Auditory Responses in Cochlear Implant Users With and Without GJB2 Deafness

Department of Otolaryngology-Head and Neck Surgery and the Molecular Genetics Laboratory, The Hospital for Sick Children, Toronto, Ontario, Canada.
The Laryngoscope (Impact Factor: 2.14). 02/2006; 116(2):317-27. DOI: 10.1097/01.mlg.0000199401.26626.4b
Source: PubMed


It is reasonable to suppose that the pattern of sensorineural damage along the length of the cochlea depends on the etiology of a hearing loss (HL). In GJB2-related deafness, we hypothesize that gap junction deficits are uniformly distributed and will result in similar damage along the length of the cochlea as compared with non-GJB2 subjects. We assessed this by measuring patterns of neural activity and hearing from apical versus basal cochlear implant electrode regions.
This was a prospective, blind, controlled study.
Blood from 301 pediatric cochlear implant users was analyzed for mutations in GJB2 by direct sequencing. After exclusion of patients with monoallelic GJB2 mutations, associated syndromes, or risk factors for HL that were not congenital, 39 children with biallelic GJB2 mutations and 58 without GJB2 mutations were evaluated. Hearing was measured before implantation at frequencies ranging from 250 Hz to 8 kHz. After implantation, neural activity at the apical and basal ends of the implanted array was measured using electrically evoked compound action potentials of the auditory nerve (ECAPs) and evoked stapedius reflexes (ESRs).
GJB2 and non-GJB2 groups were not significantly different with respect to sex, age at implantation, duration of auditory deprivation, hearing aid use, duration of aided hearing, ear implanted, implant model, or depth of insertion (P>.05). Children with GJB2-related HL had greater similarities between low- and high-frequency residual hearing and between neural activity electrically evoked at apical and basal regions of the cochlea as compared with children with non-GJB2-related HL who demonstrated larger deficits in basal regions.
Results suggest more consistent spiral ganglion survival along the length of the cochlea in GJB2-related HL as compared with non-GJB2-related HL, which appears to involve a decreasing gradient of spiral ganglion survival from the apex to the base of the cochlea. Our findings support our premise that in GJB2-related HL, dysfunction of gap junctions likely occurs to a similar degree in the apical and basal regions of the cochlea. This knowledge might be used to customize implantable devices for patients with HL in the future.

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Available from: Karen Gordon, Jun 10, 2014
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    • "These factors may each have unique effects on auditory activity in the brain prior to implantation. For example, biallelic mutations of the Gap Junction Beta-2 (GJB-2) gene causes deficits in the cochlea at likely very early stages of development with possible consequences for auditory function after implantation (Propst et al., 2006). The GJB-2 gene normally codes for the connexin-26 protein, which creates gap junctions in the cochlea necessary for the appropriate release and maintenance of electrochemical gradients. "
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    ABSTRACT: We have explored both the benefits and detriments of providing electrical input through a cochlear implant in one ear to the auditory system of young children. A cochlear implant delivers electrical pulses to stimulate the auditory nerve, providing children who are deaf with access to sound. The goals of implantation are to restrict reorganization of the deprived immature auditory brain and promote development of hearing and spoken language. It is clear that limiting the duration of deprivation is a key factor. Additional considerations are the onset, etiology, and use of residual hearing as each of these can have unique effects on auditory development in the pre-implant period. New findings show that many children receiving unilateral cochlear implants are developing mature-like brainstem and thalamo-cortical responses to sound with long term use despite these sources of variability; however, there remain considerable abnormalities in cortical function. The most apparent, determined by implanting the other ear and measuring responses to acute stimulation, is a loss of normal cortical response from the deprived ear. Recent data reveal that this can be avoided in children by early implantation of both ears simultaneously or with limited delay. We conclude that auditory development requires input early in development and from both ears.
    Full-text · Article · Oct 2013 · Frontiers in Psychology
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    • "No significant (α = 0.05) differences across ear or across electrode were found for either the ECAP, EABR or loudness measures. Propst et al. (2006) reported steeper ECAP and EABR growth functions for apical electrodes in patients with non-GJB2 etiology. Gordon et al. (2007) also reported slightly but significantly steeper EABR growth function slope for apical compared to basal stimulating electrodes in patients who used the Nucleus CI device. "
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    ABSTRACT: The goals of this study were (1) to describe the relationship between electrically evoked compound action potential (ECAP) and electrically evoked auditory brainstem response (EABR) amplitude growth functions and loudness growth functions in bilateral cochlear implant (CI) users, and (2) to determine whether matching the stimulus levels in the two ears of bilateral CI users based on equal ECAP amplitude, EABR amplitude, or current level resulted in the smallest discrepancy in loudness rating across the two ears. Ten adult, bilateral CI users participated in this study. The stimulus used to elicit loudness judgments and generate ECAP and EABR growth functions was a train of biphasic current pulses (32 μs/phase) presented at a rate of 23 pps. Loudness growth functions were obtained with a method of constant stimuli. ECAPs were measured using the implant telemetry system. EABR growth functions were recorded using surface electrodes and standard averaging techniques. Both ears of each subject were tested. For each ear, ECAP, EABR, and loudness functions were recorded using both an apical and basal stimulating electrode. Both the physiologic and psychophysical growth functions were fit using linear regression techniques. Comparison of the regression equations obtained for the two ears revealed that stimulus levels that yielded approximately equal ECAP amplitudes in the two ears were judged to differ in loudness, on average, by 20% for electrode 3 and 14% for electrode 13. Stimulation levels that evoked similar amplitude EABRs differed in loudness, on average, by 50% for electrode 3 and 13% for electrode 13. Matched stimulus current levels were judged to differ in loudness, on average, by 14% for electrode 3 and 16% for electrode 13. No significant differences in loudness discrepancy across ears derived from equal amplitude ECAP, EABR, or matched current levels were found. This study demonstrated that stimuli that evoke equal amplitude neural responses in both ears of a bilateral CI user or which are matched in current level cannot be assumed to be perceived as equally loud. No statistically significant differences in accuracy were found between ECAP, EABR, or matched current levels or between the basal and apical electrode in approximations of equal loudness.
    Full-text · Article · Jan 2012 · Ear and hearing
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    • "This is the year when further studies had come to a conclusion of superiority of GJB2 mutation carriers over non-GJB2 controls [14]. The concept of GJB2 performance superiority in CI performance was additionally reinforced within two years [7]. "
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    ABSTRACT: Clinical application of mutation screening and its effect on the outcome of cochlear implantation is widely debated. We investigated the effect of mutations in GJB2 gene on the outcome of cochlear implantation in a population with a high rate of consanguineous marriage and autosomal recessive nonsyndromic hearing loss. Two hundred and one children with profound prelingual sensorineural hearing loss were included. Forty-six patients had 35delG in GJB2. Speech awareness thresholds (SATs) and speech recognition thresholds (SRTs) improved following implantation, but there was no difference in performance between patients with GJB2-related deafness versus control (all P > 0.10). Both groups had produced their first comprehensible words within the same period of time following implantation (2.27 months in GJB2-related deaf versus 2.62 months in controls, P = 0.22). Although our findings demonstrate the need to uncover unidentified genetic causes of hereditary deafness, they do not support the current policy for genetic screening before cochlear implantation, nor prove a prognostic value.
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