Search tips
Search criteria

Results 1-25 (944027)

Clipboard (0)

Related Articles

1.  Unanesthetized Auditory Cortex Exhibits Multiple Codes for Gaps in Cochlear Implant Pulse Trains 
Cochlear implant listeners receive auditory stimulation through amplitude-modulated electric pulse trains. Auditory nerve studies in animals demonstrate qualitatively different patterns of firing elicited by low versus high pulse rates, suggesting that stimulus pulse rate might influence the transmission of temporal information through the auditory pathway. We tested in awake guinea pigs the temporal acuity of auditory cortical neurons for gaps in cochlear implant pulse trains. Consistent with results using anesthetized conditions, temporal acuity improved with increasing pulse rates. Unlike the anesthetized condition, however, cortical neurons responded in the awake state to multiple distinct features of the gap-containing pulse trains, with the dominant features varying with stimulus pulse rate. Responses to the onset of the trailing pulse train (Trail-ON) provided the most sensitive gap detection at 1,017 and 4,069 pulse-per-second (pps) rates, particularly for short (25 ms) leading pulse trains. In contrast, under conditions of 254 pps rate and long (200 ms) leading pulse trains, a sizeable fraction of units demonstrated greater temporal acuity in the form of robust responses to the offsets of the leading pulse train (Lead-OFF). Finally, TONIC responses exhibited decrements in firing rate during gaps, but were rarely the most sensitive feature. Unlike results from anesthetized conditions, temporal acuity of the most sensitive units was nearly as sharp for brief as for long leading bursts. The differences in stimulus coding across pulse rates likely originate from pulse rate-dependent variations in adaptation in the auditory nerve. Two marked differences from responses to acoustic stimulation were: first, Trail-ON responses to 4,069 pps trains encoded substantially shorter gaps than have been observed with acoustic stimuli; and second, the Lead-OFF gap coding seen for <15 ms gaps in 254 pps stimuli is not seen in responses to sounds. The current results may help to explain why moderate pulse rates around 1,000 pps are favored by many cochlear implant listeners.
PMCID: PMC3254721  PMID: 21969022
auditory prosthesis; pulse rate; guinea pig; temporal acuity; forward masking
2.  Unanesthetized Auditory Cortex Exhibits Multiple Codes for Gaps in Cochlear Implant Pulse Trains 
Cochlear implant listeners receive auditory stimulation through amplitude-modulated electric pulse trains. Auditory nerve studies in animals demonstrate qualitatively different patterns of firing elicited by low versus high pulse rates, suggesting that stimulus pulse rate might influence the transmission of temporal information through the auditory pathway. We tested in awake guinea pigs the temporal acuity of auditory cortical neurons for gaps in cochlear implant pulse trains. Consistent with results using anesthetized conditions, temporal acuity improved with increasing pulse rates. Unlike the anesthetized condition, however, cortical neurons responded in the awake state to multiple distinct features of the gap-containing pulse trains, with the dominant features varying with stimulus pulse rate. Responses to the onset of the trailing pulse train (Trail-ON) provided the most sensitive gap detection at 1,017 and 4,069 pulse-per-second (pps) rates, particularly for short (25 ms) leading pulse trains. In contrast, under conditions of 254 pps rate and long (200 ms) leading pulse trains, a sizeable fraction of units demonstrated greater temporal acuity in the form of robust responses to the offsets of the leading pulse train (Lead-OFF). Finally, TONIC responses exhibited decrements in firing rate during gaps, but were rarely the most sensitive feature. Unlike results from anesthetized conditions, temporal acuity of the most sensitive units was nearly as sharp for brief as for long leading bursts. The differences in stimulus coding across pulse rates likely originate from pulse rate-dependent variations in adaptation in the auditory nerve. Two marked differences from responses to acoustic stimulation were: first, Trail-ON responses to 4,069 pps trains encoded substantially shorter gaps than have been observed with acoustic stimuli; and second, the Lead-OFF gap coding seen for <15 ms gaps in 254 pps stimuli is not seen in responses to sounds. The current results may help to explain why moderate pulse rates around 1,000 pps are favored by many cochlear implant listeners.
PMCID: PMC3254721  PMID: 21969022
auditory prosthesis; pulse rate; guinea pig; temporal acuity; forward masking
3.  Auditory Prosthesis with a Penetrating Nerve Array 
Contemporary auditory prostheses (“cochlear implants”) employ arrays of stimulating electrodes implanted in the scala tympani of the cochlea. Such arrays have been implanted in some 100,000 profoundly or severely deaf people worldwide and arguably are the most successful of present-day neural prostheses. Nevertheless, most implant users show poor understanding of speech in noisy backgrounds, poor pitch recognition, and poor spatial hearing, even when using bilateral implants. Many of these limitations can be attributed to the remote location of stimulating electrodes relative to excitable cochlear neural elements. That is, a scala tympani electrode array lies within a bony compartment filled with electrically conductive fluid. Moreover, scala tympani arrays typically do not extend to the apical turn of the cochlea in which low frequencies are represented. In the present study, we have tested in an animal model an alternative to the conventional cochlear implant: a multielectrode array implanted directly into the auditory nerve. We monitored the specificity of stimulation of the auditory pathway by recording extracellular unit activity at 32 sites along the tonotopic axis of the inferior colliculus. The results demonstrate the activation of specific auditory nerve populations throughout essentially the entire frequency range that is represented by characteristic frequencies in the inferior colliculus. Compared to conventional scala tympani stimulation, thresholds for neural excitation are as much as 50-fold lower and interference between electrodes stimulated simultaneously is markedly reduced. The results suggest that if an intraneural stimulating array were incorporated into an auditory prosthesis system for humans, it could offer substantial improvement in hearing replacement compared to contemporary cochlear implants.
