A novel mutation in the OTOF gene in a Chinese family with auditory neuropathy.

Gene therapy for monogenic auditory neuropathy (AN) has successfully improved hearing function in target gene-deficient mice. Accurate genetic diagnosis can not only clarify the etiology but also accurately locate the lesion site, providing a basis for gene therapy and guiding patient intervention and management strategies. In this study, we collected data from a family with a pair of sisters with prelingual deafness. According to their auditory tests, subject Ⅱ-1 was diagnosed with profound sensorineural hearing loss (SNHL), Ⅱ-2 was diagnosed with AN, Ⅰ-1 was diagnosed with high-frequency SNHL, and Ⅰ-2 had normal hearing. Using whole-exome sequencing (WES), one nonsense mutation, c.4030C>T (p.R1344X), and one missense mutation, c.5000C>A (p.A1667D), in the OTOF (NM_001287489.1) gene were identified in the two siblings. Their parents were heterozygous carriers of c.5000C>A (father) and c.4030C>T (mother). We hypothesized that c.5000C>A is a novel pathogenic mutation. Thus, subject Ⅱ-1 should also be diagnosed with AN caused by OTOF mutations. These findings not only expand the OTOF gene mutation spectrum for AN but also indicate that WES is an effective approach for accurately diagnosing AN.

Coping with alpine habitats: genomic insights into the adaptation strategies of Triplostegia glandulifera (Caprifoliaceae).

How plants find a way to thrive in alpine habitats remains largely unknown. Here we present a chromosome-level genome assembly for an alpine medicinal herb, Triplostegia glandulifera (Caprifoliaceae), and 13 transcriptomes from other species of Dipsacales. We detected a whole-genome duplication event in T. glandulifera that occurred prior to the diversification of Dipsacales. Preferential gene retention after whole-genome duplication was found to contribute to increasing cold-related genes in T. glandulifera. A series of genes putatively associated with alpine adaptation (e.g. CBFs, ERF-VIIs, and RAD51C) exhibited higher expression levels in T. glandulifera than in its low-elevation relative, Lonicera japonica. Comparative genomic analysis among five pairs of high- vs low-elevation species, including a comparison of T. glandulifera and L. japonica, indicated that the gene families related to disease resistance experienced a significantly convergent contraction in alpine plants compared with their lowland relatives. The reduction in gene repertory size was largely concentrated in clades of genes for pathogen recognition (e.g. CNLs, prRLPs, and XII RLKs), while the clades for signal transduction and development remained nearly unchanged. This finding reflects an energy-saving strategy for survival in hostile alpine areas, where there is a tradeoff with less challenge from pathogens and limited resources for growth. We also identified candidate genes for alpine adaptation (e.g. RAD1, DMC1, and MSH3) that were under convergent positive selection or that exhibited a convergent acceleration in evolutionary rate in the investigated alpine plants. Overall, our study provides novel insights into the high-elevation adaptation strategies of this and other alpine plants.

A new active bone-conduction implant: surgical experiences and audiological outcomes in patients with bilateral congenital microtia.

PURPOSE: First-generation bone bridges (BBs) have demonstrated favorable safety and audiological benefits in patients with conductive hearing loss. However, studies on the effects of second-generation BBs are limited, especially among children. In this study, we aimed to explore the surgical and audiological effects of second-generation BBs in patients with bilateral congenital microtia. METHODS: This single-center prospective study included nine Mandarin-speaking patients with bilateral microtia. All the patients underwent BCI Generation 602 (BCI602; MED-EL, Innsbruck, Austria) implant surgery between September 2021 and June 2023. Audiological and sound localization tests were performed under unaided and BB-aided conditions. RESULTS: The transmastoid and retrosigmoid sinus approaches were implemented in three and six patients, respectively. No patient underwent preoperative planning, lifts were unnecessary, and no sigmoid sinus or dural compression occurred. The mean function gain at 0.5-4.0 kHz was 28.06 ± 4.55-dB HL. The word recognition scores improved significantly in quiet under the BB aided condition. Signal-to-noise ratio reduction by 10.56 ± 2.30 dB improved the speech reception threshold in noise. Patients fitted with a unilateral BB demonstrated inferior sound source localization after the initial activation. CONCLUSIONS: Second-generation BBs are safe and effective for patients with bilateral congenital microtia and may be suitable for children with mastoid hypoplasia without preoperative three-dimensional reconstruction.

Features of the speech processing network in post- and prelingually deaf cochlear implant users.

