Nerve Cuff Research Articles

Extracting impedance changes from a frequency multiplexed signal during neural activity in sciatic nerve of rat: preliminary study in vitro

Objective: To establish suitable frequency spacing and demodulation steps to use when extracting impedance changes from frequency division multiplexed (FDM) carrier signals in peripheral nerve. Approach: Experiments were performed in vitro on cadavers immediately following euthanasia. Neural activity was evoked via stimulation of nerves in the hind paw, while carrier signals were injected, and recordings obtained, with a dual ring nerve cuff implanted on the sciatic nerve. Frequency analysis of recorded compound action potentials (CAPs) and extracted impedance changes, with the latter obtained using established demodulation methods, were used to determine suitable frequency spacing of carrier signals, and bandpass filter (BPF) bandwidth and order, for a frequency multiplexed signal. Main results: CAPs and impedance changes were dominant in the frequency band 200 to 500 Hz and 100 to 200 Hz, respectively. A Tukey window was introduced to remove ringing from Gibbs phenomena. A ±750 Hz BPF bandwidth was selected to encompass 99.99% of the frequency power of the impedance change. Modelling predicted a minimum BPF order of 16 for 2 kHz spacing, and 10 for 4 kHz spacing, were required to avoid ringing from the neighbouring carrier signal, while FDM experiments verified BPF orders of 12 and 8, respectively, were required. With a notch filter centred on the neighbouring signal, a BPF order of at least 6 or 4 was required for 2 and 4 kHz, respectively. Significance: The results establish drive frequency spacing and demodulation settings for use in FDM electrical impedance tomography (EIT) experiments, as well as a method for their selection, and, for the first time, demonstrates the viability of FDM-EIT of neural activity on peripheral nerve, which will be a central aspect of future real-time neural-EIT systems and EIT-based neural prosthetics interfaces.

Persistent pain intensifies recall of consolidated fear memories

Ensembles of principal neurons in the basolateral amygdala (BLA) generate the initial engrams for fear memories, while projections from the BLA to the medial prefrontal cortex (mPFC) are essential for the encoding, transfer and storage of remote fear memories. We tested the effects of chronic pain on remote fear memories in mice.Male mice underwent classic fear conditioning by pairing a single tone (conditional stimulus, CS) with a single electric foot shock (unconditional stimulus, US). Sciatic nerve constriction was used to induce neuropathic pain at various time points before or after the fear conditioning. The mice with sciatic nerve cuffs implanted 48 h after the fear conditioning showed an increased freezing response to CS when compared to mice without cuffs or when compared to mice in which the nerve cuffing was performed 48 h before the fear conditioning. The enhancing effect of pain on consolidated fear memory was further tested and mice in which the nerve cuffing was performed 14 days after the fear conditioning also showed an increased fear response when tested 56 days later.We used immunostaining to detect morphological changes in the BLA that could suggest a mechanism for the observed increase in fear response. We found an increased number of calbindin/parvalbumin positive neurons in the BLA and increased perisomatic density of GAD65 on projection neurons that connect BLA to mPFC in mice with nerve cuffs. Despite the strong increase of c-Fos expression in BLA and mPFC that was induced by fear recall, neither the BLA to mPFC nor the mPFC to BLA projection neurons were activated in mice with nerve cuffs. Furthermore, non-injured mice had an increased fear response when BLA to mPFC projections were inhibited by a chemogenetic method.In conclusion, this study provides evidence that persistent pain has a significant impact on consolidated fear memories. Very likely the underlying mechanism for this phenomenon is increased inhibitory input onto the BLA to mPFC projection neurons, possibly from neurons with induced parvalbumin expression. Conceivably, the increased fear response to consolidated fear memory is a harbinger for the later development of anxiety and depression symptoms associated with chronic pain.

Toward the Bionic Face: A Novel Neuroprosthetic Device Paradigm for Facial Reanimation Consisting of Neural Blockade and Functional Electrical Stimulation.

