Sub-threshold depolarizing pre-pulses can enhance the efficiency of biphasic stimuli in transcutaneous neuromuscular electrical stimulation

Abstract

There is multiple evidence in the literature that a sub-threshold pre-pulse, delivered immediately prior to an electrical stimulation pulse, can alter the activation threshold of nerve fibers and motor unit recruitment characteristics. So far, previously published works combined monophasic stimuli with sub-threshold depolarizing pre-pulses (DPPs) with inconsistent findings—in some studies, the DPPs decreased the activation threshold, while in others it was increased. This work aimed to evaluate the effect of DPPs during biphasic transcutaneous electrical stimulation and to study the possible mechanism underlying those differences. Sub-threshold DPPs between 0.5 and 15 ms immediately followed by biphasic or monophasic pulses were administered to the tibial nerve; the electrophysiological muscular responses (motor-wave, M-wave) were monitored via electromyogram (EMG) recording from the soleus muscle. The data show that, under the specific studied conditions, DPPs tend to lower the threshold for nerve fiber activation rather than elevating it. DPPs with the same polarity as the leading phase of biphasic stimuli are more effective to increase the sensitivity. This work assesses for the first time the effect of DPPs on biphasic pulses, which are required to achieve charge-balanced stimulation, and it provides guidance on the effect of polarity and intensity to take full advantage of this feature. Graphical abstractIn this work, the effect of sub-threshold depolarizing pre-pulses (DPP) is investigated in a setup with transcutaneous electrical stimulation. We found that, within the tested 0–15 ms DPP duration range, the DPPs administered immediately before biphasic pulses proportionally increase the nerve excitability as visible in the M-waves recorded from the soleus muscle. Interestingly, these findings oppose published results, where DPPs, administered immediately before monophasic stimuli via implanted electrodes, led to decrease of nerve excitability.

The Effect of Sub-Threshold Pre-Pulses on Neural Activation Depends on Electrode Configuration

“…Using the bipolar electrode configuration that is relevant to stimulation via many nerve cuffs, electrode arrays and proposed electroceutical devices, we observed opposite effects of prepulses on stimulation threshold that are also in line with other published literature that does not follow the pioneer work by Grill and Mortimer [4], [11]- [13]. Most of these studies were carried out with human transcutaneous stimulation, either in a clearly bipolar configuration [11], [12] or in a monopolar setting in which the reference electrode was relatively close to the stimulated nervous structure [4].…”

“…In the same study, using a nerve cuff to stimulate the sciatic nerve in cat, the investigators described a diminishing additional effect of increasing pre-pulse duration above 5ms. All studies that tested multiple pre-pulse durations and describe a significant effect of increasing it above a duration of approximately 5ms were conducted using transcutaneous stimulation [4], [11], [12], where the tissue separating the target nerve from the electrodes is likely to influence these temporal aspects.…”

“…Mortimer and Grill described in 1995 an effect of hyperpolarizing pre-pulses (HPPs) to decrease threshold [5] and an effect of depolarizing pre-pulses (DPPs) to increase threshold for activation [5]- [7]. Over the following two decades, several studies agreed with these original findings [8]- [10], but other research groups reported opposing results, describing a decrease of stimulation threshold with DPPs [4], [11]- [13].…”

“…Sub-threshold means that the prepulse alone does not elicit action potentials (APs). Published data on the effect of such sub-threshold pre-pulses in computer simulations and various experimental settings are apparently contradictory [4]. Mortimer and Grill described in 1995 an effect of hyperpolarizing pre-pulses (HPPs) to decrease threshold [5] and an effect of depolarizing pre-pulses (DPPs) to increase threshold for activation [5]- [7].…”

An Investigation of Neural Stimulation Efficiency With Gaussian Waveforms

“…They are often biphasic so that the overall net charge injection is near zero. Many studies have been conducted to investigate variations of the rectangular biphasic waveform such as interphase gaps (IPG), asymmetric pulses [5]- [7] and pre pulses [8]- [11]. Some of these studies sought to discover whether non-rectangular stimulation waveforms might have an advantage in terms of efficiency or selectivity.…”