Low Stimulation Rates Research Articles

A Mixed-Rate Strategy on a Bilaterally-Synchronized Cochlear Implant Processor Offering the Opportunity to Provide Both Speech Understanding and Interaural Time Difference Cues.

Background/Objective: Bilaterally implanted cochlear implant (CI) users do not consistently have access to interaural time differences (ITDs). ITDs are crucial for restoring the ability to localize sounds and understand speech in noisy environments. Lack of access to ITDs is partly due to lack of communication between clinical processors across the ears and partly because processors must use relatively high rates of stimulation to encode envelope information. Speech understanding is best at higher stimulation rates, but sensitivity to ITDs in the timing of pulses is best at low stimulation rates. Methods: We implemented a practical "mixed rate" strategy that encodes ITD information using a low stimulation rate on some channels and speech information using high rates on the remaining channels. The strategy was tested using a bilaterally synchronized research processor, the CCi-MOBILE. Nine bilaterally implanted CI users were tested on speech understanding and were asked to judge the location of a sound based on ITDs encoded using this strategy. Results: Performance was similar in both tasks between the control strategy and the new strategy. Conclusions: We discuss the benefits and drawbacks of the sound coding strategy and provide guidelines for utilizing synchronized processors for developing strategies.

Cochlear implant pitch and lexical tone perception in quiet and noise using F0-rate coding

Fundamental frequency (F0) cues to voice/musical pitch can be coded by pulse-rate or amplitude modulation (AM) rate of electrical pulse-trains in cochlear implant (CI) systems. However, for most clinical strategies (e.g., ACE), temporal cues to F0 are often poorly coded, particularly for female and children's voices and/or in background noise. Strategies such as Optimized Pitch And Language (OPAL) and Fundamental Asynchronous Stimulus Timing (FAST) enhance temporal F0 cues. For OPAL, F0 is estimated and used to control the AM rate coded by electrical pulse-trains in channel containing harmonics of F0. Significant benefits of OPAL to pitch ranking, speech intonation, and Mandarin lexical tone recognition have been observed compared to ACE. For FAST, peak-timing information in channel envelopes is used to derive pulse-timing in each channel and therefore much lower stimulation rates are provided resulting in longer battery life. In bilateral CI systems, it provides better ITD sensitivity, lateralization, and spatial release from masking compared to ACE. Presented here are the results of two studies, the first explored pitch perception of harmonic tones presented in quiet and noise using experimental OPAL and FAST strategies, and the second examined Mandarin lexical tone perception in quiet and noise using ACE and OPAL in a clinical processor.

Lateralization of interaural time differences with mixed rates of stimulation in bilateral cochlear implant listeners.

While listeners with bilateral cochlear implants (BiCIs) are able to access information in both ears, they still struggle to perform well on spatial hearing tasks when compared to normal hearing listeners. This performance gap could be attributed to the high stimulation rates used for speech representation in clinical processors. Prior work has shown that spatial cues, such as interaural time differences (ITDs), are best conveyed at low rates. Further, BiCI listeners are sensitive to ITDs with a mixture of high and low rates. However, it remains unclear whether mixed-rate stimuli are perceived as unitary percepts and spatially mapped to intracranial locations. Here, electrical pulse trains were presented on five, interaurally pitch-matched electrode pairs using research processors, at either uniformly high rates, low rates, or mixed rates. Eight post-lingually deafened adults were tested on perceived intracranial lateralization of ITDs ranging from 50 to 1600 μs. Extent of lateralization depended on the location of low-rate stimulation along the electrode array: greatest in the low- and mixed-rate configurations, and smallest in the high-rate configuration. All but one listener perceived a unitary auditory object. These findings suggest that a mixed-rate processing strategy can result in good lateralization and convey a unitary auditory object with ITDs.

Repetitive nerve stimulation test in myasthenic crisis.