Facial palsy is a devastating condition potentially amenable to rehabilitation by functional electrical stimulation. Herein, a novel paradigm for unilateral facial reanimation using an implantable neuroprosthetic device is proposed and its feasibility demonstrated in a live rodent model. The paradigm comprises use of healthy-side electromyographic activity as control inputs to a system whose outputs are neural stimuli to effect symmetric facial displacements. The vexing issue of suppressing undesirable activity resulting from aberrant neural regeneration (synkinesis) or nerve transfer procedures is addressed using proximal neural blockade. Epimysial and nerve cuff electrode arrays were implanted in the faces of Wistar rats. Stimuli were delivered to evoke blinks and whisks of various durations and amplitudes. The dynamic relation between electromyographic signals and facial displacements was modeled, and model predictions were compared against measured displacements. Optimal parameters to achieve facial nerve blockade by means of high-frequency alternating current were determined, and the safety of continuous delivery was assessed. Electrode implantation was well tolerated. Blinks and whisks of tunable amplitudes and durations were evoked by controlled variation of neural stimuli parameters. Facial displacements predicted from electromyographic input modelling matched those observed with a variance-accounted-for exceeding 96 percent. Effective and reversible facial nerve blockade in awake behaving animals was achieved, without detrimental effect noted from long-term continual use. Proof-of-principle of rehabilitation of hemifacial palsy by means of a neuroprosthetic device has been demonstrated. The use of proximal neural blockade coupled with distal functional electrical stimulation may have relevance to rehabilitation of other peripheral motor nerve deficits.

Thin Film Multi-Electrode Softening Cuffs for Selective Neuromodulation

Silicone nerve cuff electrodes are commonly implanted on relatively large and accessible somatic nerves as peripheral neural interfaces. While these cuff electrodes are soft (1–50 MPa), their self-closing mechanism requires of thick walls (200–600 µm), which in turn contribute to fibrotic tissue growth around and inside the device, compromising the neural interface. We report the use of thiol-ene/acrylate shape memory polymer (SMP) for the fabrication of thin film multi-electrode softening cuffs (MSC). We fabricated multi-size MSC with eight titanium nitride (TiN) electrodes ranging from 1.35 to 13.95 × 10−4 cm2 (1–3 kΩ) and eight smaller gold (Au) electrodes (3.3 × 10−5 cm2; 750 kΩ), that soften at physiological conditions to a modulus of 550 MPa. While the SMP material is not as soft as silicone, the flexural forces of the SMP cuff are about 70–700 times lower in the MSC devices due to the 30 μm thick film compared to the 600 μm thick walls of the silicone cuffs. We demonstrated the efficacy of the MSC to record neural signals from rat sciatic and pelvic nerves (1000 µm and 200 µm diameter, respectively), and the selective fascicular stimulation by current steering. When implanted side-by-side and histologically compared 30 days thereafter, the MSC devices showed significantly less inflammation, indicated by a 70–80% reduction in ED1 positive macrophages, and 54–56% less fibrotic vimentin immunoreactivity. Together, the data supports the use of MSC as compliant and adaptable technology for the interfacing of somatic and autonomic peripheral nerves.

Compact Optical Nerve Cuff Electrode for Simultaneous Neural Activity Monitoring and Optogenetic Stimulation of Peripheral Nerves

Optogenetic stimulation of the peripheral nervous system is a novel approach to motor control, somatosensory transduction, and pain processing. Various optical stimulation tools have been developed for optogenetic stimulation using optical fibers and light-emitting diodes positioned on the peripheral nerve. However, these tools require additional sensors to monitor the limb or muscle status. We present herein a novel optical nerve cuff electrode that uses a single cuff electrode to conduct to simultaneously monitor neural activity and optogenetic stimulation of the peripheral nerve. The proposed optical nerve cuff electrode is designed with a polydimethylsiloxane substrate, on which electrodes can be positioned to record neural activity. We confirm that the illumination intensity and the electrical properties of the optical nerve cuff electrode are suitable for optical stimulation with simultaneous neural activity monitoring in Thy1::ChR2 transgenic mice. With the proposed electrode, the limb status is monitored with continuous streaming signals during the optical stimulation of anesthetized and moving animals. In conclusion, this optical nerve cuff electrode provides a new optical modulation tool for peripheral nervous system studies.

