Influence of pulse sequence, polarity and amplitude on magnetic stimulation of human and porcine peripheral nerve

1. Mammalian phrenic nerve, in a trough filled with saline, was excited by magnetic coil (MC)induced stimuli at defined stimulation sites, including t he negative-going first spatial derivative of the induced electric field al ong 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 outp ut setting was elicited by an induced damped polyphasic pulse consisting of an initial quarter-cycle hyperpolarization followed by a half-cycle depola rization compared with a predominantly 'monophasic' quarter-cycle depolariz ation. 2. Simulation studies demonstrated that the increased efficacy of the induc ed quarter-cycle hyperpolarizing-half-cycle depolarizing polyphasic pulse w as mainly attributed to the greater duration of the outward membrane curren t phase, resulting in a greater outward charge transfer afforded by the hal f-cycle (i.e. quarter-cycles 2 and 3). The advantage of a fast rising initi al quarter-cycle depolarization was more than offset by the slower rising, but longer duration depolarizing half-cycle. 3. Simulation further revealed that the quarter-cycle hyperpolarization-hal f-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 effi cacy reflects modest reversal of Na+ inactivation by the very brief initial hyperpolarization. 4. In vitro, at low bath temperature, the nerve response to an initial quar ter-cycle depolarization declined in amplitude as the second hyperpolarizin g phase progressively increased in amplitude and duration. This 'pull-down' phenomenon nearly disappeared as the bath temperature approached 37 degree s C. Possibly, at the reduced temperature, delay in generation of the actio n potential permitted the hyperpolarization phase to reduce excitation. 5. Pull-down was not observed in the thenar muscle responses to median nerv e stimulation in a normal human at normal temperature. However, pull-down e merged when the median nerve was cooled by placing ice over the forearm. 6. In a nerve at subnormal temperature straddled with non-conducting inhomo geneities, polyphasic pulses of either polarity elicited the largest respon ses. This was also seen when stimulating distal median nerve at normal temp erature. These results imply excitation by hyperpolarizing-depolarizing pul se sequences at two separate sites. Similarly, polyphasic pulses elicited t he largest responses from nerve roots and motor cortex. 7. The pull-down phenomenon has a possible clinical application in detectin g pathologically slowed activation of Na+ channels. The current direction o f the polyphasic waveform may become a significant factor with the increasi ng use of repetitive magnetic stimulators which, for technical reasons, ind uce a cosine-shaped half-cycle, preceded and followed by quarter-cycles of opposite polarity.