Electrode-tissue Interface Research Articles

Longitudinal analysis of local field potentials recorded from directional deep brain stimulation lead implants in the subthalamic nucleus

Objective. The electrode–tissue interface surrounding a deep brain stimulation (DBS) lead is known to be highly dynamic following implantation, which may have implications on the interpretation of intraoperatively recorded local field potentials (LFPs). We characterized beta-band LFP dynamics following implantation of a directional DBS lead in the sensorimotor subthalamic nucleus (STN), which is a primary target for treating Parkinson’s disease. Approach. Directional STN-DBS leads were implanted in four healthy, non-human primates. LFPs were recorded over two weeks and again 1–4 months after implantation. Impedance was measured for two weeks post-implant without stimulation to compare the reactive tissue response to changes in LFP oscillations. Beta-band (12–30 Hz) peak power was calculated from the LFP power spectra using both common average referencing (CAR) and intra-row bipolar referencing (IRBR). Results. Resting-state LFPs in two of four subjects revealed a steady increase of beta power over the initial two weeks post-implant whereas the other two subjects showed variable changes over time. Beta power variance across days was significantly larger in the first two weeks compared to 1–4 months post-implant in all three long-term subjects. Further, spatial maps of beta power several hours after implantation did not correlate with those measured two weeks or 1–4 months post-implant. CAR and IRBR beta power correlated across short- and long-term time points. However, depending on the time period, subjects showed a significant bias towards larger beta power using one referencing scheme over the other. Lastly, electrode–tissue impedance increased over the two weeks post-implant but showed no significant correlation to beta power. Significance. These results suggest that beta power in the STN may undergo significant changes following DBS lead implantation. DBS lead diameter and electrode recording configurations can affect the post-implant interpretation of oscillatory features. Such insights will be important for extrapolating results from intraoperative and externalized LFP recordings.

Inflammation at the Tissue-Electrode Interface in a Case of Rapid Deterioration in Hearing Performance Leading to Explant After Cochlear Implantation

The reasons for soft failure after cochlear implantation require investigation. This study proposes a method to study and characterize the tissue response to the array in a case of soft failure in a person undergoing reimplantation. The woman in her 50s, with an underlying autoimmune condition, received a cochlear implant using hearing preservation technique after developing profound hearing loss more than 2 kHz with a moderate loss of less than 500 Hz over a 10-year period. The case was identified as a soft failure due to deteriorating performance, discomfort, and migration over the 10 months after implantation. Impedance telemetry, speech perception measures, and audiometric thresholds are described. At explantation there was evidence of fibrosis. To use histology and immunohistochemistry to determine the cellular response of the tissue associated with the electrode array at time of explantation. Identification of the cell types, regional variations, and inflammatory marker expression in the fibrotic tissue associated with the array. Neutrophils and eosinophils were identified, along with a variable pattern of collagen deposition. CD68 and CD163-positive macrophages and T cells were variably distributed through the tissue and interleukin-1 beta and vascular endothelial growth factor receptor-2 expression was identified. The expression profile is evidence of active inflammation in the tissue despite the time since implantation. This study is the first to characterize the tissue response to the array in a person undergoing reimplantation, and who can be followed to determine the individual response to arrays. It establishes that the investigation of explanted devices after soft-failure is feasible.

A 24-Channel Neurostimulator IC With Channel-Specific Energy-Efficient Hybrid Preventive-Detective Dynamic-Precision Charge Balancing

This paper presents the design, development, and experimental characterization of a 24-channel programmable charge-balanced current-mode neurostimulator IC. Each channel is equipped with a quad-threshold voltage-based charge imbalance detection and a dedicated hybrid preventive-detective charge balancing circuit. The interplay of the preventive and detective control loops utilized for charge balancing has resulted in minimizing the power and timing overhead of the proposed strategy for maintaining a charge-neutral electrode-tissue interface, while avoiding the risk of unintended stimulation. The design offers dynamic programmability for the safe and unsafe charge imbalance thresholds, as well as for the balancing speed and precision. The IC is fabricated in a standard 0.18 μm CMOS technology with an overall active area of 2.27mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . Experimental characterization results of different circuit blocks are presented and discussed. Additionally, the IC's efficacy in conducting charge-balanced stimulation is experimentally validated under various scenarios and for the full range of stimulation current magnitude, showing the balancing accuracy, latency, and active time. Experiments are conducted both with a simplified electrical model of the interface impedance as well as in vitro. Compared to the state-of-the-art stimulators with a closed-loop charge balancer, the presented work offers the most energy-efficient charge balancing technique, the shortest required inter-pulse interval (i.e., neutralization time), and the highest balancing precision.

