Cochlear implant candidates with psychogenic hearing loss.

Abstract Conclusions: Specific requests for cochlear implantations by persons with psychogenic hearing loss are a relatively new phenomenon. A number of features seems to be over-represented in this group of patients. The existence of these requests stresses the importance of auditory brainstem response (ABR) measurements before cochlear implantation. Objective: To describe the phenomenon of patients with psychogenic hearing losses specifically requesting cochlear implantation, and to gain first insights into the characteristics of this group. Methods: Analysis of all cases seen between 2004 and 2013 at the University Hospital of Bern, Switzerland. Results: Four cochlear implant candidates with psychogenic hearing loss were identified. All were female, aged 23-51 years. Hearing thresholds ranged from 86 dB to 112 dB HL (pure-tone average 500-4000 Hz). ABRs and otoacoustic emissions (OAEs) showed bilaterally normal hearing in two subjects, and hearing thresholds between 30 and 50 dB in the other two subjects. Three subjects suffered from depression and one from a pathologic fear of cancer. Three had a history of five or more previous surgeries. Three were smokers and three reported other close family members with hearing losses. All four were hearing aid users at the time of presentation.

Cell cycle reactivation of cochlear progenitor cells in neonatal FUCCI mice by a GSK3 small molecule inhibitor.

Due to the lack of regenerative capacity of the mammalian auditory epithelium, sensory hair cell loss results in permanent hearing deficit. Nevertheless, a population of tissue resident stem/progenitor cells has been recently described. Identification of methods to trigger their activity could lead to exploitation of their potential therapeutically. Here we validate the use of transgenic mice reporting cell cycle progression (FUCCI), and stemness (Lgr5-GFP), as a valuable tool to identify regulators of cell cycle re-entry of supporting cells within the auditory epithelium. The small molecule compound CHIR99021 was used to inhibit GSK3 activity. This led to a significant increase in the fraction of proliferating sphere-forming cells, labeled by the FUCCI markers and in the percentage of Lgr5-GFP + cells, as well as a selective increase in the fraction of S-G2-M cells in the Lgr5 + population. Using whole mount cultures of the organ of Corti we detected a statistically significant increment in the fraction of proliferating Sox2 supporting cells after CHIR99021 treatment, but only rarely appearance of novel MyoVIIa+/Edu + hair cells. In conclusion, these tools provide a robust mean to identify novel regulators of auditory organ regeneration and to clarify the contribution of stem cell activity.

Development and characterization of chemical cochleostomy in the Guinea pig

OBJECTIVES Creation of an atraumatic, hearing-preservation cochleostomy is integral to the future of minimally invasive inner ear surgery. The goal of this study was to develop and characterize a novel chemical approach to cochleostomy. STUDY DESIGN Prospective animal study. SETTING Laboratory. METHODS Experimental animal study in which phosphoric acid gel (PAG) was used to decalcify the otic capsule in 25 Hartley guinea pigs. Five animals in each of 5 surgical groups were studied: (1) mechanically opening the auditory bulla alone, (2) PAG thinning of the basal turn otic capsule, leaving endosteum covered by a layer of bone, (3) micro-pick manual cochleostomy, (4) PAG chemical cochleostomy, exposing the endosteum, and (5) combined PAG/micro-pick cochleostomy, with initial chemical thinning and subsequent manual removal of the last osseous layer. Preoperative and postoperative auditory brainstem responses and otoacoustic emissions were obtained at 2, 6, 10, and 16 kHz. Hematoxylin and eosin-stained paraffin sections were compared. RESULTS Surgical and histologic findings confirmed that application of PAG provided reproducible local bone removal, and cochlear access was enabled. Statistically significant auditory threshold shifts were observed at 10 kHz (P = .048) and 16 kHz (P = .0013) following cochleostomy using PAG alone (group 4) and at 16 kHz using manual cochleostomy (group 3) (P = .028). No statistically significant, postoperative auditory threshold shifts were observed in the other groups, including PAG thinning with manual completion cochleostomy (group 5). CONCLUSION Hearing preservation cochleostomy can be performed in an animal model using a novel technique of thinning cochlear bone with PAG and manually completing cochleostomy.