The onset of hearing loss can lead to altered brain structure and functions. However, hearing restoration may also result in distinct cortical reorganization. A differential pattern of functional remodeling was observed between post- and prelingual cochlear implant users, but it remains unclear how these speech processing networks are reorganized after cochlear implantation. To explore the impact of language acquisition and hearing restoration on speech perception in cochlear implant users, we conducted assessments of brain activation, functional connectivity, and graph theory-based analysis using functional near-infrared spectroscopy. We examined the effects of speech-in-noise stimuli on three groups: postlingual cochlear implant users (n = 12), prelingual cochlear implant users (n = 10), and age-matched individuals with hearing controls (HC) (n = 22). The activation of auditory-related areas in cochlear implant users showed a lower response compared with the HC group. Wernicke's area and Broca's area demonstrated differences network attributes in speech processing networks in post- and prelingual cochlear implant users. In addition, cochlear implant users maintain a high efficiency of the speech processing network to process speech information. Taken together, our results characterize the speech processing networks, in varying noise environments, in post- and prelingual cochlear implant users and provide new insights for theories of how implantation modes impact remodeling of the speech processing functional networks.

Aging effects on dual-route speech processing networks during speech perception in noise.

Healthy aging leads to complex changes in the functional network of speech processing in a noisy environment. The dual-route neural architecture has been applied to the study of speech processing. Although evidence suggests that senescent increases activity in the brain regions across the dorsal and ventral stream regions to offset reduced periphery, the regulatory mechanism of dual-route functional networks underlying such compensation remains largely unknown. Here, by utilizing functional near-infrared spectroscopy (fNIRS), we investigated the compensatory mechanism of the dual-route functional connectivity, and its relationship with healthy aging by using a speech perception task at varying signal-to-noise ratios (SNR) in healthy individuals (young adults, middle-aged adults, and older adults). Results showed that the speech perception scores showed a significant age-related decrease with the reduction of the SNR. The analysis results of dual-route speech processing networks showed that the functional connection of Wernicke's area and homolog Wernicke's area were age-related increases. Further to clarify the age-related characteristics of the dual-route speech processing networks, graph-theoretical network analysis revealed an age-related increase in the efficiency of the networks, and the age-related differences in nodal characteristics were found both in Wernicke's area and homolog Wernicke's area under noise environment. Thus, Wernicke's area might be a key network hub to maintain efficient information transfer across the speech process network with healthy aging. Moreover, older adults would recruit more resources from the homologous Wernicke's area in a noisy environment. The recruitment of the homolog of Wernicke's area might provide a means of compensation for older adults for decoding speech in an adverse listening environment. Together, our results characterized dual-route speech processing networks at varying noise environments and provided new insight for the compensatory theories of how aging modulates the dual-route speech processing functional networks.

Effects of Age on the Auditory Cortex During Speech Perception in Noise: Evidence From Functional Near-Infrared Spectroscopy.

OBJECTIVES: Age-related speech perception difficulties may be related to a decline in central auditory processing abilities, particularly in noisy or challenging environments. However, how the activation patterns related to speech stimulation in different noise situations change with normal aging has yet to be elucidated. In this study, we aimed to investigate the effects of noisy environments and aging on patterns of auditory cortical activation. DESIGN: We analyzed the functional near-infrared spectroscopy signals of 20 young adults, 21 middle-aged adults, and 21 elderly adults, and evaluated their cortical response patterns to speech stimuli under five different signal to noise ratios (SNRs). In addition, we analyzed the behavior score, activation intensity, oxyhemoglobin variability, and dominant hemisphere, to investigate the effects of aging and noisy environments on auditory cortical activation. RESULTS: Activation intensity and oxyhemoglobin variability both showed a decreasing trend with aging at an SNR of 0 dB; we also identified a strong correlation between activation intensity and age under this condition. However, we observed an inconsistent activation pattern when the SNR was 5 dB. Furthermore, our analysis revealed that the left hemisphere may be more susceptible to aging than the right hemisphere. Activation in the right hemisphere was more evident in older adults than in the left hemisphere; in contrast, younger adults showed leftward lateralization. CONCLUSIONS: Our analysis showed that with aging, auditory cortical regions gradually become inflexible in noisy environments. Furthermore, changes in cortical activation patterns with aging may be related to SNR conditions, and that understandable speech with a low SNR ratio but still understandable may induce the highest level of activation. We also found that the left hemisphere was more affected by aging than the right hemisphere in speech perception tasks; the left-sided dominance observed in younger individuals gradually shifted to the right hemisphere with aging.

