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.

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.

Comparison of sleep questionnaires in the assessment of sleep disturbances in children with autism spectrum disorders.

BACKGROUND AND PURPOSE: The purpose of this study was to compare two parent completed questionnaires, the Modified Simonds & Parraga Sleep Questionnaire (MSPSQ) and the Children's Sleep Habits Questionnaire (CSHQ), used to characterize sleep disturbances in young children with autism spectrum disorders (ASD). Both questionnaires have been used in previous work in the assessment and treatment of children with ASD and sleep disturbance. PARTICIPANTS AND METHODS: Parents/caregivers of a sample of 124 children diagnosed with ASD with an average age of six years completed both sleep questionnaires regarding children's sleep behaviors. Internal consistency of the items for both measures was evaluated as well as the correlation between the two sleep measures. A Receiver Operating Characteristics (ROC) curve analysis was also conducted to examine the predictive power of the MSPSQ. RESULTS: More than three quarters of the sample (78%) were identified as poor sleepers on the CSHQ. Cronbach's alpha for the items on the CSHQ was 0.68 and Cronbach's alpha for items on the MSPSQ was 0.67. The total scores for MSPSQ and CSHQ were significantly correlated (r=.70, p<.01). After first identifying the poor sleepers based on the CSHQ, an area under the curve was 0.89 for the MSPSQ. Using a cut off score of 56 on the MSPSQ, sensitivity was .86 and specificity was .70. CONCLUSIONS: In this sample of children with ASD, sleep disturbances were common across all cognitive levels. Preliminary findings suggest that, similar to the CSHQ, the MSPSQ has adequate internal consistency. The two measures were also highly correlated. A preliminary cut off of 56 on the MSPSQ offers high sensitivity and specificity commensurate with the widely used CSHQ.

Conduction block of whole nerve without onset firing using combined high frequency and direct current.

This study investigates a novel technique for blocking a nerve using a combination of direct and high frequency alternating currents (HFAC). HFAC can produce a fast acting and reversible conduction block, but cause intense firing at the onset of current delivery. We hypothesized that a direct current (DC) block could be used for a very brief period in combination with HFAC to block the onset firing, and thus establish a nerve conduction block which does not transmit onset response firing to an end organ. Experiments were performed in rats to evaluate (1) nerve response to anodic and cathodic DC of various amplitudes, (2) degree of nerve activation to ramped DC, (3) a method of blocking onset firing generated by high frequency block with DC, and (4) prolonged non-electrical conduction failure caused by DC delivery. The results showed that cathodic currents produced complete block of the sciatic nerve with a mean block threshold amplitude of 1.73 mA. Ramped DC waveforms allowed for conduction block without nerve activation; however, down ramps were more reliable than up ramps. The degree of nerve activity was found to have a non-monotonic relationship with up ramp time. Block of the onset response resulting from 40 kHz current using DC was achieved in each of the six animals in which it was attempted; however, DC was found to produce a prolonged conduction failure that likely resulted from nerve damage.

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.

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.

Nerve conduction block using combined thermoelectric cooling and high frequency electrical stimulation.

Conduction block of peripheral nerves is an important technique for many basic and applied neurophysiology studies. To date, there has not been a technique which provides a quickly initiated and reversible "on-demand" conduction block which is both sustainable for long periods of time and does not generate activity in the nerve at the onset of the conduction block. In this study we evaluated the feasibility of a combined method of nerve block which utilizes two well established nerve blocking techniques in a rat and cat model: nerve cooling and electrical block using high frequency alternating currents (HFAC). This combined method effectively makes use of the contrasting features of both nerve cooling and electrical block using HFAC. The conduction block was initiated using nerve cooling, a technique which does not produce nerve "onset response" firing, a prohibitive drawback of HFAC electrical block. The conduction block was then readily transitioned into an electrical block. A long-term electrical block is likely preferential to a long-term nerve cooling block because nerve cooling block generates large amounts of exhaust heat, does not allow for fiber diameter selectivity and is known to be unsafe for prolonged 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.

Frequency- and amplitude-transitioned waveforms mitigate the onset response in high-frequency nerve block.

High-frequency alternating currents (HFAC) have proven to be a reversible and rapid method of blocking peripheral nerve conduction, holding promise for treatment of disorders associated with undesirable neuronal activity. The delivery of HFAC is characterized by a transient period of neural firing at its inception, termed the 'onset response'. The onset response is minimized for higher frequencies and higher amplitudes, but requires larger currents. However, the complete block can be maintained at lower frequencies and amplitudes, using lower currents. In this in vivo study on whole mammalian peripheral nerves, we demonstrate a method to minimize the onset response by initiating the block using a stimulation paradigm with a high frequency and large amplitude, and then transitioning to a low-frequency and low-amplitude waveform, reducing the currents required to maintain the conduction block. In five of six animals, it was possible to transition from a 30 kHz to a 10 kHz waveform without inducing any transient neural firing. The minimum transition time was 0.03 s. Transition activity was minimized or eliminated with longer transition times. The results of this study show that this method is feasible for achieving a nerve block with minimal onset responses and current amplitude requirements.

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.

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.

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.

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.