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.

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.

Evoked Potentials Reveal Noise Exposure-Related Central Auditory Changes Despite Normal Audiograms.

Purpose Complaints of auditory perceptual deficits, such as tinnitus and difficulty understanding speech in background noise, among individuals with clinically normal audiograms present a perplexing problem for audiologists. One potential explanation for these "hidden" auditory deficits is loss of the synaptic connections between the inner hair cells and their afferent auditory nerve fiber targets, a condition that has been termed cochlear synaptopathy. In animal models, cochlear synaptopathy can occur due to aging or exposure to noise or ototoxic drugs and is associated with reduced auditory brainstem response (ABR) wave I amplitudes. Decreased ABR wave I amplitudes have been demonstrated among young military Veterans and non-Veterans with a history of firearm use, suggesting that humans may also experience noise-induced synaptopathy. However, the downstream consequences of synaptopathy are unclear. Method To investigate how noise-induced reductions in wave I amplitude impact the central auditory system, the ABR, the middle latency response (MLR), and the late latency response (LLR) were measured in 65 young Veterans and non-Veterans with normal audiograms. Results In response to a click stimulus, the MLR was weaker for Veterans compared to non-Veterans, but the LLR was not reduced. In addition, low ABR wave I amplitudes were associated with a reduced MLR, but with an increased LLR. Notably, Veterans reporting tinnitus showed the largest mean LLRs. Conclusions These findings indicate that decreased peripheral auditory input leads to compensatory gain in the central auditory system, even among individuals with normal audiograms, and may impact auditory perception. This pattern of reduced MLR, but not LLR, was observed among Veterans even after statistical adjustment for sex and distortion product otoacoustic emission differences, suggesting that synaptic loss plays a role in the observed central gain. Supplemental Material https://doi.org/10.23641/asha.11977854.

Behavioral and Neural Correlates of Auditory n-Back Task in Adults With and Without Stuttering.

Purpose Adults with stuttering (AWS) exhibit compromised phonological working memory abilities, poor central auditory processing, and impaired auditory processing especially during overt speech production tasks. However, these tasks are sensitive to language disturbances already found in them. Thus, in this study, monosyllables were used ruling out the language effects, and auditory working memory ability was evaluated in AWS using the n-back task. In specific, the auditory sensory input of the working memory mechanism was evaluated. Method Thirty-two participants, 16 each of AWS and adults with no stuttering (AWNS), performed behavioral auditory 1-back and 2-back tasks. The long latency responses were also recorded during no-back and 2-back conditions from 64 electrode sites. Results Results revealed no significant differences between the groups in any of the behavioral parameters such as reaction time, accuracy, false alarm rate, or d'. N1 amplitude modulation was noted in AWNS, which was absent in AWS. The segmentation analysis showed a left hemisphere-oriented topographical distribution in the N2 region in AWS irrespective of conditions, whereas the scalp topography was right hemisphere-oriented with the involvement of parietal channels in AWNS. The timing differences existed between AWS and AWNS in the intervals that a topographical distribution lasted in all throughout the time window of analysis. Conclusion The results suggest altered neural pathway and hemispheric differences during auditory working memory tasks in AWS.

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.

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.

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.

The Middle Latency Response: A Review of Findings in Various Central Nervous System Lesions.

BACKGROUND: The middle latency response (MLR) first came to light as an auditory evoked potential in 1958. Since then, it has aroused substantial interest and investigation by clinicians and researchers alike. In recent history, its use and popularity have dwindled in tandem with various other auditory evoked potentials in audiology. One area for which MLR research and application has been overlooked is its potential value in measuring the neural integrity of the auditory thalamocortical pathway. In a broader sense, the MLR, when combined with the auditory brain stem response, can provide information concerning the status of much of the central auditory system pathways. This review is intended to provide information concerning the MLR as a measure of central auditory function for the reader to consider. PURPOSE: To review and synthesize the scientific literature regarding the potential value of the MLR in assessing the integrity of the central auditory system and to provide the reader an informed perspective on the value of the MLR in this regard. Information is also provided on the MLR generator sites and fundamental characteristics of this evoked potential essential to its clinical and or research application. RESEARCH DESIGN: A systematic review and synthesis of the literature focusing on the MLR and lesions of the central auditory system. STUDY SAMPLE: Studies and individual cases were reviewed and analyzed that evidenced documented lesions of the central auditory nervous system. DATA COLLECTION AND ANALYSIS: The authors searched and reviewed the literature (journal articles, book chapters, and books) pertaining to central auditory system lesion effects on the MLR. RESULTS: Although findings varied from study to study, overall, the MLR was reasonably sensitive and specific to neurological compromise of the central auditory system. This finding is consistent with the generator sites of this evoked potential. CONCLUSIONS: The MLR is a valuable tool for assessing the integrity of the central auditory system. It should be of interest to the clinician or researcher who focuses their attention on the function and dysfunction of the higher auditory system.

