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1.  Superior Canal Dehiscence Length and Location Influences Clinical Presentation and Audiometric and Cervical Vestibular-Evoked Myogenic Potential Testing 
Audiology & neuro-otology  2014;19(2):97-105.
Superior canal dehiscence (SCD) is caused by an absence of bony covering of the arcuate eminence or posteromedial aspect of the superior semicircular canal. However, the clinical presentation of SCD syndrome varies considerably, as some SCD patients are asymptomatic and others have auditory and/or vestibular complaints. In order to determine the basis for these observations, we examined the association between SCD length and location with: (1) auditory and vestibular signs and symptoms; (2) air conduction (AC) loss and air-bone gap (ABG) measured by pure-tone audiometric testing, and (3) cervical vestibular-evoked myogenic potential (cVEMP) thresholds. 104 patients (147 ears) underwent SCD length and location measurements using a novel method of measuring bone density along 0.2-mm radial CT sections. We found that patients with auditory symptoms have a larger dehiscence (median length: 4.5 vs. 2.7 mm) with a beginning closer to the ampulla (median location: 4.8 vs. 6.4 mm from ampulla) than patients with no auditory symptoms (only vestibular symptoms). An increase in AC threshold was found as the SCD length increased at 250 Hz (95% CI: 1.7–4.7), 500 Hz (95% CI: 0.7–3.5) and 1,000 Hz (95% CI: 0.0–2.5), and an increase in ABG as the SCD length increased at 250 Hz (95% CI: 2.0–5.3), 500 Hz (95% CI: 1.6–4.6) and 1,000 Hz (95% CI: 1.3–3.3) was also seen. Finally, a larger dehiscence was associated with lowered cVEMP thresholds at 250 Hz (95% CI: −4.4 to −0.3), 500 Hz (95% CI: −4.1 to −1.0), 750 Hz (95% CI: −4.2 to −0.7) and 1,000 Hz (95% CI: −3.6 to −0.5) and a starting location closer to the ampulla at 250 Hz (95% CI: 1.3–5.1), 750 Hz (95% CI: 0.2–3.3) and 1,000 Hz (95% CI: 0.6–3.5). These findings may help to explain the variation of signs and symptoms seen in patients with SCD syndrome.
doi:10.1159/000353920
PMCID: PMC4975610  PMID: 24434937
Superior canal dehiscence, size; Superior canal dehiscence, location; Length, auditory; Audiometry; Cervical vestibular-evoked myogenic potential
2.  Histopathology of the Human Inner Ear in Alström Syndrome 
Audiology & neuro-otology  2015;20(4):267-272.
Alström syndrome is an autosomal recessive syndromic genetic disorder caused by mutations in the ALMS1 gene. Sensorineural hearing loss occurs in greater than 85% of patients. Histopathology of the inner ear abnormalities in the human has not previously been fully described. Histopathology of the inner ear in Alström syndrome is presented in two genetically confirmed cases. The predominant histopathologic correlates of the sensorineural loss were degeneration of the organ of Corti, both inner and outer hair cells, degeneration of spiral ganglion cells, and atrophy of the stria vascularis and spiral ligament.
doi:10.1159/000381935
PMCID: PMC4540704  PMID: 26111748
Alström; ALMS1; human; histopathology; inner ear
3.  Quantification of Speech-in-Noise and Sound Localisation Abilities in Children with Unilateral Hearing Loss and Comparison to Normal Hearing Peers 
Audiology & neuro-otology  2015;20(0 1):31-37.
The study objective was to quantify abilities of children with unilateral hearing loss (UHL) on measures that address known deficits for this population; that is, speech understanding in quiet and noise, and sound localisation. Noise conditions varied by noise type and source location. Parent reports of real-world abilities were also obtained. Performance was compared to gender- and age-matched normal hearing (NH) peers. UHL performance was poorer and more varied compared to NH peers. Among the findings, age correlated with localisation ability for UHL but not NH participants. Low frequency hearing in the better ear of UHL children was associated with performance in noise; however, there was no relation for NH children. Considerable variability was evident in the outcomes of children with UHL and needs to be understood as future treatment options are considered.
doi:10.1159/000380745
PMCID: PMC4467990  PMID: 25999162
Unilateral hearing loss; speech recognition in noise; spatial hearing; localization
4.  Sound source localization by hearing preservation patients with and without symmetric, low-frequency acoustic hearing 
Audiology & neuro-otology  2015;20(3):166-171.
