CONTRALATERAL SUPPRESSION OF DISTORTION PRODUCT OTOACOUSTIC EMISSION IN CHILDREN WITH AUDITORY PROCESSING DISORDERS

Previous research has demonstrated that the amplitude of evoked emissions decreases in human sub-jects when the contralateral ear is stimulated by noise. The medial olivocochlear bundle (MOCB) is be-lieved to control this phenomenon. Recent research has examined this effect in individuals with auditory pro-cessing disorders (APD), specifically with difficulty understanding speech in noise. Results showed tran-sient evoked otoacoustic emissions (TEOAEs) were not affected by contralateral stimulation in these sub-jects. Much clinical research has measured the function of the MOCB through TEOAEs.This study will use an alternative technique, distortion product otoacoustic emissions (DPOAEs), to examine this phenomenon and evaluate the function of the MOCB. DPOAEs of individuals in a control group with normal hearing and no significant auditory processing difficulties were compared to the DPOAEs of children with signifi-cant auditory processing difficulties.Results showed that the suppression effect was observed in the control group at 2 kHz with 3 kHz of narrowband noise. For the auditory processing disorders group, no significant suppression was observed.Overall, DPOAEs showed suppression with contralateral noise, while the APD group levels increased overall.These results provide further evidence that the MOCB may have reduced function in children with APD.

Modulation of copper transporters in protection against cisplatin-induced cochlear hair cell damage

Cisplatin belongs to platinum-based drugs and is widely used in cancer chemotherapy.Ototoxicity is one of the major dose limiting side-effects of cisplatin.For toxicity to occur cisplatin must first be transported from the bloodstream into cochlear cells.Three copper transporters are considered pathways for regulating the uptake and translocation of cisplatin into cells:Ctr1,ATP7A and ATP7B.Our recent study with cochlear organotypic cultures shows that cochlear hair cells can be destroyed by cisplatin at low concentrations from 10μm to 100μn.However,high doses of cisplatin cannot damage hair cells,maybe due to intrinsic feedback reactions that increase export of platinum by ATP7B when the platinum concentration is high in extracellular space.Cimitidine is a specific copper transporter inhibitor that can block the entrance of copper and platinum,and may prevent cisplatin-induced cochlear hair cell injury.To evaluate this hypothesis,we treated cochlear organotypic cultures with cisplatin (10 μm or 50 μm) alone,or cisplatin combined with cimitidine at concentrations ranging from 10-2000 μm for 48 hours.cisplatin at 10 μm damaged about 20% hair cells.In contrast,when cimitidine (10 μm,100 μm and 2000 μm) was added to the culture,near 100% cochlear hair cell survived.At higher concentration (50 μm),cisplatin destroyed about 80% of cochlear hair cells.However,100 μmcimitidine rescued about 50% hair cells from cisplatin damage,and 2000μm cimitidine protected about 80% hair cells.The data of western blot showed that CTR1 and ATP7B expressions were increased in cisplatin treated cochlear tissue,but cimitidine significantly reduced CTR1 and ATP7B.In addition,ATP7A expression was depressed a little after cisplatin treatment.Considering that Ctr1 is involved in copper and platinum influx,but the ATP7A and ATP7B are copper export transporters,the results suggest that cimitidine can effectively block the entrance by copper transporters and stop the influx of cisplatin.

Standardization of experimental animals temporal bone sections

Preparation of the temporal bone for light microscopy is an important step in histological studies of the inner ear. Due to the complexity of structures of the inner ear, it is difficult to measure or compare structures of interest without a commonly accepted standardized measure of temporal bone sections. Therefore, standardization of temporal bone sections is very important for histological assessment of sensory hair cells and peripheral ganglion neurons in the cochlear and vestibular systems. The standardized temporal bone sectioning is oriented to a plane parallel to the outer and internal auditory canals. Sections are collected from the epitympanum to the hypotympanum to reveal layers in the order of the crista ampullaris of the superior and lateral semicircular canals, macula utriculi and macula sacculi, superior vestibular ganglion neurons, macula of saccule and inferior vestibular ganglion neurons, cochlear modiolus, endolymphatic duct and endolymphatic sac, and finally the crista ampullaris of the posterior semicircular canal. Moreover, technical details of preparing for temporal bone sectioning including fixation, decalcification, whole temporal bone staining, embedding penetration, and embedding orientation are also discussed.