The complement cascade at the Utah microelectrode-tissue interface

Devices implanted within the central nervous system (CNS) are subjected to tissue reactivity due to the lack of biocompatibility between implanted material and the cells’ microenvironment. Studies have attributed blood-brain barrier disruption, inflammation, and oxidative stress as main contributing factors that lead to electrode recording failure. The complement cascade is a part of the innate immunity that focuses on recognizing and targeting foreign objects; however, its role in the context of neural implants is substantially unknown. In this study, we implanted a non-functional 4x4 Utah microelectrode array (UEA) into the somatosensory cortex and studied the complement cascade via combined gene and immunohistochemistry quantification at acute (48-h), sub-acute (1-week), and early chronic (4-weeks) time points. The results of this study demonstrate the activation and continuation of the complement cascade at the electrode-tissue interface, illustrating the therapeutic potential of modulating the foreign body response via the complement cascade.

Measuring the Electrical Status of the Bionic Ear. Re-thinking the Impedance in Cochlear Implants.

As in any biophysical electrode-tissue environment, impedance measurement shows a complex relationship which reflects the electrical characteristics of the medium. In cochlear implants (CIs), which is mostly a stimulation-oriented device, the actual clinical approach only considers one arbitrary time-measure of the impedance. However, to determine the main electrical properties of the cochlear medium, the overall impedance and its subcomponents (i.e., access resistance and polarization impedance) should be described. We here characterized, validated and discussed a novel method to calculate impedance subcomponents based on CI measurement capabilities. With an electronic circuit of the cochlear electrode-tissue interface and its computational simulation, the access resistance and polarization impedance were modeled. Values of each electrical component were estimated through a custom-made pulse delivery routine and the acquisition of multiple data points. Using CI hardware, results fell within the electronic components nominal errors (± 10%). Considering the method’s accuracy and reliability, it is readily available to be applied in research-clinical use. In the man-machine nature of the CI, this represents the basis to optimize the communication between a CI electrode and the spiral ganglion cells.

Ultraflexible Neural Electrodes for Long-Lasting Intracortical Recording.

SummaryImplanted electrodes provide one of the most important neurotechniques for fundamental and translational neurosciences by permitting time-resolved electrical detection of individual neurons in vivo. However, conventional rigid electrodes typically cannot provide stable, long-lasting recordings. Numerous interwoven biotic and abiotic factors at the tissue-electrode interface lead to short- and long-term instability of the recording performance. Making neural electrodes flexible provides a promising approach to mitigate these challenges on the implants and at the tissue-electrode interface. Here we review the recent progress of ultraflexible neural electrodes and discuss the engineering principles, the material properties, and the implantation strategies to achieve stable tissue-electrode interface and reliable unit recordings in living brains.

Carbon nanofiber-PEDOT composite films as novel microelectrode for neural interfaces and biosensing