The aim of this paper was to study sound source localization by cochlear implant (CI) listeners with low-frequency (LF) acoustic hearing in both the operated ear and in the contralateral ear. Eight CI listeners had symmetrical LF acoustic hearing (symm) and four had asymmetric LF acoustic hearing (asymm). The effects of two variables were assessed: (i) the symmetry of the LF thresholds in the two ears and (ii) the presence/absence of bilateral acoustic amplification. Stimuli consisted of low-pass, high pass, and wide-band noise bursts presented in the frontal horizontal plane. Localization accuracy was 23 degrees of error for the symm listeners and 76 degrees of error for the asymm listeners. The presence of a unilateral CI used in conjunction with bilateral LF acoustic hearing does not impair sound source localization accuracy, but amplification for acoustic hearing can be detrimental to sound source localization accuracy.
doi:10.1159/000367883
PMCID: PMC4734375  PMID: 25832907
hearing preservation; localization; cochlear implants; hearing aids; acoustic hearing
5.  Assessment of the effects of superior canal dehiscence location and size on intracochlear sound pressures 
Audiology & neuro-otology  2014;20(1):62-71.
Superior canal dehiscence (SCD) is a defect in the bony covering of the superior semicircular canal. Patients with SCD present with a wide range of symptoms, including hearing loss, yet it is unknown whether hearing is affected by parameters such as the location of the SCD. Our previous human cadaveric temporal bone study, utilizing intracochlear pressure measurements, generally showed that an increase in dehiscence size caused a low-frequency monotonic decrease in the cochlear drive across the partition, consistent with increased hearing loss. This previous study was limited to SCD sizes including and smaller than 2 mm long and 0.7 mm wide. However, the effects of larger SCDs (>2 mm long) were not studied, although larger SCDs are seen in many patients. Therefore, to answer the effect of parameters that have not been studied, this present study assessed the effect of SCD location and the effect of large-sized SCD (>2 mm long) on intracochlear pressures. We used simultaneous measurements of sound pressures in scala vestibuli and scala tympani at the base of the cochlea to determine the sound-pressure difference across the cochlear partition – a measure of the cochlear drive in a temporal bone preparation – allowing for assessment of hearing loss. We measured the cochlear drive before and after SCDs were made at different locations (e.g., closer to the ampulla of the superior semicircular canal or closer to the common crus), and for different dehiscence sizes (including larger than 2 mm long and 0.7 mm wide). Our measurements suggest that: 1) Different SCD locations result in similar cochlear drive; 2) Larger SCDs produce larger decreases in cochlear drive at low frequencies. However, the effect of SCD size seems to saturate as the size increases above 2–3 mm long and 0.7 mm wide. Although the monotonic effect was generally consistent across ears, the quantitative amount of change in cochlear drive due to dehiscence size varied across ears. Additionally, the size of the dehiscence above which the effect on hearing saturated, varied across ears. These findings show that the location of the SCD does not generally influence the amount of hearing loss and that SCD size can help explain some of the variability of hearing loss in patients.
doi:10.1159/000366512
PMCID: PMC4298487  PMID: 25531117
superior semicircular canal dehiscence; cochlear pressure; SCD; scala vestibuli; scala tympani; cochlea; differential pressure; size; location
6.  Clinical evaluation of an image-guided cochlear implant programming strategy 
Audiology & neuro-otology  2014;19(6):400-411.
The cochlear implant (CI) has been labeled the most successful neural prosthesis. Despite this success, a significant number of CI recipients experience poor speech understanding, and, even among the best performers, restoration to normal auditory fidelity is rare. While significant research efforts have been devoted to improving stimulation strategies, few developments have led to significant hearing improvement over the past two decades. We have recently introduced image processing techniques that open a new direction for advancement in this field by making it possible, for the first time, to determine the position of implanted CI electrodes relative to the nerves they stimulate using CT images. In this article, we present results of an image-guided, patient-customized approach to stimulation that utilizes the electrode position information our image processing techniques provide. This approach allows us to identify electrodes that cause overlapping stimulation patterns and to deactivate them from a patient's map. This individualized mapping strategy yields significant improvement in speech understanding in both quiet and noise as well as improved spectral resolution in the 68 adult CI recipients studied to date. Our results indicate that image-guidance can improve hearing outcomes for many existing CI recipients without requiring additional surgery or the use of “experimental” stimulation strategies, hardware or software.
doi:10.1159/000365273
PMCID: PMC4305276  PMID: 25402603
Cochlear implant; stimulation overlap; channel interaction; customized programming
7.  The Development of Auditory Perception in Children Following Auditory Brainstem Implantation 
Audiology & neuro-otology  2014;19(6):386-394.
