Evoked Compound Action Potential Research Articles

Outcomes of ECAP-controlled closed-loop spinal cord stimulation therapy in JAPAN: how to increase patient satisfaction with spinal cord stimulation

Objective: Orthopedic surgeons commonly encounter patients with low back pain and leg pain. Despite conservative treatment, which may involve the use of weak opioids or NSAIDs, some patients do not experience improvement and may require increased dosages, contributing to concerns about opioid overuse overseas. Spinal cord stimulation (SCS) therapy, which can be trialed without surgical intervention, offers a potential treatment option. We evaluated Inceptiv (Medtronic), a generator that allows new stimulation settings using evoked compound action potentials (ECAPs)-controlled Closed-Loop technology. Methods: We evaluated six patients (four females, two males) who underwent implantation of the Inceptiv generator for SCS therapy. The average walking time (seconds) during a 2.1-meter walk and pain assessment using the Numerical Rating Scale (NRS) were conducted. Patient satisfaction was assessed using a 5-point scale: very satisfied (5), somewhat satisfied (4), neutral (3), somewhat dissatisfied (2), very dissatisfied. (1). Results: The average walking time improved from 11.8 seconds to 6.6 seconds, and the NRS score decreased from 7.6 to 4.2. Patient satisfaction was high, with four patients being very satisfied (5), one somewhat satisfied (4), and one neutral (3). Discussion: SCS therapy with Closed-Loop technology using the Inceptiv generator offers the potential to adjust electrical stimulation to minimize discomfort in daily activities and provide pain relief. It is considered a new treatment option for patients with common orthopedic conditions such as thoracolumbar compression fractures and lumbar spinal stenosis who suffer from chronic refractory pain in routine clinical practice.

Evaluation of an impedance-based method to monitor the insertion of the electrode array during cochlear implantation.

Cochlear implantation is a prevalent remedy for severe-to-profound hearing loss. Optimising outcomes and hearing preservation, and minimising insertion trauma, require precise electrode placement. Objective monitoring during the insertion process can provide valuable insights and enhance surgical precision. This study assesses the feasibility and performance of an impedance-based method for monitoring electrode insertion, compared to the surgeon's feedback. The study utilised the Insertion Monitoring Tool (IMT) research software, allowing for real-time measurement of impedance and evoked compound action potential (eCAP) during electrode insertion in 20 patient implantations. This enabled an impedance-based method to continuously assess the status of each electrode during the insertion process. The feasibility and performance was evaluated and compared to the surgeon's feedback approach. eCAP measurements focused merely on feasibility without searching specific responses. The IMT demonstrated feasibility in measuring real-time impedances and eCAP during the insertion of the electrode array. The impedance-based method exhibited potential for accurately monitoring the insertion depth with a high success rate. However, further development is needed to improve the number of usable contacts. Objective monitoring with the impedance-based method shows promise as a valuable tool to enhance the precision of cochlear implant electrode insertion respecting insertion distance estimation. The IMT research software proved feasible in recording real-time impedances and eCAP during electrode insertion. While this impedance-based method exhibits high success rates, further improvements are required to optimise the number of usable contacts. This study highlights the potential of objective monitoring techniques to enhance cochlear implantation outcomes.

Peripheral Neural Synchrony in Postlingually Deafened Adult Cochlear Implant Users.

