Electrically Evoked Compound Action Potential Responses Research Articles

Novel Variant of FDXR as a Molecular Etiology of Postlingual Post-Synaptic Auditory Neuropathy Spectrum Disorder via Mitochondrial Dysfunction: Reiteration of the Correlation between Genotype and Cochlear Implantation Outcomes.

FDXR encodes the mitochondrial ferredoxin reductase, which is associated with auditory neuropathy spectrum disorder (ANSD) and optic atrophy. Only two studies have described FDXRrelated hearing loss. The auditory rehabilitation outcomes of this disease entity have not been investigated, and the pathophysiologic mechanism is not well elucidated. Here we report a hearingimpaired subject with co-segregation of the FDXR variant and post-synaptic type ANSD, who underwent cochlear implantation (CI) with favorable outcomes. We suggest a possible pathophysiologic mechanism of adult-onset ANSD via mitochondrial dysfunction. A 35-year-old woman was ascertained to have ANSD. Exome sequencing identified the genetic cause of hearing loss, and functional study measuring mitochondrial activity was performed to provide molecular evidence of pathophysiology. Expression of FDXR in the mouse cochlea was evaluated by immunohistochemistry. Intraoperatively, electrically-evoked compound action potential (ECAP) responses were measured, and mapping parameters were adjusted accordingly. Audiological outcomes were monitored for over 1 year. In lymphoblastoid cell lines (LCLs) carrying a novel FDXR variant, decreased ATP and MtMP levels and increased ROS levels were observed compared to control LCLs. These dysfunctions were restored by administering mitochondria isolated from umbilical cord mesenchymal stem cells, confirming the pathogenic potential of this variant via mitochondrial dysfunction. Partial ECAP responses during CI and FDXR expression in the mouse cochlea indicate that FDXR-related ANSD is postsynaptic. By increasing the pulse width during mapping, the patient's CI outcomes showed significant improvement over 1-year post-CI. Post-synaptic ANSD due to a novel FDXR variant linked to mitochondrial dysfunction was identified first in a Korean, and 1-year post CI outcomes were reported for the first time in the literature. Excellent audiologic results were obtained, and our results reiterate the correlation between genotype and CI outcomes in ANSD.

Absent Intraoperative Electrically Evoked Compound Action Potential Results during Cochlear Implant Surgery: Our Experience

Intraoperative electrically evoked compound action potential (ECAP) testing during cochlear implant surgery is used to assess the integrity of implant, proper placement of electrode array, auditory nerve stimulation and to use as a preliminary tool to start a map, especially for difficult-to-test population. Sometimes, irrespective of normal or abnormal anatomical structure of the inner ear, ECAP response can be absent in one or more recording electrodes intraoperatively due to many factors. This report presents four pediatric cases who underwent cochlear implantation at our center. One of the cases had a hypoplastic auditory nerve and the rest had normal inner ear anatomy. Intraoperatively, two of the cases had absent neural responses in all the electrodes whereas in the remaining two absent neural response was found in single and in three basal electrodes. Postoperatively, in all the cases, neural response had recovered, except the one with hypoplastic nerve, which recovered only in few electrodes.

Effect of congenital inner ear malformations (IEMs) on electrically evoked compound action potential (ECAP) responses in cochlear implant children.

The study was designed to assess the electrically evoked compound action potential (ECAP) responses in children with inner ear malformations compared to children with normal inner ear anatomy. The study included 235 prelingual deaf children who were implanted in cochlear implant unit in King Fahad University hospital-Imam Abdulrahman Bin Faisel University. Subjects were using either Cochlear Nucleus or Medel cochlear implant devices. We had 171 (64.5%) subjects with normal inner ear anatomy and 94 (35.5%) subjects with inner ear malformations (IEMs) and they were classified into 6 groups according to inner ear anatomy. Fourteen subjects (14.9%) subjects had enlarged vestibular aqueduct (EVA), 30 (32%) subjects had Mondini deformity, 25 (26.6%) subjects had incomplete partition type two (IPII), 9 (9.6%) subjects had incomplete partition type one (IPI) and 16 (17%) subjects had hypoplastic cochlea type III or IV. Intraoperative electrically evoked compound action potential (ECAP) responses were analyzed and compared in all subjects. Measurable ECAP responses can be elicited in patients with IEMs in most of the channels. Severe malformations can affect the prevalence of measuring ECAP and getting identifiable waveform morphology. Additionally, increased thresholds and lower slope of AGF was observed in IEMs specially in more severe malformations (e.g. IPI). IPI patients with better word recognition scores tended to show more identifiable ECAP measurements. This could suggest the presence of some correlation between ECAP responses and patients' performance after cochlear implantation.