A clear need exists for novel nanostructured materials that are capable to meet the performance criteria of a number of neuronal therapies including neural recording, stimulation and sensing of bioactive molecules at the electrode-tissue interface. By combining Poly (3,4-ethylenedioxythiophene) (PEDOT), with Carbon Nanofibers (CNFs), we demonstrate a versatile approach for the synthesis of a novel composite material PEDOT:CNF with remarkable electrochemical properties, combining low impedance, high surface area, high charge injection capability and reliable neurotransmitters monitoring using amperometric techniques. The oxidized CNFs were utilized as dopants of PEDOT to prepare the composite coatings through electrochemical deposition on neural microelectrodes arrays (MEA). The PEDOT:CNF modified microelectrodes demonstrated the low specific impedance of 1.28 MΩ μm2 at 1 kHz and results in unrivalled charge injection limit of 10.03 mC/cm2 when compared to other reported organic electrode nanomaterials. Furthermore, amperometric detection performances were determined for the neurotransmitters dopamine and serotonin, exhibiting linear concentration range from 0.1 to 9 μM and from 0.06 to 9 μM respectively, high sensitivities (44.54 pA/nM.μm2 and 71.08 pA/nM.μm2, respectively) and low detection limits (0.045 μM and 0.056 μM, respectively). Cell viability was investigated on PEDOT:CNF coated microelectrodes to show that the composite material does not advocate any cytotoxicity. Taken together, these results suggest the great potential of PEDOT:CNF composite for developing next-generation multifunctional microelectrodes for applications in neural therapies.

A microfluidic system integrated with shape memory alloy valves for a safe direct current delivery system.

Direct current (DC) has potential as a clinical and scientific tool to accelerate wound healing, increase the permeability of the skin to drug treatment and modulate neural activity. But long duration delivery of DC unavoidably causes hazardous electrolysis at the tissue-electrode interface. To be able to deliver long duration DC, we previously proposed a design for a safe direct current stimulator (SDCS). This device uses alternating current that does not cause chemical reactions at the metal electrodes within the device, but delivers ionic direct current output to the tissue via microfluidic valves. We previously developed and published designs of multiple SDCS components including microfluidic, electronic, data processing, and energy systems. In this paper we focus on the development of the integrated microfluidics needed by the SDCS system. We developed a fabrication method and characterized valve performance within the multi-valve microfluidic system. We used poly-dimethylsiloxane (PDMS) to fabricate three microfluidic chips that integrated valves actuated by 50-µm Nitinol (NiTi) shape memory alloy (SMA) wire. We tested system operation by driving SMA valves with a current pulse and recording the valve response with an electrical assay. The valve operation complied with the SDCS system requirements. The time for valves to open was rapid at 0.177 ± 0.04 seconds, and the time for the valves to close was 0.265 ± 0.05 seconds. Open microfluidic channel impedance for unrestricted ionic current flow was 15.90 ± 8.28 kΩ and it increased by a factor of 40 to restrict ionic current flow at 678 ± 102 kΩ for the closed valves.

Self-Tuning Deep Brain Stimulation Controller for Suppression of Beta Oscillations: Analytical Derivation and Numerical Validation.

Closed-loop control strategies for deep brain stimulation (DBS) in Parkinson's disease offer the potential to provide more effective control of patient symptoms and fewer side effects than continuous stimulation, while reducing battery consumption. Most of the closed-loop methods proposed and tested to-date rely on controller parameters, such as controller gains, that remain constant over time. While the controller may operate effectively close to the operating point for which it is set, providing benefits when compared to conventional open-loop DBS, it may perform sub-optimally if the operating conditions evolve. Such changes may result from, for example, diurnal variation in symptoms, disease progression or changes in the properties of the electrode-tissue interface. In contrast, an adaptive or “self-tuning” control mechanism has the potential to accommodate slowly varying changes in system properties over a period of days, months, or years. Such an adaptive mechanism would automatically adjust the controller parameters to maintain the desired performance while limiting side effects, despite changes in the system operating point. In this paper, two neural modeling approaches are utilized to derive and test an adaptive control scheme for closed-loop DBS, whereby the gain of a feedback controller is continuously adjusted to sustain suppression of pathological beta-band oscillatory activity at a desired target level. First, the controller is derived based on a simplified firing-rate model of the reciprocally connected subthalamic nucleus (STN) and globus pallidus (GPe). Its efficacy is shown both when pathological oscillations are generated endogenously within the STN-GPe network and when they arise in response to exogenous cortical STN inputs. To account for more realistic biological features, the control scheme is then tested in a physiologically detailed model of the cortical basal ganglia network, comprised of individual conductance-based spiking neurons, and simulates the coupled DBS electric field and STN local field potential. Compared to proportional feedback methods without gain adaptation, the proposed adaptive controller was able to suppress beta-band oscillations with less power consumption, even as the properties of the controlled system evolve over time due to alterations in the target for beta suppression, beta fluctuations and variations in the electrode impedance.