This paper reports a noninvasive method for quantifying neural synchrony in the cochlear nerve (i.e., peripheral neural synchrony) in cochlear implant (CI) users, which allows for evaluating this physiological phenomenon in human CI users for the first time in the literature. In addition, this study assessed how peripheral neural synchrony was correlated with temporal resolution acuity and speech perception outcomes measured in quiet and in noise in postlingually deafened adult CI users. It tested the hypothesis that peripheral neural synchrony was an important factor for temporal resolution acuity and speech perception outcomes in noise in postlingually deafened adult CI users. Study participants included 24 postlingually deafened adult CI users with a Cochlear™ Nucleus® device. Three study participants were implanted bilaterally, and each ear was tested separately. For each of the 27 implanted ears tested in this study, 400 sweeps of the electrically evoked compound action potential (eCAP) were measured at four electrode locations across the electrode array. Peripheral neural synchrony was quantified at each electrode location using the phase-locking value (PLV), which is a measure of trial-by-trial phase coherence among eCAP sweeps/trials. Temporal resolution acuity was evaluated by measuring the within-channel gap detection threshold (GDT) using a three-alternative, forced-choice procedure in a subgroup of 20 participants (23 implanted ears). For each ear tested in these participants, GDTs were measured at two electrode locations with a large difference in PLVs. For 26 implanted ears tested in 23 participants, speech perception performance was evaluated using consonant-nucleus-consonant (CNC) word lists presented in quiet and in noise at signal to noise ratios (SNRs) of +10 and +5 dB. Linear Mixed effect Models were used to evaluate the effect of electrode location on the PLV and the effect of the PLV on GDT after controlling for the stimulation level effects. Pearson product-moment correlation tests were used to assess the correlations between PLVs, CNC word scores measured in different conditions, and the degree of noise effect on CNC word scores. There was a significant effect of electrode location on the PLV after controlling for the effect of stimulation level. There was a significant effect of the PLV on GDT after controlling for the effects of stimulation level, where higher PLVs (greater synchrony) led to lower GDTs (better temporal resolution acuity). PLVs were not significantly correlated with CNC word scores measured in any listening condition or the effect of competing background noise presented at an SNR of +10 dB on CNC word scores. In contrast, there was a significant negative correlation between the PLV and the degree of noise effect on CNC word scores for a competing background noise presented at an SNR of +5 dB, where higher PLVs (greater synchrony) correlated with smaller noise effects on CNC word scores. This newly developed method can be used to assess peripheral neural synchrony in CI users, a physiological phenomenon that has not been systematically evaluated in electrical hearing. Poorer peripheral neural synchrony leads to lower temporal resolution acuity and is correlated with a larger detrimental effect of competing background noise presented at an SNR of 5 dB on speech perception performance in postlingually deafened adult CI users.

First evidence of a biomarker-based dose-response relationship in chronic pain using physiological closed-loop spinal cord stimulation

Background and objectivesIn spinal cord stimulation (SCS) therapy, electricity is the medication delivered to the spinal cord for pain relief. In contrast to conventional medication where dose is determined by...

Neurophysiological outcomes that sustained clinically significant improvements over 3 years of physiologic ECAP-controlled closed-loop spinal cord stimulation for the treatment of chronic pain

IntroductionA novel, spinal cord stimulation (SCS) system with a physiologic closed-loop (CL) feedback mechanism controlled by evoked compound action potentials (ECAPs) enables the optimization of physiologic neural dose and the...

Comparison of Two Measurement Paradigms to Determine Electrically Evoked Cochlear Nerve Responses and Their Correlation to Cochlear Nerve Cross-section in Infants and Young Children With Cochlear Implant.

Electrically evoked compound action potentials (ECAPs) are used for intra-/postoperative monitoring with intracochlear stimulation of cochlear implants. ECAPs are recorded in MED-EL (Innsbruck, Austria) implants using auditory response telemetry (ART), which has been further developed with automatic threshold determination as AutoART. The success of an ECAP measurement also depends on the number of available spiral ganglion cells and the bipolar neurons of the cochlear nerve (CN). It is assumed that a higher population of spiral ganglion cell implies a larger CN cross-sectional area (CSA), which consequently affects ECAP measurements. Intraoperative ECAP measurements from 19 implanted ears of children aged 8 to 18 months were retrospectively evaluated. A comparison and correlation of ART/AutoART ECAP thresholds/slopes at electrodes E2 (apical), E6 (medial), E10 (basal), and averaged E1 to E12 with CN CSA on magnetic resonance imaging was performed. A Pearson correlation of the ART/AutoART ECAP thresholds/slopes for E2/E6/E10 and the averaged electrodes E1 to E12 showed a significant correlation. The CN CSA did not correlate significantly with the averaged ART/AutoART ECAP thresholds/slopes across all 12 electrodes. AutoART provides reliable measurements and is therefore a suitable alternative to ART. No significant influence of CN CSA on ECAP thresholds/slopes was observed. A predictive evaluation of the success of ECAP measurements based on CN CSA for a clinical setting cannot be made according to the present data.

Effects of Intraoperative Cochlear Implant Electrode Conditioning on Impedances and Electrically Evoked Compound Action Potentials.