Gene disruption of p27Kip1 allows cell proliferation in the postnatal and adult organ of Corti

Hearing loss is most often the result of hair-cell degeneration due to genetic abnormalities or ototoxic and traumatic insults. In the postembryonic and adult mammalian auditory sensory epithelium, the organ of Corti, no hair-cell regeneration has ever been observed. However, nonmammalian hair-cell epithelia are capable of regenerating sensory hair cells as a consequence of nonsensory supporting-cell proliferation. The supporting cells of the organ of Corti are highly specialized, terminally differentiated cell types that apparently are incapable of proliferation. At the molecular level terminally differentiated cells have been shown to express high levels of cell-cycle inhibitors, in particular, cyclin-dependent kinase inhibitors [Parker, S. B., et al. (1995) Science 267, 1024–1027], which are thought to be responsible for preventing these cells from reentering the cell cycle. Here we report that the cyclin-dependent kinase inhibitor p27Kip1 is selectively expressed in the supporting-cell population of the organ of Corti. Effects of p27Kip1-gene disruption include ongoing cell proliferation in postnatal and adult mouse organ of Corti at time points well after mitosis normally has ceased during embryonic development. This suggests that release from p27Kip1-induced cell-cycle arrest is sufficient to allow supporting-cell proliferation to occur. This finding may provide an important pathway for inducing hair-cell regeneration in the mammalian hearing organ.

GTP-binding protein βγ subunits mediate presynaptic calcium current inhibition by GABAB receptor

A variety of GTP-binding protein (G protein)-coupled receptors are expressed at the nerve terminals of central synapses and play modulatory roles in transmitter release. At the calyx of Held, a rat auditory brainstem synapse, activation of presynaptic γ-aminobutyric acid type B receptors (GABAB receptors) or metabotropic glutamate receptors inhibits presynaptic P/Q-type Ca2+ channel currents via activation of G proteins, thereby attenuating transmitter release. To identify the heterotrimeric G protein subunits involved in this presynaptic inhibition, we loaded G protein βγ subunits (Gβγ) directly into the calyceal nerve terminal through whole-cell patch pipettes. Gβγ slowed the activation of presynaptic Ca2+ currents (IpCa) and attenuated its amplitude in a manner similar to the externally applied baclofen, a GABAB receptor agonist. The effects of both Gβγ and baclofen were relieved after strong depolarization of the nerve terminal. In addition, Gβγ partially occluded the inhibitory effect of baclofen on IpCa. In contrast, guanosine 5′-O-(3-thiotriphosphate)-bound Goα loaded into the calyx had no effect. Immunocytochemical examination revealed that the subtype of G proteins Go, but not the Gi, subtype, is expressed in the calyceal nerve terminal. These results suggest that presynaptic inhibition mediated by G protein-coupled receptors occurs primarily by means of the direct interaction of Go βγ subunits with presynaptic Ca2+ channels.

O efeito da estimulação top-down e bottom-up no potencial evocado auditivo de tronco encefálico com estímulo complexo

