Emily L. Foldes

Design, fabrication and evaluation of a conforming circumpolar peripheral nerve cuff electrode for acute experimental use.

Nerve cuff electrodes are a principle tool of basic and applied electro-neurophysiology studies and are championed for their ability to achieve good nerve recruitment with low thresholds. We describe the design and method of fabrication for a novel circumpolar peripheral nerve electrode for acute experimental use. This cylindrical cuff-style electrode provides approximately 270° of radial electrode contact with a nerve for each of an arbitrary number of contacts, has a profile that allows for simple placement and removal in an acute nerve preparation, and is designed for adjustment of the cylindrical diameter to ensure a close fit on the nerve. For each electrode, the electrical contacts were cut from 25 μm platinum foil as an array so as to maintain their positions relative to each other within the cuff. Lead wires were welded to each intended contact. The structure was then molded in silicone elastomer, after which the individual contacts were electrically isolated. The final electrode was curved into a cylindrical shape with an inner diameter corresponding to that of the intended target nerve. The positions of these contacts were well maintained during the molding and shaping process and failure rates during fabrication due to contact displacements were very low. Established electrochemical measurements were made on one electrode to confirm expected behavior for a platinum electrode and to measure the electrode impedance to applied voltages at different frequencies. These electrodes have been successfully used for nerve stimulation, recording, and conduction block in a number of different acute animal experiments by several investigators.

Conduction Block of Peripheral Nerve Using High Frequency Alternating Currents Delivered through an Intrafascicular Electrode

Many diseases are characterized by undesired or pathological neural activity. The local delivery of high‐frequency currents has been shown to be an effective method for blocking neural conduction in peripheral nerves and may provide a therapy for these conditions. To date, all studies of high‐frequency conduction block have utilized extraneural (cuff) electrodes to achieve conduction block. In this study we show that high‐frequency conduction block is feasible using intrafascicular electrodes. Muscle Nerve, 2010

Effect of Bipolar Cuff Electrode Design on Block Thresholds in High-Frequency Electrical Neural Conduction Block

Many medical conditions are characterized by undesired or pathological peripheral neurological activity. The local delivery of high-frequency alternating currents (HFAC) has been shown to be a fast acting and quickly reversible method of blocking neural conduction and may provide a treatment alternative for eliminating pathological neural activity in these conditions. This work represents the first formal study of electrode design for high-frequency nerve block, and demonstrates that the interpolar separation distance for a bipolar electrode influences the current amplitudes required to achieve conduction block in both computer simulations and mammalian whole nerve experiments. The minimal current required to achieve block is also dependent on the diameter of the fibers being blocked and the electrode-fiber distance. Single fiber simulations suggest that minimizing the block threshold can be achieved by maximizing both the bipolar activating function (by adjusting the bipolar electrode contact separation distance) and a synergistic addition of membrane sodium currents generated by each of the two bipolar electrode contacts. For a rat sciatic nerve, 1.0-2.0 mm represented the optimal interpolar distance for minimizing current delivery.

Effect of Nerve Cuff Electrode Geometry on Onset Response Firing in High-Frequency Nerve Conduction Block

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.

Electrical conduction block in large nerves: high-frequency current delivery in the nonhuman primate.

Recent studies have made significant progress toward the clinical implementation of high‐frequency conduction block (HFB) of peripheral nerves. However, these studies were performed in small nerves, and questions remain regarding the nature of HFB in large‐diameter nerves. This study in nonhuman primates shows reliable conduction block in large‐diameter nerves (up to 4.1 mm) with relatively low‐threshold current amplitude and only moderate nerve discharge prior to the onset of block. Muscle Nerve, 2011

Separated interface nerve electrode prevents direct current induced nerve damage

Direct current, DC, can be used to quickly and reversibly block activity in excitable tissue, or to quickly and reversibly increase or decrease the natural excitability of a neuronal population. However, the practical use of DC to control neuronal activity has been extremely limited due to the rapid tissue damage caused by its use. We show that a separated interface nerve electrode, SINE, is a much safer method to deliver DC to excitable tissue and may be valuable as a laboratory research tool or potentially for clinical treatment of disease.

Electrode design for high frequency block: Effect of bipolar separation on block thresholds and the onset response

The delivery of high frequency alternating currents (HFAC) to peripheral nerves has been shown to produce a rapid and reversible nerve conduction block at the site of the electrode, and holds therapeutic promise for diseases associated with undesired or pathological neural activity. It has been known since 1939 that the configuration of an electrode used for nerve block can impact the quality of the block, but to date no formal study of the impact of electrode design on high frequency nerve block has been performed. Using a mammalian small animal model, it is demonstrated that the contact separation distance for a bipolar nerve cuff electrode can impact two important factors related to high frequency nerve block: the amplitude of HFAC required to block the nerve (block threshold), and the degree to which the transient “onset response” which always occurs when HFAC is first applied to peripheral nerves, is present. This study suggests that a bipolar electrode with a separation distance of 1.0 mm minimizes current delivery while producing high frequency block with a minimal onset response in the rat sciatic nerve.

Reduction of the onset response in high frequency nerve block with amplitude ramps from non-zero amplitudes

High frequency alternating current (HFAC) waveforms reversibly block conduction in mammalian peripheral nerves. The initiation of the HFAC produces an onset response in the nerve before complete block occurs. An amplitude ramp, starting from zero amplitude, is ineffective in eliminating this onset response. In fact, it makes the onset worse. We postulated that initiating the ramp from a non-zero amplitude would produce a different effect on the onset. This was tested in an in-vivo rat sciatic nerve model. HFAC was applied at supra block threshold amplitudes and then reduced to a lower amplitude (0%, 25% 50 %, 75% and 90% of the suprathreshold amplitude). The amplitude was then increased again to the original supra block threshold amplitude. This normally produces a second period of onset response if increased as a step. However, an amplitude ramp was successful in eliminating this onset. This was always possible for the ramps up from 50%, 75 % and 90% block threshold amplitude, but never from 0% or 25% of the block threshold amplitude. This maneuver can potentially be used to maintain complete nerve block, transition to partial block and then resume complete block without initiating another onset.

Counted cycles method to quantify the onset response in high-frequency peripheral nerve block

The clinical use of high frequency alternating current (HFAC) to block nerve conduction in peripheral nerves is limited due to the large volley of nerve activity generated at the initiation of HFAC. This “onset response” must be characterized in order to determine if it is possible to eliminate it. In this study, preliminary experiments were conducted in an in-vivo animal model using counted cycles of HFAC to investigate and quantify the onset response. Using this method, it is possible to show quantitatively that the onset response has two phases with distinct characteristics. Eliminating the onset response is likely to require addressing each phase independently. It was also possible to show that HFAC establishes a complete block of nerve activity in 50–100 ms.