Electrically Evoked Compound Action Potential Amplitude Research Articles

Intraoperative Compound Action Potentials as a Predictor of Postoperative Cortical Auditory Evoked Potentials in Cochlear Implant Users.

Electrically evoked cortical auditory evoked potentials (ECAEPs) are central brain responses to auditory stimuli that correlate with post-operative cochlear implant (CI) hearing outcomes. They differ from electrically evoked compound action potentials (ECAPs) which are peripheral responses that can be elicited intraoperatively and may also predict CI hearing outcomes. It is not known to what degree ECAP and ECAEP responses are associated with each other. Such a correlation, if present, may allow for an earlier and more accurate prediction of post-operative hearing outcomes. This retrospective study involved 42 adult CI users. Threshold levels and amplitude growth function slopes of intraoperative ECAPs were compared to the latencies and peak-to-peak amplitudes of postoperative ECAEP responses at three different cochlear electrode array sites (apical, medial, and basal). A weak positive relationship was found between intraoperative ECAP thresholds and ECAEP N1-P2 peak-to-peak amplitude (r=0.301, p=0.005). Time between ECAP and ECAEP measurements was weakly correlated with P1-N1 peak-to-peak amplitude (r=0.321, p=0.002) and ECAEP N1-P2 peak-to-peak amplitude (r=0.340, p=0.001). ECAP amplitude growth function (AGF) slopes varied by electrode location (χ²=26.701, df = 2, p=0. 000002). These results suggest that intraoperative ECAP responses do not robustly predict postoperative ECAEP responses, providing caution against the use of ECAPs as a predictive tool for CI hearing outcomes.

Age-related changes in gap detection thresholds in adult cochlear-implant users: Effects of stimulus level and electrode-to-neural interface

Aging is associated with reduced sensitivity to brief temporal gaps in auditory stimuli. Although gap detection is a relative strength among late-deafened cochlear-implant users, aging and electrode-to-neural interface (ENI) factors may contribute to temporal processing difficulties. Because aging may negatively impact perception particularly at very low and very high input levels, we hypothesized larger gap detection thresholds (GDTs) at poor-ENI electrodes and an interaction between age and level such that GDT improvement with increased level would be less evident in older listeners. GDTs were measured on three electrodes selected to span a range of good-to-poor ENI based on electrically-evoked compound action potential amplitude growth or threshold sensitivity to increased pulse rate. GDTs were assessed using constant-amplitude single-electrode 1000-pps pulse trains presented at 40/60/80/100% dynamic range. In preliminary data (N = 4), GDTs averaged 3 ms at 100%DR and 40 ms at 40%DR. Listeners with better average ENI metrics displayed better GDTs. Within-subject, an advantage for best-ENI electrode over poorer-ENI electrodes was evident only at low levels. Finding an interaction between age and level such that temporal processing is impaired at both low and high (but not mid) levels for older listeners may help elucidate the contributions of peripheral versus central factors.

The Effects of Stimulus Repetition Rate on Electrically Evoked Auditory Brainstem Potentials in Postlingually Deafened Adult Cochlear Implant Recipients.

Background: By using outcome prediction scores, it is possible to distinguish between good and poor performers with cochlear implants (CI) after CI implantation. The reasons for poor performance, despite good basic conditions, can be manifold. On the one hand, the postoperative fitting may be inadequate; on the other, neurophysiological disease processes may impair speech understanding with a CI. These disease processes are not yet fully understood. In acoustics, it is known that the auditory brainstem responses (ABR) and their latencies and amplitudes allow differential diagnosis based on reference values for normal-hearing individuals. The aim of this study was to provide reference values for electrically evoked brainstem responses (EABRs) in terms of rate-dependent latencies and amplitudes. Methods: 20 ears of 18 experienced adult CI recipients with a predicted and measured good postoperative word recognition score were recruited from the clinic's patient pool. In the same stimulation mode and intensity we measured latencies and interpeak-latencies of EABRs and electrically evoked compound action potentials (ECAPs). With a defined supra-threshold stimulation intensity above the individual ECAP threshold, we applied stimulation at several rates between 11 and 91 stimuli per second. Results: We found rate dependences for EABR latency t3 and t5 in the order of 0.19 ms and 0.37 ms, respectively, while ECAP was not affected by rate. Correspondingly, the interpeak intervals' rate dependences for t5-t1, t5-t3 and t3-t1 were of the order of 0.37 ms, 0.18 ms and 0.19 ms. Comparing the EABR amplitudes between the stimulation rates 11/s and 81/s, we found that at 81/s the amplitudes were significantly reduced down: to 73% for A3 and 81% for A5. These rate dependences of latency and amplitude in EABR have characteristics comparable to those of acoustic ABR. Conclusions: These data may serve to provide reference values for EABR and ECAP latencies, interpeak intervals and amplitudes with respect to stimulation rate. Altered response patterns of ECAPs and EABRs to normalised stimulation modes could be used in the future to describe and classify neuropathological processes in a better-differentiated way.

