Charge-balanced Biphasic Current Pulses Research Articles

NeuralTree: A 256-Channel 0.227-μJ/Class Versatile Neural Activity Classification and Closed-Loop Neuromodulation SoC.

Closed-loop neural interfaces with on-chip machine learning can detect and suppress disease symptoms in neurological disorders or restore lost functions in paralyzed patients. While high-density neural recording can provide rich neural activity information for accurate disease-state detection, existing systems have low channel counts and poor scalability, which could limit their therapeutic efficacy. This work presents a highly scalable and versatile closed-loop neural interface SoC that can overcome these limitations. A 256-channel time-division multiplexed (TDM) front-end with a two-step fast-settling mixed-signal DC servo loop (DSL) is proposed to record high-spatial-resolution neural activity and perform channel-selective brain-state inference. A tree-structured neural network (NeuralTree) classification processor extracts a rich set of neural biomarkers in a patient- and disease-specific manner. Trained with an energy-aware learning algorithm, the NeuralTree classifier detects the symptoms of underlying disorders (e.g., epilepsy and movement disorders) at an optimal energy-accuracy trade-off. A 16-channel high-voltage (HV) compliant neurostimulator closes the therapeutic loop by delivering charge-balanced biphasic current pulses to the brain. The proposed SoC was fabricated in 65nm CMOS and achieved a 0.227μJ/class energy efficiency in a compact area of 0.014mm2/channel. The SoC was extensively verified on human electroencephalography (EEG) and intracranial EEG (iEEG) epilepsy datasets, obtaining 95.6%/94% sensitivity and 96.8%/96.9% specificity, respectively. In-vivo neural recordings using soft μECoG arrays and multi-domain biomarker extraction were further performed on a rat model of epilepsy. In addition, for the first time in literature, on-chip classification of rest-state tremor in Parkinson's disease (PD) from human local field potentials (LFPs) was demonstrated.

In vivo feasibility of epiretinal stimulation using ultrananocrystalline diamond electrodes

Objective. Due to their increased proximity to retinal ganglion cells (RGCs), epiretinal visual prostheses present the opportunity for eliciting phosphenes with low thresholds through direct RGC activation. This study characterised the in vivo performance of a novel prototype monolithic epiretinal prosthesis, containing Nitrogen incorporated ultrananocrystalline (N-UNCD) diamond electrodes. Approach. A prototype implant containing up to twenty-five 120 × 120 µm N-UNCD electrodes was implanted into 16 anaesthetised cats and attached to the retina either using a single tack or via magnetic coupling with a suprachoroidally placed magnet. Multiunit responses to retinal stimulation using charge-balanced biphasic current pulses were recorded acutely in the visual cortex using a multichannel planar array. Several stimulus parameters were varied including; the stimulating electrode, stimulus polarity, phase duration, return configuration and the number of electrodes stimulated simultaneously. Main results. The rigid nature of the device and its form factor necessitated complex surgical procedures. Surgeries were considered successful in 10/16 animals and cortical responses to single electrode stimulation obtained in eight animals. Clinical imaging and histological outcomes showed severe retinal trauma caused by the device in situ in many instances. Cortical measures were found to significantly depend on the surgical outcomes of individual experiments, phase duration, return configuration and the number of electrodes stimulated simultaneously, but not stimulus polarity. Cortical thresholds were also found to increase over time within an experiment. Significance. The study successfully demonstrated that an epiretinal prosthesis containing diamond electrodes could produce cortical activity with high precision, albeit only in a small number of cases. Both surgical approaches were highly challenging in terms of reliable and consistent attachment to and stabilisation against the retina, and often resulted in severe retinal trauma. There are key challenges (device form factor and attachment technique) to be resolved for such a device to progress towards clinical application, as current surgical techniques are unable to address these issues.

