Browsing by Subject "Hearing loss"
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Item Autophagy proteins are essential for aminoglycoside-induced hearing loss(Taylor & Francis, 2023) Li, Jinan; Liu, Chang; Müller, Ulrich; Zhao, Bo; Otolaryngology -- Head and Neck Surgery, School of MedicineAminoglycosides (AGs) are widely used to treat severe infections. However, systemically administered AGs preferentially kill cochlear hair cells, resulting in irreversible hearing loss. Recently, we found that AGs bind to RIPOR2 and trigger its rapid translocation in cochlear hair cells. Reducing RIPOR2 expression entirely prevents AG-induced hair cell death and subsequent hearing loss in mice. Next using yeast two-hybrid screening, we found that RIPOR2 interacts with GABARAP, a key macroautophagy/autophagy pathway protein. Following AG treatment, RIPOR2 colocalizes with GABARAP and regulates the activation of autophagy. Remarkably, reducing the expression of GABARAP, or another key autophagy protein MAP1LC3B/LC3B, entirely prevents AG-induced hair cell death and subsequent hearing loss in mice. Furthermore, we found that AGs activate the autophagy pathway specific to mitochondria. Reducing the expression of PINK1 or PRKN/parkin, two key mitophagy proteins, protects hair cells against AG toxicity. Thus, our findings demonstrated that RIPOR2-mediated autophagic dysfunction is essential for AG-induced hearing loss and provided potential therapeutic strategies for preventing AG toxicity.Item Biallelic Loss-of-Function Variants in BICD1 Are Associated with Peripheral Neuropathy and Hearing Loss(MDPI, 2023-05-17) Hirsch, Yoel; Chung, Wendy K.; Novoselov, Sergey; Weimer, Louis H.; Rossor, Alexander; LeDuc, Charles A.; McPartland, Amanda J.; Cabrera, Ernesto; Ekstein, Josef; Scher, Sholem; Nelson, Rick F.; Schiavo, Giampietro; Henderson, Lindsay B.; Booth, Kevin T. A.; Otolaryngology -- Head and Neck Surgery, School of MedicineHearing loss and peripheral neuropathy are two clinical entities that are genetically and phenotypically heterogeneous and sometimes co-occurring. Using exome sequencing and targeted segregation analysis, we investigated the genetic etiology of peripheral neuropathy and hearing loss in a large Ashkenazi Jewish family. Moreover, we assessed the production of the candidate protein via western blotting of lysates from fibroblasts from an affected individual and an unaffected control. Pathogenic variants in known disease genes associated with hearing loss and peripheral neuropathy were excluded. A homozygous frameshift variant in the BICD1 gene, c.1683dup (p.(Arg562Thrfs*18)), was identified in the proband and segregated with hearing loss and peripheral neuropathy in the family. The BIDC1 RNA analysis from patient fibroblasts showed a modest reduction in gene transcripts compared to the controls. In contrast, protein could not be detected in fibroblasts from a homozygous c.1683dup individual, whereas BICD1 was detected in an unaffected individual. Our findings indicate that bi-allelic loss-of-function variants in BICD1 are associated with hearing loss and peripheral neuropathy. Definitive evidence that bi-allelic loss-of-function variants in BICD1 cause peripheral neuropathy and hearing loss will require the identification of other families and individuals with similar variants with the same phenotype.Item Cochlear Implantation in US Military Veterans: A Single Institution Study(Sage, 2023-05-12) Totten, Douglas J.; Saltagi, Abdul; Libich, Karen; Pisoni, David B.; Nelson, Rick F.; Otolaryngology -- Head and Neck Surgery, School of MedicineObjective: Military veterans have high rates of noise-induced hearing loss (NIHL) which is associated with more significant spiral ganglion neuronal loss. This study explores the relationship between NIHL and cochlear implant (CI) outcomes in veterans. Study design: Retrospective case series of veterans who underwent CI between 2019 and 2021. Setting: Veterans Health Administration hospital. Methods: AzBio Sentence Test, Consonant-Nucleus-Consonant (CNC) scores, and Speech, Spatial, and Qualities of Hearing Scale (SSQ) were measured pre- and postoperatively. Linear regression assessed relationships between outcomes and noise exposure history, etiology of hearing loss, duration of hearing loss, and Self-Administered Gerocognitive Exam (SAGE) scores. Results: Fifty-two male veterans were implanted at an average (standard deviation) age of 75.0 (9.2) years without major complications. The average duration of hearing loss was 36.0 (18.4) years. The average time of hearing aid use was 21.2 (15.4) years. Noise exposure was reported in 51.3% of patients. Objectively, AzBio and CNC scores 6 months postoperatively showed significant improvement of 48% and 39%, respectively. Subjectively, average 6-month SSQ scores showed significant improvement by 34 points (p < .0001). Younger age, SAGE score ≥17, and shorter duration of amplification were associated with higher postoperative AzBio scores. Greater improvement in AzBio and CNC scores was associated with lower preoperative scores. Noise exposure was not associated with any difference in CI performance. Conclusion: Despite high levels of noise exposure and advanced age, veterans derive substantial benefits from cochlear implantation. SAGE score ≥17 may be predictive of overall CI outcomes. Noise exposure does not impact CI outcomes.Item Consensus interpretation of the p.Met34Thr and p.Val37Ile variants in GJB2 by the ClinGen Hearing Loss Expert