Abstracts

Rationale: Vagus nerve stimulation (VNS) for medically refractory epilepsy requires optimization of stimulation parameters to improve clinical outcome. In this study, various VNS intensities were tested in their capacity to modulate cortical excitability in the direct cortical stimulation model.Methods: Rats (n=15) were implanted with a cuff-electrode around the cervical left vagus nerve and with stimulation electrodes placed bilaterally on the rat motor cortex. VNS (30 Hz, 500 sec, 30 sec ON/300 sec OFF) at 4 different intensities (0, 0.25, 0.5 and 1 mA) was administered randomly in each rat at 4 consecutive days. For each stimulus intensity, the motor seizure threshold (MST) was assessed before (MSTbaseline) and immediately after 1 h of VNS (MSTVNS), during two sessions. Overall mean difference between MSTVNS and MSTbaseline (i.e. MSTdelta) was calculated for each stimulus intensity.Results: An overall significant increase in MSTdelta was observed following 1 h of VNS at 0.25 mA compared to SHAM stimulation (63.9 A 12.7 A vs 2.8 A 12.6 A respectively; p = 0.001). VNS at 0.5 mA also significantly increased the MSTdelta compared to SHAM stimulation (44.9 A 12.7 A vs 2.8 A 12.6 A respectively; p = 0.021). No difference in MSTdelta could be found between the highest (1 mA) and lowest (0 mA) stimulation group (1 A 12.3 A vs 2.8 A 12.6 A respectively; p = 0.079), nor between VNS at 0.25 mA and VNS at 0.5 mA (p = 0.300).Conclusions: VNS induced an intensity-dependent, U-shaped reduction in cortical excitability in the direct cortical stimulation model. The greatest effect was observed for VNS at moderate intensity (0.25 mA).