A bidirectional neural interface SoC with an integrated spike recorder, microstimulator, and low-power processor for real-time stimulus artifact rejection

This paper presents a neural interface system-on-chip (SoC) featuring combined spike recording, electrical microstimulation, and real-time stimulus artifact rejection (SAR) for bidirectional interfacing with the nervous system. The SoC integrates a spike-recording front-end with input noise voltage of 3.42 μVrms (0.5 Hz---50 kHz), microstimulating back-end for delivering charge-balanced monophasic or asymmetric biphasic current pulses of <100 μA with passive discharge, and μW-level digital signal processing (DSP) unit for real-time SAR based on template subtraction. The DSP unit initializes its embedded 16b, 4 K static random-access memory with the first recorded stimulus artifact to reduce the operation time in generating an accurate artifact template signal for subtraction. Fabricated in AMS 0.35 μm 2P/4M CMOS, the 3.1 × 3.1-mm2 SoC has been characterized in benchtop tests and neurobiological experiments with isolated buccal ganglia of an Aplysia californica (a marine mollusk). The SoC can successfully remove mV-range stimulus artifacts with duration up to ~115 ms from the contaminated neural data in real time and recover µV-range extracellular neural spikes that occur on the tail end of the artifacts. The average root-mean-square (rms) value of the pre-processed stimulus artifact is reduced by a factor of ~24---30 post-processing, with DSP unit power consumption of <25 µW from 1.5 V.

Enhanced regeneration of rabbit mandibular defects through a combined treatment of electrical stimulation and rhBMP-2 application

We evaluated the new bone regeneration of a rabbit mandibular defect using hBMSCs under electrical stimulation combined with rhBMP-2 in this study. An inner scaffold prepared by setting a collagen sponge with hBMSCs and hydrogel was placed into a polycaprolactone (PCL) outer box, and an electrical stimulation device was installed between the inner scaffold and the outer box. There were three experimental groups depending on electrical stimulation and application of rhBMP-2. The experimental group was divided into the following three groups. Group 1, in which rhBMP-2 (5μg/defect) was added to hydrogel and electrical stimulation was not applied; Group 2, in which rhBMP-2 (5μg/defect) was added as in Group 1 and electrical stimulation was applied; and Group 3, in which electrical stimulation was applied and rhBMP-2 (5 μg/defect) was injected directly into defect site. The delivered electrical stimulation was charge-balanced bi-phasic electric current pulses, and electrical stimulation was conducted for 7days. The stimulation parameters of the bi-phasic electrical current set at an amplitude of 20μA, a duration of 100μs and a frequency of 100Hz. Four weeks after surgery, new bone formation in each group was evaluated using radiography, histology, and micro-computed tomography(μCT). Groups 2 and 3 exhibited a significant increase in new bone formation compared to Group 1, while Group 3 showed the highest level of new bone regeneration. In a comparison between two groups, Group 2 showed a higher bone volume (BV) by 260% (p<0.01) compared with Group 1, and Group 3 showed a higher BV by 442% (p<0.01) compared with Group 1. The trend of the bone surface density (ratio of new bone to the real defect volume, BS/TV), trabecular number, and connectivity was identical to that of the BV. The total bone mineral density (BMD) of Groups 2 and 3 showed values higher by the ratios of 103% (p<0.01) and 107.5% (p<0.01) compared with Group 1, respectively. Part BMD for Groups 2 and 3 showed higher values by the ratios of 104.9% (p<0.01) and 122.4% (p<0.01) compared with Group 1, respectively. These results suggest that the combined treatment of electrical stimulation, hBMSCs, a collagen sponge, hydrogel, and rhBMP-2 was effective for bone regeneration of large-size mandibular defects. The application of rhBMP-2 with an injection following electrical stimulation demonstrated better efficiency as regards bone regeneration.

F021 Myographic recording of the electrically elicited stapedius reflex

Increasing numbers of cochlear implant subjects have some level of residual hearing at the time of implantation. The present study examined whether (i) hair cells that have survived one pathological insult (aminoglycoside deafening), can survive and function following long-term cochlear implantation and electrical stimulation (ES); and (ii) chronic ES in these cochleae results in greater trophic support of spiral ganglion neurons (SGNs) compared with cochleae devoid of hair cells. Eight cats, with either partial (n = 4) or severe (n = 4) sensorineural hearing loss, were bilaterally implanted with scala tympani electrode arrays 2 months after deafening, and received unilateral ES using charge balanced biphasic current pulses for periods of up to 235 days. Frequency-specific compound action potentials and click-evoked auditory brainstem responses (ABRs) were recorded periodically to monitor the residual acoustic hearing. Electrically evoked ABRs (EABRs) were recorded to confirm the stimulus levels were 3–6 dB above the EABR threshold. On completion of the ES program the cochleae were examined histologically. Partially deafened animals showed no significant increase in acoustic thresholds over the implantation period. Moreover, chronic ES of an electrode array located in the base of the cochlea did not adversely affect hair cells in the middle or apical turns. There was evidence of a small but statistically significant rescue of SGNs in the middle and apical turns of stimulated cochleae in animals with partial hearing. Chronic ES did not, however, prevent a reduction in SGN density for the severely deaf cohort, although SGNs adjacent to the stimulating electrodes did exhibit a significant increase in soma area (p < 0.01). In sum, chronic ES in partial hearing animals does not adversely affect functioning residual hair cells apical to the electrode array. Moreover, while there is an increase in the soma area of SGNs close to the stimulating electrodes in severely deaf cochleae, this trophic effect does not result in increased SGN survival.

