Tracking small sensory nerve action potentials in human axonal excitability studies

Background: Excitability studies on normal and diseased human axons in vivo have been greatly enhanced by fast non-invasive threshold-tracking techniques, using surface stimulation and recording. Although sensory axons are often more affected in disease, most studies to date have focussed on motor axons, because of technical difficulties in resolving pathologically small nerve volleys in the presence of noise and stimulus artefact. New methods: This paper describes techniques for tracking low-amplitude compound action potentials, using a battery-powered, isolated preamplifier of simple construction with high common mode rejection (>125 dB [balanced inputs]) and low noise (<0.4 mu V referred to inputs [shorted]). Results: We demonstrate the preamplifier's capability by tracking targets as small as 2 mu V for a full range of excitability measurements without the usual distortion due to residual stimulus artefact and without the need for clamping, additional filtering or ensemble averaging. Comparison with existing methods: In practice, threshold-tracking studies have been unable to study sensory axons when the maximal compound sensory action potential was less than about 15 mu V. The techniques and amplifier in the present study allow measurements to be made from nerve with maximal responses less than half that size, and we present three recordings in patients with pathologically small nerve action potentials <= 7 mu V. Conclusions: Based on measurements of stimulus artefact distortion, noise and the performance in experiments, we conclude that the techniques described here will facilitate the study of diseased axons for which the sensory potentials have high thresholds and may be only a few microvolts in amplitude. (C) 2018 Elsevier B.V. All rights reserved.