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Kevin L. Kilgore - One of the best experts on this subject based on the ideXlab platform.
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temporary persistence of Conduction Block after prolonged kilohertz frequency alternating current on rat sciatic nerve
Journal of Neural Engineering, 2018Co-Authors: Kevin L. Kilgore, Narendra Bhadra, Niloy Bhadra, Emily Foldes, Tina VrabecAbstract:Objective. Application of kilohertz frequency alternating current (KHFAC) waveforms can result in nerve Conduction Block that is induced in less than a second. Conduction recovers within seconds when KHFAC is applied for about 5–10 min. This study investigated the effect of repeated and prolonged application of KHFAC on rat sciatic nerve with bipolar platinum electrodes. Approach. Varying durations of KHFAC at signal amplitudes for Conduction Block with intervals of no stimulus were studied. Nerve Conduction was monitored by recording peak Gastrocnemius muscle force utilizing stimulation electrodes proximal (PS) and distal (DS) to a Blocking electrode. The PS signal traveled through the Block zone on the nerve, while the DS went directly to the motor end-plate junction. The PS/DS force ratio provided a measure of Conduction patency of the nerve in the Block zone. Main results. Conduction recovery times were found to be significantly affected by the cumulative duration of KHFAC application. Peak stimulated muscle force returned to pre-Block levels immediately after cessation of KHFAC delivery when it was applied for less than about 15 min. They fell significantly but recovered to near pre-Block levels for cumulative stimulus of 50 ± 20 min, for the tested On/Off times and frequencies. Conduction recovered in two phases, an initial fast one (60–80% recovery), followed by a slower phase. No permanent Conduction Block was seen at the end of the observation period during any experiment. Significance. This carry-over Block effect may be exploited to provide continuous Conduction Block in peripheral nerves without continuous application of KHFAC.
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electrical Conduction Block in large nerves high frequency current delivery in the nonhuman primate
Muscle & Nerve, 2011Co-Authors: Michael D Ackermann, Emily L. Foldes, Kevin L. Kilgore, Niloy Bhadra, Christian Ethier, Emily R Oby, Dustin J Tyler, Matthew J Bauman, Lee E MillerAbstract: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.
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Conduction Block of whole nerve without onset firing using combined high frequency and direct current
Medical & Biological Engineering & Computing, 2011Co-Authors: Emily L. Foldes, Kevin L. Kilgore, Michael D Ackermann, Niloy BhadraAbstract: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.
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effect of nerve cuff electrode geometry on onset response firing in high frequency nerve Conduction Block
IEEE Transactions on Neural Systems and Rehabilitation Engineering, 2010Co-Authors: Michael D Ackermann, Emily L. Foldes, Narendra Bhadra, X Wang, Kevin L. KilgoreAbstract: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.
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Conduction Block of peripheral nerve using high frequency alternating currents delivered through an intrafascicular electrode
Muscle & Nerve, 2010Co-Authors: Michael D Ackermann, Emily L. Foldes, Kevin L. Kilgore, Niloy BhadraAbstract: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.
Changfeng Tai - One of the best experts on this subject based on the ideXlab platform.
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Conduction Block of mammalian myelinated nerve by local cooling to 15 30 c after a brief heating
Journal of Neurophysiology, 2016Co-Authors: Zhaocun Zhang, James R Roppolo, Timothy D Lyon, Brian T Kadow, Bing Shen, Jicheng Wang, Andy Lee, Audry Kang, William C De Groat, Changfeng TaiAbstract:This study aimed at understanding thermal effects on nerve Conduction and developing new methods to produce a reversible thermal Block of axonal Conduction in mammalian myelinated nerves. In 13 cats under α-chloralose anesthesia, Conduction Block of pudendal nerves (n = 20) by cooling (5-30°C) or heating (42-54°C) a small segment (9 mm) of the nerve was monitored by the urethral striated muscle contractions and increases in intraurethral pressure induced by intermittent (5 s on and 20 s off) electrical stimulation (50 Hz, 0.2 ms) of the nerve. Cold Block was observed at 5-15°C while heat Block occurred at 50-54°C. A complete cold Block up to 10 min was fully reversible, but a complete heat Block was only reversible when the heating duration was less than 1.3 ± 0.1 min. A brief (<1 min) reversible complete heat Block at 50-54°C or 15 min of nonBlock mild heating at 46-48°C significantly increased the cold Block temperature to 15-30°C. The effect of heating on cold Block fully reversed within ∼40 min. This study discovered a novel method to Block mammalian myelinated nerves at 15-30°C, providing the possibility to develop an implantable device to Block axonal Conduction and treat many chronic disorders. The effect of heating on cold Block is of considerable interest because it raises many basic scientific questions that may help reveal the mechanisms underlying cold or heat Block of axonal Conduction.
