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Auditory neuropathy (AN) is a hearing disorder characterized by disruption of temporal coding of acoustic signals in the auditory nerve resulting from lesions involving auditory nerve fibers, the inner hair cells, or their synapses with auditory nerve terminals. Disruption of auditory nerve discharge underlies both the absence of auditory brainstem responses (ABRs) and impairment of speech perception. AN may be related to genetic disorders or result from a wide range of other etiologies. It can be identified either as an isolated disorder (isolated AN) or associated with multisystem involvement (non-isolated AN). Effectiveness and choice of assistive devices depend crucially upon etiology, site of lesion, and stage of the disease. Cochlear implants constitute an effective rehabilitative tool able to restore speech perception in many patients with genetic AN, especially those affected by the isolated form of the disorder. Some children with isolated AN have proved to be good hearing aid users, showing satisfactory open-set speech perception abilities in the aided condition. Over 50% of children discharged from neonatal intensive care units showing the electrophysiological profile of AN (absent ABRs, presence of otoacoustic emissions) benefit from hearing aid use, the provision of amplification resulting in remarkable improvement in speech perception. It can be concluded that differences in cochlear implant outcome or hearing aid use in patients with AN are related to the pathophysiological mechanisms underlying alteration of auditory nerve discharge associated with individual etiologies.

Objective: The aim of this study was to disclose possible inner ear abnormalities/pathologies by means of high-resolution computed tomography (HRCT) of the temporal bone (TBHRCT) in children with unilateral hearing loss (UHL). Methods: Retrospective review of audiological evaluation and TBHRCT in 22 children with UHL. Results: Two thirds of the children showed profound hearing loss. Review of HRCT scans identified inner ear malformations/pathologies in 9 (41%) cases and a high jugular bulb (HJB), always dehiscent with the vestibular aqueduct, in another 5 (22%). Inner ear malformations included enlarged vestibular aqueduct, common cavity and cochleovestibular hypoplasia, while labyrinthine ossification was the detected pathology. In 1 child, the common cavity of the right ear was associated with congenital melanocytic naevus of the left eyelid and lipomeningocele. To the best of our knowledge, this condition has never been described. Conclusions: The aetiology of UHL may be revealed in more than half of patients by means of TBHRCT. Besides common inner ear abnormalities, TBHRCT should be evaluated carefully to rule out HJB, dehiscences, diverticulum or erosion of inner ear structures.

The mechanotransduction process in hair cells in the inner ear is associated with the influx of calcium from the endolymph. Calcium is exported back to the endolymph via the splice variant w/a of the PMCA2 of the stereocilia membrane. To further investigate the role of the pump, we have identified and characterized a novel ENU-induced mouse mutation, Tommy, in the PMCA2 gene. The mutation causes a non-conservative E629K change in the second intracellular loop of the pump that harbors the active site. Tommy mice show profound hearing impairment from P18, with significant differences in hearing thresholds between wild type and heterozygotes. Expression of mutant PMCA2 in CHO cells shows calcium extrusion impairment; specifically, the long term, non-stimulated calcium extrusion activity of the pump is inhibited. Calcium extrusion was investigated directly in neonatal organotypic cultures of the utricle sensory epithelium in Tommy mice. Confocal imaging combined with flash photolysis of caged calcium showed impairment of calcium export in both Tommy heterozygotes and homozygotes. Immunofluorescence studies of the organ of Corti in homozygous Tommy mice showed a progressive base to apex degeneration of hair cells after P40. Our results on the Tommy mutation along with previously observed interactions between cadherin-23 and PMCA2 mutations in mouse and humans underline the importance of maintaining the appropriate calcium concentrations in the endolymph to control the rigidity of cadherin and ensure the function of interstereocilia links, including tip links, of the stereocilia bundle.

Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goitre and defective iodide organification. Congenital and profound hearing loss is the hallmark of the syndrome, while goitre and thyroid dysfunction are highly variable even within the same family. Clinical features are due to altered formation of pendrin, a chloride/iodide transporter protein expressed in the inner ear, thyroid gland and kidney. A novel substitution was found in exon 7 of the pendrin encoding gene (SLC26A4) that leads to a stop codon, S314X. The new variation was found in compound heterozygosity with L445W mutation in a hearing impaired patient with bilateral Mondini's dysplasia and goitre.

Nonsyndromic sensorineural hearing impairment is inherited in a predominantly autosomal recessive manner in up to 70% of cases. The gene more often involved is GJB2, encoding the gap junction protein Connexin 26. We report here a novel missense mutation in the GJB2 gene found in a Tunisian family. A homozygous change C/G at nucleotide 263 was detected in the 4-year-old girl of this family, affected by congenital moderate hearing loss. This transversion leads to the replacement of a highly conserved alanine with glycine at codon 88 (A88G). The consanguineous parents of the child are healthy carriers of the mutation.

The outcome of cochlear implantation in patients with deafness of prelingual onset is largely unpredictable due to high individual variability. This study evaluated speech perception performances in a group of 18 prelingually deafened subjects (aged 13–30 years) which was homogeneous with respect to duration of deafness, hearing aid use before cochlear implantation, mode of communication and administration of auditory-oral speech therapy. Word discrimination length, word and sentence identification, phoneme identification and word and sentence recognition were tested before cochlear implantation and at 6 months, 1, 2 and 3 years of cochlear implant use. Scores on all tests significantly improved after cochlear implantation, although mean values were lower compared to those achieved by postlingually deafened patients. Speech performances on both word and sentence recognition continued to increase over time also beyond 1 year after cochlear implantation. Moreover, scores on sentence recognition tests were significantly higher compared to disyllabic words at 3 years of cochlear implant use. The presence of an auditory input delivered by hearing aids before cochlear implantation associated with auditory-oral therapy and a good level of education may positively influence the cochlear implant outcome in prelingually deafened adults.