The current study investigates whether, during a Cochlear Implant (CI) surgery, conditioning (i.e. applying short bursts of electrical stimulation) within a saline solution can have positive effects on subsequent intra-operative measurements. We hypothesize that, based on previous research, the impedance values will be reduced, and that the reproducibility of Electrically Evoked Compound Action Potentials (ECAPs) is improved as a result of conditioning. We conditioned half of the electrode contacts, within a saline solution, before CI insertion, using 23 MED-EL implants. Impedance was measured for both the conditioned and non-conditioned groups at five time points. Repeated ECAP recordings were measured and compared between the conditioned and non-conditioned groups. Impedance of the electrode contacts were reduced by 31% after conditioning in saline solution; however, there were no clinically relevant differences after the implantation of the electrode array. The hypothesis that measurement reproducibility would be increased after conditioning could not be confirmed with our data. Within the saline solution, we observed that 44% of the electrode contacts were covered with air bubbles, which most disappeared after implantation. However, these air bubbles limited the effectiveness of the conditioning within the saline solution. Lastly, the effect of conditioning on the reference electrode stimulation was approximately 16% of the total reduction in impedance. Our data does not suggest that intraoperative conditioning is clinically required for cochlear implantation with MED-EL implants. Additionally, an in-vivo ECAP recording can be considered as a method of conditioning the electrode contacts. We confirm that the common clinical practice does not need to be changed.

Insights Into Electrophysiological Metrics of Cochlear Health in Cochlear Implant Users Using a Computational Model

PurposeThe hearing outcomes of cochlear implant users depend on the functional status of the electrode-neuron interface inside the cochlea. This can be assessed by measuring electrically evoked compound action potentials (eCAPs). Variations in cochlear neural health and survival are reflected in eCAP-based metrics. The difficulty in translating promising results from animal studies into clinical use has raised questions about to what degree eCAP-based metrics are influenced by non-neural factors. Here, we addressed these questions using a computational model.MethodsA 2-D computational model was designed to simulate how electrical signals from the stimulating electrode reach the auditory nerve fibers distributed along the cochlea, evoking action potentials that can be recorded as compound responses at the recording electrodes. Effects of physiologically relevant variations in neural survival and in electrode-neuron and stimulating-recording electrode distances on eCAP amplitude growth functions (AGFs) were investigated.ResultsIn line with existing literature, the predicted eCAP AGF slopes and the inter-phase gap (IPG) effects depended on the neural survival, but only when the IPG effect was calculated as the difference between the slopes of the two AGFs expressed in linear input–output scale. As expected, shallower eCAP AGF slopes were obtained for increased stimulating-recording electrode distance and larger eCAP thresholds for greater electrode-neuron distance. These non-neural factors had also minor interference on the predicted IPG effect.ConclusionsThe model predictions demonstrate previously found dependencies of eCAP metrics on neural survival and non-neural aspects. The present findings confirm data from animal studies and provide insights into applying described metrics in clinical practice.

A flexible, thin-film microchannel electrode array device for selective subdiaphragmatic vagus nerve recording

The vagus nerve (VN) plays an important role in regulating physiological conditions in the gastrointestinal (GI) tract by communicating via the parasympathetic pathway to the enteric nervous system (ENS). However, the lack of knowledge in the neurophysiology of the VN and GI tract limits the development of advanced treatments for autonomic dysfunctions related to the VN. To better understand the complicated underlying mechanisms of the VN-GI tract neurophysiology, it is necessary to use an advanced device enabled by microfabrication technologies. Among several candidates including intraneural probe array and extraneural cuff electrodes, microchannel electrode array devices can be used to interface with smaller numbers of nerve fibers by securing them in the separate channel structures. Previous microchannel electrode array devices to interface teased nerve structures are relatively bulky with thickness around 200 µm. The thick design can potentially harm the delicate tissue structures, including the nerve itself. In this paper, we present a flexible thin film based microchannel electrode array device (thickness: 11.5 µm) that can interface with one of the subdiaphragmatic nerve branches of the VN in a rat. We demonstrated recording evoked compound action potentials (ECAP) from a transected nerve ending that has multiple nerve fibers. Moreover, our analysis confirmed that the signals are from C-fibers that are critical in regulating autonomic neurophysiology in the GI tract.