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mechanism of nerve Conduction Block induced by high frequency biphasic electrical currents
IEEE Transactions on Biomedical Engineering, 2006Co-Authors: Xu Zhang, James R Roppolo, W C De Groat, Changfeng TaiAbstract:The mechanisms of nerve Conduction Block induced by high-frequency biphasic electrical currents were investigated using a lumped circuit model of the myelinated axon based on Frankenhaeuser-Huxley (FH) model or Chiu-Ritchie-Rogart-Stagg-Sweeney (CRRSS) model. The FH model revealed that the constant activation of potassium channels at the node under the Block electrode, rather than inactivation of sodium channels, is the likely mechanism underlying Conduction Block of myelinated axons induced by high-frequency biphasic stimulation. However, the CRRSS model revealed a different Blocking mechanism where the complete inactivation of sodium channels at the nodes next to the Block electrode caused the nerve Conduction Block. The stimulation frequencies to observe Conduction Block in FH model agree with the observations from animal experiments (greater than 6 kHz), but much higher frequencies are required in CRRSS model (greater than 15 kHz). This frequency difference indicated that the constant activation of potassium channels might be the underlying mechanism of Conduction Block observed in animal experiments. Using the FH model, this study also showed that the axons could recover from Conduction Block within 1 ms after termination of the Blocking stimulation, which also agrees very well with the animal experiments where nerve Block could be reversed immediately once the Blocking stimulation was removed. This simulation study, which revealed two possible mechanisms of nerve Conduction Block in myelinated axons induced by high-frequency biphasic stimulation, can guide future animal experiments as well as optimize stimulation waveforms for electrical nerve Block in clinical applications
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simulation analysis of Conduction Block in myelinated axons induced by high frequency biphasic rectangular pulses
IEEE Transactions on Biomedical Engineering, 2006Co-Authors: Xu Zhang, James R Roppolo, W C De Groat, Changfeng TaiAbstract:Nerve Conduction Block induced by high-frequency biphasic rectangular pulses was analyzed using a lumped circuit model of the myelinated axon based on Frankenhaeuser-Huxley (FH) equations. At the temperature of 37 /spl deg/C, axons of different diameters (2-20 /spl mu/m) can be Blocked completely at supra-threshold intensities when the stimulation frequency is above 10 kHz. However, at stimulation frequencies between 6 kHz and 9 kHz, both nerve Block and repetitive firing of action potentials can be observed at different stimulation intensities. When the stimulation frequency is below 6 kHz, nerve Block does not occur regardless of stimulation intensity. Larger diameter axons have a lower threshold intensity to induce Conduction Block. When temperature is reduced from 37 /spl deg/C to 20 /spl deg/C, the lowest frequency to completely Block large axons (diameters 10-20 /spl mu/m) decreased from 8 kHz to 4 kHz. This simulation study can guide future animal experiments as well as optimize stimulation waveforms for electrical nerve Block in clinical applications.
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simulation analysis of Conduction Block in unmyelinated axons induced by high frequency biphasic electrical currents
IEEE Transactions on Biomedical Engineering, 2005Co-Authors: Changfeng Tai, W C De Groat, James R RoppoloAbstract:Nerve Conduction Block induced by high-frequency biphasic electrical currents is analyzed using a lumped circuit model of the unmyelinated axon based on Hodgkin-Huxley equations. Axons of different diameters (5-20 /spl mu/m) can not be Blocked completely when the stimulation frequency is between 2 kHz and 4 kHz. However, when the stimulation frequency is above 4 kHz, all axons can be Blocked. At high-frequency a higher stimulation intensity is needed to Block nerve Conduction. The larger diameter axon has a lower threshold intensity for Conduction Block. The stimulation waveform in which the pulsewidth changes with frequency is more effective in Blocking nerve Conduction than the waveform in which the pulsewidth is fixed. The activation of potassium channels, rather than inactivation of sodium channels, is the possible mechanism underlying the nerve Conduction Block of the unmyelinated axon. This simulation study further increases our understanding of axonal Conduction Block induced by high-frequency biphasic currents, and can guide future animal experiments as well as optimize stimulation waveforms that might be used for electrical nerve Block in clinical applications.
