Trauma-specific insults to the cochlear nucleus in the rat.

The effect of acoustic overstimulation on the neuronal number of the cochlear nucleus (CN) was investigated by using unbiased stereological methods in rats. We found that, after 9 weeks of recovery, neurons in the anteroventral cochlear nucleus (AVCN) degenerated, whereas those in the posteroventral and dorsal cochlear nuclei (PVCN and DCN) were preserved. The noise trauma induced near complete loss of the outer hair cells throughout the cochlea, and the inner hair cells were preserved only in the more apical regions. This pattern of selective loss of AVCN neurons in this study was different from trauma induced by auditory deafferentation by mechanical compression of auditory neurons. In contrast to noise trauma, mechanical compression caused loss of neurons in the PVCN and DCN. After 5 weeks of recovery from mechanical compression, there was no loss of inner or outer hair cells. These findings indicate that auditory deprivation, induced by different experimental manipulations, can have strikingly different consequences for the central auditory system. We hypothesized that AVCN neuronal death was induced by excitotoxic mechanisms via AMPA-type glutamate receptors and that excitatory neuronal circuits developed after acoustic overstimulation protected the PVCN and DCN against neuronal death. The results of the present study demonstrate that hearing loss from different etiologies will cause different patterns of neuronal degeneration in the CN. These findings are important for enhancing the performance of cochlear implants and auditory brainstem implants, because diverse types of hearing loss can selectively affect neuronal degeneration of the CN.

Localization of septin proteins in the mouse cochlea.

Septins are a family of GTP binding proteins that are well conserved in eukaryotic species except plants. Septins contribute to the lateral compartmentalization of membranes, cortical rigidity, and the regulation of membrane trafficking by associating with membrane lipids, actin, and microtubules. The organ of Corti in the cochlea has pivotal roles in auditory perception and includes two kinds of highly polarized cells, hair and supporting cells, both of which are rich in actin and microtubules. To identify the roles of septins in the cochlea, we analyzed the localization of three septin proteins, septin 4 (SEPT4), septin 5 (SEPT5), and septin 7 (SEPT7) that are abundantly expressed in brain tissues, and also examined auditory functions of Sept4 and Sept5 null mice. SEPT4, SEPT5, and SEPT7 were expressed in inner and outer pillar cells and Deiters' cells but the distribution patterns of each protein in Deiters' cells were different. SEPT4 and SEPT7 were expressed in the phalangeal process where SEPT5 was not detected. In addition to these cells SEPT5 and SEPT7 were co-localized with presynaptic vesicles of efferent nerve terminals. Only SEPT7 was expressed in the cochlea at embryonic stages. Although expression patterns of septin proteins suggested their important roles in the function of the cochlea, both Sept4 and Sept5 null mice had similar auditory functions to their wild type littermates. Immunohistochemical analysis of Sept4 null mice showed that compensatory expression of SEPT5 in the phalangeal process of Deiters' cells may have caused functional compensation of hearing ability in Sept4 null mice.

Effect of amplitude modulation of background noise on auditory-evoked magnetic fields.

Although it is known that amplitude modulation of a background masker improves signal detection, its effects on supra-threshold sounds are still unclear. In this study, the effects of amplitude modulation of a background masker on supra-threshold sounds were evaluated using a whole-head magnetoencephalography system. We compared the auditory-evoked magnetic fields recorded with a 500-Hz tone-burst of supra-threshold level with either random speech-spectrum noise (Unmodulated noise) or amplitude-modulated noise (Modulated noise) in 10 young normal-hearing subjects. The sounds were presented binauraly. The strengths of the N100m in the two noise conditions were examined. The masking effect of Modulated noise on supra-threshold sound was stronger than that of Unmodulated noise, a finding opposite to that on peri-threshold sound. The growth rate of the N100m strengths in the Modulated noise condition was less than that in the Unmodulated noise condition in the left hemisphere, whereas they were not different in the right hemisphere, suggesting that the left hemisphere was more susceptible to the envelope fluctuation.

An animal experimental model of auditory neuropathy induced in rats by auditory nerve compression.

Several animal models of auditory neuropathy (AN) have been produced by employing pharmacological agents to damage auditory neurons or hair cells selectively. The specificity of pharmacological lesions is generally assessed by observation of visible structural damage but it is difficult to localize the delivery, which could lead to functional side effects in other anatomical structures. Although genetic analyses of human AN patients have provided important information on the pathophysiology of AN, specific genetic defects have not been fully correlated with functional deficits in the auditory nervous system. To address this problem, we compressed rat auditory nerves to assess neural degeneration for up to 35 weeks. The method produced a good model of auditory neuropathy, including profound deterioration of the auditory brainstem response and preservation of both cochlear microphonics and distortion product otoacoustic emissions. Histological examination revealed that in spite of profound degeneration of the auditory nerve, the hair cells remained intact. The model provides a complementary alternative to those based on pharmacological lesions and genetic analyses of AN patients and should allow analysis of the pathophysiology of auditory neuropathy with less risk of the results being confounded by unknown deficits in other cell types.

Clinical characteristics of delayed endolymphatic hydrops: long-term results of hearing and efficacy of hyperbaric oxygenation therapy.

CONCLUSION: Diuretics significantly improved hearing in patients with contralateral-type DEH, whereas they did not inpatients with ipsilateral-type DEH. OBJECTIVE: We report a review of 26 cases of DEH treated in recent 6 years. PATIENTS AND METHODS: The study group comprised 22 contralateral and 4 ipsilateral types of DEH. The efficacy of diuretics on the improvement in hearing was examined quantitatively. The efficacy of hyperbaric oxygenation therapy (HBO) on hearing was examined in six patients. RESULTS: The general properties of these cases were similar to those reported previously, except for the high proportion of patients with contralateral-type DEH. Diuretics significantly improved the hearing of patients with contralateral-type DEH. In contrast, no significant improvement by diuretics was noted in ipsilateral-type DEH.