Psychophysical and Electrophysiological Parameters of the Auditory Analyzer as Indicators of the Effectiveness of Cochlear Implantation in Children with Bilateral Deafness

Background. The results of rehabilitation of patients with deafness after cochlear implantation (CI) depends on many factors related on both the individual characteristics of the patient and the technical parameters of auditory nerve stimulation — fitting of the CI system processor. Article presents the results of a study of the relationship between psychophysical (subjective) auditory sensations and electrophysiological (objective) responses of the structures of the auditory analyzer to electrical stimulation. Aims — to evaluate the relationship between the electrophysiological responses of the auditory analyzer and the psychophysical parameters of the thresholds of sound perception and speech intelligibility in patients with deafness after CI. Methods. The study involved 88 patients with IV bilateral sensorineural hearing loss, borderline with deafness, aged 6 to 17 years 11 months, among whom 54.5% (n = 48) of girls and 45.5% (n = 40) of boys. Of the patients included in the follow-up, 40% (n = 35) underwent unilateral CI; 60% (n = 53) of children underwent bilateral sequential CI. In our study, slightly more than half of the patients (51.1%) had experience using the CI system for more than 5 years. At the first stage of the study, we studied the relationship between sound perception thresholds (tonal audiometry in a free field) and registered ASSR (auditory steady state response) thresholds in patients with deafness receiving rehabilitation after CI surgery. The relationship between behavioral and electrophysiological (objective) thresholds was assessed by comparing the results of tonal threshold audiometry and the responses received during ASSR registration to acoustic stimulation in a free field. At the second stage, patients with indications for processor fitting (decreased speech intelligibility, uncomfortable sensations) underwent speech audiometry, evoked compound action potentials (ECAP) registration, according to the results of which the parameters of the CI processor were changed. Results. Research data showed the effectiveness of the approach of including the ECAP registration test, followed by the creation of a fitting card and correction of the level of auditory nerve stimulation under the control of speech audiometry in the protocol of fitting the CI processor. Conclusions. The results of the conducted studies allow us to recommend the use of the developed method of objective recording of sound perception thresholds in patients with CI as one of the indicators of the effectiveness of CI in the early period of auditory-speech rehabilitation in patients with undeveloped speech skills and when it is impossible to conduct objective tests accompanied by supra-threshold stimulation of the auditory nerve.

The Effect of Electrode Position on Behavioral and Electrophysiologic Measurements in Perimodiolar Cochlear Implants.

The shape and position of cochlear implant electrodes could potentially influence speech perception, as this determines the proximity of implant electrodes to the spiral ganglion. However, the literature to date reveals no consistent association between speech perception and either the proximity of electrode to the medial cochlear wall or the depth of insertion. These relationships were explored in a group of implant recipients receiving the same precurved electrode. This was a retrospective study of adults who underwent cochlear implantation with Cochlear Ltd.'s Slim Perimodiolar electrode at the Royal Victorian Eye and Ear Hospital between 2015 and 2018 (n = 52). Postoperative images were obtained using cone beam computed tomography (CBCT) and analyzed by multi-planar reconstruction to identify the position of the electrode contacts within the cochlea, including estimates of the proximity of the electrodes to the medial cochlear wall or modiolus and the angular depth of insertion. Consonant-vowel-consonant (CVC) monosyllabic phonemes were determined preoperatively, and at 3 and 12 months postoperatively. Electrically evoked compound action potential (ECAP) thresholds and impedance were measured from the implant array immediately after implantation. The relationships between electrode position and speech perception, electrode impedance, and ECAP threshold were an analyzed by Pearson correlation. Age had a negative impact on speech perception at 3 months but not 12 months. None of the electrode-wide measures of proximity between electrode contacts and the modiolus, nor measures of proximity to the medial cochlear wall, nor the angular depth of insertion of the most apical electrode correlated with speech perception. However, there was a moderate correlation between speech perception and the position of the most basal electrode contacts; poorer speech perception was associated with a greater distance to the modiolus. ECAP thresholds were inversely related to the distance between electrode contacts and the modiolus, but there was no clear association between this distance and impedance. Speech perception was significantly affected by the proximity of the most basal electrodes to the modiolus, suggesting that positioning of these electrodes may be important for optimizing speech perception. ECAP thresholds might provide an indication of this proximity, allowing for its optimization during surgery.

ART and AutoART ECAP measurements and cochlear nerve anatomy as predictors in adult cochlear implant recipients.

