Neural dissociation of the acoustic and cognitive representation of voice identity.

Recognising a speaker's identity by the sound of their voice is important for successful interaction. The skill depends on our ability to discriminate minute variations in the acoustics of the vocal signal. Performance on voice identity assessments varies widely across the population. The neural underpinnings of this ability and its individual differences, however, remain poorly understood. Here we provide critical tests of a theoretical framework for the neural processing stages of voice identity and address how individual differences in identity discrimination mediate activation in this neural network. We scanned 40 individuals on an fMRI adaptation task involving voices drawn from morphed continua between two personally familiar identities. Analyses dissociated neuronal effects induced by repetition of acoustically similar morphs from those induced by a switch in perceived identity. Activation in temporal voice-sensitive areas decreased with acoustic similarity between consecutive stimuli. This repetition suppression effect was mediated by the performance on an independent voice assessment and this result highlights an important functional role of adaptive coding in voice expertise. Bilateral anterior insulae and medial frontal gyri responded to a switch in perceived voice identity compared to an acoustically equidistant switch within identity. Our results support a multistep model of voice identity perception.

Auditory phenotype of Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital malformation and intellectual disability syndrome resulting from variants in DHCR7. Auditory characteristics of persons with SLOS have been described in limited case reports but have not been systematically evaluated. The objective of this study is to describe the auditory phenotype in SLOS. Age- and ability-appropriate hearing evaluations were conducted on 32 patients with SLOS. A subset of 21 had auditory brainstem response testing, from which an auditory neural phenotype is described. Peripheral or retrocochlear auditory dysfunction was observed in at least one ear of 65.6% (21) of the patients in our SLOS cohort. The audiometric phenotype was heterogeneous and included conductive, mixed, and sensorineural hearing loss. The most common presentation was a slight to mild conductive hearing loss, although profound sensorineural hearing loss was also observed. Abnormal auditory brainstem responses indicative of retrocochlear dysfunction were identified in 21.9% of the patients. Many were difficult to test behaviorally and required objective assessment methods to estimate hearing sensitivity. Individuals with SLOS are likely to have hearing loss that may impact communication, including speech and language development. Routine audiologic surveillance should be conducted to ensure prompt management of hearing loss.

Auditory distortions: origins and functions.

To enhance weak sounds while compressing the dynamic intensity range, auditory sensory cells amplify sound-induced vibrations in a nonlinear, intensity-dependent manner. In the course of this process, instantaneous waveform distortion is produced, with two conspicuous kinds of interwoven consequences, the introduction of new sound frequencies absent from the original stimuli, which are audible and detectable in the ear canal as otoacoustic emissions, and the possibility for an interfering sound to suppress the response to a probe tone, thereby enhancing contrast among frequency components. We review how the diverse manifestations of auditory nonlinearity originate in the gating principle of their mechanoelectrical transduction channels; how they depend on the coordinated opening of these ion channels ensured by connecting elements; and their links to the dynamic behavior of auditory sensory cells. This paper also reviews how the complex properties of waves traveling through the cochlea shape the manifestations of auditory nonlinearity. Examination methods based on the detection of distortions open noninvasive windows on the modes of activity of mechanosensitive structures in auditory sensory cells and on the distribution of sites of nonlinearity along the cochlear tonotopic axis, helpful for deciphering cochlear molecular physiology in hearing-impaired animal models. Otoacoustic emissions enable fast tests of peripheral sound processing in patients. The study of auditory distortions also contributes to the understanding of the perception of complex sounds.

Age-Related Hearing Loss in C57BL/6J Mice Is Associated with Mitophagy Impairment in the Central Auditory System.