Auditory brainstem implants (ABI) can provide useful auditory perception and language development in deaf children who are not able to use a cochlear implant (CI). We prospectively followed-up a consecutive group of 64 deaf children up to 12 years following ABI implantation. The etiology of deafness in these children was: cochlear nerve aplasia in 49, auditory neuropathy in 1, cochlear malformations in 8, bilateral cochlear post-meningitic ossification in 3, NF2 in 2, and bilateral cochlear fractures due to a head injury in 1. Thirty five children had other congenital non-auditory disabilities. Twenty two children had previous CIs with no benefit. Fifty eight children were fitted with the Cochlear 24 ABI device and six with the MedEl ABI device and all children followed the same rehabilitation program. Auditory perceptual abilities were evaluated on the Categories of Auditory Performance (CAP) scale. No child was lost to follow-up and there were no exclusions from the study. All children showed significant improvement in auditory perception with implant experience. Seven children (11%) were able to achieve the highest score on the CAP test; they were able to converse on the telephone within 3 years of implantation. Twenty children (31.3%) achieved open set speech recognition (CAP score of 5 or greater) and 30 (46.9%) achieved a CAP level of 4 or greater. Of the 29 children without non-auditory disabilities, 18 (62%) achieved a CAP score of 5 or greater with the ABI. All children showed continued improvements in auditory skills over time. The long-term results of ABI implantation reveal significant auditory benefit in most children, and open set auditory recognition in many.
doi:10.1159/000363684
PMCID: PMC4289463  PMID: 25377987
Auditory perception; Prelingually deaf children; Cochlear malformation; ossification; fracture; cochlear nerve aplasia; auditory brainstem implant; Outcome; Auditory perception
8.  Bimodal cochlear implants: The role of acoustic signal level in determining speech perception benefit 
Audiology & neuro-otology  2014;19(4):234-238.
The aim of this project was to determine, for bimodal cochlear implant (CI) patients, i.e., patients with low-frequency hearing in the ear contralateral to the implant, how speech understanding varies as a function of the difference in level between the CI signal and the acoustic signal. The data suggest that (i) acoustic signals perceived as significantly softer than a CI signal can contribute to speech understanding in the bimodal condition, (ii) acoustic signals that are slightly softer than, or balanced with, a CI signal provide the largest benefit to speech understanding and (iii) acoustic signals presented at MCL provide nearly as much benefit as signals that have been balanced with a CI signal.
doi:10.1159/000360070
PMCID: PMC4201875  PMID: 24992987
9.  Optimizing Ocular Vestibular Evoked Myogenic Potential Testing for Superior Semicircular Canal Dehiscence Syndrome: Electrode Placement 
Audiology & neuro-otology  2014;19(4):239-247.
Objective
To compare the sensitivity and specificity of ocular vestibular evoked myogenic potentials (oVEMP) using two electrode montages for the diagnosis of superior canal dehiscence syndrome (SCDS).
Subjects
16 SCDS patients (17 affected-SCDS ears, 15 contralateral-SCDS ears) and 12 controls (24 ears).
Methods
OVEMPs were recorded in response to 500 Hz tone bursts using 2 electrode montages. For both montages the active electrode was placed approximately 5 mm below each eye and a ground electrode on the sternum. For montage 1(standard) the reference electrode was centered 2 cm below each active electrode. For montage 2 the reference electrode was placed on the chin.
Results
For either montage, the separation between oVEMP amplitudes in affected-SCDS ears and controls was significant (p<0.001), with excellent sensitivity and specificity (>90%).
Conclusion
oVEMP recordings with the standard montage remain a reliable method for evaluation of SCDS.
doi:10.1159/000360124
PMCID: PMC4310219  PMID: 24993062
vestibular; VEMP; otolith; superior canal dehiscence syndrome; oVEMP
10.  Correlation Between Histologic and Radiographic Reconstruction of Intracochlear Electrode Position in Human Temporal Bones 
Audiology & neuro-otology  2014;19(3):184-192.
In our laboratory, human temporal bone specimens from patients who in life have undergone cochlear implantation are routinely processed with the implant in situ, embedded in araldite, sectioned at 20 μm and serially photographed during cutting, stained with toluidine blue and mounted on glass slides. From the images, 2D and 3D reconstructions can be made and a very accurate implant insertion depth can be calculated from the 3D reconstructions. However, this method precludes subsequent special stains and further molecular investigations of the tissue including proteomics and immunostaining which is now possible with celloidin embedded tissue. In this study, we correlated measurement of the implant array insertion depth calculated from histologic 3D reconstruction with that measured from 3D radiologic multiplanar reconstruction.
Four human temporal bones with cochlear implants underwent post-fixation pre-processing CT imaging with a Siemens Somatom Sensation Scanner. The CT scans from these four bones were downloaded into the Voxar software application, reformatted using the multiplanar reconstruction tool, viewed in three dimensions and measurements of intracochlear insertion lengths of the implants were obtained. The bones were processed routinely for in situ araldite embedding, serial images were made of the block during sectioning, post-processed using PV-Wave® software, aligned with Amira® software, and used to create histologic 3D reconstructions. From these 3D reconstructions, the insertion depth of the electrode array was mathematically calculated.