Drive and measurement electrode patterns for electrode impedance tomography (EIT) imaging of neural activity in peripheral nerve

Objective; To establish the performance of several drive and measurement patterns in EIT imaging of neural activity in peripheral nerve, which involves large impedance changes in the nerve’s anisotropic length axis. Approach; Twelve drive and measurement electrode patterns are compared using a finite element (FE) four-cylindrical shell model of a peripheral nerve and a 32 channel dual-ring nerve cuff. The central layer of the FE model contains impedance changes representative of neural activity of −0.30 in length axis and −8.8 × 10−4 in the radial axis. Six of the electrode patterns generate longitudinal drive current, which runs parallel to the anisotropic axis, while the remaining six patterns generate transverse drive current, which runs perpendicular to the anisotropic axis. Main results; Of the twelve patterns evaluated, transverse current patterns produce higher resolution than longitudinal current patterns but are also more susceptible to noise and errors, and exhibit poorer sensitivity to impedance changes in central sample locations. Three of the six longitudinal current patterns considered can reconstruct fascicle level impedance changes with up to 0.2 mV noise and error, which corresponds to between −5.5 and +0.18 dB of the normalised signal standard deviation. Reducing the spacing between the two electrode rings in all longitudinal current patterns reduced the signal to error ratio across all depth locations of the sample. Significance; Electrode patterns which target the large impedance change in the anisotropic length axis can provide improved robustness against noise and errors, which is a critical step towards real time EIT imaging of neural activity in peripheral nerve.

The mechanics of agonistic muscles

IntroductionIn this study, we tested two assumptions that have been made in experimental studies on muscle mechanics: (i) that the torque-angle properties are similar among agonistic muscles crossing a joint, and (ii) that the sum of the torque capacity of individual muscles adds up to the torque capacity of the agonist group. MethodsMaximum isometric torque measurements were made using a specifically designed animal knee extension dynamometer for the intact rabbit quadriceps muscles (n = 10) for knee angles between 60 and 120°. The nerve branches of the vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) muscles were carefully dissected, and a custom made nerve cuff electrode was implanted on each branch. Knee extensor torques were measured for four maximal activation conditions at each knee angle: VL activation, VM activation, RF activation, and activation of all three muscles together. ResultsWith the exception of VL, the torque-angle relationships of the individual muscles did not have the shape of the torque-angle relationship obtained when all muscles were activated simultaneously. Furthermore, the maximum torque capacity obtained by adding the individual torque capacities of VL, VM and RF was approximately 20% higher than the torques produced when the three muscles were activated simultaneously. DiscussionThese results bring into question our understanding of in-vivo muscle contraction and challenge assumptions that are sometimes made in human and animal muscle force analyses.

High-density peripheral nerve cuffs restore natural sensation to individuals with lower-limb amputations

Objective. Sensory input in lower-limb amputees is critically important to maintaining balance, preventing falls, negotiating uneven terrain, responding to unexpected perturbations, and developing the confidence required for societal participation and public interactions in unfamiliar environments. Despite noteworthy advances in robotic prostheses for lower-limb amputees, such as microprocessor knees and powered ankles, natural somatosensory feedback from the lost limb has not yet been incorporated in current prosthetic technologies. Approach. In this work, we report eliciting somatic sensation with neural stimulation delivered by chronically-implanted, non-penetrating nerve cuff electrodes in two transtibial amputees. High-density, flexible, 16-contact nerve cuff electrodes were surgically implanted for the selective activation of sensory fascicles in the nerves of the posterior thigh above the knee. Electrical pulses at safe levels were delivered to the nerves by an external stimulator via percutaneous leads attached to the cuff electrodes. Main results. The neural stimulation was perceived by participants as sensation originating from the missing limb. We quantitatively and qualitatively ascertained the intensity, modality as well as the location and stability of the perceived sensations. Stimulation through individual contacts within the nerve cuffs evoked repeatable sensations of various modalities and at discrete locations projected to the missing toes, foot and ankle, as well as in the residual limb. In addition, we observed a high overlap in reported locations between distal versus proximal cuffs suggesting that the same sensory responses could be elicited from more proximal points on the nerve. Significance. Based on these findings, the high-density cuff technology is suitable for restoring natural sensation to lower-limb amputees and could be utilized in developing a neuroprosthesis with natural sensory feedback. The overlap in reported locations between proximal and distal cuffs indicates that our approach might be applicable to transfemoral amputees where distal muscles and branches of sciatic nerve are not available.