The purpose of this retrospective study is to compare the results of electrically evoked compound action potential (ECAP) measurements using automatic auditory response telemetry (AutoART) with those obtained by ART in adults. The study also aimed to evaluate the predictive value of intraoperative ART and AutoART ECAPs for speech intelligibility (SI) and hearing success (HS), and to determine if cochlear nerve (CN) cross-sectional area (CSA) obtained preoperatively by magnetic resonance imaging (MRI) scans could predict ART and AutoART ECAPs and SI and HS outcome. The study analyzed and correlated ART and AutoART ECAP thresholds at electrodes E2, E6, and E10, as well as averaged ECAP thresholds over electrodes E1-E12, using data from 32 implants. Correlations were also examined for ART and AutoART ECAP slopes. In addition, averaged ART and AutoART ECAP thresholds and slopes over all 12 electrodes for each participant were correlated with CN CSA measured from MRI sequences. SI of the monosyllabic Freiburg Speech Test at 65 dB sound pressure level was examined along with averaged ART and AutoART thresholds and slopes over all 12 electrodes. A parallel analysis was performed for HS, derived from the difference between baseline and 6-month SI. Finally, correlations between CN CSA and SI, as well as CN CSA and HS were examined. The results of the study showed a significant positive correlation between ART and AutoART ECAP thresholds and as well as slopes for E2, E6, E10 and averaged thresholds and slopes of E1-E12. However, no significant correlation was observed between ART and AutoART averaged ECAP thresholds and slopes and either SI and HS or CN CSA. Furthermore, no significant correlation was found between CN CSA and SI and HS. While AutoART is a reliable and safe program for measuring ECAPs in adults, the study found no preoperative prognostic information on intraoperative ECAP results using parameters extracted from current MRI sequences or pre-/intraoperative information on subsequent hearing outcome using ECAP and CN CSA.

Evoked compound action potential (ECAP)-controlled closed-loop spinal cord stimulation in an experimental model of neuropathic pain in rats

BackgroundPreclinical models of spinal cord stimulation (SCS) are lacking objective measurements to inform translationally applicable SCS parameters. The evoked compound action potential (ECAP) represents a measure of dorsal column fiber activation. This measure approximates the onset of SCS-induced sensations in humans and provides effective analgesia when used with ECAP-controlled closed-loop (CL)-SCS systems. Therefore, ECAPs may provide an objective surrogate for SCS dose in preclinical models that may support better understanding of SCS mechanisms and further translations to the clinics. This study assessed, for the first time, the feasibility of recording ECAPs and applying ECAP-controlled CL-SCS in freely behaving rats subjected to an experimental model of neuropathic pain.MethodsAdult male Sprague–Dawley rats (200–300 g) were subjected to spared nerve injury (SNI). A custom-made six-contact lead was implanted epidurally covering T11-L3, as confirmed by computed tomography or X-ray. A specially designed multi-channel system was used to record ECAPs and to apply ECAP-controlled CL-SCS for 30 min at 50 Hz 200 µs. The responses of dorsal column fibers to SCS were characterized and sensitivity towards mechanical and cold stimuli were assessed to determine analgesic effects from ECAP-controlled CL-SCS. Comparisons between SNI rats and their controls as well as between stimulation parameters were made using omnibus analysis of variance (ANOVA) tests and t-tests.ResultsThe recorded ECAPs showed the characteristic triphasic morphology and the ECAP amplitude (mV) increased as higher currents (mA) were applied in both SNI animals and controls (SNI SCS-ON and sham SCS-ON). Importantly, the use of ECAP-based SCS dose, implemented in ECAP-controlled CL-SCS, significantly reduced mechanical and cold hypersensitivity in SNI SCS-ON animals through the constant and controlled activation of dorsal column fibers. An analysis of conduction velocities of the evoked signals confirmed the involvement of large, myelinated fibers.ConclusionsThe use of ECAP-based SCS dose implemented in ECAP-controlled CL-SCS produced analgesia in animals subjected to an experimental model of neuropathic pain. This approach may offer a better method for translating SCS parameters between species that will improve understanding of the mechanisms of SCS action to further advance future clinical applications.

A Virtual Inner Ear Model Selects Ramped Pulse Shapes for Vestibular Afferent Stimulation.

Bilateral vestibular deficiency (BVD) results in chronic dizziness, blurry vision when moving the head, and postural instability. Vestibular prostheses (VPs) show promise as a treatment, but the VP-restored vestibulo-ocular reflex (VOR) gain in human trials falls short of expectations. We hypothesize that the slope of the rising ramp in stimulation pulses plays an important role in the recruitment of vestibular afferent units. To test this hypothesis, we utilized customized programming to generate ramped pulses with different slopes, testing their efficacy in inducing electrically evoked compound action potentials (eCAPs) and current spread via bench tests and simulations in a virtual inner model created in this study. The results confirmed that the slope of the ramping pulses influenced the recruitment of vestibular afferent units. Subsequently, an optimized stimulation pulse train was identified using model simulations, exhibiting improved modulation of vestibular afferent activity. This optimized slope not only reduced the excitation spread within the semicircular canals (SCCs) but also expanded the neural dynamic range. While the model simulations exhibited promising results, in vitro and in vivo experiments are warranted to validate the findings of this study in future investigations.

