Charge-balanced Current Pulses Research Articles

In situ polymerization of conducting polymers around living neural cells: Cellular effect study

Conducting polymer has been directly polymerized around living neural cells or in the cortex with the aim of creating an intimate contact between implantable electrical devices and electrogenetic cells. The long term cellular effect after conductive polymer coating, a critical issue for practical applications, has not been reported. In this study, poly(3,4-ethylenedioxythiophene) PEDOT was directly polymerized around the living primary neural and PC12 cells under varying current densities, potentials and charge-balanced current pulses. The cell morphology, nuclei evolution, and cell viability post PEDOT polymerization were studied at different time points. The aim of this study was to investigate the immediate and long-term cellular response towards in-situ polymerization of conductive polymers and to provide experimental information on the feasibility of this technique in practical applications.

Platinum dissolution and tissue response following long-term electrical stimulation at high charge densities

Objective. Established guidelines for safe levels of electrical stimulation for neural prostheses are based on a limited range of the stimulus parameters used clinically. Recent studies have reported particulate platinum (Pt) associated with long-term clinical use of these devices, highlighting the need for more carefully defined safety limits. We previously reported no adverse effects of Pt corrosion products in the cochleae of guinea pigs following 4 weeks of electrical stimulation using charge densities far greater than the published safe limits for cochlear implants. The present study examines the histopathological effects of Pt within the cochlea following continuous stimulation at a charge density well above the defined safe limits for periods up to 6 months. Approach. Six cats were bilaterally implanted with Pt electrode arrays and unilaterally stimulated using charge balanced current pulses at a charge density of 267 μC cm−2 phase−1 using a tripolar electrode configuration. Electrochemical measurements were made throughout the implant duration and evoked potentials recorded at the outset and on completion of the stimulation program. Cochleae were examined histologically for particulate Pt, tissue response, and auditory nerve survival; electrodes were examined for surface corrosion; and cochlea, brain, kidney, and liver tissue analysed for trace levels of Pt. Main results. Chronic stimulation resulted in both a significant increase in tissue response and particulate Pt within the tissue capsule surrounding the electrode array compared with implanted, unstimulated control cochleae. Importantly, there was no stimulus-induced loss of auditory neurons (ANs) or increase in evoked potential thresholds. Stimulated electrodes were significantly more corroded compared with unstimulated electrodes. Trace analysis revealed Pt in both stimulated and control cochleae although significantly greater levels were detected within stimulated cochleae. There was no evidence of Pt in brain or liver; however, trace levels of Pt were recorded in the kidneys of two animals. Finally, increased charge storage capacity and charge injection limit reflected the more extensive electrode corrosion associated with stimulated electrodes. Significance. Long-term electrical stimulation of Pt electrodes at a charge density well above existing safety limits and nearly an order of magnitude higher than levels used clinically, does not adversely affect the AN population or reduce neural function, despite a stimulus-induced tissue response and the accumulation of Pt corrosion product. The mechanism resulting in Pt within the unstimulated cochlea is unclear, while the level of Pt observed systemically following stimulation at these very high charge densities does not appear to be of clinical significance.

Chronic intracochlear electrical stimulation at high charge densities results in platinum dissolution but not neural loss or functional changes in vivo