We recorded cochlear potentials by transtympanic electrocochleography (ECochG) in three hearing-impaired children with GJB2 mutation who showed otoacoustic emissions. Pure tone thresholds, distortion product otoacoustic emissions (DPOAEs) and, auditory brainstem responses (ABRs) were also obtained. Subjects 1 (35delG/35delG) and 3 (M34T/wt) had profound hearing loss and showed the picture of auditory neuropathy (AN) as DPOAEs were detected with absent ABRs in both ears. The hearing impairment found in subject 2 (35delG/35delG) was profound in the right ear and moderate in the left ear. Both DPOAEs and ABRs with normal latencies and morphology were recorded only from the left ear. On the ECochG recording the cochlear microphonic was obtained from all children. No compound action potential (CAP) was detected in subject 1. A neural response was recorded only from the left ear in subject 2 with a threshold corresponding to the audiometric threshold while no CAP was detected on the right side. The ECochG obtained from subject 3 showed a low-amplitude broad negative deflection which was identifiable down to low stimulus levels. This response decreased in amplitude and duration when utilizing a high-rate stimulation paradigm. The amount of amplitude reduction was close to that calculated for normal ears, thus revealing the presence of an adapting neural component. These findings indicate that patients with GJB2 mutations and preserved outer hair cells function could present with the picture of AN. The hearing impairment is underlain by a selective inner hair cell loss or a lesion involving the synapses and/or the auditory nerve terminals. We suggest that neonatal hyperbilirubinemia may play a role in protecting outer hair cells against the damage induced by GJB2 mutations.

Santarelli et al. reveal that hearing impairments in patients carrying OPA1 missense mutations are the result of disordered synchrony in auditory nerve fibre activity owing to degeneration of terminal dendrites. Cochlear implantation improves speech perception and synchronous activation of auditory pathways in these patients by bypassing the lesion site., Hearing impairment is the second most prevalent clinical feature after optic atrophy in dominant optic atrophy associated with mutations in the OPA1 gene. In this study we characterized the hearing dysfunction in OPA1-linked disorders and provided effective rehabilitative options to improve speech perception. We studied two groups of OPA1 subjects, one comprising 11 patients (seven males; age range 13–79 years) carrying OPA1 mutations inducing haploinsufficiency, the other, 10 subjects (three males; age range 5–58 years) carrying OPA1 missense mutations. Both groups underwent audiometric assessment with pure tone and speech perception evaluation, and otoacoustic emissions and auditory brainstem response recording. Cochlear potentials were recorded through transtympanic electrocochleography from the group of patients harbouring OPA1 missense mutations and were compared to recordings obtained from 20 control subjects with normal hearing and from 19 subjects with cochlear hearing loss. Eight patients carrying OPA1 missense mutations underwent cochlear implantation. Speech perception measures and electrically-evoked auditory nerve and brainstem responses were obtained after 1 year of cochlear implant use. Nine of 11 patients carrying OPA1 mutations inducing haploinsufficiency had normal hearing function. In contrast, all but one subject harbouring OPA1 missense mutations displayed impaired speech perception, abnormal brainstem responses and presence of otoacoustic emissions consistent with auditory neuropathy. In electrocochleography recordings, cochlear microphonic had enhanced amplitudes while summating potential showed normal latency and peak amplitude consistent with preservation of both outer and inner hair cell activities. After cancelling the cochlear microphonic, the synchronized neural response seen in both normally-hearing controls and subjects with cochlear hearing loss was replaced by a prolonged, low-amplitude negative potential that decreased in both amplitude and duration during rapid stimulation consistent with neural generation. The use of cochlear implant improved speech perception in all but one patient. Brainstem potentials were recorded in response to electrical stimulation in five of six subjects, whereas no compound action potential was evoked from the auditory nerve through the cochlear implant. These findings indicate that underlying the hearing impairment in patients carrying OPA1 missense mutations is a disordered synchrony in auditory nerve fibre activity resulting from neural degeneration affecting the terminal dendrites. Cochlear implantation improves speech perception and synchronous activation of auditory pathways by bypassing the site of lesion.

To evaluate the effects of a volatile anesthetic, isoflurane, on auditory brainstem responses (ABRs) and middle latency responses (MLRs) recorded in rats.ABRs and MLRs evoked by click stimuli were simultaneously recorded in eight rats in the awake condition and during anesthesia with isoflurane at clinically relevant concentrations.Vertex-recorded ABRs showed a significant increase in the latency of waves I-IV during anesthesia and the latency changes appeared to be significantly related to the isoflurane concentration. The I-IV interval also appeared to be significantly increased in comparison to the awake condition, while minor changes in ABR amplitudes were induced by isoflurane. MLRs, which were recorded by means of epidural electrodes implanted over the auditory cortex, appeared to be attenuated in amplitude and increased in latency during anesthesia. Only latency changes appeared to be significantly related to the isoflurane concentration. Moreover, "bursts" of high amplitude MLRs were observed during anesthesia at each concentration.The present findings indicate that both ABR and MLR latencies are increased by isoflurane in a concentration-dependent manner, whilst the anesthetic-induced attenuation in amplitude does not appear to be related to the isoflurane concentration.

