Toward Safety Protocols for Peripheral Nerve Stimulation (PNS): A Computational and Experimental Approach.

As the clinical applicability of peripheral nerve stimulation (PNS) expands, the need for PNS-specific safety criteria becomes pressing. This study addresses this need, utilizing a novel machine learning and computational bio-electromagnetics modeling platform to establish a safety criterion that captures the effects of fields and currents induced on axons. Our approach is comprised of three steps: experimentation, model creation, and predictive simulation.

Machine learning enables non-Gaussian investigation of changes to peripheral nerves related to electrical stimulation.

Electrical stimulation of the peripheral nervous system (PNS) is becoming increasingly important for the therapeutic treatment of numerous disorders. Thus, as peripheral nerves are increasingly the target of electrical stimulation, it is critical to determine how, and when, electrical stimulation results in anatomical changes in neural tissue. We introduce here a convolutional neural network and support vector machines for cell segmentation and analysis of histological samples of the sciatic nerve of rats stimulated with varying current intensities.

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.

Neuropathological effects of chronically implanted, intracortical microelectrodes in a tetraplegic patient.

Intracortical microelectrode arrays (MEA) can be used as part of a brain-machine interface system to provide sensory feedback control of an artificial limb to assist persons with tetraplegia. Variability in functionality of electrodes has been reported but few studies in humans have examined the impact of chronic brain tissue responses revealed postmortem on electrode performanceIn a tetraplegic man, recording MEAs were implanted into the anterior intraparietal area and Brodmann's area 5 (BA5) of the posterior parietal cortex and a recording and stimulation array was implanted in BA1 of the primary somatosensory cortex (S1). The participant expired from unrelated causes seven months after MEA implantation.

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.

PRIMA subretinal wireless photovoltaic microchip implantation in non-human primate and feline models.

Purpose: To evaluate the surgical technique for subretinal implantation of two sizes of PRIMA photovoltaic wireless microchip in two animal models, and refine these surgical procedures for human trials.

Methods: Cats and Macaca fascicularis primates with healthy retina underwent vitrectomy surgery and were implanted with subretinal wireless photovoltaic microchip at the macula/central retina. The 1.

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.

Correlations between histology and neuronal activity recorded by microelectrodes implanted chronically in the cerebral cortex.

Objective: To quantify relations between the neuronal activity recorded with chronically-implanted intracortical microelectrodes and the histology of the surrounding tissue, using radial distance from the tip sites and time after array implantation as parameters.

Approach: 'Utah'-type intracortical microelectrode arrays were implanted into cats' sensorimotor cortex for 275-364 days. The brain tissue around the implants was immuno-stained for the neuronal marker NeuN and for the astrocyte marker GFAP.

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.

Electrical performance of penetrating microelectrodes chronically implanted in cat cortex.

Penetrating microelectrode arrays with 2000 μm (2) sputtered iridium oxide (SIROF) electrode sites were implanted in cat cerebral cortex, and their long-term electrochemical performance evaluated in vivo by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and current pulsing. Measurements were made from days 33 to 328 postimplantation. The CV-defined charge storage capacity, measured at 50 mV/s, increased linearly with time over the course of implantation for two arrays and was unchanged for one array.

Electrical performance of penetrating microelectrodes chronically implanted in cat cortex.

Penetrating multielectrode arrays with electrode coatings of sputtered iridium oxide (SIROF) have been implanted chronically in cat cortex for periods over 300 days. The ability of these electrodes to inject charge at levels above expected thresholds for neural excitation has been examined in vivo by measurements of voltage transients in response to current-controlled, cathodal stimulation pulsing. The effect of current pulse width from 150 μs to 500 μs and voltage biasing of the electrodes in the interpulse period at two levels, 0.

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.

Neuronal loss due to prolonged controlled-current stimulation with chronically implanted microelectrodes in the cat cerebral cortex.

Activated iridium microelectrodes were implanted for 450-1282 days in the sensorimotor cortex of seven adult domestic cats and then pulsed for 240 h (8 h per day for 30 days) at 50 Hz. Continuous stimulation at 2 nC/phase and with a geometric charge density of 100 microC cm(-2) produced no detectable change in neuronal density in the tissue surrounding the microelectrode tips. However, pulsing with a continuous 100% duty cycle at 4 nC/phase and with a geometric charge density of 200 microC cm(-2) induced loss of cortical neurons over a radius of at least 150 microm from the electrode tips.

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.

Spinal hyperexcitability and bladder hyperreflexia during reversible frontal cortical inactivation induced by low-frequency electrical stimulation in the cat.

