Cochlear Implant Outcomes in Patients With TMTC2-Associated Sensorineural Hearing Loss and Auditory Neuropathy/Auditory Dys-Synchrony.

OBJECTIVE: To investigate the outcomes of cochlear implantation in patients with TMTC2-associated sensorineural hearing loss and auditory neuropathy/auditory dys-synchrony. PATIENTS: Adult and pediatric cochlear implant (CI) patients followed in an academic center who tested positive for TMTC2 genetic variant rs35725509. INTERVENTION: Cochlear implantation. MAIN OUTCOME MEASURES: Speech perception scores in quiet. RESULTS: Ten CI patients were identified with TMTC2 variant rs35725509 out of 157 patients who underwent genetic testing (i.e., 6.3% of patients tested). All demonstrated progressive, bilateral hearing loss with severe-to-profound audiometric thresholds preoperatively. Pre-CI and 1-year post-CI speech recognition percent correct scores were compared. Post-CI speech perception (mean 61.0%, standard deviation 31.4%) was significantly higher than pre-CI speech perception (mean 21.0%, standard deviation 27.0%) (p = 0.002). Individually, 9 of the 10 subjects experienced significant improvements in speech perception pre- to post-CI (p < 0.05). Electrically evoked compound action potential measures were available for five patients, and all showed normal electrically evoked compound action potential thresholds. CONCLUSION: Patients with TMTC2-associated sensorineural hearing loss and auditory neuropathy/auditory dys-synchrony have significantly improved speech perception outcomes with cochlear implantation and should be considered candidates for this intervention if there are no other contraindications.

In vivo biodistribution and ototoxicity assessment of cationic liposomal-ceftriaxone via noninvasive trans-tympanic delivery in chinchilla models: Implications for otitis media therapy.

OBJECTIVES: We report the in vivo biodistribution and ototoxicity of cationic liposomal-ceftriaxone (CFX) delivered via ear drop formulation in adult chinchilla. METHODS: CFX was encapsulated in liposomes with size of ∼100 nm and surface charge of +20 mV. 100 µl liposomes or free drug was applied twice daily in both external ear canals of adult chinchillas for either 3 or 10 days. Study groups included free ceftriaxone (CFX, Day 3: n = 4, Day 10: n = 8), liposomal ceftriaxone (CFX-Lipo, Day 3: n = 4, Day 10: n = 8), and a systemic control group (Day 3: n = 4, Day 10: n = 4). Ceftriaxone delivery to the middle ear and systemic circulation was quantified by HPLC assays. Liposome transport was visualized via confocal microscopy. Auditory brainstem response (ABR) tests and cochlear histology were used to assess ototoxicity. RESULTS: Liposomal ceftriaxone (CFX-Lipo) displayed a ∼658-fold increase in drug delivery efficiency in the middle ear relative to the free CFX (8.548 ± 0.4638% vs. 0.013 ± 0.0009%, %Injected dose, Mean ± SEM). CFX measured in blood serum (48.2 ± 7.78 ng/ml) following CFX-Lipo treatment in ear was 41-fold lower compared to systemic free-CFX treatment (1990.7 ± 617.34 ng/ml). ABR tests and histological analysis indicated no ototoxicity due to the treatment. CONCLUSION: Cationic liposomal encapsulation results in potent drug delivery across the tympanic membrane to the middle ear with minimal systemic exposure and no ototoxicity.

Chronic tympanic membrane perforation repair with a collagen-based scaffold: An in vivo model.

OBJECTIVE: The aim of this study was to assess the in vivo efficacy of a novel regenerative collagen-based scaffold developed by the Royal College of Surgeons in Ireland in a chronic tympanic membrane perforation (TMP) using a chinchilla model. METHODS: Bilateral TMPs were induced in 17 mixed gender chinchillas using tympanic membrane resection followed by a mixture of topical Mitomycin C and dexamethasone for 3 days. These were monitored with weekly otoscopy for 8 weeks. Animals were excluded if signs of infection developed in the follow up period (n = 8). At 8 weeks, intervention began and 18 TMPs were assigned to either treatment with the collagen-based scaffold (treated group) or spontaneous healing (control group). Animals were euthanized 6 weeks post-intervention. Otoscopic imaging and auditory brain response (ABR) were conducted at baseline, 8 weeks post-TMP induction and 6 weeks post-intervention. All TMPs were then evaluated at 6 weeks post-intervention and bullae underwent histologic evaluation. RESULTS: At 6 weeks post-intervention, otoscopic imaging demonstrated various degrees of healing in the treated ears. The treated group was noted to have an increased rate of healing when compared to the control group. Histologic evaluation demonstrated a variation in the degree of perforation healing within groups, with some animals in the treated group showing high levels of perforation healing. At 8 weeks after the TMP procedure, most of the animals had worsened hearing response. At 6-week post the collagen-based scaffold treatment, about 50 % (4/8) of the treated ears had improved in hearing response as compared to those of non-treated ears. CONCLUSION: Given the initial histologic evidence of partial healing in scaffold-treated ears, the post-intervention period should be extended to monitor the potential for complete healing. Given the overall positive findings related to healing with the scaffold-treated ears, this material warrants further investigation.