Positioning the Nerve Cuff Distally on the Sciatic Nerve Improves the Classification of Ankle-Movement Proprioceptive ENG Signals.

Recording of neural signals from intact peripheral nerves in patients with spinal cord injury or stroke survivors offers the possibility for the development of closed-loop sensorimotor prostheses. However, questions remain over the positioning of neural interfaces such that the separability of neural data recorded from the peripheral nerves is improved. Afferent electroneurographic signals were recorded with nerve cuffs placed on the sciatic nerve of rats in response to various mechanical stimuli to the hindpaw. The mean absolute value of the signal was extracted and fed into classifiers. The performance of the classifier was evaluated when information was available from a single cuff placed either distally or proximally on the sciatic nerve. Results confirmed earlier findings that proprioceptive ENG signals, elicited by the movement of the ankle, can be identified and separated in neural recordings made with a cuff electrode. In addition, classification scores improved when the nerve cuff was placed distally on the nerve rather than proximally, taking advantage of the nerve's underlying anatomy.

Stimulation of peripheral nerves using conductive hydrogel electrodes.

Nerve block via electrical stimulation of nerves requires a device capable of transferring large amounts of charge across the neural interface on chronic time scales. Current metal electrode designs are limited in their ability to safely and effectively deliver this charge in a stable manner. Conductive hydrogel (CH) coatings are a promising alternative to metal electrodes for neural interfacing devices. This study assessed the performance of CH electrodes compared to platinum-iridium (PtIr) electrodes in commercial nerve cuff devices in both the in vitro and acute in vivo environments. CH electrodes were found to have higher charge storage capacities and lower impedances compared to bare PtIr electrodes. Application of CH coatings also resulted in a three-fold increase in in vivo charge injection limit. These significant improvements in electrochemical properties will allow for the design of smaller and safer stimulating devices for nerve block applications.

Matlab software for impedance spectroscopy designed for neuroscience applications

BackgroundMetal electrodes are a mainstay of neuroscience. Characterization of the electrical impedance properties of these cuffs is important to ensure successful and repeatable fabrication, achieve a target impedance, revise novel designs, and quantify the success or failure of implantation and any potential subsequent damage or encapsulation by scar tissue. New methodsImpedances are frequently characterized using lumped-parameter circuit models of the electrode–electrolyte interface. Open-source tools to gather and analyze these frequency sweep data are lacking. Here, we present such software, in the form of Matlab code, which includes a GUI. It automatically acquires frequency sweep data and subsequently fits a simplified Randles model to these data, over a user specified frequency range, providing the user with the model parameter estimates. Also, it can measure an unknown impedance of an element over a range of frequencies, as long as an external resistor can be added for the measurements. ResultsThe tool was tested on five bright platinum nerve cuffs in vitro. The average charge transfer resistance, solution resistance, CPE value, and impedance magnitude were estimated. Comparison to existing methodsThe measured values of the impedance of cuffs were in agreement with the literature (Wei and Grill, 2009). Variation between cuffs fabricated as consistently as possible amounted to 10% for impedance magnitude and 4° for impedance phase. ConclusionThe results show that this low-cost tool can be used to characterize a cuff across different conditions including after implantation. The latter makes it useful for a longer-term study of electrode viability.

Sciatic nerve stimulation and its effects on upper airway resistance in the anesthetized rabbit model relevant to sleep apnea.