Objective. Although there are useful guidelines defining the boundary between damaging and non-damaging electrical stimulation they were derived from acute studies using large surface area electrodes in direct contact with cortical neurons. These parameters are a small subset of the parameters used by neural stimulators. More recently, histological examination of cochleae from patients that were long-term cochlear implant users have shown evidence of particulate platinum (Pt). The pathophysiological effect of Pt within the cochlea is unknown. We examined the response of the cochlea to stimulus levels beyond those regarded as safe, and to evaluate the pathophysiological response of the cochlea following chronic stimulation at charge densities designed to induce Pt corrosion in vivo. Approach. 19 guinea pigs were systemically deafened and implanted with a cochlear electrode array containing eight Pt electrodes of 0.05, 0.075 or 0.2 mm2 area. Animals were electrically stimulated continuously for 28 d using charge balanced current pulses at charge densities of 400, 267 or 100 µC/cm2/phase. Electrically-evoked auditory brainstem responses (EABRs) were recorded to monitor neural function. On completion of stimulation electrodes were examined using scanning electron microscopy (SEM) and cochleae examined histology. Finally, analysis of Pt was measured using energy dispersive x-ray spectroscopy (EDS) and inductively coupled plasma mass spectrometry (ICP-MS). Main results. Compared with unstimulated control electrodes and electrodes stimulated at 100 µC/cm2/phase, stimulation at 267 or 400 µC/cm2/phase resulted in significant Pt corrosion. Cochleae stimulated at these high charge densities contained particulate Pt. The extent of the foreign body response depended on the level of stimulation; cochleae stimulated at 267 or 400 µC/cm2/phase exhibited an extensive tissue response that included a focal region of necrosis close to the electrode. Despite chronic stimulation at high charge densities there was no loss of auditory neurons (ANs) in stimulated cochleae compared with their contralateral controls. Indeed, we report a statistically significant increase in AN density proximal to electrodes stimulated at 267 or 400 µC/cm2/phase. Finally, there was no evidence of a reduction in AN function associated with chronic stimulation at 100, 267 or 400 µC/cm2/phase as evidenced by stable EABR thresholds over the stimulation program. Significance. Chronic electrical stimulation of Pt electrodes at 267 or 400 µC/cm2/phase evoked a vigorous tissue response and produced Pt corrosion products that were located close to the electrode. Despite these changes at the electrode/tissue interface there was no evidence of neural loss or a reduction in neural function.

A sensory feedback system for prosthetic hand based on evoked tactile sensation.

The lack of reliable sensory feedback has been one of the barriers in prosthetic hand development. Restoring sensory function from prosthetic hand to amputee remains a great challenge to neural engineering. In this paper, we present the development of a sensory feedback system based on the phenomenon of evoked tactile sensation (ETS) at the stump skin of residual limb induced by transcutaneous electrical nerve stimulation (TENS). The system could map a dynamic pattern of stimuli to an electrode placed on the corresponding projected finger areas on the stump skin. A pressure transducer placed at the tip of prosthetic fingers was used to sense contact pressure, and a high performance DSP processor sampled pressure signals, and calculated the amplitude of feedback stimulation in real-time. Biphasic and charge-balanced current pulses with amplitude modulation generated by a multi-channel laboratory stimulator were delivered to activate sensory nerves beneath the skin. We tested this sensory feedback system in amputee subjects. Preliminary results showed that the subjects could perceive different levels of pressure at the tip of prosthetic finger through evoked tactile sensation (ETS) with distinct grades and modalities. We demonstrated the feasibility to restore the perceptual sensation from prosthetic fingers to amputee based on the phenomenon of evoked tactile sensation (ETS) with TENS.

The PennBMBI: Design of a General Purpose Wireless Brain-Machine-Brain Interface System.

In this paper, a general purpose wireless Brain-Machine-Brain Interface (BMBI) system is presented. The system integrates four battery-powered wireless devices for the implementation of a closed-loop sensorimotor neural interface, including a neural signal analyzer, a neural stimulator, a body-area sensor node and a graphic user interface implemented on the PC end. The neural signal analyzer features a four channel analog front-end with configurable bandpass filter, gain stage, digitization resolution, and sampling rate. The target frequency band is configurable from EEG to single unit activity. A noise floor of 4.69 μVrms is achieved over a bandwidth from 0.05 Hz to 6 kHz. Digital filtering, neural feature extraction, spike detection, sensing-stimulating modulation, and compressed sensing measurement are realized in a central processing unit integrated in the analyzer. A flash memory card is also integrated in the analyzer. A 2-channel neural stimulator with a compliance voltage up to ± 12 V is included. The stimulator is capable of delivering unipolar or bipolar, charge-balanced current pulses with programmable pulse shape, amplitude, width, pulse train frequency and latency. A multi-functional sensor node, including an accelerometer, a temperature sensor, a flexiforce sensor and a general sensor extension port has been designed. A computer interface is designed to monitor, control and configure all aforementioned devices via a wireless link, according to a custom designed communication protocol. Wireless closed-loop operation between the sensory devices, neural stimulator, and neural signal analyzer can be configured. The proposed system was designed to link two sites in the brain, bridging the brain and external hardware, as well as creating new sensory and motor pathways for clinical practice. Bench test and in vivo experiments are performed to verify the functions and performances of the system.

