Penetrating Electrode Research Articles

Large-scale neural recordings with single neuron resolution using Neuropixels probes in human cortex.

Recent advances in multi-electrode array technology have made it possible to monitor large neuronal ensembles at cellular resolution in animal models. In humans, however, current approaches restrict recordings to a few neurons per penetrating electrode or combine the signals of thousands of neurons in local field potential (LFP) recordings. Here we describe a new probe variant and set of techniques that enable simultaneous recording from over 200 well-isolated cortical single units in human participants during intraoperative neurosurgical procedures using silicon Neuropixels probes. We characterized a diversity of extracellular waveforms with eight separable single-unit classes, with differing firing rates, locations along the length of the electrode array, waveform spatial spread and modulation by LFP events such as inter-ictal discharges and burst suppression. Although some challenges remain in creating a turnkey recording system, high-density silicon arrays provide a path for studying human-specific cognitive processes and their dysfunction at unprecedented spatiotemporal resolution.

Ampere-level CO2reduction to multicarbon products over a copper gas penetration electrode

A hierarchical micro/nanostructured Cu(100)-rich copper hollow fiber as a gas penetration electrode (GPE) efficiently reduces CO2to C2+products.

Raising the stakes for cortical visual prostheses.

In this issue of the JCI, the dream of restoring useful vision to blind individuals with neurotechnology moves one step closer to realization. Fernández et al. implanted an electrode array with 96 penetrating electrodes in the visual cortex of a blind patient who had been without light perception for 16 years due to optic neuropathy. Remarkably, the patient was able to perceive visual patterns created by passing current through array electrodes. The use of a penetrating electrode array meant that action potentials from single neurons could be recorded to study the neural response to stimulation. Compared with electrodes resting on the cortical surface, penetrating electrodes require one-tenth the current to create a visual percept. However, patterned electrical stimulation often fails to produce the expected percept for penetrating and surface electrode arrays, highlighting the need for further research to untangle the relationship between stimulus and perception.

Symptom: Unilateral Hearing Loss

Symptom: Unilateral Hearing Loss

Microstimulation-evoked neural responses in visual cortex are depth dependent

BackgroundCortical visual prostheses often use penetrating electrode arrays to deliver microstimulation to the visual cortex. To optimize electrode placement within the cortex, the neural responses to microstimulation at different cortical depths must first be understood. ObjectiveWe investigated how the neural responses evoked by microstimulation in cortex varied with cortical depth, of both stimulation and response. MethodsA 32-channel single shank electrode array was inserted into the primary visual cortex of anaesthetized rats, such that it spanned all cortical layers. Microstimulation with currents up to 14 μA (single biphasic pulse, 200 μs per phase) was applied at depths spanning 1600 μm, while simultaneously recording neural activity on all channels within a response window 2.25–11 ms. ResultsStimulation elicited elevated neuronal firing rates at all depths of cortex. Compared to deep sites, superficial stimulation sites responded with higher firing rates at a given current and had lower thresholds. The laminar spread of evoked activity across cortical depth depended on stimulation depth, in line with anatomical models. ConclusionStimulation in the superficial layers of visual cortex evokes local neural activity with the lowest thresholds, and stimulation in the deep layers evoked the most activity across the cortical column. In conjunction with perceptual reports, these data suggest that the optimal electrode placement for cortical microstimulation prostheses has electrodes positioned in layers 2/3, and at the top of layer 5.

Penetrating glassy carbon neural electrode arrays for brain-machine interfaces.

This paper presents a fabrication method for glassy carbon neural electrode arrays that combines 3D printing and chemical pyrolysis technology. The carbon electrodes have excellent biological compatibility and can be used in neural signal recording. A pretreated Si wafer is used as the substrate for 3D printing, and then, stereolithography 3D printing technology is employed to print photosensitive resin into a cone shape. Next, chemical pyrolysis is applied to convert the 3D prints into glassy carbon electrodes and modify the electrochemical performance of the carbon electrodes. Finally, the glassy carbon electrodes are packed with conductive wires and PDMS. The proposed fabrication method simplifies the manufacturing process of carbon materials, and electrodes can be fabricated without the need of deep reactive ion etching (DRIE). The height of the carbon electrodes is 1.5mm, and the exposure area of the tips is 0.78mm2, which is convenient for the implantation procedure. The specific capacitance of the glassy carbon arrays is higher than that of a platinum electrode (9.18 mF/cm2 vs 3.32 mF/cm2, respectively), and the impedance at 1kHz is lower (7.1 kΩ vs 8.8 kΩ). The carbon electrodes were tested in vivo, and they showed excellent performance in neural signal recording. The signal-to-noise ratio of the carbon electrodes is 50.73 ± 6.11, which is higher than that of the Pt electrode (20.15 ± 5.32) under the same testing conditions. The proposed fabrication method of glassy carbon electrodes provides a novel approach to manufacture penetrating electrodes for nerve interfaces in biomedical engineering and microelectromechanical systems.

Selectivity of afferent microstimulation at the DRG using epineural and penetrating electrode arrays

Objective. We have shown previously that microstimulation of the lumbar dorsal root ganglia (L5-L7 DRG) using penetrating microelectrodes, selectively recruits distal branches of the sciatic and femoral nerves in an acute preparation. However, a variety of challenges limit the clinical translatability of DRG microstimulation via penetrating electrodes. For clinical translation of a DRG somatosensory neural interface, electrodes placed on the epineural surface of the DRG may be a viable path forward. The goal of this study was to evaluate the recruitment properties of epineural electrodes and compare their performance with that of penetrating electrodes. Here, we compare the number of selectively recruited distal nerve branches and the threshold stimulus intensities between penetrating and epineural electrode arrays. Approach. Antidromically propagating action potentials were recorded from multiple distal branches of the femoral and sciatic nerves in response to epineural stimulation on 11 ganglia in four cats to quantify the selectivity of DRG stimulation. Compound action potentials (CAPs) were recorded using nerve cuff electrodes implanted around up to nine distal branches of the femoral and sciatic nerve trunks. We also tested stimulation selectivity with penetrating microelectrode arrays implanted into ten ganglia in four cats. A binary search was carried out to identify the minimum stimulus intensity that evoked a response at any of the distal cuffs, as well as whether the threshold response selectively occurred in only a single distal nerve branch. Main results. Stimulation evoked activity in just a single peripheral nerve through 67% of epineural electrodes (35/52) and through 79% of the penetrating microelectrodes (240/308). The recruitment threshold (median = 9.67 nC/phase) and dynamic range of epineural stimulation (median = 1.01 nC/phase) were significantly higher than penetrating stimulation (0.90 nC/phase and 0.36 nC/phase, respectively). However, the pattern of peripheral nerves recruited for each DRG were similar for stimulation through epineural and penetrating electrodes. Significance. Despite higher recruitment thresholds, epineural stimulation provides comparable selectivity and superior dynamic range to penetrating electrodes. These results suggest that it may be possible to achieve a highly selective neural interface with the DRG without penetrating the epineurium.

Direct Electrical Stimulation in Electrocorticographic Brain-Computer Interfaces: Enabling Technologies for Input to Cortex.

Electrocorticographic brain computer interfaces (ECoG-BCIs) offer tremendous opportunities for restoring function in individuals suffering from neurological damage and for advancing basic neuroscience knowledge. ECoG electrodes are already commonly used clinically for monitoring epilepsy and have greater spatial specificity in recording neuronal activity than techniques such as electroencephalography (EEG). Much work to date in the field has focused on using ECoG signals recorded from cortex as control outputs for driving end effectors. An equally important but less explored application of an ECoG-BCI is directing input into cortex using ECoG electrodes for direct electrical stimulation (DES). Combining DES with ECoG recording enables a truly bidirectional BCI, where information is both read from and written to the brain. We discuss the advantages and opportunities, as well as the barriers and challenges presented by using DES in an ECoG-BCI. In this article, we review ECoG electrodes, the physics and physiology of DES, and the use of electrical stimulation of the brain for the clinical treatment of disorders such as epilepsy and Parkinson’s disease. We briefly discuss some of the translational, regulatory, financial, and ethical concerns regarding ECoG-BCIs. Next, we describe the use of ECoG-based DES for providing sensory feedback and for probing and modifying cortical connectivity. We explore future directions, which may draw on invasive animal studies with penetrating and surface electrodes as well as non-invasive stimulation methods such as transcranial magnetic stimulation (TMS). We conclude by describing enabling technologies, such as smaller ECoG electrodes for more precise targeting of cortical areas, signal processing strategies for simultaneous stimulation and recording, and computational modeling and algorithms for tailoring stimulation to each individual brain.

3D Reconstruction of the Intracortical Volume Around a Hybrid Microelectrode Array.

Extensive research using penetrating electrodes implanted in the central and peripheral nervous systems has been performed for many decades with significant advances made in recent years. While penetrating devices provide proximity to individual neurons in vivo, they suffer from declining performance over the course of months and often fail within a year. 2D histology studies using serial tissue sections have been extremely insightful in identifying and quantifying factors such as astroglial scar formation and neuronal death around the implant sites that may be contributing to failures. However, 2D histology has limitations in providing a holistic picture of the problems occurring at the electrode-tissue interface and struggles to analyze tissue below the electrode tips where the electrode tracks are no longer visible. In this study, we present 3D reconstruction of serial sections to overcome the limitations of 2D histological analysis. We used a cohort of software: XuvStitch, AutoAligner, and Imaris coupled with custom MATLAB programming to correct warping effects. Once the 3D image volume was reconstructed, we were able to use Imaris to quantify neuronal densities around the electrode tips of a hybrid microelectrode array incorporating Blackrock, Microprobes, and NeuroNexus electrodes in the same implant. This paper presents proof-of-concept and detailed methodological description of a technique which can be used to quantify neuronal densities in future studies of implanted electrodes.

Focal activation of neuronal circuits induced by microstimulation in the visual cortex

Objective. Microstimulation to the cortical tissue applied with penetrating electrodes delivers current that spreads concentrically around the electrode tip and is known to evoke focal visual sensations, i.e. phosphenes. However, to date, there is no direct evidence depicting the spatiotemporal properties of neuronal activity induced immediately after microstimulation and how such activity drives the subsequent local cortical circuits. Approach. In the present study, we imaged the spatiotemporal distribution of action potentials (APs) directly induced by microstimulation and the subsequent trans-synaptic signal propagation using a voltage-sensitive dye (VSD) and a calcium-sensitive dye (CaSD) in slice preparations of the mouse primary visual cortex. Main results. The directly induced APs were confined to the close vicinity of the electrode tip, and the effective distance of excitation was proportional to the square root of the current intensity. The excitation around the electrode tip in layer IV mainly propagated to layer II/III to further induce the subsequent focal activation in downstream local cortical circuits. The extent of activation in the downstream circuits was restrained by competitive interactions between excitatory and inhibitory signals. Namely, the spread of the excitation to lateral neighbor neurons along the layer II/III was confined by the delayed inhibition that also spread laterally at a faster rate. Significance. These observations indicate that dynamic interactions between excitatory and inhibitory signals play a critical role in the focal activation of a cortical circuit in response to intracortical microstimulation and, therefore, in evoking a localized phosphene.

Recording single- and multi-unit neuronal action potentials from the surface of the dorsal root ganglion

The dorsal root ganglia (DRG) contain cell bodies of primary afferent neurons, which are frequently studied by recording extracellularly with penetrating microelectrodes inserted into the DRG. We aimed to isolate single- and multi-unit activity from primary afferents in the lumbar DRG using non-penetrating electrode arrays and to characterize the relationship of that activity with limb position and movement. The left sixth and seventh lumbar DRG (L6-L7) were instrumented with penetrating and non-penetrating electrode arrays to record neural activity during passive hindlimb movement in 7 anesthetized cats. We found that the non-penetrating arrays could record both multi-unit and well-isolated single-unit activity from the surface of the DRG, although with smaller signal to noise ratios (SNRs) compared to penetrating electrodes. Across all recorded units, the median SNR was 1.1 for non-penetrating electrodes and 1.6 for penetrating electrodes. Although the non-penetrating arrays were not anchored to the DRG or surrounding tissues, the spike amplitudes did not change (<1% change from baseline spike amplitude) when the limb was moved passively over a limited range of motion (~20 degrees at the hip). Units of various sensory fiber types were recorded, with 20% of units identified as primary muscle spindles, 37% as secondary muscle spindles, and 24% as cutaneous afferents. Our study suggests that non-penetrating electrode arrays can record modulated single- and multi-unit neural activity of various sensory fiber types from the DRG surface.

Transparent, Flexible, Penetrating Microelectrode Arrays with Capabilities of Single-Unit Electrophysiology.

Accurately mapping neuronal activity across brain networks is critical to understand behaviors, yet it is very challenging due to the need of tools with both high spatial and temporal resolutions. Here, penetrating arrays of flexible microelectrodes made of low-impedance nanomeshes are presented, which are capable of recording single-unit electrophysiological neuronal activity and at the same time, transparent, allowing to bridge electrical and optical brain mapping modalities. These 32 transparent penetrating electrodes with site area, 225 µm2 , have a low impedance of ≈149 kΩ at 1 kHz, an adequate charge injection limit of ≈0.76 mC cm-2 , and up to 100% yield. Mechanical bending tests reveal that the array is robust up to 1000 bending cycles, and its high transmittance of 67% at 550 nm makes it suitable for combining with various optical methods. A temporary stiffening using polyethylene glycol allows the penetrating nanomesh arrays to be inserted into the brain minimally invasively, with in vivo validation of recordings of spontaneous and evoked single-unit activity of neurons across layers of the mouse visual cortex. Together, these results establish a novel neurotechnology-transparent, flexible, penetrating microelectrode arrays-which possesses great potential for brain research.

Single electro-optic curve for RGB colours in blue-phase liquid crystal display

ABSTRACTThe double-layer penetration electrode structure is proposed to obtain the low-operating voltage blue-phase liquid crystal display (BPLCD) with single electro-optic curve for red-green-blue (RGB) colours in every pixel, which is more suitable for the field-sequential-colour display. The different influences of electrode’s parameters and driving methods on the electro-optical properties of the proposed BPLCD are investigated. The results demonstrate that the operating voltage can be reduced from 53.80 V to 23.00 V for red colour. Besides, the coincident voltage-dependent transmittance curves for RGB colours are obtained by adjusting the applied voltage of sub-electrode. Thus, RGB lights can pass through every pixel with single electro-optic curve, which is good for resolution enhancement and single gamma driving. Besides, the maximum gamma shift of the proposed BPLCD is less than 0.1099 at 60° polar angle for the red colour, and the gamma shift difference between red and blue colours is only 0.0542. If the high dielectric constant material is used as the protrusion, the operating voltage can be further decreased, which is close to that of the BPLCD with wall-shaped electrode structure.

Polydimethylsiloxane (PDMS)-Based Flexible Optical Electrodes with Conductive Composite Hydrogels Integrated Probe for Optogenetics.

Optical electrodes are important tools for optogenetic research. Flexible optical electrodes represent a refinement over traditional fiber-based electrodes because they contact with target cells gently by reducing mechanical mismatch, thereby enhancing their long-term, stable signal acquisition capability. Until now, little attention has been paid to flexible intracortical optical electrodes. Here, we reported a novel flexible penetrating optical electrode with a probe made of composite hydrogels. We used polydimethylsiloxane (PDMS), a kind of transparent material, to fabricate waveguide by capillary assembly method with two tungsten wires inside providing mechanic support. Then one tungsten wire was withdrawn out and the microchannel was filled with hydrogel composed of polyvinyl alcohol (PVA), multi-walled carbon nanotubes (MWCNT), poly(3,4-ethylenedioxythiophene) (PEDOT), and polystyrene sulfonate (PSS) as an electrical recording and stimulation probe. With PDMS as the waveguide and PVA/MWCNT/PEDOT/PSS hydrogel as the electroprobe, the optical electrode becomes a flexible package. The morphology observed by scanning electron microscopy showed that the PVA/MWCNT/PEDOT/PSS hydrogel had a loose surface structure, which would allow the effective adhesion to target neurons. A buckling test showed that our electrode maintained bending strength comparable to that of previously reported flexible penetrating electrodes. Finally, the electrical properties showed a lower impedance and higher charge capacity after PEDOT/PSS modification. The flexible penetrating optical electrode we developed may be used for long-term in vivo optogenetics studies.