Introdução: Crianças com transtorno fonológico (TF) apresentam dificuldade na percepção de fala, em processar estímulos acústicos quando apresentados de forma rápida e em sequência. A percepção dos sons complexos da fala, dependem da integridade no processo de codificação analisado pelo Sistema Nervoso Auditivo. Por meio do Potencial Evocado Auditivo de Tronco Encefálico com estímulo complexo (PEATEc) é possível investigar a representação neural dos sons em níveis corticais e obter informações diretas sobre como a estrutura do som da sílaba falada é codificada no sistema auditivo. Porém, acredita-se que esse potencial sofre interferências tanto de processos bottom-up quanto top-down, o que não se sabe é quanto e como cada um desses processos modifica as respostas do PEATEc. Uma das formas de investigar a real influência dos aspectos top-down e bottom-up nos resultados do PEATEc é estimulando separadamente esses dois processos por meio do treinamento auditivo e da terapia fonoaudiológica. Objetivo: Verificar o impacto da estimulação sensorial (processamento bottom-up) e cognitiva (processamento top-down), separadamente, nos diferentes domínios da resposta eletrofisiológica do PEATEc. Método: Participaram deste estudo 11 crianças diagnosticadas com TF, com idades entre 7 e 10:11, submetidas a avaliação comportamental e eletrofisiológica e então dividas nos grupos Bottom-up (B-U) (N=6) e Top-down T-D (N=5). A estimulação bottom-up foi voltada ao treinamento das habilidades sensoriais, através de softwares de computador. A estimulação top-down foi realizada por meio de tarefas para estimular as habilidades cognitiva por meio do Programa de Estimulação Fonoaudiológica (PEF). Ambas as estimulações foram aplicadas uma vez por semana, num período de aproximadamente 45 minutos por 12 semanas. Resultados: O grupo B-U apresentou melhoras em relação aos domínios onset e harmônicos e no valor da pontuação do escore após ser submetido à estimulação bottom-up. Por sua vez, após serem submetidos à estimulação top-down, o grupo T-D apresentou melhoras em relação aos domínios onset, espectro-temporal, fronteiras do envelope e harmônicos e para os valores da pontuação do escore. Conclusão: Diante dos resultados obtidos neste estudo, foi possível observar que a estimulação sensorial (processamento bottom-up) e a estimulação cognitiva (processamento top-down) mostraram impactar de forma diferente a resposta eletrofisiológica do PEATEc

Age-related functional and structural retinal modifications in the Igf1−/− null mouse

Background. Mutations in the gene encoding human insulin-like growth factor-I (IGF-I) cause syndromic neurosensorial deafness. To understand the precise role of IGF-I in retinal physiology, we have studied the morphology and electrophysiology of the retina of the Igf1−/− mice in comparison with that of the Igf1+/− and Igf1+/+ animals during aging. Methods. Serological concentrations of IGF-I, glycemia and body weight were determined in Igf1+/+, Igf1+/− and Igf1−/− mice at different times up to 360 days of age. We have analyzed hearing by recording the auditory brainstem responses (ABR), the retinal function by electroretinographic (ERG) responses and the retinal morphology by immunohistochemical labeling on retinal preparations at different ages. Results. IGF-I levels are gradually reduced with aging in the mouse. Deaf Igf1−/− mice had an almost flat scotopic ERG response and a photopic ERG response of very small amplitude at postnatal age 360 days (P360). At the same age, Igf1+/− mice still showed both scotopic and photopic ERG responses, but a significant decrease in the ERG wave amplitudes was observed when compared with those of Igf1+/+ mice. Immunohistochemical analysis showed that P360 Igf1−/− mice suffered important structural modifications in the first synapse of the retinal pathway, that affected mainly the postsynaptic processes from horizontal and bipolar cells. A decrease in bassoon and synaptophysin staining in both rod and cone synaptic terminals suggested a reduced photoreceptor output to the inner retina. Retinal morphology of the P360 Igf1+/− mice showed only small alterations in the horizontal and bipolar cell processes, when compared with Igf1+/+ mice of matched age. Conclusions. In the mouse, IGF-I deficit causes an age-related visual loss, besides a congenital deafness. The present results support the use of the Igf1−/− mouse as a new model for the study of human syndromic deaf-blindness.

Neural population coding is optimized by discrete tuning curves

The sigmoidal tuning curve that maximizes the mutual information for a Poisson neuron, or population of Poisson neurons, is obtained. The optimal tuning curve is found to have a discrete structure that results in a quantization of the input signal. The number of quantization levels undergoes a hierarchy of phase transitions as the length of the coding window is varied. We postulate, using the mammalian auditory system as an example, that the presence of a subpopulation structure within a neural population is consistent with an optimal neural code.