Selective peripheral nerve recording using simulated human median nerve activity and convolutional neural networks

BackgroundIt is difficult to create intuitive methods of controlling prosthetic limbs, often resulting in abandonment. Peripheral nerve interfaces can be used to convert motor intent into commands to a prosthesis. The Extraneural Spatiotemporal Compound Action Potentials Extraction Network (ESCAPE-NET) is a convolutional neural network (CNN) that has previously been demonstrated to be effective at discriminating neural sources in rat sciatic nerves. ESCAPE-NET was designed to operate using data from multi-channel nerve cuff arrays, and use the resulting spatiotemporal signatures to classify individual naturally evoked compound action potentials (nCAPs) based on differing source fascicles. The applicability of this approach to larger and more complex nerves is not well understood. To support future translation to humans, the objective of this study was to characterize the performance of this approach in a computational model of the human median nerve.MethodsUsing a cross-sectional immunohistochemistry image of a human median nerve, a finite-element model was generated and used to simulate extraneural recordings. ESCAPE-NET was used to classify nCAPs based on source location, for varying numbers of sources and noise levels. The performance of ESCAPE-NET was also compared to ResNet-50 and MobileNet-V2 in the context of classifying human nerve cuff data.ResultsClassification accuracy was found to be inversely related to the number of nCAP sources in ESCAPE-NET (3-class: 97.8% ± 0.1%; 10-class: 89.3% ± 5.4% in low-noise conditions, 3-class: 70.3% ± 0.1%; 10-class: 52.5% ± 0.3% in high-noise conditions). ESCAPE-NET overall outperformed both MobileNet-V2 (3-class: 96.5% ± 1.1%; 10-class: 84.9% ± 1.7% in low-noise conditions, 3-class: 86.0% ± 0.6%; 10-class: 41.4% ± 0.9% in high-noise conditions) and ResNet-50 (3-class: 71.2% ± 18.6%; 10-class: 40.1% ± 22.5% in low-noise conditions, 3-class: 81.3% ± 4.4%; 10-class: 31.9% ± 4.4% in high-noise conditions).ConclusionAll three networks were found to learn to differentiate nCAPs from different sources, as evidenced by performance levels well above chance in all cases. ESCAPE-NET was found to have the most robust performance, despite decreasing performance as the number of classes increased, and as noise was varied. These results provide valuable translational guidelines for designing neural interfaces for human use.

Optimizing the efficiency of ECAP measurements due to interpolation

ABSTRACT: Background Thresholds of electrically evoked compound action potentials (TECAP) may serve as starting points for electrophysiologically based fitting of cochlear implants. Absent TECAP data at single electrodes reduces the number of data points available for fitting and can be substituted by interpolation of measured data points. Aim To compare complete TECAP profiles with interpolated TECAP profiles of 5/22 (∼22.7%) and 11/22 (50%) electrode contacts. Material and methods Single-centre, retrospective, observational study of data from 624 ears implanted with a Slim Modiolar (CI ×32) or Contour Advance (CI ×12, CI24RE(CA)) electrode array (Cochlear Ltd). The deviation of the complete measured TECAP profile from the same profile with missing and therefore interpolated TECAP values was quantified. Results Interpolated TECAP profiles significantly differ from complete measured profiles especially at the basal and apical electrodes. Reference data for Slim Modiolar and Contour Advance electrodes mean profiles are provided. Conclusions and significance Reducing the number of measured TECAP electrodes has to be weighted against losses in the TECAP accuracy of interpolated values. A clinically acceptable compromise may be a reduction from 22 to 11 even non-equidistant data points. While reducing ECAP measurement time, it is accompanied by a minimal loss of accuracy of the TECAP threshold profile.

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.