Aging is associated with functional and morphological changes in the sensory organs, including the auditory system. Mitophagy, a process that regulates the turnover of dysfunctional mitochondria, is impaired with aging. This study aimed to investigate the effect of aging on mitophagy in the central auditory system using an age-related hearing loss mouse model. C57BL/6J mice were divided into the following four groups based on age: 1-, 6-, 12-, and 18-month groups. The hearing ability was evaluated by measuring the auditory brainstem response (ABR) thresholds. The mitochondrial DNA damage level and the expression of mitophagy-related genes, and proteins were investigated by real-time polymerase chain reaction and Western blot analyses. The colocalization of mitophagosomes and lysosomes in the mouse auditory cortex and inferior colliculus was analyzed by immunofluorescence analysis. The expression of genes involved in mitophagy, such as PINK1, Parkin, and BNIP3 in the mouse auditory cortex and inferior colliculus, was investigated by immunohistochemical staining. The ABR threshold increased with aging. In addition to the mitochondrial DNA integrity, the mRNA levels of PINK1, Parkin, NIX, and BNIP3, as well as the protein levels of PINK1, Parkin, BNIP3, COX4, LC3B, mitochondrial oxidative phosphorylation (OXPHOS) subunits I-IV in the mouse auditory cortex significantly decreased with aging. The immunofluorescence analysis revealed that the colocalization of mitophagosomes and lysosomes in the mouse auditory cortex and inferior colliculus decreased with aging. The immunohistochemical analysis revealed that the expression of PINK1, Parkin, and BNIP3 decreased in the mouse auditory cortex and inferior colliculus with aging. These findings indicate that aging-associated impaired mitophagy may contribute to the cellular changes observed in an aged central auditory system, which result in age-related hearing loss. Thus, the induction of mitophagy can be a potential therapeutic strategy for age-related hearing loss.

Nicotinic acetylcholine receptor subunit α7-knockout mice exhibit degraded auditory temporal processing.

The CHRNA7 gene that encodes the α7-subunit of the nicotinic acetylcholine receptor (α7-nAChR) has been associated with some autism spectrum disorders and other neurodevelopmental conditions characterized, in part, by auditory and language impairment. These conditions may include auditory processing disorders that represent impaired timing of neural activity, often accompanied by problems understanding speech. Here, we measure timing properties of sound-evoked activity via the auditory brainstem response (ABR) of α7-nAChR knockout mice of both sexes and wild-type colony controls. We find a significant timing delay in evoked ABR signals that represents midbrain activity in knockouts. We also examine spike-timing properties of neurons in the inferior colliculus, a midbrain nucleus that exhibits high levels of α7-nAChR during development. We find delays of evoked responses along with degraded spiking precision in knockout animals. We find similar timing deficits in responses of neurons in the superior paraolivary nucleus and ventral nucleus of the lateral lemniscus, which are brainstem nuclei thought to shape temporal precision in the midbrain. In addition, we find that other measures of temporal acuity including forward masking and gap detection are impaired for knockout animals. We conclude that altered temporal processing at the level of the brainstem in α7-nAChR-deficient mice may contribute to degraded spike timing in the midbrain, which may underlie the observed timing delay in the ABR signals. Our findings are consistent with a role for the α7-nAChR in types of neurodevelopmental and auditory processing disorders and we identify potential neural targets for intervention.NEW & NOTEWORTHY Disrupted signaling via the α7-nicotinic acetylcholine receptor (α7-nAChR) is associated with neurodevelopmental disorders that include impaired auditory processing. The underlying causes of dysfunction are not known but a common feature is abnormal timing of neural activity. We examined temporal processing of α7-nAChR knockout mice and wild-type controls. We found degraded spike timing of neurons in knockout animals, which manifests at the level of the auditory brainstem and midbrain.

Peripheral auditory dysfunction secondary to traumatic brain injury: a systematic review of literature.

PRIMARY OBJECTIVE: To understand the effects of non-blast-related TBI on peripheral auditory function in adults, as measured through basic and advanced audiological assessments. BACKGROUND: Despite numerous studies demonstrating hearing loss post TBI there has been no systematic investigation of the prevalence, nature and severity of peripheral hearing loss. DATA IDENTIFICATION: An English-language systematic search using MEDLINE, CINAHL, PsychINFO, PubMed and hand-searching of reference lists was conducted from 1 January 1990 to 31 October 2016. STUDY SELECTION: After independent review by the authors, 20 of 281 originally identified articles were retained. DATA EXTRACTION: Audiological findings were extracted and synthesized across studies. RESULTS: Using the Oxford Centre for Evidence Based Medicine levels of evidence (2009), 3b was the highest level of evidence within the review. Sensorineural hearing loss was the most consistent auditory deficit reported post TBI. CONCLUSION: The range and frequency of auditory dysfunction in patients with TBI remain unclear. Future research should focus on understanding the nature, frequency and change of auditory deficits over time following TBI. Knowledge in this area will provide crucial information for clinicians and facilitate the development of diagnostic and best practice guidelines which currently are lacking for the management of this patient population.

Quantitative analysis tool for clinical functional MRI in mild traumatic brain injury.

