Effects of Neural Refractoriness on Spatio-temporal Variability in Spike Initiations with Electrical Stimulation

In this paper, the effects of neural refractoriness on action potential (spike) initiations with electrical stimulation are investigated using computer modeling and simulation techniques. The computational model was composed of a myelinated nerve fiber with 50 nodes of Ranvier, each consisting of stochastic sodium and potassium channels, making it possible to represent the fluctuations of spike initiation. A series of two-pulse stimuli was presented by a stimulating electrode above the central (26th) node of Ranvier. The amplitude of the first (masker) pulse stimulus was set such that the masker pulse stimulus evoked spikes on each trial, while that of the second (probe) pulse stimulus was set such that the probe pulse stimulus evoked spikes on a half of trials, threshold values. Then the transmembrane potentials in response to the probe pulse stimulus were recorded at each node (i.e., 1-50 nodes) in order to determine the spike initiation node and time. From the observation of the spike initiation node and time, a spatio-temporal histogram as well as a spatial variability and a temporal variability of spike initiations was generated which allowed us to interpret fluctuations in spike initiation node and time. It was shown that the distribution of spike initiations tended to become greater spatially and longer temporally as the masker-probe intervals (MPIs) of the two-pulse stimuli shortened. It was also shown that the number of activated sodium channels as functions of space and time tended to become smaller due to inactivation of sodium channels and varied spatially and temporally as MPIs shortened. These findings may imply that the stochastic sodium channels during a relative refractory period may contribute to enhancing the fluctuations in spike initiations, and give us an insight into encoding information with electric stimuli to improve the performance of the prosthetic devices, especially cochlear implants.