The range of insertion depths was 15.9 mm (case #1) to 26.6 mm (case #4). The two methods, radiographic multiplanar reconstruction and 3D reconstruction, differed by 0.4 – 0.9%. This provides confidence that important localization information about the electrode in situ can be gleaned from CT scans, thereby allowing us to extract the implants prior to processing for celloidin embedment and allow further techniques such as special stains and immunostaining to be accomplished in order to evaluate molecular mechanisms involved in cochlear implantation.
doi:10.1159/000358003
PMCID: PMC4123416  PMID: 24686209
temporal bone; cochlear implant; intracochlear length; CT; multiplanar reconstruction; histology; celloidin
11.  The Benefits of Bimodal Hearing: Effect of Frequency Region and Acoustic Bandwidth 
Audiology & neuro-otology  2014;19(3):151-163.
We examined the effects of acoustic bandwidth on bimodal benefit for speech recognition in adults with a cochlear implant (CI) in one ear and low-frequency acoustic hearing in the contralateral ear. The primary aims were to (1) replicate with a steeper filter roll-off to examine the low-pass bandwidth required to obtain bimodal benefit for speech recognition and expand results to include different signal-to-noise ratios (SNRs) and talker genders, (2) determine whether the bimodal benefit increased with acoustic low-pass bandwidth and (3) determine whether an equivalent bimodal benefit was obtained with acoustic signals of similar low-pass and pass band bandwidth, but different center frequencies. Speech recognition was assessed using words presented in quiet and sentences in noise (+10, +5 and 0 dB SNRs). Acoustic stimuli presented to the nonimplanted ear were filtered into the following bands: <125, 125–250, <250, 250–500, <500, 250–750, <750 Hz and wide-band (full, nonfiltered bandwidth). The primary findings were: (1) the minimum acoustic low-pass bandwidth that produced a significant bimodal benefit was <250 Hz for male talkers in quiet and for female talkers in multitalker babble, but <125 Hz for male talkers in background noise, and the observed bimodal benefit did not vary significantly with SNR; (2) the bimodal benefit increased systematically with acoustic low-pass bandwidth up to <750 Hz for a male talker in quiet and female talkers in noise and up to <500 Hz for male talkers in noise, and (3) a similar bimodal benefit was obtained with low-pass and band-pass-filtered stimuli with different center frequencies (e.g. <250 vs. 250–500 Hz), meaning multiple frequency regions contain useful cues for bimodal benefit. Clinical implications are that (1) all aidable frequencies should be amplified in individuals with bimodal hearing, and (2) verification of audibility at 125Hz is unnecessary unless it is the only aidable frequency.
doi:10.1159/000357588
PMCID: PMC4104148  PMID: 24556850
Bimodal hearing; Bimodal benefit; Cochlear implants; Acoustic bandwidth
12.  Availability of binaural cues for bilateral implant recipients and bimodal listeners with and without preserved hearing in the implanted ear 
Audiology & neuro-otology  2013;19(1):57-71.
The purpose of the current study was to examine the availability of binaural cues for adult, bilateral cochlear implant (CI) patients, bimodal patients and hearing preservation patients using a multiple baseline, observational study design. Speech recognition was assessed using the Bamford-Kowal-Bench Speech-In-Noise (BKB-SIN) test as well as the AzBio sentences [Spahr et al., 2012] presented in a multi-talker babble at +5 dB signal-to-noise ratio (SNR). Test conditions included speech at 0° with noise presented at 0° (S0N0), 90° (S0N90), and 270° (S0N270). Estimates of summation, head shadow (HS), squelch, and spatial release from masking (SRM) were calculated. Though none of the subject groups consistently showed access to binaural cues, the hearing preservation patients exhibited a significant correlation between summation and squelch whereas the bilateral and bimodal participants did not. That is, the two effects associated with binaural hearing—summation and squelch—were positively correlated for only the listeners with bilateral acoustic hearing. This finding provides evidence for the supposition that implant recipients with bilateral acoustic hearing have access to binaural cues which should, in theory, provide greater benefit in noisy listening environments. It is likely, however, that the chosen test environment negatively affected the outcomes. Specifically, the spatially separated noise conditions directed noise toward the mic port of the behind-the-ear (BTE) hearing aid and implant processor. Thus it is possible that in more realistic listening environments for which the diffuse noise is not directed toward the processor/hearing aid mic, hearing preservation patients have binaural hearing cues for improved speech understanding.
doi:10.1159/000355700
PMCID: PMC3932362  PMID: 24356514
13.  Gentamicin concentration gradients in scala tympani perilymph following systemic applications 
Audiology & neuro-otology  2013;18(6):383-391.