Obstructive sleep apnea (OSA) is a disorder characterized by collapse of the velopharynx and/or oropharynx during sleep when drive to the upper airway is reduced. Here, we explore an indirect approach for activation of upper airway muscles that might affect airway dynamics, namely, unilateral electrical stimulation of the afferent fibers of the sciatic nerve, in an anesthetized rabbit model. A nerve cuff electrode was placed around the sciatic and hypoglossal nerves to deliver stimulus while airflow, air pressure, and alae nasi electromyogram (EMG) were monitored both before and after sciatic transection. Sciatic nerve stimulation increased respiratory effort, rate, and alae nasi EMG, which persisted for seconds after stimulation; however, upper airway resistance was unchanged. Hypoglossal stimulation reduced resistance without altering drive. Although sciatic nerve stimulation is not ideal for treating OSA, it remains a target for altering respiratory drive. NEW & NOTEWORTHY Previously, sciatic nerve stimulation has been shown to activate upper airway and chest wall muscles. The supposition that resistance through the upper airway would be reduced with this afferent reflex was disproven. Findings were in contrast with the effect of hypoglossal nerve stimulation, which was shown to decrease resistance without changing muscle activation or ventilatory drive.

Influence of nerve cuff channel count and implantation site on the separability of afferent ENG

Objective. Recording of neural signals from intact peripheral nerves in patients with spinal cord injury or stroke survivors offers the possibility for the development of closed-loop sensorimotor prostheses. Nerve cuffs have been found to provide stable recordings from peripheral nerves for prolonged periods of time. However, questions remain over the design and positioning of nerve cuffs such that the separability of neural data recorded from the peripheral nerves is improved. Approach. Afferent electroneurographic (ENG) signals were recorded with nerve cuffs placed on the sciatic nerve of rats in response to various mechanical stimuli to the hindpaw. The mean absolute value of the signal was extracted and input to a classifier. The performance of the classifier was evaluated under two conditions: (1) when information from either a 3- or 16-channel cuff was used; (2) when information was available from a cuff placed either distally or proximally along the nerve. Main results. We show that both 3- and 16-channel cuffs were able to separate afferent ENG signals with an accuracy greater than chance. The highest classification scores were achieved when the classifier was fed with information obtained from a 16-channel cuff placed distally. While the 16-channel cuff always outperformed the 3-channel cuff, the difference in performance was increased when the 16-channel cuff was placed distally rather than proximally on the nerve. Significance. The results indicate that increasing the complexity of a nerve cuff may only be advantageous if the nerve cuff is to be implanted distally, where the nerve has begun to divide into individual fascicles.

Case Studies in Neuroscience: Sensations elicited and discrimination ability from nerve cuff stimulation in an amputee over time.

The present case study details sensations elicited by electrical stimulation of peripheral nerve axons using an implanted nerve cuff electrode, in a participant with a transhumeral amputation. The participant uses an osseointegrated electromechanical interface, which enables skeletal attachment of the prosthesis and long-term, stable, bidirectional communication between the implanted electrodes and prosthetic arm. We focused on evoking somatosensory percepts, where we tracked and quantified the evolution of perceived sensations in the missing hand, which were evoked from electrical stimulation of the nerve, for over 2 yr. These sensations included small, pointlike areas of either vibration or pushing, to larger sensations over wider areas, indicating the recruitment of a few and many afferents, respectively. Furthermore, we used a two-alternative forced choice paradigm to measure the level of discrimination between trains of brief electrical stimuli, to gauge what the participant could reliably distinguish between. At best, the participant was able to distinguish a 0.5-Hz difference and on average acquired a 3.8-Hz just-noticeable difference at a more stringent psychophysical level. The current work shows the feasibility for long-term sensory feedback in prostheses, via electrical axonal stimulation, where small and relatively stable percepts were felt that may be used to deliver graded sensory feedback. This opens up opportunities for signaling feedback during movements (e.g., for precision grip), but also for conveying more complex cutaneous sensations, such as texture. NEW & NOTEWORTHY We demonstrate the long-term stability and generation of sensations from electrical peripheral nerve stimulation in an amputee, through an osseointegrated implant. We find that perceived tactilelike sensations could be generated for over 2 yr, in the missing hand. This is useful for prosthetic development and the implementation of feedback in artificial body parts.