Auditory system dysfunction in Alzheimer disease and its prodromal states: A review.

Recent findings suggest that both peripheral and central auditory system dysfunction occur in the prodromal stages of Alzheimer Disease (AD), and therefore may represent early indicators of the disease. In addition, loss of auditory function itself leads to communication difficulties, social isolation and poor quality of life for both patients with AD and their caregivers. Developing a greater understanding of auditory dysfunction in early AD may shed light on the mechanisms of disease progression and carry diagnostic and therapeutic importance. Herein, we review the literature on hearing abilities in AD and its prodromal stages investigated through methods such as pure-tone audiometry, dichotic listening tasks, and evoked response potentials. We propose that screening for peripheral and central auditory dysfunction in at-risk populations is a low-cost and effective means to identify early AD pathology and provides an entry point for therapeutic interventions that enhance the quality of life of AD patients.

Hidden hearing loss and endbulbs of Held: Evidence for central pathology before detection of ABR threshold increases.

Reductions in sound-evoked activity in the auditory nerve due to hearing loss have been shown to cause pathological changes in central auditory structures. Hearing loss due strictly to the aging process are less well documented. In this study of CBA/CaH mice, we provide evidence for age-related pathology in the endbulb of Held, a large axosomatic ending arising from myelinated auditory nerve fibers. Endbulbs are known to be involved in the processing of temporal cues used for sound localization and speech comprehension. Hearing thresholds as measured by auditory brainstem response (ABR) thresholds remained stable up to one year, whereas suprathreshold amplitudes of early ABR waves decreased by up to 50% in older mice, similar to that reported for age-related cochlear synaptopathy (Sergeyenko et al., 2013). The reduction of ABR response magnitude with age correlated closely in time with the gradual atrophy of endbulbs of Held, and is consistent with the hypothesis that endbulb integrity is dependent upon normal levels of spike activity in the auditory nerve. These results indicate that central auditory pathologies emerge as consequence of so-called "hidden" hearing loss and suggest that such brain changes require consideration when devising therapeutic interventions.

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.

Auditory distance perception in humans: a review of cues, development, neuronal bases, and effects of sensory loss.

Auditory distance perception plays a major role in spatial awareness, enabling location of objects and avoidance of obstacles in the environment. However, it remains under-researched relative to studies of the directional aspect of sound localization. This review focuses on the following four aspects of auditory distance perception: cue processing, development, consequences of visual and auditory loss, and neurological bases. The several auditory distance cues vary in their effective ranges in peripersonal and extrapersonal space. The primary cues are sound level, reverberation, and frequency. Nonperceptual factors, including the importance of the auditory event to the listener, also can affect perceived distance. Basic internal representations of auditory distance emerge at approximately 6 months of age in humans. Although visual information plays an important role in calibrating auditory space, sensorimotor contingencies can be used for calibration when vision is unavailable. Blind individuals often manifest supranormal abilities to judge relative distance but show a deficit in absolute distance judgments. Following hearing loss, the use of auditory level as a distance cue remains robust, while the reverberation cue becomes less effective. Previous studies have not found evidence that hearing-aid processing affects perceived auditory distance. Studies investigating the brain areas involved in processing different acoustic distance cues are described. Finally, suggestions are given for further research on auditory distance perception, including broader investigation of how background noise and multiple sound sources affect perceived auditory distance for those with sensory loss.

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.

Future advances.