Audiogram Configuration, Molecular Etiology, and Outcome of Cochlear Implantation in Postlingual Auditory Neuropathy Spectrum Disorder.

To explore the diverse molecular etiologies of postlingual auditory neuropathy spectrum disorder (ANSD) and report on the electrically evoked compound action potential (ECAP) thresholds and the outcome of cochlear implantation (CI). Patients with late-onset, progressive hearing loss who went through molecular genetic testing were enrolled. Type of sensorineural hearing loss (SNHL) was classified as flat, reverse-slope, midfrequency, downsloping, or ski slope. We identified postlingual ANSD subjects through diagnostic tracts applied differently depending on the degree of SNHL. For CI recipients, individual ECAP thresholds, postoperative speech perception abilities, and the genetic cause were analyzed. The detection rate of ANSD among patients with postlingual SNHL was 5.1% (15/293 probands). Diverse genetic etiologies were identified in 7 (46.6%) of the 15 postlingual ANSD subjects, the genetic cause being found exclusively in subjects with reverse-slope SNHL. The pattern of intraoperative ECAP responses was also diverse and showed some correlation with the genetic etiology. Despite the diverse molecular etiology and ECAP responses, CI in postlingual ANSD patients, including those with features involving the postsynaptic component, yielded significant improvements in speech understanding. This study proposes a differentiated diagnostic approach that focuses on both poor speech discrimination and reverse-slope hearing loss for the diagnosis of ANSD. Based on the improvement of speech understanding from all cochlear implantees with ANSD as well as the correlation between the genetic etiology and ECAP thresholds, we suggest that CI can significantly benefit ANSD subjects even those with unknown etiologies unless there is overt peripheral neuropathy.

Toward neural health measurements for cochlear implantation: The relationship among electrode positioning, the electrically evoked action potential, impedances and behavioral stimulation levels.

Estimating differences in neural health across different sites within the individual cochlea potentially enables clinical applications for subjects with a cochlear implant. The electrically evoked compound action potential (ECAP) is a measure of neural excitability that possibly provides an indication of a neural condition. There are many factors, however, that affect this measure and increase the uncertainty of its interpretation. To better characterize the ECAP response, its relationship with electrode positioning, impedances, and behavioral stimulation levels was explored. A total of 14 adult subjects implanted with an Advanced Bionics cochlear electrode array were prospectively followed up from surgery to 6 months postoperative. Insertion depth, distance to the modiolus, and distance to the medial wall were assessed for each electrode by postoperative CT analysis. ECAPs were measured intraoperatively and at three visits postoperatively on all 16 electrodes using the NRI feature of clinical programming software and characterized using multiple parameters. Impedances and behavioral stimulation levels were measured at every fitting session. Patterns in ECAPs and impedances were consistent over time, but high variability existed among subjects and between different positions in the cochlea. Electrodes located closer to the apex of the cochlea and closer to the modiolus generally showed higher neural excitation and higher impedances. Maximum loudness comfort levels were correlated strongly with the level of current needed to elicit a response of 100 μV ECAP. Multiple factors contribute to the ECAP response in subjects with a cochlear implant. Further research might address whether the ECAP parameters used in this study will benefit clinical electrode fitting or the assessment of auditory neuron integrity.

Effect of inner ear malformations on intraoperative ECAP thresholds and postoperative auditory performance.

ObjectivesThis study sought to characterize the influence of inner ear malformations (IEMs) on intraoperative electrically evoked compound action potential (ECAP) and auditory performance to better understand the underlying pathophysiology related to variabilities in cochlear implant (CI) outcomes that individuals with malformed cochlea may present.MethodsThe medical records of 222 ears implanted with Cochlear Nucleus CI were reviewed. Of the total, 64 ears had radiologic evidence of IEMs, and 158 ears were normal. Individuals with IEMs were grouped based on the severity of anomalies; 38 had mild IEMs (e.g., enlarged vestibular aqueduct, incomplete partition type II, etc.) and 26 had severe IEMs (e.g., cochlear nerve hypoplasia, common cavity, etc.). Intraoperative ECAP thresholds obtained via neural response telemetry (NRT) and the categories of auditory performance (CAP) scores measured at 12 months postoperative were compared and correlated.ResultsAbsent ECAP responses were more apparent in the IEM group. ECAP thresholds were significantly elevated in the severe IEM group, while the mild IEM group had ECAP thresholds comparable to the normal group. The mild IEM group achieved CAP scores similar to the normal control. Patients in the severe IEM group showed significantly lower CAP scores at 12 months postoperative. Significant negative relationships existed between ECAP thresholds and CAP scores obtained from all subjects.ConclusionMeasurable ECAP responses and NRT thresholds varied across groups. The inverse relationship between NRT thresholds and CAP scores may suggest that electrophysiological responses measured during surgery may potentially be indicative of postoperative performance in our CI population.Level of Evidence2b.

