Inversion of the current-distance relationship by transient depolarization

The objective of this research was to develop a technique to excite selectively nerve fibers distant from an electrode without exciting nerve fibers close to the electrode. The shape of the stimulus current waveform was designed based on the nonlinear conductance properties of neuronal sodium channels. Models of mammalian peripheral myelinated axons and experimental measurements on cat sciatic nerve were used to determine the effects of subthreshold polarization on neural excitability and recruitment. Subthreshold membrane depolarization generated a transient decrease in neural excitability and thus an increase in the threshold for stimulation by a subsequent stimulus pulse. The decrease in excitability increased as the duration and amplitude of the subthreshold depolarization were increased, and the increase in threshold was greater for fibers close to the electrode. When a depolarizing stimulus pulse was applied immediately after the subthreshold depolarization, nerve fibers far from the electrode could be stimulated without stimulating fibers close to the electrode. Subthreshold depolarizing prepulses inverted the current-distance relationship and allowed selective stimulation of nerve fibers far from the electrode.