Response properties of electrically evoked potential elicited by multi-channel penetrative optic nerve stimulation in rabbits

Visual prosthesis is a potential way to restore partial vision for the patients with degenerative retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Optic nerve stimulation with penetrating microelectrode array has been suggested as a possible method for visual prosthesis. The purpose of this study was to investigate the feasibility and basic response properties of cortical responses elicited by optic nerve stimulation with penetrating electrodes in rabbits. In this study, three triangularly or linearly configured platinum-iridium wire electrodes were inserted into the optic nerves of rabbits for electrical stimulation. The charge-balanced current pulses with amplitudes ranging from 10 to 100 microA at 0.5 ms pulse duration were used as the electrical stimuli. The electrically evoked potentials (EEPs) were recorded with a 16-channel silver-ball electrode array in the rabbit visual cortex. Our experimental results showed that the activities of visual cortex could be effectively evoked by the optic nerve stimulation with penetrating electrodes. The threshold of current and charge density to elicit EEPs under optic nerve stimulation at 0.5 ms pulse duration was 20.3 +/- 7.5 microA and 37.8 +/- 13.9 microC/cm(2), respectively. Current stimuli with cathode-first pulses elicited larger cortical responses than that with anode-first pulses. The amplitude of P1 and extent of EEPs increased as the stimulating current amplitude increased, while the latency of P1 decreased. The spatial distributions of multi-channel EEPs in visual cortex demonstrated distinctively different properties under stimulation with different orientations of the stimulating electrodes.

Deafness alters auditory nerve fibre responses to cochlear implant stimulation

Here we characterized the relationship between duration of sensorineural hearing loss and the response of the auditory nerve to electrical stimulus rate. Electrophysiological recordings were made from undeafened guinea pigs and those ototoxically deafened for either 5 weeks or 6 months. Auditory neuron survival decreased significantly with the duration of deafness. Extracellular recordings were made from auditory nerve fibres responding to biphasic, charge-balanced current pulses delivered at rates of 20 and 200 pulses/s via a monopolar scala tympani stimulating electrode. The response to 20 pulses/s electrical stimulation of the deafened cochlea exhibited a decrease in spike latency, unaltered temporal jitter and unaltered dynamic range (of nerve firing rate against stimulus current), and a reduction in threshold after 6 months of deafness. The response to a 200-pulse/s stimulus was similar except that the dynamic range was greater than with 20 pulses/s and was also greater in deafened animals than in undeafened animals. Deafness and pulse rate are related; in deaf animals spike recovery appears to be complete between successive stimulus pulses at a low rate (20 pulses/s), but incomplete between pulses at a moderate pulse rate (200 pulses/s). These results suggest that changes in the function of individual auditory nerve fibres after deafness may affect clinical responses during high-rate stimulation such as that used in contemporary speech processing strategies, but not during lower rate stimulation such as that used to record evoked potentials.

Electrical Stimulation of Mammalian Retinal Ganglion Cells With Multielectrode Arrays

Existing epiretinal implants for the blind are designed to electrically stimulate large groups of surviving retinal neurons using a small number of electrodes with diameters of several hundred micrometers. To increase the spatial resolution of artificial sight, electrodes much smaller than those currently in use are desirable. In this study, we stimulated and recorded ganglion cells in isolated pieces of rat, guinea pig, and monkey retina. We used microfabricated hexagonal arrays of 61 platinum disk electrodes with diameters between 6 and 25 microm, spaced 60 microm apart. Charge-balanced current pulses evoked one or two spikes at latencies as short as 0.2 ms, and typically only one or a few recorded ganglion cells were stimulated. Application of several synaptic blockers did not abolish the evoked responses, implying direct activation of ganglion cells. Threshold charge densities were typically <0.1 mC/cm2 for a pulse duration of 100 micros, corresponding to charge thresholds of <100 pC. Stimulation remained effective after several hours and at high frequencies. To show that closely spaced electrodes can elicit independent ganglion cell responses, we used the multielectrode array to stimulate several nearby ganglion cells simultaneously. From these data, we conclude that electrical stimulation of mammalian retina with small-diameter electrode arrays is achievable and can provide high temporal and spatial precision at low charge densities. We review previous epiretinal stimulation studies and discuss our results in the context of 32 other publications, comparing threshold parameters and safety limits.