Cochlear Implant Performance in Candidates With Moderate Hearing Loss Qualifying in Noise.

OBJECTIVE: To determine postcochlear implantation performance for patients qualifying on preimplant testing in noise. STUDY DESIGN: Retrospective chart review of cochlear implant recipients. MAIN OUTCOME MEASURE: Performance on word and sentence testing in the implanted ear and bimodal condition were compared between pre- and postimplantation time points. RESULTS: At 2-years postimplantation, CNC testing in quiet in the implanted ear improved from an average percent correct score of 14.0 ±â€Š12.1% to 54.9 ±â€Š14.8% (n = 20, p < 0.0001, d = 3.0) for those qualifying at +8, and from 23.4 ±â€Š15.6% to 55.5 ±â€Š19.4% (n = 28, p < 0.0001, d = 1.8) for those qualifying at +5. Likewise, AzBio in quiet in the implanted ear improved from an average % correct score of 19.9 ±â€Š16.0% to 75.1 ±â€Š11.8% (n = 20, p < 0.0001, d = 4.0) for those qualifying at +8, and from 46.2 ±â€Š21.7% to 74.1 ±â€Š21.3% (n = 27, p < 0.0001, d = 1.4) for those qualifying at +5. CNC and AzBio performance in quiet in the bimodal condition also improved with those qualifying at +8 and +5 having similar average scores at 2-years post activation. For those qualifying at +8, performance improved on CNC and AzBio in the implanted ear in 95% of patients and in the bimodal condition in 89% of patients. The proportion of patients improving on both tests for those qualifying at +5 at 2 years was 85% in the implanted ear, and 72% in the bimodal condition. CONCLUSION: The majority of patients qualifying for cochlear implantation with the addition of noise showed improved speech perception in quiet. These data provide useful counseling tools for patients considering cochlear implantation who do not meet traditional eligibility requirements when tested in quiet.

A Longitudinal Comparison of Environmental Sound Recognition in Adults With Hearing Aids Before and After Cochlear Implantation.

Purpose The aims of this study were (a) to longitudinally assess environmental sound recognition (ESR) before and after cochlear implantation in a sample of postlingually deafened adults and (b) to assess the extent to which spectro-temporal processing abilities influence ESR with cochlear implants (CIs). Method In a longitudinal cohort study, 20 postlingually deafened adults were tested with hearing aids on the Familiar Environmental Sound Test-Identification and AzBio sentences in quiet pre-CI and 6 months post-CI. A subset of 11 participants were also tested 12 months post-CI. Pre-CI spectro-temporal processing was assessed using the Spectral-temporally Modulated Ripple Test. Results Average ESR accuracy pre-CI (M = 63.60%) was not significantly different from ESR accuracy at 6 months (M = 65.40%) or 12 months (M = 69.09%) post-CI. In 11 participants (55%), however, ESR improved following implantation by 10.91 percentage points, on average. Pre-CI ESR correlated moderately and significantly with pre-CI and 12-month post-CI AzBio scores, with a trend toward significance for AzBio performance at 6 months. Pre-CI spectro-temporal processing was moderately associated with ESR at 6 and 12 months post-CI but not with speech recognition post-CI. Conclusions The present findings failed to demonstrate an overall significant improvement in ESR following implantation. Nevertheless, more than half of our sample showed some degree of improvement in ESR. Several environmental sounds were poorly identified both before and after implantation. Spectro-temporal processing ability prior to implantation appears to predict postimplantation performance for ESR. These findings indicate the need for greater attention to ESR following cochlear implantation and for developing individualized targets for ESR rehabilitation. Supplemental Material https://doi.org/10.23641/asha.13876745.

Improved Speech Intelligibility in Subjects With Stable Sensorineural Hearing Loss Following Intratympanic Dosing of FX-322 in a Phase 1b Study.