Functional magnetic resonance imaging (fMRI) has been available commercially for clinical diagnostic use for many years. However, both clinical interpretation of fMRI by a neuroradiologist and quantitative analysis of fMRI data can require significant personnel resources that exceed reimbursement. In this report, a fully automated computer-based quantification methodology (Enumerated Auditory Response, EAR) has been developed to provide an auditory fMRI assessment of patients who have suffered a mild traumatic brain injury. Fifty-five study participants with interpretable auditory fMRI sequence data were assessed by EAR analysis, as well as both clinical radiologist fMRI interpretation and voxelwise general linear model (GLM) analysis. Comparison between the clinical interpretation and the two computer analysis methods resulted in 67% concordance (identical), 32% nearconcordance (one level difference), and 1% discordant. Comparison between the clinical computer-based quantification (EAR) and GLM analysis yielded significant correlations in right and left ear responses (p⟨0.05) for the full subject group. Automated fMRI quantification analysis equivalent to EAR might be appropriate for both future research projects with constrained resources, as well as possible routine clinical use.

Central auditory processing disorders after mild traumatic brain injury.

Auditory processing disorders are common following mild traumatic brain injury (mTBI), but the neurocircuitry involved is not well understood. The present study used functional MRI to examine auditory cortex activation patterns during a passive listening task in a normative population and mTBI patients with and without clinical central auditory processing deficits (APD) as defined by the SCAN-3:A clinical battery. Patients with mTBI had overall patterns of lower auditory cortex activation during the listening tasks as compared to normative controls. A significant lateralization pattern (pairwise t-test; p⟨0.05) was observed in normative controls and in those with mTBI and APD during single-side stimulation. Additionally, baseline connectivity between left and right auditory cortices was lower in mTBI patients than in controls (p=0.01) and significantly reduced in the mTBI with APD group (p=0.008). Correlation was also observed between bilateral task-related activation and competing words subscore of the SCAN-3:A. These findings suggest the passive listening task is well suited to probe auditory function in military personnel with an mTBI diagnosis. Further, the study supports the use of multiple approaches for detecting and assessing central auditory deficits to improve monitoring of short- and long-term outcomes.

Adverse effects of pesticides on central auditory functions in tobacco growers.

OBJECTIVE: To investigate the effects of exposure to pesticides on the central auditory functions (CAF) of Brazilian tobacco growers. DESIGN: This was a cross-sectional study carried out between 2010 and 2012. Participants were evaluated with two behavioural procedures to investigate CAF, the random gap detection test (RGDT) and the dichotic digit test in Portuguese (DDT). STUDY SAMPLE: A total of 22 growers exposed to pesticides (study group) and 21 subjects who were not exposed to pesticides (control group) were selected. RESULTS: No significant differences between groups were observed for pure-tone thresholds. A significant association between pesticide exposure and the results for RGDT and DDT was found. Significant differences between pesticide-exposed and nonexposed subjects were found for RGDT frequency average and DDT binaural average, when including age and hearing level as covariates. Age was significantly associated with RGDT frequency average, DDT left ear score, DDT binaural average and DDT right ear advantage. Hearing levels were not significantly associated with any of the test scores. The relative risk of failing the DDT and RGDT for the study group was 1.88 (95% CI: 1.10-3.20) and 1.74 (95% CI: 1.06-2.86), respectively, as compared with the control group. CONCLUSIONS: The results showed that tobacco growers exposed to pesticides exhibited signs of central auditory dysfunction characterised by decrements in temporal processing and binaural integration processes/abilities.

Environmental acoustic enrichment promotes recovery from developmentally degraded auditory cortical processing.

It has previously been shown that environmental enrichment can enhance structural plasticity in the brain and thereby improve cognitive and behavioral function. In this study, we reared developmentally noise-exposed rats in an acoustic-enriched environment for ∼4 weeks to investigate whether or not enrichment could restore developmentally degraded behavioral and neuronal processing of sound frequency. We found that noise-exposed rats had significantly elevated sound frequency discrimination thresholds compared with age-matched naive rats. Environmental acoustic enrichment nearly restored to normal the behavioral deficit resulting from early disrupted acoustic inputs. Signs of both degraded frequency selectivity of neurons as measured by the bandwidth of frequency tuning curves and decreased long-term potentiation of field potentials recorded in the primary auditory cortex of these noise-exposed rats also were reversed partially. The observed behavioral and physiological effects induced by enrichment were accompanied by recovery of cortical expressions of certain NMDA and GABAA receptor subunits and brain-derived neurotrophic factor. These studies in a rodent model show that environmental acoustic enrichment promotes recovery from early noise-induced auditory cortical dysfunction and indicate a therapeutic potential of this noninvasive approach for normalizing neurological function from pathologies that cause hearing and associated language impairments in older children and adults.