Abnormal white and gray matter functional connectivity is associated with cognitive dysfunction in presbycusis.

Presbycusis is characterized by high-frequency hearing loss and is closely associated with cognitive decline. Previous studies have observed functional reorganization of gray matter in presbycusis, but the information transmission between gray matter and white matter remains ill-defined. Using resting-state functional magnetic resonance imaging, we investigated differences in functional connectivity (GM-GM, WM-WM, and GM-WM) between 60 patients with presbycusis and 57 healthy controls. Subsequently, we examined the correlation between these connectivity differences with high-frequency hearing loss as well as cognitive impairment. Our results revealed significant alterations in functional connectivity involving the body of the corpus callosum, posterior limbs of the internal capsule, retrolenticular region of the internal capsule, and the gray matter regions in presbycusis. Notably, disrupted functional connectivity was observed between the body of the corpus callosum and ventral anterior cingulate cortex in presbycusis, which was associated with impaired attention. Additionally, enhanced functional connectivity was found in presbycusis between the internal capsule and the ventral auditory processing stream, which was related to impaired cognition in multiple domains. These two patterns of altered functional connectivity between gray matter and white matter may involve both bottom-up and top-down regulation of cognitive function. These findings provide novel insights into understanding cognitive compensation and resource redistribution mechanisms in presbycusis.

Analysis of audiological outcomes of children referred from a universal newborn hearing screening program over 9 years in Beijing, China.

Universal newborn hearing screening (UNHS) and audiological diagnosis are crucial for children with congenital hearing loss (HL). The objective of this study was to analyze hearing screening techniques, audiological outcomes and risk factors among children referred from a UNHS program in Beijing. A retrospective analysis was performed in children who were referred to our hospital after failing UNHS during a 9-year period. A series of audiological diagnostic tests were administered to each case, to confirm and determine the type and degree of HL. Risk factors for HL were collected. Of 1839 cases, 53.0% were referred after only transient evoked otoacoustic emission (TEOAE) testing, 46.1% were screened by a combination of TEOAE and automatic auditory brainstem response (AABR) testing, and 1.0% were referred after only AABR testing. HL was confirmed in 55.7% of cases. Ears with screening results that led to referral experienced a more severe degree of HL than those with results that passed. Risk factors for HL were identified in 113 (6.1%) cases. The main risk factors included craniofacial anomalies (2.7%), length of stay in the neonatal intensive care unit longer than 5 days (2.4%) and birth weight less than 1500 g (0.8%). The statistical data showed that age (P < 0.001) and risk factors, including craniofacial anomalies (P < 0.001) and low birth weight (P = 0.048), were associated with the presence of HL. This study suggested that hearing screening plays an important role in the early detection of HL and that children with risk factors should be closely monitored.

Comparisons of air-conduction hearing thresholds between manual and automated methods in a commercial audiometer.

Objective: To investigate the correlation of air-conduction thresholds between automated audiometry in a non-isolated environment and manual audiometry in participants with normal hearing and different degrees of hearing loss. Methods: Eighty-three participants aged 11-88 years old underwent automated pure-tone audiometry in a non-acoustically isolated environment, and the results were compared with those of manual pure-tone audiometry performed in a standard acoustically isolated booth, with the order of testing randomised. Six frequencies of 250, 500, 1,000, 2000, 4,000 and 8,000 Hz were tested. Results: All 166 ears were completed and 996 valid hearing threshold data were obtained, with 28 data exceeding the 95% confidence interval in the Bland-Altman plot, accounting for 2.81% of all data. The means and standard deviations of the differences for the six frequencies from 250 to 8,000 Hz were, respectively, 0.63 ± 5.31, 0.69 ± 4.50, 0.45 ± 4.99, 0.3 ± 6.2, -0.15 ± 4.8, and 0.21 ± 4.97 dB. The correlation coefficients of the two test results for normal hearing, mild, moderate, severe and above hearing loss groups were 0.95, 0.92, 0.97, and 0.96, respectively. The correlation coefficient of the automated and manual audiometry thresholds for the age groups under 40 years, 40-60 years, and 60 years above, were 0.98, 0.97 and 0.97, respectively, with all being statistically significant (p < 0.01). The response time of the three age groups were 791 ± 181 ms, 900 ± 190 ms and 1,063 ± 332 ms, respectively, and there was a significant difference between the groups under 40 years and over 60 years. Conclusion: There was good consistency between automated pure-tone audiometry in a non-acoustically isolated environment and manual pure-tone audiometry in participants with different hearing levels and different age groups.