In prior studies it was shown that round window membrane (RWM) application of gentamicin produced a robust baso-apical concentration gradient in the perilymph of scala tympani (ST) with peak concentrations in the basal turn of ST. These gradients potentially contribute to the clinical efficacy and safety of intratympanic gentamicin applications for the treatment of Meniere’s disease. The present study aimed to establish the distribution of gentamicin along ST perilymph after systemic applications.
Gentamicin sulfate was applied intravenously in the amounts of 100, 300 and 600 mg/kg/bw over a period of three hours or as a 300 mg/kg/bw subcutaneous bolus injection. Three and five hours after the start of the application perilymph of ST was aspirated from the cochlea apex of the right and left cochlea, respectively. Ten sequential 1 μL-perilymph samples from the apex of each cochlea were quantitatively analyzed using a fluorescence polarization immunoassay.
In contrast to local RWM delivery, systemic application of gentamicin resulted in highest perilymph levels in the apex of the cochlea with decreasing concentrations towards the basal regions of ST. The absolute gentamicin concentrations increased with amount of drug applied and time before sampling.
While the basal-apical gradient measured after local drug applications to the RW niche is likely the result of the direct uptake of drugs into the perilymph of the ST, distribution by diffusion and a very low perilymph flow towards the cochlear apex, computer simulations suggested that the apical-basal gradient observed with these systemic applications can be explained by higher entry rates of gentamicin in the apex compared to the basal turns of the cochlea. It is also possible that gentamicin enters perilymph indirectly from blood via the endolymph. In this case the faster kinetics in apical turns could be due to the smaller cross-sectional area of scala tympani relative to endolymph in the apical turns.
doi:10.1159/000355283
PMCID: PMC3918439  PMID: 24192668
cochlea; drug delivery; gentamicin; inner ear; ototoxicity; perilymph; pharmacokinetics; guinea pig
14.  A Novel Otoferlin Splice-Site Mutation in Siblings with Auditory Neuropathy Spectrum Disorder 
Audiology & neuro-otology  2013;18(6):10.1159/000354978.
We characterize a novel otoferlin (OTOF) mutation discovered in a sibling pair diagnosed with ANSD and investigate auditory nerve function through their cochlear implants. Genetic sequencing revealed a homozygous mutation at the OTOF splice donor site of exon 28 (IVS28+1 G>T) in both siblings. Functional investigation showed that the intronic sequence between exons 28 and 29 was retained in the mutated minigenes that were expressed in 293T cells. Auditory nerve compound action potential recovery functions in the siblings demonstrated different rates of neural recovery, with sibling AN1 showing rapid recovery (1.14 ms) and AN2 showing average recovery (.78 ms) compared to subjects with sensorineural hearing loss (SNHL) (average: adults .71 ms; children .85 ms). Differences in neural recovery were consistent with speech perception differences between the siblings. Genotype information may indicate site of lesion in hearing loss; however, additional, as yet, unknown factors may impact clinical outcomes and must be considered.
doi:10.1159/000354978
PMCID: PMC3877672  PMID: 24135434
15.  Histopathology of the Clarion Cochlear Implant Electrode Positioner in a Human Subject 
Audiology & neuro-otology  2013;18(4):223-227.
A silastic electrode positioner was introduced by the Advanced Bionics Corporation in 1999 and it was designed to achieve a perimodiolar position of the stimulating electrode. The positioner was voluntarily recalled in the United States in July 2002 due to an apparent higher risk of bacterial meningitis in patients in whom the electrode positioner had been placed. A detailed histopathologic study of the positioner in the human has not previously been published. The histopathologic findings in a 74-year old woman who underwent bilateral cochlear implantation using the positioner are presented. Findings including a large track caused by the combined electrode and its positioner with considerable disruption of the basilar membrane and osseous spiral lamina. Although there was a fibrous sheath around the electrode and positioner at the cochleostomy in both ears, this fibrous sheath did not extend deeply into the cochlea except at the apical end of the electrode beyond the positioner. This resulted in a large fluid space around and between the positioner and electrode within the cochlea and presumably in fluid continuity with the CSF space. Possible clinical implications are discussed.
doi:10.1159/000351300
PMCID: PMC4189082  PMID: 23774789
Histopathology; Clarion Cochlear Implant; Positioner; Human
16.  Influence of cochleostomy and cochlear implant insertion on drug gradients following intratympanic application in guinea pigs 
Audiology & neuro-otology  2013;18(5):10.1159/000353534.