Phosphatidylinositol phosphate kinase type 1γ (PIPKIγ) is a key enzyme in the generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ] and is expressed at high levels in the nervous system. Homozygous knockout mice lacking this enzyme die postnatally within 24 h, whereas PIPKIγ +/− siblings breed normally and have no reported phenotype. Here we show that adult PIPKIγ +/− mice have dramatically elevated hearing thresholds for high-frequency sounds. During the first postnatal week we observed a reduction of ATP-dependent Ca 2+ signaling activity in cochlear nonsensory cells. Because Ca 2+ signaling under these conditions depends on inositol-1,4,5-trisphosphate generation from phospholipase C (PLC)-dependent hydrolysis of PI(4,5)P 2 , we conclude that ( i ) PIPKIγ is primarily responsible for the synthesis of the receptor-regulated PLC-sensitive PI(4,5)P 2 pool in the cell syncytia that supports auditory hair cells; ( ii ) spatially graded impairment of this signaling pathway in cochlear nonsensory cells causes a selective alteration in the acquisition of hearing in PIPKIγ +/− mice. This mouse model also suggests that PIPKIγ may determine the level of gap junction contribution to cochlear development.

Eustachian tube (ET) primary tumors and tumor-like lesions are rare diseases presenting with common ear, nose and throat symptoms. Pathology can range from developmental anomalies to high malignant neoplasms. Hence this review aimed at suggesting a classification and outline relevant aspects of ET primary tumors and tumor-like lesions, describing clinical findings, diagnostic management and therapeutic approaches. MEDLINE, CINAHL, OVIDSP, HIGHWIRE, and GOOGLE databases were searched from inception to July 2011 for relevant studies. Further papers were identified by examining the reference lists of all included. Sixty-five papers met the inclusion criteria, enclosing 78 cases. Case reports are increasing in the past few years. Benign lesions and tumor-like lesions of ET have been reported. Moreover, melanomas, carcinomas, and sarcomas can affect the ET as a primary site.

Objectives Cochlear-implanted deaf children having additional disabilities may develop speech perception and language skills at a slower pace than their implanted peers without such disorders. Nevertheless, it has been shown that, even for these special cases, cochlear implantation (CI) provides benefits for a larger range of neuropsychological functions including social and relational skills. These benefits are frequently mentioned by parents, but rarely objectively measured by tests. This article presents a new evaluation tool aimed at assessing the global benefits offered by CI in these special cases. Design The new tool has been designed as a closed-format questionnaire, divided into five areas. It is based on observing the frequency of preselected behaviors in daily activities, which imply specific social, neuropsychological, and perceptual skills. The questionnaire has been presented to the parents of 50 deaf children with additional disabilities, before and at least 6 months after CI. Results The data show significant improvements in all investigated areas. However, not all skills improve in the same way, and only those skills related to language and communication correlate positively with time after implantation. The present article further discusses changes in skills for which parents have higher expectations, such as the preferred communication mode, speech intelligibility, and the ability to communicate on the telephone. Conclusions The questionnaire has a simple-to-use format, and it has been proven to be sufficiently sensitive for the detection of changes in each examined area. Because the questionnaire is based on observed behaviors, it can be used even when other existing tests involve tasks that are too complex for these children.

Objective: Our objective was to compare acoustically-and electrically-evoked potentials of the auditory nerve in patients with postsynaptic or presynaptic auditory neuropathy with underlying mutations in the OPA1 or OTOF gene. Study design: Transtympanic electrocochleography (ECochG) was recorded from two adult patients carrying the R445H OPA1 mutation, and from five children with mutations in the OTOF gene. Cochlear potentials to clicks or tone-bursts were compared to recordings obtained from 16 normally hearing subjects. Electrically-evoked neural responses recorded through the cochlear implant were also obtained. Results: The cochlear microphonic (CM) was recorded from all subjects, with normal amplitudes. After cancelling the CM, cochlear potentials were of negative polarity with reduced amplitude and prolonged duration compared to controls in both groups of patients. Prolonged negative responses were recorded as low as 50-90dB below behavioural threshold in subjects with OTOF mutations whereas in the OPA1 disorder the prolonged potentials were correlated with hearing threshold. A compound action potential (CAP) was superimposed on the prolonged activity at high stimulation intensity in two children with mutations in the OTOF gene while CAPs were absent in the OPA1 disorder. Electrically-evoked compound action potentials (e-CAPs) were only recorded from subjects with OTOF mutations following cochlear implantation. Conclusions: The findings are consistent with abnormal function of distal portions of auditory nerve fibres in patients carrying the OPA1 mutation whereas the low-threshold prolonged potentials recorded from children with mutations in the OTOF gene are consistent with abnormal neurotransmitter release resulting in reduced dendritic activation and impairment of spike initiation. © 2011 Informa Healthcare.

The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6, encoding connexin30, which appear to be coordinately regulated in the inner ear. In this work, we investigated the expression and function of connexin26 and connexin30 from postnatal day 5 to adult age in double transgenic Cx26(Sox10Cre) mice, which we obtained by crossing connexin26 floxed mice with a deleter Sox10-Cre line. Cx26(Sox10Cre) mice presented with complete connexin26 ablation in the epithelial gap junction network of the cochlea, whereas connexin30 expression was developmentally delayed; immunolabeling patterns for both connexins were normal in the cochlear lateral wall. In vivo electrophysiological measurements in Cx26(Sox10Cre) mice revealed profound hearing loss accompanied by reduction of endocochlear potential, and functional experiments performed in postnatal cochlear organotypic cultures showed impaired gap junction coupling. Transduction of these cultures with a bovine adeno associated virus vector restored connexin26 protein expression and rescued gap junction coupling. These results suggest that restoration of normal connexin levels by gene delivery via recombinant adeno associated virus could be a way to rescue hearing function in DFNB1 mouse models and, in future, lead to the development of therapeutic interventions in humans.