Herein we report our experience with the repetitive nerve stimulation (RNS) test in myasthenia gravis (MG) crisis. The various parameters of the RNS tests in 26 patients with MG crisis were analyzed. In 18 (69%) patients, MG crisis is the first manifestation of MG. RNS tests were abnormal in 24 (92%) patients by decrement at low-rate stimulation in any of 4 tested muscles. Three patterns of abnormality were found: MG pattern (decrement at low-rate stimulation) in 23 patients; Lambert-Eaton myasthenic syndrome pattern in 1 patient; and cholinergic crisis pattern in 1 patient. During MG crisis, the RNS test can serve as a rapid and sensitive diagnostic tool for MG in a majority of patients. Muscle Nerve 59:544-544, 2019.

Fast acquisition of full-range auditory event-related potentials using an interleaved deconvolution approach.

This work relates to recent advances in the field of auditory event-related potentials (ERP), specifically deconvolution-based ERP acquisition and single-trial processing. An efficient stimulus sequence optimization method for ERP deconvolution is proposed, achieving consistent noise attenuation within a broad designated frequency range. Furthermore, a stimulus presentation paradigm for the fast, interleaved acquisition of auditory brainstem, middle-latency and late responses featuring alternating periods of high-rate deconvolution sequences, and subsequent low-rate stimulation is investigated in 20 normal hearing subjects. Deconvolved sequence responses containing early and middle-latency ERP components are fused with subsequent late responses using a time-frequency resolved weighted averaging method based on cross-trial regularity, yielding a uniform signal-to-noise ratio of the full-range auditory ERP across investigated timescales. Obtained average ERP waveforms exhibit morphologies consistent with both literature values and reference recordings acquired in 15 normal hearing subjects using a prior art approach to full-range auditory ERP acquisition, with all prominent waves being visible in the grand average waveforms. Results suggest the proposed interleaved stimulus presentation and associated ERP processing methodology to be suitable for the fast, reliable extraction of full-range auditory processing correlates in future ERP studies.

Increased Vulnerability to Atrial Fibrillation Is Associated With Increased Susceptibility to Alternans in Old Sheep.

BackgroundAtrial fibrillation (AF) is common in the elderly, but rare in the young; however, the changes that occur with age that promote AF are not fully understood. Action potential (AP) alternans may be involved in the initiation of AF. Using a translationally relevant model, we investigated whether age‐associated atrial vulnerability to AF was associated with susceptibility to AP alternans.Methods and Results AF was induced in conscious young and old sheep using 50 Hz burst pacing. Old sheep were more vulnerable to AF. Monophasic and cellular APs were recorded from the right atrium in vivo and from myocytes isolated from the left and right atrial appendages. AP alternans occurred at lower stimulation frequencies in old sheep than young in vivo (old, 3.0±0.1 Hz; young, 3.3±0.1 Hz; P<0.05) and in isolated myocytes (old, 1.6±0.1 Hz; young, 2.0±0.1 Hz; P<0.05). Simultaneous recordings of [Ca2+]i and membrane potential in myocytes showed that alternans of APs and [Ca2+]i often occurred together. However, at low stimulation rates [Ca2+]i alternans could occur without AP alternans, whereas at high stimulation rates AP alternans could still be observed despite disabling Ca2+ cycling using thapsigargin.ConclusionsWe have shown, for the first time in a large mammalian model, that aging is associated with increased duration of AF and susceptibility to AP alternans. We suggest that instabilities in Ca2+ handling initiate alternans at low stimulation rates, but that AP restitution alone can sustain alternans at higher rates.

Examination of Prosody and Timbre Perception in Adults With Cochlear Implants Comparing Different Fine Structure Coding Strategies.

