-related potentials (ERP).

Methods: Thirteen depressive patients (mean Hamilton depression score (HAMD) at baseline=24.2) receiving VNS were investigated prior to implantation and 10 weeks after standard cycling VNS. Stimulation intensity was 0.94+/-0.46 mA, pulse width 0.250 mus, and frequency 20 Hz. 1 h prior to follow-up investigation, VNS was turned off. Auditory ERP were elicited using a standard auditory oddball paradigm and were recorded with 29-channel EEG.

Results: Post VNS, grand averages of the auditory ERP did not show significant differences as compared to baseline recording. However, differential effects were found when separating ERP of responders (N=5, mean HAMD post VNS=8.8) and non-responders (N=8, mean HAMD post VNS=22.4). In VNS responders only, P300 at midline electrodes Fz and Cz was significantly increased and correlated with HAMD scores.

Conclusion: Auditory ERP seem to provide a useful tool for investigating VNS-induced changes concerning information processing in major depressive disorder. In our sample, enhancement of P300 distinguished VNS responders from non-responders 10 weeks after therapy onset. Our findings may be relevant for the understanding of both neurophysiological mechanism of action of VNS and pathophysiology of depression.