A fully implantable stimulator for use in small laboratory animals

This paper describes a low cost, fully implantable, single channel stimulator that can be manufactured in a research laboratory. The stimulator generates charge-balanced biphasic current pulses which are delivered to a bipolar electrode array for chronic stimulation of neural tissue in free-running laboratory animals such as rats and mice. The system is magnetically coupled and contains no batteries or external leadwires. The subject is placed in a chamber surrounded by three orthogonal coils of wire which are driven to generate a magnetic field. Currents are induced in wire coils in the implanted stimulator then regulated to produce biphasic current pulses with fixed amplitude of up to 500 μA. Phase duration is adjustable from 25 to 250 μs per phase. Charge balance is maintained by capacitive coupling and shorting of the electrodes between pulses. Stimulus rate can be continuously varied, and the temporal precision of the stimulus means that the stimulator can be used in behavioural experiments or for generating electrically evoked potentials. We describe the application of this stimulator for chronic electrical stimulation of the auditory nerve (i.e. a cochlear implant); however it will have application in other areas of neuroscience requiring controlled safe electrical stimulation of neural tissue over extended periods. Circuit diagrams and manufacturing details are provided as supplementary data.

Does cochlear implantation and electrical stimulation affect residual hair cells and spiral ganglion neurons?

Increasing numbers of cochlear implant subjects have some level of residual hearing at the time of implantation. The present study examined whether (i) hair cells that have survived one pathological insult (aminoglycoside deafening), can survive and function following long-term cochlear implantation and electrical stimulation (ES); and (ii) chronic ES in these cochleae results in greater trophic support of spiral ganglion neurons (SGNs) compared with cochleae devoid of hair cells. Eight cats, with either partial ( n = 4) or severe ( n = 4) sensorineural hearing loss, were bilaterally implanted with scala tympani electrode arrays 2 months after deafening, and received unilateral ES using charge balanced biphasic current pulses for periods of up to 235 days. Frequency-specific compound action potentials and click-evoked auditory brainstem responses (ABRs) were recorded periodically to monitor the residual acoustic hearing. Electrically evoked ABRs (EABRs) were recorded to confirm the stimulus levels were 3–6 dB above the EABR threshold. On completion of the ES program the cochleae were examined histologically. Partially deafened animals showed no significant increase in acoustic thresholds over the implantation period. Moreover, chronic ES of an electrode array located in the base of the cochlea did not adversely affect hair cells in the middle or apical turns. There was evidence of a small but statistically significant rescue of SGNs in the middle and apical turns of stimulated cochleae in animals with partial hearing. Chronic ES did not, however, prevent a reduction in SGN density for the severely deaf cohort, although SGNs adjacent to the stimulating electrodes did exhibit a significant increase in soma area ( p < 0.01). In sum, chronic ES in partial hearing animals does not adversely affect functioning residual hair cells apical to the electrode array. Moreover, while there is an increase in the soma area of SGNs close to the stimulating electrodes in severely deaf cochleae, this trophic effect does not result in increased SGN survival.

Organization in the descending tracts of the dorsolateral funiculus in the cat

Organization of the fibers in the descending tracts of the dorsolateral funiculus of the cervical spinal cord was investigated in cats. The spinal cord was penetrated with microelectrodes at 400 μm intervals in the medio-lateral direction at the c5/c6 and c6/c7 segmental borders. Silicon substrate microelectrodes with a linear arrangement of activated iridium contacts were used. The stimulus consisted of a 20 ms train of charge balanced biphasic current pulses at 330 Hz. The evoked activities from selected forelimb muscles were acquired into computer. Only the data points with an activation threshold of less than 35 μA were considered in the analysis. Muscle contractions were mostly in the form of short twitches. In both spinal segments, an area of high threshold was found in the middle of the dorsolateral funiculus. Majority of the muscles studied had a dorsal or ventral concentration of activation points. The distal muscles were mostly activated in the ventro-lateral aspect of the funiculus, while the elbow muscle maps spread to both dorsal and ventral sides. These results show a functional organization in both cervical segments studied, with overlapping regions between the areas dedicated for each forelimb muscle.