Panel(Springer Nature, 2019-11) Shen, Jun; Oza, Andrea M.; Del Castillo, Ignacio; Duzkale, Hatice; Matsunaga, Tatsuo; Pandya, Arti; Kang, Hyunseok P.; Mar-Heyming, Rebecca; Guha, Saurav; Moyer, Krista; Lo, Christine; Kenna, Margaret; Alexander, John J.; Zhang, Yan; Hirsch, Yoel; Luo, Minjie; Cao, Ye; Choy, Kwong Wai; Cheng, Yen-Fu; Avraham, Karen B.; Hu, Xinhua; Garrido, Gema; Moreno-Pelayo, Miguel A.; Greinwald, John; Zhang, Kejian; Zeng, Yukun; Brownstein, Zippora; Basel-Salmon, Lina; Davidov, Bella; Frydman, Moshe; Weiden, Tzvi; Nagan, Narasimhan; Willis, Alecia; Hemphill, Sarah E.; Grant, Andrew R.; Siegert, Rebecca K.; DiStefano, Marina T.; Amr, Sami S.; Rehm, Heidi L.; Abou Tayoun, Ahmad N.; Clin Gen Hearing Loss Working Group; Biostatistics, School of Public HealthPurpose: Pathogenic variants in GJB2 are the most common cause of autosomal recessive sensorineural hearing loss. The classification of c.101T>C/p.Met34Thr and c.109G>A/p.Val37Ile in GJB2 are controversial. Therefore, an expert consensus is required for the interpretation of these two variants. Methods: The ClinGen Hearing Loss Expert Panel collected published data and shared unpublished information from contributing laboratories and clinics regarding the two variants. Functional, computational, allelic, and segregation data were also obtained. Case-control statistical analyses were performed. Results: The panel reviewed the synthesized information, and classified the p.Met34Thr and p.Val37Ile variants utilizing professional variant interpretation guidelines and professional judgment. We found that p.Met34Thr and p.Val37Ile are significantly overrepresented in hearing loss patients, compared with population controls. Individuals homozygous or compound heterozygous for p.Met34Thr or p.Val37Ile typically manifest mild to moderate hearing loss. Several other types of evidence also support pathogenic roles for these two variants. Conclusion: Resolving controversies in variant classification requires coordinated effort among a panel of international multi-institutional experts to share data, standardize classification guidelines, review evidence, and reach a consensus. We concluded that p.Met34Thr and p.Val37Ile variants in GJB2 are pathogenic for autosomal recessive nonsyndromic hearing loss with variable expressivity and incomplete penetrance.Item Effects of stimulus variability on speech perception in listeners with hearing impairment(ASHA, 1997) Kirk, Karen Iler; Pisoni, David B.; Miyamoto, R. Christopher; Otolaryngology -- Head and Neck Surgery, School of MedicineTraditional word-recognition tests typically use phonetically balanced (PB) word lists produced by one talker at one speaking rate. Intelligibility measures based on these tests may not adequately evaluate the perceptual processes used to perceive speech under more natural listening conditions involving many sources of stimulus variability. The purpose of this study was to examine the influence of stimulus variability and lexical difficulty on the speech-perception abilities of 17 adults with mild-to-moderate hearing loss. The effects of stimulus variability were studied by comparing word-identification performance in single-talker versus multiple-talker conditions and at different speaking rates. Lexical difficulty was assessed by comparing recognition of "easy" words (i.e., words that occur frequently and have few phonemically similar neighbors) with "hard" words (i.e., words that occur infrequently and have many similar neighbors). Subjects also completed a 20-item questionnaire to rate their speech understanding abilities in daily listening situations. Both sources of stimulus variability produced significant effects on speech intelligibility. Identification scores were poorer in the multiple-talker condition than in the single-talker condition, and word-recognition performance decreased as speaking rate increased. Lexical effects on speech intelligibility were also observed. Word-recognition performance was significantly higher for lexically easy words than lexically hard words. Finally, word-recognition performance was correlated with scores on the self-report questionnaire rating speech understanding under natural listening conditions. The pattern of results suggest that perceptually robust speech-discrimination tests are able to assess several underlying aspects of speech perception in the laboratory and clinic that appear to generalize to conditions encountered in natural listening situations where the listener is faced with many different sources of stimulus variability. That is, word-recognition performance measured under conditions where the talker varied from trial to trial was better correlated with self-reports of listening ability than was performance in a single-talker condition where variability was constrained.Item Exceptional Speech Recognition Outcomes After Cochlear Implantation: Lessons From Two Case Studies(American Speech-Language-Hearing Association, 2022) Herbert, Carolyn J.; Pisoni, David B.; Kronenberger, William G.; Nelson, Rick F.; Otolaryngology -- Head and Neck Surgery, School of MedicinePurpose: Individual differences and variability in outcomes following cochlear implantation (CI) in patients with hearing loss remain significant unresolved clinical problems. Case reports of specific individuals allow for detailed examination of the information processing mechanisms underlying variability in outcomes. Two adults who displayed exceptionally good postoperative CI