OBJECTIVES: There are no approved pharmacologic therapies for chronic sensorineural hearing loss (SNHL). The combination of CHIR99021+valproic acid (CV, FX-322) has been shown to regenerate mammalian cochlear hair cells ex vivo. The objectives were to characterize the cochlear pharmacokinetic profile of CV in guinea pigs, then measure FX-322 in human perilymph samples, and finally assess safety and audiometric effects of FX-322 in humans with chronic SNHL. STUDY DESIGNS: Middle ear residence, cochlear distribution, and elimination profiles of FX-322 were assessed in guinea pigs. Human perilymph sampling following intratympanic FX-322 dosing was performed in an open-label study in cochlear implant subjects. Unilateral intratympanic FX-322 was assessed in a Phase 1b prospective, randomized, double-blinded, placebo-controlled clinical trial. SETTING: Three private otolaryngology practices in the US. PATIENTS: Individuals diagnosed with mild to moderately severe chronic SNHL (≤70 dB standard pure-tone average) in one or both ears that was stable for ≥6 months, medical histories consistent with noise-induced or idiopathic sudden SNHL, and no significant vestibular symptoms. INTERVENTIONS: Intratympanic FX-322. MAIN OUTCOME MEASURES: Pharmacokinetics of FX-322 in perilymph and safety and audiometric effects. RESULTS: After intratympanic delivery in guinea pigs and humans, FX-322 levels in the cochlear extended high-frequency region were observed and projected to be pharmacologically active in humans. A single dose of FX-322 in SNHL subjects was well tolerated with mild, transient treatment-related adverse events (n = 15 FX-322 vs 8 placebo). Of the six patients treated with FX-322 who had baseline word recognition in quiet scores below 90%, four showed clinically meaningful improvements (absolute word recognition improved 18-42%, exceeding the 95% confidence interval determined by previously published criteria). No significant changes in placebo-injected ears were observed. At the group level, FX-322 subjects outperformed placebo group in word recognition in quiet when averaged across all time points, with a mean improvement from baseline of 18.9% (p = 0.029). For words in noise, the treated group showed a mean 1.3 dB signal-to-noise ratio improvement (p = 0.012) relative to their baseline scores while placebo-treated subjects did not (-0.21 dB, p = 0.71). CONCLUSIONS: Delivery of FX-322 to the extended high-frequency region of the cochlea is well tolerated and enhances speech recognition performance in multiple subjects with stable chronic hearing loss.

Auditory brainstem responses in aging dark agouti rats.

The present study examined auditory function across age in the dark agouti (DA) rat strain. Auditory brainstem responses (ABRs) were measured for frequencies 8, 16, and 32 kHz in male and female DA rats from 3 to 18 months of age. Hearing thresholds and absolute and interpeak latencies (IPLs) were analyzed. Male hearing thresholds remained stable for the first year of life and then significantly increased at 18 months across all frequencies; female hearing remained stable at all tested ages out to 18 months. At 12 months, male DA rats showed significantly longer absolute latencies by age (i.e., compared with 3-month-old males) and sex (compared with 12-month-old females), with no differences in IPLs. At 18 months, female DA rats showed significantly longer absolute latencies with age (compared with 3-month-old females) and sex (compared with 18-month-old males), particularly for the later waves. Female IPLs were also significantly longer with age and by sex for the later waves. This report supports the feasibility of using male DA rats in studies to investigate age-related hearing loss (ARHL; presbycusis).

Development of in-house genetic screening for pediatric hearing loss.

OBJECTIVES: To evaluate the efficiency of in-house genetic testing for mutations causing the most common types of inherited, nonsyndromic, sensorineural hearing loss (SNHL). METHODS: Retrospective cohort study of 200 patients at a single, pediatric medical center with suspected or confirmed hearing loss who underwent either send out vs in-house genetic testing for mutations in GJB2/GJB6, SLC26A4, and MTRNR1. Primary outcome measure was the difference in mean turnaround time for send-out vs in-house genetic testing. Additional outcomes included associations between audiometric findings and genetic test results. RESULTS: One hundred four send-out tests were performed between October 2010 and June 2014, and 100 in-house tests were performed between November 2014 and November 2016. The mean turnaround time for send-out testing was 53.7 days. The mean turnaround time for in-house testing was 18.9 days. This difference was statistically significant (P < .001). The largest component of turnaround time was the amount of time elapsed between receipt of specimen in the lab and final test result. These intervals were 47.0 and 18.3 days for send-out and in-house tests, respectively. Notably, the longest turnaround time for in-house testing (43 days) was less than the average turnaround time for send-out testing. In addition, we identified two simple audiometric parameters (ie, bilateral newborn hearing screen referral and audiometry showing symmetric SNHL) that may increase diagnostic yield of genetic testing. CONCLUSIONS: The development of in-house genetic testing programs for inherited SNHL can significantly reduce testing turnaround times. Newborn hearing screening and audiometry results can help clinicians identify patients most likely to benefit from genetic testing. LEVEL OF EVIDENCE: IV.

