Hearing Research最新文献_第5页

Preclinical methods to determine output of the floating mass transducer in forward and reverse stimulation 确定浮动质量传感器在正向和反向刺激下输出的临床前方法。

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-02-01 Epub Date: 2026-01-02 DOI: 10.1016/j.heares.2026.109525

David Stauske , Hamidreza Mojallal , Nils Prenzler , Hannes Maier , Mohammad Ghoncheh

Objective

Our experimental study evaluated the efficiency of sound transmission with the Floating Mass Transducer (FMT) in forward (incus short process, SP) and reverse (round window, RW) stimulation modes using different coupling configurations.

Methods

Using laser Doppler vibrometry (LDV) at the stapes and intracochlear pressure difference (ICPD) the equivalent sound pressure level output was determined according to ASTM standard. Coupling configurations included the Vibroplasty-SP-Coupler, the Vibroplasty-RW-Coupler, and the research RW-Precision-Coupler. Reverse stimulation was studied with both intact and disrupted ossicular chains.

Results

In forward stimulation with SP of the incus coupling, output levels increased from 200 Hz to ∼1.26 kHz and remained constant up to 8 kHz. LDV and ICPD yielded similar results in forward stimulation. In reverse stimulation, both RW coupling methods showed resonance peaks at 1.5–2 kHz, though output amplitudes were ∼10–12 dB lower than in forward stimulation. The RW-Precision-Coupler produced higher output with less variability than the Vibroplasty-RW-Coupler. In mid-frequency range (0.6 - 1.5 kHz) the output levels measured with LDV and ICPD were similar for forward and reverse stimulation, but ICPD indicated higher outputs at low and high frequencies. Variability was greater in reverse stimulation while intact versus disrupted ossicular chains showed no significant differences in reverse stimulation.

Conclusion

LDV is well-established for assessing forward stimulation, while ICPD is more accurate in reverse stimulation. Despite lower overall output, RW stimulation frequency characteristics are preserved, supporting its clinical relevance when forward stimulation is not feasible.

目的：本实验研究评估了浮动质量换能器（FMT）在不同耦合配置下，在正向（incus short process， SP）和反向（round window， RW）激励模式下的声传输效率。方法：采用激光多普勒振动仪（LDV）测量镫骨和耳蜗内压差（ICPD），按ASTM标准测定等效声压级输出。耦合配置包括振动塑性- sp -耦合器、振动塑性- rw -耦合器和研究中的rw - precision -耦合器。研究了完整和断裂听骨链的反向刺激。结果：在诱导耦合SP的正向刺激下，输出电平从200 Hz增加到~ 1.26 kHz，并保持恒定直至8 kHz。LDV和ICPD的正向刺激效果相似。在反向刺激下，两种RW耦合方法都显示出1.5-2 kHz的共振峰，尽管输出幅度比正向刺激低~ 10-12 dB。RW-Precision-Coupler比振动塑性- rw - coupler产量更高，变动性更小。在中频范围内（0.6 - 1.5 kHz）， LDV和ICPD测量的正向和反向刺激的输出水平相似，但ICPD显示低频和高频的输出更高。反向刺激的变异性更大，而完整的听骨链和断裂的听骨链在反向刺激中没有显着差异。结论：LDV可用于正向刺激的评估，而ICPD对反向刺激的评估更为准确。尽管总体输出较低，但RW刺激频率特征得以保留，在正向刺激不可行的情况下支持其临床相关性。

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引用次数: 0

Chronic salicylate administration induces transcriptomic and metabolomic remodeling in the rat cochlear nucleus and hippocampus 慢性给药水杨酸诱导大鼠耳蜗核和海马的转录组和代谢组重塑。

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-02-01 Epub Date: 2026-01-03 DOI: 10.1016/j.heares.2026.109526

Shichu Sun , Shuai Cheng , Shifu Li , Miao Zhao , Shiqi Jing , Yuhua Wang , You Zhou