THE EFFECTS OF SALICYLATE ON AUDITORY EVOKED POTENTIAL AMPLITWDE FROM THE AUDITORY CORTEX AND AUDITORY BRAINSTEM

Tinnitus has often been studied using salicylate in animal models as they are capable of inducing tempo-rary hearing loss and tinnitus. Studies have recently observed enhancement of auditory evoked responses of the auditory cortex (AC) post salicylate treatment which is also shown to be related to tinnitus like behavior in rats. The aim of this study was to observe if enhancements of the AC post salicylate treatment are also present at structures in the brainstem. Four male Sprague Dawley rats with AC implanted electrodes were tested for both AC and auditory brainstem response (ABR) recordings pre and post 250 mg/kg intraperitone-al injections of salicylate. The responses were recorded as the peak to trough amplitudes of P1-N1 (AC), ABR wave V, and ABR waveⅡ. AC responses resulted in statistically significant enhancement of ampli-tude at 2 hours post salicylate with 90 dB stimuli tone bursts of 4, 8, 12, and 20 kHz. Wave V of ABR re-sponses at 90 dB resulted in a statistically significant reduction of amplitude 2 hours post salicylate and a mean decrease of amplitude of 31%for 16 kHz. WaveⅡamplitudes at 2 hours post treatment were signifi-cantly reduced for 4, 12, and 20 kHz stimuli at 90 dB SPL. Our results suggest that the enhancement chang-es of the AC related to salicylate induced tinnitus are generated superior to the level of the inferior colliculus and may originate in the AC.

FIRING PROPERTY OF INFERIOR COLLICULUS NEURONS AFFECTED BY FMR1 GENE MUTATION

Fragile X syndrome is the most common form of inherited mental retardation affecting up to 1 in 4000 individuals. The syn- drome is induced by a mutation in the FMR1 gene, causing a deficiency in its gene by-product FMRP. Impairment in the nor- mal functioning of FMRP leads to learning and memory deficits and heightened sensitivity to sensory stimuli, including sound （hyperacusis）. The molecular basis of fragile X syndrome is thoroughly understood; however, the neural mechanisms underly- ing hyperacusis have not yet been determined. As the inferior colliculus （IC） is the principal midbrain nucleus of the auditory pathway, the current study addresses the questions underlying the neural mechanism of hyperacusis within the IC of fragile X mice. Acute experiments were performed in which electrophysiological recordings of the IC in FMR1-KO and WT mice were measured. Results showed that Q-values for WT were significantly larger than that of FMR-1 KO mice, indicating that WT mice exhibit sharper tuning curves than FMR1-KO mice. We also found the ratio of the monotonic neurons in the KO mice was much higher than the WT mice. These results suggest that lack of FMRP in the auditory system affects the developmental maturation and function of structures within the auditory pathway, and in this case specifically the IC. The dysfunction ob- served within the auditory neural pathway and in particular the IC may be related to the increased susceptibility to sound as seen in individuals with fragile X syndrome. Our study may help on understanding the mechanisms of the fragile X syndrome and hyperacusis.

实验动物标准颞骨切片规范

颞骨切片技术是观察和评估实验性内耳病理学改变的重要手段。由于内耳复杂的迷宫式立体结构,从不同方向和角度获取的颞骨切片很难进行相互间的组织病理学比较。因此,统一颞骨标准切片技术规范,对于评判内耳听觉感受器和前庭各个平衡感受器以及耳蜗和前庭周边神经元的病变部位和病变程度十分重要,因为只有统一了规范的颞骨样品制备和切片角度,才有可能对实验性内耳病变做出正确的比较和评判。颞骨切片的标准方向是将切片平面平行于外耳道和内听道的水平面,从上鼓室向下鼓室方向依次收集到的需要进行重点评估的切片层次分别为上半规管壶腹嵴和外半规管壶腹嵴、椭圆囊斑和球囊斑及前庭上神经元、球囊斑和前庭下神经元、耳蜗中轴、内淋巴管及内淋巴囊、以及后半规管壶腹嵴。本文还根据作者的实践经验讨论了颞骨切片样品制备过程中有关样品固定、脱钙、颞骨整体染色、渗透和定向包埋等技术细节,期望能对从事内耳病理学研究的同道有所帮助。

Attitudes Toward People Who Stutter in the Chinese Context: An Exploratory Study on the Impact of Knowledge Sources

The public’s attitudes can affect the experience of stuttering of people who stutter.This study investigated the attitudes held by the public about people who stutter in China.A web-based written survey with closed and open-ended questions was implemented to develop a rich understanding.One hundred and two respondents in 26 provinces and 3 municipalities provided comments on people who stutter in their life aspects such as personality,speech,social life,work,life participation,education,dating and marriage,capability,and communication skills.The predominantly negative attitudes towards the overall domains were identified.Attitudes to people who stutter varied according to the different sources of knowledge.Familiarity with people who stutter might reduce stereotypes.However,knowledge from the media might aggravate stereotypes.Implications and future research orientation were also discussed.