Results of a 2-Year Prospective Multicenter Study Evaluating Long-term Audiological and Clinical Outcomes of a Transcutaneous Implant for Bone Conduction Hearing.

OBJECTIVE(S): To evaluate 2-year audiological and clinical outcomes of a transcutaneous implant for bone conduction hearing of a previously published 6-month evaluation. DESIGN: Fifty-four unilaterally implanted adult patients with conductive or mild mixed hearing loss or single-sided sensorineural deafness were included in this prospective multicenter study. Follow-up visits were scheduled post-surgery at 10 days; 4, 6, and 12 weeks; 6, 12, and 24 months. Main outcomes were audiological benefit, patient-reported outcomes (PROs), soft tissue status, pain, numbness, implant survival, and daily usage. RESULTS: In the study population, the transcutaneous implant resulted in statistically significant improvement in objective hearing test and PROs compared with the unaided situation. Soft tissue complications were observed in 4.6% of the patients per visit. Pain/discomfort and numbness were initially reported in the majority of the patients, but declined over time; approximately 9% of patients reported some degree of numbness and 15% (slight) pain/discomfort after 2 years. During the 24-month period, two implant magnets were removed (3.7%), while two other implants were converted to the percutaneous counterpart (3.7%). At the final visit, 89.6% (n = 42 out of 47) of the patients used their sound processor, with a median daily usage of 6 h/d (range, 0-18 h/d). CONCLUSIONS: After 24 months, the transcutaneous implant provided statistically significant mean improvement in objective and subjective hearing performance as well as PROs compared with the preoperative unaided condition and had a low soft tissue complication rate. The test device could be considered as an alternative treatment option for appropriately selected and counseled patients.

Audiological and clinical outcomes of a transcutaneous bone conduction hearing implant: Six-month results from a multicentre study.

OBJECTIVES: To compare the hearing performance of patients with conductive and mild mixed hearing loss and single-sided sensorineural deafness provided with a new transcutaneous bone conduction hearing implant (the Baha Attract System) with unaided hearing as well as aided with a sound processor on a softband. Furthermore, to evaluate safety and subjective benefit before and after implantation of the test device. PARTICIPANTS: Fifty-four adult patients in five participating centres were enrolled in this prospective study. Baseline data were collected during a pre-operative visit, and after a softband trial, all patients were implanted unilaterally. Follow-up visits were scheduled at 10 days, 4, 6, 12 weeks and 6 months. MAIN OUTCOME MEASURES: Free-field hearing thresholds pure-tone average (PTA4 in dB HL; mean threshold at 500, 1000, 2000, 4000 Hz; primary outcome measure). Individual free-field hearing thresholds, speech recognition in quiet and in noise, soft tissue status during follow-up and subjective benefit as measured with the Abbreviated Profile of Hearing Aid Benefit (APHAB), Speech, Spatial and Qualities of Hearing Scale (SSQ) and Health Utilities Index (HUI) questionnaires. RESULTS: Implantation of the Baha Attract System resulted in favourable audiological outcomes compared to unaided conditions. On the primary outcome parameter, a statistically significant improvement was observed compared to unaided hearing for the patients with conductive/mixed hearing loss (mean PTA4 difference -20.8 dB HL, SD 9.8; P < 0.0001) and for the patients with single-sided sensorineural deafness (SSD) (mean PTA4 difference -21.6 dB HL, SD 12.2; P < 0.0001). During all audiology tests, the non-test ear was blocked. Statistically significant improvements were also recorded in speech tests in quiet and noise compared to unaided hearing for the conductive/mixed hearing loss group and for speech in quiet in the SSD group. Compared to the pre-operative measurement with softband, no significant differences were recorded in the PTA4 free-field hearing threshold or the other audiological outcomes in either of the groups (P > 0.05). Soft tissue-related issues observed during follow-up included numbness, pain/discomfort at the implant site and to a lesser extent pressure-related skin complications. A declining trend was noted in the rate of these complications during follow-up. Approximately 20% of patients reported some degree of numbness and 38% (slight) pain/discomfort at final follow-up of 6 months. Good results on the subjective benefit questionnaires were observed, with statistically significant improvements on APHAB and SSQ questionnaires, and on the hearing attribute of HUI3. CONCLUSIONS: The Baha Attract System provided a significant improvement in hearing performance and subjective benefit compared to the pre-operative unaided condition (with the non-test ear blocked). Hearing performance of the Baha Attract was similar to a test situation with the same sound processor on a softband. A proportion of the patients reported numbness and pain/discomfort at the implant site during follow-up, especially during the first post-operative weeks. Based on the results of the current multicentre study, the Baha Attract can be considered as a treatment option for patients with the aforementioned hearing losses. Especially in the SSD patients, a careful selection procedure is warranted. Therefore, a pre-operative trial should be part of the decision-making process before fitting a patient with the Baha Attract System.