The Effects of Zinc on Proprioceptive Sensory Function and Nerve Conduction

Zinc (Zn2+) is an essential element that can promote proper organ function, cell growth, and immune response; it can also, however, be present in too great a quantity. Zinc toxicity caused by overexposure may result in both minor and major physiological effects, with chronic exposure at low levels and acute exposure at high levels being harmful or even toxic. This investigation examines the effects of acute exposure to relatively high concentrations of Zn2+ on sensory nerve function and nerve conduction. A proprioceptive nerve in marine crab (Callinectes sapidus) limbs was used as a model to assess the effects of Zn2+ on stretch-activated channels (SACs) and evoked nerve conduction. Exposure to Zn2+ slowed nerve condition rapidly; however, several minutes were required before the SACs in sensory endings were affected. A depression in conduction speed and an increase followed by a decrease in amplitude were observed for the evoked compound action potential, while the frequency of nerve activity upon joint movement and stretching of the chordotonal organ significantly decreased. These altered responses could be partially reversed via extensive flushing with fresh saline to remove the zinc. This indicates that subtle, long-term exposure to Zn2+ may alter an organism’s SAC function for channels related to proprioception and nerve conduction.

Electrically evoked compound action potential in children following cochlear implantation and its correlation with cochlear nerve diameter

Background: The study evaluated changes in the threshold of ECAP recorded during cochlear implantation, at switch on, after three months and six months following cochlear implantation. It further assessed the correlation between the ECAP threshold with T and C levels and the cochlear nerve diameter measured preoperatively. Methods: A prospective study of 42 prelingually deaf children who underwent cochlear implantation was conducted. The ECAP threshold values intra-operatively, at switch on, three months and six months were recorded and analysed. The T and C levels were assessed six months postoperatively, and correlation with the ECAP threshold was analysed. The diameter of the cochlear nerve was recorded, and its correlation with the ECAP threshold was determined. Results: Over six months, the basal, central and apical electrodes showed a statistically significant reduction in ECAP threshold of 11.64%, 4.67% and 25.81%, respectively, in candidates implanted with Advanced Bionics implant and 18.89%, 12.78% and 14.08%, respectively in candidates implanted with Nucleus implant. The ECAP thresholds were lower for the apical electrodes. No correlation was found between the ECAP threshold and T and C levels. A correlation between the cochlear nerve diameter and ECAP was not statistically significant. Conclusions: There was a statistically significant change in the ECAP threshold over six months. There was no statistically significant correlation between the ECAP thresholds and T and C levels. The value of ECAP thresholds to measure C and T values need to be relooked. There was no correlation between the cochlear nerve diameter and the ECAP threshold.

The efficacy of a TrkB monoclonal antibody agonist in preserving the auditory nerve in deafened guinea pigs

The auditory nerve typically degenerates following loss of cochlear hair cells or synapses. In the case of hair cell loss neural degeneration hinders restoration of hearing through a cochlear implant, and in the case of synaptopathy suprathreshold hearing is affected, potentially degrading speech perception in noise. It has been established that neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) can mitigate auditory nerve degeneration. Several potential BDNF mimetics have also been investigated for neurotrophic effects in the cochlea. A recent in vitro study showed favorable effects of M3, a TrkB monoclonal antibody agonist, when compared with BDNF. In the present study we set out to examine the effect of M3 on auditory nerve preservation in vivo. Thirty-one guinea pigs were bilaterally deafened, and unilaterally treated with a single 3-µl dose of 7 mg/ml, 0.7 mg/ml M3 or vehicle-only by means of a small gelatin sponge two weeks later. During the experiment and analyses the experimenters were blinded to the three treatment groups. Four weeks after treatment, we assessed the treatment effect (1) histologically, by quantifying survival of SGCs and their peripheral processes (PPs); and (2) electrophysiologically, with two different paradigms of electrically evoked compound action potential (eCAP) recordings shown to be indicative of neural health: single-pulse stimulation with varying inter-phase gap (IPG), and pulse-train stimulation with varying inter-pulse interval. We observed a consistent and significant preservative effect of M3 on SGC survival in the lower basal turn (approximately 40% more survival than in the untreated contralateral cochlea), but also in the upper middle and lower apical turn of the cochlea. This effect was similar for the two treatment groups. Survival of PPs showed a trend similar to that of the SGCs, but was only significantly higher for the highest dose of M3. The protective effect of M3 on SGCs was not reflected in any of the eCAP measures: no statistically significant differences were observed between groups in IPG effect nor between the M3 treatment groups and the control group using the pulse-train stimulation paradigm. In short, while a clear effect of M3 was observed on SGC survival, this was not clearly translated into functional preservation.