A Hybrid 3D Printing and Robotic-assisted Embedding Approach for Design and Fabrication of Nerve Cuffs with Integrated Locking Mechanisms

ABSTRACTThe ability to interface electronic materials with the peripheral nervous system is required for stimulation and monitoring of neural signals. Thus, the design and engineering of robust neural interfaces that maintain material-tissue contact in the presence of material or tissue micromotion offer the potential to conduct novel measurements and develop future therapies that require chronic interface with the peripheral nervous system. However, such remains an open challenge given the constraints of existing materials sets and manufacturing approaches for design and fabrication of neural interfaces. Here, we investigated the potential to leverage a rapid prototyping approach for the design and fabrication of nerve cuffs that contain supporting features to mechanically stabilize the interaction between cuff electrodes and peripheral nerve. A hybrid 3D printing and robotic-embedding (i.e., pick-and-place) system was used to design and fabricate silicone nerve cuffs (800 µm diameter) containing conforming platinum (Pt) electrodes. We demonstrate that the electrical impedance of the cuff electrodes can be reduced by deposition of the conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) on cuff electrodes via a post-processing electropolymerization technique. The computer-aided design and manufacturing approach was also used to design and integrate supporting features to the cuff that mechanically stabilize the interface between the cuff electrodes and the peripheral nerve. Both ‘self-locking’ and suture-assisted locking mechanisms are demonstrated based on the principle of making geometric alterations to the cuff opening via 3D printing. Ultimately, this work shows 3D printing offers considerable opportunity to integrate supporting features, and potentially even novel electronic materials, into nerve cuffs that can support the design and engineering of next generation neural interfaces.

Chronic Nerve Health Following Implantation of Nerve Cuff Electrodes Designed for the Proximal Femoral Nerve (S37.001)

Chronic Nerve Health Following Implantation of Nerve Cuff Electrodes Designed for the Proximal Femoral Nerve (S37.001)

Chronic cuffing of cervical vagus nerve inhibits efferent fiber integrity in rat model

Objective. Numerous studies of vagal nerve stimulation (VNS) have been published showing it to be a potential treatment for chronic inflammation and other related diseases and disorders. Studies in recent years have shown that electrical stimulation of the vagal efferent fibers can artificially modulate cytokine levels and reduce systematic inflammation. Most VNS research in the treatment of inflammation have been acute studies on rodent subjects. Our study tested VNS on freely moving animals by stimulating and recording from the cervical vagus with nerve cuff electrodes over an extended period of time. Approach. We used methods of electrical stimulation, retrograde tracing (using Fluorogold) and post necropsy histological analysis of nerve tissue, flow cytometry to measure plasma cytokine levels, and MRI scanning of gastric emptying. This novel combination of methods allowed examination of physiological aspects of VNS previously unexplored. Main results. Through our study of 53 rat subjects, we found that chronically cuffing the left cervical vagus nerve suppressed efferent Fluorogold transport in 43 of 44 animals (36 showed complete suppression). Measured cytokine levels and gastric emptying rates concurrently showed nominal differences between chronically cuffed rats and those tested with similar acute methods. Meanwhile, results of electrophysiological and histological tests of the cuffed nerves revealed them to be otherwise healthy, consistent with previous literature. Significance. We hypothesize that due to these unforeseen and unexplored physiological consequences of the chronically cuffed vagus nerve in a rat, that inflammatory modulation and other vagal effects by VNS may become unreliable in chronic studies. Given our findings, we submit that it would benefit the VNS community to re-examine methods used in previous literature to verify the efficacy of the rat model for chronic VNS studies.

A model of electrical impedance tomography implemented in nerve-cuff for neural-prosthetics control