This study aimed to investigate whether adults with cochlear implants benefit from a change of fine structure (FS) coding strategies regarding the discrimination of prosodic speech cues, timbre cues, and the identification of natural instruments. The FS processing (FSP) coding strategy was compared to 2 settings of the FS4 strategy. A longitudinal crossover, double-blinded study was conducted. This study consisted of 2 parts, with 14 participants in the first part and 12 participants in the second part. Each part lasted 3 months, in which participants were alternately fitted with either the established FSP strategy or 1 of the 2 newly developed FS4 settings. Participants had to complete an intonation identification test; a timbre discrimination test in which 1 of 2 isolated cues changed, either the spectral centroid or the spectral irregularity; and an instrument identification test. A significant effect was seen in the discrimination of spectral irregularity with 1 of the 2 FS4 settings. The improvement was seen in the FS4 setting in which the upper envelope channels had a low stimulation rate. This improvement was not seen with the FS4 setting that had a higher stimulation rate on the envelope channels. In general, the FSP strategy and the 2 settings of the FS4 strategy provided similar levels in the perception of prosody and timbre cues, as well as in the identification of instruments.

Mixed stimulation rates to improve sensitivity of interaural timing differences in bilateral cochlear implant listeners.

Normal hearing listeners extract small interaural time differences (ITDs) and interaural level differences (ILDs) to locate sounds and segregate targets from noise. Bilateral cochlear implant listeners show poor sensitivity to ITDs when using clinical processors. This is because common clinical stimulation approaches use high rates [∼1000 pulses per-second (pps)] for each electrode in order to provide good speech representation, but sensitivity to ITDs is best at low rates of stimulation (∼100-300 pps). Mixing rates of stimulation across the array is a potential solution. Here, ITD sensitivity for a number of mixed-rate configurations that were designed to preserve speech envelope cues using high-rate stimulation and spatial hearing using low rate stimulation was examined. Results showed that ITD sensitivity in mixed-rate configurations when only one low rate electrode was included generally yielded ITD thresholds comparable to a configuration with low rates only. Low rate stimulation at basal or middle regions on the electrode array yielded the best sensitivity to ITDs. This work provides critical evidence that supports the use of mixed-rate strategies for improving ITD sensitivity in bilateral cochlear implant users.

The role of onset cues for lateralization of an auditory object in bilateral cochlear implant listeners

In bilateral cochlear implant (BiCI) listeners, a common strategy for improving sensitivity to interaural timing differences (ITDs) is to introduce low rate stimulation in some channels. Previous work showed that BiCI listeners can lateralize a single sound with a constant ITD at every pulse of a low rate stimulus. However, in reverberant environments, ITDs for a target sound can change over a short period of time. Previously we have shown that BiCI listeners had difficulty using the ITD in the first pulse of a low-rate pulse train to lateralize a stimulus when the subsequent pulses had ITDs that varied over time. Hence, we hypothesized that a more salient onset is needed in order to restore ITD sensitivity in BiCI listeners when using low rate stimulation. In this study, we measured the number of pulses with a consistent ITD that is needed at the onset in order for BiCI listeners to reliably perceive one sound in the correct location. Results suggest that BiCI listeners need at least five pulses with consistent ITDs in order to report a single auditory object that is correctly lateralized. These results have important implications for low rate strategies aimed at restoring ITD sensitivity to BiCI listeners.

Using Neural Response Telemetry to Monitor Physiological Responses to Acoustic Stimulation in Hybrid Cochlear Implant Users.