Nanotunnels within Poly(3,4-ethylenedioxythiophene)-Carbon Nanotube Composite for Highly Sensitive Neural Interfacing.

Neural electrodes are developed for direct communication with neural tissues for theranostics. Although various strategies have been employed to improve performance, creating an intimate electrode-tissue interface with high electrical fidelity remains a great challenge. Here, we report the rational design of a tunnel-like electrode coating comprising poly(3,4-ethylenedioxythiophene) (PEDOT) and carbon nanotubes (CNTs) for highly sensitive neural recording. The coated electrode shows a 50-fold reduction in electrochemical impedance at the biologically relevant frequency of 1 kHz, compared to the bare gold electrode. The incorporation of CNT significantly reinforces the nanotunnel structure and improves coating adhesion by ∼1.5 fold. In vitro primary neuron culture confirms an intimate contact between neurons and the PEDOT-CNT nanotunnel. During acute in vivo nerve recording, the coated electrode enables the capture of high-fidelity neural signals with low susceptibility to electrical noise and reveals the potential for precisely decoding sensory information through mechanical and thermal stimulation. These findings indicate that the PEDOT-CNT nanotunnel composite serves as an active interfacing material for neural electrodes, contributing to neural prosthesis and brain-machine interface.

Surface Modifications of an Organic Polymer-Based Microwire Platform for Sustained Release of an Anti-Inflammatory Drug.

Brain machine interfaces (BMIs), introduced into the daily lives of individuals with injuries or disorders of the nervous system such as spinal cord injury, stroke, or amyotrophic lateral sclerosis, can improve the quality of life. BMIs rely on the capability of microelectrode arrays to monitor the activity of large populations of neurons. However, maintaining a stable, chronic electrode-tissue interface that can record neuronal activity with a high signal-to-noise ratio is a key challenge that has limited the translation of such technologies. An electrode implant injury leads to a chronic foreign body response that is well-characterized and shown to affect the electrode-tissue interface stability. Several strategies have been applied to modulate the immune response, including the application of immunomodulatory drugs applied both systemically and locally. While the use of passive drug release at the site of injury has been exploited to minimize neuroinflammation, this strategy has all but failed as a bolus of anti-inflammatory drugs is released at predetermined times that are often inconsistent with the ongoing innate inflammatory process. Common strategies do not focus on the proper anchorage of soft hydrogel scaffolds on electrode surfaces, which often results in delamination of the porous network from electrodes. In this study, we developed a microwire platform that features a robust yet soft biocompatible hydrogel coating, enabling long-lasting drug release via formation of drug aggregates and dismantlement of hydrophilic biodegradable three-dimensional polymer networks. Facile surface chemistry is developed to functionalize polyimide-coated electrodes with the covalently anchored porous hydrogel network bearing large numbers of highly biodegradable ester groups. Exponential long-lasting drug release is achieved using such hydrogels. We show that the initial state of dexamethasone (Dex) used to formulate the hydrogel precursor solution plays a cardinal role in engineering hydrophilic networks that enable a sustained and long-lasting release of the anti-inflammatory agent. Furthermore, utilization of a high loading ratio that exceeds the solubility of Dex leads to the encapsulation of Dex aggregates that regulate the release of this anti-inflammatory agent. To validate the anti-inflammatory effect of the hydrogel-functionalized Dex-loaded microwires, an in vivo preliminary study was performed in adult male rats (n = 10) for the acute time points of 48 h and 7 days post implant. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the mRNA expression of certain inflammatory-related genes. In general, a decrease in fold-change expression was observed for all genes tested for Dex-loaded wires compared with controls (functionalized but no drug). The engineering of hybrid microwires enables a sustained release of the anti-inflammatory agent over extended periods of time, thus paving the way to fabricate neuroprosthetic devices capable of attenuating the foreign body response.

