Conduction block in peripheral nerves: effect of high frequency stimulation on different fiber types
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Selective stimulation and conduction block of specific nerve fibers has been a major area of research in neuroscience. The potential clinical and neurophysiological applications have warranted reliable techniques for transiently blocking conduction through nerves. High Frequency Alternating Current (HFAC) waveforms have been found to induce a reversible and repeatable block in peripheral nerves; however the effect of these waveforms on the neural activity of individual fiber types is currently unknown. Understanding this effect is critical if clinical applications are to be pursued. This dissertation work utilized extracellular electrophysiological techniques to characterize the activity of different fiber type populations in peripheral nerves during application of HFAC waveforms. First, we investigated the phenomenon in the homogeneous unmyelinated nerves of the sea-slug, Aplysia californica. Although complete reversible block was demonstrated in these nerves, a non-monotonic relationship of block threshold to frequency was found which differed from previously published work in the field. We then investigated the effect of HFAC waveforms on amphibian mixed nerves and studied the response of specific fiber types by isolating different components of the compound action potential. We validated our results from the Aplysia nerves by determining the block thresholds of the larger diameter, myelinated A-fibers and comparing them with those of the smaller diameter, unmyelinated C-fibers. We also showed that block threshold behavior during application of the HFAC waveform depends on the nerve fiber type, and this property can be used to selectively block specific fiber types. Finally, we examined the recovery time after block induction in unmyelinated nerves and found that recovery from block was dependent on the duration of application of the HFAC waveform. The time-dependent distribution of the recovery time and the non-monotonic threshold behavior in the smaller diameter unmyelinated nerves indicate that multiple mechanisms are involved in block induction using HFAC waveforms, and these mechanisms are dependent not only on the blocking stimulus but also on the characteristics of the nerve fiber. Overall, this work demonstrates that HFAC waveforms may enable inherent peripheral nerve properties to be exploited for potential clinical applications related to the treatment of unwanted neural activity.