Locally-applied drugs can protect residual hearing following cochlear implantation. The influence of cochlear implantation on drug levels in scala tympani (ST) after round window application was investigated in guinea pigs using the marker trimethylphenlyammonium (TMPA) measured in real-time with TMPA-selective microelectrodes. TMPA concentration in the upper basal turn of ST rapidly increased during implantation and then declined due to cerebrospinal fluid entering ST at the cochlear aqueduct and exiting at the cochleostomy. The TMPA increase was found to be caused by the cochleostomy drilling, if the burr tip partially entered ST. TMPA distribution in the second turn was less affected by implantation procedures. These findings show that basal turn drug levels may be changed during implantation and the changes may need to be considered in the interpretation of therapeutic effects of drugs in conjunction with implantation.
doi:10.1159/000353534
PMCID: PMC3872819  PMID: 24008355
Cochleostomy; perforation; cochlear implant; electrode; pharmacokinetics; drug distribution; computational modeling
17.  Preclinical and Clinical Studies of Unrelieved Aural Fullness following Intratympanic Gentamicin Injection in Patients with Intractable Ménière’s Disease 
Audiology & neuro-otology  2013;18(5):297-306.
Objective
To clarify whether gentamicin affects vestibular dark cells in guinea pigs and relieves patients of aural fullness with intractable Ménière’s disease following intratympanic administration.
Materials and Methods
Purified gentamicin-Texas Red (GTTR) was injected intratympanically in guinea pigs that were sacrificed at 1, 3, 7, 14 and 28 days. GTTR uptake was examined in hair cells, and transitional cells and dark cells in vestibular end-organs were examined. Specific attention was paid to its distribution in dark cells under confocal microscopy, and the ultrastructure of dark cells using electron microscopy, following intratympanic injection.
Results
Dark cells in the semicircular canals showed weak GTTR uptake at 1, 3, 7, 14 and 28 days after intratympanic injection, with no significant differences at various time points after injection. However, the adjacent transitional cells demonstrated intense GTTR uptake that was retained for at least 28 days. Ultrastructural studies demonstrated negligible characteristics associated with apoptosis or necrosis in these dark cells. The tight junctions between dark cells showed no signs of disruption at 7 or 28 days after injection.
Conclusion
Intratympanic gentamicin has little direct impact on vestibular dark cells.
Clinical Application
A modified low-dose titration intratympanic approach was used in 29 patients with intractable vertigo and the clinical outcomes were followed. Aural fullness following intratympanic gentamicin injection was not relieved based on our subjective scales, demonstrated by no statistically significant difference between preinjection (4.16 ± 3.08) and postinjection (3.58 ± 2.93; p > 0.05) aural fullness scores. Vertigo control was achieved in 88% of patients, with hearing deterioration identified in 16% of patients. Intratympanic gentamicin administration might not lead to relief of aural fullness in patients with intractable vertigo, although it can achieve a high vertigo control rate with some cochleotoxicity.
doi:10.1159/000351805
PMCID: PMC3962045  PMID: 24008307
Gentamicin; Intratympanic injection; Dark cells; Ménière’s disease; Aural fullness
18.  Using Temporal Modulation Sensitivity to Select Stimulation Sites for Processor MAPs in Cochlear Implant Listeners 
Audiology & neuro-otology  2013;18(4):10.1159/000351302.
Previous studies in our laboratory showed that temporal acuity as assessed by modulation detection thresholds (MDTs) varied across activation sites and that this site-to-site variability was subject specific. Using two 10-channel MAPs, the previous experiments showed that processor MAPs that had better across-site mean (ASM) MDTs yielded better speech recognition than MAPs with poorer ASM MDTs tested in the same subject. The current study extends our earlier work on developing more optimal fitting strategies to test the feasibility of using a site-selection approach in the clinical domain. This study examined the hypothesis that revising the clinical speech processor MAP for cochlear implant (CI) recipients by turning off selected sites that have poorer temporal acuity and reallocating frequencies to the remaining electrodes would lead to improved speech recognition. Twelve CI recipients participated in the experiments. We found that site selection procedure based on MDTs in the presence of a masker resulted in improved performance on consonant recognition and recognition of sentences in noise. In contrast, vowel recognition was poorer with the experimental MAP than with the clinical MAP, possibly due to reduced spectral resolution when sites were removed from the experimental MAP. Overall, these results suggest a promising path for improving recipient outcomes using personalized processor-fitting strategies based on a psychophysical measure of temporal acuity.
doi:10.1159/000351302
PMCID: PMC3874548  PMID: 23881208
Cochlear implantation; across-site differences; speech recognition; modulation detection thresholds; personalized processor fitting
19.  Long-Term Speech and Language Outcomes in Prelingually Deaf Children, Adolescents and Young Adults Who Received Cochlear Implants in Childhood 
Audiology & neuro-otology  2013;18(5):289-296.