PMCID: PMC2538356  PMID: 17265124
auditory nerve; cat; cochlear implant; cochlear nerve; intraneural electrical stimulation; inferior colliculus
4.  Encoding and decoding amplitude-modulated cochlear implant stimuli—a point process analysis 
Cochlear implant speech processors stimulate the auditory nerve by delivering amplitude-modulated electrical pulse trains to intracochlear electrodes. Studying how auditory nerve cells encode modulation information is of fundamental importance, therefore, to understanding cochlear implant function and improving speech perception in cochlear implant users. In this paper, we analyze simulated responses of the auditory nerve to amplitude-modulated cochlear implant stimuli using a point process model. First, we quantify the information encoded in the spike trains by testing an ideal observer’s ability to detect amplitude modulation in a two-alternative forced-choice task. We vary the amount of information available to the observer to probe how spike timing and averaged firing rate encode modulation. Second, we construct a neural decoding method that predicts several qualitative trends observed in psychophysical tests of amplitude modulation detection in cochlear implant listeners. We find that modulation information is primarily available in the sequence of spike times. The performance of an ideal observer, however, is inconsistent with observed trends in psychophysical data. Using a neural decoding method that jitters spike times to degrade its temporal resolution and then computes a common measure of phase locking from spike trains of a heterogeneous population of model nerve cells, we predict the correct qualitative dependence of modulation detection thresholds on modulation frequency and stimulus level. The decoder does not predict the observed loss of modulation sensitivity at high carrier pulse rates, but this framework can be applied to future models that better represent auditory nerve responses to high carrier pulse rate stimuli. The supplemental material of this article contains the article’s data in an active, re-usable format.
PMCID: PMC2898280  PMID: 20177761
Point process model; Cochlear implant; Auditory nerve; Amplitude modulation; Neural coding
5.  Gradients and Modulation of K+ Channels Optimize Temporal Accuracy in Networks of Auditory Neurons 
PLoS Computational Biology  2012;8(3):e1002424.
Accurate timing of action potentials is required for neurons in auditory brainstem nuclei to encode the frequency and phase of incoming sound stimuli. Many such neurons express “high threshold” Kv3-family channels that are required for firing at high rates (>∼200 Hz). Kv3 channels are expressed in gradients along the medial-lateral tonotopic axis of the nuclei. Numerical simulations of auditory brainstem neurons were used to calculate the input-output relations of ensembles of 1–50 neurons, stimulated at rates between 100–1500 Hz. Individual neurons with different levels of potassium currents differ in their ability to follow specific rates of stimulation but all perform poorly when the stimulus rate is greater than the maximal firing rate of the neurons. The temporal accuracy of the combined synaptic output of an ensemble is, however, enhanced by the presence of gradients in Kv3 channel levels over that measured when neurons express uniform levels of channels. Surprisingly, at high rates of stimulation, temporal accuracy is also enhanced by the occurrence of random spontaneous activity, such as is normally observed in the absence of sound stimulation. For any pattern of stimulation, however, greatest accuracy is observed when, in the presence of spontaneous activity, the levels of potassium conductance in all of the neurons is adjusted to that found in the subset of neurons that respond better than their neighbors. This optimization of response by adjusting the K+ conductance occurs for stimulus patterns containing either single and or multiple frequencies in the phase-locking range. The findings suggest that gradients of channel expression are required for normal auditory processing and that changes in levels of potassium currents across the nuclei, by mechanisms such as protein phosphorylation and rapid changes in channel synthesis, adapt the nuclei to the ongoing auditory environment.
Author Summary
In order to detect the nature and location of a sound stimulus, neurons in the central auditory system have to fire at very high rates with extreme temporal precision. Specifically, they have to be able to follow changes in an auditory stimulus at rates of up to 2000 Hz or more and to lock their action potentials to the stimuli with a precision of only a few microseconds. An individual neuron, however, cannot fire at such high rates, and the intrinsic electrical properties of neurons, such as the relative refractory period that follows each action potential, severely limits accuracy of timing at high rates. The intrinsic excitability of neurons is governed by the potassium channels that they express. It has been found in auditory brainstem nuclei that there exist gradients of these channels such that each neuron typically has a different number of channels than its neighbors. In this study, computational models based on measurements in auditory neurons demonstrate that, in the presence of random spontaneous activity such as is normally observed in auditory neurons, rapid adjustments of levels of potassium current within neurons along the gradient are required to allow the ensemble to transmit accurate timing information. The findings suggest that regulation of potassium channels within gradients is an integral component of auditory processing.
PMCID: PMC3305353  PMID: 22438799
6.  Laser Stimulation of Single Auditory Nerve Fibers 
The Laryngoscope  2010;120(10):2071-2082.
One limitation with cochlear implants is the difficulty stimulating spatially discrete spiral ganglion cell groups because of electrode interactions. Multipolar electrodes have improved on this some, but also at the cost of much higher device power consumption. Recently, it has been shown that spatially selective stimulation of the auditory nerve is possible with a mid-infrared laser aimed at the spiral ganglion via the round window. However, these neurons must be driven at adequate rates for optical radiation to be useful in cochlear implants. We herein use single-fiber recordings to characterize the responses of auditory neurons to optical radiation.
Study Design
In vivo study using normal-hearing adult gerbils.
Two diode lasers were used for stimulation of the auditory nerve. They operated between 1.844 μm and 1.873 μm, with pulse durations of 35 μs to 1,000 μs, and at repetition rates up to 1,000 pulses per second (pps). The laser outputs were coupled to a 200-μm-diameter optical fiber placed against the round window membrane and oriented toward the spiral ganglion. The auditory nerve was exposed through a craniotomy, and recordings were taken from single fibers during acoustic and laser stimulation.
Action potentials occurred 2.5 ms to 4.0 ms after the laser pulse. The latency jitter was up to 3 ms. Maximum rates of discharge averaged 97 ± 52.5 action potentials per second. The neurons did not strictly respond to the laser at stimulation rates over 100 pps.