A hierarchy of phase transitions in optimal neuronal coding:from binary to M-ary discrete optimal codes

We have investigated how optimal coding for neural systems changes with the time available for decoding. Optimization was in terms of maximizing information transmission. We have estimated the parameters for Poisson neurons that optimize Shannon transinformation with the assumption of rate coding. We observed a hierarchy of phase transitions from binary coding, for small decoding times, toward discrete (M-ary) coding with two, three and more quantization levels for larger decoding times. We postulate that the presence of subpopulations with specific neural characteristics could be a signiture of an optimal population coding scheme and we use the mammalian auditory system as an example.

A comparison of sound localisation techniques using cross-correlation and spiking neural networks for mobile robotics

This paper outlines the development of a crosscorrelation algorithm and a spiking neural network (SNN) for sound localisation based on real sound recorded in a noisy and dynamic environment by a mobile robot. The SNN architecture aims to simulate the sound localisation ability of the mammalian auditory pathways by exploiting the binaural cue of interaural time difference (ITD). The medial superior olive was the inspiration for the SNN architecture which required the integration of an encoding layer which produced biologically realistic spike trains, a model of the bushy cells found in the cochlear nucleus and a supervised learning algorithm. The experimental results demonstrate that biologically inspired sound localisation achieved using a SNN can compare favourably to the more classical technique of cross-correlation.

Brainstem auditory-evoked potential in Boxer dogs

Brainstem auditory-evoked potential (BAEP) has been widely used for different purposes in veterinary practice and is commonly used to identify inherited deafness and presbycusis. In this study, 43 Boxer dogs were evaluated using the BAEP. Deafness was diagnosed in 3 dogs (2 bilateral and 1 unilateral) allowing the remaining 40 Boxers to be included for normative data analysis including an evaluation on the influence of age on the BAEP. The animals were divided into 2 groups of 20 Boxers each based on age. The mean age was 4.54 years (range, 1-8) in group I, and 9.83 years (range, 8.5-12) in group II. The mean latency for I, III, and V waves were 1.14 (±0.07), 2.64 (±0.11), and 3.48 (±0.10) ms in group I, and 1.20 (±0.12), 2.73 (±0.15), and 3.58 (±0.22) ms in group II, respectively. The mean inter-peak latencies for the I-III, III-V and I-V intervals were 1.50 (±0.15), 0.84 (±0.15), and 2.34 (±0.11) ms in group I, and 1.53 (±0.16), 0.85 (±0.15), and 2.38 (±0.19) ms in group II, respectively. Latencies of waves I and III were significant different between group I and II. For the I-III, III-V and I-V intervals, no significant differences were observed between the 2 groups. As far as we know, this is the first normative study of BAEP obtained from Boxer dogs.

Predictive values of neurological examination, otoscopic examination and brainstem auditory evoked response (BAER) in calves with otisis media-interna

Présentement, le diagnostic d’otite moyenne-interne chez le veau est basé sur la présence de signes cliniques appropriés ainsi que les tests diagnostiques tels que la radiographie et la tomodensitométrie. L’objectif de cette étude prospective était d’évaluer les valeurs prédictives de l’examen neurologique, l’examen otoscopique et le test des potentiels auditifs évoqués (PAE) dans le diagnostic d’otite moyenne-interne chez le veau, en utilisant la tomodensitométrie comme test standard. Le deuxième objectif était de définir les valeurs de référence pour le PAE chez le veau normal et d’en décrire les anomalies chez des veaux atteints d’otite moyenne-interne. Dix-sept veaux de race Holstein entre 5-7 semaines d’âge ont été inclus. Tous les veaux ont eu un examen neurologique, un examen otoscopique et une évaluation des PAEs. Les veaux ont été tranquillisés avec de la xylazine intraveineuse (0,05-0,15mg/kg) pour la tomodensitométrie des bulles tympaniques afin d’évaluer pour la présence d’otite moyenne-interne. Selon les résultats de la tomodensitométrie, 11 des 17 veaux étaient atteints avec otite moyenne, 4 de façon unilatérale et 7 bilatéralement. Cinq ondes ont été identifiées de façon constante sur les tracés des PAEs des 6 veaux normaux. Les valeurs positives prédictives pour le PAE, l’examen neurologique et l’examen otoscopique étaient 94,7%, 91,7% et 66,7% respectivement. D’un point de vue clinique, le test le plus fiable dans le diagnostic d’otite moyenne-interne chez le veau est le PAE. Les anomalies ont été observées au PAE avant le développement des signes neurologiques chez certains veaux.