Characteristics of responsiveness of cochlear nerve to electrical stimulation in patients with cochlear nerve deficiency

Objectives: This study aimed to evaluate the responsiveness of cochlear nerve to electrical stimulation in patients with cochlear nerve deficiency(CND), to compare their results with those measured in implanted children with normal-sized cochlear nerves, and to investigate the characteristics of the cochlear nerve injury of children with CND. Methods: Participants were children who underwent cochlear implantation at Shandong Provincial ENT Hospital from January 2012 to January 2020, including CND group and control group. The CND group included 51 subjects (male:20; female: 31) who were diagnosed with CND and had normal cochlea. For the CND group, four children had been bilaterally implanted, the mean implantation age was (2.7±1.5) years old. The control group included 21 subjects (male:10; femal:11) who had normal-sized cochlear nerve and normal cochlea. For the control group, all children had been unilaterally implanted except one, and the mean implantation age was (3.0±1.9)years old. Three subjects in the CND group used CI422 electrode arrays, and all the other subjects used CI24RECA/CI512 electrode arrays. The electrically evoked compound action potentials (ECAP) had been tried to record for each electrode using Custom Sound EP software (v. 4.3, Cochlear Ltd.) at least six months post first activation. Furthermore, ECAP amplitude growth functions (AGF) were measured at multiple electrode locations across the electrode array. Generalized linear mixed effect models with the subject group and electrode location as the fixed effects and subjects as the random effect were used to compare results of ECAP measurements. Results: In the control group, ECAP could been recorded at all electrodes (100%), but it could only be recorded in 71% (859/1 210) electrodes in the CND group. Additionally, the percentage of electrodes with measurable ECAP decreased from electrode 1 to electrode 22 in the CND group. Compared to the control group, the ECAP thresholds significantly increased, the ECAP amplitudes and AGF slopes significantly decreased, and the ECAP latency significantly increased in the CND group (P<0.01). GLMM showed that the stimulating site had a significant effect on the ECAP threshold, maximum amplitude, and AGF slope (P<0.01), but had no significant effect on the ECAP latency (P>0.05) in the CND group. However, the stimulating site had no significant effects on the ECAP measurements in the control group. Furthermore, the functional status of cochlear nerve varied greatly among CND group. From electrode 1 to electrode 22, the ECAP thresholds gradually increased, the ECAP maximum amplitudes and AGF slopes gradually decreased in the CND group. Conclusion: Compared with patients with normal-sized cochlear nerve, not only the number of residual spinal ganglion neurons reduce,but also the function of spinal ganglion neurons damages in CND patients. The degree of cochlea nerve deterioration varies greatly among CND patients. Generally, the deterioration of cochlear nerve tends to increase from the basal to the apical site of the cochlea.

SpeedCAP: An Efficient Method for Estimating Neural Activation Patterns Using Electrically Evoked Compound Action-Potentials in Cochlear Implant Users.