Auditory neurons can be stimulated by a laser beam passing through the round window membrane and driven at rates sufficient for useful auditory information. Optical stimulation and electrical stimulation have different characteristics; which could be selectively exploited in future cochlear implants.
Level of Evidence
Not applicable.
PMCID: PMC3411104  PMID: 20830761
Cochlear implant; neuroprosthesis; optical stimulation; spatial selectivity; spiral ganglion cell
7.  Neural representation in the auditory midbrain of the envelope of vocalizations based on a peripheral ear model 
The auditory midbrain implant (AMI) consists of a single shank array (20 sites) for stimulation along the tonotopic axis of the central nucleus of the inferior colliculus (ICC) and has been safely implanted in deaf patients who cannot benefit from a cochlear implant (CI). The AMI improves lip-reading abilities and environmental awareness in the implanted patients. However, the AMI cannot achieve the high levels of speech perception possible with the CI. It appears the AMI can transmit sufficient spectral cues but with limited temporal cues required for speech understanding. Currently, the AMI uses a CI-based strategy, which was originally designed to stimulate each frequency region along the cochlea with amplitude-modulated pulse trains matching the envelope of the bandpass-filtered sound components. However, it is unclear if this type of stimulation with only a single site within each frequency lamina of the ICC can elicit sufficient temporal cues for speech perception. At least speech understanding in quiet is still possible with envelope cues as low as 50 Hz. Therefore, we investigated how ICC neurons follow the bandpass-filtered envelope structure of natural stimuli in ketamine-anesthetized guinea pigs. We identified a subset of ICC neurons that could closely follow the envelope structure (up to ß100 Hz) of a diverse set of species-specific calls, which was revealed by using a peripheral ear model to estimate the true bandpass-filtered envelopes observed by the brain. Although previous studies have suggested a complex neural transformation from the auditory nerve to the ICC, our data suggest that the brain maintains a robust temporal code in a subset of ICC neurons matching the envelope structure of natural stimuli. Clinically, these findings suggest that a CI-based strategy may still be effective for the AMI if the appropriate neurons are entrained to the envelope of the acoustic stimulus and can transmit sufficient temporal cues to higher centers.
PMCID: PMC3800787  PMID: 24155694
auditory brainstem implant; cochlear implant; envelope; inferior colliculus; model; phase locking; speech; temporal code
8.  Spatial Channel Interactions in Cochlear Implants 
Journal of neural engineering  2011;8(4):046029.
The modern multi-channel cochlear implant is widely considered to be the most successful neural prosthesis for its ability to restore partial hearing to post-lingually deafened adults and to allow essentially normal language development in pre-lingually deafened children. However, the implant performance varies greatly in individuals and is still limited in background noise, tonal language understanding, and music perception. One main cause for the individual variability and the limited performance in cochlear implants is spatial channel interaction from the stimulating electrodes to the auditory nerve and brain. Here we systematically examined spatial channel interactions at the physical, physiological, and perceptual levels in the same 5 modern cochlear implant subjects. The physical interaction was examined using an electric field imaging technique, which measured voltage distribution as a function of electrode position in the cochlea in response to stimulation of a single electrode. The physiological interaction was examined by recording electrically evoked compound action potentials as a function of electrode position in response to stimulation of the same single electrode position. The perceptual interactions were characterized by changes in detection threshold as well as loudness summation in response to in-phase or out-of-phase dual-electrode stimulation. To minimize potentially confounding effects of temporal factors on spatial channel interactions, stimulus rates were limited to 100 Hz or lower in all measures. Several quantitative channel interaction indexes were developed to define and compare the width, slope, and symmetry of the spatial excitation patterns derived from these physical, physiological, and perceptual measures. The electric field imaging data revealed a broad but uniformly asymmetrical intracochlear electric field pattern, with the apical side producing wider half-width and shallower slope than the basal side. On the contrary, the evoked compound action potential and perceptual channel interaction data showed much greater individual variability. It is likely that actual reduction in neural and higher level interactions, instead of simple sharpening of electric current field, would be the key to predict and hopefully improve the variable cochlear implant performance. The present results are obtained with auditory prostheses but can be applied to other neural prostheses, in which independent spatial channels, rather than high stimulation rate, are critical to their performance.
PMCID: PMC3190971  PMID: 21750370
Electric stimulation; Auditory nerve; Electric field; Compound action potential; Threshold; Loudness; Neural interface; Neural prosthesis
9.  Factors Influencing Neurotrophic Effects of Electrical Stimulation in the Deafened Developing Auditory System 
Hearing research  2008;242(1-2):86-99.
Research in animal models has demonstrated that electrical stimulation from a cochlear implant (CI) may help prevent degeneration of the cochlear spiral ganglion (SG) neurons after deafness. In cats deafened early in life, effective stimulation of the auditory nerve with complex signals for several months preserved a greater density of SG neurons in the stimulated cochleae as compared to the contralateral deafened ear. However, SG survival was still far from normal even with early intervention with an implant. Thus, pharmacologic agents and neurotrophic factors that might be used in combination with an implant are of great interest. Exogenous administration of GM1 ganglioside significantly reduces SG degeneration in deafened animals studied at 7–8 weeks of age, but after several months of stimulation, GM1-treated animals show only modestly better preservation of SG density compared to age-matched non-treated animals. A significant factor influencing neurotrophic effects in animal models is insertion trauma, which results in significant regional SG degeneration. Thus, an important goal is to further improve human CI electrode designs and insertion techniques to minimize trauma.