Analysis of Smooth Cepstral Peak Prominence in Hypokinetic Dysarthria Associated With Parkinson’s Disease

Smoothed cepstral peak prominence(CPPs)is a measurement of the distance from the prominent cepstral peak to the linear regression line directly beneath it.Variations of CPPs data acquisition and analysis lead to the complexity of the clinical cut-off values,and there are no agreeable values for a specific voice disorder,such as hypokinetic dysarthria associated with Parkinson’s disease(PD).This study examined the CPPs in people with hypokinetic dysarthria associated with PD compared with healthy participants.Results demonstrated significant differences in speech tasks of sustained vowel and connected speech,with CPPs of connected speech more sensitive to dysphonia and gender difference in PD participants.Males in PD participants presented higher CPPs for sustained vowels and lower CPPs for connected speech than females.It is implied that a consistent clinical application protocol is necessary,and multiple acoustic measures are needed to ensure the accuracy of clinical decisions.

Acoustic trauma-induced auditory cortex enhancement and tinnitus

There is growing evidence suggests that noise-induced cochlear damage may lead to hyperexcitability in the central auditory system(CAS)which may give rise to tinnitus.However,the correlation between the onset of the neurophysiological changes in the CAS and the onset of tinnitus has not been well studied.To investigate this relationship,chronic electrodes were implanted into the auditory cortex(AC) and sound evoked activities were measured from awake rats before and after noise exposure.The auditory brainstem response(ABR) was used to assess the degree of noise-induced hearing loss.Tinnitus was evaluated by measuring gap-induced prepulse inhibition(gap-PPI).Rats were exposed monaurally to a high-intensity narrowband noise centered at 12 kHz at a level of 120 dB SPL for 1 h.After the noise exposure,all the rats developed either permanent(>2 weeks) or temporary(<3 days) hearing loss in the exposed ear(s).The AC amplitudes increased significantly 4 h after the noise exposure.Most of the exposed rats also showed decreased gap-PPI.The post-exposure AC enhancement showed a positive correlation with the amount of hearing loss.The onset of tinnitus-like behavior was happened after the onset of AC enhancement.

Acoustic startle reflex and pre-pulse inhibition in tinnitus patients

Gap induced pie-pulse inhibition(Gap-PPI) of acoustic startle reflex has been used as a measurement of tinnitus in animal models.However,whether this test is sensitive to detect tinnitus in humans is still unclear.Based on the testing procedure used in animal studies,a human subject testing method was formulated and conducted to investigate if a similar result could be found in tinnitus patients.Audiologic and tinnitus assessments and acoustic startle reflex measurements were performed on seven tinnitus subjects and nine age matched subjects without tinnitus.There was no significant difference found between the control and tinnitus group on the Gap-PPl across the frequencies evaluated.The amplitude of the startle response in the tinnitus group with normal hearing thresholds was significantly higher than the control group and those with tinnitus and hearing loss.This preliminary result suggests that hyperexcitability in the central auditory system may be involved in tinnitus.There was no correlation between hearing thresholds and the increased amplitude of startle response.