Potential Implications of Slim Modiolar Electrodes for Severely Malformed Cochleae: A Comparison With the Straight Array With Circumferential Electrodes.

ObjectivesMalformations of the inner ear account for approximately 20% of cases of congenital deafness. In current practice, straight arrays with circumferential electrodes (i.e., full-banded electrodes) are widely used in severely malformed cochleae. However, the unpredictability of the location of residual spiral ganglion neurons in such malformations argues against obligatorily using full-banded electrodes in all cases. Here, we present our experience of electrically evoked compound action potential (ECAP) and radiography-based selection of an appropriate electrode for severely malformed cochleae.MethodsThree patients with severely malformed cochleae, showing cochlear hypoplasia type II (CH-II), incomplete partition type I (IP-I), and cochlear aplasia with a dilated vestibule (CADV), respectively, were included, and the cochlear nerve deficiency (CND) was evaluated. A full-banded electrode (CI24RE(ST)) and slim modiolar electrode (CI632) were alternately inserted to compare ECAP responses and electrode position.ResultsIn patient 1 (CH-II with CND), who had initially undergone cochlear implantation (CI) using a lateral wall electrode (CI422), revision CI was performed due to incomplete insertion of CI422 and resultant unsatisfactory performance by explanting the CI422 and re-inserting the CI24RE(ST) and CI632 sequentially. Although both electrodes elicited reliable ECAP responses with correct positioning, CI24RE(ST) showed overall lower ECAP thresholds compared to CI632; thus, CI24RE(ST) was selected. In patient 2 (IP-I with CND), CI632 elicited superior ECAP responses relative to CI24RE(ST), with correct positioning of the electrode; CI632 was chosen. In patient 3 (CADV), CI632 did not elicit an ECAP response, while meaningful ECAP responses were obtained with the CI24RE(ST) array once correct positioning was achieved. All patients’ auditory performance markedly improved postoperatively.ConclusionThe ECAP and radiography-based strategy to identify an appropriate electrode may be useful for severely malformed cochleae, leading to enhanced functional outcomes. The practice of sticking to full-banded straight electrodes may not always be optimal for IP-I and CH-II.

Identifying Cochlear Implant Channels With Relatively Poor Electrode-Neuron Interfaces Using the Electrically Evoked Compound Action Potential.

The primary objective of this study was to quantify local (within ear) and global (between ear) variation in the cochlear implant (CI) electrode-neuron interface (ENI) using the electrically evoked compound action potential (ECAP). We tested the hypothesis that, within an ear, ECAP measures can be used to identify channels with presumed good and poor ENIs, which may be influenced by a combination of spiral ganglion neuron (SGN) density, electrode position, and cochlear resistivity. We also hypothesized that ECAP responses would reflect age-related differences in the global quality of the ENI between younger and older listeners who theoretically differ in SGN density. Data were obtained from 18 implanted ears (13 individuals) with Advanced Bionics HiRes 90K devices. Six participants (8 ears) were adolescents or young adults (age range: 14-32 years), and 7 participants (10 ears) were older adults (age range: 54-88 years). In each ear, single-channel auditory detection thresholds were measured on channels 2 through 15 in response to a spatially focused electrode configuration (steered quadrupolar; focusing coefficient = 0.9). ECAP amplitudes, amplitude growth function (AGF) slopes, and thresholds were assessed on a subset of channels in each ear in response to three interphase gaps (0, 7, and 30 µs). ECAP peak amplitudes were assessed on all channels between 2 and 15. AGFs and ECAP thresholds were measured on the two nonadjacent channels with the lowest and highest focused behavioral thresholds in each ear. ECAP responses were compared across low- and high-threshold channels and between younger and older CI listeners. Channels that were estimated to interface poorly with the auditory nerve (i.e., high-focused-threshold channels) had steeper ECAP AGF slopes, smaller dynamic ranges, and higher ECAP thresholds than channels with low focused thresholds. Younger listeners had steeper ECAP AGF slopes and larger ECAP peak amplitudes than older listeners. Moreover, younger listeners showed greater interphase gap sensitivity for ECAP amplitude than older listeners. ECAP responses may be used to quantify both local (within ear) and global (between ear) variation in the quality of the ENI. Results of this study support future investigation into the use of ECAP responses in site-selection CI programming strategies. The present results also support a growing body of evidence suggesting that adolescents and young adults with CIs may have denser populations of functional SGNs relative to older adults. Potential differences in global SGN integrity between younger and older listeners warrant investigation of optimal CI programming interventions based on their divergent hearing histories.