Effect of interphase gap and pulse duration on electrically evoked potentials is correlated with auditory nerve survival

We investigated the effect of pulse duration (PD) and interphase-gap (IPG) on the electrically-evoked auditory brain stem response (EABR) and viiith nerve compound action potential (ECAP) of deafened guinea pigs in order to test the hypothesis that the extent of change in these neural responses is affected by the histological status of the auditory nerve. Fifteen guinea pigs were deafened by co-administration of kanamycin and furosemide. Animals were acutely implanted with an 8-band electrode array at 1, 4 or 12 weeks following deafening. EABR and ECAP input/output functions were recorded in response to charge balanced biphasic current pulses. We determined the change in current required to equalize; (i) the EABR amplitude when the duration of the current pulse was doubled (104–208 μs/phase); and (ii) the EABR and ECAP amplitudes when the IPG was increased from 8 to 58 μs using a 104 μs/phase current pulse. Following the completion of each experiment the cochleae were examined quantitatively for spiral ganglion neuron survival. As expected, the current level required to evoke an EABR with equal amplitude was lower when the animal was stimulated with current pulses of 208 compared with 104 μs/phase. Moreover, the current level required to evoke EABR/ECAPs with equal amplitude was lower when current pulses had an IPG of 58 versus 8 μs. Importantly, there was a reduction in the magnitude of this effect with greater neural loss; the reduced efficacy of changing both PD and IPG on these electrically-evoked potentials was statistically correlated with neural survival. These results may provide a tool for investigating the contribution of auditory nerve survival to clinical performance among cochlear implant subjects.

Speech recognition with a cochlear implant using triphasic charge-balanced pulses

ObjectiveTypically, symmetrical charge-balanced biphasic current pulses are used in cochlear implants to ensure biological safety. Theoretically, monophasic pulses are more effective, but potentially noxious, stimuli. In this study we charge-balanced such monophasic pulses during selected non-stimulated intervals, effectively leading to triphasic pulses with a 4:1 amplitude ratio between the cathodic and anodic phases. Apart from ensuring safety, this is also expected to reduce power consumption and channel interaction. Material and MethodsSeven experienced Clarion CII cochlear implant users with a multichannel (12–16 channels) monopolar continuous interleaved sampling (CIS) strategy participated in the study. Three different CIS strategies were fitted using the Clarion Research Interface (CRI-2). The reference was an implementation of each subject's own CIS program. The two strategies tested used triphasic pulses on the same channels, one with half-wave rectification (TP-HWR) and one without rectification (TP-NoR) at the input. Directly after fitting (i.e. without any training), speech perception (phoneme score on consonant–vowel–consonant words) was measured in silence (sound-only) and in speech-shaped background noise with signal:noise ratios (SNRs) of +5 and 0 dB. ResultsSpeech perception with the reference via the CRI-2 was equal to that of the free-field condition with the subjects’ own speech processor. With the TP-NoR strategy, speech perception improved significantly (from 89% to 93%) in silence and in the 0-dB SNR condition (from 43% to 49%). With a SNR of +5 dB, performance was stable at ≈66%. With the TP-HWR strategy, performance increased significantly in the 0- and +5-dB SNR conditions, to 55% and 74%, respectively. Power consumption was reduced in both strategies, to 30% and 36% for TP-HWR and TP-NoR, respectively. Conclusion The new triphasic strategies are most promising, with respect to both their improved speech perception and reduced power requirements. The optimal parameters will have to be identified following long-term use.

Chronic electrical stimulation of the auditory nerve using high surface area (HiQ) platinum electrodes