Comparison of Electrical Stimulation Thresholds in Normal and Retinal Degenerated Mouse Retina

To compare the threshold for electrically elicited action potentials of retinal ganglion cells in normal mouse retina and photoreceptor degenerated (rd) mouse retina. Microelectrode recordings were made from retinal ganglion cells of normal and rd mice. Mice with a genetically based retinal degeneration (rd mice) were grown to the age of 16 weeks, when light-evoked responses could no longer be recorded. A bare wire was placed in the vitreous to stimulate the retina with charge-balanced current pulses. The following pulse shapes were investigated: single, square biphasic pulse, single sine wave, and biphasic pulse trains. Normal mice had significantly lower stimulus thresholds than rd mice for all pulse shapes. In normal and rd mice, short pulses were more efficient with respect to total charge used, but required a higher current. In normal mice, sine wave stimulation was significantly more efficient than a biphasic pulse of the same duration. No difference was noted between sine wave and square wave stimulation in rd mice. Pulse trains offered little benefit over single pulses. The amount of electrical charge required to elicit an action potential is dependent on the condition of the retina and the shape of the stimulus pulse used to deliver the charge.

A Chip for an Implantable Neural Stimulator

This paper describes a chip for a multichannel neural stimulator for functional electrical stimulation (FES). The purpose of FES is to restore muscular control in disabled patients. The chip performs all the signal processing required in an implanted neural stimulator. The power and digital data transmission to the stimulator passes through a 5 MHz inductive link. From the signals transmitted to the stimulator, the chip is able to generate charge-balanced current pulses with a controllable length up to 256 μs and an amplitude up to 2 mA, for stimulation of nerve fibers. The quiescent current consumption of the chip is approx. 650 μA at supply voltages of 6–12 V, and its size is 3.9×3.5 mm^2. It has 4 output channels for use in a multipolar cuff electrode.

Comparison of Current Waveforms for the Electrical Stimulation of Residual Low Frequency Hearing

Many cochlear prostheses employ charge-balanced biphasic current pulses. These pulses have little energy at low frequencies resulting in limited stimulation of low frequency hearing by mechanical responses to the electrical stimulus. However, if electro-mechanical transduction within the cochlea is nonlinear, electrical stimulation with asymmetric, charge-balanced current pulses may result in a mechanical response with significantly more low frequency energy. We estimated the mechanical response at low frequencies to pulsatile electrical stimulation of the cochlea. The auditory nerve compound action potential evoked by low frequency tones was forward-masked by a train of symmetric or asymmetric current pulses. Masking by asymmetric current pulses was not significantly different from masking by symmetric pulses matched for pulse duration and charge. In conclusion, there appears to be no advantage to using asymmetric current pulses for the mechanical stimulation of residual low frequency hearing by electrical stimulation of the cochlea.

Charge Injection Properties of Thermally-Prepared Iridium Oxide Films

ABSTRACTMultilayered Ir oxide films were prepared on Ti and Pt:Ir electrodes by the thermal decomposition of successive layers of alcohol solutions of IrCl3. The charge capacity of the thermally-formed Ir oxide films (TIROF) and the reversibility of surface oxide-related reactions were evaluated in a physiological saline solution using potential sweep and current pulse techniques. The TIROF-coated electrodes had electrochemical properties similar to an Ir electrode coated with an anodically-formed oxide. The charge injection limits before gassing ranged from 5–10 mC/cm2 for TIROF-Ti and 1–3 mC/cm2 for TIROF-Pt:Ir with biphasic, charge-balanced current pulses of 0.2 ms duration. No Pt dissolution was detected during &gt;100 hr stimulation with TIROF-Pt:Ir electrodes. Small amounts of Ir dissolution were detected which might result from passive leaching of residual chloride complexes of Ir. The TIROF coatings remained firmly attached to the substrate metal during long term pulsing and abrasion tests. The properties of TIROF coatings, e.g., high charge capacity for reversible charge injection and good abrasion and corrosion resistance, are of great advantage for neural prosthesis applications.