outcomes shortly after activation were administered a novel battery of auditory, speech recognition, and neurocognitive processing tests. Method: A case study of two adult CI recipients with postlingually acquired hearing loss who displayed excellent postoperative speech recognition scores within 3 months of initial activation. Preoperative City University of New York sentence testing and a postoperative battery of sensitive speech recognition tests were combined with auditory and visual neurocognitive information processing tests to uncover their strengths, weaknesses, and milestones. Results: Preactivation CUNY auditory-only (A) scores were < 5% correct while the auditory + visual (A + V) scores were > 74%. Acoustically with their CIs, both participants' scores on speech recognition, environmental sound identification and speech in noise tests exceeded average CI users scores by 1-2 standard deviations. On nonacoustic visual measures of language and neurocognitive functioning, both participants achieved above average scores compared with normal hearing adults in vocabulary knowledge, rapid phonological coding of visually presented words and nonwords, verbal working memory, and executive functioning. Conclusions: Measures of multisensory (A + V) speech recognition and visual neurocognitive functioning were associated with excellent speech recognition outcomes in two postlingual adult CI recipients. These neurocognitive information processing domains may underlie the exceptional speech recognition performance of these two patients and offer new directions for research explaining variability in postimplant outcomes. Results further suggest that current clinical outcome measures should be expanded beyond the conventional speech recognition measures to include more sensitive robust tests of speech recognition as well as neurocognitive measures of working memory, vocabulary, lexical access, and executive functioning.Item Executive functioning and spoken language skills in young children with hearing aids and cochlear implants: Longitudinal findings(Frontiers Media, 2022-09-23) Jamsek, Izabela A.; Kronenberger, William G.; Pisoni, David B.; Holt, Rachael Frush; Psychiatry, School of MedicineDeaf or hard-of-hearing (DHH) children who use auditory-oral communication display considerable variability in spoken language and executive functioning outcomes. Furthermore, language and executive functioning skills are strongly associated with each other in DHH children, which may be relevant for explaining this variability in outcomes. However, longitudinal investigations of language and executive functioning during the important preschool period of development in DHH children are rare. This study examined the predictive, reciprocal associations between executive functioning and spoken language over a 1-year period in samples of 53 DHH and 59 typically hearing (TH) children between ages 3-8 years at baseline. Participants were assessed on measures of receptive spoken language (vocabulary, sentence comprehension, and following spoken directions) and caregiver-completed executive functioning child behavior checklists during two in-person home visits separated by 1 year. In the sample of DHH children, better executive functioning at baseline (Time 1) was associated with better performance on the higher-order language measures (sentence comprehension and following spoken directions) 1 year later (Time 2). In contrast, none of the Time 1 language measures were associated with better executive functioning in Time 2 in the DHH sample. TH children showed no significant language-executive functioning correlations over the 1-year study period. In regression analyses controlling for Time 1 language scores, Time 1 executive functioning predicted Time 2 language outcomes in the combined DHH and TH samples, and for vocabulary, that association was stronger in the DHH than in the TH sample. In contrast, after controlling for Time 1 executive functioning, none of the regression analyses predicting Time 2 executive functioning from Time 1 language were statistically significant. These results are the first findings to demonstrate that everyday parent-rated executive functioning behaviors predict basic (vocabulary) and higher-order (comprehension, following directions) spoken language development 1 year later in young (3-8 year old) DHH children, even after accounting for initial baseline language skills.Item Extraordinary Speech and Language Outcomes After Auditory Brainstem Implantation: Guidance From a Case Study(American Speech-Language-Hearing Association, 2023) Herbert, Carolyn J.; Kronenberger, William G.; Wolfert, Kim; Nelson, Rick F.; Yates, Charles W.; Pisoni, David B.; Otolaryngology -- Head and Neck Surgery, School of MedicinePurpose: Large individual differences and poor speech recognition outcomes are routinely observed in most patients who have received auditory brainstem implants (ABIs). A case report of an ABI recipient with exceptionally good speech recognition outcomes presents an opportunity to better understand the core information processing mechanisms that underlie variability and individual differences in outcomes. Method: A case study is reported of an adult ABI recipient (ID-006) with postlingually acquired, Neurofibromatosis Type 2 (NF2)-related hearing loss who displayed exceptional postoperative speech recognition scores. A novel battery of assessment measures was used to evaluate ID-006's auditory, cognitive, and linguistic