Electrically evoked compound action-potentials (ECAPs) can be recorded using the electrodes in a cochlear implant (CI) and represent the synchronous responses of the electrically stimulated auditory nerve. ECAPs can be obtained using a forward-masking method that measures the neural response to a probe and masker electrode separately and in combination. The panoramic ECAP (PECAP) analyses measured ECAPs obtained using multiple combinations of masker and probe electrodes and uses a nonlinear optimization algorithm to estimate current spread from each electrode and neural health along the cochlea. However, the measurement of ECAPs from multiple combinations of electrodes is too time consuming for use in clinics. Here, we propose and evaluate SpeedCAP, a speedy method for obtaining the PECAP measurements that minimizes recording time by exploiting redundancies between multiple ECAP measures. In the first study, 11 users of Cochlear Ltd. CIs took part. ECAPs were recorded using the forward-masking artifact-cancelation technique at the most comfortable loudness level (MCL) for every combination of masker and probe electrodes for all active electrodes in the users' MAPs, as per the standard PECAP recording paradigm. The same current levels and recording parameters were then used to collect ECAPs in the same users with the SpeedCAP method. The ECAP amplitudes were then compared between the two conditions, as were the corresponding estimates of neural health and current spread calculated using the PECAP method previously described by Garcia et al. The second study measured SpeedCAP intraoperatively in 8 CI patients and with all maskers and probes presented at the same current level to assess feasibility. ECAPs for the subset of conditions where the masker and probe were presented on the same electrode were compared with those obtained using the slower approach leveraged by the standard clinical software. Data collection time was reduced from ≈45 to ≈8 minutes. There were no significant differences between normalized root mean squared error (RMSE) repeatability metrics for post-operative PECAP and SpeedCAP data, nor for the RMSEs calculated between PECAP and SpeedCAP data. The comparison achieved 80% power to detect effect sizes down to 8.2% RMSE. When between-participant differences were removed, both the neural-health (r = 0.73) and current-spread (r = 0.65) estimates were significantly correlated (p < 0.0001, df = 218) between SpeedCAP and PECAP conditions across all electrodes, and showed RMSE errors of 12.7 ± 4.7% and 16.8 ± 8.8%, respectively (with the ± margins representing 95% confidence intervals). Valid ECAPs were obtained in all patients in the second study, demonstrating intraoperative feasibility of SpeedCAP. No significant differences in RMSEs were detectable between post- and intra-operative ECAP measurements, with the comparison achieving 80% power to detect effect sizes down to 13.3% RMSE. The improved efficiency of SpeedCAP provides time savings facilitating multi-electrode ECAP recordings in routine clinical practice. SpeedCAP data collection is sufficiently quick to record intraoperatively, and adds no more than 8.2% error to the ECAP amplitudes. Such measurements could thereafter be submitted to models such as PECAP to provide patient-specific patterns of neural activation to inform programming of clinical MAPs and identify causes of poor performance at the electrode-nerve interface of CI users. The speed and accuracy of these measurements also opens up a wide range of additional research questions to be addressed.

A phenomenological computational model of the evoked action potential fitted to human cochlear implant responses.

There is a growing interest in biomedical engineering in developing procedures that provide accurate simulations of the neural response to electrical stimulus produced by implants. Moreover, recent research focuses on models that take into account individual patient characteristics.We present a phenomenological computational model that is customized with the patient’s data provided by the electrically evoked compound action potential (ECAP) for simulating the neural response to electrical stimulus produced by the electrodes of cochlear implants (CIs). The model links the input currents of the electrodes to the simulated ECAP.Potentials and currents are calculated by solving the quasi-static approximation of the Maxwell equations with the finite element method (FEM). In ECAPs recording, an active electrode generates a current that elicits action potentials in the surrounding auditory nerve fibers (ANFs). The sum of these action potentials is registered by other nearby electrode. Our computational model emulates this phenomenon introducing a set of line current sources replacing the ANFs by a set of virtual neurons (VNs). To fit the ECAP amplitudes we assign a suitable weight to each VN related with the probability of an ANF to be excited. This probability is expressed by a cumulative beta distribution parameterized by two shape parameters that are calculated by means of a differential evolution algorithm (DE). Being the weights function of the current density, any change in the design of the CI affecting the current density produces changes in the weights and, therefore, in the simulated ECAP, which confers to our model a predictive capacity.The results of the validation with ECAP data from two patients are presented, achieving a satisfactory fit of the experimental data with those provided by the proposed computational model.

Toward a method of achieving balanced stimulation of bilateral auditory nerves: Evidence from children receiving matched and unmatched bilateral cochlear implants simultaneously

ObjectivesTo identify whether mismatched bilateral cochlear implants compromise balanced stimulation of the two auditory nerves and establish asymmetric hearing in children. MethodsBehavioural and electrophysiological measures were completed in 47 children receiving bilateral CIs in the same surgery (simultaneously): 27 children received a peri‑modiolar N24RE array in one ear and a 422 anti-modiolar array in the other (experimental group) and 20 children received 2 peri‑modiolar arrays (control group). Differences in current levels between the two devices were measured by electrically evoked compound action potentials (ECAPs) at the time of surgery. These data were compared with minimum and maximum comfortably loud levels programmed in each speech processor (T-levels, C-levels, respectively) after 12 months of bilateral CI use. Asymmetries in functional hearing between arrays were measured in open set speech perception testing between 3 to 5 years of CI use. ResultsHigher current levels were required from the anti-modiolar than peri‑modiolar array to evoke balanced interaural ECAP amplitudes (mismatched group: mean ± SD difference: -9.9 ± 22.6; matched group: -0.8 ± 26.5). This difference was larger in the experimental group than control group (t = -2.51; p = 0.016) and remained constant with increases in current level from ECAP threshold to maximum amplitudes (dynamic range) in many but not all children in both groups. T and C-levels were poorly predictive of levels needed to evoke balanced ECAP amplitudes in children with mismatched devices (F(1, 312) = 1.3, p = 0.263). Speech perception scores were more asymmetric between ears in children using bilateral mismatched arrays (mean ± SD: 73.8 ± 16.4 at the peri‑modiolar array; 57.7 ± 26.4 at the anti-modiolar array), compared to children with bilateral matched arrays (right ear: 78.0 ± 10.4; left ear: 74.9 ± 13.5). ConclusionHigher current level requirements at the anti-modiolar array compared to the peri‑modiolar array in children with bilateral mismatched CIs are not fully accounted for in device programming. Mismatched electrodes in children receiving bilateral cochlear implants increases the risk of asymmetric hearing.

