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Auditory resting-state functional connectivity in tinnitus and modulation with transcranial direct current stimulation

Minami Shujiro B., Oishi Naoki, Watabe Takahisa, Uno Kimiichi, Kaga Kimitaka, Ogawa Kaoru

Acta Oto-Laryngologica 135 （ 12 ） 1286 - 1292 2015.12

ISSN 0001-6489

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Conclusions: The functional connectivity (FC) between the right and left auditory cortex is weak in tinnitus patients. Transcranial direct current stimulation (tDCS) over the auditory cortex has potential as a tool to modulate auditory-based FC. Objective: This study investigated the effects of applying tDCS in tinnitus patients, and searched for modulation of brain networks in resting-state functional magnetic resonance imaging (rs-fMRI) through an analysis of FC with the stimulated brain region. Subjects and methods: Nine male patients with chronic tinnitus and 10 male volunteers with normal hearing were enrolled. The subjects were evaluated with rs-fMRI immediately before and after tDCS. The tinnitus patients filled out the self-evaluation questionnaires designed to measure tinnitus conditions before tDCS treatment and 1 week afterwards. Results: The FC between the right and left auditory cortex was significantly weaker in tinnitus patients than in controls. After tDCS treatment, in the tinnitus group, the primary auditory cortex showed a reduction in the amount of statistically significant connectivity with the somatosensory area and motor area, but maintained strong significant connectivity (p < 0.005) with the auditory area and insular cortex. In contrast, in the control group, there remained strong significant connectivity between the primary auditory cortex and the somatosensory area, motor area, insular cortex, and auditory area.
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Metformin protects against gentamicin-induced hair cell death in vitro but not ototoxicity in vivo

Oishi Naoki, Kendall Ann, Schacht Jochen

Neuroscience Letters 583 65 - 69 2014.11

ISSN 0304-3940

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Metformin (N,N-dimethylbiguanidine) is a widely employed oral hypoglycemic agent for the management of type 2 diabetes mellitus. Its antioxidant properties and safe clinical use raise the possibility of preventing gentamicin-induced hearing loss in patients. Therefore, we screened the usefulness of metformin against gentamicin toxicity in murine cochlear explants and in the guinea pig in vivo. We confirmed in organ culture that metformin blocks the gentamicin-induced translocation of endonuclease G into the nucleus of outer hair cells and attenuates hair cell loss. In vivo, gentamicin treatment with 80, 100, or 130 mg/kg body weight for 14 days induced significant threshold shifts as determined by auditory brain stem responses. Metformin (30, 75, or 100 mg/kg for 14 days) was well tolerated without any indication of auditory side effects. However, co-administration of metformin with gentamicin in various permutations did not prevent loss of auditory function. On the contrary, combined treatment at higher dosages aggravated the gentamicin-induced threshold shifts and caused additional adverse reactions including body weight loss and premature deaths in some animals. These results caution against the use of metformin co-treatment with aminoglycosides and confirm the need for in vivo studies in order to evaluate potentially protective agents selected by in vitro screens.
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A case of intractable suspected perilymph fistula with severe depression

Goto Fumiyuki, Oishi Naoki, Tsutsumi Tomoko, Ogawa Kaoru

Psychiatry Investigation 11 （ 4 ） 499 - 501 2014

ISSN 1738-3684

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A 68-year-old woman presented dizziness whenever she put her finger into the right ear and also complained of water-streaming tinnitus, which indicated she would have been suffering from perilymph fistula. An exploratory tympanotomy was conducted. Leakage of perilymph from the round window was suspected, although the cochlin-tomoprotein (CTP) results were negative. After the procedure, the patient’s finger-induced dizziness, tinnitus, and vertigo spells disappeared completely. However, her dizzy symptom did not improve. The patient also complained of general fatigue, weight loss, and insomnia, which led us to suspect comorbid depression. Antidepressants and vestibular rehabilitation treatment resulted in a significant improvement in her dizziness. Although it is not apparent whether the patient had a perilymph fistula, this case demonstrates the importance of evaluating not only physical symptoms but also psychological comorbidity, especially when the physical symptoms are intractable despite treatment.
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Long-term effects of tinnitus retraining therapy involving monaural noise generators

