To treat diseases associated with vagal nerve control of peripheral organs, it is necessary to selectively activate efferent and afferent fibers in the vagus. As a result of the nerve’s complex anatomy, fiber-specific activation proves challenging. Spatially selective neuromodulation using micromagnetic stimulation(
- NSF-PAR ID:
- 10417527
- Publisher / Repository:
- IOP Publishing
- Date Published:
- Journal Name:
- Journal of Neural Engineering
- Volume:
- 20
- Issue:
- 3
- ISSN:
- 1741-2560
- Page Range / eLocation ID:
- Article No. 036022
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract μ MS) is showing incredible promise. This neuromodulation technique uses microcoils(μ coils) to generate magnetic fields by powering them with a time-varying current. Following the principles of Faraday’s law of induction, a highly directional electric field is induced in the nerve from the magnetic field. In this study on rodent cervical vagus, a solenoidalμ coil was oriented at an angle to left and right branches of the nerve. The aim of this study was to measure changes in the mean arterial pressure (MAP) and heart rate (HR) followingμ MS of the vagus. Theμ coils were powered by a single-cycle sinusoidal current varying in pulse widths(PW = 100, 500, and 1000μ sec) at a frequency of 20 Hz. Under the influence of isoflurane,μ MS of the left vagus at 1000μ sec PW led to an average drop in MAP of 16.75 mmHg(n = 7). In contrast,μ MS of the right vagus under isoflurane resulted in an average drop of 11.93 mmHg in the MAP(n = 7). Surprisingly, there were no changes in HR to either right or left vagalμ MS suggesting the drop in MAP associated with vagusμ MS was the result of stimulation of afferent, but not efferent fibers. In urethane anesthetized rats, no changes in either MAP or HR were observed uponμ MS of the right or left vagus(n = 3). These findings suggest the choice of anesthesia plays a key role in determining the efficacy ofμ MS on the vagal nerve. Absence of HR modulation uponμ MS could offer alternative treatment options using VNS with fewer heart-related side-effects. -
Abstract Background The purpose of this study was to evaluate if kilohertz frequency alternating current (KHFAC) stimulation of peripheral nerve could serve as a treatment for lumbar radiculopathy. Prior work shows that KHFAC stimulation can treat sciatica resulting from chronic sciatic nerve constriction. Here, we evaluate if KHFAC stimulation is also beneficial in a more physiologic model of low back pain which mimics nucleus pulposus (NP) impingement of a lumbar dorsal root ganglion (DRG).
Methods To mimic a lumbar radiculopathy, autologous tail NP was harvested and placed upon the right L5 nerve root and DRG. During the same surgery, a cuff electrode was implanted around the sciatic nerve with wires routed to a headcap for delivery of KHFAC stimulation. Male Lewis rats (3 mo.,
n = 18) were separated into 3 groups: NP injury + KHFAC stimulation (n = 7), NP injury + sham cuff (n = 6), and sham injury + sham cuff (n = 5). Prior to surgery and for 2 weeks following surgery, animal tactile sensitivity, gait, and static weight bearing were evaluated.Results KHFAC stimulation of the sciatic nerve decreased behavioral evidence of pain and disability. Without KHFAC stimulation, injured animals had heightened tactile sensitivity compared to baseline (
p < 0.05), with tactile allodynia reversed during KHFAC stimulation (p < 0.01). Midfoot flexion during locomotion was decreased after injury but improved with KHFAC stimulation (p < 0.05). Animals also placed more weight on their injured limb when KHFAC stimulation was applied (p < 0.05). Electrophysiology measurements at end point showed decreased, but not blocked, compound nerve action potentials with KHFAC stimulation (p < 0.05).Conclusions KHFAC stimulation decreases hypersensitivity but does not cause additional gait compensations. This supports the idea that KHFAC stimulation applied to a peripheral nerve may be able to treat chronic pain resulting from sciatic nerve root inflammation.