Using the electrically-evoked compound action potential (ECAP) interphase gap effect to select electrode stimulation sites in cochlear implant users

Studies in cochlear implanted animals show that the IPG Effect for ECAP growth functions (i.e., the magnitude of the change in ECAP amplitude growth function (AGF) slope or peak amplitude when the interphase gap (IPG) is increased) can be used to estimate the densities of spiral ganglion neurons (SGNs) near the electrode stimulation and recording sites. In humans, the same ECAP IPG Effect measures correlate with speech recognition performance. The present study examined the efficacy of selecting electrode sites for stimulation based on the IPG Effect, in order to improve performance of CI users on speech recognition tasks.We measured the ECAP IPG Effect for peak amplitude in adult (>18 years old) CI users (N= 18 ears), and created experimental programs to stimulate electrodes with either the highest or lowest ECAP IPG Effect for peak amplitude. Subjects also listened to a program without any electrodes deactivated. In a subset of subject ears (11/18), we compared performance differences between the experimental programs to post-operative computerized tomography (CT) scans to examine underlying factors that might contribute to the efficacy of an electrode site-selection approach.For sentences-in-noise, average performance was better when subjects listened to the experimental program that stimulated electrodes with the highest rather than the lowest IPG Effect for ECAP peak amplitude. A similar pattern was noted for transmission and perception of consonant place cues in a consonant recognition task. However, on average, performance when listening to a program with higher IPG Effect values was equal to that when listening with all electrodes activated. Results also suggest that scalar location (scala tympani or vestibuli) should be considered when using an ECAP-based electrode site-selection procedure to optimize CI performance.

Correlation of Electrically Evoked Compound Action Potential Amplitude Growth Function Slope and Anamnestic Parameters in Cochlear Implant Patients-Identification of Predictors for the Neuronal Health Status.

Cochlear implants (CI) are the treatment of choice in profoundly deaf patients. Measuring the electrically evoked compound action potential (ECAP) has become an important tool for verifying the function of the spiral ganglion neurons (SGN), which are the target cells of the CI stimulation. ECAP measurement is only possible after electrode insertion. No information about the neuronal health status is available before cochlear implantation. We investigated possible correlations between the ECAP amplitude growth function (AGF) slope and anamnestic parameters to identify possible predictors for SGN health status and therefore for CI outcome. The study included patients being implanted with various electrode array lengths. Correlation analysis was performed for the mean AGF slope of the whole array, for separate electrodes as well as for grouped electrodes of the apical, medial, and basal region, with duration of deafness, age at implantation, residual hearing (grouped for electrode length), and etiology. The mean ECAP AGF slopes decreased from apical to basal. They were not correlated to the length of the electrode array or any etiology. For the mean of the full array or when grouped for the apical, middle, and basal part, the ECAP AGF slope was negatively correlated to the duration of hearing loss and the age at implantation. Since a significant negative correlation of the ECAP AGF slope and age at cochlear implantation and duration of deafness was observed, this study supports the statement that early implantation of a CI is recommended for sensorineural hearing loss. Additional factors such as the cochlear coverage and insertion angle influence the ECAP AGF slope and performance of the patient and should be included in future multifactorial analysis to study predictive parameters for the CI outcome.

Electrophysiological Estimates of the Electrode-Neuron Interface Differ Between Younger and Older Listeners With Cochlear Implants.