Another important issue for studies of neurotrophic effects in the developing auditory system is the potential role of critical periods. Studies examining animals deafened at 30 days of age (rather than at birth) have explored whether a brief initial period of normal auditory experience affects the vulnerability of the SG or cochlear nucleus (CN) to auditory deprivation. Interestingly, SG survival in animals deafened at 30-days was not significantly different from age-matched neonatally deafened animals, but significant differences were observed in the central auditory system. CN volume was significantly closer to normal in the animals deafened at 30 days as compared to neonatally deafened animals. However, no difference was observed between the stimulated and contralateral CN volumes in either deafened group. Measurements of AVCN spherical cell somata showed that after later onset of deafness in the 30-day deafened group, mean cell size was significantly closer to normal than in the neonatally deafened group. Further, electrical stimulation elicited a significant increase in spherical cell size in the CN ipsilateral to the implant as compared to the contralateral CN in both deafened groups.
Neuronal tracer studies have examined the primary afferent projections from the SG to the CN in neonatally deafened cats. CN projections exhibit a clear cochleotopic organization despite severe auditory deprivation from birth. However, when normalized for the smaller CN size after deafness, projections were 30–50% broader than normal. After unilateral electrical stimulation there was no difference between projections from the stimulated and non-stimulated ears. These findings suggest that early normal auditory experience may be essential for the normal development (or subsequent maintenance) of the topographic precision of SG-to-CN projections. After early deafness, the CN volume is markedly smaller than normal, and the spatial precision of SG projections that underlie frequency resolution in the central auditory system is reduced. Electrical stimulation over several months did not reduce or exacerbate these degenerative changes. If similar principles pertain in the human auditory system, then findings in animal models suggest that the basic cochleotopic organization of neural projections in the central auditory system is probably intact even in congenitally deaf individuals. However, the reduced spatial resolution of the primary afferent projections in our studies suggests that there may be inherent limitations for CI stimulation in congenitally deaf subjects. Spatial (spectral) selectivity of stimulation delivered on adjacent CI channels may be poorer due to the greater overlap of SG central axons representing nearby frequencies. Such CI users may be more dependent upon temporal features of electrical stimuli, and it may be advantageous to enhance the salience of such cues, for example, by removing some electrodes from the processor “map” to reduce channel interaction.
PMCID: PMC2516744  PMID: 18573324
auditory deprivation; auditory nerve; cochlear implant; cochlear nucleus; cochlear spiral ganglion; electrical stimulation; GM1 ganglioside; selegiline; neonatal deafness; primary afferents; neurotrophins
10.  Enhancement and Distortion in the Temporal Representation of Sounds in the Ventral Cochlear Nucleus of Chinchillas and Cats 
PLoS ONE  2012;7(9):e44286.
A subset of neurons in the cochlear nucleus (CN) of the auditory brainstem has the ability to enhance the auditory nerve's temporal representation of stimulating sounds. These neurons reside in the ventral region of the CN (VCN) and are usually known as highly synchronized, or high-sync, neurons. Most published reports about the existence and properties of high-sync neurons are based on recordings performed on a VCN output tract—not the VCN itself—of cats. In other species, comprehensive studies detailing the properties of high-sync neurons, or even acknowledging their existence, are missing.
Examination of the responses of a population of VCN neurons in chinchillas revealed that a subset of those neurons have temporal properties similar to high-sync neurons in the cat. Phase locking and entrainment—the ability of a neuron to fire action potentials at a certain stimulus phase and at almost every stimulus period, respectively—have similar maximum values in cats and chinchillas. Ranges of characteristic frequencies for high-sync neurons in chinchillas and cats extend up to 600 and 1000 Hz, respectively. Enhancement of temporal processing relative to auditory nerve fibers (ANFs), which has been shown previously in cats using tonal and white-noise stimuli, is also demonstrated here in the responses of VCN neurons to synthetic and spoken vowel sounds.
Along with the large amount of phase locking displayed by some VCN neurons there occurs a deterioration in the spectral representation of the stimuli (tones or vowels). High-sync neurons exhibit a greater distortion in their responses to tones or vowels than do other types of VCN neurons and auditory nerve fibers.
Standard deviations of first-spike latency measured in responses of high-sync neurons are lower than similar values measured in ANFs' responses. This might indicate a role of high-sync neurons in other tasks beyond sound localization.
PMCID: PMC3445608  PMID: 23028514
11.  Changes Across Time in the Temporal Responses of Auditory Nerve Fibers Stimulated by Electric Pulse Trains 
Most auditory prostheses use modulated electric pulse trains to excite the auditory nerve. There are, however, scant data regarding the effects of pulse trains on auditory nerve fiber (ANF) responses across the duration of such stimuli. We examined how temporal ANF properties changed with level and pulse rate across 300-ms pulse trains. Four measures were examined: (1) first-spike latency, (2) interspike interval (ISI), (3) vector strength (VS), and (4) Fano factor (FF, an index of the temporal variability of responsiveness). Data were obtained using 250-, 1,000-, and 5,000-pulse/s stimuli. First-spike latency decreased with increasing spike rate, with relatively small decrements observed for 5,000-pulse/s trains, presumably reflecting integration. ISIs to low-rate (250 pulse/s) trains were strongly locked to the stimuli, whereas ISIs evoked with 5,000-pulse/s trains were dominated by refractory and adaptation effects. Across time, VS decreased for low-rate trains but not for 5,000-pulse/s stimuli. At relatively high spike rates (>200 spike/s), VS values for 5,000-pulse/s trains were lower than those obtained with 250-pulse/s stimuli (even after accounting for the smaller periods of the 5,000-pulse/s stimuli), indicating a desynchronizing effect of high-rate stimuli. FF measures also indicated a desynchronizing effect of high-rate trains. Across a wide range of response rates, FF underwent relatively fast increases (i.e., within 100 ms) for 5,000-pulse/s stimuli. With a few exceptions, ISI, VS, and FF measures approached asymptotic values within the 300-ms duration of the low- and high-rate trains. These findings may have implications for designs of cochlear implant stimulus protocols, understanding electrically evoked compound action potentials, and interpretation of neural measures obtained at central nuclei, which depend on understanding the output of the auditory nerve.