High surface area cochlear implant electrodes with much smaller geometric surface areas than current designs might be used in the future to increase the number of stimulating electrodes along the carrier. Potential problems with an increase in charge density for a common stimulus resulting from decreasing the geometric surface area would be reduced by the enlarged real surface area of such electrodes. Electrochemically modified (HiQ) platinum (Pt) electrodes, with a real surface area ∼75 times greater than the current standard Pt electrodes of the same geometric size, had shown in vitro a low polarization ( Z pol) and electrode impedance ( Z e), as well as a low residual direct current (DC). In this study we examined the chronic performance of HiQ electrodes in cats, which were bilaterally implanted with a two-channel HiQ or standard Pt scala tympani electrode array and unilaterally stimulated for periods of up to 2390 h. Stimuli consisted of 50 μs/phase charge-balanced biphasic current pulses presented at 2000 pulses/s/channel with a 50% duty cycle. Electrode impedance ( Z e), access resistance ( R a) and polarization impedance ( Z pol) were calculated from current and voltage measurements obtained periodically throughout the implantation period. Immediately following implantation HiQ electrodes showed a significantly smaller Z pol, resulting in a reduced Z e ( P<0.0001) compared to standard electrodes, while there was no significant difference between R a of both electrode designs ( P=0.91). Subsequently, Z e generally increased mainly due to a rise in R a, which dominated Z e and obliterated the effect of a lower Z pol on Z e in HiQ electrodes. Peak R a levels correlated closely ( r=0.85) with the amount of intracochlear fibrous tissue found adjacent to the array. Following explantation of the array, voltage waveforms for both electrode designs recorded in saline were again very similar to those recorded immediately after implantation. Mean DC levels were consistently lower for HiQ electrodes compared with standard electrodes (22.45 nA vs 134.7 nA). Histopathological examination of corresponding cochlear sections comparing the stimulated test side with the unstimulated control side showed no significant difference ( P>0.05) for either animals implanted with HiQ electrodes ( n=6) or standard electrodes ( n=2). Nor were there any significant differences between the spiral ganglion cell density of the basal turn implanted with HiQ or standard electrodes for both the stimulated test ( P=0.31) and the unstimulated control side ( P=0.84). Although these findings are based on a small group of animals implanted with standard electrodes ( n=2), and those negative statistical results could potentially be due to the small sample size, similar spiral ganglion cell survival was found in a previous study of a larger group of animals using standard electrodes stimulated with the same stimulus paradigm as in the present study [Xu et al. (1997) Hear. Res. 105, 1–29]. Our data indicate that while some initial advantages of HiQ electrodes are lost during chronic implantation due to intracochlear fibrous tissue growth, low DC levels and the high surface area appear to be maintained, suggesting that HiQ electrodes may have important clinical applications.

Does electrical stimulation of deaf cochleae prevent spiral ganglion degeneration?

Thirty-six drug deafened guinea pigs were studied to determine how electrical stimulation of the cochlea affects spiral ganglion cell (SGC) survival. Animals were divided into two groups, extracochlear and intracochlear stimulation, and each group was further divided into four stimulus subgroups: no stimulation (implanted controls), the inferior colliculus electrically evoked potential (ICEEP) threshold−2 dB, ICEEP threshold+2 dB, and ICEEP threshold+6 dB. Stimuli consisted of 200 μs/phase charge balanced biphasic current pulses presented at 100 pulses per second using monopolar stimulation. Animals were stimulated 5 h/day, 5 days per week, for 8 weeks. The animals were then perfused and the cochleae serially sectioned at 4 μm saving every 8th section. We counted the number of intact SGCs, those containing a nucleus with chromatin, in each 20% segment of the cochlea and also measured SGC densities (number of neurons per mm 2 of Rosenthal’s canal). The number of surviving spiral ganglion neurons was not significantly different ( P>0.05) between the implanted and the unimplanted ears in any of the experimental groups. However, the spiral ganglion neuron densities were significantly elevated in the electrically stimulated ears ( P<0.001) but not in the implanted but not chronically stimulated ears ( P>0.05). We measured the volume of Rosenthal’s canal in one subgroup (ICEEP threshold+2 dB) and found a decrease in this volume in the stimulated ear compared to the unstimulated ear ( P<0.01). These findings support the hypothesis that chronic monopolar electrical intracochlear or extracochlear stimulation is not a neurotrophic factor, increasing spiral ganglion neuron survival, but instead causes a narrowing of Rosenthal’s canal that accounts for the increased spiral ganglion neuronal densities seen in the stimulated cochleae.