Usefulness of measuring electrically evoked auditory brainstem responses in children with inner ear malformations during cochlear implantation

Conclusions: EABR is a reliable and effective way of objectively confirming device function and implant-responsiveness of the peripheral auditory neurons up to the level of the brainstem in cases of inner ear malformation. Objective: To investigate the usefulness of measuring the intra-operative electrically evoked compound action potential (ECAP) and electrically evoked auditory brainstem response (EABR) in patients with and without congenital inner ear anomalies during cochlear implantation. Method: Thirty-eight consecutive children (40 ears) aged 5 or younger with congenital profound hearing loss. Twenty-four (25 ears) lacked congenital inner ear anomalies. The 14 patients (15 ears) with a malformation had common cavities (four ears), incomplete partition type I (three ears), cochlea hypoplasia type III (three ears), enlarged vestibular aqueduct (four ears), and cochlear nerve canal stenosis (one ear). Main outcome measures are ECAP and EABR responses. Results: Of the 25 ears lacking any malformation, 21, three, and one showed ‘Good’, ‘Variable’, and ‘No’ ECAP responses, respectively, and 24 and one showed ‘Good’ and ‘Variable’ intra-cochlear responses, respectively. Of the 15 ears with a malformation, two showed ‘Good’ ECAP responses, nine had ‘Variable’ ECAP responses, and four showed ‘No’ ECAP responses. Moreover, five showed ‘Good’ EABR responses and 10 showed ‘Variable’ EABR responses.

The relation between auditory-nerve temporal responses and perceptual rate integration in cochlear implants

The purpose of this study was to examine auditory-nerve temporal response properties and their relation to psychophysical threshold for electrical pulse trains of varying rates (“rate integration”). The primary hypothesis was that better rate integration (steeper slope) would be correlated with smaller decrements in ECAP amplitude as a function of stimulation rate (shallower slope of the amplitude-rate function), reflecting a larger percentage of the neural population contributing more synchronously to each pulse in the train. Data were obtained for 26 ears in 23 cochlear-implant recipients. Electrically evoked compound action potential (ECAP) amplitudes were measured in response to each of 21 pulses in a pulse train for the following rates: 900, 1200, 1800, 2400, and 3500 pps. Psychophysical thresholds were obtained using a 3-interval, forced-choice adaptive procedure for 300-ms pulse trains of the same rates as used for the ECAP measures, which formed the rate-integration function. For each electrode, the slope of the psychophysical rate-integration function was compared to the following ECAP measures: (1) slope of the function comparing average normalized ECAP amplitude across pulses versus stimulation rate (“adaptation”), (2) the rate that produced the maximum alternation depth across the pulse train, and (3) rate at which the alternating pattern ceased (stochastic rate). Results showed no significant relations between the slope of the rate-integration function and any of the ECAP measures when data were collapsed across subjects. However, group data showed that both threshold and average ECAP amplitude decreased with increased stimulus rate, and within-subject analyses showed significant positive correlations between psychophysical thresholds and mean ECAP response amplitudes across the pulse train. These data suggest that ECAP temporal response patterns are complex and further study is required to better understand the relative contributions of adaptation, desynchronization, and firing probabilities of individual neurons that contribute to the aggregate ECAP response.