Inhalation of Hydrocarbon Jet Fuel Suppress Central Auditory Nervous System Function.

More than 800 million L/d of hydrocarbon fuels is used to power cars, boats, and jet airplanes. The weekly consumption of these fuels necessarily puts the public at risk for repeated inhalation exposure. Recent studies showed that exposure to hydrocarbon jet fuel produces lethality in presynaptic sensory cells, leading to hearing loss, especially in the presence of noise. However, the effects of hydrocarbon jet fuel on the central auditory nervous system (CANS) have not received much attention. It is important to investigate the effects of hydrocarbons on the CANS in order to complete current knowledge regarding the ototoxic profile of such exposures. The objective of the current study was to determine whether inhalation exposure to hydrocarbon jet fuel might affect the functions of the CANS. Male Fischer 344 rats were randomly divided into four groups (control, noise, fuel, and fuel + noise). The structural and functional integrity of presynaptic sensory cells was determined in each group. Neurotransmission in both peripheral and central auditory pathways was simultaneously evaluated in order to identify and differentiate between peripheral and central dysfunctions. There were no detectable effects on pre- and postsynaptic peripheral functions. However, the responsiveness of the brain was significantly depressed and neural transmission time was markedly delayed. The development of CANS dysfunctions in the general public and the military due to cumulative exposure to hydrocarbon fuels may represent a significant but currently unrecognized public health issue.

Behavioral and neural discrimination of speech sounds after moderate or intense noise exposure in rats.

OBJECTIVES: Hearing loss is a commonly experienced disability in a variety of populations including veterans and the elderly and can often cause significant impairment in the ability to understand spoken language. In this study, we tested the hypothesis that neural and behavioral responses to speech will be differentially impaired in an animal model after two forms of hearing loss. DESIGN: Sixteen female Sprague-Dawley rats were exposed to one of two types of broadband noise which was either moderate or intense. In nine of these rats, auditory cortex recordings were taken 4 weeks after noise exposure (NE). The other seven were pretrained on a speech sound discrimination task prior to NE and were then tested on the same task after hearing loss. RESULTS: Following intense NE, rats had few neural responses to speech stimuli. These rats were able to detect speech sounds but were no longer able to discriminate between speech sounds. Following moderate NE, rats had reorganized cortical maps and altered neural responses to speech stimuli but were still able to accurately discriminate between similar speech sounds during behavioral testing. CONCLUSIONS: These results suggest that rats are able to adjust to the neural changes after moderate NE and discriminate speech sounds, but they are not able to recover behavioral abilities after intense NE. Animal models could help clarify the adaptive and pathological neural changes that contribute to speech processing in hearing-impaired populations and could be used to test potential behavioral and pharmacological therapies.

Xylene-induced auditory dysfunction in humans.

OBJECTIVES: Animal data indicate that xylene induces cochlear dysfunction, characterized by the loss of outer hair cells. There is little evidence regarding xylene-induced ototoxicity in humans. The aim of the study was to investigate the possible adverse effects of xylene on the peripheral and central auditory system in humans. DESIGN: A total of 30 medical laboratory workers who had been exposed to a mixture of xylene isomers, together with 30 nonexposed control participants matched for gender, age, and educational level were selected. Participants of both groups were not exposed to noise levels above 85 dBA time-weighted average. All participants were evaluated with a comprehensive audiological test battery, which included measures of peripheral and central auditory function. Peripheral auditory measures included pure-tone audiometry and distortion product otoacoustic emissions. Behavioral measures of central auditory function included a pitch pattern sequence test, an adaptive test of temporal resolution, a dichotic digit test, and a masking level difference test. The auditory brainstem response was used to objectively evaluate the function of the auditory pathways at the brainstem level. Speech perception in quiet and in noise was evaluated using the Hearing In Noise Test (HINT). The xylene-exposed participants were extensively evaluated with regard to their exposure to both noise and xylene. Noise dosimetry was conducted over an 8-hr work shift to obtain noise-exposure levels for each xylene-exposed worker. Airborne xylene concentrations were obtained at 11 different workstations throughout the medical laboratories, and methyl hippuric acid levels per gram of creatinine in urine were obtained for each xylene-exposed subject. Finally, a detailed interview exploring current and past solvent and noise exposure was conducted. RESULTS: The xylene-exposed participants showed significantly worse pure-tone thresholds in comparison with the nonexposed participants. The xylene-exposed participants demonstrated significantly worse results than the control group participants for the pitch pattern sequence test, dichotic digit test, HINT, and the auditory brainstem response (absolute and interpeak latencies). No significant differences between the xylene-exposed and nonexposed participants were observed for distortion product otoacoustic emissions, adaptive test of temporal resolution, or the masking level difference test. A significant correlation between the concentrations of methyl hippuric acid in urine and pure-tone thresholds (2 to 8 kHz) was found in xylene-exposed workers. Also, participants with high cumulative dose of xylene exposure presented with poorer test results than participants with low cumulative dose of xylene exposure. CONCLUSIONS: The results of the present research suggest that xylene is associated with adverse central auditory effects and poorer sound detection abilities in humans. A major limitation of the study is that the results found among xylene-exposed participants cannot be proved to be permanent, and thus further research should be conducted to clarify this limitation. Workers exposed to this chemical should be routinely evaluated with a comprehensive audiological test battery, to detect early signs of auditory dysfunction.