Salicylate reliably induces tinnitus, yet its systemic effects on the central auditory and limbic systems remain incompletely characterized. Through integrated transcriptomic and metabolomic profiling of the rat cochlear nucleus and hippocampus, we observed pronounced region-specific remodeling following chronic tinnitus-inducing salicylate treatment. All differential and enrichment analyses were filtered using a nominal p-value cutoff (p < 0.05) without multiple-testing correction; thus, the findings should be interpreted as exploratory. We identified 150 differentially expressed genes (DEGs) and 70 differentially expressed metabolites (DEMs) in the cochlear nucleus, and 550 DEGs alongside 71 DEMs in the hippocampus. In the cochlear nucleus, DEGs were enriched in neuroactive ligand-receptor interaction, cell adhesion, TNF signaling, ABC transporters, and Hippo signaling pathways. Concurrently, DEMs were enriched in cholesterol metabolism, choline metabolism, aldosterone and cortisol synthesis, primary bile acid biosynthesis, and vitamin digestion and absorption. Multi-omics integration highlighted a synergistic network involving bile secretion, cholesterol metabolism, and ABC transporters. In the hippocampus, DEGs were associated with extracellular matrix (ECM)-receptor interaction, phagosome, apoptosis, PI3K-Akt signaling pathway, focal adhesion, Hippo signaling pathway, fatty acid elongation, and proteoglycans in cancer. DEMs were enriched in choline metabolism, glycerophospholipid metabolism, cholesterol metabolism, vitamin digestion and absorption, retrograde endocannabinoid signaling, primary bile acid biosynthesis, linoleic acid metabolism, alpha-linolenic acid metabolism, and phenylalanine metabolism. Integrative analysis revealed correlated networks involving, primary bile acid biosynthesis, bile secretion, cholesterol metabolism, ABC transporters, and choline metabolism. These findings provide a comprehensive view of the neurobiological mechanisms underlying salicylate-induced tinnitus, demonstrating robust region-specific remodeling within auditory and limbic structures. Our results suggest chronic salicylate exposure disrupts critical bioenergetic and signaling pathways, contributing to aberrant neural excitability in the auditory pathway and cognitive-affective impairments mediated by the hippocampus.

水杨酸盐可靠地诱发耳鸣，但其对中枢听觉和边缘系统的全身性影响仍不完全明确。通过对大鼠耳蜗核和海马的综合转录组学和代谢组学分析，我们观察到慢性耳鸣诱导水杨酸治疗后明显的区域特异性重塑。所有差异分析和富集分析均使用名义p值截断（p < 0.05）进行过滤，未进行多重检验校正；因此，研究结果应被解释为探索性的。我们在耳蜗核中鉴定了150个差异表达基因（deg）和70个差异表达代谢物（dem），在海马中鉴定了550个差异表达基因和71个差异表达代谢物。在耳蜗核中，deg在神经活性配体-受体相互作用、细胞粘附、TNF信号、ABC转运蛋白和Hippo信号通路中富集。同时，dem在胆固醇代谢、胆碱代谢、醛固酮和皮质醇合成、原发性胆汁酸生物合成和维生素消化吸收等方面富集。多组学整合强调了涉及胆汁分泌、胆固醇代谢和ABC转运蛋白的协同网络。在海马中，deg与细胞外基质(ECM)-受体相互作用、吞噬体、细胞凋亡、PI3K-Akt信号通路、局灶黏附、Hippo信号通路、脂肪酸延伸和癌症蛋白聚糖相关。dms富含胆碱代谢、甘油磷脂代谢、胆固醇代谢、维生素消化吸收、逆行内源性大麻素信号、初级胆汁酸生物合成、亚油酸代谢、α -亚麻酸代谢和苯丙氨酸代谢。综合分析显示，相关网络涉及初级胆汁酸生物合成、胆汁分泌、胆固醇代谢、ABC转运蛋白和胆碱代谢。这些发现为水杨酸诱发耳鸣的神经生物学机制提供了一个全面的观点，证明了听觉和边缘结构中强大的区域特异性重塑。我们的研究结果表明，长期暴露在水杨酸中会破坏关键的生物能量和信号通路，导致听觉通路中异常的神经兴奋性和海马介导的认知情感障碍。

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引用次数: 0

Investigating the mechanisms of ageing and neuroinflammation in age-related hearing loss: A proteomic analysis 研究年龄相关性听力损失中衰老和神经炎症的机制：蛋白质组学分析。

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-02-01 Epub Date: 2026-01-07 DOI: 10.1016/j.heares.2026.109529

Yan Wang , Chanyuan Zhang , Xiaohui Ma , He Zhao , Qi Wang , Limei Cui , Liang Chen , Yan Sun

Background

Age-related hearing loss (ARHL) is a prevalent neurodegenerative condition commonly linked to aging and chronic inflammation. However, there is currently a lack of substantial proteomic evidence elucidating the underlying mechanisms within the brain.