Future advances in the auditory systems are difficult to predict, and only educated guesses are possible. It is expected that innovative technologies in the field of neuroscience will be applied to the auditory system. Optogenetics, Brainbow, and CLARITY will improve our knowledge of the working of neural auditory networks and the relationship between sound and language, providing a dynamic picture of the brain in action. CLARITY makes brain tissue transparent and offers a three-dimensional view of neural networks, which, combined with genetically labeling neurons with multiple, distinct colors (Optogenetics), will provide detailed information of the complex brain system. Molecular functional magnetic resonance imaging (MRI) will allow the study of neurotransmitters detectable by MRI and their function in the auditory pathways. The Human Connectome project will study the patterns of distributed brain activity that underlie virtually all aspects of cognition and behavior and determine if abnormalities in the distributed patterns of activity may result in hearing and behavior disorders. Similarly, the programs of Big Brain and ENIGMA will improve our understanding of auditory disorders. New stem-cell therapy and gene therapies therapy may bring about a partial restoration of hearing for impaired patients by inducing regeneration of cochlear hair cells.

Central auditory processing outcome after stroke in children.

OBJECTIVE: To investigate central auditory processing in children with unilateral stroke and to verify whether the hemisphere affected by the lesion influenced auditory competence. METHOD: 23 children (13 male) between 7 and 16 years old were evaluated through speech-in-noise tests (auditory closure); dichotic digit test and staggered spondaic word test (selective attention); pitch pattern and duration pattern sequence tests (temporal processing) and their results were compared with control children. Auditory competence was established according to the performance in auditory analysis ability. RESULTS: Was verified similar performance between groups in auditory closure ability and pronounced deficits in selective attention and temporal processing abilities. Most children with stroke showed an impaired auditory ability in a moderate degree. CONCLUSION: Children with stroke showed deficits in auditory processing and the degree of impairment was not related to the hemisphere affected by the lesion.

Central auditory processing outcome after stroke in children / Processamento auditivo central em crianças com acidente vascular cerebral

Objective To investigate central auditory processing in children with unilateral stroke and to verify whether the hemisphere affected by the lesion influenced auditory competence. Method 23 children (13 male) between 7 and 16 years old were evaluated through speech-in-noise tests (auditory closure); dichotic digit test and staggered spondaic word test (selective attention); pitch pattern and duration pattern sequence tests (temporal processing) and their results were compared with control children. Auditory competence was established according to the performance in auditory analysis ability. Results Was verified similar performance between groups in auditory closure ability and pronounced deficits in selective attention and temporal processing abilities. Most children with stroke showed an impaired auditory ability in a moderate degree. Conclusion Children with stroke showed deficits in auditory processing and the degree of impairment was not related to the hemisphere affected by the lesion. .

Objetivo Investigar as habilidades de processamento auditivo central em crianças com acidente vascular cerebral (AVC) unilateral e verificar se o hemisfério cerebral afetado influiu na competência auditiva. Método 23 crianças (13 meninos) entre 7 e 16 anos foram avaliados através dos testes de fala com ruído (fechamento auditivo); dicótico de dígitos e de dissílabos alternados (atenção seletiva); padrão temporal de frequência e duração (processamento temporal) e seus resultados comparados aos de crianças controles. A competência auditiva foi estabelecida segundo o desempenho na habilidade de análise auditiva. Resultados Foi constatado desempenho similar entre os grupos na habilidade de fechamento auditivo e défices acentuados nas habilidades de atenção seletiva e processamento temporal. A maioria das crianças com AVC apresentou comprometimento da habilidade auditiva em grau moderado. Conclusão Crianças com AVC apresentaram alterações do processamento auditivo e o grau do comprometimento não se relacionou com o hemisfério afetado pela lesão. .

Noise-induced tinnitus: auditory evoked potential in symptomatic and asymptomatic patients.

OBJECTIVES: We evaluated the central auditory pathways in workers with noise-induced tinnitus with normal hearing thresholds, compared the auditory brainstem response results in groups with and without tinnitus and correlated the tinnitus location to the auditory brainstem response findings in individuals with a history of occupational noise exposure. METHOD: Sixty individuals participated in the study and the following procedures were performed: anamnesis, immittance measures, pure-tone air conduction thresholds at all frequencies between 0.25-8 kHz and auditory brainstem response. RESULTS: The mean auditory brainstem response latencies were lower in the Control group than in the Tinnitus group, but no significant differences between the groups were observed. Qualitative analysis showed more alterations in the lower brainstem in the Tinnitus group. The strongest relationship between tinnitus location and auditory brainstem response alterations was detected in individuals with bilateral tinnitus and bilateral auditory brainstem response alterations compared with patients with unilateral alterations. CONCLUSION: Our findings suggest the occurrence of a possible dysfunction in the central auditory nervous system (brainstem) in individuals with noise-induced tinnitus and a normal hearing threshold.