Patient-reported auditory functions after stroke of the central auditory pathway.

BACKGROUND AND PURPOSE: Auditory functional limitations experienced by patients after stroke of the central auditory pathways remain underinvestigated. Purpose- To measure patient-reported hearing difficulties in everyday life in nonaphasic patients with stroke of the auditory brain versus normal control subjects. To examine how hearing difficulties correlate with auditory tests and site of lesion in individual cases. METHODS: We recruited 21 individuals with auditory brain stroke (excluding those with aphasia) diagnosed on the basis of a brain MRI conducted 1 to 2 weeks after the stroke and assessed in the chronic stage of stroke. Twenty-three controls matched for age and hearing were also recruited. All subjects completed the Amsterdam Inventory for Auditory Disability (consisting of subscales of sound detection, recognition, localization, speech in quiet, speech in noise) and underwent baseline audiometry and central auditory processing tests (dichotic digits, frequency and duration patterns, gaps in noise). RESULTS: Sound recognition and localization subscores of the inventory were significantly worse in case subjects versus control subjects, with severe and significant functional limitation (z score >3) reported by 9 out of 21 case subjects. None of the inventory subscales correlated with audiometric thresholds, but localization and recognition subscales showed a moderate to strong correlation with dichotic digits (left ear) and pattern tests. CONCLUSIONS: A substantial proportion of patients may experience and report severe auditory functional limitations not limited to speech sounds after stroke of the auditory brain. A hearing questionnaire may help identify patients who require more extensive assessment to inform rehabilitation plans.

Plasticity in the developing auditory cortex: evidence from children with sensorineural hearing loss and auditory neuropathy spectrum disorder.

The developing auditory cortex is highly plastic. As such, the cortex is both primed to mature normally and at risk for reorganizing abnormally, depending upon numerous factors that determine central maturation. From a clinical perspective, at least two major components of development can be manipulated: (1) input to the cortex and (2) the timing of cortical input. Children with sensorineural hearing loss (SNHL) and auditory neuropathy spectrum disorder (ANSD) have provided a model of early deprivation of sensory input to the cortex and demonstrated the resulting plasticity and development that can occur upon introduction of stimulation. In this article, we review several fundamental principles of cortical development and plasticity and discuss the clinical applications in children with SNHL and ANSD who receive intervention with hearing aids and/or cochlear implants.

Onset coding is degraded in auditory nerve fibers from mutant mice lacking synaptic ribbons.

Synaptic ribbons, found at the presynaptic membrane of sensory cells in both ear and eye, have been implicated in the vesicle-pool dynamics of synaptic transmission. To elucidate ribbon function, we characterized the response properties of single auditory nerve fibers in mice lacking Bassoon, a scaffolding protein involved in anchoring ribbons to the membrane. In bassoon mutants, immunohistochemistry showed that fewer than 3% of the hair cells' afferent synapses retained anchored ribbons. Auditory nerve fibers from mutants had normal threshold, dynamic range, and postonset adaptation in response to tone bursts, and they were able to phase lock with normal precision to amplitude-modulated tones. However, spontaneous and sound-evoked discharge rates were reduced, and the reliability of spikes, particularly at stimulus onset, was significantly degraded as shown by an increased variance of first-spike latencies. Modeling based on in vitro studies of normal and mutant hair cells links these findings to reduced release rates at the synapse. The degradation of response reliability in these mutants suggests that the ribbon and/or Bassoon normally facilitate high rates of exocytosis and that its absence significantly compromises the temporal resolving power of the auditory system.

