The Sensitivity of the Electrically Stimulated Auditory Nerve to Amplitude Modulation Cues Declines With Advanced Age.

OBJECTIVES: This study aimed to investigate effects of aging and duration of deafness on sensitivity of the auditory nerve (AN) to amplitude modulation (AM) cues delivered using trains of biphasic pulses in adult cochlear implant (CI) users. DESIGN: There were 21 postlingually deaf adult CI users who participated in this study. All study participants used a Cochlear Nucleus device with a full electrode array insertion in the test ear. The stimulus was a 200-ms pulse train with a pulse rate of 2000 pulses per second. This carrier pulse train was sinusodially AM at four modulation rates (20, 40, 100, 200 Hz). The peak amplitude of the modulated pulse train was the maximum comfortable level (i.e., C level) measured for the carrier pulse train. The electrically evoked compound action potential (eCAP) to each of the 20 pulses selected over the last two AM cycles were measured. In addition, eCAPs to single pulses were measured with the probe levels corresponding to the levels of 20 selected pulses from each AM pulse train. There were seven electrodes across the array evaluated in 16 subjects (i.e., electrodes 3 or 4, 6, 9, 12, 15, 18, and 21). For the remaining five subjects, 4 to 5 electrodes were tested due to impedance issues or time constraints. The modulated response amplitude ratio (MRAR) was calculated as the ratio of the difference in the maximum and the minimum eCAP amplitude measured for the AM pulse train to that measured for the single pulse, and served as the dependent variable. Age at time of testing and duration of deafness measured/defined using three criteria served as the independent variables. Linear Mixed Models were used to assess the effects of age at testing and duration of deafness on the MRAR. RESULTS: Age at testing had a strong, negative effect on the MRAR. For each subject, the duration of deafness varied substantially depending on how it was defined/measured, which demonstrates the difficulty of accurately measuring the duration of deafness in adult CI users. There was no clear or reliable trend showing a relationship between the MRAR measured at any AM rate and duration of deafness defined by any criteria. After controlling for the effect of age at testing, MRARs measured at 200 Hz and basal electrode locations (i.e., electrodes 3 and 6) were larger than those measured at any other AM rate and apical electrode locations (i.e., electrodes 18 and 21). CONCLUSIONS: The AN sensitivity to AM cues implemented in the pulse-train stimulation significantly declines with advanced age. Accurately measuring duration of deafness in adult CI users is challenging, which, at least partially, might have accounted for the inconclusive findings in the relationship between the duration of deafness and the AN sensitivity to AM cues in this study.

Prediction of the Functional Status of the Cochlear Nerve in Individual Cochlear Implant Users Using Machine Learning and Electrophysiological Measures.

OBJECTIVES: This study aimed to create an objective predictive model for assessing the functional status of the cochlear nerve (CN) in individual cochlear implant (CI) users. DESIGN: Study participants included 23 children with cochlear nerve deficiency (CND), 29 children with normal-sized CNs (NSCNs), and 20 adults with various etiologies of hearing loss. Eight participants were bilateral CI users and were tested in both ears. As a result, a total of 80 ears were tested in this study. All participants used Cochlear Nucleus CIs in their test ears. For each participant, the CN refractory recovery function and input/output (I/O) function were measured using electrophysiological measures of the electrically evoked compound action potential (eCAP) at three electrode sites across the electrode array. Refractory recovery time constants were estimated using statistical modeling with an exponential decay function. Slopes of I/O functions were estimated using linear regression. The eCAP parameters used as input variables in the predictive model were absolute refractory recovery time estimated based on the refractory recovery function, eCAP threshold, slope of the eCAP I/O function, and negative-peak (i.e., N1) latency. The output variable of the predictive model was CN index, an indicator for the functional status of the CN. Predictive models were created by performing linear regression, support vector machine regression, and logistic regression with eCAP parameters from children with CND and the children with NSCNs. One-way analysis of variance with post hoc analysis with Tukey's honest significant difference criterion was used to compare study variables among study groups. RESULTS: All three machine learning algorithms created two distinct distributions of CN indices for children with CND and children with NSCNs. Variations in CN index when calculated using different machine learning techniques were observed for adult CI users. Regardless of these variations, CN indices calculated using all three techniques in adult CI users were significantly correlated with Consonant-Nucleus-Consonant word and AzBio sentence scores measured in quiet. The five oldest CI users had smaller CN indices than the five youngest CI users in this study. CONCLUSIONS: The functional status of the CN for individual CI users was estimated by our newly developed analytical models. Model predictions of CN function for individual adult CI users were positively and significantly correlated with speech perception performance. The models presented in this study may be useful for understanding and/or predicting CI outcomes for individual patients.