This study investigated long-term speech and language outcomes in 51 prelingually deaf children, adolescents, and young adults who received cochlear implants (CIs) prior to 7 years of age and used their implants for at least 7 years. Average speech perception scores were similar to those found in prior research with other samples of experienced CI users. Mean language test scores were lower than norm-referenced scores from nationally representative normal-hearing, typically-developing samples, although a majority of the CI users scored within one standard deviation of the normative mean or higher on the Peabody Picture Vocabulary Test, Fourth Edition (63%) and Clinical Evaluation of Language Fundamentals, Fourth Edition (69%). Speech perception scores were negatively associated with a meningitic etiology of hearing loss, older age at implantation, poorer pre-implant unaided pure tone average thresholds, lower family income, and the use of Total Communication. Users of CIs for 15 years or more were more likely to have these characteristics and were more likely to score lower on measures of speech perception compared to users of CIs for 14 years or less. The aggregation of these risk factors in the > 15 years of CI use subgroup accounts for their lower speech perception scores and may stem from more conservative CI candidacy criteria in use at the beginning of pediatric cochlear implantation.
doi:10.1159/000353405
PMCID: PMC3895537  PMID: 23988907
cochlear implant; deafness; language; speech perception; children; prelingual hearing loss
20.  Time-Frequency Analysis of Transient-Evoked Otoacoustic Emissions in Children exposed to Carboplatin Chemotherapy 
Audiology & neuro-otology  2012;18(2):71-82.
The aims of this study were to characterize and quantify time-frequency changes in transient-evoked otoacoustic emissions (TEOAEs) recorded in children diagnosed with retinoblastoma who were receiving carboplatin chemotherapy. A signal processing technique, the wavelet transform (WT), was used to analyze TEOAE waveforms in narrow-band frequency components. Ten children (aged 3–72 months) diagnosed with unilateral or bilateral retinoblastoma were enrolled in the study. TEOAEs were acquired from the children with linear sequences of 70 dB peSPL clicks. After WT analysis, TEOAE energy, latency, and normalized energy in the narrow-band frequency components were compared before and during carboplatin (average dose 1693 mg/m2) chemotherapy treatment. On a group basis, no significant differences (p>0.05) in pre- and post-carboplatin TEOAE energy, latency, or normalized energy were observed. There were decreases in normalized energy on an individual basis in 10/18 ears in the sample. Exposure to carboplatin chemotherapy did not cause significant changes in TEOAE energy, latency, and normalized energy during treatment. However, long-term monitoring of hearing with measurements of TEOAEs is warranted given the risks of delayed hearing loss in some children receiving carboplatin chemotherapy.
doi:10.1159/000343909
PMCID: PMC3777667  PMID: 23147804
Carboplatin; Children; Cochlea; Ototoxicity; TEOAE; Wavelet
21.  Cortical Encoding of Pitch Contour Changes in Cochlear Implant Users: A Mismatch Negativity Study 
Audiology & neuro-otology  2013;18(5):10.1159/000351802.
A better understanding of melodic pitch perception in cochlear implants (CIs) may guide signal processing and/or rehabilitation techniques to improve CI patients' music perception and appreciation. In this study, the mismatch negativity (MMN) in response to infrequent changes in five-tone pitch contours was obtained in CI users and normal hearing (NH) listeners. Melodic contour identification (MCI) was also measured. Results showed that MCI performance was poorer in CI subjects than in NH subjects; The MMNs were missing in all CI subjects for the 1-semitone contours. The MMNs with the 5-semitone contours were observed in a smaller proportion of CI subjects than in NH subjects. Results suggest that encoding of pitch contour changes in CI users appears to be degraded, most likely due to the limited pitch cues provided by the CI and deafness-related compromise of brain substrates.
doi:10.1159/000351802
PMCID: PMC3823678  PMID: 23920129
cochlear implant; music perception; pitch contour; mismatch negativity; electrophysiology
22.  Hypoxia-Inducible Factor and Vascular Endothelial Growth Factor Pathway for the Study of Hypoxia in a New Model of Otitis Media with Effusion 
Audiology & neuro-otology  2012;17(6):349-356.