Improved Speech Perception in Cochlear Implant Users With Interleaved High-Rate Pulse Trains.

OBJECTIVE: Electrical stimulation with a cochlear implant (CI) elicits abnormally high neural synchrony, which poses significant challenges for speech perception. Previous investigations showed that constant-amplitude high-rate pulse trains (HRPs) desynchronize neural responses and improve stimulus encoding. The study objective was to investigate the effects of HRP on speech perception in adult CI users. STUDY DESIGN: Prospective, within-subject design. SETTING: Tertiary CI center. PATIENTS: Ten adult CI recipients. INTERVENTION: Sentence stimuli were created by modifying a basic continuous interleaved sampling (CIS) strategy (1,000 pulses per second; pps) with interleaved biphasic pulse trains (3,000 pps) on even electrodes. Institute of Electrical and Electronics Engineers sentences in quiet and in noise were tested without HRP, and with HRPs of various stimulation levels. MAIN OUTCOME MEASURE: Sentence perception in percent correct was calculated for all conditions. The highest speech perception score with HRP stimulation was defined as "max-HRP." RESULTS: Group analyses showed significantly improved sentence perception in background noise with HRPs (p < 0.001). There was no significant difference for sentence perception in quiet for the group. However, seven of 10 subjects experienced some benefit from HRP stimuli in quiet and the degree of HRP benefit showed significant relationships with baseline performance and age at implantation, indicating that HRP stimuli may be most beneficial for older patients or poorer performers. CONCLUSIONS: Significant improvement in speech perception in noise was observed with HRP stimuli. Some recipients may also benefit from HRP stimulation in quiet. Interleaved HRPs hold promise as a novel stimulation paradigm with clinical sound processing strategies to improve patient performance.

TMTC2 variant associated with sensorineural hearing loss and auditory neuropathy spectrum disorder in a family dyad.

BACKGROUND: Sensorineural hearing loss (SNHL) is a common form of hearing loss that can be inherited or triggered by environmental insults; auditory neuropathy spectrum disorder (ANSD) is a SNHL subtype with unique diagnostic criteria. The genetic factors associated with these impairments are vast and diverse, but causal genetic factors are rarely characterized. METHODS: A family dyad, both cochlear implant recipients, presented with a hearing history of bilateral, progressive SNHL, and ANSD. Whole-exome sequencing was performed to identify coding sequence variants shared by both family members, and screened against genes relevant to hearing loss and variants known to be associated with SNHL and ANSD. RESULTS: Both family members are successful cochlear implant users, demonstrating effective auditory nerve stimulation with their devices. Genetic analyses revealed a mutation (rs35725509) in the TMTC2 gene, which has been reported previously as a likely genetic cause of SNHL in another family of Northern European descent. CONCLUSION: This study represents the first confirmation of the rs35725509 variant in an independent family as a likely cause for the complex hearing loss phenotype (SNHL and ANSD) observed in this family dyad.

Tablet-based Screening for Hearing Loss: Feasibility of Testing in Nonspecialty Locations.

OBJECTIVE: To determine the feasibility of audiometric screening with tablet-based applications in typical clinic locations: examination room and clinic waiting area. STUDY DESIGN: A randomized prospective study. SETTING: Tertiary referral center. PATIENTS: Participants included 107 adult patients referred for audiometric testing to assess hearing loss. INTERVENTION: Each patient completed standard audiometry testing and one of three tablet-based audiometric applications that included pure-tone air conduction testing. The tablet-based audiometric testing was completed in a quiet examination room and a clinic waiting area using noise-cancellation headphones. A 5-question patient satisfaction survey was completed at the end of the testing. MAIN OUTCOME MEASURE: Thresholds at each frequency were compared with those obtained from tablet-based audiometric applications in a quiet examination room and clinic waiting area. Sensitivity and specificity of each tablet-based audiogram in detecting a hearing loss at each frequency was determined. RESULTS: All three tablet-based audiometric applications were user-friendly for hearing screening. However, one application was shown to be feasible and the most accurate of the three tested with 92% of thresholds within 10 dB of conventional audiometry across all test conditions. This application had a sensitivity of 96 to 100% and specificity of 72 to 85% for identifying a hearing loss in each frequency tested. Variability was noted among applications between testing in a quiet clinic room and testing in the clinic waiting area. Patients showed no preference for either conventional audiometry or the tablet-based device. CONCLUSION: Tablet-based audiometric applications can be used to screen for hearing loss in typical clinic locations. This tool does not replace standard audiometry testing but allows for screening for hearing disorders when appropriate and in settings without access to audiometric equipment.