Electro-thermal therapy: Microsecond duration pulsed electric field tissue ablation with dynamic temperature control algorithms

Electro-thermal therapy (ETT) is a new cancer treatment modality which combines the use of high voltage pulsed electric fields, dynamic energy delivery rates, and closed loop thermal control algorithms to rapidly and reproducibly create focal ablations. This study examines the ablative potential and profile of pulsed electric field treatments delivered in conjunction with precise temperature control algorithms. An ex vivo perfused liver model was utilized to demonstrate the capability of 5000 V 2 μs duration bipolar electrical pulses and dynamic temperature control algorithms to produce ablations. Using a three applicator array, 4 cm ablation zones were created in under 27 min. In this configuration, the algorithms were able to rapidly achieve and maintain temperatures of 80 °C at the tissue-electrode interface. A simplified single applicator and grounding pad approach was used to correlate the measured ablation zones to electric field isocontours in order to determine lethal electric field thresholds of 708 V/cm and 867 V/cm for 45 °C and 60 °C treatments, respectively. These results establish ETT as a viable method for hepatic tumor treatment with ablation profiles equivalent to other energy based techniques. The single applicator and multi-applicator approaches demonstrated may enable the treatment of complex tumor geometries. The flexibility of ETT temperature control yields a malleable intervention which gives clinicians robust control over the ablation modality, treatment time, and safety profile.

Analysis of the capacitance of minimally insulated parallel wires implanted in biological tissue.

State of the art bioelectronic implants are using thin cables for therapeutic electrical stimulation. If cable insulation is thin, biological tissue surrounding cables can be unintentionally stimulated. The capacitance of the cable must be much less than the stimulating electrodes to ensure stimulating currents are delivered to the electrode-tissue interface. This work derives and experimentally validates a model to determine the capacitance of parallel cables implanted in biological tissue. Biological tissue has a high relative permittivity, so the capacitance of cabling implanted in the human body depends on cable insulation thickness. Simulations and measurements demonstrate that insulation thickness influences the capacitance of implanted parallel cables across almost two orders of magnitude: from 20 pF/m to 700 pF/m. The results are verified using four different methods: solving the Laplacian numerically from first principles, using a commercially available electrostatic solver, and measuring twelve different parallel pairs of wires using two different potentiostats. Cable capacitance simulations and measurements are performed in air, a porcine blood pool and porcine muscle tissue. The results do not differ by more than 30% for a given cable across simulation and measurement methodologies. The modelling in this work can be used to design cabling for minimally-invasive biomedical implants.

Evaluation of a conducting elastomeric composite material for intramuscular electrode application

Electrical stimulation of the muscle has been proven efficacious in preventing atrophy and/or reanimating paralyzed muscles. Intramuscular electrodes made from metals have significantly higher Young's Moduli than the muscle tissues, which has the potential to cause chronic inflammation and decrease device performance. Here, we present an intramuscular electrode made from an elastomeric conducting polymer composite consisting of PEDOT-PEG copolymer, silicone and carbon nanotubes (CNT) with fluorosilicone insulation. The electrode wire has a Young's modulus of 804 (±99) kPa, which better mimics the muscle tissue modulus than conventional stainless steel (SS) electrodes. Additionally, the non-metallic composition enables metal-artifact free CT and MR imaging. These soft wire (SW) electrodes present comparable electrical impedance to SS electrodes of similar geometric surface area, activate muscle at a lower threshold, and maintain stable electrical properties in vivo up to 4 weeks. Histologically, the SW electrodes elicited significantly less fibrotic encapsulation and less IBA-1 positive macrophage accumulation than the SS electrodes at one and three months. Further phenotyping the macrophages with the iNOS (pro-inflammatory) and ARG-1 (pro-healing) markers revealed significantly less presence of pro-inflammatory macrophage around SW implants at one month. By three months, there was a significant increase in pro-healing macrophages (ARG-1) around the SW implants but not around the SS implants. Furthermore, a larger number of AchR clusters closer to SW implants were found at both time points compared to SS implants. These results suggest that a softer implant encourages a more intimate and healthier electrode-tissue interface. Statement of significanceIntramuscular electrodes made from metals have significantly higher Young's Moduli than the muscle tissues, which has the potential to cause chronic inflammation and decrease device performance. Here, we present an intramuscular electrode made from an elastomeric conducting polymer composite consisting of PEDOT-PEG copolymer, silicone and carbon nanotubes with fluorosilicone insulation. This elastomeric composite results in an electrode wire with a Young's modulus mimicking that of the muscle tissue, which elicits significantly less foreign body response compared to stainless steel wires. The lack of metal in this composite also enables metal-artifact free MRI and CT imaging.