Niloy Bhadra - One of the best experts on this subject based on the ideXlab platform.
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temporary persistence of Conduction Block after prolonged kilohertz frequency alternating current on rat sciatic nerve
Journal of Neural Engineering, 2018Co-Authors: Kevin L. Kilgore, Narendra Bhadra, Niloy Bhadra, Emily Foldes, Tina VrabecAbstract:Objective. Application of kilohertz frequency alternating current (KHFAC) waveforms can result in nerve Conduction Block that is induced in less than a second. Conduction recovers within seconds when KHFAC is applied for about 5–10 min. This study investigated the effect of repeated and prolonged application of KHFAC on rat sciatic nerve with bipolar platinum electrodes. Approach. Varying durations of KHFAC at signal amplitudes for Conduction Block with intervals of no stimulus were studied. Nerve Conduction was monitored by recording peak Gastrocnemius muscle force utilizing stimulation electrodes proximal (PS) and distal (DS) to a Blocking electrode. The PS signal traveled through the Block zone on the nerve, while the DS went directly to the motor end-plate junction. The PS/DS force ratio provided a measure of Conduction patency of the nerve in the Block zone. Main results. Conduction recovery times were found to be significantly affected by the cumulative duration of KHFAC application. Peak stimulated muscle force returned to pre-Block levels immediately after cessation of KHFAC delivery when it was applied for less than about 15 min. They fell significantly but recovered to near pre-Block levels for cumulative stimulus of 50 ± 20 min, for the tested On/Off times and frequencies. Conduction recovered in two phases, an initial fast one (60–80% recovery), followed by a slower phase. No permanent Conduction Block was seen at the end of the observation period during any experiment. Significance. This carry-over Block effect may be exploited to provide continuous Conduction Block in peripheral nerves without continuous application of KHFAC.
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dynamics and sensitivity analysis of high frequency Conduction Block
Journal of Neural Engineering, 2011Co-Authors: Michael D Ackermann, Niloy Bhadra, Meana Gerges, Peter J ThomasAbstract:The local delivery of extracellular high-frequency stimulation (HFS) has been shown to be a fast acting and quickly reversible method of Blocking neural Conduction and is currently being pursued for several clinical indications. However, the mechanism for this type of nerve Block remains unclear. In this study, we investigate two hypotheses: (1) depolarizing currents promote Conduction Block via inactivation of sodium channels and (2) the gating dynamics of the fast sodium channel are the primary determinate of minimal Blocking frequency. Hypothesis 1 was investigated using a combined modeling and experimental study to investigate the effect of depolarizing and hyperpolarizing currents on high-frequency Block. The results of the modeling study show that both depolarizing and hyperpolarizing currents play an important role in Conduction Block and that the conductance to each of three ionic currents increases relative to resting values during HFS. However, depolarizing currents were found to promote the Blocking effect, and hyperpolarizing currents were found to diminish the Blocking effect. Inward sodium currents were larger than the sum of the outward currents, resulting in a net depolarization of the nodal membrane. Our experimental results support these findings and closely match results from the equivalent modeling scenario: intra-peritoneal administration of the persistent sodium channel Blocker ranolazine resulted in an increase in the amplitude of HFS required to produce Conduction Block in rats, confirming that depolarizing currents promote the Conduction Block phenomenon. Hypothesis 2 was investigated using a spectral analysis of the channel gating variables in a single-fiber axon model. The results of this study suggested a relationship between the dynamical properties of specific ion channel gating elements and the contributions of corresponding conductances to Block onset. Specifically, we show that the dynamics of the fast sodium inactivation gate are too slow to track the high-frequency changes in membrane potential during HFS, and that the behavior of the fast sodium current was dominated by the low-frequency depolarization of the membrane. As a result, in the Blocked state, only 5.4% of nodal sodium channels were found to be in the activatable state in the node closest to the Blocking electrode, resulting in Conduction Block. Moreover, we find that the corner frequency for the persistent sodium channel activation gate corresponds to the frequency below which high-frequency stimuli of arbitrary amplitude are incapable of inducing Conduction Block.