ACOUSTIC STARTLE RESPONSE AFFECTED BY AGING AND CHOLINERGIC NEUROTRANSMITTERS

The acoustic startle response has been used to evaluate tinnitus and hyperacusis in animal models. Gap induced prepulse in- hibition of the acoustic startle reflex （gap-PPI） is affected by tinnitus and loudness changes. Since tinnitus and reduced sound tolerance are commonly seen in elderly, we measured gap-PPI in Fischer 344 rats, an aging related hearing loss model, at dif- ferent agcs： 3-5 months, 9-12 months, and 15-17 months. The startle response was induced by three different intensity of sound： 105, 95 and 85 dB SPL. Gap-PPI was induced by different duration of silent gaps from 1 to 100 ms. When thc startle was induced by 105 dB SPL sound intensity, the gap-PPI induced by 50 ms silent gap was significantly lower than those in- duced by 25 or 100 ms duration, showing a ＂notch＂ in the gap-PPI function. The ＂notch＂ disappeared with the reduction of startle sound, suggesting the ＂notch＂ may be related with hyper-sensitivity to loud sound. As the intensity of the stimulus de- creased, the appearance of the hyperacusis-like effect decreased more quickly for the youngest group of rats. We also tested scopolamine, a muscarinic acetylcholine receptor antagonist, and mecamylamine, a nicotinic acetylcholine receptor antago- nist, on the effect of gap-PPI. When scopolamine was administered, the results indicated no addition effect on the hyperacu- sis-like phenomenon in the two older groups. Mecamylamine, the nicotinic antagonist also showed effects on the appearance of hyperacusis on rats in different ages. The information derived from the study will be fundamental for the further research in determining the cause and treatment for hyperacusis.

Tinnitus and hyperacusis in children: clinic reports and basic research

Objective Tinnitus and hyperacusis are subjective symptoms which can be reponeu tJy p^t, lJ ： age. Although tinnitus and hyperacusis can have a negative effect on child development, these symptoms are commonly overlooked by their parents and clinicians. In this paper, we review clinical reports on tinnitus and hyperacusis in children and basic scientific studies on these disorders in order to provide updates of these disorders in the pediatric population. Recent studies have found that tinnitus and hyperacusis are not uncommon in children, especially in those with conductive and sensorineural hearing loss. The parents and clinicians should pay attention when children show abnormal behaviors and especially when they develop hearing loss. Since there is no objective measurement for tinnitus and hyperacusis, the diagnosis in children can be challenging. Tinnitus and hyperacusis are also common in Williams syndrome and autism but the mechanisms are still not clear. High doses of salicylate and noise exposure can in- duce tinnitus. Animal studies have determined lack of inhibition in the auditory cortex and the inferior colliculus may be critical for tinnitus and hyperacusis generation. The non-classic auditory system may also be involved in the aware- ness and tolerance of tinnitus and hyperacusis.

A new approach to endocochlear potential and potassium ion concentration measures in mini pig models

Mini pig models are large mammals and their ears are more similar with human beings in structure and development than other animals.However,the study on porcine ears is still in the initial stage and there is no description of an ideal operation approach to endocochlear potential and potassium ion concentration measurements.In this article,we describe a pre-auricular surgical approach to access the middle and inner ear for endocochlear potential and potassium ion concentration measures in mini pig models.Ten one-week old normal mini pigs were used in the study.The bulla of the temporal bone was accessed via a pre-auricular approach for endocochlear potential and potassium ion concentration measurements.The condition of the animals during the first post—experiment 24 h was observed.One animal died during surgery.The preauricular approach improved protection and preservation of relevant nervous and vascular elements including the facial nerve and carotid artery.So,the pre-auricular approach can be used for endocochlear potential and potassium ion concentration measurements with improved nerve and artery preservation mini pigs.

灰鼠下丘近场记录未观察到掩蔽级差(Masking Level Difference)现象

目的 以往的实验中采用近场电极记录方法发现了听皮层电位的掩蔽级差(Masking level difference,MLD)样改变,本实验采用同样技术观察下丘的MLD是否存在。方法6只健康成年灰鼠,手术植入右侧下丘电极,术后恢复期7-10天,然后在无麻醉状态下进行下丘电位的测试。短纯音条件的测试(500 Hz短纯音)共设:双耳同相纯青(b0),双耳反相纯音(bπ),左耳纯音(le)和右耳纯音(re)四个条件,用以观察纯音本身参数对实验的影响。MLD条件的测试(500 Hz短纯音+白噪声)共设:双耳同相噪声反相纯音(n0sπ),双耳同相噪声同相纯音(n0s0),双耳同相噪声左耳纯音(n0sl),左耳噪声左耳纯音(nlsl),双耳同相噪声右耳纯音(n0sr)和右耳噪声右耳纯音(nrsr)六个条件。结果 纯音条件组的右侧声刺激(re)得到较弱的诱发电位。MLD条件组中下丘电位的噪声掩蔽阈,潜伏期和振幅的分析未发现各组数据间有明显差异。结论 采用近电场电极记录方法不能发现下丘的MLD样活动,但能发现皮层的MLD样活动。研究结果支持MLD完成于脑干以上水平的观点。