The aim of this study was to describe the clinical features of hearing loss due to mutations on connexin 26/30 coding genes (GJB2/GJB6). Mutations in the GJB2 gene are found to account for approximately 50% of cases of autosomal recessive non-syndromic deafness. Several European studies have estimated that the GJB2 healthy carrier condition involves about 2-4% of the population, with the 35delG mutations being the most common. A 342-kb deletion truncating the GJB6 gene (encoding connexin-30) has been associated with autosomal recessive non-syndromic deafness, mostly as digenic inheritance of the Cx30 deletion/Cx26 mutation. The following retrospective study describes audiological features and genotypes of a large cohort of 376 Italian hearing-impaired patients who underwent genetic screening for the GJB2/GJB6 genes and received follow-up care at our centre between January 2002 and October 2006. Sixteen different genotypes causing deafness in more than 27% of patients with either biallelic mutations or digenic inheritance GJB2/GJB6 were identified. The most frequent mutations were 35delG, M34T, L90P, and R184P.

OBJECTIVE To compare speech perception performance in children fitted with previous generation Nucleus sound processor, Sprint or Esprit 3G, and the Freedom, the most recently released system from the Cochlear Corporation that features a larger input dynamic range. STUDY DESIGN Prospective intrasubject comparative study. SETTING University Medical Center. SUBJECTS Seventeen prelingually deafened children who had received the Nucleus 24 cochlear implant and used the Sprint or Esprit 3G sound processor. INTERVENTION Cochlear implantation with Cochlear device. MAIN OUTCOME MEASURES Speech perception was evaluated at baseline (Sprint, n = 11; Esprit 3G, n = 6) and after 1 month's experience with the Freedom sound processor. Identification and recognition of disyllabic words and identification of vowels were performed via recorded voice in quiet (70 dB [A]), in the presence of background noise at various levels of signal-to-noise ratio (+10, +5, 0, -5) and at a soft presentation level (60 dB [A]). Consonant identification and recognition of disyllabic words, trisyllabic words, and sentences were evaluated in live voice. Frequency discrimination was measured in a subset of subjects (n = 5) by using an adaptive, 3-interval, 3-alternative, forced-choice procedure. RESULTS Identification of disyllabic words administered at a soft presentation level showed a significant increase when switching to the Freedom compared with the previously worn processor in children using the Sprint or Esprit 3G. Identification and recognition of disyllabic words in the presence of background noise as well as consonant identification and sentence recognition increased significantly for the Freedom compared with the previously worn device only in children fitted with the Sprint. Frequency discrimination was significantly better when switching to the Freedom compared with the previously worn processor. CONCLUSION Serial comparisons revealed that that speech perception performance evaluated in children aged 5 to 15 years was superior with the Freedom than previous generations of Nucleus sound processors. These differences are deemed to ensue from an increased input dynamic range, a feature that offers potentially enhanced phonemic discrimination.

Otoferlin is involved in neurotransmitter release at the synapse between inner hair cells (IHCs) and auditory nerve fibres, and mutations in the OTOF gene result in severe to profound hearing loss. Abnormal sound-evoked cochlear potentials were recorded with transtympanic electrocochleography from four children with otoferlin (OTOF) mutations to evaluate physiological effects in humans of abnormal neurotransmitter release from IHCs. The subjects were profoundly deaf with absent auditory brainstem responses and preserved otoacoustic emissions consistent with auditory neuropathy. Two children were compound heterozygotes for mutations c.2732-2735dupAGCT and p.Ala964Glu; one subject was homozygous for mutation p.Phe1795Cys, and one was compound heterozygote for two novel mutations c.1609delG in exon 16 and c.1966delC in exon 18. Cochlear potentials evoked by clicks from 60 to 120 dB peak equivalent sound pressure level were compared to recordings obtained from 16 normally hearing children. Cochlear microphonic (CM) was recorded with normal amplitudes from all but one ear. After cancelling CM, cochlear potentials were of negative polarity with reduced amplitude and prolonged duration compared to controls. These cochlear potentials were recorded as low as 50-90 dB below behavioural thresholds in contrast to the close correlation in controls between cochlear potentials and behavioural threshold. Summating potential was identified in five out of eight ears with normal latency whilst auditory nerve compound action potentials were either absent or of low amplitude. Stimulation at high rates reduced amplitude and duration of the prolonged potentials, consistent with neural generation. This study suggests that mechano-electrical transduction and cochlear amplification are normal in patients with OTOF mutations. The low-amplitude prolonged negative potentials are consistent with decreased neurotransmitter release resulting in abnormal dendritic activation and impairment of auditory nerve firing. © 2009 Association for Research in Otolaryngology.

Objective: Transtympanic electrocochleography (ECochG) was recorded bilaterally in children and adults with auditory neuropathy (AN) to evaluate receptor and neural generators. Methods: Test stimuli were clicks from 60 to 120 dB p.e. SPL. Measures obtained from eight AN subjects were compared to 16 normally hearing children. Results: Receptor cochlear microphonics (CMs) in AN were of normal or enhanced amplitude. Neural compound action potentials (CAPs) and receptor summating potentials (SPs) were identified in five AN ears. ECochG potentials in those ears without CAPs were of negative polarity and of normal or prolonged duration. We used adaptation to rapid stimulus rates to distinguish whether the generators of the negative potentials were of neural or receptor origin. Adaptation in controls resulted in amplitude reduction of CAP twice that of SP without affecting the duration of ECochG potentials. In seven AN ears without CAP and with prolonged negative potential, adaptation was accompanied by reduction of both amplitude and duration of the negative potential to control values consistent with neural generation. In four ears without CAP and with normal duration potentials, adaptation was without effect consistent with receptor generation. In five AN ears with CAP, there was reduction in amplitude of CAP and SP as controls but with a significant decrease in response duration. Conclusions: Three patterns of cochlear potentials were identified in AN: (1) presence of receptor SP without CAP consistent with pre-synaptic disorder of inner hair cells; (2) presence of both SP and CAP consistent with post-synaptic disorder of proximal auditory nerve; (3) presence of prolonged neural potentials without a CAP consistent with post-synaptic disorder of nerve terminals. Significance: Cochlear potential measures may identify pre- and post-synaptic disorders of inner hair cells and auditory nerves in AN. © 2008 International Federation of Clinical Neurophysiology.