Reduction in excitability of the auditory nerve following acute electrical stimulation at high stimulus rates: III. Capacitive versus non-capacitive coupling of the stimulating electrodes

Safe electrical stimulation of neural tissue is typically achieved using charge-balanced biphasic current pulses, which are designed to minimize the generation of direct current (DC) and the production of harmful electrochemical products. However, due to the kinetics of the charge injection process, neural stimulators must also use capacitive coupling or electrode shorting techniques, to ensure DC levels are minimal. Previous studies have reported a reduction in excitability of the auditory nerve following acute simulation at high rates and intensities. Elevated levels of DC were reported in these studies despite using charge-balanced biphasic pulses and electrode shorting. The present study was designed to investigate the extent to which DC contributed to these stimulus induced reductions in auditory nerve excitability. Adult guinea pigs were bilaterally implanted and unilaterally stimulated for two hours using charge-balanced biphasic current pulses and stimulus rates of 200, 400 or 1000 pulses/s (pps) at a stimulus intensity well above clinical levels (0.34 μC/phase). DC levels were controlled using either electrode shorting, or electrode shorting with capacitive coupling. Electrically evoked auditory brainstem responses (EABRs) were recorded before and periodically following the acute stimulation. It was found that the extent of reduction in the EABR amplitude was a function of stimulus rate. While there was little change in the EABR following stimulation at 200 pps, significant post-stimulus reductions in the EABR amplitude were observed at stimulus rates of 400 and 1000 pps during the three hour post-stimulus monitoring period. Stimulation using capacitively coupled electrodes, which eliminated all DCs, showed reductions in EABR amplitudes similar to those observed following stimulation using electrode shorting alone. While there was no significant difference in the extent of reduction in EABR amplitudes for capacitive coupling versus electrode shorting at stimulus rates of 200 pps ( P>0.05) and 400 pps ( P>0.05), there was a significant difference at 1000 pps ( P<0.001). The present findings indicate that the major component of the stimulus induced reductions observed in auditory nerve excitability appear to be associated with stimulus induced neuronal activity, although elevated levels of DC (>2.5 μA) can also contribute to these changes. However, although statistically significant, the effects of DC are very small compared to the effects of high rate, high intensity stimulation per se.

Chronic Study on the Neuronal Excitability of the Cochlear Nuclei of the Cat Following Electrical Stimulation

To examine the safety of auditory brainstem prosthesis, the cat cochlear nuclei were implanted and stimulated chronically with bipolar surface electrodes using charge-balanced biphasic current pulses at rates of 250 pulses/s. The stimulation was continuous 16 h/day for up to 12 weeks. The electrically-evoked auditory brainstem response (EABR) was used to monitor neuronal excitability of the cochlear nuclei following the chronic electrical stimulation. The body weight, respiration, and body temperature of the cats were monitored throughout the experiment. The amplitudes and latencies of the EABR waves were measured fortnightly and compared before, during and after the electrical stimulation. The results showed that the respiration, body weight and body temperature of the cats remained within normal limits during the chronic stimulation. During the stimulation, no change was found in the EABR waveform, but a decreased threshold and wider dynamic range were observed after the stimulation. There was no significant change in the amplitudes and latencies of the EABR waves after stimulation. The present findings suggest that chronic bipolar electrical stimulation with surface electrodes at rates of 250 pulses/s is safe for neuronal excitability of the cochlear nuclei in the cat.

Reduction in excitability of the auditory nerve following electrical stimulation at high stimulus rates. II. Comparison of fixed amplitude with amplitude modulated stimuli

We have previously shown that acute electrical stimulation of the auditory nerve using charge-balanced biphasic current pulses presented continuously can lead to a prolonged decrement in auditory nerve excitability (Tykocinski et al., Hear. Res. 88 (1995), 124–142). This work also demonstrated a reduction in electrically evoked auditory brainstem response (EABR) amplitude decrement when using an otherwise equivalent pulse train with a 50% duty cycle. In the present study we have extended this work in order to compare the effects of electrical stimulation using both fixed amplitude electrical pulse trains and amplitude modulated (AM) pulse trains that more accurately model the dynamic stimulus paradigms used in cochlear implants. EABRs were recorded from guinea pigs following acute stimulation using AM trains of charge-balanced biphasic current pulses. The extent of stimulus-induced reductions in the EABR were compared with our previous results using either fixed amplitude continuous, or 50% duty cycle pulse trains operating at 0.34 μC/phase (2 mA, 170 μs/phase) at 400 or 1000 pulses/s (Tykocinski et al., Hear. Res. 88 (1995) 124–142). The AM pulse train, operating at the same rates, was based on a 1-s sequence of the most extensively activated electrode of a Nucleus Mini-22 cochlear implant using the SPEAK speech processing strategy exposed to 4-talker babble, and delivered the same total charge as the fixed amplitude 50% duty cycle pulse train. Two hours of continuous stimulation induced a significant, rate-dependent reduction in auditory nerve excitability, and showed only a slight post-stimulus recovery for monitoring periods of up to 6 hours. Following 2 or 4 h of stimulation using an otherwise equivalent pulse train with a 50% duty cycle or the AM pulse train, significantly less reduction in the EABR was observed, and recovery to pre-stimulus levels was generally rapid and complete. These differences in the extent of the recovery between the continuous waveform and both the 50% duty cycle and AM waveforms were statistically significant for both 400 and 1000 pulses/s stimuli. Consistent with our previous results, the stimulus changes observed using AM pulse trains were rate dependent, with higher rate stimuli evoking more extensive stimulus-induced changes. The present findings show that while stimulus-induced reductions in neural excitability are dependent on the extent of stimulus-induced neuronal activity, the use of an AM stimulus paradigm further reduces post-stimulus neural fatigue.