Methods

The study employed proteomic techniques to identify proteins as biomarkers for ARHL and to investigate and predict their underlying pathogenic mechanisms and potential intervention targets.

Results

In studying the impact of aging on ARHL, we found significant expression of 7 hearing-related proteins. including Mbp, Mag, Plp1, Orm1, Orm2, Tubb2b, Tuba3aa, and Tuba4a. These proteins were enriched in the ceramide-related pathway (CAMS), sphingolipid pathway, and microtubule transport pathway. Further investigations into the impact of chronic neuroinflammation, particularly reflecting the activation of microglial, revealed an improvement in hearing following the inhibition of microglial activation. Additionally, two proteins significantly associated with hearing were discovered to be expressed in the cochlear nucleus. Mag, Orm1, enriched in CAMs and sphingolipid pathways.

Conclusions

In conclusion, we predict that aging may hinder the microtubule transport pathway, affect the CAMS and acidic glycoprotein pathways, influence the differential expression of proteins, thereby leading to the occurrence and development of ARHL. After the inhibition of microglia, key proteins of the CAMS and acidic glycoprotein pathways appeared among the differentially expressed proteins, which suggests that aging may induce ARHL by affecting myelin stripping in microglia, ultimately promoting the development of ARHL.

背景：年龄相关性听力损失（ARHL）是一种常见的神经退行性疾病，通常与衰老和慢性炎症有关。然而，目前缺乏大量的蛋白质组学证据来阐明大脑内部的潜在机制。方法：采用蛋白质组学技术鉴定作为ARHL生物标志物的蛋白质，并研究和预测其潜在的致病机制和潜在的干预靶点。结果：在研究衰老对ARHL的影响时，我们发现7种听力相关蛋白显著表达。包括Mbp、Mag、Plp1、Orm1、Orm2、Tubb2b、Tuba3aa和Tuba4a。这些蛋白在神经酰胺相关途径（CAMS）、鞘脂途径和微管运输途径中富集。对慢性神经炎症影响的进一步研究，特别是反映小胶质细胞激活的研究，揭示了抑制小胶质细胞激活后听力的改善。此外，两种与听力显著相关的蛋白被发现在耳蜗核中表达。Mag, Orm1，富含CAMs和鞘脂通路。结论：综上所述，我们预测衰老可能阻碍微管转运途径，影响CAMS和酸性糖蛋白途径，影响蛋白的差异表达，从而导致ARHL的发生发展。在小胶质细胞受到抑制后，差异表达蛋白中出现了CAMS通路和酸性糖蛋白通路的关键蛋白，提示衰老可能通过影响小胶质细胞髓磷脂剥离而诱发ARHL，最终促进ARHL的发展。

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引用次数: 0

Ageing and the auditory nerve: Hearing sensitivity and endbulb synapses 衰老和听觉神经：听觉敏感性和终球突触。

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-02-01 Epub Date: 2026-01-09 DOI: 10.1016/j.heares.2026.109536

David K. Ryugo , Satoshi Nishitani

Age-related hearing loss impairs speech understanding for socialization and music appreciation for enjoyment, both of which compromise quality of life and can lead to cognitive decline. It has previously been shown that while standard audiometric hearing thresholds can remain normal over time, speech understanding in noise is more difficult and there is the emergence of tinnitus. These specific hearing difficulties are not revealed by standard audiograms but we now know that they have been attributed to loss of high threshold auditory nerve fibers caused by the disappearance of terminal endings under inner hair cells. This loss can be measured by a reduction of evoked activity in the auditory nerve and atrophy of central auditory nerve endings in the anteroventral cochlear nucleus called endbulbs of Held. In the present study, we used age-graded cohorts of mice to compare hearing loss to the structure of auditory nerve synapses using serial section electron microscopy. We demonstrated a pathologic expansion and flattening of their synapses against spherical bushy cells in the rostral anteroventral cochlear nucleus in older mice with hearing loss. These changes portend impairments in sound processing and emphasize the importance of identifying “hidden” hearing loss for potential rehabilitation.