Multicenter US Clinical Trial With an Electric-Acoustic Stimulation (EAS) System in Adults: Final Outcomes.

OBJECTIVE: To demonstrate the safety and effectiveness of the MED-EL Electric-Acoustic Stimulation (EAS) System, for adults with residual low-frequency hearing and severe-to-profound hearing loss in the mid to high frequencies. STUDY DESIGN: Prospective, repeated measures. SETTING: Multicenter, hospital. PATIENTS: Seventy-three subjects implanted with PULSAR or SONATA cochlear implants with FLEX electrode arrays. INTERVENTION: Subjects were fit postoperatively with an audio processor, combining electric stimulation and acoustic amplification. MAIN OUTCOME MEASURES: Unaided thresholds were measured preoperatively and at 3, 6, and 12 months postactivation. Speech perception was assessed at these intervals using City University of New York sentences in noise and consonant-nucleus-consonant words in quiet. Subjective benefit was assessed at these intervals via the Abbreviated Profile of Hearing Aid Benefit and Hearing Device Satisfaction Scale questionnaires. RESULTS: Sixty-seven of 73 subjects (92%) completed outcome measures for all study intervals. Of those 67 subjects, 79% experienced less than a 30 dB HL low-frequency pure-tone average (250-1000 Hz) shift, and 97% were able to use the acoustic unit at 12 months postactivation. In the EAS condition, 94% of subjects performed similarly to or better than their preoperative performance on City University of New York sentences in noise at 12 months postactivation, with 85% demonstrating improvement. Ninety-seven percent of subjects performed similarly or better on consonant-nucleus-consonant words in quiet, with 84% demonstrating improvement. CONCLUSION: The MED-EL EAS System is a safe and effective treatment option for adults with normal hearing to moderate sensorineural hearing loss in the low frequencies and severe-to-profound sensorineural hearing loss in the high frequencies who do not benefit from traditional amplification.

Clinical Outcomes of the Cochlear™ Nucleus(®) 5 Cochlear Implant System and SmartSound™ 2 Signal Processing.

BACKGROUND: While published data exist regarding cochlear implant (CI) outcomes from large academic programs, evidence of benefit based on national, multicenter clinical trials is needed for information regarding typical patient outcomes of devices implanted by U.S. centers representing larger academic to smaller hospital-based programs. PURPOSE: This nationwide trial evaluated outcomes in a group of newly implanted adult recipients of the Cochlear™ Nucleus(®) 5 CI system and SmartSound™ 2 signal processing. Unlike previous clinical trials, the AzBio sentence test was used and represents recent transition in our field to use of more challenging test materials. It was hypothesized that (1) speech perception scores in quiet with SmartSound™ 2 signal processing would not be statistically different from previous-generation devices; (2) speech perception scores in noise with SmartSound™ 2 signal processing would be better with enhanced microphone directionality; (3) speech perception scores in noise will be better with the preferred SmartSound™ 2 program for listening in noise; and (4) cochlear implantation would improve quality of life as assessed by the updated Health Utility Index Mark 3 (HUI3). A secondary purpose was to examine the relationships among the current and previously used speech perception tests of the Minimum Speech Test Battery (MSTB). It was hypothesized that speech perception scores within the same test interval would show predictive relationships. RESEARCH DESIGN: Prospective, single-arm, repeated-measures study across 13 CI centers in the United States between February 2010 and June 2012. The participating centers ranged from larger academic to smaller hospital-based programs to accurately represent the diversity of programs in the United States. STUDY SAMPLE: Participants were 38 postlingually deafened adult CI candidates. DATA COLLECTION AND ANALYSIS: Primary measures were Consonant-Nucleus-Consonant (CNC) words in quiet and the AzBio Sentence Test in Quiet (AzBioQ) and in Noise (AzBioN) tested at preoperative, and 3-, 6-, and 12-mo postactivation intervals. Quality of life was measured with the HUI3. For the secondary objective, statistical analyses were performed to investigate the predictive properties between current and previously used MSTB tests. RESULTS: Mean CNC scores were significantly higher compared to the Nucleus(®) 24 Contour™ at 3 mo (p < 0.05) postactivation and showed no difference compared to the Nucleus(®) Freedom™ at 6 mo postactivation. Both SmartSound™ 2 FOCUS and NOISE programs provided significant improvements in performance in noise over the EVERYDAY program (p < 0.001), and performance with the FOCUS program was significantly better compared to the NOISE program (p < 0.001). Speech perception in noise was not related to patients' subjective program preferences. Quality-of-life outcomes showed significant improvements from the preoperative to 6-mo postactivation interval (p < 0.05-0.001). Strong and significant correlations were found between preoperative CNC and AzBioQ and preoperative Hearing-in-Noise Test sentences in Quiet (HINTQ) and AzBioQ. At 12-mo postactivation, there were strong and highly significant correlations between CNC and AzBioQ, HINTQ and AzBioQ, and Hearing-in-Noise Test sentences in Noise and AzBioN (all p < 0.001). CONCLUSIONS: Results of this national clinical trial showed significant improvements in speech perception and quality of life following cochlear implantation. SmartSound™ 2 signal processing features showed a significant benefit of FOCUS when listening in noise, although preference of signal processing feature did not correlate with performance. Significant correlations were observed between speech perception tests. The findings of this study can be applied in clinical assessment, programming, and follow-up for CI candidates and recipients.