The primary objective of this study was to quantify differences in evoked potential correlates of spiral ganglion neuron (SGN) density between younger and older individuals with cochlear implants (CIs) using the electrically evoked compound action potential (ECAP). In human temporal bone studies and in animal models, SGN density is the lowest in older subjects and in those who experienced long durations of deafness during life. SGN density also varies as a function of age at implantation and hearing loss etiology. Taken together, it is likely that younger listeners who were deafened and implanted during childhood have denser populations of SGNs than older individuals who were deafened and implanted later in life. In animals, ECAP amplitudes, amplitude growth function (AGF) slopes, and their sensitivity to stimulus interphase gap (IPG) are predictive of SGN density. The authors hypothesized that younger listeners who were deafened and implanted as children would demonstrate larger ECAP amplitudes, steeper AGF slopes, and greater IPG sensitivity than older, adult-deafened and implanted listeners. Data were obtained from 22 implanted ears (18 individuals). Thirteen ears (9 individuals) were deafened and implanted as children (child-implanted group), and nine ears (9 individuals) were deafened and implanted as adults (adult-implanted group). The groups differed significantly on a number of demographic variables that are implicitly related to SGN density: (1) chronological age; (2) age at implantation; and (3) duration of preimplantation hearing loss. ECAP amplitudes, AGF linear slopes, and thresholds were assessed on a subset of electrodes in each ear in response to two IPGs (7 and 30 µsec). Speech recognition was assessed using a medial vowel identification task. Compared with the adult-implanted listeners, individuals in the child-implanted group demonstrated larger changes in ECAP amplitude when the IPG of the stimulus was increased from 7 to 30 µsec (i.e., greater IPG sensitivity). On average, child-implanted participants also had larger ECAP amplitudes and steeper AGF linear slopes than the adult-implanted participants, irrespective of IPG. IPG sensitivity for AGF linear slope and ECAP threshold did not differ between age groups. Vowel recognition performance was not correlated with any of the ECAP measures assessed in this study. The results of this study support the theory that young CI listeners who were deafened and implanted during childhood may have denser neural populations than older listeners who were deafened and implanted as adults. Potential between-group differences in SGN integrity emphasize a need to investigate optimized CI programming parameters for younger and older listeners.

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.

Evoked Compound Action Potentials Reveal Spinal Cord Dorsal Column Neuroanatomy

The electrically evoked compound action potential (ECAP) is a measure of the response from a population of fibers to an electrical stimulus. ECAPs can be assessed during spinal cord stimulation (SCS) to elucidate the relationship between stimulation, electrophysiological response, and neuromodulation. This has consequences for the design and programming of SCS devices. Sheep were implanted with linear epidural SCS leads. After a stimulating pulse, electrodes recorded ECAPs sequentially as they propagated orthodromically or antidromically. After filtering, amplification, and signal processing, ECAP amplitude and dispersion (width) was measured, and conduction velocity was calculated. Similar clinical data was also collected. A single-neuron computer model that simulated large-diameter sensory axons was used to explore and explain the observations. ECAPs, both animal and human, have a triphasic structure, with P1, N1, and P2 peaks. Conduction velocity in sheep was 109 ms-1 , which indicates that the underlying neural population includes fibers of up to 20 μm in diameter. For travel in both directions, propagation distance was associated with decrease in amplitude and increase in dispersion. Importantly, characteristics of these changes shifted abruptly at various positions along the cord. ECAP dispersion increases with propagation distance due to the contribution of slow-conducting small-diameter fibers as the signal propagates away from the source. An analysis of the discontinuities in ECAP dispersion changes with propagation revealed that these are due to the termination of smaller-diameter, slower-conducting fibers at corresponding segmental levels. The implications regarding SCS lead placement, toward the goal of maximizing clinical benefit while minimizing side-effects, are discussed. John Parker is the founder and CEO of Saluda Medical and holds stock options. Milan Obradovic, Nastaran Hesam Shariati, Dean M. Karantonis, Peter Single, James Laird-Wah, Robert Gorman and Mark Bickerstaff are employees of Saluda Medical with stock options. At the time the data was collected for the study, Prof. Cousins was a paid consultant for Saluda Medical. John Parker, Milan Obradovic, Dean Karantonis, James Laird-Wah, Robert Gorman and Peter Single are co-inventors in one or more patents related to the topics discussed in this work.

Changes over time in the electrically evoked compound action potential (ECAP) interphase gap (IPG) effect following cochlear implantation in Guinea pigs

