Cochlear origin of 2f1-f2 distortion products assessed by using 2 types of mutant mice

Mutant mice with a particular type of cochlear pathology are excellent models to study the functional role of various structures in the cochlea. In order to assess the contribution of inner and outer hair cells to the generation of distortion product emissions (DPEs) we have recorded the 2f1-f2 DPE in a control group of CBA mice, which have normal numbers of inner and outer hair cells and two different types of mutant mice: the Bronx-waltzer mice and the Wv/Wv mice. In the Bronx waltzer mutant mice, 70% of inner hair cells are missing whereas the outer hair cells are present in normal number. The distortion product emissions 2f1-f2 is clearly recordable with a 10-20 dB lower magnitude as compared to normal CBA control mice. The homozygous Wv/Wv mutant mice on the other hand present a selective outer hair cell loss as a constant defect with no progressive degeneration of the organ of Corti and an essentially normal inner hair cell population. The cubic distortion products 2f1-f2 could not be detected in all but one animal. Therefore, the present study strongly suggests, that the outer hair cells are critically involved in the production of DPEs.     

Electrical stimulation of the cochlear nerve in deafness mice

The deafness mouse mutant provides a useful animal model for studying the central consequences of complete auditory deprivation during development. The object of this study was to record inferior colliculus-evoked potentials in mutant and control mice, using short electrical pulses to stimulate either the whole cochlea or the cochlear nerve directly. In both experiments, evoked potentials were readily recorded in the mutant and control mice, indicating that some central connections are functional, even though the auditory pathway has received no stimulus-related input throughout development. The results are relevant to the clinical problem of restoring auditory function in the profoundly deaf using peripheral electrical stimulation.     

Cochlear ablation in mice lacking SHP-1 results in an extended period of cell death of anteroventral cochlear nucleus neurons

Cochlear ablation results in the death of anteroventral cochlear nucleus (AVCN) neurons from birth to approximately postnatal day 14 (P14) in the murine brainstem. It is not known whether microglial activation contributes to AVCN neuronal death following deafferentation. In order to determine whether microglial activation helps to define the period of neuronal susceptibility within AVCN, we performed unilateral cochlear ablation on mice lacking the protein tyrosine phosphatase SHP-1 (me/me). These mice have been shown to have an exaggerated microglial response following ischemic injury. In the present study, the glial and neuronal response to deafferentation within AVCN was examined in wild-type and me/me mice at P5, P14, and P21. Lack of SHP-1 results in robust microglial but not astrocyte activation within the ablated P14 me/me AVCN. These mice also exhibit approximately 28% neuronal death at P14, a time when normal wild-type littermate controls show little cell death. Glial activation and neuronal loss at P5 and P21 were similar between the two phenotypes, suggesting a role of activated microglia in inducing neuronal death beyond P14 but not P21. These results indicate that activated microglia may participate in determining whether neurons in AVCN live or die following deafferentation.     

Tonotopic changes in 2-deoxyglucose activity in chick cochlear nucleus during hair cell loss and regeneration

Following cochlear ablation, auditory neurons in the central nervous system (CNS) undergo alterations in morphology and function, including neuronal cell death. The trigger for these CNS changes is the abrupt cessation of eighth nerve fiber activity. Gentamicin can cause ototoxic damage to cochlear hair cells responsible for high frequency hearing. In birds, these hair cells can regenerate. Therefore, gentamicin causes a partial, yet reversible insult to the ear. It is not known how this partial hair cell damage affects excitatory input to the cochlear nucleus. We examined chick cochlear nucleus activity during hair cell loss and regeneration by measuring 2-deoxyglucose (2DG) uptake. Normal animals showed a rostral to caudal gradient of 2DG activity, with higher activity in caudal regions. When hair cells are damaged (2, 5 days), 2DG uptake is decreased in cochlear nucleus. When hair cells regenerate (9, 16, 28 days), 2DG uptake returns to control levels. This decrease and subsequent return of activity only occurs in the rostral, high frequency region of the cochlear nucleus. No changes are seen in the caudal, low frequency region. These results suggest that changes in activity of cochlear nucleus occur at a similar time course to anatomical changes in the cochlea.     