Association of TMTC2 With Human Nonsyndromic Sensorineural Hearing Loss.

IMPORTANCE: Sensorineural hearing loss (SNHL) is commonly caused by conditions that affect cochlear structures or the auditory nerve, and the genes identified as causing SNHL to date only explain a fraction of the overall genetic risk for this debilitating disorder. It is likely that other genes and mutations also cause SNHL. OBJECTIVE: To identify a candidate gene that causes bilateral, symmetric, progressive SNHL in a large multigeneration family of Northern European descent. DESIGN, SETTING, AND PARTICIPANTS: In this prospective genotype and phenotype study performed from January 1, 2006, through April 1, 2016, a 6-generation family of Northern European descent with 19 individuals having reported early-onset hearing loss suggestive of an autosomal dominant inheritance were studied at a tertiary academic medical center. In addition, 179 unrelated adult individuals with SNHL and 186 adult individuals reporting nondeafness were examined. MAIN OUTCOMES AND MEASURES: Sensorineural hearing loss. RESULTS: Nine family members (5 women [55.6%]) provided clinical audiometric and medical records that documented hearing loss. The hearing loss is characterized as bilateral, symmetric, progressive SNHL that reached severe to profound loss in childhood. Audiometric configurations demonstrated a characteristic dip at 1000 to 2000 Hz. All affected family members wear hearing aids or have undergone cochlear implantation. Exome sequencing and linkage and association analyses identified a fully penetrant sequence variant (rs35725509) on chromosome 12q21 (logarithm of odds, 3.3) in the TMTC2 gene region that segregates with SNHL in this family. This gene explains the SNHL occurrence in this family. The variant is also associated with SNHL in a cohort of 363 unrelated individuals (179 patients with confirmed SNHL and 184 controls, P = 7 × 10-4). CONCLUSIONS AND RELEVANCE: A previously uncharacterized gene, TMTC2, has been identified as a candidate for causing progressive SNHL in humans. This finding identifies a novel locus that causes autosomal dominant SNHL and therefore a more detailed understanding of the genetic basis of SNHL. Because TMTC2 has not been previously reported to regulate auditory function, the discovery reveals a potentially new, uncharacterized mechanism of hearing loss.

Temporal and spectral contributions to musical instrument identification and discrimination among cochlear implant users.

OBJECTIVE: To investigate the contributions of envelope and fine-structure to the perception of timbre by cochlear implant (CI) users as compared to normal hearing (NH) listeners. METHODS: This was a prospective cohort comparison study. Normal hearing and cochlear implant patients were tested. Three experiments were performed in sound field using musical notes altered to affect the characteristic pitch of an instrument and the acoustic envelope. Experiment 1 assessed the ability to identify the instrument playing each note, while experiments 2 and 3 assessed the ability to discriminate the different stimuli. RESULTS: Normal hearing subjects performed better than CI subjects in all instrument identification tasks, reaching statistical significance for 4 of 5 stimulus conditions. Within the CI population, acoustic envelope modifications did not significantly affect instrument identification or discrimination. With envelope and pitch cues removed, fine structure discrimination performance was similar between normal hearing and CI users for the majority of conditions, but some specific instrument comparisons were significantly more challenging for CI users. CONCLUSIONS: Cochlear implant users perform significantly worse than normal hearing listeners on tasks of instrument identification. However, cochlear implant listeners can discriminate differences in envelope and some fine structure components of musical instrument sounds as well as normal hearing listeners. The results indicated that certain fine structure cues are important for cochlear implant users to make discrimination judgments, and therefore may affect interpretation toward associating with a specific instrument for identification.

Evaluation of a spectral subtraction strategy to suppress reverberant energy in cochlear implant devices.