The electrically-evoked compound action potential (ECAP) is correlated with spiral ganglion neuron (SGN) density in cochlear implanted animals. In a previous study, we showed that ECAP amplitude growth function (AGF) linear slopes for stimuli with a constant interphase gap (IPG) changed significantly over time following implantation. Related studies have also shown that 1) IPG sensitivity for ECAP measures (“IPG Effect”) is related to SGN density in animals and 2) the ECAP IPG Effect is related to speech recognition performance in humans with cochlear implants. The current study examined how the ECAP IPG Effect changed following cochlear implantation in four non-deafened guinea pigs with residual inner hair cells (IHCs) and 5 deafened, neurotrophin-treated guinea pigs. Simple impedances were measured on the same days as the ECAP measures. Generally, non-deafened implanted animals with higher SGN survival demonstrated higher ECAP AGF linear slope and peak amplitude values than the deafened, implanted guinea pigs. The ECAP IPG Effect for the AGF slopes and peak amplitudes was also larger in the hearing animals. The N1 latencies for a constant IPG were not different between groups, but the N1 latency IPG Effect was smaller in the non-deafened, implanted animals. Similar to previously reported results, ECAP measures using a fixed or changing IPG required as many as three months after implantation before a stable point could be calculated, but this was dependent on the animal and condition. For all ECAP measures most animals showed greater variance in the first 30 days post-implantation. Post-implantation changes in ECAPs and impedances were not correlated with one another. Results from this study are helpful for estimating the mechanisms underlying ECAP characteristics and have implications for clinical application of the ECAP measures in long-term human cochlear implant recipients. Specifically, these measures could help to monitor neural health over a period of time, or during a time of stability these measures could be used to help select electrode sites for activation in clinical programming.

Assessing the Relationship Between the Electrically Evoked Compound Action Potential and Speech Recognition Abilities in Bilateral Cochlear Implant Recipients.

The primary objective of the present study was to examine the relationship between suprathreshold electrically evoked compound action potential (ECAP) measures and speech recognition abilities in bilateral cochlear implant listeners. We tested the hypothesis that the magnitude of ear differences in ECAP measures within a subject (right-left) could predict the difference in speech recognition performance abilities between that subject's ears (right-left). To better control for across-subject variables that contribute to speech understanding, the present study used a within-subject design. Subjects were 10 bilaterally implanted adult cochlear implant recipients. We measured ECAP amplitudes and slopes of the amplitude growth function in both ears for each subject. We examined how each of these measures changed when increasing the interphase gap of the biphasic pulses. Previous animal studies have shown correlations between these ECAP measures and auditory nerve survival. Speech recognition measures included speech reception thresholds for sentences in background noise, as well as phoneme discrimination in quiet and in noise. Results showed that the between-ear difference (right-left) of one specific ECAP measure (increase in amplitude growth function slope as the interphase gap increased from 7 to 30 µs) was significantly related to the between-ear difference (right-left) in speech recognition. Frequency-specific response patterns for ECAP data and consonant transmission cues support the hypothesis that this particular ECAP measure may represent localized functional acuity. The results add to a growing body of literature suggesting that when using a well-controlled research design, there is evidence that underlying neural function is related to postoperative performance with a cochlear implant.

Using Electrically-evoked Compound Action Potentials to Estimate Perceptive Levels in Experienced Adult Cochlear Implant Users.

The cochlear implant (CI) fitting level prediction accuracy of electrically-evoked compound action potential (ECAP) should be enhanced by the addition of demographic data in models. No accurate automated fitting of CI based on ECAP has yet been proposed. We recorded ECAP in 45 adults who had been using MED-EL CIs for more than 11 months and collected the most comfortable loudness level (MCL) used for CI fitting (prog-MCL), perception thresholds (meas-THR), and MCL (meas-MCL) measured with the stimulation used for ECAP recording. Linear mixed models taking into account cochlear site factors were computed to explain prog-MCL, meas-MCL, and meas-THR. Cochlear region and ECAP threshold were predictors of the three levels. In addition, significant predictors were the ECAP amplitude for the prog-MCL and the duration of deafness for the prog-MCL and the meas-THR. Estimations were more accurate for the meas-THR, then the meas-MCL, and finally the prog-MCL. These results show that 1) ECAP thresholds are more closely related to perception threshold than to comfort level, 2) predictions are more accurate when the inter-subject and cochlear regions variations are considered, and 3) differences between the stimulations used for ECAP recording and for CI fitting make it difficult to accurately predict the prog-MCL from the ECAP recording. Predicted prog-MCL could be used as bases for fitting but should be used with care to avoid any uncomfortable or painful stimulation.