This report describes the results of a series of experiments where we use the neural response telemetry (NRT) system of the Nucleus cochlear implant (CI) to measure the response of the peripheral auditory system to acoustic stimulation in Nucleus Hybrid CI users. The objectives of this study were to determine whether they could separate responses from hair cells and neurons and to evaluate the stability of these measures over time. Forty-four CI users participated. They all had residual acoustic hearing and used a Nucleus Hybrid S8, S12, or L24 CI or the standard lateral wall CI422 implant. The NRT system of the CI was used to trigger an acoustic stimulus (500-Hz tone burst or click), which was presented at a low stimulation rate (10, 15, or 50 per second) to the implanted ear via an insert earphone and to record the cochlear microphonic, the auditory nerve neurophonic and the compound action potential (CAP) from an apical intracochlear electrode. To record acoustically evoked responses, a longer time window than is available with the commercial NRT software is required. This limitation was circumvented by making multiple recordings for each stimulus using different time delays between the onset of stimulation and the onset of averaging. These recordings were then concatenated off-line. Matched recordings elicited using positive and negative polarity stimuli were added off-line to emphasize neural potentials (SUM) and subtracted off-line to emphasize potentials primarily generated by cochlear hair cells (DIF). These assumptions regarding the origin of the SUM and DIF components were tested by comparing the magnitude of these derived responses recorded using various stimulation rates. Magnitudes of the SUM and DIF components were compared with each other and with behavioral thresholds. SUM and DIF components were identified for most subjects, consistent with both hair cell and neural responses to acoustic stimulation. For a subset of the study participants, the DIF components grew as stimulus level was increased, but little or no SUM components were identified. Latency of the CAPs in response to click stimuli was long relative to reports in the literature of recordings obtained using extracochlear electrodes. This difference in response latency and general morphology of the CAPs recorded was likely due to differences across subjects in hearing loss configuration. The use of high stimulation rates tended to decrease SUM and CAP components more than DIF components. We suggest this effect reflects neural adaptation. In some individuals, repeated measures were made over intervals as long as 9 months. Changes over time in DIF, SUM, and CAP thresholds mirrored changes in audiometric threshold for the subjects who experienced loss of acoustic hearing in the implanted ear. The Nucleus NRT software can be used to record peripheral responses to acoustic stimulation at threshold and suprathreshold levels, providing a window into the status of the auditory hair cells and the primary afferent nerve fibers. These acoustically evoked responses are sensitive to changes in hearing status and consequently could be useful in characterizing the specific pathophysiology of the hearing loss experienced by this population of CI users.

Ca2 +-activated Cl− current is antiarrhythmic by reducing both spatial and temporal heterogeneity of cardiac repolarization

The role of Ca2+-activated Cl− current (ICl(Ca)) in cardiac arrhythmias is still controversial. It can generate delayed afterdepolarizations in Ca2+-overloaded cells while in other studies incidence of early afterdepolarization (EAD) was reduced by ICl(Ca). Therefore our goal was to examine the role of ICl(Ca) in spatial and temporal heterogeneity of cardiac repolarization and EAD formation.Experiments were performed on isolated canine cardiomyocytes originating from various regions of the left ventricle; subepicardial, midmyocardial and subendocardial cells, as well as apical and basal cells of the midmyocardium. ICl(Ca) was blocked by 0.5mmol/L 9-anthracene carboxylic acid (9-AC). Action potential (AP) changes were tested with sharp microelectrode recording. Whole-cell 9-AC-sensitive current was measured with either square pulse voltage-clamp or AP voltage-clamp (APVC). Protein expression of TMEM16A and Bestrophin-3, ion channel proteins mediating ICl(Ca), was detected by Western blot.9-AC reduced phase-1 repolarization in every tested cell. 9-AC also increased AP duration in a reverse rate-dependent manner in all cell types except for subepicardial cells. Neither ICl(Ca) density recorded with square pulses nor the normalized expressions of TMEM16A and Bestrophin-3 proteins differed significantly among the examined groups of cells. The early outward component of ICl(Ca) was significantly larger in subepicardial than in subendocardial cells in APVC setting. Applying a typical subepicardial AP as a command pulse resulted in a significantly larger early outward component in both subepicardial and subendocardial cells, compared to experiments when a typical subendocardial AP was applied.Inhibiting ICl(Ca) by 9-AC generated EADs at low stimulation rates and their incidence increased upon beta-adrenergic stimulation. 9-AC increased the short-term variability of repolarization also.We suggest a protective role for ICl(Ca) against risk of arrhythmias by reducing spatial and temporal heterogeneity of cardiac repolarization and EAD formation.