The smearing effects of room reverberation can significantly impair the ability of cochlear implant (CI) listeners to understand speech. To ameliorate the effects of reverberation, current dereverberation algorithms focus on recovering the direct sound from the reverberated signal by inverse filtering the reverberation process. This contribution describes and evaluates a spectral subtraction (SS) strategy capable of suppressing late reflections. Late reflections are the most detrimental to speech intelligibility by CI listeners as reverberation increases. By tackling only the late part of reflections, it is shown that users of CI devices can benefit from the proposed strategy even in highly reverberant rooms. The proposed strategy is also compared against an ideal reverberant (binary) masking approach. Speech intelligibility results indicate that the proposed SS solution is able to suppress additive reverberant energy to a degree comparable to that achieved by an ideal binary mask. The added advantage is that the SS strategy proposed in this work can allow for a potentially real-time implementation in clinical CI processors.

Differences in Perception of Musical Stimuli among Acoustic, Electric, and Combined Modality Listeners.

BACKGROUND: Cochlear implants have shown vast improvements in speech understanding for those with severe to profound hearing loss; however, music perception remains a challenge for electric hearing. It is unclear whether the difficulties arise from limitations of sound processing, the nature of a damaged auditory system, or a combination of both. PURPOSE: To examine music perception performance with different acoustic and electric hearing configurations. RESEARCH DESIGN: Chord discrimination and timbre perception were tested in subjects representing four daily-use listening configurations: unilateral cochlear implant (CI), contralateral bimodal (CIHA), bilateral hearing aid (HAHA) and normal-hearing (NH) listeners. A same-different task was used for discrimination of two chords played on piano. Timbre perception was assessed using a 10-instrument forced-choice identification task. STUDY SAMPLE: Fourteen adults were included in each group, none of whom were professional musicians. DATA COLLECTION AND ANALYSIS: The number of correct responses was divided by the total number of presentations to calculate scores in percent correct. Data analyses were performed with Kruskal-Wallis one-way analysis of variance and linear regression. RESULTS: Chord discrimination showed a narrow range of performance across groups, with mean scores ranging between 72.5% (CI) and 88.9% (NH). Significant differences were seen between the NH and all hearing-impaired groups. Both the HAHA and CIHA groups performed significantly better than the CI groups, and no significant differences were observed between the HAHA and CIHA groups. Timbre perception was significantly poorer for the hearing-impaired groups (mean scores ranged from 50.3-73.9%) compared to NH (95.2%). Significantly better performance was observed in the HAHA group as compared to both groups with electric hearing (CI and CIHA). There was no significant difference in performance between the CIHA and CI groups. Timbre perception was a significantly more difficult task than chord discrimination for both the CI and CIHA groups, yet the easier task for the NH group. A significant difference between the two tasks was not seen in the HAHA group. CONCLUSIONS: Having impaired hearing decreases performance compared to NH across both chord discrimination and timbre perception tasks. For chord discrimination, having acoustic hearing improved performance compared to electric hearing only. Timbre perception distinguished those with acoustic hearing from those with electric hearing. Those with bilateral acoustic hearing, even if damaged, performed significantly better on this task than those requiring electrical stimulation, which may indicate that CI sound processing fails to capture and deliver the necessary acoustic cues for timbre perception. Further analysis of timbre characteristics in electric hearing may contribute to advancements in programming strategies to obtain optimal hearing outcomes.

The role of age on cochlear implant performance, use, and health utility: a multicenter clinical trial.

OBJECTIVE: To use data obtained in a multicenter clinical trial to evaluate factors affecting performance with an implant, with special emphasis on the effect of age on performance. STUDY DESIGN AND SETTING: Post hoc analyses of data collected during a multicenter prospective study to evaluate performance with a recently introduced cochlear implant (CI) system conducted at 13 academic centers in the United States. Subjects participated in speech recognition testing in quiet and noise and completed questionnaires regarding health utility and processor use. PATIENTS: Thirty-eight adults with moderate to profound hearing loss who ranged in age from 18 to 89 years. Subjects were divided into younger (<65 yr, n = 20) and older (≥65 yr, n = 18) groups for the analyses. INTERVENTION: All subjects received a multichannel CI system. Preimplant to postimplant change in speech recognition was evaluated for each group, and the performance of the two groups was compared. Postimplant performance of older subjects who scored greater than 40% preimplant on HINT (Hearing in Noise Test) sentences was also evaluated. Linear regression was used to further evaluate the effects of variables on outcomes. RESULTS: Both younger and older subjects demonstrated significant improvement in speech recognition and hearing health utility after receiving a CI, and differences between groups were insignificant. Older subjects who scored greater than 40% preoperatively on HINT sentences demonstrated a significant improvement in speech recognition. CONCLUSION: Both older and younger patients can receive significant improvement in speech recognition and health utility after receiving a CI.