Facilitation and refractoriness of the electrically evoked compound action potential

In this study we aim to resolve the contributions of facilitation and refractoriness at very short pulse intervals. Measurements of the refractory properties of the electrically evoked compound action potential (ECAP) of the auditory nerve in cochlear implant (CI) users at inter pulse intervals below 300 μs are influenced by facilitation and recovery effects. ECAPs were recorded using masker pulses with a wide range of current levels relative to the probe pulse levels, for three suprathreshold probe levels and pulse intervals from 13 to 200 μs. Evoked potentials were measured for 21 CI patients by using the masked response extraction artifact cancellation procedure.During analysis of the measurements the stimulation current was not used as absolute value, but in relation to the patient's individual ECAP threshold. This enabled a more general approach to describe facilitation as a probe level independent effect. Maximum facilitation was found for all tested inter pulse intervals at masker levels near patient's individual ECAP threshold, independent from probe level. For short inter pulse intervals an increased N1P1 amplitude was measured for subthreshold masker levels down to 120 CL below patient's individual ECAP threshold in contrast to the recreated state.ECAPs recorded with inter pulse intervals up to 200 μs are influenced by facilitation and recovery. Facilitation effects are most pronounced for masker levels at or below ECAP threshold, while recovery effects increase with higher masker levels above ECAP threshold. The local maximum of the ECAP amplitude for masker levels around ECAP threshold can be explained by the mutual influence of maximum facilitation and minimal refractoriness.

Relationship Between Peripheral and Psychophysical Measures of Amplitude Modulation Detection in Cochlear Implant Users.

This study investigates the relationship between electrophysiological and psychophysical measures of amplitude modulation (AM) detection. Prior studies have reported both measures of AM detection recorded separately from cochlear implant (CI) users and acutely deafened animals, but no study has made both measures in the same CI users. Animal studies suggest a progressive loss of high-frequency encoding as one ascends the auditory pathway from the auditory nerve to the cortex. Because the CI speech processor uses the envelope of an ongoing acoustic signal to modulate pulse trains that are subsequently delivered to the intracochlear electrodes, it is of interest to explore auditory nerve responses to modulated stimuli. In addition, psychophysical AM detection abilities have been correlated with speech perception outcomes. Thus, the goal was to explore how the auditory nerve responds to AM stimuli and to relate those physiologic measures to perception. Eight patients using Cochlear Ltd. Implants participated in this study. Electrically evoked compound action potentials (ECAPs) were recorded using a 4000 pps pulse train that was sinusoidally amplitude modulated at 125, 250, 500, and 1000 Hz rates. Responses were measured for each pulse over at least one modulation cycle for an apical, medial, and basal electrode. Psychophysical modulation detection thresholds (MDTs) were also measured via a three-alternative forced choice, two-down, one-up adaptive procedure using the same modulation frequencies and electrodes. ECAPs were recorded from individual pulses in the AM pulse train. ECAP amplitudes varied sinusoidally, reflecting the sinusoidal variation in the stimulus. A modulated response amplitude (MRA) metric was calculated as the difference in the maximal and minimum ECAP amplitudes over the modulation cycles. MRA increased as modulation frequency increased, with no apparent cutoff (up to 1000 Hz). In contrast, MDTs increased as the modulation frequency increased. This trend is inconsistent with the physiologic measures. For a fixed modulation frequency, correlations were observed between MDTs and MRAs; this trend was evident at all frequencies except 1000 Hz (although only statistically significant for 250 and 500 Hz AM rates), possibly an indication of central limitations in processing of high modulation frequencies. Finally, peripheral responses were larger and psychophysical thresholds were lower in the apical electrodes relative to basal and medial electrodes, which may reflect better cochlear health and neural survival evidenced by lower preoperative low-frequency audiometric thresholds and steeper growth of neural responses in ECAP amplitude growth functions for apical electrodes. Robust ECAPs were recorded for all modulation frequencies tested. ECAP amplitudes varied sinusoidally, reflecting the periodicity of the modulated stimuli. MRAs increased as the modulation frequency increased, a trend we attribute to neural adaptation. For low modulation frequencies, there are multiple current steps between the peak and valley of the modulation cycle, which means successive stimuli are more similar to one another and neural responses are more likely to adapt. Higher MRAs were correlated with lower psychophysical thresholds at low modulation frequencies but not at 1000 Hz, implying a central limitation to processing of modulated stimuli.

Effect of stimulus level on the temporal response properties of the auditory nerve in cochlear implants