Inagaki Yozo, Oishi Naoki, Kanzaki Sho, Wakabayashi Satoko, Fujioka Masato, Watabe Takahisa, Watanabe Reiko, Wasano Koichiro, Yamada Hiroyuki, Kojima Takashi, Shinden Seiichi, Ogawa Kaoru

Journal of Otolaryngology of Japan 117 （ 2 ） 116 - 121 2014

ISSN 0030-6622

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We have previously reported on the effects of tinnitus retraining therapy (TRT) involving monaural noise generators (NGs) up to 24 months after the start of treatment (Eur Arch Otorhinolaryngol. 2013 Feb; 270(2): 443-8.) but very few reports exist about the long-term effects of TRT for periods of over 2 years. The aim of this study was to report the effects of TRT involving monaural NGs more than 24 months after the start of treatment. Thirty-three patients with chronic tinnitus were included in this study. All received directive counseling and monaural NGs without any other combination treatment. Effects were evaluated with the Tinnitus Handicap Inventory (THI) at their final visits to our clinic (average 31 months after the start of treatment). The average THI scores significantly improved from 55.3 ± 19.7 at baseline to 33.5 ±23.3 at their final visits. Seventeen patients (52%) improved by more than 20 points from the baseline. Eleven patients who were treated with TRT for more than 3 years were individually observed in a detailed manner. Some of them experienced aggravation of their symptoms after 2 years' successful treatments. This study suggests that, although TRT seems effective more than 2 years after the start of treatment, the clinical course of each patient can vary and we need to follow them periodically depending on their situations and symptoms.
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Tumor necrosis factor-alpha-mutant mice exhibit high frequency hearing loss

Oishi Naoki, Chen Jun, Zheng Hong Wei, Hill Kayla, Schacht Jochen, Sha Su Hua

JARO - Journal of the Association for Research in Otolaryngology 14 （ 6 ） 801 - 811 2013.12

ISSN 1525-3961

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Exogenous tumor necrosis factor-alpha (TNF-α) plays a role in auditory hair cell death by altering the expression of apoptosis-related genes in response to noxious stimuli. Little is known, however, about the function of TNF-α in normal hair cell physiology. We, therefore, investigated the cochlear morphology and auditory function of TNF-α-deficient mice. Auditory evoked brainstem response showed significantly higher thresholds, especially at higher frequencies, in 1-month-old TNF-α^-/- mice as compared to TNF-α^+/- and wild type (WT); hearing loss did not progress further from 1 to 4 months of age. There was no difference in the gross morphology of the organ of Corti, lateral wall, and spiral ganglion cells in TNF-α^-/- mice compared to WT mice at 4 months of age, nor were there differences in the anatomy of the auditory ossicles. Outer hair cells were completely intact in surface preparations of the organ of Corti of TNF-α^-/- mice, and synaptic ribbon counts of TNF-α^-/- and WT mice at 4 months of age were similar. Reduced amplitudes of distortion product otoacoustic emissions, however, indicated dysfunction of outer hair cells in TNF-α^-/- mice. Scanning electron microscopy revealed that stereocilia were sporadically absent in the basal turn and distorted in the middle turn. In summary, our results demonstrate that TNF-α-mutant mice exhibit early hearing loss, especially at higher frequencies, and that loss or malformation of the stereocilia of outer hair cells appears to be a contributing factor. © 2013 Association for Research in Otolaryngology.
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Papers, etc., Registered in KOARA 【 Display / hide 】

Elucidation of developmental mechanisms of the bilateral vestibular schwannoma in neurofibromatosis type 2 using patient-derived iPS cells

Ōishi, Naoki

科学研究費補助金研究成果報告書 2018
Regulation of hair cell microstructure and auditory function by Hippo pathway

Ōishi, Naoki

科学研究費補助金研究成果報告書 2018
Endoplasmic stress response in cochlear culture

Ōishi, Naoki

科学研究費補助金研究成果報告書 2018
In vitro "virtual biopsy" of cochlear cells by using Wolfram syndrome patients derived hiPSCs

Ōishi, Naoki

科学研究費補助金研究成果報告書 2017
Tinnitus in aging model mice

Oishi, Naoki

科学研究費補助金研究成果報告書 2016

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

聴神経腫瘍の聴力予後改善に向けた新規聴覚誘発電位測定法およびアルゴリズムの開発

2021.04

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2024.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator
蝸牛培養細胞における小胞体ストレス応答

2016.04

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2019.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator