Charge Injection Enhancement Comparisons of Iridium Oxide Microelectrodes and Using a Portable Neurostimulator.

Microelectrodes are desired to deliver more charges to neural tissues while under electrochemical safety limits. Applying anodic bias potential during neurostimulation is a known technique for charge enhancement. Here, we investigated the levels of charge enhancement with anodic bias potential and using a custom-designed portable neurostimulator.

Short-Term Effects of Gamma Stimulation on Neuroinflammation at the Tissue-Electrode Interface in Motor Cortex.

Objectives: The reliability of long-term neural recordings as therapeutic interventions for motor and sensory disorders is hampered by the brain tissue response. Previous work showed that flickering light at gamma frequencies (ie, 20-50 Hz) causes enhanced microglial recruitment in the visual cortex. The effects of gamma stimulation on glial cells surrounding implanted neural electrodes are not well understood.

A portable neurostimulator circuit with anodic bias enhances stimulation injection capacity.

Electrochemically safe and efficient charge injection for neural stimulation necessitates monitoring of polarization and enhanced charge injection capacity of the stimulating electrodes. In this work, we present improved microstimulation capability by developing a custom-designed multichannel portable neurostimulator with a fully programmable anodic bias circuitry and voltage transient monitoring feature.We developed a 16-channel multichannel neurostimulator system, compared charge injection capacities as a function of anodic bias potentials, and demonstrated convenient control of the system by a custom-designed user interface allowing bidirectional wireless data transmission of stimulation parameters and recorded voltage transients.

A Diagnostic Circuit for Crosstalk Detection in Microelectrode Arrays.

Current leakage between channels in microelectrode arrays is a sign of device failure and can lead to shorting of neural signals. The purpose of this project is to detect crosstalk between 32 channels of electrodes. We designed an embedded crosstalk detection system that can stimulate each electrode individually with a constant-current pulse and record voltage transients of the stimulated and adjacent electrodes to generate a matrix of crosstalk values.

Maximizing Charge Injection Limits of Iridium Oxide Electrodes with a Programmable Anodic Bias Circuit.

Efficacious stimulation of neural tissues requires high charge injection capacity while minimizing electrode polarization. Applying anodic bias on certain electrode materials is a way to enhance charge injection both and . We developed an embedded neurostimulator system that enabled a digital control of user-defined bias levels, without requiring a potentiometer or external voltage source.

A Simple Table-Top Technique for Multi-Signal Pseudo-Extracellular Recording.

Validation of neural probe performance often includes implantation in live animals, to assess ability to detect and distinguish signals generated by individual neurons. While this method is informative, an effective alternative would streamline device development and improve ethical considerations by reducing the use of animals in the validation of neural recording devices. Here, we describe a simple system using ball electrodes to apply multiple neural waveforms to phosphate buffered saline, which are simultaneously recorded by a microelectrode probe.

Configuring intracortical microelectrode arrays and stimulus parameters to minimize neuron loss during prolonged intracortical electrical stimulation.

Background: Previous studies have shown that neurons of the cerebral cortex can be injured by implantation of, and stimulation with, implanted microelectrodes.

Objectives: Objective 1 was to determine parameters of microstimulation delivered through multisite intracortical microelectrode arrays that will activate neurons of the feline cerebral cortex without causing loss of neurons.

Objective: 2 was to determine if the stimulus parameters that induced loss of cortical neurons differed for all cortical neurons vs.

Unprotected sidewalls of implantable silicon-based neural probes and conformal coating as a solution.

Silicon-based implantable neural devices have great translational potential as a means to deliver various treatments for neurological disorders. However, they are currently held back by uncertain longevity following chronic exposure to body fluids. Conventional deposition techniques cover only the horizontal surfaces which contain active electronics, electrode sites, and conducting traces.

Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum.

Colorectal hypersensitivity and sensitization of both mechanosensitive and mechanically insensitive afferents develop after intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in the mouse, a model of postinfectious irritable bowel syndrome. In mice in which ∼80% of extrinsic colorectal afferents were labeled genetically using the promotor for vesicular glutamate transporter type 2 (VGLUT2), we systematically quantified the morphology of VGLUT2-positive axons in mouse colorectum 7-28 days following intracolonic TNBS treatment. After removal, the colorectum was distended (20 mmHg), fixed with paraformaldehyde, and optically cleared to image VGLUT2-positive axons throughout the colorectal wall thickness.

Intraspinal stimulation with a silicon-based 3D chronic microelectrode array for bladder voiding in cats.

Bladder dysfunction is a significant and largely unaddressed problem for people living with spinal cord injury (SCI). Intermittent catheterization does not provide volitional control of micturition and has numerous side effects. Targeted electrical microstimulation of the spinal cord has been previously explored for restoring such volitional control in the animal model of experimental SCI.

Fabrication and modeling of recessed traces for silicon-based neural microelectrodes.

Objective: Chronically-implanted neural microelectrodes are powerful tools for neuroscience research and emerging clinical applications, but their usefulness is limited by their tendency to fail after months in vivo. One failure mode is the degradation of insulation materials that protect the conductive traces from the saline environment.

Approach: Studies have shown that material degradation is accelerated by mechanical stresses, which tend to concentrate on raised topographies such as conducting traces.

Gelatin embedding and LED autofluorescence reduction for rodent spinal cord histology.

We present two innovations in histological technique for rodent spinal cord: gelatin embedding and LED photobleaching. Gelatin embedding uses liquid gelatin solution to permeate delicate biological structures then solidify to provide mechanical support throughout dissection, vibratome sectioning, and staining. LED photobleaching uses high-intensity visible light during blocking and primary incubations to reduce autofluorescence in tissue sections before fluorescent secondaries are added.

A Wireless Neurostimulator System with an Embedded ARM™ Microprocessor.

In this study, a novel multi-layer printed circuit board (PCB)-based neurostimulator system with an embedded microprocessor is presented for applications in neuroprosthesis. The system integrates rechargeable batteries, a power management block, adjustable constant-current waveforms, voltage transient monitoring, and evoked neural response recording. The system can be configured to select channels among the 16 stimulation channels via Bluetooth communication wirelessly.

Recessed Traces for Planarized Passivation of Chronic Neural Microelectrodes.

Implantable microfabricated neural electrodes have numerous neuroscientific research and clinical applications. However, these devices are prone to failure after several months in vivo. One mechanism is failure of passivation layers followed by corrosion of metal traces in the saline environment.

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 , 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.

Responses of neurons in the feline inferior colliculus to modulated electrical stimuli applied on and within the ventral cochlear nucleus; Implications for an advanced auditory brainstem implant.

Auditory brainstem implants (ABIs) can restore useful hearing to persons with deafness who cannot benefit from cochlear implants. However, the quality of hearing restored by ABIs rarely is comparable to that provided by cochlear implants in persons for whom those are appropriate. In an animal model, we evaluated elements of a prototype of an ABI in which the functions of macroelectrodes on the surface of the dorsal cochlear nucleus would be integrated with the function of multiple penetrating microelectrodes implanted into the ventral cochlear nucleus.

Extracellular single-unit recordings from peripheral nerve axons in vitro by a novel multichannel microelectrode array.

The peripheral nervous system (PNS) is an attractive target for modulation of afferent input (e.g., nociceptive input signaling tissue damage) to the central nervous system.

A multispectral LED array for the reduction of background autofluorescence in brain tissue.

The presence of fixative-induced and cellular-derived artifactual autofluorescences (AAFs) presents a challenge in histological analysis involving immunofluorescence. We have established a simple and highly effective method for the reduction of AAFs that are ubiquitous in fixed mammalian brain and other tissues. A compact AAF-quenching photo-irradiation device was constructed using a commercially available light emitting diode (LED) array, cooling unit, and supporting components.

Encoding of the amplitude modulation of pulsatile electrical stimulation in the feline cochlear nucleus by neurons in the inferior colliculus; effects of stimulus pulse rate.

Objectives: Persons without a functional auditory nerve cannot benefit from cochlear implants, but some hearing can be restored by an auditory brainstem implant (ABI) with stimulating electrodes implanted on the surface of the cochlear nucleus (CN). Most users benefit from their ABI, but speech recognition tends to be poorer than for users of cochlear implants. Psychophysical studies suggest that poor modulation detection may contribute to the limited performance of ABI users.

In vivo validation of custom-designed silicon-based microelectrode arrays for long-term neural recording and stimulation.

We developed and validated silicon-based neural probes for neural stimulating and recording in long-term implantation in the brain. The probes combine the deep reactive ion etching process and mechanical shaping of their tip region, yielding a mechanically sturdy shank with a sharpened tip to reduce insertion force into the brain and spinal cord, particularly, with multiple shanks in the same array. The arrays' insertion forces have been quantified in vitro.

Neuronal activity evoked in the inferior colliculus of the cat by surface macroelectrodes and penetrating microelectrodes implanted in the cochlear nucleus.

Persons lacking functional auditory nerves cannot benefit from cochlear implants, but an auditory brainstem implant (ABI) utilizing stimulating electrodes adjacent to or on their cochlear nucleus (CN) can restore some hearing. We are investigating the feasibility of supplementing these surface electrodes with penetrating microstimulating electrodes within the ventral CN (VCN), and how the two types of electrodes can be used synergistically. Multiunit neuronal responses evoked by VCN electrical stimulation with surface electrodes and microelectrodes were recorded in the inferior colliculus (ICC) of five cats.

Bidirectional telemetry controller for neuroprosthetic devices.

We present versatile multifunctional programmable controller with bidirectional data telemetry, implemented using existing commercial microchips and standard Bluetooth protocol, which adds convenience, reliability, and ease-of-use to neuroprosthetic devices. Controller, weighing 190 g, is placed on animal's back and provides bidirectional sustained telemetry rate of 500 kb/s , allowing real-time control of stimulation parameters and viewing of acquired data. In continuously-active state, controller consumes approximately 420 mW and operates without recharge for 8 h .

A new chronic neural probe with electroplated iridium oxide microelectrodes.

We have developed a silicon-based neural microelectrode system for long-term neural recording and stimulation. Our aim is to design robust silicon-based microelectrode arrays that are suitable for implantation into various targets in the brain and spinal cord. The microelectrode sites were electroplated with iridium oxide, thereby reducing the AC impedance and increasing charge storage capacity, compared to gold electrodes.

Custom-designed high-density conformal planar multielectrode arrays for brain slice electrophysiology.

Multielectrode arrays have enabled electrophysiological experiments exploring spatio-temporal dynamics previously unattainable with single electrode recordings. The finite number of electrodes in planar MEAs (pMEAs), however, imposes a trade-off between the spatial resolution and the recording area. This limitation was circumvented in this paper through the custom design of experiment-specific tissue-conformal high-density pMEAs (cMEAs).