The Effects of GJB2 or SLC26A4 Gene Mutations on Neural Response of the Electrically Stimulated Auditory Nerve in Children.

OBJECTIVES: This study aimed to (1) investigate the effect of GJB2 and SLC26A4 gene mutations on auditory nerve function in pediatric cochlear implant users and (2) compare their results with those measured in implanted children with idiopathic hearing loss. DESIGN: Participants included 20 children with biallelic GJB2 mutations, 16 children with biallelic SLC26A4 mutations, and 19 children with idiopathic hearing loss. All subjects except for two in the SLC26A4 group had concurrent Mondini malformation and enlarged vestibular aqueduct. All subjects used Cochlear Nucleus devices in their test ears. For each subject, electrophysiological measures of the electrically evoked compound action potential (eCAP) were recorded using both anodic- and cathodic-leading biphasic pulses. Dependent variables (DVs) of interest included slope of eCAP input/output (I/O) function, the eCAP threshold, and eCAP amplitude measured at the maximum comfortable level (C level) of the anodic-leading stimulus (i.e., the anodic C level). Slopes of eCAP I/O functions were estimated using statistical modeling with a linear regression function. These DVs were measured at three electrode locations across the electrode array. Generalized linear mixed effect models were used to evaluate the effects of study group, stimulus polarity, and electrode location on each DV. RESULTS: Steeper slopes of eCAP I/O function, lower eCAP thresholds, and larger eCAP amplitude at the anodic C level were measured for the anodic-leading stimulus compared with the cathodic-leading stimulus in all subject groups. Children with GJB2 mutations showed steeper slopes of eCAP I/O function and larger eCAP amplitudes at the anodic C level than children with SLC26A4 mutations and children with idiopathic hearing loss for both the anodic- and cathodic-leading stimuli. In addition, children with GJB2 mutations showed a smaller increase in eCAP amplitude when the stimulus changed from the cathodic-leading pulse to the anodic-leading pulse (i.e., smaller polarity effect) than children with idiopathic hearing loss. There was no statistically significant difference in slope of eCAP I/O function, eCAP amplitude at the anodic C level, or the size of polarity effect on all three DVs between children with SLC26A4 mutations and children with idiopathic hearing loss. These results suggested that better auditory nerve function was associated with GJB2 but not with SLC26A4 mutations when compared with idiopathic hearing loss. In addition, significant effects of electrode location were observed for slope of eCAP I/O function and the eCAP threshold. CONCLUSIONS: GJB2 and SLC26A4 gene mutations did not alter polarity sensitivity of auditory nerve fibers to electrical stimulation. The anodic-leading stimulus was generally more effective in activating auditory nerve fibers than the cathodic-leading stimulus, despite the presence of GJB2 or SLC26A4 mutations. Patients with GJB2 mutations appeared to have better functional status of the auditory nerve than patients with SLC26A4 mutations who had concurrent Mondini malformation and enlarged vestibular aqueduct and patients with idiopathic hearing loss.

Recommendations for Measuring the Electrically Evoked Compound Action Potential in Children With Cochlear Nerve Deficiency.

OBJECTIVES: This study reports a method for measuring the electrically evoked compound action potential (eCAP) in children with cochlear nerve deficiency (CND). DESIGN: This method was developed based on experience with 50 children with CND who were Cochlear Nucleus cochlear implant users. RESULTS: This method includes three recommended steps conducted with recommended stimulating and recording parameters: initial screen, pulse phase duration optimization, and eCAP threshold determination (i.e., identifying the lowest stimulation level that can evoke an eCAP). Compared with the manufacturer-default parameters, the recommended parameters used in this method yielded a higher success rate for measuring the eCAP in children with CND. CONCLUSIONS: The eCAP can be measured successfully in children with CND using recommended parameters. This specific method is suitable for measuring the eCAP in children with CND in clinical settings. However, it is not suitable for intraoperative eCAP recordings due to the extensive testing time required.