Spinal hyperexcitability and hyperreflexia gradually develop in the majority of stroke patients. These pathologies develop as a result of reduced cortical modulation of spinal reflexes, mediated largely indirectly via relays in the brainstem and other subcortical structures. Cortical control of spinal reflexes is markedly different in small animals, such as rodents, while in some larger species, such as cats, it is more comparable to that in humans.

Audiologic outcomes with the penetrating electrode auditory brainstem implant.

Objective: The penetrating electrode auditory brainstem implant (PABI) is an extension of auditory brainstem implant (ABI) technology originally developed for individuals deafened by neurofibromatosis type 2. Whereas the conventional ABI uses surface electrodes on the cochlear nuclei, the PABI uses 8 or 10 penetrating microelectrodes in conjunction with a separate array of 10 or 12 surface electrodes. The goals of the PABI were to use microstimulation to reduce threshold current levels, increase the range of pitch percepts, and improve electrode selectivity and speech recognition.

Cochlear nucleus auditory prostheses.

Persons who lack an auditory nerve cannot benefit from cochlear implants, but a prosthesis utilizing an electrode array implanted on the surface of the cochlear nucleus can restore some hearing. Worldwide, more than 500 persons have received these "auditory brainstem implants," most commonly after removal of the tumors that occur with Type 2 Neurofibromatosis (NF2). Typically, the ABIs provide these individuals with improved speech perception when combined with lip-reading and useful perception of environmental sounds, but little open-set speech recognition.

Intraspinal stimulation for bladder voiding in cats before and after chronic spinal cord injury.

The long-term objective of this study is to develop neural prostheses for people with spinal cord injuries who are unable to voluntarily control their bladder. This feasibility study was performed in 22 adult cats. We implanted an array of microelectrodes into locations in the sacral spinal cord that are involved in the control of micturition reflexes.

Performance of multisite silicon microprobes implanted chronically in the ventral cochlear nucleus of the cat.

A central auditory prosthesis based on microstimulation within the ventral cochlear nucleus (VCN) offers a means of restoring hearing to persons whose auditory nerve has been destroyed bilaterally and cannot benefit from cochlear implants. Arrays of silicon probes with 16 stimulating sites were implanted into the VCN of adult cats, for up to 314 days. Compound neuronal responses evoked from the sites in the VCN were recorded periodically in the central nucleus of the contralateral inferior colliculus (ICC).

Intracortical visual prosthesis research - approach and progress.

Following the early work of Brindley in the late 1960's, the NIH began intramural and extramural funding for stimulation of the primary visual coretex using fine-wire electrodes that are inserted into area VI for the prupose of restoring vision in individuals with blindness. More recently researchers with experience in this projectbecame part of our multi-institutional team with the intention to identify and close technological gaps so that the intracortical approach might be tested in humans on a chronic basis. Our team has formulated an approach for testing a prototype system in a human volunteer.

"Safe" charge-injection waveforms for iridium oxide (AIROF) microelectrodes.

Use of anodic bias improves the charge-injection limits of activated iridium oxide (AIROF) microelectrodes. Asymmetric waveforms, in which the charge balancing anodic phase is delivered at a lower current density and longer pulse width, has been found to allow for higher values of anodic bias voltages, thus maximizing the AIROF charge-injection capacity. Limiting the voltage excursion of the AIROF below the value at which electrolysis of water occurs is essential to maintaining the long-term viability of implanted electrodes.

Basis of electrical stimulation of the cochlea and the cochlear nucleus.

Sensorineural hearing loss is the most common form of deafness in humans. In patients with a severe-profound sensorineural hearing loss therapeutic intervention can only be achieved by direct electrical stimulation of the auditory nerve via a cochlear implant, or - in cases where a cochlear implant is not a surgical option - neurons within the central auditory pathway via an auditory brainstem implant. This paper reviews the basis of electrical stimulation of these structures with an emphasis on pathophysiology and safety.

Microelectrode array for chronic deep-brain microstimulation and recording.

We have developed an array of microelectrodes that is suitable for long-term implantation into the subthalamic nucleus (STN) or the globus pallidus and is able to record from single neurons, as well as deliver localized microstimulation. This device can be used to investigate the mechanisms by which deep brain stimulation can ameliorate the symptoms of Parkinson's disease and other movement disorders, and also may be the basis for a new clinical tool for the treatment of Parkinson's disease, by capitalizing on the high spatial specificity of intranuclear microstimulation. The array includes 16 activated iridium microelectrodes, 5-6 mm in length, within a cluster approximately 1.