Codon optimization and improved delivery/immunization regimen enhance the immune response against wild-type and drug-resistant HIV-1 reverse transcriptase, preserving its Th2-polarity

DNA vaccines require a considerable enhancement of immunogenicity. Here, we optimized a prototype DNA vaccine against drug-resistant HIV-1 based on a weak Th2-immunogen, HIV-1 reverse transcriptase (RT). We designed expression-optimized genes encoding inactivated wild-type and drug-resistant RTs (RT-DNAs) and introduced them into mice by intradermal injections followed by electroporation. RT-DNAs were administered as single or double primes with or without cyclic-di-GMP, or as a prime followed by boost with RT-DNA mixed with a luciferase-encoding plasmid (“surrogate challenge”). Repeated primes improved cellular responses and broadened epitope specificity. Addition of cyclic-di-GMP induced a transient increase in IFN-γ production. The strongest anti-RT immune response was achieved in a prime-boost protocol with electroporation by short 100V pulses done using penetrating electrodes. The RT-specific response, dominated by CD4+ T-cells, targeted epitopes at aa 199–220 and aa 528–543. Drug-resistance mutations disrupted the epitope at aa 205–220, while the CTL epitope at aa 202–210 was not affected. Overall, multiparametric optimization of RT strengthened its Th2- performance. A rapid loss of RT/luciferase-expressing cells in the surrogate challenge experiment revealed a lytic potential of anti-RT response. Such lytic CD4+ response would be beneficial for an HIV vaccine due to its comparative insensitivity to immune escape.

Long term performance of porous platinum coated neural electrodes.

Over the last several years, there has been a growing interest in neural implants for the study and diagnostics of neurological disorders as well as for the symptomatic treatment of central nervous system related diseases. One of the major challenges is the trade-off between small electrode sizes for high selectivity between single neurons and large electrode-tissue interface areas for excellent stimulation and recording properties. This paper presents an approach of increasing the real surface area of the electrodes by creating a surface microstructure. Two major novelties let this work stand out from existing approaches which mainly make use of porous coatings such as platinum black or iridium oxide, or Poly(3,4-ethylenedioxythiophene) (PEDOT). Roughening is carried out by a dry etching process on the silicon electrode core before being coated by a sputtered platinum layer, eliminating complicated deposition processes as for the materials described above. The technology is compatible with any commonly used coating material. In addition, the surface roughening is compatible with high aspect ratio penetrating electrode arrays such as the well-established Utah electrode array, whose unique geometry presents a challenge in the surface modification of active electrode sites. The dry etching process is well characterized and yields a high controllability of pore size and depth. This paper confirms the superior electrochemical properties including impedance, charge injection capacity, and charge storage capacity of surface engineered electrode arrays compared to conventional arrays over a period of 12weeks. Furthermore, mechanical stability of the modified electrodes was tested by implantation in the brain of a recently deceased rat. In conclusion, the larger interface surface of the electrodes does not only decrease the impedance which should lead to enhanced Signal to noise ratio (SNR) for recording purposes, but also yields higher charge injection capacities, which improve the stimulation characteristics of the implants.

Intratumoral IL-12 gene electrotransfer-mediated regression of established B16F10 melanoma protects against rechallenge

Abstract Melanoma is an aggressive tumor with limited treatment options and poor prognosis. Interleukin-12 (IL-12) is a potent cytokine mediating antitumor activity. However, it has only achieved modest antitumor effects in clinical trials, often accompanied by unacceptable adverse events. We evaluated whether intratumoral delivery of a plasmid encoding IL-12 using gene electrotransfer (GET) to control the dose could induce rejection of an established poorly immunogenic tumor and avoid dose dependent toxicities. We treated B16F10 murine melanoma 3 times in 1 week by intratumoral injection of pUMVC3mIL-12 plasmid (pmIL-12, 50 μg) followed by GET. The GET protocols were; EP1 (six 300 V/cm, 100 μs pulses with an array of 6 penetrating electrodes), EP2 (ten 600 V/cm, 5ms pulses with non-penetrating caliper electrodes). Localized delivery of pmIL-12 with GET in the tumor microenvironment, significantly delayed disease development and prolonged disease free survival and induced long term immune memory protecting against rechallenge. The response was associated with a significant reduction in Treg and MDSC infiltration in B16F10 melanoma and increase of Granzyme B. Mice treated with pmIL-12 EP1 that achieved protection against rechallenge were observed to have CD62LlowCD44high memory T cells. Interestingly, pmIL-12 demonstrated stronger anti-tumor effects than pmIL-12 delivered by EP2. By manipulation of GET parameters the onset, level and duration of IL-12 protein expression can be controlled, resulting in meaningful therapeutic effects without associated IL-12 toxicities. Furthermore, the approach induced systemic antitumor immune activity and memory and therefore might have an impact against other types of metastatic disease.