Effects of cochlear ablation on noise induced hyperactivity in the hamster dorsal cochlear nucleus: implications for the origin of noise induced tinnitus

Chronic increases in multiunit spontaneous activity are induced in the dorsal cochlear nucleus (DCN) following exposures to intense sound. This hyperactivity has been implicated as a neurophysiological correlate of noise induced tinnitus. However, it is not known whether this hyperactivity originates centrally, or instead, reflects an increase in the level of spontaneous input from the auditory nerve. In the present study we addressed this issue by testing whether hyperactivity, induced in the DCN by previous exposure to intense sound, persists after ipsilateral cochlear input to the DCN has been removed. To induce hyperactivity, Syrian golden hamsters were exposed under anesthesia to an intense pure tone (122-127 dB SPL at 10 kHz) for 4 h. Additional hamsters, which were anesthetized for 4 h, but not tone exposed, served as controls. Electrophysiological recordings of spontaneous activity were performed on the surface of the left DCN in animals in which the ipsilateral cochlea was either intact or ablated. The degree of cochlear removal was determined by microdissection and histologic evaluation of the cochlea after completion of each recording session. Comparisons between the levels of activity recorded in animals with and without intact cochleas revealed that the induced hyperactivity in the DCN persisted after both partial and complete cochlear ablations. These results indicate that the maintenance of hyperactivity is not dependent on input from the ipsilateral cochlea, implying that hyperactivity originates centrally.     

Sodium pentobarbital abolishes bursting spontaneous activity of dorsal cochlear nucleus in rat brain slices

There is evidence that pentobarbital, a commonly used anesthetic, can affect neuronal activity, but its effects on particular neurons of the dorsal cochlear nucleus (DCN) are not well known. Bursting (complex spiking) spontaneous activity has been observed in the DCN in brain slice preparations and in recordings from unanesthetized decerebrate animals, but seldom in experiments with anesthetized animals. This study investigated the effects of pentobarbital on spontaneous activity in the DCN in brain slices. Most extracellularly recorded bursting neurons decreased firing rates and reversibly changed their firing to simple spiking with irregular intervals during pentobarbital. Some reversibly stopped firing after the change to an irregular pattern. Most neurons with regular spontaneous activity (simple spiking) showed decreased firing rates and more irregular intervals during pentobarbital. The results also suggest some involvement of gamma-aminobutyric acid type A receptors in the pentobarbital effects.     

Changes of 2-deoxyglucose uptake in the rat auditory pathway after bilateral ablation of the cochlea

It has been reported that the area of decreased glucose metabolism in the FDG-PET of prelingually deaf children correlates significantly with speech performance after cochlear implantation. In this study, we undertook to confirm changes of glucose metabolism in the cerebral cortex using an animal model with age-matching groups to completely exclude the influence of age differences between the deaf and normal-hearing groups. The cochlea was ablated bilaterally at a postnatal 10-14 days in the deaf groups; 3-4 deaf and normal rats were included at each time point at 1, 2, 4 and 8 weeks and 7 months after ablation. After injecting 2-deoxyglucose intraperitoneally, digitalized autoradiographic images were obtained, and analyzed by using two different methods; 3-dimensional voxel-wise statistical analysis and conventional 2-dimensional densitometry. The hypometabolic area analyzed using 3-dimensional analysis and the differences of optical density between normal and deaf as determined by densitometry were widest and most prominent between 4 and 8 weeks after ablation. Differences were not significant before 2 weeks or after 7 months after ablation. This result shows that the hypometabolic area becomes prominent after a critical period and it decreases as the duration of deafness increases. We believe that cross-modal plasticity may be the mechanism of changes in glucose metabolism and that this result reinforced the usefulness of evaluating hypometabolic area using FDG-PET in deaf children.     

Plasticity of spontaneous neural activity in the dorsal cochlear nucleus after intense sound exposure

Increases in multiunit spontaneous activity (hyperactivity) can be induced in the dorsal cochlear nucleus (DCN) by intense sound exposure. This hyperactivity has been observed in the hamster and rat following exposure to a 10 kHz tone at a level of 125-130 dB SPL for a period of 4 h. The present study demonstrates that the onset of this hyperactivity is not immediate, but develops in the DCN between 2 and 5 days after exposure. Mean rates of multiunit spontaneous activity increased sharply from below normal levels at day 2 to higher than normal levels at day 5. The mean magnitude of activity continued to increase more gradually over the next 6 months. During this period, changes in the distribution of hyperactivity across the tonotopic array were also noted. The hyperactivity was more broadly distributed across the DCN at the early post-exposure times (5 and 14 days) than at later post-exposure recovery times (30 and 180 days), and peak activity was found at increasingly more medial positions over this time frame. These changes over time indicate that the mechanisms leading to hyperactivity following intense sound exposure are more complex than previously realized.     