The hypoxia-inducible factor and vascular endothelial growth factor (HIF-VEGF) pathway in hypoxic conditions of the middle ear due to dysfunction of the eustachian tube is still unknown, but it is considered as one pathogenetic mechanism in otitis media. This study was designed to investigate the possible involvement of the HIF-VEFG pathway in otitis media with effusion induced by dysfunction of the eustachian tube. We adopted a soft palate approach to obstruct the orifice of the eustachian tube to establish otitis media in a rat model. Auditory evoked brainstem response and tympanometry were used as hearing function tests, hypoxia-related factors were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of hypoxia-related proteins was detected by Western blot and immunostaining. The model of otitis media with effusion was successfully induced by cauterizing the orifice of the eustachian tube. RT-PCR showed up-regulation of hypoxia-related factors in cauterized ears. Western blot and immunostaining showed that the expression of hypoxia-related proteins in cauterized ears was increased. Hypoxia-induced vascular proliferation and an increase in permeability may be one pathogenetic mechanism of otitis media due to dysfunction of the eustachian tube.
doi:10.1159/000341163
PMCID: PMC3637049  PMID: 22907120
Animal model; Dysfunction; Eustachian tube; Hypoxia-inducible factor-1 α; Vascular endothelial growth factor
23.  Effects of Lower Frequency-to-Electrode Allocations on Speech and Pitch Perception with the Hybrid Short-Electrode Cochlear Implant 
Audiology & neuro-otology  2012;17(6):357-372.
Because some users of a Hybrid short-electrode cochlear implant (CI) lose their low-frequency residual hearing after receiving the CI, we tested whether increasing the CI speech processor frequency allocation range to include lower frequencies improves speech perception in these individuals. A secondary goal was to see if pitch perception changed after experience with the new CI frequency allocation. Three subjects who had lost all residual hearing in the implanted ear were recruited to use an experimental CI frequency allocation with a lower frequency cutoff than their current clinical frequency allocation. Speech and pitch perception results were collected at multiple time points throughout the study. In general, subjects showed little or no improvement for speech recognition with the experimental allocation when the CI was worn with a hearing aid in the contralateral ear. However, all three subjects showed changes in pitch perception that followed the changes in frequency allocations over time, consistent with previous studies showing that pitch perception changes upon provision of a CI.
doi:10.1159/000341165
PMCID: PMC3519932  PMID: 22907151
short-electrode; Hybrid; electro-acoustic stimulation; cochlear implant; pitch; speech perception; plasticity
24.  The Effect of Superior Semicircular Canal Dehiscence on Intracochlear Sound Pressures 
Audiology & neuro-otology  2012;17(5):338-348.
Semicircular canal dehiscence (SCD) is a pathological opening in the bony wall of the inner ear that can result in conductive hearing loss. The hearing loss is variable across patients, and the precise mechanism and source of variability are not fully understood. Simultaneous measurements of basal intracochlear sound pressures in scala vestibuli (SV) and scala tympani (ST) enable quantification of the differential pressure across the cochlear partition, the stimulus that excites the cochlear partition. We used intracochlear sound pressure measurements in cadaveric preparations to study the effects of SCD size. Sound-induced pressures in SV and ST, as well as stapes velocity and ear-canal pressure were measured simultaneously for various sizes of SCD followed by SCD patching. Our results showed that at low frequencies (<600 Hz), SCD decreased the pressure in both SV and ST, as well as differential pressure, and these effects became more pronounced as dehiscence size was increased. Near 100 Hz, SV decreased about 10 dB for a 0.5 mm dehiscence and 20 dB for a 2 mm dehiscence, while ST decreased about 8 dB for a 0.5 mm dehiscence and 18 dB for a 2mm dehiscence. Differential pressure decreased about 10 dB for a 0.5 mm dehiscence and about 20 dB for a 2 mm dehiscense at 100 Hz. In some ears, for frequencies above 1 kHz, the smallest pinpoint dehiscence had bigger effects on the differential pressure (10 dB decrease) than larger dehiscenses (less than 10 dB decrease), suggesting larger hearing losses in this frequency range. These effects due to SCD were reversible by patching the dehiscence. We also showed that under certain circumstances such as SCD, stapes velocity is not related to how the ear can transduce sound across the cochlear partition because it is not directly related to the differential pressure, emphasizing that certain pathologies cannot be fully assessed by measurements such as stapes velocity.
doi:10.1159/000339653
PMCID: PMC3541532  PMID: 22814034
superior semicircular canal dehiscence; cochlear pressure; SCD; scala vestibuli; scala tympani; cochlea; differential pressure
25.  Effects of computer-assisted speech training on Mandarin-speaking hearing-impaired children 
Audiology & neuro-otology  2007;12(5):307-312.
The present study investigated whether moderate amounts of computer-assisted speech training can improve the speech recognition performance of hearing-impaired children. Ten Mandarin-speaking children (3 hearing aid users and 7 cochlear implant users) participated in the study. Training was conducted at home using a personal computer for one half-hour per day, five days per week, for a period of 10 weeks. Results showed significant improvements in subjects’ vowel, consonant, and tone recognition performance after training. The improved performance was largely retained two months after training was completed. These results suggest that moderate amounts of auditory training, using a computer-based auditory rehabilitation tool with minimal supervision, can be effective in improving the speech performance of hearing-impaired children.
doi:10.1159/000103211
PMCID: PMC3580209  PMID: 17536199

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