Effect of nerve cuff electrode geometry on onset response firing in high-frequency nerve conduction block

Abstract

The delivery of high-frequency alternating currents has been shown to produce a focal and reversible conduction block in whole nerve and is a potential therapeutic option for various diseases and disorders involving pathological or undesired neurological activity. However, delivery of high-frequency alternating current to a nerve produces a finite burst of neuronal firing, called the onset response, before the nerve is blocked. Reduction or elimination of the onset response is very important to moving this type of nerve block into clinical applications since the onset response is likely to result in undesired muscle contraction and pain. This paper describes a study of the effect of nerve cuff electrode geometry (specifically, bipolar contact separation distance), and waveform amplitude on the magnitude and duration of the onset response. Electrode geometry and waveform amplitude were both found to affect these measures. The magnitude and duration of the onset response showed a monotonic relationship with bipolar separation distance and amplitude. The duration of the onset response varied by as much as 820% on average for combinations of different electrode geometries and waveform amplitudes. Bipolar electrodes with a contact separation distance of 0.5 mm resulted in the briefest onset response on average. Furthermore, the data presented in this study provide some insight into a biophysical explanation for the onset response. These data suggest that the onset response consists of two different phases: one phase which is responsive to experimental variables such as electrode geometry and waveform amplitude, and one which is not and appears to be inherent to the transition to the blocked state. This study has implications for nerve block electrode and stimulation parameter selection for clinical therapy systems and basic neurophysiology studies.

Fig. 1

Typical gastrocnemius muscle force when HFAC is delivered to the sciatic nerve. Circle designates approximate timing of Phase I of the response. Double arrow designates approximate timing of Phase II of the onset response. Each of the three measures of onset response is schematically depicted in this trial plot.

Fig. 2

Diagram of the experimental setup showing nerve cuff electrode placement. A tripolar proximal stimulating electrode was always used. HFAC blocking nerve cuff electrodes of various geometries were placed at the branch point for the common peroneal nerve for each of the block randomized trials. The inset shows a cross sectional depiction of a J-cuff electrode on the sciatic nerve.

Fig. 3

Block threshold trial for a bipolar electrode with contact separation of 1.0 mm. Supramaximal twitches are delivered at ~1 Hz through the proximal electrode as designated by the black arrows. As indicated by the grey bar, the HFAC is turned on at approximately 6.5 s with an amplitude of 9.0 mA and is decremented in 0.1 mA steps until conduction block is no longer complete. The circle designates the first twitch conducted by a partially conducting nerve. Full conduction is restored by the following proximal stimulation pulse.

Fig. 4

Muscle force recordings from bipolar high-frequency onset burst trials. (a) Typical onset response for an electrode with a bipolar separation distance of 4.0 mm at 100% block threshold. (b) Typical onset response for an electrode with a bipolar separation distance of 0.5 mm at 200% block threshold. (c) Extreme onset response for an electrode with a bipolar separation distance of 4.0 mm at 100% block threshold. (d) Extreme onset response for an electrode with a bipolar separation distance of 0.5 mm at 200% block threshold.

Fig. 5

Peak force with bipolar separation distance and HFAC amplitude for the five rats (475 observations in total). Error bars represent the standard error of the mean (Note: standard deviation is √24 =~ 4.9 times larger than the SEM). The grey shaded region represents the approximate range of experimentally measured proximal twitch force.

Fig. 6

Integral of onset response with bipolar separation distance and HFAC amplitude for the five rats (475 observations in total). Error bars represent the standard error of the mean (Note: standard deviation is √24 =~ 4.9 times larger than the SEM). The grey shaded region represents the approximate range of the integral of experimentally measured proximal twitch force.

Fig. 7

Time for muscle force to decay to 5% of peak value with bipolar separation distance and HFAC amplitude for the five rats (475 observations in total). Error bars represent the standard error of the mean (Note: standard deviation is √24 =~ 4.9 times larger than the SEM).