Modulation of spontaneous activity by acetylcholine receptors in the rat dorsal cochlear nucleus in vivo

In vitro studies have implicated muscarinic acetylcholine receptors (mAChRs) in the modulation of spontaneous activity (SA) of neurons in the rat dorsal cochlear nucleus (DCN) (Chen et al., 1994,1998). Early studies suggest that cholinergic pathways also modulate SA in vivo, but these effects have not been investigated pharmacologically. The purpose of the present study was to determine whether multiunit SA can be modulated in vivo by application of cholinergic agents to the surface of the DCN. Sprague Dawley rats were used in the current experiment. The influence of cholinergic activation on SA was tested by applying carbachol (5–500 μM) to the DCN surface while recording multiunit SA at a depth of 250 μm. Out of a total of 32 sites tested, all but 2 (94%) showed well-defined responses to carbachol, characterized by suppression, activation or a combination of both (two-component responses). The most common responses were pure suppression and suppression accompanied by transient activation. Both the proportion of sites showing suppressive responses and the magnitude of suppression averaged across sites increased with dose. Although the proportion of sites showing pure activation in response to carbachol decreased with dose, there was no clear trend in the magnitude of activation with dose. The suppressive responses to high doses of carbachol were blocked by pre-application of atropine. These results extend previous work by suggesting that muscarinic receptors play an important role in the modulation of SA in vivo.     

Cochlear implantation in adults with single-sided deafness: generic and disease-specific long-term quality of life

European Archives of Oto-Rhino-Laryngology - To determine the 2-year outcome of health-related quality of life (HRQoL) in adults who received a cochlear implant (CI) for single-sided deafness...     

The effects of cochlear implantation in Japanese single-sided deafness patients: five case reports

Conclusion Cochlear implantation (CI) for Japanese single-sided deafness patients resulted in improved speech perception, increased sound localization accuracy, and reduced tinnitus handicap. Objectives This study reports results for five adult SSD cases with CI, focusing on the benefits they obtained in terms of speech recognition, sound localization, and tinnitus handicap. Methods Five Japanese patients meeting the eligibility criteria were included in this study. All patients were implanted with a fully inserted MED-EL Concerto FLEX28® implant (MED-EL, Innsbruck, Austria). Speech perception outcomes in noise, as well as sound localization and tinnitus disturbance, were assessed pre-surgically and at 1, 3, 6, and 12 months after CI activation. Results The Japanese monosyllable test score in noise improved gradually after implantation. In some cases, speech perception ability appeared unstable, particularly in the first 1–6 months after implantation. The sound localization ability showed marked improvement in all cases, with the disturbance to daily life caused by tinnitus also decreasing in all cases from the early post-operative period.     

Expression of adhesion molecular proteins in the cochlear lateral wall of normal and PARP-1 mutant mice

Sound can damage peripheral cochlear function through a number of mechanisms, and emerging evidence suggests that inflammation may be one of them. Using immunohistochemistry and poly (ADP-ribose) polymerase-1 (PARP-1) mutant mice, we tested whether PARP-1 contributes to loud-sound induced cochlear lateral wall damage by triggering inflammatory effects, including upregulating intercellular adhesion molecule-1 (ICAM-1), P-selectin and platelet-endothelial cell-adhesion molecule-1 (PECAM-1). In control conditions, we found that there was no detectable poly-ADP-ribose (PAR) in the marginal cells and microvessels. ICAM-1 was expressed only at low levels in the vessels of the stria vascularis and the spiral ligament. P-selectin and PECAM-1 were barely detected and only in the vessels of the spiral ligament. Following loud-sound exposure, PAR was detected in numbers of marginal cells and some vessels of the spiral ligament. Also, an elevated expression of ICAM-1 was demonstrated in some vessels of the stria vascularis and spiral ligament. Increased expression of P-selectin and PECAM-1 were mainly located in the vessels of the spiral ligament, while increased populations of non-migrated and migrated leukocytes were observed in the area of the spiral ligament. However, neither increased expression of adhesion proteins nor increased population of leukocytes, were observed in the PARP-1 knockout mouse. We thus conclude that loud-sound stress activates the expression of adhesion molecular proteins in the lateral wall and that PARP-1 modulates inflammation-linked protein expression and leukocyte migration.     