Effect of ECAP-Based Choice of Stimulation Rate on Speech-Perception Performance

The objective determination of an optimal stimulation rate for CI users could save time and take the uncertainty out of choosing a rate based on patient preference. Electrically evoked compound action potential (ECAP) temporal response patterns vary across stimulation rates and cochlear regions, and could be useful in objectively predicting an optimal rate. Given that only one rate of stimulation can be used for current CI devices, we propose two potential ways to investigate whether a rate that produces stochastic ECAP responses (termed stochastic rate) can be used to predict an optimal stimulation rate. The first approach follows that of , which compared performance across three cochlear regions using limited electrode sets. This approach, which has inherent limitations, may provide insight into the effects of region-specific stochastic rates on performance. The second, more direct, approach is to compare speech perception for full-array maps that each uses a stochastic rate from a different region of the cochlea. Using both of these methods in a set of two acute experiments, the goal of the present study was to assess the effects of stochastic rate on speech perception. Speech-perception stimuli included the Hearing in Noise Test (HINT sentences), Consonant-Nucleus-Consonant (CNC) phonemes, and Iowa Medial Consonants. For Experiment 1, 22 ears in 20 CI recipients were tested in three map conditions (basal-only, middle-only, and apical-only electrode sets) using the subject's daily-use stimulation rate to first explore the level of performance possible with region-specific maps. A one-way repeated-measures analysis of variance (RM ANOVA) was used to examine the effect of electrode region on performance. A subset of nine subjects was tested with three additional maps (basal-only, middle-only, and apical-only electrode sets) using the region-specific stochastic rate, as measured in a previous study. A two-way RM ANOVA was used to assess the effects of electrode region and per-channel stimulation rate on performance for this subgroup. For Experiment 2, the same subset of nine subjects was tested with four full-array maps that each used either the daily-use stimulation rate or one of the stochastic rates. A one-way RM ANOVA was used to examine the effect of stimulation rate on performance. For Experiment 1, average performance with the daily-use rate and the stochastic rate was significantly better using the middle electrode set for HINT sentences and CNC phonemes. Perception of medial consonants was similar using the basal and middle electrode sets, and both of these were better than consonant perception with the apical region. For the subgroup of subjects tested with both the daily and stochastic rates, results revealed that stimulation rate did not have a significant effect on performance. For Experiment 2, results revealed no significant differences in performance using full-array maps with different stochastic rates or with the daily-use rate. Speech-perception scores were higher using the middle electrode set than with the basal or apical sets; however, this may have resulted from less spectral compression for the middle-region map. The effect of using stochastic rate as an optimal stimulation rate requires further investigation. A longer acclimatization period may be more likely to show differences in performance using stochastic rates versus daily-use rates.

Determining Electrically Evoked Compound Action Potential Thresholds

Current cochlear implants (CIs) have telemetry capabilities for measuring the electrically evoked compound action potential (ECAP). Neural Response Telemetry (Cochlear) and Neural Response Imaging (Advanced Bionics [AB]) can measure ECAP responses across a range of stimulus levels to obtain an amplitude growth function. Software-specific algorithms automatically mark the leading negative peak, N1, and the following positive peak/plateau, P2, and apply linear regression to estimate ECAP threshold. Alternatively, clinicians may apply expert judgments to modify the peak markers placed by the software algorithms, or use visual detection to identify the lowest level yielding a measurable ECAP response. The goals of this study were to: (1) assess the variability between human and computer decisions for (a) marking N1 and P2 and (b) determining linear-regression threshold (LRT) and visual-detection threshold (VDT); and (2) compare LRT and VDT methods within and across human- and computer-decision methods. ECAP amplitude-growth functions were measured for three electrodes in each of 20 ears (10 Cochlear Nucleus® 24RE/CI512, and 10 AB CII/90K). LRT, defined as the current level yielding an ECAP with zero amplitude, was calculated for both computer- (C-LRT) and human-picked peaks (H-LRT). VDT, defined as the lowest level resulting in a measurable ECAP response, was also calculated for both computer- (C-VDT) and human-picked peaks (H-VDT). Because Neural Response Imaging assigns peak markers to all waveforms but does not include waveforms with amplitudes less than 20 μV in its regression calculation, C-VDT for AB subjects was defined as the lowest current level yielding an amplitude of 20 μV or more. Overall, there were significant correlations between human and computer decisions for peak-marker placement, LRT, and VDT for both manufacturers (r = 0.78-1.00, p < 0.001). For Cochlear devices, LRT and VDT correlated equally well for both computer- and human-picked peaks (r = 0.98-0.99, p < 0.001), which likely reflects the well-defined Neural Response Telemetry algorithm and the lower noise floor in the 24RE and CI512 devices. For AB devices, correlations between LRT and VDT for both peak-picker methods were weaker than for Cochlear devices (r = 0.69-0.85, p < 0.001), which likely reflect the higher noise floor of the system. Disagreement between computer and human decisions regarding the presence of an ECAP response occurred for 5 % of traces for Cochlear devices and 2.1 % of traces for AB devices. Results indicate that human and computer peak-picking methods can be used with similar accuracy for both Cochlear and AB devices. Either C-VDT or C-LRT can be used with equal confidence for Cochlear 24RE and CI512 recipients because both methods are strongly correlated with human decisions. However, for AB devices, greater variability exists between different threshold-determination methods. This finding should be considered in the context of using ECAP measures to assist with programming CIs.