PMCID: PMC2536806  PMID: 18204987
cochlear implant; electric stimulation; auditory nerve; single fiber; refractoriness; adaptation; vector strength; desynchronization; Fano factor
12.  Effects of Vestibular Prosthesis Electrode Implantation and Stimulation on Hearing in Rhesus Monkeys 
Hearing research  2010;277(1-2):204-210.
To investigate the effects of vestibular prosthesis electrode implantation and activation on hearing in rhesus monkeys, we measured auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE) in four rhesus monkeys before and after unilateral implantation of vestibular prosthesis electrodes in each of 3 left semicircular canals (SCC). Each of the 3 left SCCs were implanted with electrodes via a transmastoid approach. Right ears, which served as controls, were not surgically manipulated. Hearing tests were conducted before implantation (BI) and then 4 weeks post implantation both without electrical stimulation (NS) and with electrical stimulation (S). During the latter condition, prosthetic electrical stimuli encoding 3 dimensions of head angular velocity were delivered to the 3 ampullary branches of the left vestibular nerve via each of 3 electrode pairs of a multichannel vestibular prosthesis. Electrical stimuli comprised charge-balanced biphasic pulses at a baseline rate of 94 pulses/sec, with pulse frequency modulated from 48–222 pulses/s by head angular velocity. ABR hearing thresholds to clicks and tone pips at 1, 2, and 4 kHz increased by 5–10 dB from BI to NS and increased another ~5 dB from NS to S in implanted ears. No significant change was seen in right ears. DPOAE amplitudes decreased by 2–14 dB from BI to NS in implanted ears. There was a slight but insignificant decrease of DPOAE amplitude and a corresponding increase of DPOAE/Noise floor ratio between NS and S in implanted ears.
Vestibular prosthesis electrode implantation and activation have small but measurable effects on hearing in rhesus monkeys. Coupled with the clinical observation that patients with cochlear implants only rarely exhibit signs of vestibular injury or spurious vestibular nerve stimulation, these results suggest that although implantation and activation of multichannel vestibular prosthesis electrodes in human will carry a risk of hearing loss, that loss is not likely to be severe.
PMCID: PMC3081362  PMID: 21195755
multichannel; vestibular prosthesis; electrode; implantation; electrical stimulation; hearing; labyrinth; vestibular; vestibular implant
13.  Electrophysiological Validation of a Human Prototype Auditory Midbrain Implant in a Guinea Pig Model 
The auditory midbrain implant (AMI) is a new treatment for hearing restoration in patients with neural deafness or surgically inaccessible cochleae who cannot benefit from cochlear implants (CI). This includes neurofibromatosis type II (NF2) patients who, due to development and/or removal of vestibular schwannomas, usually experience complete damage of their auditory nerves. Although the auditory brainstem implant (ABI) provides sound awareness and aids lip-reading capabilities for these NF2 patients, it generally only achieves hearing performance levels comparable with a single-channel CI. In collaboration with Cochlear Ltd. (Lane Cove, Australia), we developed a human prototype AMI, which is designed for electrical stimulation along the well-defined tonotopic gradient of the inferior colliculus central nucleus (ICC). Considering that better speech perception and hearing performance has been correlated with a greater number of discriminable frequency channels of information available, the ability of the AMI to effectively activate discrete frequency regions within the ICC may enable better hearing performance than achieved by the ABI. Therefore, the goal of this study was to investigate if our AMI array could achieve low-threshold, frequency-specific activation within the ICC, and whether the levels for ICC activation via AMI stimulation were within safe limits for human application. We electrically stimulated different frequency regions within the ICC via the AMI array and recorded the corresponding neural activity in the primary auditory cortex (A1) using a multisite silicon probe in ketamine-anesthetized guinea pigs. Based on our results, AMI stimulation achieves lower thresholds and more localized, frequency-specific activation than CI stimulation. Furthermore, AMI stimulation achieves cortical activation with current levels that are within safe limits for central nervous system stimulation. This study confirms that our AMI design is sufficient for ensuring safe and effective activation of the ICC, and warrants further studies to translate the AMI into clinical application.
PMCID: PMC2504634  PMID: 17075701
auditory prosthesis; inferior colliculus; auditory cortex; electrical stimulation; NF2; deep brain stimulation
14.  Changes in Pitch with a Cochlear Implant Over Time 
In the normal auditory system, the perceived pitch of a tone is closely linked to the cochlear place of vibration. It has generally been assumed that high-rate electrical stimulation by a cochlear implant electrode also evokes a pitch sensation corresponding to the electrode’s cochlear place (“place” code) and stimulation rate (“temporal” code). However, other factors may affect electric pitch sensation, such as a substantial loss of nearby nerve fibers or even higher-level perceptual changes due to experience. The goals of this study were to measure electric pitch sensations in hybrid (short-electrode) cochlear implant patients and to examine which factors might contribute to the perceived pitch. To look at effects of experience, electric pitch sensations were compared with acoustic tone references presented to the non-implanted ear at various stages of implant use, ranging from hookup to 5 years. Here, we show that electric pitch perception often shifts in frequency, sometimes by as much as two octaves, during the first few years of implant use. Additional pitch measurements in more recently implanted patients at shorter time intervals up to 1 year of implant use suggest two likely contributions to these observed pitch shifts: intersession variability (up to one octave) and slow, systematic changes over time. We also found that the early pitch sensations for a constant electrode location can vary greatly across subjects and that these variations are strongly correlated with speech reception performance. Specifically, patients with an early low-pitch sensation tend to perform poorly with the implant compared to those with an early high-pitch sensation, which may be linked to less nerve survival in the basal end of the cochlea in the low-pitch patients. In contrast, late pitch sensations show no correlation with speech perception. These results together suggest that early pitch sensations may more closely reflect peripheral innervation patterns, while later pitch sensations may reflect higher-level, experience-dependent changes. These pitch shifts over time not only raise questions for strict place-based theories of pitch perception, but also imply that experience may have a greater influence on cochlear implant perception than previously thought.