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Abstract Objective. Retinal prosthetics offer partial restoration of sight to patients blinded by retinal degenerative diseases through electrical stimulation of the remaining neurons. Decreasing the pixel size enables increasing prosthetic visual acuity, as demonstrated in animal models of retinal degeneration. However, scaling down the size of planar pixels is limited by the reduced penetration depth of the electric field in tissue. We investigated 3-dimensional (3d) structures on top of photovoltaic arrays for enhanced penetration of the electric field, permitting higher resolution implants.Approach. 3D COMSOL models of subretinal photovoltaic arrays were developed to accurately quantify the electrodynamics during stimulation and verified through comparison to flat photovoltaic arrays. Models were applied to optimize the design of 3D electrode structures (pillars and honeycombs). Return electrodes on honeycomb walls vertically align the electric field with bipolar cells for optimal stimulation. Pillars elevate the active electrode, thus improving proximity to target neurons. The optimized 3D structures were electroplated onto existing flat subretinal prostheses.Main results. Simulations demonstrate that despite exposed conductive sidewalls, charge mostly flows via high-capacitance sputtered iridium oxide films topping the 3D structures. The 24μ m height of honeycomb structures was optimized for integration with the inner nuclear layer cells in the rat retina, whilst 35μ m tall pillars were optimized for penetrating the debris layer in human patients. Implantation of released 3D arrays demonstrates mechanical robustness, with histology demonstrating successful integration of 3D structures with the rat retinain-vivo .Significance . Electroplated 3D honeycomb structures produce vertically oriented electric fields, providing low stimulation thresholds, high spatial resolution, and high contrast for pixel sizes down to 20μ m. Pillar electrodes offer an alternative for extending past the debris layer. Electroplating of 3D structures is compatible with the fabrication process of flat photovoltaic arrays, enabling much more efficient retinal stimulation. -
Abstract To address limitations in current approaches for treating large peripheral nerve defects, the presented study evaluated the feasibility of functional material-mediated physical stimuli on peripheral nerve regeneration. Electrospun piezoelectric poly(vinylidene fluoride-trifluoroethylene) nanofibers were utilized to deliver mechanical actuation-activated electrical stimulation to nerve cells/tissues in a non-invasive manner. Using morphologically and piezoelectrically optimized nanofibers for neurite extension and Schwann cell maturation based on in vitro experiments, piezoelectric nerve conduits were synthesized and implanted in a rat sciatic nerve transection model to bridge a critical-sized sciatic nerve defect (15 mm). A therapeutic shockwave system was utilized to periodically activate the piezoelectric effect of the implanted nerve conduit on demand. The piezoelectric nerve conduit-mediated mechano-electrical stimulation (MES) induced enhanced peripheral nerve regeneration, resulting in full axon reconnection with myelin regeneration from the proximal to the distal ends over the critical-sized nerve gap. In comparison, a control group, in which the implanted piezoelectric conduits were not activated in vivo, failed to exhibit such nerve regeneration. In addition, at both proximal and distal ends of the implanted conduits, a decreased number of damaged myelination (ovoids), an increased number of myelinated nerves, and a larger axonal diameter were observed under the MES condition as compared to the control condition. Furthermore, unlike the control group, the MES condition exhibited a superior functional nerve recovery, assessed by walking track analysis and polarization-sensitive optical coherence tomography, demonstrating the significant potential of the piezoelectric conduit-based physical stimulation approach for the treatment of peripheral nerve injury.
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Abstract Objective. Transcutaneous electrical stimulation of peripheral nerves is a common technique to assist or rehabilitate impaired muscle activation. However, conventional stimulation paradigms activate nerve fibers synchronously with action potentials time-locked with stimulation pulses. Such synchronous activation limits fine control of muscle force due to synchronized force twitches. Accordingly, we developed a subthreshold high-frequency stimulation waveform with the goal of activating axons asynchronously.Approach. We evaluated our waveform experimentally and through model simulations. During the experiment, we delivered continuous subthreshold pulses at frequencies of 16.67, 12.5, or 10 kHz transcutaneously to the median and ulnar nerves. We obtained high-density electromyographic (EMG) signals and fingertip forces to quantify the axonal activation patterns. We used a conventional 30 Hz stimulation waveform and the associated voluntary muscle activation for comparison. We modeled stimulation of biophysically realistic myelinated mammalian axons using a simplified volume conductor model to solve for extracellular electric potentials. We compared the firing properties under kHz and conventional 30 Hz stimulation.Main results. EMG activity evoked by kHz stimulation showed high entropy values similar to voluntary EMG activity, indicating asynchronous axon firing activity. In contrast, we observed low entropy values in EMG evoked by conventional 30 Hz stimulation. The muscle forces evoked by kHz stimulation also showed more stable force profiles across repeated trials compared with 30 Hz stimulation. Our simulation results provide direct evidence of asynchronous firing patterns across a population of axons in response to kHz frequency stimulation, while 30 Hz stimulation elicited synchronized time-locked responses across the population.Significance. We demonstrate that the continuous subthreshold high-frequency stimulation waveform can elicit asynchronous axon firing patterns, which can lead to finer control of muscle forces.