Electrically Evoked Compound Action Potential Measures for Virtual Channels Versus Physical Electrodes

The number of distinct pitch percepts for cochlear implant (CI) listeners is somewhat limited by the number of physical electrodes in the array. Newer-generation CIs have the capability to potentially increase this number by stimulating areas of the cochlea between the physical electrodes. Currently, this is achieved by electrically coupling adjacent electrodes or by simultaneously activating two electrodes with independent current sources (i.e., current steering). Presumably, either type of dual-electrode stimulation will generate neural excitation patterns that are intermediate to those generated by either physical electrode alone (henceforth termed virtual channel). However, it is not clear whether virtual-channel stimulation yields neural recruitment patterns with similar shapes and rates of growth as compared with each physical electrode alone. The purpose of this study was to compare basic electrically evoked compound action potential (ECAP) measures for physical electrodes and virtual channels to determine whether properties of the respective excitation patterns were similar. Data were collected for 12 adult CI recipients (six Nucleus Freedom CI24RE, two Advanced Bionics HiResolution 90K, and four Advanced Bionics CII). ECAP responses were measured for a set of three adjacent physical electrodes and two corresponding intermediate virtual channels (e.g., physical electrodes 4, 5, and 6 and virtual channels 4 + 5 and 5 + 6) at three positions along the electrode array (basal, middle, and apical). Virtual channels for Nucleus subjects were produced via electrical coupling of adjacent electrode pairs (dual-electrode mode). For Advanced Bionics subjects, virtual channels were produced via simultaneous, in-phase stimulation of adjacent electrode pairs with 50% of the total current delivered to each electrode in the pair. Specific ECAP measures were as follows: (1) threshold and slope of the input/output functions, (2) amplitude for a masker-probe interval of 1500 μsecs (measure of refractory recovery), and (3) relative location of spread of excitation (SOE) functions among virtual channels and adjacent physical electrodes. Measures for virtual channels were compared with those for the flanking physical electrodes using a multivariate analysis of variance. There were no statistically significant differences between physical electrodes and virtual channels for ECAP thresholds, slope of the input/output function, or refractory recovery. On average, SOE functions for the virtual channels were spatially located approximately halfway between SOE functions for the adjacent physical electrodes. Results from this study suggest that virtual channels produce neural recruitment patterns with properties similar to those elicited by the adjacent physical electrodes.

Effect of Stimulus and Recording Parameters on Spatial Spread of Excitation and Masking Patterns Obtained With the Electrically Evoked Compound Action Potential in Cochlear Implants

Spread of excitation within the cochlea in response to electrical stimulation can be measured with the electrically evoked compound action potential (ECAP). Different spread of excitation measurement techniques have been reported in the literature. One method uses a fixed stimulus location while varying the recording electrode along the length of the implanted array. This results in a relatively coarse estimate of spatial spread (SS) along the cochlea. Another method uses a forward-masking paradigm to evaluate the relative overlap of stimulated neural populations between electrodes. Both the probe and recording electrodes are fixed in location while a masker stimulus is systematically applied across electrodes. This method, which yields a more precise estimate of spatial excitation patterns, is termed spatial masking (SM). Five experiments were conducted to examine potential effects of stimulus and/or recording parameters on SS and SM patterns. Experiment 1 examined whether SS patterns were systematically broader than SM patterns across electrodes and subjects. Experiments 2 and 3 evaluated the effects of stimulus level on SS and SM patterns, respectively, to determine whether increased stimulus level systematically resulted in broader patterns. Experiment 4 evaluated whether recording electrode location affected SM patterns, and Experiment 5 evaluated whether SM patterns varied significantly across repeated trials within a test session. Data were collected for 27 ears in 26 adult and teenage subjects (N = 6 ears with Advanced Bionics CII, N = 8 ears with Advanced Bionics HiRes 90K, N = 10 ears with Nucleus 24R[CS], N = 3 ears with Nucleus 24RE[CA] Freedom). A standard forward-masking subtraction paradigm was used for all ECAP measures. For SS patterns, the masker and probe were fixed on the same electrode at the same level while the recording electrode varied across the remaining electrodes in the array. For SM patterns, the probe and recording locations were fixed while the masker location varied across all electrodes except the recording electrode. In experiment 1, SS patterns were broader than SM patterns. Subjects with Advanced Bionics devices exhibited relatively broad patterns for both measures, whereas Nucleus subjects typically exhibited narrower SM functions relative to SS functions. In experiments 2 and 3, there was a significant effect of stimulus level on the spread of both SS and SM patterns in roughly one-third of measures in each experiment. In experiment 4, there was a significant effect of recording electrode location on the width/spread of SM patterns for only 11.5% of comparisons. In experiment 5, there were no significant differences in SM amplitudes across repeated trials for 94% of comparisons, which suggests that ECAP measures are highly robust within a test session. Results showed that SS functions were generally broader than SM functions, which suggests that SS measures reflect volume conduction of the ECAP response along the length of the cochlea. Differences in the spread of SM functions across devices are likely due to differences in modiolar proximity between the respective electrode array designs. Stimulus level had a more significant effect on the spread of SM functions than recording electrode location. Finally, ECAP measures were shown to be highly stable across repeated measurements within a test session; however, repeatability was not assessed across sessions or over extended time intervals.