Electrode impedance changes after implantation of a dexamethasone-eluting intracochlear array

Postoperative inflammation and the formation of fibrotic tissue around the intracochlear electrode array are often held responsible for negative outcomes in cochlear implant recipients. Here we test the effectiveness of intracochlear delivery of dexamethasone via a drug-eluting electrode array in reducing fibrotic tissue formation, assessed via measurement of both monopolar and four-point electrode impedance. Adult guinea pigs were bilaterally implanted with a dexamethasone-eluting array (left ear) and a standard non-eluting array (right ear). Arrays were electrically stimulated daily for 4 weeks, commencing 1 week after implantation, and impedance measured both before and after stimulation. Histological assessment of the tissue was made at the end of the 5-week period. The dexamethasone-eluting array did not reduce monopolar (MP1 + 2) electrode impedance over the course of 5 weeks, and no significant difference was observed in fibrotic tissue, new bone growth, or spiral ganglion neuron density between array types. However, four-point impedance, which provides an indication of the local environment at the neural-tissue interface, was significantly lower in the presence of dexamethasone. A strong relationship was seen between four-point and monopolar impedance for individual electrode arrays, with the exception of the standard array after daily electrical stimulation. This group instead showed a significant correlation between the final four-point impedance measure and percentage of fibrous tissue and new bone growth. In conclusion, this study demonstrated that dexamethasone influences four-point electrode impedance as well as the relationship between fibrotic tissue and impedance, and that both outcomes are shaped by daily electrical stimulation. These results suggest a change occurs at the local tissue-electrode interface in the presence of sustained, intracochlear release of dexamethasone.

Zwitterionic polymer/polydopamine coating reduce acute inflammatory tissue responses to neural implants

The inflammatory brain tissue response to implanted neural electrode devices has hindered the longevity of these implants. Zwitterionic polymers have a potent anti-fouling effect that decreases the foreign body response to subcutaneous implants. In this study, we developed a nanoscale anti-fouling coating composed of zwitterionic poly (sulfobetaine methacrylate) (PSB) and polydopamine (PDA) for neural probes. The addition of PDA improved the stability of the coating compared to PSB alone, without compromising the anti-fouling properties of the film. PDA-PSB coating reduced protein adsorption by 89% compared to bare Si samples, while fibroblast adhesion was reduced by 86%. PDA-PSB coated silicon based neural probes were implanted into mouse brain, and the inflammatory tissue responses to the implants were assessed by immunohistochemistry one week after implantation. The PSB-PDA coated implants showed a significantly decreased expression of glial fibrillary acidic protein (GFAP), a marker for reactive astrocytes, within 70 μm from the electrode-tissue interface (p < 0.05). Additionally, the coating reduced the microglia activation as shown in decreased Iba-1 and lectin staining, and improved blood-brain barrier integrity indicated by reduced immunoglobulin (IgG) leakage into the tissue around the probes. These findings demonstrate that anti-fouling zwitterionic coating is effective in suppressing the acute inflammatory brain tissue response to implants, and should be further investigated for its potential to improve chronic performance of neural implants.

When Bio Meets Technology: Biohybrid Neural Interfaces.

The development of electronics capable of interfacing with the nervous system is a rapidly advancing field with applications in basic science and clinical translation. Devices containing arrays of electrodes can be used in the study of cells grown in culture or can be implanted into damaged or dysfunctional tissue to restore normal function. While devices are typically designed and used exclusively for one of these two purposes, there have been increasing efforts in developing implantable electrode arrays capable of housing cultured cells, referred to as biohybrid implants. Once implanted, the cells within these implants integrate into the tissue, serving as a mediator of the electrode-tissue interface. This biological component offers unique advantages to these implant designs, providing better tissue integration and potentially long-term stability. Herein, an overview of current research into biohybrid devices, as well as the historical background that led to their development are provided, based on the host anatomical location for which they are designed (CNS, PNS, or special senses). Finally, a summary of the key challenges of this technology and potential future research directions are presented.