Autosomal recessive nonsyndromic hearing impairment (NSHI) is a heterogeneous condition, for which 53 genetic loci have been reported, and 29 genes have been identified to date. One of these, OTOF, encodes otoferlin, a membrane-anchored calcium-binding protein that plays a role in the exocytosis of synaptic vesicles at the auditory inner hair cell ribbon synapse. We have investigated the prevalence and spectrum of deafness-causing mutations in the OTOF gene. Cohorts of 708 Spanish, 83 Colombian, and 30 Argentinean unrelated subjects with autosomal recessive NSHI were screened for the common p.Gln829X mutation. In compound heterozygotes, the second mutant allele was identified by DNA sequencing. In total, 23 Spanish, two Colombian and two Argentinean subjects were shown to carry two mutant alleles of OTOF. Of these, one Colombian and 13 Spanish subjects presented with auditory neuropathy. In addition, a cohort of 20 unrelated subjects with a diagnosis of auditory neuropathy, from several countries, was screened for mutations in OTOF by DNA sequencing. A total of 11 of these subjects were shown to carry two mutant alleles of OTOF. In total, 18 pathogenic and four neutral novel alleles of the OTOF gene were identified. Haplotype analysis for markers close to OTOF suggests a common founder for the novel c.2905_2923delinsCTCCGAGCGCA mutation, frequently found in Argentina. Our results confirm that mutation of the OTOF gene correlates with a phenotype of prelingual, profound NSHI, and indicate that OTOF mutations are a major cause of inherited auditory neuropathy. Hum Mutat 29(6), 823–831, 2008. © 2008 Wiley-Liss, Inc.

The outcome of cochlear implantation in patients with deafness of prelingual onset is largely unpredictable due to high individual variability. This study evaluated speech perception performances in a group of 18 prelingually deafened subjects (aged 13-30 years) which was homogeneous with respect to duration of deafness, hearing aid use before cochlear implantation, mode of communication and administration of auditory-oral speech therapy. Word discrimination length, word and sentence identification, phoneme identification and word and sentence recognition were tested before cochlear implantation and at 6 months, 1, 2 and 3 years of cochlear implant use. Scores on all tests significantly improved after cochlear implantation, although mean values were lower compared to those achieved by postlingually deafened patients. Speech performances on both word and sentence recognition continued to increase over time also beyond 1 year after cochlear implantation. Moreover, scores on sentence recognition tests were significantly higher compared to disyllabic words at 3 years of cochlear implant use. The presence of an auditory input delivered by hearing aids before cochlear implantation associated with auditory-oral therapy and a good level of education may positively influence the cochlear implant outcome in prelingually deafened adults.

The issue of cochlear implantation in deaf children with associated disabilities is an emerging subject. Currently, there is no consensus on whether to implant children with multiple impairments; moreover, it may be difficult to evaluate these children with standard tests pre- or post-implantation. In addition, these children often have poor speech perception and language skills, making assessment more difficult. Despite these factors, these children often receive important benefits in daily life, with an overall improvement in quality of life. In the present study, post-implant outcomes of 23 profoundly deaf children with neuropsychiatric disorders were analysed, using objective measures of speech perception, and a questionnaire administered to the parents, aimed at evaluating the benefits in daily life after implantation. The results were quite variable, but overall positive, in terms of speech perception, communication abilities, and improvement in quality of life. The findings add an additional piece of evidence to support the effectiveness of cochlear implantation in these special cases.

We report the results of speech perception and electrophysiological evaluation of the auditory periphery performed before and after cochlear implantation in a 18-year-old girl with systemic sclerosis (SS) who presented the clinical picture of auditory neuropathy. Transtympanic electrocochleography (ECochG) in response to 0.1 ms clicks was recorded 1 month before cochlear implantation on both sides while the electrically evoked neural response was obtained intraoperatively in the right ear through cochlear implant stimulation. The ECochG recordings revealed the presence of the cochlear microphonic with normal amplitude and threshold on both sides. A compound action potential was only detected in the left ear at high stimulation intensity, while the electrically evoked neural response was clearly identifiable at all the recording sites during neural response telemetry. Standardized speech perception tests were performed 1 month before cochlear implantation and several times after cochlear implant connection. Speech perception scores were close to chance before cochlear implantation while they showed a remarkable improvement thereafter. The results of this study show that subjects affected by SS could present the clinical picture of auditory neuropathy which is possibly underlain by lesions involving the distal portion of auditory nerve fibers and/or synapses with inner hair cells. The restoration of synchronous neural discharge could be achieved by electrical stimulation through cochlear implant.

In the literature there is limited research on the interaction of language and arithmetic performance of deaf students, although previous studies have demonstrated that many of these students are delayed in both their language acquisition and arithmetic performance. The focus of the first part of this work is a brief review of the literature on acquisition of learning abilities in prelingually deaf children with hearing aids and cochlear implants. Children who experience severe to profound deafness early in their life have a better prognosis for normal literacy development than ever before. In fact, the restoration of the auditory threshold allows children to achieve language and learning abilities like normally hearing children. In the second part we describe our initial experiences in the field. We discuss some preliminary results of an investigation of the longitudinal development of cognitive abilities related to numerical cognition in hearing-impaired children who have had a hearing aid or a cochlear implant at a young age. Specifically, we analyse the development of numerical abilities related to verbal abilities (such as those implied in counting tasks), reading and writing numbers, and analogical numerical abilities (such as those based on quantity recognition as in number comparison and number seriation).