Electrophysiological characteristics of inferior colliculus neurons in mutant mice with hereditary absence of cochlear outer hair cells

One strain of homozygous Kit^W-v mice (formerly known as W^v/W^v) lack 98% of the cochlear outer hair cells (OHCs) from birth. Inner hair cells (IHCs) and supporting cells develop normally. Thus, this strain is an attractive model to study the effect of complete OHC absence on central frequency representation. Frequency threshold curves were recorded along the tonotopic axis of inferior colliculus (IC) in mutant and control mice of the genetic background strain (C57BL/6J) and a different outbred strain (NMRI/wild mouse hybrids) known to be free of any cochlear pathology. The average threshold level of neurons in the mutants was 100 dB sound pressure level, 60 dB higher than in C57BL/6J and NMRI mice. Their tuning curves lacked the sharply tuned tip. In the C57BL/6J mice, although younger than four months, abnormal tuning curves were found for about 30% of the neurons, especially in the high frequency range. No abnormal tuning curves were found in the NMRI mice. The bandwidth of the tuning curves, measured at 10 dB above threshold, was on average 1.27 octaves in mutants, 0.62 octaves in C57BL/6J mice, and 0.34 octaves in NMRI mice. The range for the high cut-off frequency of the tuning curves at 10 dB above threshold was 6.4–61.1 kHz in the NMRI and 7–59.5 kHz in C57BL/6J. In the mutants, the range was limited to 11.1–41.7 kHz. The tonotopic gradient based on the cut-off frequency was less steep in the IC of the mutants than in both control groups.     

Cochlear implantation in adults with unilateral deafness: A review of the assessment/evaluation protocols

Objectives: Cochlear implantation is becoming widely used outside the tertiary research centers for treatment of unilateral deafness (UD). No consensus exists, however, on the most suitable assessment/evaluation protocols for this group of adult patients. This paper aims to review the assessment and evaluation protocols used by various research groups and to propose a protocol for the use in the clinical setting.

Methods: The PubMed, Embase, and Cochrane Library databases were searched with the keywords ‘cochlear’, ‘implant’, ‘single-sided’, ‘deafness’, ‘adults’, ‘unilateral’, and ‘deafness’. The words were either used individually, combined in pairs, or in groups of 5. All articles reporting on prospective studies, retrospective studies, or case studies were included.

Results: Sixteen published studies met the inclusion criteria. Measures of hearing performance, tinnitus, subjective quality of hearing, and quality of life varied greatly among studies.

Discussion: Adaptive speech in noise testing, localization, tinnitus measurement questionnaires, and self-rated hearing improvement are widely used among the research groups. These tools in conjunction assess and evaluate the main issues associated with UD.

Conclusion: The test battery most commonly used to assess and evaluate adult cochlea implant users with UD consists of (a) a subjective self-rating of hearing performance, (b) localization testing, and (c) the adaptive speech in noise testing conducted in at least the following three spatial configurations: speech and noise presented from the front (S0/N0), speech presented from the front and noise presented to the good hearing ear (S0/Nhe), and speech presented to the implanted ear and noise presented to the hearing ear (Sci/Nhe).     

Cochlear implants in special cases: deafness in the presence of disabilities and/or associated problems

The aim of the present study is to construct a reference model with the indication for the attitude, the requirements and the resources needed in order to be able to deal with deafness in the presence of disabilities or associated problems. The study group consisted of 13 adults and 18 children affected by profound deafness, with associated problems and disabilities, who were implanted with Clarion and Med-El devices. Selection criteria for candidacy to cochlear implantation and counselling, hospitalization, fitting and speech therapy/rehabilitation are described. Findings were assessed evaluating: (i) use of acoustic feedback, on the ground of Erber's model; (ii) self-sufficiency: assessed by a questionnaire; and (iii) social and family relationships: qualitative judgment based on direct observation, analysis of drawings and structured interviews with family, teachers and therapists. The whole group showed benefit from cochlear implantation, with particular satisfaction for post-lingual deaf-blind adults, as well as for subjects with associated psychopathologies and mental retardation. In conclusion, cochlear implants can improve life quality in profoundly deaf subjects with associated disabilities, increasing both listening and communication skills as well as self-sufficiency while family and social relationships tend to remain stable.     

Catecholamine content of cochlear and facial nerves. High-performance liquid chromatography analyses in normal and mutant mice

The catecholamine content in cochlear and facial nerves was determined using high-performance liquid chromatography coupled with electro-chemical detection. Minute amounts of norepinephrine were detected in both nerves in normal CBA/CBA mice and homozygotic jerker mouse mutants, whereas norepinephrine was found only in the facial nerve in the dancer heterozygotic mouse mutant. Dopamine and epinephrine were not detected in any of the mouse strains.