Reproducibility of indices of axonal excitability in human subjects

Abstract

Objectives: Different indices of axonal excitability are now being measured in human subjects, both normal volunteers undergoing some test manoeuvre and patients with a variety of peripheral nerve disorders. The reproducibility of these indices has not previously been established, and was determined for cutaneous afferents in the median nerve of 12 healthy subjects, using threshold tracking techniques.Methods: Refractoriness and supernormality were determined as the change in stimulus current required to produce a predetermined target potential when conditioned by a supramaximal stimulus at appropriate conditioning-test intervals. Strength-duration time constant was calculated from the threshold currents using unconditioned test stimuli of 0.1 ms and 1.0 ms. The effects of changes in membrane potential on these indices was assessed by applying subthreshold DC currents (from 50% depolarizing to 50% hyperpolarizing), using the reciprocal of threshold (i.e., ‘excitability’) as an indicator of membrane potential. The intraindividual reproducibility was determined by repeating the study on each subject up to 10 times.Results: Refractoriness and supernormality were variable between subjects (mean±SD of 31.5±9.5% and 13.2±3.8%, respectively) and within subjects (coefficient of variation 0.2104 and 0.21849, respectively). τSD showed even greater interindividual variability (499.2±115 μs) and intraindividual variability (coefficient of variation 0.2339). The slopes of relationships between each of the indices and axonal ‘excitability’ suggest that refractoriness is extremely sensitive to changes in excitability (0.9767±0.1907), τSD less so (0.3766±0.1322), supernormality least (0.2223±0.1268).Conclusions: Under controlled conditions, refractoriness is the most sensitive and least variable of the indices of axonal excitability. However, small decreases in temperature greatly increase refractoriness but have little effect on τSD. Given that 3 indices reflect different biophysical mechanisms, nodal and internodal, greater insight into the functional state of peripheral nerve axons will come when there are coherent changes in all 3 indices.