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electrical Conduction Block in large nerves high frequency current delivery in the nonhuman primate
Muscle & Nerve, 2011Co-Authors: Michael D Ackermann, Emily L. Foldes, Kevin L. Kilgore, Niloy Bhadra, Christian Ethier, Emily R Oby, Dustin J Tyler, Matthew J Bauman, Lee E MillerAbstract: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.
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Conduction Block of whole nerve without onset firing using combined high frequency and direct current
Medical & Biological Engineering & Computing, 2011Co-Authors: Emily L. Foldes, Kevin L. Kilgore, Michael D Ackermann, Niloy BhadraAbstract: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.
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Conduction Block of peripheral nerve using high frequency alternating currents delivered through an intrafascicular electrode
Muscle & Nerve, 2010Co-Authors: Michael D Ackermann, Emily L. Foldes, Kevin L. Kilgore, Niloy BhadraAbstract: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.
Lippincott Williams Wilkins - One of the best experts on this subject based on the ideXlab platform.
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correction to association of rate dependent Conduction Block between eccentric coronary sinus to left atrial connections with inducible atrial fibrillation and flutter
Circulation-arrhythmia and Electrophysiology, 2017Co-Authors: Lippincott Williams WilkinsAbstract:In the article by Huang et al, “Association of Rate-Dependent Conduction Block Between Eccentric Coronary Sinus to Left Atrial Connections with Inducible Atrial Fibrillation and Flutter”, …
Norman Latov - One of the best experts on this subject based on the ideXlab platform.
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experimental Conduction Block induced by serum from a patient with anti gm1 antibodies
Annals of Neurology, 1992Co-Authors: Maria Santoro, A Uncini, Massimo Corbo, Susan M Staugaitis, Florian P Thomas, Arthur P Hays, Norman LatovAbstract:: Increased titers of antibodies to GM1 ganglioside in humans are associated with lower motor neuron disease and predominantly motor neuropathy with or without Conduction Block. To investigate the possible mechanism of these antibodies, we injected the serum of a patient with anti-GM1 antibodies who had motor neuron disease and multifocal motor Conduction Block, into rat sciatic nerve. When injected with fresh human complement, the serum-induced Conduction Block with temporal dispersion and deposits of immunoglobulin were detected at the nodes of Ranvier. Electron microscopic studies revealed demyelination in 6.5% of the fibers. After preabsorption with GM1, the serum had no effect, suggesting that the anti-GM1 antibodies were responsible for the Conduction abnormalities.
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multifocal motor neuropathy with Conduction Block is it a distinct clinical entity
Neurology, 1992Co-Authors: Dale J Lange, A Uncini, Arthur P Hays, Norman Latov, Werner Trojaborg, D S Younger, D M Blake, Michio Hirano, S M Burns, Robert E LovelaceAbstract:We studied 169 patients with motor neuron disease. Seventeen showed abnormal amplitude reduction of the compound muscle action potential. Ten had focal loss of both amplitude and area across a specific segment (Conduction Block). Eight of the 10 had slowing of Conduction across that segment. Nine were men and had prominent hand involvement. Six had probable or definite upper motor neuron signs. Five of the 10 showed immunologic abnormalities (elevated GM 1 antibody titers or paraproteinemia), and eight had had symptoms for more than 4 years. Seven of the 17 patients showed loss of amplitude without corresponding loss of area and focal slowing of Conduction (temporal dispersion). Five of the seven were men, five had prominent hand involvement, and five had definite or probable upper motor neuron signs. Two had immunologic abnormalities, and only one had had symptoms for longer than 4 years. Among 152 patients with no abnormality of Conduction, 64% were men, hands were dominantly involved in 34%, upper motor neuron signs were definite or probable in 72%, and 3% had immunologic abnormalities. None had symptoms for more than 4 years. Because there were so many exceptions, we could not define a unique syndrome by criteria involving Conduction Block, GM 1 antibodies, or lack of upper motor neuron signs. The clinical syndrome associated with multifocal Conduction Block seemed uniform, however, and patients with Conduction Block had slower progression if there were no upper motor neuron signs.