information processing skills. Results: Seventeen years following ABI activation, ID-006 scored 77.6% correct on the AzBio Sentences in quiet. On auditory processing tasks, ID-006 scored higher on tasks with meaningful sentences and much lower on tasks that relied exclusively on audibility. ID-006 also demonstrated exceptionally strong abilities on several cognitive and linguistic information processing tasks. Conclusions: Results from a novel battery of information processing tests suggest that ID-006 relies extensively on top-down predictive processing and cognitive control strategies to efficiently encode and process auditory information provided by his ABI. Results suggest that current measures of outcomes and benefits should be expanded beyond conventional speech recognition measures to include more sensitive and robust measures of speech recognition as well as neurocognitive measures such as executive function, working memory, and lexical access.Item Family Environmental Dynamics Differentially Influence Spoken Language Development in Children With and Without Hearing Loss(American Speech-Language-Hearing Association, 2022) Holt, Rachael Frush; Kronenberger, William G.; Pisoni, David B.; Psychiatry, School of MedicinePurpose: The aim of this study was to evaluate whether families of children with sensorineural hearing loss (SNHL) are organized similarly to those of typically developing, typically hearing (TH) children and whether the dimensions of family dynamics and environment are related to spoken language development similarly in children with and without SNHL. Method: Primary caregivers of children with SNHL (n = 63) or TH (n = 65) completed the Family Environment Scale-Fourth Edition (FES-4) to assess multiple dimensions of family environment. Children's receptive vocabulary was assessed with the Peabody Picture Vocabulary Test-Fourth Edition, and their receptive language was assessed by an age-appropriate version of the Concepts and Following Directions subtest of the Clinical Evaluation of Language Fundamentals and the Sentence Comprehension subscale of the Comprehensive Assessment of Spoken Language-Second Edition. Principal component analysis was used to examine the dimensional structure of the family environment. Results: Three higher order components were derived from FES-4 subscales for both families of children with SNHL and with TH: Supportive, Controlling, and Conflicted. However, the composition of the factors themselves differed between the two groups. For the TH group, most family environment measures on the FES-4 were not associated with language outcomes. In contrast, for children with SNHL, families who were more supportive, less controlling, and less conflicted had children with better language skills. Conclusions: Three well-accepted dimensions of family dynamics and functioning apply to families of children with SNHL, but their composition differs from those of families with TH children. Family environmental dynamics were much more strongly associated with language outcomes in children with SNHL than in their TH peers. The spoken language development of children with SNHL, in particular, is better in families that provide high levels of support for each other and, in particular, low levels of control, disorganization, and conflict, reflecting the fragile nature of their spoken language development.Item Family-Level Executive Functioning and At-Risk Pediatric Hearing Loss Outcomes(American Speech-Language-Hearing Association, 2021) Blank, Andrew; Frush Holt, Rachael; Pisoni, David B.; Kronenberger, William G.; Otolaryngology -- Head and Neck Surgery, School of MedicinePurpose: Using a new measure of family-level executive functioning (EF; the Family Characteristics Scale [FCS]), we investigated associations between family-level EF, spoken language, and neurocognitive skills in children with hearing loss (HL), compared to children with normal hearing. Method: Parents of children with HL (n = 61) or children with normal hearing (n = 65) completed the FCS-Parent, and clinicians evaluated families using the FCS-Examiner. Children completed an age-appropriate version of the Concepts and Following Directions subtest of the Clinical Evaluation of Language Fundamentals and the Peabody Picture Vocabulary Test–Fourth Edition. Child EF was assessed via the parent report Behavior Rating Inventory of Executive Function. Results: Two higher order components were derived from FCS subscales: Family Inhibition and Family Organization. For both samples, Family Inhibition was positively associated with child inhibition, child shifting, and child language comprehension skills. Family Organization was differentially associated with child inhibition, working memory, and planning/organization skills across the samples. Additionally, Family Inhibition was associated with child planning and organization skills for children with HL. Conclusions: Results support the FCS as a measure of family-level EF. Family-level inhibition related to better child inhibition, flexibility/shifting, and language comprehension across both samples and to better planning and organization skills in children with HL. As children with HL experienced greater difficulties in EF, families demonstrated greater organization, possibly as a compensatory measure. Results suggest that inhibition and organization at a family level may be important targets for the development of novel interventions to promote EF and language outcomes for children with HL.