Neurotransmitter Modulation Relates with Tinnitus Signal Generation and Management

Tinnitus is a subjective perception of phantom sound that currently cannot be objectively measured. However, there is growing evidence suggesting that the biological source of tinnitus may exist in one or more than one place in the auditory pathway. Recent studies have found that neurotransmitters or modulators, such as glutamate, γ-aminobutyric acid(GABA), serotonin, dynorphin, dopamine, neurosteroid, acetylcholine(ACh) and substance P, are involved in tinnitus generation. Animal and human studies have shown that some of these neurotransmitters and the agonists or antagonists of their receptors either affect tinnitus behaviors or demonstrate some degree of treatment effects on tinnitus. However, due to the unclear biological mechanisms of tinnitus and side effects of these drugs, the value of clinical usage of such drugs in treating tinnitus is yet to be established. Revealing the relationship between tinnitus and neurotransmitter receptor functions will help identify more effective drugs for tinnitus treatment. This article reviews the literature of neurophysiological studies on tinnitus in both animal and human subject studies at various levels of the auditory pathway.

Otoacoustic emissions recorded in people with chronic migraine

Migraine,a moderate to severe chronic headache occurring on one or both sides,is a common disease affects young people.Although hearing loss in subjects with migraine is not rare,the correlation of migraine with hearing loss is not clear.In this study,we examined hearing loss in young migraine subjects to determine if migraine may be a factor in causing cochlear dysfunction.Seven college students with migraine and three age matched subjects without history of migraine were assessed using extended high frequency audiometry and distortion product otoacoustic emissions(DPOAEs).There was no significant difference in regular audiomeiry threshold between the migraine group and the control group.However,high frequency audiometry(9-16 kHz) showed thresholds at 25 dB nHL or higher in six out of twenty ears in the migraine group.The amplitude of DPOAEs were reduced for more than 10 dB in the migraine group in comparison with the control group.These data suggest that migraine may affect cochlear dysfunction evidenced by the reduced amplitude of DPOAE and high frequency pure-tone audiometry.

卡铂损伤南美栗鼠耳蜗内毛细胞及对听觉复合动作电位的影响

目的通过卡铂耳蜗损伤模型,观察成年南美栗鼠耳蜗听神经复合动作电位(compound action potential,CAP)及其基底膜内、外毛细胞密度,探讨内毛细胞损害程度与CAP振幅、阈值改变的关系。方法18只成年南美栗鼠经耳科学检查后按随机数字表法分为3组(每组6只):A组为对照组,B组和C组分别接受1次和2次卡铂注射(76 mg/kg,腹腔注射,2次注射间隔1周)。B组和C组动物在卡铂注射后30 d、A组在相应时间行终点功能测试。经下鼓室径路将记录电极安放到麻醉后南美栗鼠的圆窗龛,记录短声(click)及0.5、1、2、4、8、16 kHz短纯音刺激下的CAP。测试结束后处死动物。耳蜗基底膜铺片经琥珀酸脱氢酶组织化学染色标记毛细胞,在光学显微镜下对全耳蜗基底膜铺片连续高清拍摄,统计毛细胞数量及基底膜长度,计算10%基底膜长度内耳蜗内、外毛细胞的数量作为毛细胞密度。采用GraphPad 6软件进行统计学处理。结果A组成年南美栗鼠click及0.5、1、2、4、8、16 kHz短纯音声刺激CAP阈值分别为(7.1±2.6)、(25.4±5.0)、(24.6±5.4)、(10.4±5.0)、(0.4±1.4)、(4.2±6.3)和(17.1±14.1)dB SPL(±s,n=12)。A组单个耳蜗毛细胞总数为(8936±643)个(±s,n=7),全耳蜗基底膜长度为(17.73±1.01)mm(n=12)。与A组相比,B组动物CAP阈值未见明显变化,但CAP饱和振幅降低了40%并伴有约40%的内毛细胞缺失。C组动物CAP明显升高并损失了近90%的内毛细胞。结论成年南美栗鼠短纯音CAP阈值在2、4、8 kHz最低,在低频或高频时阈值略有升高。卡铂造成的部分内毛细胞损伤与CAP振幅改变有良好的对应关系,但在内毛细胞损失40%时并不改变CAP的阈值,当内毛细胞缺失超过80%时,CAP阈值的升高不可避免。