The potential evoked by a ‘train’ of N equally spaced auditory clicks, with an inter-click period shorter than the duration of the response to an isolated click, is said to be a steady-state response (SSR). Extracting the individual responses evoked by the clicks of the train during steady state can be key to understanding of the neurophysiological mechanisms underlying SSR generation. In the literature, this task has been dealt with only under the (unwarranted) assumption that the response of the system does not vary during the presentation of the clicks, i.e. no neurophysiological adaptation is present. In this work, a new, non-parametric algorithm is proposed that, relaxing the time-invariance hypothesis, allows the extraction from the SSR of the N waveforms individually evoked by the N clicks of the train. The performance of the approach is evaluated on simulated SSRs and on real data recorded from the temporal cortex of awake rats. Results show that the method is able to detect and assess possible adaptation of the neurophysiological system in the generation of SSRs.

Auditory steady-state responses (SSRs) are believed to result from superimposition of middle latency responses (MLRs) evoked by individual stimuli during repetitive stimulation. Our previous studies showed that besides linear addition of MLRs, other phenomena, mainly related to the adaptive properties of neural sources, interact in a complex way to generate the SSRs recorded from the temporal cortex of awake rats. The aim of this study was to evaluate the effects of the inhalational general anesthetic, isoflurane, on MLRs and SSRs at several repetition rates (30-60 Hz) recorded from the temporal cortex of rats. Auditory evoked potentials were obtained by means of epidural electrodes in the awake condition and during anesthesia at three isoflurane concentrations (0.38, 0.76 and 1.13 vol.% in oxygen). MLR latency significantly increased during anesthesia in a concentration-dependent manner, while MLR amplitude, even when significantly attenuated with respect to the mean awake baseline value, failed to correlate with isoflurane concentration. SSRs decreased in amplitude and increased in phase during anesthesia in a concentration-dependent manner and the anesthetic-induced decrease of SSR amplitude appeared to be higher than the corresponding MLR attenuation. SSR prediction curves synthesized by linear addition of MLRs failed to predict SSRs in both amplitude and phase. Moreover, phase discrepancies proved to be higher during anesthesia. Our results suggest that MLRs and SSRs recorded from the temporal cortex of the rat exhibit differential sensitivity to isoflurane and that isoflurane could enhance the role of rate-dependent effects in SSR generation.

Several approaches, based on different assumptions and with various degree of theoretical sophistication and implementation complexity, have been developed for improving the measurement of evoked potentials (EP) performed by conventional averaging (CA). In many of these methods, one of the major challenges is the exploitation of a priori knowledge. In this paper, we present a new method where the 2nd-order statistical information on the background EEG and on the unknown EP, necessary for the optimal filtering of each sweep in a Bayesian estimation framework, is, respectively, estimated from pre-stimulus data and obtained through a multiple integration of a white noise process model. The latter model is flexible (i.e. it can be employed for a large class of EP) and simple enough to be easily identifiable from the post-stimulus data thanks to a smoothing criterion. The mean EP is determined as the weighted average of the filtered sweeps, where each weight is inversely proportional to the expected value of the norm of the correspondent filter error, a quantity determinable thanks to the employment of the Bayesian approach. The performance of the new approach is shown on both simulated and real auditory EP. A signal-to-noise ratio enhancement is obtained that can allow the (possibly automatic) identification of peak latencies and amplitudes with less sweeps than those required by CA. For cochlear EP, the method also allows the audiology investigator to gather new and clinically important information. The possibility of handling single-sweep analysis with further development of the method is also addressed.

In electrocochleography (ECochG) compound action potential (CAP) and summation potential (SP) are usually separated from the cochlear microphonic (CM) by the CM cancellation technique consisting in averaging the responses evoked by rarefaction and condensation clicks. With the aim of analysing the ECochG responses evoked by monophasic clicks, we developed a numerical method based on the theory of optimal filtering, which makes no assumptions about the unknown potentials. The application of the filtering technique to the ECochG recordings obtained from 6 normally hearing children and 10 children with cochlear hearing loss allowed us to perform CAP extraction in cases where CM was not cancelled by the conventional method. Differences in SP amplitude and polarity were found between rarefaction and condensation click-evoked responses in cochlear hearing losses.

The cochlear microphonic potential (CM) and the compound action potential (CAP) cannot be measured separately but only in combination. In the literature their individual estimates are conventionally recovered by the so-called CM cancellation technique. This method averages the potential obtained in response to rarefaction and condensation clicks under the assumption that changing the polarity of the clicks only affects the CM sign and does not alter the CAP in any way. However, both theory and evidence suggest that these hypotheses can be critical. In addition, recent contributions in the electrocochleography (ECochG) literature suggested that assessing the influence of stimulus polarity on the evoked CAP may constitute an indicator of clinical usefulness which the CM cancellation method cannot supply. In this work we propose a new algorithm to estimate the cochlear potentials evoked from positive clicks, CAP+ and CM+, and those evoked from negative clicks, CAP– and CM–, by processing the same kind and amount of data employed in the CM cancellation method. The application to real data taken from 3 subjects exhibiting quantitatively and qualitatively different ECochG responses at various levels of stimulation intensity is presented. In addition, simulated problems where the true CAP and CM are known are studied to permit a fair assessment of the proposed technique. Results suggest that the new algorithm is potentially able to point out small differences between CAP+ and CAP–. This encourages its further employment on a larger scale.

Clinically used drugs and chemical agents may potentially cause adverse effects to the human auditory and vestibular systems. Many of them, such as aminoglycosides and cisplatin, can play a critical role in the treatment of serious or life-threatening diseases; others, like loop diuretics or salycilates, offer such important therapeutical effects compared to the ototoxic side effects that the ototoxicity risk can be considered to be of minor importance. The problem of ototoxic side effects is more acute in developing countries, where highly effective and low-cost drugs are more easily prescribed without adequate monitoring. Medical awareness of doses, forms of administration, populations at risk, and possible synergism is necessary in order to develop appropriate care in the prescription of drugs with ototoxic side effects. Relatively recent issues such as risk-benefit analysis, patient-informed consent, and quality-of-life considerations, particularly when life expectancy can be low, are also to be considered. At present, a uniform method of monitoring for all potentially ototoxic therapeutics does not seem reasonable or practical. It is recommended, however, that individual auditory function be noted for a particular drug being employed. Protocols and exams should be easy, quick, sensitive, reliable, and as objective as possible. Benefits of audiological monitoring include the opportunity to change the patient's treatment course, improvement of patient and family awareness of the impact of hearing impairment, and timely prescription of amplification devices. Finally, particular attention should be paid to high-risk populations such as neonatal intensive care unit patients.

Cochlear and retrocochlear lesions may be differentiated by a diagnostic index (D5), which is derived from the patient's auditory brain-stem wave V latency and pure-tone hearing threshold at 2 to 4 kHz. The D5 values obtained from 49 cases of acoustic neuroma (AN) have been shown to share some properties with D5 values of patients with cochlear hearing loss (280 cases), indicating a lesser prolongation of wave V latency in cases with pronounced hearing loss. Assuming this finding is indicative of some degree of cochlear impairment concomitant to the neural dysfunction, AN data were corrected in an attempt to remove the effects of cochlear impairment. The resulting D5 values could reflect the delay in wave V solely due to the neural dysfunction. A significant relationship between these D5 values and tumour size seems to support this hypothesis.

Elderly people often complain of difficulty in speech discrimination, especially in noise environments. The effects of 4 competing noises on sentence intelligibility were evaluated: speech noise, cocktail party noise, traffic noise and continuous discourse. A comparison was made between young and old normally hearing subjects and young and old hearing-impaired subjects with similar audiograms. The old people with normal hearing had slightly reduced discrimination compared to the young during competing speech noise and cocktail noise. Discrimination in the hearing-impaired elderly was also significantly worse than in the young people with normals hearing, during competing cocktail party noise, traffic noise and continuous discourse. The young hearing-impaired had results between young normal-hearing subjects and old hearing-impaired, except for continuous discourse. Thus the effects of age on speech discrimination in noise are subtle, becoming more pronounced in the presence of hearing loss. Age-related changes in primary speech discrimination were particularly evident during competing continuous discourse.

The whole pattern of the fast, middle and long latency auditory evoked potentials (AEP) was recorded simultaneously from the scalp surface of 13 normal-hearing adults. The individual responses were displayed on a nonlinear time axis in order to improve identification of the components. Stimulation consisted of 2048 unfiltered clicks, delivered monaurally at 80, 60, 40 dB HL with an ISI of 750 ms. Changes in mean latency and amplitude of each AEP component were statistically evaluated in relation to intensity and electrode montage (vertex-mastoid ipsi- and contralateral to the stimulated ear). The latencies of fast components I-VI and the slow P1 increase significantly with declining stimulus intensity. The amplitudes of the fast, I, II, III, V and the slow P1-N1, P2-N2 decrease significantly with intensity. As regards differences due to the electrode montage the contralateral recording causes significant changes in latency of the fast potentials up to wave IV, and changes in amplitude of the fast up to wave V, and of the slow P1-N1 and P2-N2. Therefore, as their latency and amplitude seem to be less closely related to the stimulus and electrode placement, the middle components behave differently, compared with the preceding and following components. Based on parametric comparisons of potentials ranging widely in latency, but each one evoked by an equal sensory input, this kind of AEP evaluation may be useful both for neurophysiological and clinical studies of the whole auditory pathway function.

The brainstem responses (BER) evoked by binaural clicks (0.1 ms) with interaural time differences (delta t) from 0 to 3.5 ms were studied in 6 normal subjects. The responses analysis was carried out via computer in two different ways: (a) Comparison between binaural BER and templates obtained with the addition of two monaural BERs. (b) Extraction from the binaural BER of the second delayed pattern. The results suggest that an algebraic addition of the responses from the two stimulated sides is the main mechanism of the binaural BER generation. In comparison with the templates, the binaural response shows some differences which are evident at delta t = 0--1.5 ms and are limited in the region of VI and VII waves. Such differences are caused essentially to an amplitude decrease of the second pattern--that is response to the delayed stimulus--mainly at delta t 1.5 ms. However these results do not allow us to say if the phenomenon recorded at the surface is due to central adaptation or to specific mechanism of binaural interaction.

Auditory MLR and ABR were recorded simultaneously in 9 children under general anaesthesia, after electrocochleography had demonstrated a normal hearing threshold. In contrast to the ABR components which in all cases appeared to be clearly recognizable, and with latencies within the normal range, MLR revealed gross abnormalities represented by instability of the components and abnormal latency of the detectable peaks. Since such variations in the MLR pattern may be thought of as a direct consequence of general anaesthesia, it seems likely that these potentials reflect a neural activity which, in children, is affected by CNS drugs.

On September 28, 1759, Count Francesco Algarotti, writing from Riolo, informed the Bolognese painter, Prospero Pesci, that he had ordered from Canaletto a scene of the Rialto Bridge in Venice. Instead of the customary buildings, however, this painting contained only edifices by Palladio, including the bridge itself, which was the project of the great Vicentine architect. On the left could be seen the Palazzo Chiericati of Vicenza, while en the right was the Basilica, also of Vicenza.1

The first heart sound was studied in 20 normal subjects. The phonocardiogram (PCG) was recorded from apical and mid-precordial areas using microphone with a flat response curve from 0.2 to 8, 000Hz. It was stored, together with a simultaneous electrocardiogram, on an FM analog tape recorder (linear frequency response from 0 to 4, 000Hz), fitted with a filter with weighting curve B according to the American National Standard Institute. A linear (SPL) recording was also made. The signal was fed through a digital converter into a minicomputer and the frequency distribution of the first heart sound was analyzed using Fast Fourier Transform. These data were stored and the average spectra were calculated for both B and SPL. The SPL spectra from both apex and mid-precordium showed a maximum intensity of about 80 dB between 12-20Hz, decreasing progressively to a constant level of 35 dB between 110-120Hz. The spectra obtained from both areas using filter B showed a maximum intensity of 40-50dB between 20-60Hz, decreasing to 30dB at 112Hz and remaining constant thereafter. It is important to emphasize that the dB values in B and SPL are absolute, since they refer to a standard reference weighting.It appears that the SPL recording is more valuable in that it allows the study of all components of the PCG signal. The spectra obtained in this study will be used as a standard for future research in various pathological conditions.

Auditory evoked potentials (AEP) can be simultaneously recorded on-line as a succession of 11 waves, through a single input channel of a mini-computer. Since the response waves differ widely in frequency, a computing routine has been developed to display the whole response pattern in a single picture. Based upon a non-linear samples reduction of the digitized response, this routine allows a logarithmic transformation of the time axis. The method improves the identification of the AEP components and provides an objective estimate of the central auditory pathway for both neurophysiological and neuroclinical studies.

The hearing level of 133 railway workers who also hunted for sport was evaluated and compared with that of 82 non-hunting colleagues. Both groups were affected by hearing loss, mostly involving the high-frequency range. Hunters were found to differ from non-hunters by having significantly worse hearing threshold in the ear contralateral to the shoulder supporting the firearm. The interaural threshold difference at 4 kHz was related to the number of rounds fired and exposure duration, thus providing an estimate of the adverse effect of gunfire noise to which the hunters had been exposed.

The present study is focused on spectrum analysis as a useful method of processing the PCG in order to obtain the frequency spectral distribution of normal heart sounds. Thirty normal subjects aged from 17 to 34 were studied. PCG was recorded on the fourth intercostal space at the left sternal border using a sound level meter coupled with a standard 6 ml cavity. The microphone had a linear response from 0.2 to 8,000 Hz. The signal was filtered with the standard B network according to the ANSI specifications and was registered on a four track FM tape recorder. A four channel analyzer with a microprocessor for off-line elaborations was used with 10 KHz sampling frequency. The PCG signal was triggered by a QRS detector on the R wave of the simultaneously recorded ECG. Fast Fourier transform was performed employing either a four channel analyzer with a microprocessor, or an A/D converter with a computer. Finally the results of the analysis were statistically elaborated. The described procedures permit to obtain a direct and exact tracing of the acoustic features of the heart, thus representing an attempt to come closer to the standardization and automatic analysis of the phonocardiographic technique.

The auditory brainstem responses (ABRs) obtained in 47 subjects with asymmetric hearing loss (12 with surgically confirmed cerebello-pontine angle tumours, 35 without otoneurologic and/or neuroradiologic evidence of tumour) were evaluated by means of an index named delta V. The calculation of this index was based upon the patient's wave V absolute latency obtained at a fixed intensity of 90 dB HL and the value of latency predictable by means of the normative data. The index clearly separates retrocochlear from cochlear sites of lesion. Moreover delta V values obtained in defined cochlear lesions show a linear relation with the patient's pure tone hearing loss at 2 and 4 kHz; this behaviour is probably due to a reduction of the auditory dynamic range in the recruiting ears. delta V appears to have clinical usefulness because of two main points: first it is based upon an evaluation of the monaurally evoked ABR; second, it improves the diagnostic specificity of the responses. The rate of false positive results can be further reduced by combining delta V and IT5 values.

The auditory brain-stem responses (ABR) in 19 patients with confirmed cerebellopontine angle tumours are evaluated in relation to the hearing threshold as obtained by pure-tone audiometry. ABR pathological alterations, in terms of either absence or presence of components, appear to relate to the suprathreshold stimulus intensity and to match the changes which can be observed in subjects with normal hearing, when stimulated at the equivalent suprathreshold intensity. Of the diagnostic indexes considered (I-V interval, IT5, delta V), IT5 and delta V could be evaluated in the largest patient population. They may be used in combination to enhance their sensitivity in retrocochlear lesion detection.

The deaf child must receive sound amplification before he reaches the age of two years. At this age the hearing threshold is best measured objectively by electrocochleography (ECochG) and auditory brainstem response (ABR) audiometry. When used correctly, both methods allow an exact threshold estimation which is informative enough for adequate hearing aid prescription. Both methods have advantages and disadvantages when used in children. The advantages of ECochG are: (a) a more exact threshold estimation and (b) strictly monaural evaluation. The advantages of ABR are: (a) ease of performance; it is not invasive and does not require general anaesthesia and (b) allows for exploration of higher levels in the auditory pathway up to the midbrain. We believe that ECochG and ABR are compatible and complementary in the diagnosis of childhood deafness. ABR could be used in first instance, while ECochG could be reserved for doubtful cases and for those who cannot be adequately sedated. Extra-audiological factors such as the availability of anaesthetists and varying hospital facilities, play a further role in determining the choice of electric response technique.