Limb-girdle congenital myasthenic syndrome in a Chinese family with novel mutations in MUSK gene and literature review

ObjectivesTo describe the clinical and genetic features of a Chinese congenital myasthenic syndromes (CMS) patient with two novel missense mutations in muscle specific receptor tyrosine kinase (MUSK) gene and review 15 MUSK-related CMS patients from 8 countries. MethodsThe patient was a 30-year-old man with chronic progressively proximal limb weakness for 22 years and diagnosed as muscular dystrophy before. Serum creatine kinase (CK) was normal. Repetitive nerve stimulation (RNS) test showed decrements at low rate stimulation. Weakness became worse after conventional doses of pyridostigmine. Mild multiple atrophy of thigh and leg muscle was observed in MRI. Open muscle biopsy and genetic analysis were performed. One hundred healthy individuals were set for control. ResultsMuscle biopsy showed mild variation in fiber size. Two missense mutations in MUSK gene (p.P650T and p.I795S) were identified in the patient. The mutation of p.I795S was identified in his father and p.P650T in his mother. Both of them were not detected among the healthy controls and predicted to be damaging or disease causing by prediction tools. ConclusionIn this study, we identified a limb-girdle CMS (LG-CMS) patient carrying two novel heterozygous missense mutations in MUSK gene. CMS related genes should be analyzed in patients with limb-girdle weakness, normal CK, decrement of CMAP at RNS and mild change in muscle biopsy or MRI.

Qualities of Single Electrode Stimulation as a Function of Rate and Place of Stimulation with a Cochlear Implant.

Although it has been shown previously that changes in temporal coding produce changes in pitch in all cochlear regions, research has suggested that temporal coding might be best encoded in relatively apical locations. The authors hypothesized that although temporal coding may provide useable information at any cochlear location, low rates of stimulation might provide better sound quality in apical regions that are more likely to encode temporal information in the normal ear. In the present study, sound qualities of single electrode pulse trains were scaled to provide insight into the combined effects of cochlear location and stimulation rate on sound quality. Ten long-term users of MED-EL cochlear implants with 31-mm electrode arrays (Standard or FLEX) were asked to scale the sound quality of single electrode pulse trains in terms of how "Clean," "Noisy," "High," and "Annoying" they sounded. Pulse trains were presented on most electrodes between 1 and 12 representing the entire range of the long electrode array at stimulation rates of 100, 150, 200, 400, or 1500 pulses per second. Although high rates of stimulation are scaled as having a Clean sound quality across the entire array, only the most apical electrodes (typically 1 through 3) were considered Clean at low rates. Low rates on electrodes 6 through 12 were not rated as Clean, whereas the low-rate quality of electrodes 4 and 5 were typically in between. Scaling of Noisy responses provided an approximately inverse pattern as Clean responses. High responses show the trade-off between rate and place of stimulation on pitch. Because High responses did not correlate with Clean responses, subjects were not rating sound quality based on pitch. If explicit temporal coding is to be provided in a cochlear implant, it is likely to sound better when provided apically. In addition, the finding that low rates sound clean only at apical places of stimulation is consistent with previous findings that a change in rate of stimulation corresponds to an equivalent change in perceived pitch at apical locations. Collectively, the data strongly suggest that temporal coding with a cochlear implant is optimally provided by electrodes placed well into the second cochlear turn.

Restoring sensitivity to interaural timing differences in bilateral cochlear implant listeners using multi-electrode stimulation

Identification and discrimination of sound sources in complex auditory environments is facilitated for normal-hearing listeners from access to interaural time differences (ITDs). For patients fitted with bilateral cochlear implants (BiCI), binaural sensitivity is harder to achieve due to several factors, including asynchronous interaural processing. BiCI listeners have shown good ITD sensitivity with low rates of electrical stimulation; however, low-rate delivery of ITD cues is unrealistic for the high-rate pulsatile stimulation required to achieve good speech understanding. One solution is to present a mix of high- and low-rate stimulation on different electrodes, preserving both speech recognition and sound localization ability. In the present study, a binaural benefit was observed in a mixed-rate strategy under direct electrical stimulation: ITD sensitivity was measured in a two-alternative forced-choice discrimination task, using seven multi-electrode conditions. We hypothesized that by introducing low-rate ITDs at a few electrodes alongside high-rate ITDs at remaining electrodes provides sufficient ITD cues for sound localization. The present data suggests the binaural system of BiCI listeners can extract pertinent cues to achieve ITD sensitivity even when high-rate ITD information is presented at the majority of the cochlear locations. This lends to a possibility in implementation of ITD cues to current processing strategies.

Interaural time difference sensitivity with high rate electrical pulse trains in bilateral cochlear implant users

Interaural time differences (ITDs) are an important cue for obtaining binaural hearing benefits. Bilateral cochlear implant (BiCI) users have shown poor ITD sensitivity when using clinical processors, but have some ITD sensitivity with carefully controlled stimuli presented using synchronized research processors. In BiCI users, low stimulation rates yield best ITD sensitivity, but declines as the stimulation rate increases. However, high rates are typically needed for good speech understanding, which poses a conundrum for maximizing the benefit of BiCIs. Aperiodic high-rate stimulation has been shown to promote ITD sensitivity. However, it is uncertain whether this improvement is due to changes in the loudness level, which may provide an envelope ITD cue. In this study, we tested this hypothesis by measuring ITD just noticeable differences (JNDs) with 4000-Hz electrical pulse trains. Pulse trains either had: (1) constant amplitude and rate; (2) aperiodic timing in the pulses; and (3) aperiodic timing + a random amplitude applied to each pulse. Results have implications in determining whether aperiodic high-rate stimulation can be useful for restoring ITD sensitivity. [Work supported by NIH-NIDCD (R01DC003083 to Ruth Litovsky) and NIH-NICHD (P30HD03352 to the Waisman Center).]

Human iPS cell model of type 3 long QT syndrome recapitulates drug-based phenotype correction.

Long QT syndrome is a potentially life-threatening disease characterized by delayed repolarization of cardiomyocytes, QT interval prolongation in the electrocardiogram, and a high risk for sudden cardiac death caused by ventricular arrhythmia. The genetic type 3 of this syndrome (LQT3) is caused by gain-of-function mutations in the SCN5A cardiac sodium channel gene which mediates the fast Nav1.5 current during action potential initiation. Here, we report the analysis of LQT3 human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). These were generated from a patient with a heterozygous p.R1644H mutation in SCN5A known to interfere with fast channel inactivation. LQT3 hiPSC-CMs recapitulated pathognomonic electrophysiological features of the disease, such as an accelerated recovery from inactivation of sodium currents as well as action potential prolongation, especially at low stimulation rates. In addition, unlike previously described LQT3 hiPSC models, we observed a high incidence of early after depolarizations (EADs) which is a trigger mechanism for arrhythmia in LQT3. Administration of specific sodium channel inhibitors was found to shorten action and field potential durations specifically in LQT3 hiPSC-CMs and antagonized EADs in a dose-dependent manner. These findings were in full agreement with the pharmacological response profile of the underlying patient and of other patients from the same family. Thus, our data demonstrate the utility of patient-specific LQT3 hiPSCs for assessing pharmacological responses to putative drugs and for improving treatment efficacies.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-016-0530-0) contains supplementary material, which is available to authorized users.

Interaction of electrically evoked activity with intrinsic dynamics of cultured cortical networks with and without functional fast GABAergic synaptic transmission.