Electrochemical methods for analysing and controlling charge transfer at the electrode–tissue interface

Abstract There have been rapid advances in the development of new materials for use in electrode–tissue interfacing. The development of conducting polymers, conducting hydrogels, carbon nanotubes, graphene and other conducting materials has provided a rich landscape for controlling charge transfer at the electrode–tissue interface and hence to monitor and manipulate cell behaviour. These materials have been used in tissue-engineered constructs to direct and control cell proliferation, growth and differentiation. However, their translation to clinical devices has been less successful. In this review, the use of electroanalytical techniques to develop an understanding of charge transfer at the electrode–tissue interface is discussed. In particular, the impact of solution and electrode conditions on charge injection capacity is demonstrated. The importance of standardised testing methods and the correlation of electrochemical and electrophysiological performance show the limitations of empirical studies and help define key electrode properties for clinical devices. The development of a sound theoretical basis for charge transfer at this increasingly important interface is being advocated to improve clinical outcomes and device lifetime and reduce power usage.

Heterosynaptic facilitation of mechanical nociceptive input is dependent on the frequency of conditioning stimulation.

High-frequency burstlike electrical conditioning stimulation (HFS) applied to human skin induces an increase in mechanical pinprick sensitivity of the surrounding unconditioned skin (a phenomenon known as secondary hyperalgesia). The present study assessed the effect of frequency of conditioning stimulation on the development of this increased pinprick sensitivity in humans. In a first experiment, we compared the increase in pinprick sensitivity induced by HFS, using monophasic non-charge-compensated pulses and biphasic charge-compensated pulses. High-frequency stimulation, traditionally delivered with non-charge-compensated square-wave pulses, may induce a cumulative depolarization of primary afferents and/or changes in pH at the electrode-tissue interface due to the accumulation of a net residue charge after each pulse. Both could contribute to the development of the increased pinprick sensitivity in a frequency-dependent fashion. We found no significant difference in the increase in pinprick sensitivity between HFS delivered with charge-compensated and non-charge-compensated pulses, indicating that the possible contribution of charge accumulation when non-charge-compensated pulses are used is negligible. In a second experiment, we assessed the effect of different frequencies of conditioning stimulation (5, 20, 42, and 100 Hz) using charge-compensated pulses on the development of increased pinprick sensitivity. The maximal increase in pinprick sensitivity was observed at intermediate frequencies of stimulation (20 and 42 Hz). It is hypothesized that the stronger increase in pinprick sensitivity at intermediate frequencies may be related to the stronger release of substance P and/or neurokinin-1 receptor activation expressed at lamina I neurons after C-fiber stimulation.NEW & NOTEWORTHY Burstlike electrical conditioning stimulation applied to human skin induces an increase in pinprick sensitivity in the surrounding unconditioned skin (a phenomenon referred to as secondary hyperalgesia). Here we show that the development of the increase in pinprick sensitivity is dependent on the frequency of the burstlike electrical conditioning stimulation.

General Voltage Injection Device for Immunity Test of Active Implantable Neurostimulators to Electromagnetic Fields over the Frequency Range 16.6Hz to 80MHz.

A general voltage injection testing device is presented to test the immunity of active implantable neurostimulator (INS) to electromagnetic fields over the frequency range 16.6Hz to 80MHz. The proposed device consists of test circuit and transfer tooling, which is designed to conduct Electromagnetic Compatibility (EMC) test of INS with output-only functionality. In the test circuit, a tissue-electrode interface model and its board layout are provided to satisfy impedance continuity and test channel consistency. In order to adapt to different types of stimulators and electrode specifications, transfer circuits and several kinds of transfer tooling are created. In accordance with ISO14708-3, Voltage injection tests have been carried out with the device and an INS with 16 electrodes. The results show that the device can meet test requirements and is useful for EMC test. Besides, the device can provide references for other manufacturers and organizations to accomplish voltage injection test.