Influence of pulse sequence, polarity and amplitude on magnetic stimulation of human and porcine peripheral nerve
Authors: Maccabee P. J. , Nagarajan S. S. , Amassian V. E. , Durand D. M. , Szabo A. Z. , Ahad A. B. , Cracco R. Q. , Lai K. S. , Eberle L. P. 
Published: September 2004

Mammalian phrenic nerve, in a trough filled with saline, was excited by magnetic coil (MC)‐induced stimuli at defined stimulation sites, including the negative‐going first spatial derivative of the induced electric field along a straight nerve, at a bend in the nerve, and at a cut nerve ending. At all such sites, the largest amplitude response for a given stimulator output setting was elicited by an induced damped polyphasic pulse consisting of an initial quarter‐cycle hyperpolarization followed by a half‐cycle depolarization compared with a predominantly ‘monophasic’ quarter‐cycle depolarization.
Simulation studies demonstrated that the increased efficacy of the induced quarter‐cycle hyperpolarizing‐half‐cycle depolarizing polyphasic pulse was mainly attributed to the greater duration of the outward membrane current phase, resulting in a greater outward charge transfer afforded by the half‐cycle (i.e. quarter‐cycles 2 and 3). The advantage of a fast rising initial quarter‐cycle depolarization was more than offset by the slower rising, but longer duration depolarizing half‐cycle.
Simulation further revealed that the quarter‐cycle hyperpolarization‐half‐cycle depolarization showed only a 2.6 % lowering of peak outward current and a 3.5 % lowering of outward charge transfer at threshold, compared with a half‐cycle depolarization alone. Presumably, this slight increase in efficacy reflects modest reversal of Na+ inactivation by the very brief initial hyperpolarization.
In vitro, at low bath temperature, the nerve response to an initial quarter‐cycle depolarization declined in amplitude as the second hyperpolarizing phase progressively increased in amplitude and duration. This ‘pull‐down’ phenomenon nearly disappeared as the bath temperature approached 37 °C. Possibly, at the reduced temperature, delay in generation of the action potential permitted the hyperpolarization phase to reduce excitation.
Pull‐down was not observed in the thenar muscle responses to median nerve stimulation in a normal human at normal temperature. However, pull‐down emerged when the median nerve was cooled by placing ice over the forearm.
In a nerve at subnormal temperature straddled with non‐conducting inhomogeneities, polyphasic pulses of either polarity elicited the largest responses. This was also seen when stimulating distal median nerve at normal temperature. These results imply excitation by hyperpolarizing‐depolarizing pulse sequences at two separate sites. Similarly, polyphasic pulses elicited the largest responses from nerve roots and motor cortex.
The pull‐down phenomenon has a possible clinical application in detecting pathologically slowed activation of Na+ channels. The current direction of the polyphasic waveform may become a significant factor with the increasing use of repetitive magnetic stimulators which, for technical reasons, induce a cosine‐shaped half‐cycle, preceded and followed by quarter‐cycles of opposite polarity.