Effects of continuous masking noise on tone-evoked magnetic fields in humans.

Two different types of steep loudness growth have been reported in detail in psychoacoustical studies but have rarely been evaluated by objective methods in humans. One occurs in inner-ear hearing-impaired patients and is known as loudness recruitment. Another similar phenomenon is observed in healthy subjects with concurrent presence of background noise. Concerning the first type, our previous study using magnetoencephalography (MEG) showed that enhancement of the dipole moment of N100m with increase in stimulus intensity was greater in patients than in normal individuals. However, it is unclear whether the enhancement of activity in auditory cortex will also be detected with background noise in healthy subjects. To elucidate the effects of continuous background noise on tone-evoked cortical activity, we measured auditory-evoked magnetic fields (AEFs) from 7 normal-hearing subjects in two different conditions, with and without 55 dB SPL continuous masking white noise (noise/quiet conditions). The stimuli were 200 ms 1-kHz tones delivered monaurally and randomly at 4 different intensities (40-70 dB SPL) with constant 1-s interstimulus intervals. The N100m increased in amplitude and decreased in latency as a function of stimulus intensity in both noise and quiet conditions. The dipole moment of N100m was significantly smaller in the noise than in the quiet condition, showing that continuous background noise suppresses the strength of tone-evoked cortical responses. The mechanisms underlying these two psychoacoustically similar phenomena of rapid loudness growth thus differ.

Right hemispheric predominance in the segregation of mistuned partials.

To elucidate the central mechanisms of sound segregation, we compared responses to a harmonic sound and a mistuned sound using a whole-head magnetoencephalography system. The harmonic sound was composed of a 200-Hz tone and its 2nd to 12th harmonics. The mistuned sound had, instead of the 600-Hz harmonic, a 696-Hz tone. In the right hemisphere, the amplitude of N100m responses evoked by the mistuned sound was significantly larger and the peak latency significantly longer than that evoked by the harmonic sound, suggesting that the right hemisphere plays a more important role than the left in detecting mistuned partials.

Steroid injection to vocal nodules using fiberoptic laryngeal surgery under topical anesthesia.

Since 1990, we have performed steroid injection into the vocal fold by fiberoptic laryngeal surgery (FLS) under local anesthesia. In this study, the usefulness of this method was evaluated in 28 patients with vocal nodules. Under monitoring using a fiberoptic laryngoscope, a curved injection needle was inserted via the oral cavity and steroid was injected. Endoscopic findings showed that the vocal nodule had disappeared in 17 patients of the 27 patients and decreased in 10 after injection. The maximum phonation time was 10.9 s before operation and 13.9 s after operation, showing a significant increase (P<0.05), and the mean flow rate also showed a significant improvement (P<0.05). The patients self-rating concerning hoarseness demonstrated great improvement after injection. This technique can be performed under local anesthesia in combination with voice therapy on an outpatient basis, and it is considered to be useful for treating vocal nodules.

Inner ear hearing loss modulates ipsilateral temporal lobe activation by monaural speech stimuli.

We examined cortical activation by speech in patients with moderate inner ear hearing loss using PET to investigate the response of the language network to insufficient speech input. We made two word lists, well-perceived words and poorly-perceived words, and measured rCBF during monaural presentation of these words. Well-perceived words activated bilateral temporal lobes, bilateral inferior frontal gyri (IFG) and left angular gyrus (AG) regardless of the ear stimulated, Poorly-perceived words activated contralateral temporal lobe and bilateral IFG, while little or no activation was observed in the ipsilateral temporal lobe and left AG. Insufficient activation of the temporal lobe ipsilateral to the ear stimulated might correlated with less accurate word comprehension in patients with inner ear hearing loss.

A novel technique for inducing local inner ear damage.

With significant development of mouse genomics and the availability of transgenic and knockout mice, the mouse will be the preferred animal model for inner ear research. However, few studies have used mice as experimental animals for examination of hair cell degeneration, because of their relative resistance to ototoxic agents and difficulties in surgical treatment. This study presents a model for induction of apoptotic cell death in sensory epithelia of the mouse inner ear using injection of neomycin into the posterior semicircular canal. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay revealed that local application of neomycin produced sufficient induction of apoptotic cell death in both auditory and vestibular epithelia over a definite time course. Supplementation of the general caspase-inhibitor significantly reduced induction of TUNEL-positive cells, indicating caspase-dependency of apoptotic cell death observed in the present model. In addition, the approach to the posterior semicircular canal was an easy technique, and sham-operation induced no significant induction of TUNEL-positive cells. This model, hence, enables the use of various genetic tools in studies for mechanisms of hair cell apoptosis.

Fiberoptic laryngeal surgery for vocal process granuloma.

We developed a technique of fiberoptic laryngeal surgery for the treatment of vocal process granulomas. In this system, the granuloma can be removed relatively easily and repeatedly under topical anesthesia on an outpatient basis. We treated 27 patients for a total of 4 intubation granulomas and 23 contact granulomas. Ten of the 23 contact granulomas recurred after the initial surgery, but the intubation granulomas did not recur. Most of the recurrent lesions were resolved by fewer than 3 procedures, and all patients were finally cured. Although conservative therapies such as voice therapy and proton pump inhibitors have recently prevailed, surgical removal remains useful in treating vocal process granulomas. Fiberoptic laryngeal surgery facilitates repeated surgical procedures.