PMCID: PMC2538353  PMID: 17347777
cochlear implant; hybrid; frequency; tonotopy; speech; plasticity
15.  A hardware model of the auditory periphery to transduce acoustic signals into neural activity 
To improve the performance of cochlear implants, we have integrated a microdevice into a model of the auditory periphery with the goal of creating a microprocessor. We constructed an artificial peripheral auditory system using a hybrid model in which polyvinylidene difluoride was used as a piezoelectric sensor to convert mechanical stimuli into electric signals. To produce frequency selectivity, the slit on a stainless steel base plate was designed such that the local resonance frequency of the membrane over the slit reflected the transfer function. In the acoustic sensor, electric signals were generated based on the piezoelectric effect from local stress in the membrane. The electrodes on the resonating plate produced relatively large electric output signals. The signals were fed into a computer model that mimicked some functions of inner hair cells, inner hair cell–auditory nerve synapses, and auditory nerve fibers. In general, the responses of the model to pure-tone burst and complex stimuli accurately represented the discharge rates of high-spontaneous-rate auditory nerve fibers across a range of frequencies greater than 1 kHz and middle to high sound pressure levels. Thus, the model provides a tool to understand information processing in the peripheral auditory system and a basic design for connecting artificial acoustic sensors to the peripheral auditory nervous system. Finally, we discuss the need for stimulus control with an appropriate model of the auditory periphery based on auditory brainstem responses that were electrically evoked by different temporal pulse patterns with the same pulse number.
PMCID: PMC3840400  PMID: 24324432
acoustic sensor; computer model; digital signal processor; piezoelectric film; electrically evoked auditory brainstem response
16.  Better Temporal Neural Coding with Cochlear Implants in Awake Animals 
Both the performance of cochlear implant (CI) listeners and the responses of auditory neurons show limits in temporal processing at high frequencies. However, the upper limit of temporal coding of pulse train stimuli in the inferior colliculus (IC) of anesthetized animals appears to be lower than that observed in corresponding perceptual tasks. We hypothesize that the neural rate limits have been underestimated due to the effect of anesthesia. To test this hypothesis, we developed a chronic, awake rabbit preparation for recording responses of single IC neurons to CI stimulation without the confound of anesthesia, and compared these data with earlier recordings from the IC of anesthetized cats. Stimuli were periodic trains of biphasic pulses with rates varying from 20 to 1280 pulses per second (pps). We found that the maximum pulse rates that elicited sustained firing and phase-locked responses were 2–3 times higher in the IC of awake rabbits than in anesthetized cats. Moreover, about 25% of IC neurons in awake rabbit showed sustained responses to periodic pulse trains at much higher pulse rates (> 1000 pps) than observed in anesthetized animals. Similar differences were observed in single units whose responses to pulse trains were monitored while the animal was given an injection of an ultra short-acting anesthetic. In general, the physiological rate limits of IC neurons in awake rabbit are more consistent with the psychophysical limits in human CI subjects compared to the data from anesthetized animals.
PMCID: PMC3726256  PMID: 23716241
cochlear implants; temporal coding; inferior colliculus; anesthesia
17.  Direct Recordings from the Auditory Cortex in a Cochlear Implant User 
Electrical stimulation of the auditory nerve with a cochlear implant (CI) is the method of choice for treatment of severe-to-profound hearing loss. Understanding how the human auditory cortex responds to CI stimulation is important for advances in stimulation paradigms and rehabilitation strategies. In this study, auditory cortical responses to CI stimulation were recorded intracranially in a neurosurgical patient to examine directly the functional organization of the auditory cortex and compare the findings with those obtained in normal-hearing subjects. The subject was a bilateral CI user with a 20-year history of deafness and refractory epilepsy. As part of the epilepsy treatment, a subdural grid electrode was implanted over the left temporal lobe. Pure tones, click trains, sinusoidal amplitude-modulated noise, and speech were presented via the auxiliary input of the right CI speech processor. Additional experiments were conducted with bilateral CI stimulation. Auditory event-related changes in cortical activity, characterized by the averaged evoked potential and event-related band power, were localized to posterolateral superior temporal gyrus. Responses were stable across recording sessions and were abolished under general anesthesia. Response latency decreased and magnitude increased with increasing stimulus level. More apical intracochlear stimulation yielded the largest responses. Cortical evoked potentials were phase-locked to the temporal modulations of periodic stimuli and speech utterances. Bilateral electrical stimulation resulted in minimal artifact contamination. This study demonstrates the feasibility of intracranial electrophysiological recordings of responses to CI stimulation in a human subject, shows that cortical response properties may be similar to those obtained in normal-hearing individuals, and provides a basis for future comparisons with extracranial recordings.
PMCID: PMC3642273  PMID: 23519390
averaged evoked potential; cortical plasticity; electrical stimulation; electrocorticography; high gamma; intracranial electrophysiology
18.  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 five weeks or six months. Auditory neuron survival decreased significantly with the duration of deafness. Extracellular recordings were made from auditory nerve fibrefibrefibrefibres 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 six months of deafness. The response to a 200 pulses/s stimulus was similar except that the dynamic range was greater compared to 20 pulses/s and was also greater in deafened animals compared to 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 pulse/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.
PMCID: PMC2112941  PMID: 17650121
Hearing loss; electrical stimulation; spiral ganglion; neurodegeneration; guinea pig
19.  Short-Term Synaptic Depression Is Topographically Distributed in the Cochlear Nucleus of the Chicken 
The Journal of Neuroscience  2014;34(4):1314-1324.