Estimating mechanical responses to pulsatile electrical stimulation of the cochlea

This study estimated the mechanical response of the cochlea to pulsatile electrical stimulation of the scala tympani of the cat. The auditory nerve compound action potential evoked by an acoustic probe was forward-masked by a train of charge-balanced biphasic current pulses. Masking as a function of probe frequency reflected the excitation pattern of the response to the masker and resembled the spectrum of the electrical stimulus. Both pulse rate and pulse width influenced the degree of masking. The vibration of a region of the basilar membrane was estimated by recording the local cochlear microphonic evoked by biphasic pulses. The amplitude of the cochlear microphonic was proportional to the amplitude of the spectral component of the electrical stimulus to which the local cochlear microphonic was tuned. These results are consistent with the generation of a mechanical response to the electrical stimulus.

Chronic electrical stimulation of the auditory nerve at high stimulus rates: a physiological and histopathological study

A major factor associated with recent improvements in the clinical performance of cochlear implant patients has been the development of speech-processing strategies based on high stimulation rates. While these processing strategies show clear clinical advantage, we know little of their long-term safety implications. The present study was designed to evaluate the physiological and histopathological effects of long-term intracochlear electrical stimulation using these high rates. Thirteen normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods of up to 2100 h using either two pairs of bipolar or three monopolar stimulating electrodes. Stimuli consisted of short duration (25–50 μs/phase) charge-balanced biphasic current pulses presented at 1000 pulses per second (pps) per channel for monopolar stimulation, and 2000 pps/channel for bipolar stimulation. The electrodes were shorted between current pulses to minimize any residual direct current, and the pulse trains were presented using a 50% duty cycle (500 ms on; 500 ms off) in order to simulate speech. Both acoustic (ABR) and electrical (EABR) auditory brainstem responses were recorded periodically during the chronic stimulation program. All cochleas showed an increase in the click-evoked ABR threshold following implant surgery; however, recovery to near-normal levels occurred in approximately half of the stimulated cochleas 1 month post-operatively. The use of frequency-specific stimuli indicated that the most extensive hearing loss generally occurred in the high-frequency basal region of the cochlea (12 and 24 kHz) adjacent to the stimulating electrode. However, thresholds at lower frequencies (2, 4 and 8 kHz), appeared at near-normal levels despite long-term electrode implantation and electrical stimulation. Our longitudinal EABR results showed a statistically significant increase in threshold in nearly 40% of the chronically stimulated electrodes evaluated; however, the gradient of the EABR input/output (I/O) function (evoked potential response amplitude versus stimulus current) generally remained quite stable throughout the chronic stimulation period. Histopathological examination of the cochleas showed no statistically significant difference in ganglion cell densities between cochleas using monopolar and bipolar electrode configurations (P = 0.67), and no evidence of cochlear damage caused by high-rate electrical stimulation when compared with control cochleas. Indeed, there was no statistically significant relationship between spiral ganglion cell density and electrical stimulation (P = 0.459), or between the extent of loss of inner (IHC, P = 0.86) or outer (OHC, P = 0.30) hair cells and electrical stimulation. Spiral ganglion cell loss was, however, influenced by the degree of inflammation (P = 0.016) and electrode insertion trauma. These histopathological findings were consistent with the physiological data. Finally, electrode impedance, measured at completion of the chronic stimulation program, showed close correlation with the degree of tissue response adjacent to the electrode array. These results indicated that chronic intracochlear electrical stimulation, using carefully controlled charge-balanced biphasic current pulses at stimulus rates of up to 2000 pps/channel, does not appear to adversely affect residual auditory nerve elements or the cochlea in general. This study provides an important basis for the safe application of improved speech-processing strategies based on high-rate electrical stimulation.

