A brain-spinal interface (BSI) system-on-chip (SoC) for closed-loop cortically-controlled intraspinal microstimulation

This paper reports on a fully miniaturized brain-spinal interface system for closed-loop cortically-controlled intraspinal microstimulation (ISMS). Fabricated in AMS 0.35 µm two-poly four-metal complementary metal–oxide–semiconductor technology, this system-on-chip measures ~ 3.46 mm × 3.46 mm and incorporates two identical 4-channel modules, each comprising a spike-recording front-end, embedded digital signal processing (DSP) unit, and programmable stimulating back-end. The DSP unit is capable of generating multichannel trigger signals for a wide array of ISMS triggering patterns based on real-time discrimination of a programmable number of intracortical neural spikes within a pre-specified time-bin duration via thresholding and user-adjustable time–amplitude windowing. The system is validated experimentally using an anesthetized rat model of a spinal cord contusion injury at the T8 level. Multichannel neural spikes are recorded from the cerebral cortex and converted in real time into electrical stimuli delivered to the lumbar spinal cord below the level of the injury, resulting in distinct patterns of hindlimb muscle activation

Fatigue Resistibility and Stimulus Strength Using Intraspinal Microstimulation vs. Intramuscular Stimulation in a Rat Model: Case Study

Spinal Cord Injury is a devastating injury that has drastic effects on an individual’s daily living activities. The current devices and methods of direct muscle, peripheral nerve cuff, and epidural stimulation are bulky, easily fatigable, require large stimulation parameters, and/ or difficult to use. Intraspinal Micro stimulation (ISMS) suggests a more fatigue resistant method at lower stimulation parameters that will help restore locomotion, bladder control, and sexual function in an individual. The research conducted herein shows ISMS evokes a linear positive relationship between stimulus strength and muscle contraction force that is comparable to clinically used methods of Intramuscular stimulation. Research has also shown that fatigue resistance appears to be similar in the two stimulation parameters. The study concludes that ISMS compares to clinically used methods and therefore suggests potential of this method to help Spinal Cord Injury victims to help aid in activities of daily living

Enhancing Nervous System Recovery through Neurobiologics, Neural Interface Training, and Neurorehabilitation.

After an initial period of recovery, human neurological injury has long been thought to be static. In order to improve quality of life for those suffering from stroke, spinal cord injury, or traumatic brain injury, researchers have been working to restore the nervous system and reduce neurological deficits through a number of mechanisms. For example, neurobiologists have been identifying and manipulating components of the intra- and extracellular milieu to alter the regenerative potential of neurons, neuro-engineers have been producing brain-machine and neural interfaces that circumvent lesions to restore functionality, and neurorehabilitation experts have been developing new ways to revitalize the nervous system even in chronic disease. While each of these areas holds promise, their individual paths to clinical relevance remain difficult. Nonetheless, these methods are now able to synergistically enhance recovery of native motor function to levels which were previously believed to be impossible. Furthermore, such recovery can even persist after training, and for the first time there is evidence of functional axonal regrowth and rewiring in the central nervous system of animal models. To attain this type of regeneration, rehabilitation paradigms that pair cortically-based intent with activation of affected circuits and positive neurofeedback appear to be required-a phenomenon which raises new and far reaching questions about the underlying relationship between conscious action and neural repair. For this reason, we argue that multi-modal therapy will be necessary to facilitate a truly robust recovery, and that the success of investigational microscopic techniques may depend on their integration into macroscopic frameworks that include task-based neurorehabilitation. We further identify critical components of future neural repair strategies and explore the most updated knowledge, progress, and challenges in the fields of cellular neuronal repair, neural interfacing, and neurorehabilitation, all with the goal of better understanding neurological injury and how to improve recovery

Poly(3,4-ethylenedioxythiophene) as a Micro-Neural Interface Material for Electrostimulation

Chronic microstimulation-based devices are being investigated to treat conditions such as blindness, deafness, pain, paralysis, and epilepsy. Small-area electrodes are desired to achieve high selectivity. However, a major trade-off with electrode miniaturization is an increase in impedance and charge density requirements. Thus, the development of novel materials with lower interfacial impedance and enhanced charge storage capacity is essential for the development of micro-neural interface-based neuroprostheses. In this report, we study the use of conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) as a neural interface material for microstimulation of small-area iridium electrodes on silicon-substrate arrays. Characterized by electrochemical impedance spectroscopy, electrodeposition of PEDOT results in lower interfacial impedance at physiologically relevant frequencies, with the 1 kHz impedance magnitude being 23.3 ± 0.7 kΩ, compared to 113.6 ± 3.5 kΩ for iridium oxide (IrOx) on 177 μm2 sites. Further, PEDOT exhibits enhanced charge storage capacity at 75.6 ± 5.4 mC/cm2 compared to 28.8 ± 0.3 mC/cm2 for IrOx, characterized by cyclic voltammetry (50 mV/s). These improvements at the electrode interface were corroborated by observation of the voltage excursions that result from constant current pulsing. The PEDOT coatings provide both a lower amplitude voltage and a more ohmic representation of the applied current compared to IrOx. During repetitive pulsing, PEDOT-coated electrodes show stable performance and little change in electrical properties, even at relatively high current densities which cause IrOx instability. These findings support the potential of PEDOT coatings as a micro-neural interface material for electrostimulation

Conditional Electrical Stimulation in Animal and Human Models for Neurogenic Bladder: Working Toward a Neuroprosthesis