In the auditory system, sounds are processed in parallel frequency-tuned circuits, beginning in the cochlea. Activity of auditory nerve fibers reflects this frequency-specific topographic pattern, known as tonotopy, and imparts frequency tuning onto their postsynaptic target neurons in the cochlear nucleus. In birds, cochlear nucleus magnocellularis (NM) neurons encode the temporal properties of acoustic stimuli by “locking” discharges to a particular phase of the input signal. Physiological specializations exist in gradients corresponding to the tonotopic axis in NM that reflect the characteristic frequency (CF) of their auditory nerve fiber inputs. One feature of NM neurons that has not been investigated across the tonotopic axis is short-term synaptic plasticity. NM offers a rather homogeneous population of neurons with a distinct topographical distribution of synaptic properties that is ideal for the investigation of specialized synaptic plasticity. Here we demonstrate for the first time that short-term synaptic depression (STD) is expressed topographically, where unitary high CF synapses are more robust with repeated stimulation. Correspondingly, high CF synapses drive spiking more reliably than their low CF counterparts. We show that postsynaptic AMPA receptor desensitization does not contribute to the observed difference in STD. Further, rate of recovery from depression, a presynaptic property, does not differ tonotopically. Rather, we show that another presynaptic feature, readily releasable pool (RRP) size, is tonotopically distributed and inversely correlated with vesicle release probability. Mathematical model results demonstrate that these properties of vesicle dynamics are sufficient to explain the observed tonotopic distribution of STD.
PMCID: PMC3898291  PMID: 24453322
tonotopy; topographic map; synaptic plasticity; short-term synaptic depression; release probability; readily releasable pool
20.  Envelope Enhancement Increases Cortical Sensitivity to Interaural Envelope Delays with Acoustic and Electric Hearing 
PLoS ONE  2014;9(8):e104097.
Evidence from human psychophysical and animal electrophysiological studies suggests that sensitivity to interaural time delay (ITD) in the modulating envelope of a high-frequency carrier can be enhanced using half-wave rectified stimuli. Recent evidence has shown potential benefits of equivalent electrical stimuli to deaf individuals with bilateral cochlear implants (CIs). In the current study we assessed the effects of envelope shape on ITD sensitivity in the primary auditory cortex of normal-hearing ferrets, and profoundly-deaf animals with bilateral CIs. In normal-hearing animals, cortical sensitivity to ITDs (±1 ms in 0.1-ms steps) was assessed in response to dichotically-presented i) sinusoidal amplitude-modulated (SAM) and ii) half-wave rectified (HWR) tones (100-ms duration; 70 dB SPL) presented at the best-frequency of the unit over a range of modulation frequencies. In separate experiments, adult ferrets were deafened with neomycin administration and bilaterally-implanted with intra-cochlear electrode arrays. Electrically-evoked auditory brainstem responses (EABRs) were recorded in response to bipolar electrical stimulation of the apical pair of electrodes with singe biphasic current pulses (40 µs per phase) over a range of current levels to measure hearing thresholds. Subsequently, we recorded cortical sensitivity to ITDs (±800 µs in 80-µs steps) within the envelope of SAM and HWR biphasic-pulse trains (40 µs per phase; 6000 pulses per second, 100-ms duration) over a range of modulation frequencies. In normal-hearing animals, nearly a third of cortical neurons were sensitive to envelope-ITDs in response to SAM tones. In deaf animals with bilateral CI, the proportion of ITD-sensitive cortical neurons was approximately a fifth in response to SAM pulse trains. In normal-hearing and deaf animals with bilateral CI the proportion of ITD sensitive units and neural sensitivity to ITDs increased in response to HWR, compared with SAM stimuli. Consequently, novel stimulation strategies based on envelope enhancement may prove beneficial to individuals with bilateral cochlear implants.
PMCID: PMC4122409  PMID: 25093417
21.  The Polarity Sensitivity of the Electrically Stimulated Human Auditory Nerve Measured at the Level of the Brainstem 
Recent behavioral studies have suggested that the human auditory nerve of cochlear implant (CI) users is mainly excited by the positive (anodic) polarity. Those findings were only obtained using asymmetric pseudomonophasic (PS) pulses where the effect of one phase was measured in the presence of a counteracting phase of opposite polarity, longer duration, and lower amplitude than the former phase. It was assumed that only the short high-amplitude phase was responsible for the excitation. Similarly, it has been shown that electrically evoked compound action potentials could only be obtained in response to the anodic phases of asymmetric pulses. Here, experiment 1 measured electrically evoked auditory brainstem responses to standard symmetric, PS, reversed pseudomonophasic, and reversed pseudomonophasic with inter-phase gap (6 ms) pulses presented for both polarities. Responses were time locked to the short high-amplitude phase of asymmetric pulses and were smaller, but still measurable, when that phase was cathodic than when it was anodic. This provides the first evidence that cathodic stimulation can excite the auditory system of human CI listeners and confirms that this stimulation is nevertheless less effective than for the anodic polarity. A second experiment studied the polarity sensitivity at different intensities by means of a loudness balancing task between pseudomonophasic anodic (PSA) and pseudomonophasic cathodic (PSC) stimuli. Previous studies had demonstrated greater sensitivity to anodic stimulation only for stimuli producing loud percepts. The results showed that PSC stimuli required higher amplitudes than PSA stimuli to reach the same loudness and that this held for current levels ranging from 10 to 100 % of the dynamic range.
PMCID: PMC3642274  PMID: 23479187
cochlear implants; objective measures; psychophysics; polarity sensitivity; electrically evoked auditory brainstem responses; asymmetric pulse shapes; EABR
22.  Electrically-Evoked Frequency-Following Response (EFFR) in the Auditory Brainstem of Guinea Pigs 
PLoS ONE  2014;9(9):e106719.
