The interaction of pulse width and current intensity on the extent of cortical plasticity evoked by vagus nerve stimulation

BACKGROUND Repeatedly pairing a tone with a brief burst of vagus nerve stimulation (VNS) results in a reorganization of primary auditory cortex (A1). The plasticity-enhancing and memory-enhancing effects of VNS follow an inverted-U response to stimulation intensity, in which moderate intensity currents yield greater effects than low or high intensity currents. It is not known how other stimulation parameters effect the plasticity-enhancing effects of VNS. OBJECTIVE We sought to investigate the effect of pulse-width and intensity on VNS efficacy. Here, we used the extent of plasticity induced by VNS-tone pairing to assess VNS efficacy. METHODS Rats were exposed to a 9 kHz tone paired to VNS with varying current intensities and pulse widths. Cortical plasticity was measured as changes in the percent of area of primary auditory cortex responding to a range of sounds in VNS-treated rats relative to naïve rats. RESULTS We find that a combination of low current intensity (200 μA) and short pulse duration (100 μs) is insufficient to drive cortical plasticity. Increasing the pulse duration to 500 μs results in a reorganization of receptive fields in A1 auditory cortex. The extent of plasticity engaged under these conditions is less than that driven by conditions previously reported to drive robust plasticity (800 μA with 100 μs wide pulses). CONCLUSION These results suggest that the plasticity-enhancing and memory-enhancing effects of VNS follow an inverted-U response of stimulation current that is influenced by pulse width. Furthermore, shorter pulse widths may offer a clinical advantage when determining optimal stimulation current. These findings may facilitate determination of optimal VNS parameters for clinical application.

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