Analysis of transient otoacoustic emissions and brainstem evoked auditory potentials in neonates with hyperbilirubinemia

A hiperbilirrubinemia é tóxica às vias auditivas e ao sistema nervoso central, deixando sequelas como surdez e encefalopatia. OBJETIVOS: avaliar a audição de neonatos portadores de hiperbilirrubinemia, utilizando-se a pesquisa das emissões otoacústicas evocadas transientes (EOAET) e dos potenciais evocados auditivos do tronco encefálico (PEATE). Estudo prospectivo. CASUÍSTICA E MÉTODOS: Constituíram-se dois grupos: GI (n-25), neonatos com hiperbilirrubinemia; GII (n-22), neonatos sem hiperbilirrubinemia e sem fatores de risco para surdez. Todos os neonatos tinham até 60 dias de vida e foram submetidos à EOAET e ao PEATE. RESULTADOS: 12 neonatos de GI e 10 de GII eram meninas e 13 de GI e 12 de GII eram meninos. As EOAET estavam presentes em todas as crianças, porém com amplitudes menores em GI, especialmente nas frequências de 2 e 3KHz (p < 0,05). No PEATE, observou-se discreto prolongamento de PV e de LI-V em GI. As alterações observadas nesses testes não se correlacionaram aos níveis séricos da bilirrubinemia. CONCLUSÕES: em neonatos portadores de hiperbilirrubinemia, menores amplitudes das EOAET e discreto prolongamento de PV e de LI-V foram constatados indicando comprometimento coclear e retrococlear das vias auditivas, salientando-se a importância da utilização e da interpretação minuciosa de ambos os testes nessas avaliações.

Normative study and evaluation of age influence on Brainstem auditory evoked potentials in mixed breed dogs]

The aim of this paper was to obtain normative data of auditory evoked potentials from 34 mixed breed dogs and evaluate the age influence. The animals were divided in two groups of different ages and auditory evoked potential was performed with a 85dB stimulus intensity. Group 1 included 16 dogs between 1 and 8 years of age, and group 2 included 18 dogs with over 8 years of age. The length and head diameter were measured and there was no statistical difference between the two groups. In group 1, mean latencies of waves I, III, and V were 1.13; 2.64, and 3.45ms, and the intervals I-III, III-V, and I-V were 1.51; 0.81, and 2.32 ms, respectively. In group 2, the mean latencies of waves I, III and V were 1.15, 2.62, and 3.55ms, and the intervals I-III, III-V, and I-V were 1.47, 0.93, and 2.40ms, respectively. The latencies observed in this study were similar to previous studies conducted by other authors. It was observed that significant differences were present for wave V and intervals III-V and I-V latencies when comparing groups with different ages, consequently this characteristic must be considered during BAEP result interpretation.

Brainstem auditory evoked potential testing in Dalmatian dogs in Brazil

The brain stem auditory-evoked potential (BAEP) is an electrophysiologic test that detects and records the electrical activity in the auditory system from cochlea to midbrain, generated after an acoustic stimulus applied to the external ear. The aim of this study is to obtain normative data for BAEP in Dalmatian dogs in order to apply this to the evaluation of deafness and other neurologic disorders. BAEP were recorded from 30 Dalmatian dogs for a normative Brazilian study. Mean latencies for waves I, III, and V were 1.14 (±0.09), 2.62 (±0.10), and 3.46 (±0.14) ms, respectively. Mean inter-peak latencies for I-III, III-V, and I-V intervals were 1.48 (±0.17), 0.84 (±0.12), and 2.31 (±0.18) ms, respectively. Unilateral abnormalities were found in 16.7% of animals and bilateral deafness was seen in one dog. The normative data obtained in this paper is compatible with other published data. As far as we know this is the first report of deafness occurrence in Dalmatian dogs in Brazil.