Electrically Evoked Responses in the Rabbit Cortex Induced by Current Steering With Penetrating Optic Nerve Electrodes.

Current steering is a neural stimulation strategy that uses simultaneous stimulation of adjacent electrodes to produce additional intermediate stimulation sites and thus improves spatial resolution. We investigated the feasibility of current steering using electrophysiological and computational methods after implanting paired penetrating electrodes into the rabbit's optic nerve (ON). Penetrating electrodes at different interelectrode distances were implanted into the ON and electrically evoked cortical potentials (EEPs) in V1 recorded with a 6 × 8 array. The current thresholds, EEP amplitudes, and spatial distributions were analyzed during current steering. Computational simulation studies were performed based on finite element models to calculate the area and spatial distribution of recruited ON fibers using a current steering stimulation strategy. Threshold reduction and EEP amplitude enhancement were found with simultaneous stimulation of closely spaced electrode pairs. Spatially shifted cortical responses were achieved using current steering, whereas the amplitudes and spatial spreads of the responses were similar to that elicited by a single electrode. Computational simulations suggested that the centroid of the ON recruitment area could be modulated by current steering while the total recruitment area did not show any appreciable variability at a fixed current intensity. Current steering is a useful strategy to enhance the spatial resolution of an ON prosthesis without increasing the number of physical electrodes. This study provides useful information for optimizing the design of stimulation strategies with a penetrating ON prosthesis.

A Stretchable Microneedle Electrode Array for Stimulating and Measuring Intramuscular Electromyographic Activity.

We have developed a stretchablemicroneedle electrode array (sMEA) to stimulate andmeasure the electrical activity of muscle across multiple sites. The technology provides the signal fidelity and spatial resolution of intramuscular electrodesacross a large area of tissue. Our sMEA is composed of a polydimethylsiloxane (PDMS) substrate, conductive-PDMS traces, and stainless-steel penetrating electrodes. The traces and microneedles maintain a resistance of less than 10 [Formula: see text] when stretched up to a ~63% tensile strain, which allows for the full range of physiological motion of felinemuscle. The device and its constituent materials are cytocompatible for at least 28 days in vivo. When implanted in vivo, the device measures electromyographic (EMG) activity with clear compound motor unit action potentials. The sMEA also maintains a stable connection with moving muscle while electrically stimulating the tissue. This technology has direct application to wearable sensors, neuroprostheses, and electrophysiological studies of animals and humans.

Hierarchical Hybrids of Mesoporous NiCo2O4 Needles/Graphene/Carbon Nanotubes with High Performance for Lithium Ion Batteries and Oxygen Reduction Reactions

AbstractThree‐dimensional (3D) hierarchical NiCo2O4‐graphene/carbon nanotube (NiCo‐G/CNT) hybrids with NiCo2O4 needles deposited on a conductive G/CNT template have been facilely produced by a co‐precipitation method. Mesoporous NiCo2O4 needles endow the NiCo‐G/CNT hybrids with high specific surface area, which allows good electrolyte penetration and large electrode–electrolyte contact area, leading to fast ion and electron transfer and excellent strain accommodation. The unique hierarchical structures of NiCo‐G/CNT hybrids ensure complete exposure of their active sites and endow them with dual functionalities that allow them to serve as high‐performance electrodes for both lithium‐ion batteries and oxygen reduction reactions. In particular, the NiCo4‐G/CNT sample delivers a remarkable specific capacitance of 1392 mAh g−1 at current density of 0.1 A g−1, and achieves high electrocatalytic activity with long‐term stability for ORR. This preparation strategy is simple and effective, and can be conveniently extended to fabricate other kinds of binary‐oxide‐based materials for energy‐storage applications.