Intensity-dependent modulatory effects of vagus nerve stimulation on cortical excitability

Objectives: Vagus nerve stimulation (VNS) is an effective treatment for refractory epilepsy. It remains unknown whether VNS efficacy is dependent on output current intensity. The present study investigated the effect of various VNS output current intensities on cortical excitability in the motor cortex stimulation rat model. The hypothesis was that output current intensities in the lower range are sufficient to significantly affect cortical excitability. Material and methods: VNS at four output current intensities (0 mA, 0.25 mA, 0.5 mA and 1 mA) was randomly administered in rats (n = 15) on four consecutive days. Per output current intensity, the animals underwent five-one-hour periods: (i) baseline, (ii) VNS1, (iii) wash-out1, (iv) VNS2 and (v) wash-out2. After each one-hour period, the motor seizure threshold (MST) was measured and compared to baseline (i.e. {increment}MST baseline , {increment}MST VNS1 , {increment}MST wash-out1 , {increment}MST VNS2 and {increment}MST wash-out2 ). Finally, the mean {increment}MST baseline , mean {increment}MST wash-out1 , mean {increment}MST wash-out2 and mean {increment}MST VNS per VNS output current intensity were calculated. Results: No differences were found between the mean {increment}MST baseline , mean {increment}MST wash-out1 and mean {increment}MST wash-out2 within each VNS output current intensity. The mean {increment}MST VNS at 0 mA, 0.25 mA, 0.5 mA and 1 mA was 15.3 ± 14.6 μA, 101.8 ± 23.5 μA, 108.1 ± 24.4 μA and 85.7 ± 18.1 μA respectively. The mean {increment}MST VNS at 0.25 mA, 0.5 mA and 1 mA were significantly larger compared to the mean {increment}MST VNS at 0 mA (P = 0.002 for 0.25 mA; P = 0.001 for 0.5 mA; P = 0.011 for 1 mA). Conclusions: This study confirms efficacy of VNS in the motor cortex stimulation rat model and indicates that, of the output current intensities tested, 0.25 mA is sufficient to decrease cortical excitability and higher output current intensities may not be required. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.