Using Evoked Compound Action Potentials to Assess Activation of Electrodes and Predict C-Levels in the Tempo+ Cochlear Implant Speech Processor

In this study, we analyze how electrically evoked compound action potential (ECAP) responses can be used to assess whether electrodes should be activated in the map and to estimate C levels in the Med-El Tempo+ Cochlear Implant Speech Processor. ECAP thresholds were measured using the ECAP Recording System of the Pulsar CI implant. Twenty-one postlingually and 28 prelingually deafened patients participated in this study. The relationship between ECAP responses and the activation of electrodes was analyzed. Because an error in the estimation of T levels (behavioral thresholds) has less effect on hearing quality than an error in the estimation of C levels in the Tempo+ cochlear implant speech processor (maximum comfort levels), correlation and regression analyses were performed between ECAP thresholds and C levels. The observation of an evoked potential generally implied that the electrode was activated because only 3.5% of electrodes that yielded measurable evoked responses were deactivated, because of collateral stimulations or an unpleasant hearing sensation. In contrast, the absence of an evoked potential did not imply that an electrode should be deactivated, because 20% of these electrodes provided a useful auditory sensation. ECAP responses did not predict the absolute behavioral comfort levels because of the excessive error between behavioral C levels and those derived from ECAP thresholds (the mean relative error is 43.78%). However, by applying a normalization procedure, ECAP measurements allowed the C-level profile to be predicted with a mean relative error of 6%; that is, they provided useful data to determine the C level of each electrode relative to the average C level of the patient. ECAP is a reliable and an useful objective measurement that can assist in the fitting of the Tempo+ cochlear implant speech processor. From results presented in this work, a protocol is proposed for fitting this cochlear implant system. This protocol facilitates appropriate cochlear implant fitting, particularly for children or uncooperative patients.

Neural adaptation and the ECAP response threshold: A pilot study

The electrically evoked compound action potential (ECAP) amplitude resulting from a train of pulses of finite duration (100 ms or 200 ms) was found to vary inversely to the stimulation rate (pulse rate), corroborating well with neural adaptation results from a previous study (Dillier et al., 2005). Amplitude growth functions based on these adapted responses yield thresholds (TNRT) that increase with increasing pulse rate, contrary to behavioural thresholds, which are known to vary inversely with the stimulation rate. Adaptation effects are therefore a confounding factor that must be accounted for when attempting to compare behavioural and objective measures. Copyright © 2009 John Wiley & Sons, Ltd.

Effects of temporal properties on compound action potentials in response to amplitude-modulated electric pulse trains in guinea pigs