Central auditory function in early Alzheimer's disease and in mild cognitive impairment.

OBJECTIVE: to investigate auditory function in subjects with early Alzheimer's disease, mild cognitive impairment and with subjective memory complaints, in search of signs of central auditory processing dysfunction even in early stages of cognitive impairment. DESIGN AND SUBJECTS: a consecutive group of men and women, referred to the Memory Clinic at the Karolinska University Hospital, was approached for inclusion in this prospective study. One hundred and thirty-six subjects, mean age 64 years (range 50-78 years), diagnosed with Alzheimer's disease (n = 43), mild cognitive impairment (n = 59) or with subjective memory complaints (n = 34), were included. METHODS: auditory function was assessed with pure tone audiometry, speech perception in quiet and in background noise and dichotic digits tests with two or three digits. RESULTS: pure tone audiometry and speech perception scores in quiet and in background noise were normal for age and without between-group differences. Dichotic digits tests showed strongly significant differences between the three groups, where the Alzheimer's disease group performed significantly poorer than the other two groups, with the mild cognitive impairment group in an intermediate position. CONCLUSIONS: our results demonstrate that central auditory processing dysfunction is highly evident in subjects with Alzheimer's disease, and to a considerable extent even in subjects with mild cognitive impairment.

Nonsense mutation in TMEM126A causing autosomal recessive optic atrophy and auditory neuropathy.

PURPOSE: To define the phenotype and elucidate the molecular basis for an autosomal recessively inherited optic atrophy and auditory neuropathy in a consanguineous family with two affected children. METHODS: Family members underwent detailed ophthalmologic, electrophysiological, and audiological assessments. An autozygosity mapping strategy using high-density single nucleotide polymorphism microarrays and microsatellite markers was used to detect regions of genome homozygosity that might contain the disease gene. Candidate genes were then screened for mutations by direct sequencing. RESULTS: Both affected subjects had poor vision from birth and complained of progressive visual loss over time. Current visual acuity ranged from 6/60 to 6/120. Fundus examination revealed bilateral temporal optic nerve pallor in both patients with otherwise normal retinal findings. International-standard full-field electroretinograms were normal in both individuals, with no evidence of generalized retinal dysfunction. Pattern cortical visual evoked potentials were grossly abnormal bilaterally in both cases. The pattern electroretinogram N95:P50 ratio was subnormal, and the P50 was of shortened peak time bilaterally in both patients. The electrophysiological findings were consistent with bilateral retinal ganglion cell/optic nerve dysfunction. Audiological investigation in both siblings revealed abnormalities falling within the auditory neuropathy/dysynchrony spectrum. There were no auditory symptoms and good outer hair cell function (as demonstrated by transient evoked otoacoustic emissions) but impaired inner hair cell/neural function with abnormal stapedial reflex thresholds and abnormal or absent auditory brainstem-evoked responses. The single nucleotide polymorphism microarray data demonstrated a 24.17 Mb region of homozygosity at 11q14.1-11q22.3, which was confirmed by microsatellite marker analysis. The candidate target region contained the transmembrane protein 126A (TMEM126A) gene, and direct sequencing identified a previously described nonsense mutation (c.163C>T; p.Arg55X). CONCLUSIONS: We describe the first detailed phenotyping of patients with autosomal recessive TMEM126A-associated optic atrophy and auditory neuropathy. These findings will facilitate the identification of individuals with this recently described disorder.

Synchronous auditory nerve activity in the carboplatin-chinchilla model of auditory neuropathy.

Two hallmark features of auditory neuropathy (AN) are normal outer hair cell function in the presence of an absent/abnormal auditory brainstem response (ABR). Studies of human AN patients are unable to determine whether disruption of the ABR is the result of a reduction of neural input, a loss of auditory nerve fiber (ANF) synchrony, or both. Neurophysiological data from the carboplatin model of AN reveal intact neural synchrony in the auditory nerve and inferior colliculus, despite significant reductions in neural input. These data suggest that (1), intact neural synchrony is available to support an ABR following carboplatin treatment and, (2), impaired spike timing intrinsic to neurons is required for the disruption of the ABR observed in human AN.