Objective: In neural interfaces for peripheral nerve a trade-off exists between the level of invasiveness and the selectivity of neural recordings. In this study, we implement electrical impedance tomography (EIT) in a nerve cuff with the aim to investigate the achievable level of selectivity. Approach: Established modelling approaches in neural-EIT are expanded on to be used, for the first time, on myelinated fibres which are abundant in mammalian peripheral nerves and transmit motor commands. The model is then used to evaluate the viability of using EIT with a nerve cuff to record neural activity in peripheral nerves. Main results: Fibre impedance models indicate activity in unmyelinated fibres can be screened out from activity in myelinated fibres using operating frequencies above 100 Hz. At 1 kHz the transverse impedance magnitude, which is perpendicular to the fibre length axis, of inactive intra-fascicle tissue and the fraction change during neural activity are estimated to be 1142 Ω cm and −8.8 × 10−4, respectively. At 1 kHz and 10 mm spacing between the impedance measurement electrode pair, the longitudinal impedance magnitude, which is parallel to the fibre length axis, and the fraction change during neural activity are estimated to be 328 Ω cm and −0.30, respectively. We show that a novel EIT drive and measurement electrode pattern which utilises longitudinal current and longitudinal differential boundary voltage measurements could distinguish activity in different fascicles, as well as simultaneous activity in multiple fascicles, of a three-fascicle mammalian nerve using simulated data. Significance: The results of this study provide an estimate of the transient change in impedance of intra-fascicle tissue during neural activity in mammalian nerve, and present a viable EIT electrode pattern, both of which are critical steps towards implementing EIT in a nerve cuff for a recording neural interface.

Evaluation of high-density, multi-contact nerve cuffs for activation of grasp muscles in monkeys

Objective. The objective of this work was to evaluate whether nerve cuffs can selectively activate hand muscles for functional electrical stimulation (FES). FES typically involves identifying and implanting electrodes in many individual muscles, but nerve cuffs only require implantation at a single site around the nerve. This method is surgically more attractive. Nerve cuffs may also more effectively stimulate intrinsic hand muscles, which are difficult to implant and stimulate without spillover to adjacent muscles. Approach. To evaluate its ability to selectively activate muscles, we implanted and tested the flat interface nerve electrode (FINE), which is designed to selectively stimulate peripheral nerves that innervate multiple muscles (Tyler and Durand 2002 IEEE Trans. Neural Syst. Rehabil. Eng. 10 294–303). We implanted FINEs on the nerves and bipolar intramuscular wires for recording compound muscle action potentials (CMAPs) from up to 20 muscles in each arm of six monkeys. We then collected recruitment curves while the animals were anesthetized. Main result. A single FINE implanted on an upper extremity nerve in the monkey can selectively activate muscles or small groups of muscles to produce multiple, independent hand functions. Significance. FINE cuffs can serve as a viable supplement to intramuscular electrodes in FES systems, where they can better activate intrinsic and extrinsic muscles with lower currents and less extensive surgery.

Tibial Nerve Stimulation to Drive Genital Sexual Arousal in an Anesthetized Female Rat

BackgroundThere is clinical evidence that percutaneous tibial nerve stimulation can positively benefit women with female sexual interest/arousal disorder, yet no studies have explored the potential mechanisms further. AimTo investigate the effect of tibial nerve stimulation on vaginal blood perfusion (VBP) in an anesthetized rat model. Methods16 ketamine-anesthetized rats were surgically implanted with a nerve cuff electrode on 1 tibial nerve. The tibial nerve was stimulated for 30 minutes continuously or non-continuously at a frequency of 10 to 25 Hz. OutcomesVBP was measured with laser Doppler flowmetry and analyzed using a wavelet transform of time-frequency representations with a focus on the neurogenic energy range (0.076–0.200 Hz). Results25 of 33 (75.8%) stimulation periods had at least a 500% increase in laser Doppler flowmetry neurogenic energy compared with baseline. This increase was most common within 20 to 35 minutes after the start of stimulation. There was no statistically significant difference for frequency used or estrous cycle stage. Clinical TranslationThe results of this study provide further support for percutaneous tibial nerve stimulation as an alternative treatment option for women with genital arousal aspects of female sexual interest/arousal disorder. Strengths and LimitationsThis study successfully demonstrates the ability of tibial nerve stimulation to increase VBP. However, further studies to determine parameter optimization and to illuminate neural mechanisms are needed. Further studies also are necessary to determine effects of repeated stimulation sessions. ConclusionLong-duration tibial stimulation was successful at driving increases in the neurogenic component of VBP, providing evidence that tibial nerve stimulation could be used to treat genital arousal aspects of female sexual interest/arousal disorder by improving pelvic blood flow.Zimmerman LL, Rice IC, Berger MB, Bruns TM. Tibial Nerve Stimulation to Drive Genital Sexual Arousal in an Anesthetized Female Rat. J Sex Med 2018;15:296–303.