Sacral neuromodulation has had a tremendous impact on the treatment of urinary incontinence and lower urinary tract symptoms for patients with neurologic conditions. This stimulation does not use real-time data from the body or input from the patient. Incorporating this is the goal of those pursuing a neuroprosthesis to enhance bladder function for these patients. Investigators have demonstrated the effectiveness of conditional (also called closed-loop) feedback in animal models as well as limited human studies. Dorsal genital nerve, pudendal nerve, S3 afferent nerve roots, S1 and S2 ganglia have all been used as targets for stimulation. Most of these have also been used as sources of afferent nerve information using sophisticated nerve electrode arrays and filtering algorithms to detect significant bladder events and even to estimate the fullness of the bladder. There are problems with afferent nerve sensing, however. Some of these include sensor migration and low signal to noise ratios. Implantable pressure sensors have also been investigated that have their own unique challenges, such as erosion and sensor drift. As technology improves, an intelligent neuroprosthesis with the ability to sense significant bladder events and stimulate as needed will evolve

Central nervous system microstimulation: Towards selective micro-neuromodulation

Electrical stimulation technologies capable of modulating neural activity are well established for neuroscientific research and neurotherapeutics. Recent micro-neuromodulation experimental results continue to explain neural processing complexity and suggest the potential for assistive technologies capable of restoring or repairing of basic function. Nonetheless, performance is dependent upon the specificity of the stimulation. Increasingly specific stimulation is hypothesized to be achieved by progressively smaller interfaces. Miniaturization is a current focus of neural implants due to improvements in mitigation of the body's foreign body response. It is likely that these exciting technologies will offer the promise to provide large-scale micro-neuromodulation in the future. Here, we highlight recent successes of assistive technologies through bidirectional neuroprostheses currently being used to repair or restore basic brain functionality. Furthermore, we introduce recent neuromodulation technologies that might improve the effectiveness of these neuroprosthetic interfaces by increasing their chronic stability and microstimulation specificity. We suggest a vision where the natural progression of innovative technologies and scientific knowledge enables the ability to selectively micro-neuromodulate every neuron in the brain

In vitro biocompatibility evaluation of functional electrically stimulating microelectrodes on primary glia

Neural interfacing devices interact with the central nervous system to alleviate functional deficits arising from disease or injury. This often entails the use of invasive microelectrode implants that elicit inflammatory responses from glial cells and leads to loss of device function. Previous work focused on improving implant biocompatibility by modifying electrode composition; here, we investigated the direct effects of electrical stimulation on glial cells at the electrode interface. A high-throughput in vitro system that assesses primary glial cell response to biphasic stimulation waveforms at 0 mA, 0.15 mA, and 1.5 mA was developed and optimized. Primary mixed glial cell cultures were generated from heterozygous CX3CR-1+/EGFP mice, electrically stimulated for 4 h/day over 3 days using 75 μm platinum-iridium microelectrodes, and biomarker immunofluorescence was measured. Electrodes were then imaged on a scanning electron microscope to assess sustained electrode damage. Fluorescence and electron microscopy analyses suggest varying degrees of localized responses for each biomarker assayed (Hoescht, EGFP, GFAP, and IL-1β), a result that expands on comparable in vivo models. This system allows for the comparison of a breadth of electrical stimulation parameters, and opens another avenue through which neural interfacing device developers can improve biocompatibility and longevity of electrodes in tissue

A charge-metering method for voltage-mode neural stimulation

AbstractElectrical neural stimulation is the technique used to modulate neural activity by inducing an instantaneous charge imbalance. This is typically achieved by injecting a constant current and controlling the stimulation time. However, constant voltage stimulation is found to be more energy-efficient although it is challenging to control the amount of charge delivered. This paper presents a novel, fully integrated circuit for facilitating charge-metering in constant voltage stimulation. It utilises two complementary stimulation paths. Each path includes a small capacitor, a comparator and a counter. They form a mixed-signal integrator that integrates the stimulation current onto the capacitor while monitoring its voltage against a threshold using the comparator. The pulses from the comparator are used to increment the counter and reset the capacitor. Therefore, by knowing the value of the capacitor, threshold voltage and output of the counter, the quantity of charge delivered can be calculated. The system has been fabricated in 0.18μm CMOS technology, occupying a total active area of 339μm×110μm. Experimental results were taken using: (1) a resistor–capacitor EEI model and (2) platinum electrodes with ringer solution. The viability of this method in recruiting action potentials has been demonstrated using a cuff electrode with Xenopus sciatic nerve. For a 10nC target charge delivery, the results of (2) show a charge delivery error of 3.4% and a typical residual charge of 77.19pC without passive charge recycling. The total power consumption is 45μW. The performance is comparable with other publications. Therefore, the proposed stimulation method can be used as a new approach for neural stimulation

New stimulation device to drive multiple transverse intrafascicular electrodes and achieve highly selective and rich neural responses

Peripheral Nerve Stimulation (PNS) is a promising approach in functional restoration following neural impairments. Although it proves to be advantageous in the number of implantation sites provided compared with intramuscular or epimysial stimulation and the fact that it does not require daily placement, as is the case with surface electrodes, the further advancement of PNS paradigms is hampered by the limitation of spatial selectivity due to the current spread and variations of nerve physiology. New electrode designs such as the Transverse Intrafascicular Multichannel Electrode (TIME) were proposed to resolve this issue, but their use was limited by a lack of innovative multichannel stimulation devices. In this study, we introduce a new portable multichannel stimulator-called STIMEP-and implement different stimulation protocols in rats to test its versatility and unveil the potential of its combined use with TIME electrodes in rehabilitation protocols. We developed and tested various stimulation paradigms in a single fascicle and thereafter implanted two TIMEs. We also tested its stimulation using two different waveforms. The results highlighted the versatility of this new stimulation device and advocated for the parameterizing of a hyperpolarizing phase before depolarization as well as the use of small pulse widths when stimulating with multiple electrodes