The electrically evoked compound action potential (ECAP) of the auditory nerve in response to amplitude-modulated pulse trains varies over time, but the response amplitudes are not linearly proportional to the level of stimulus pulses. At least two mechanisms could contribute to the deviations of the ECAP response pattern from that of the stimulus envelope. The first mechanism is time-invariant or stationary that reflects the non-linear growth of response amplitude with changes in stimulus level that is evident in the response to single pulses. This can be considered a time-invariant or stationary effect. The second mechanism is time-variant or non-stationary and reflects neural refractoriness and adaptation. The purpose of this study was to characterize the auditory nerve responses to amplitude-modulated pulse trains and also to evaluate the extent to which the stationary and non-stationary effects may contribute to those responses. ECAP amplitudes were predicted from single-pulse growth functions of the auditory nerve to account for time-invariant effects. Linear regression was performed on the measured vs. predicted ECAP amplitudes to quantify the discrepancies between the two datasets, thereby separating the influence of non-linear growth from time-varying effects on ECAP amplitudes. The results demonstrated a bandpass function of the modulated response amplitudes, with a low-cutoff modulation frequency at 300 Hz and a high-cutoff modulation frequency at 800 Hz, depending on the carrier pulse rate. The relative contribution of the temporal effects on ECAP amplitudes is greatest at low stimulus levels and low modulation depths.

A telemetria de respostas neurais no sistema de implante coclear multicanal nucleus 24: revisão da literatura

A telemetria de respostas neurais (NRT) é uma nova técnica disponível no implante coclear Nucleus 24 (Cochlear Corporation) que permite o registro do potencial de ação composto eletricamente evocado (ECAP) peri ou pós-opertoriamente, utilizando apenas os equipamentos normalmente necessários para a programação do processador de fala do implante coclear. O objetivo deste artigo é descrever o procedimento da NRT e algumas de suas aplicações clínicas e de pesquisa. A literatura relata que a técnica da NRT possui algumas vantagens sobre outros procedimentos objetivos e que as respostas do ECAP podem ser úteis para estimar limiares e níveis de máximo conforto para a estimulação elétrica. Outras pesquisas são necessárias para verificar como estas medidas podem ser utilizadas no estudo das propriedades das estruturas remanescentes do nervo coclear.

Auditory response to intracochlear electric stimuli following furosemide treatment

The influence of functional hair cells on electrical stimulation of the auditory nerve is an important issue as individuals with significant residual hearing are now cochlear implant candidates. Previous work has shown that chemical deafening during the course of acute experiments changes the auditory nerve’s responses to electrical stimulation [Third Quarterly Progress Report, NIH contract N01-DC-9-2106 (2000), Final Report, NIH Contract N01-DC-9-2106 (2002)]. This study extended that work by investigating the changes and subsequent recovery following furosemide injections which reversibly impair hair-cell function [Hear. Res. (1980) 79–89; Hear. Res. 14 (1984) 305–314, J. Physiol. 347 (1984) 685–696; Hear. Res. 71 (1993) 202–207]. Acoustic sensitivity of guinea pig subjects was repeatedly monitored with the click-evoked compound action potential. Responses to single biphasic electric pulses and biphasic electric pulse trains delivered by a monopolar intracochlear electrode were also repeatedly assessed using the electrically evoked compound action potential (ECAP). Our measures demonstrated a clear relationship between the state of hair-cell function and ECAP responses, as changes in the latter coincided with the loss or recovery of acoustic sensitivity. ECAP growth functions demonstrated increased slope and increased maximum (saturation) amplitude. Both trends were reversible and followed approximately the time course of post-furosemide hearing recovery. Additional changes were observed using electric pulse-train stimulation: (1) the magnitude of ECAP amplitude alternation (observed in response to successive stimulus pulses) increased, (2) the degree of ECAP adaptation (measured 80–100 ms after pulse-train onset) increased, and (3) the degree of refractoriness (measured by the ratio of ECAP amplitudes to the second and first pulses) tended to increase. All these trends are consistent with the hypothesis that functional hair cells desynchronize the population of auditory nerve fibers, thereby changing the electrically evoked responses. Viable hair cells may therefore provide positive effects on auditory response to electric stimuli delivered to implant patients with residual hearing, as they may enhance the random activity of the stimulated nerve.

The neuronal response to electrical constant-amplitude pulse train stimulation: additive Gaussian noise

Experimental results from humans and animals show that electrically evoked compound action potential (EAP) responses to constant-amplitude pulse train stimulation can demonstrate an alternating pattern, due to the combined effects of highly synchronized responses to electrical stimulation and refractory effects (Wilson et al., 1994). One way to improve signal representation is to reduce the level of across-fiber synchrony and hence, the level of the amplitude alternation. To accomplish this goal, we have examined EAP responses in the presence of Gaussian noise added to the pulse train stimulus. Addition of Gaussian noise at a level approximately −30 dB relative to EAP threshold to the pulse trains decreased the amount of alternation, indicating that stochastic resonance may be induced in the auditory nerve. The use of some type of conditioning stimulus such as Gaussian noise may provide a more ‘normal’ neural response pattern.