It is still a difficult clinical issue to decide whether a patient is a suitable candidate for a cochlear implant and to plan postoperative rehabilitation, especially for some special cases, such as auditory neuropathy. A partial solution to these problems is to preoperatively evaluate the functional integrity of the auditory neural pathways. For evaluating the strength of phase-locking of auditory neurons, which was not reflected in previous methods using electrically evoked auditory brainstem response (EABR), a new method for recording phase-locking related auditory responses to electrical stimulation, called the electrically evoked frequency-following response (EFFR), was developed and evaluated using guinea pigs. The main objective was to assess feasibility of the method by testing whether the recorded signals reflected auditory neural responses or artifacts. The results showed the following: 1) the recorded signals were evoked by neuron responses rather than by artifact; 2) responses evoked by periodic signals were significantly higher than those evoked by the white noise; 3) the latency of the responses fell in the expected range; 4) the responses decreased significantly after death of the guinea pigs; and 5) the responses decreased significantly when the animal was replaced by an electrical resistance. All of these results suggest the method was valid. Recording obtained using complex tones with a missing fundamental component and using pure tones with various frequencies were consistent with those obtained using acoustic stimulation in previous studies.
PMCID: PMC4171095  PMID: 25244253
23.  Music Perception with Cochlear Implants: A Review 
Trends in Amplification  2004;8(2):49-82.
The acceptance of cochlear implantation as an effective and safe treatment for deafness has increased steadily over the past quarter century. The earliest devices were the first implanted prostheses found to be successful in compensating partially for lost sensory function by direct electrical stimulation of nerves. Initially, the main intention was to provide limited auditory sensations to people with profound or total sensorineural hearing impairment in both ears. Although the first cochlear implants aimed to provide patients with little more than awareness of environmental sounds and some cues to assist visual speech-reading, the technology has advanced rapidly. Currently, most people with modern cochlear implant systems can understand speech using the device alone, at least in favorable listening conditions. In recent years, an increasing research effort has been directed towards implant users’ perception of nonspeech sounds, especially music. This paper reviews that research, discusses the published experimental results in terms of both psychophysical observations and device function, and concludes with some practical suggestions about how perception of music might be enhanced for implant recipients in the future. The most significant findings of past research are: (1) On average, implant users perceive rhythm about as well as listeners with normal hearing; (2) Even with technically sophisticated multiple-channel sound processors, recognition of melodies, especially without rhythmic or verbal cues, is poor, with performance at little better than chance levels for many implant users; (3) Perception of timbre, which is usually evaluated by experimental procedures that require subjects to identify musical instrument sounds, is generally unsatisfactory; (4) Implant users tend to rate the quality of musical sounds as less pleasant than listeners with normal hearing; (5) Auditory training programs that have been devised specifically to provide implant users with structured musical listening experience may improve the subjective acceptability of music that is heard through a prosthesis; (6) Pitch perception might be improved by designing innovative sound processors that use both temporal and spatial patterns of electric stimulation more effectively and precisely to overcome the inherent limitations of signal coding in existing implant systems; (7) For the growing population of implant recipients who have usable acoustic hearing, at least for low-frequency sounds, perception of music is likely to be much better with combined acoustic and electric stimulation than is typical for deaf people who rely solely on the hearing provided by their prostheses.
PMCID: PMC4111359  PMID: 15497033
24.  A fully implantable stimulator for use in small laboratory animals 
Journal of neuroscience methods  2007;166(2):168-177.
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 – 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.
PMCID: PMC2001238  PMID: 17897719
electrical stimulation; cochlear implant; neural prostheses; stimulator; mouse
25.  A Clinical Study of Cortical Auditory Evoked Potentials in Cochlear Implantees 
Normal maturation of central auditory pathways is a precondition for the optimal development of speech and language skills in children. The temporal cortex gets acoustically tagged due to auditory stimulation and important changes occur in the higher auditory centers due to hearing loss of any type and degree. Cochlear implantation increases auditory sensitivity by direct electrical activation of auditory nerve fibers, enabling phonemic awareness, discrimination and identification ultimately yielding speech understanding. Early implantation stimulates a brain that has not been re-organized and will therefore be more receptive to auditory input and greater auditory capacity. Cortical potentials have enabled us to objectively study this phenomenon. To assess the outcomes of Cochlear implants on the auditory cortex by analyzing cortical auditory evoked potentials (CAEPs) in the habilitation period. This prospective clinical study was performed in 30 pre-lingual candidates with varied etiology of deafness who underwent cochlear implantation at our institute over the last 1 year. The study group had two cohorts (group-1: 0–8 years and group-2: 8–15 years) which included candidates with normal inner ear and no syndromes or handicaps. All implantees in the study group underwent CAEP testing at 6 months and 1 year post-implantation and comparison of the CAEP wave parameters (P1 amplitude, P1 latency and P1 morphology) were done between the two cohorts. In children Implanted early (group-1) there was an early onset rapid increase in P1 amplitude along with a decrease in P1 latency during the follow-up period. Significant change in the CAEP wave morphology was also notable in group-1 unlike in group-2. Candidates who experienced less than 3 years of auditory deprivation before implantation showed P1 latencies, which fell into the range of normal children within 6 months of habilitation. Children with more than 6 years of auditory deprivation, however, generally did not develop normal P1 latencies or morphology even after 1 year of habilitation. The overall outcome with CAEP was much better in group-1 as compared to group-2 and the observations were is in comparison with the existing world literature. The advent of CAEP has objectively proved beyond doubt that there is a critical age for stimulating the auditory brain via cochlear implantation. There is considerable evidence for a developmental sensitive period, during which the auditory cortex is highly plastic. If sensory input is deprived to the auditory system during this sensitive period, then the central auditory system is susceptible to large scale reorganization. Restoring input to the auditory system by Cochlear Implant at an early age can provide the stimulation necessary to preserve the auditory pathways. However, if auditory input is not restored until after this developmental period, then the cross-modal reorganized pathways may exhibits abnormal functional characteristics as observed in recorded P1 amplitude, latencies and morphologies of CAEPs.
PMCID: PMC3889379  PMID: 24427719
Cochlear implants; Central auditory processing; Cortical auditory evoked potentials (CAEPs)

Results 1-25 (944027)