Electrically evoked compound action potentials (ECAPs) have been used to examine temporal response patterns of the auditory nerve in cochlear implant (CI) recipients. ECAP responses to individual pulses in a pulse train vary across stimulation rates for individual CI users. For very slow rates, auditory neurons have ample time to discharge, recover, and respond to each pulse in the train. As the pulse rate increases, an alternating ECAP-amplitude pattern occurs. As the stimulation rate increases further, the alternating pattern eventually ceases and the overall ECAP amplitudes are diminished, yielding a relatively stochastic state that presumably reflects a combination of adaptation, desynchronization, and facilitation across fibers. Because CIs operate over a range of current levels in everyday use, it is important to understand auditory-nerve responses to pulse trains over a range of levels. The effect of stimulus level on ECAP temporal response patterns in human CI users has not been well studied. The first goal of this study was to examine the effect of stimulus level on various aspects of ECAP temporal responses to pulse-train stimuli. Because higher stimulus levels yield more synchronous responses and faster recovery, it was hypothesized that: (1) the maximum alternation would occur at slower rates for lower levels and faster rates at higher levels, (2) the alternation depth at its maximum would be smaller for lower levels, (3) the rate that produces a stochastic state (‘stochastic rate’) would decrease with level, (4) adaptation would be greater for lower levels as a result of slower recovery, and (5) refractory-recovery time constants would be longer (slower) for lower levels, consistent with earlier studies. The second goal of this study was to examine how refractory-recovery time constants relate specifically to maximum alternation and stochastic rate. Data were collected for 12 ears in 10 CI recipients. ECAPs were recorded in response to each of 13 pulses in an equal-amplitude pulse train ranging in rate from 900–3500 pps for three levels (low, medium, high). The results generally supported hypotheses 1–4; there were no significant effects of level on the refractory-recovery time constants (hypothesis 5). When data were pooled across level, there was a significant negative correlation between alternation depth and refractory recovery time. Understanding the effects of stimulus level on auditory-nerve responses may provide further insight into improving the use of objective measures for potentially optimizing speech-processing strategies.

Intracochlear Recordings of Acoustically and Electrically Evoked Potentials in Nucleus Hybrid L24 Cochlear Implant Users and Their Relationship to Speech Perception.

The Hybrid cochlear implant (CI) has been developed for individuals with high frequency hearing loss who retain good low frequency hearing. Outcomes have been encouraging but individual variability is high; the health of the cochlea and the auditory nerve may be important factors driving outcomes. Electrically evoked compound action potentials (ECAPs) reflect the response of the auditory nerve to electrical stimulation while electrocochleography (ECochG) reflects the response of the cochlear hair cells and auditory nerve to acoustic stimulation. In this study both ECAPs and ECochG responses were recorded from Nucleus Hybrid L24 CI users. Correlations between these two measures of peripheral auditory function and speech perception are reported. This retrospective study includes data from 25 L24 CI users. ECAPs and ECochG responses were recorded from an intracochlear electrode using stimuli presented at or near maximum acceptable loudness levels. Speech perception was assessed using Consonant-Nucleus-Consonant (CNC) word lists presented in quiet and AzBio sentences presented at a +5 dB signal-to-noise ratio in both the combined acoustic and electric (A+E) and electric (E) alone listening modes. Acoustic gain was calculated by subtracting these two scores. Correlations between these physiologic and speech perception measures were then computed. ECAP amplitudes recorded from the most apical electrode were significantly correlated with CNC scores measured in the E alone (r = 0.56) and A+E conditions (r = 0.64), but not with performance on the AzBio test. ECochG responses recorded using the most apical electrode in the intracochlear array but evoked using a 500 Hz tone burst were not correlated with either the scores on the CNC or AzBio tests. However, ECochG amplitude was correlated with a composite metric relating the additional benefit of acoustic gain in noise relative to quiet conditions (r = 0.67). Both measures can be recorded from Hybrid L24 CI users and both ECAP and ECochG measures may result in more complete characterization of speech perception outcomes than either measure alone.

The relation between ECAP measurements and the effect of rate on behavioral thresholds in cochlear implant users

It has been shown that electrically evoked compound action potential (ECAP) thresholds are not sufficiently predictive of behavioral thresholds to allow their use as a totally objective method to program a cochlear implant. Previous animal studies have shown that two other ECAP parameters (the ECAP amplitude growth slope and the effect on ECAPs of changing the phase duration (PD) or interphase gap (IPG)), and the way that behavioral thresholds change with increasing rate of stimulation, are associated with cochlear health. This experiment tested the hypotheses that a) the degree to which behavioral thresholds change with rate of stimulation is associated with either or both of those two ECAP parameters, and that b) the accuracy of ECAP thresholds for predicting behavioral thresholds at clinically relevant rates can be increased by including those additional ECAP parameters. Both these hypotheses were confirmed by the data. The ECAP slope was associated with within-subject variation across electrode positions of both behavioral thresholds and the change of thresholds with increasing rate. The effect of changes in IPG or PD on ECAPs was moderately associated with between-subjects variations in both average absolute behavioral thresholds and the average effect of rate on thresholds. The inclusion of the IPG/PD effect to predict average absolute behavioral thresholds for each subject and inclusion of the ECAP growth slope to predict variation in relative thresholds across electrode positions in the same subject led to a significant increase in accuracy of the predicted behavioral thresholds.