Acute Study on the Neuronal Excitablility of the Cochlear Nuclei of the Guinea Pig Following Electrical Stimulation

Liu X, McPhee G, Seldon HL, Clark GM Acute study on the neuronal excitability of the cochlear nuclei of the guinea pig following electrical stimulation. Acta Otolaryngol (Stockh) 1997; 117: 363-375.To help deaf patients who cannot benefit from the cochlear implant due to interruption of the auditory nerve, a central auditory prosthesis has been developed to directly stimulate the cochlear nucleus in the brainstem. The electrode array lies on the surface of the cochlear nucleus and is designed to stimulate at 250 pulses/sec. To examine the safety of this prosthesis, guinea pig cochlear nuclei were stimulated acutely with bipolar surface electrodes using charge-balanced biphasic current pulses at rates of 250, 500 or 1,000 pulses/s and charge intensities of 1.8, 2.8, 3.5 or 7.1 μC/phasecm-2. The electrically evoked auditory brainstem response (EABR) was used to monitor neuronal excitability of the cochlear nuclei following this acute electrical stimulation. Respiration rate and body temperature were also monitored during the experiment. The amplitudes and latencies of the EABR waves were measured and compared among the before, during and after stimulation periods. The results showed that respiration rate and body temperature remained within normal limits for the duration of the acute stimulation. During and after electrical stimulation, no change was found in the EABR waveform, dynamic ranges and threshold with up to 6 h direct continuous stimulation of the cochlear nucleus. There was no significant change in the amplitudes and latencies of the EABR waves after stimulation. However, a slight temporary reduction in the amplitude of the EABR waves was observed at 30-60 min during the course of acute stimulation using the highest charge density (7.1,μC/phasecm-2). This reduction showed a stronger correlation with the stimulus current, charge/phase and charge density than threshold. The present findings suggest that acute bipolar electrical stimulation with surface electrodes at rates up to 1,000 pulses/s and charge density up to 7.1 μC/phase cm-2 is safe for neuronal excitability of the cochlear nucleus in guinea pig.

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.

Reduction in excitability of the auditory nerve following electrical stimulation at high stimulus rates

While recent studies have suggested that electrical stimulation of the auditory nerve at high stimulus rates (e.g., 1000 pulses/s) may lead to an improved detection of the fine temporal components in speech among cochlear implant patients, neurophysiological studies have indicated that such stimulation could place metabolic stress on the auditory nerve, which may lead to neural degeneration. To examine this issue we recorded the electrically evoked auditory brainstem response (EABR) of guinea pigs following acute bipolar intracochlear electrical stimulation using charge-balanced biphasic current pulses at stimulus rates varying from 100 to 1000 pulses/s and stimulus intensities ranging from 0.16 to 1.0 μC/phase. Charge density was held constant (∼ 75 μC cm −2 geom/phase) in those experiments. To monitor the recovery in excitability of the auditory nerve following this acute stimulation, EABR thresholds, wave I and III amplitudes and their latencies were determined for periods of up to 12 h following the acute stimulation. Higher stimulus rates and, to a lesser extent, higher intensities led to greater decrements in the post-stimulus EABR amplitude and prolonged the recovery period. While continuous stimulation at 100 pulses/s induced no decrement in the EABR, stimulation at 200 and 400 pulses/s produced an increasingly significant post-stimulus reduction of the EABR amplitude, which showed only partial recovery during the monitoring period. No EABR response could be evoked immediately following stimulation at 1000 pulses/s, using a probe intensity 16–19 dB below the stimulus intensity. However, partial EABR recovery was observed for wave III following stimulation at the lowest stimulus intensity (0.16 μC/phase). These stimulus-induced reductions in the EABR amplitude were also reflected in increased thresholds and latencies. Providing stimulus rate and intensity were held constant, stimulation at different charge densities (37.7, 75.5 and 150.7 μC cm −2 geom/phase) had no influence on the post-stimulus EABR recovery. Significantly, the introduction of a 50% duty cycle into the stimulus pulse train resulted in a more rapid and complete post-stimulus recovery of the EABR compared to continuous stimulation. These data suggest that stimulus rate is a major contributor to the observed reduction in excitability of the electrically stimulated auditory nerve. This reduction may be a result of an activity-induced depletion of neural energy resources required to maintain homeostasis. The present findings have implications for the design of safe speech-processing strategies for use in multichannel cochlear implants.