Dependence of excitability indices on membrane channel dynamics, myelin impedance, electrode location and stimulus waveforms in myelinated and unmyelinated fibre models.

Neuronal excitability is determined in a complex way by several interacting factors, such as membrane dynamics, fibre geometry, electrode configuration, myelin impedance, neuronal terminations[Formula: see text] This study aims to increase understanding in excitability, by investigating the impact of these factors on different models of myelinated and unmyelinated fibres (five well-known membrane models are combined with three electrostimulation models, that take into account the spatial structure of the neuron). Several excitability indices (rheobase, polarity ratio, bi/monophasic ratio, time constants[Formula: see text]) are calculated during extensive parameter sweeps, allowing us to obtain novel findings on how these factors interact, e.g. how the dependency of excitability indices on the fibre diameter and myelin impedance is influenced by the electrode location and membrane dynamics. It was found that excitability is profoundly impacted by the used membrane model and the location of the neuronal terminations. The approximation of infinite myelin impedance was investigated by two implementations of the spatially extended non-linear node model. The impact of this approximation on the time constant of strength-duration plots is significant, most importantly in the Frankenhaeuser-Huxley membrane model for large electrode-neuron separations. Finally, a multi-compartmental model for C-fibres is used to determine the impact of the absence of internodes on excitability. Graphical Abstract Electrostimulation models, obtained by combining five membrane models with three representations of the neuronal cable equation, are fed with electrode and stimulus input parameters. The dependency of neuronal excitability on the interaction of these input parameters is determined by deriving excitability indices from the spatiotemporal model response. The impact of the myelin impedance and the fibre diameter on neural excitability is also considered.