The modulation of neuronal activity by means of electrical stimulation is a successful therapeutic approach for patients suffering from a variety of central nervous system disorders. Prototypic networks formed by cultured cortical neurons represent an important model system to gain general insights in the input–output relationships of neuronal tissue. These networks undergo a multitude of developmental changes during their maturation, such as the excitatory–inhibitory shift of the neurotransmitter GABA. Very few studies have addressed how the output properties to a given stimulus change with ongoing development. Here, we investigate input–output relationships of cultured cortical networks by probing cultures with and without functional GABAAergic synaptic transmission with a set of stimulation paradigms at various stages of maturation. On the cellular level, low stimulation rates (<15 Hz) led to reliable neuronal responses; higher rates were increasingly ineffective. Similarly, on the network level, lowest stimulation rates (<0.1 Hz) lead to maximal output rates at all ages, indicating a network wide refractory period after each stimulus. In cultures aged 3 weeks and older, a gradual recovery of the network excitability within tens of milliseconds was in contrast to an abrupt recovery after about 5 s in cultures with absent GABAAergic synaptic transmission. In these GABA deficient cultures evoked responses were prolonged and had multiple discharges. Furthermore, the network excitability changed periodically, with a very slow spontaneous change of the overall network activity in the minute range, which was not observed in cultures with absent GABAAergic synaptic transmission. The electrically evoked activity of cultured cortical networks, therefore, is governed by at least two potentially interacting mechanisms: A refractory period in the order of a few seconds and a very slow GABA dependent oscillation of the network excitability.

Stimulating on multiple electrodes can improve temporal pitch perception

Objective: The objective of this study was to test if stimulating multiple electrodes can improve temporal pitch ranking performance at low and high stimulation rates. Design: Temporal pitch cues are usually based on modifying the stimulation rate of the implant and thereby provide a continuum of pitches on a single electrode up to approximately 300 Hz. Study sample: Ten cochlear implant subjects were asked to pitch rank stimuli presented with direct electrical stimulation. The pulses were applied on one, three, six, or eleven electrodes. In one of the conditions the current amplitude of each pulse was randomly varied between 0 and 100%. Their frequency ranged from 100 up to 500 pps. Results: Listeners showed the previously reported performance pattern in most conditions with very good performance at the lowest standard rates and deteriorating performance to near chance level at the highest rate tested. Performance with eleven electrodes was significantly better than performance with one electrode at 500 pps. Conclusion: Stimulating on multiple electrodes can improve temporal pitch perception.

Modeling Binaural Responses in the Auditory Brainstem to Electric Stimulation of the Auditory Nerve

Bilateral cochlear implants (CIs) provide improvements in sound localization and speech perception in noise over unilateral CIs. However, the benefits arise mainly from the perception of interaural level differences, while bilateral CI listeners' sensitivity to interaural time difference (ITD) is poorer than normal. To help understand this limitation, a set of ITD-sensitive neural models was developed to study binaural responses to electric stimulation. Our working hypothesis was that central auditory processing is normal with bilateral CIs so that the abnormality in the response to electric stimulation at the level of the auditory nerve fibers (ANFs) is the source of the limited ITD sensitivity. A descriptive model of ANF response to both acoustic and electric stimulation was implemented and used to drive a simplified biophysical model of neurons in the medial superior olive (MSO). The model's ITD sensitivity was found to depend strongly on the specific configurations of membrane and synaptic parameters for different stimulation rates. Specifically, stronger excitatory synaptic inputs and faster membrane responses were required for the model neurons to be ITD-sensitive at high stimulation rates, whereas weaker excitatory synaptic input and slower membrane responses were necessary at low stimulation rates, for both electric and acoustic stimulation. This finding raises the possibility of frequency-dependent differences in neural mechanisms of binaural processing; limitations in ITD sensitivity with bilateral CIs may be due to a mismatch between stimulation rate and cell parameters in ITD-sensitive neurons.

Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location

Objective. Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. Approach. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Main results. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. Significance. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation.