P300 Event-Related Potentials Applied Synchronously with Vagus Nerve Stimulation for Response Prediction in Epilepsy

Vagus Nerve Stimulation (VNS) is an established adjunctive therapy for patients living with refractory epilepsy. Despite its effectiveness, identifying responders from non-responders to the treatment remains challenging. Recent clinical experiments hold the promise that the analysis of the relation between VNS and P300 Evoked Response Potential (ERP) could serve as a discriminatory biomarker. Previous literature addressed the impact of VNS on P300 while mixing epochs with stimulation and pause periods. However, the immediate effects of VNS (i.e., only during stimulation periods) on the P300 have not been investigated yet, and collecting epochs solely during these periods could provide valuable new insights into literature. This study introduces a novel experimental setup designed for the real-time detection of VNS bursts to evoke P300 stimuli under different experimental conditions, including VNS pulse trains. The setup enables reliable detection of VNS pulses, precise timing to oddball task stimuli, and monitoring of the patient's response to the task. The obtained results present a proof-of-concept of a setup able to detect online VNS bursts accurately to elicit oddball paradigm tasks during VNS periods. Moreover, the signals collected and post-processed on five subjects show the feasibility to investigate the brain modulatory effect of VNS when coupled with ERP eliciting auditory stimuli.Clinical Relevance- This device offers a complementary approach to current experimental protocols and could enhance our understanding of VNS. It allows for investigating both the traditional intermittent effects and the acute impact of stimulation. In epilepsy, the direct link between electrical pulses and brain activity during VNS has yet to be studied.