与年龄相关的听力损失损害了社交的语言理解和享受的音乐欣赏，这两者都会损害生活质量并导致认知能力下降。先前的研究表明，虽然标准的听力阈值可以随着时间的推移保持正常，但在噪音中理解语言更加困难，并且会出现耳鸣。这些特殊的听力障碍不能通过标准听力图显示出来，但我们现在知道，它们是由于内毛细胞下的末梢消失引起的高阈值听神经纤维的损失。这种损失可以通过听神经诱发活动的减少和耳蜗前腹侧核中听神经末梢的萎缩来测量。在本研究中，我们使用年龄分级的小鼠队列，使用连续切片电子显微镜比较听力损失与听神经突触结构。我们证明了老年听力损失小鼠耳蜗核吻侧前腹侧球形丛状细胞对其突触的病理扩张和变平。这些变化预示着声音处理的障碍，并强调了识别“隐性”听力损失对潜在康复的重要性。

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引用次数: 0

Altered intrinsic brain connectivity in misophonia, with and without hyperacusis 伴有或不伴有听觉亢进的恐音症患者的内在脑连通性改变

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-02-01 Epub Date: 2025-12-26 DOI: 10.1016/j.heares.2025.109521

Shagun Ajmera , Rafay A. Khan , Gibbeum Kim , Namitha Jain , Ariana Castro , Howard Berenbaum , Fatima T. Husain

Misophonia and loudness hyperacusis are debilitating sound intolerance conditions marked by extreme emotional and physiological responses to everyday sounds. Although frequently co-occurring, their distinct neural correlates remain poorly delineated. In an exploratory data-driven analysis, we identified neural-connectivity based markers of misophonia among cortical and subcortical networks in the brain using resting-state fMRI data. We leveraged an optimized and cross-validated machine learning framework to sift through >85 thousand functional connections and to evaluate detectability of misophonia, in isolation and when comorbid with hyperacusis. Participants were rigorously categorized using structured interviews into misophonia-only (MI), misophonia with hyperacusis (MH), and control (CTR) groups. Classifier models trained on individual functional connectivity distinguished both MI and MH from CTR, with 63 % and 67 % test prediction accuracy respectively. Core misophonia-related alterations consistently emerged across both groups, particularly in salience, somatomotor, and frontoparietal control networks, implying disruptions in emotion regulation, motor inhibition, and attentional control, respectively. Specific to misophonia-only were connectivity abnormalities in the basal ganglia and subcortex, suggesting a neural dissociation between MI and MH conditions. In contrast, connectivity trends unique to MH revealed networks implicated in higher-order visual processing, likely reflecting hyperacusis-linked processes. These findings offer a refined neurobiological dissociation between misophonia and hyperacusis and underscore the importance of careful diagnostic separation in both research and clinical contexts. By isolating misophonia-relevant brain networks, our results provide actionable insight into the development of precise neuroscience-informed interventions. In particular, they support psychology-based therapy to target dysfunctional connectivity in salience and control circuits for treating misophonia.

恐音症和响度听觉亢进是一种使人衰弱的声音不耐受症状，其特征是对日常声音的极端情绪和生理反应。虽然它们经常同时发生，但它们独特的神经关联仍然没有得到很好的描述。在一项探索性数据驱动分析中，我们利用静息状态fMRI数据在大脑皮层和皮层下网络中确定了基于神经连通性的恐音症标志物。我们利用优化和交叉验证的机器学习框架筛选了8.5万个功能连接，并评估了恐音症的可检测性，包括孤立的恐音症和与听觉亢进合并症。参与者通过结构化访谈被严格地分为单纯恐音症（MI）、恐音症伴听觉亢进（MH）和对照组（CTR）。在单个功能连接上训练的分类器模型将MI和MH与CTR区分开来，测试预测准确率分别为63%和67%。核心恐音症相关的改变在两组中都一致出现，特别是在显著性、躯体运动和额顶叶控制网络中，这意味着情绪调节、运动抑制和注意力控制分别受到破坏。仅恐音症患者基底神经节和皮层下的连通性异常，表明MI和MH之间存在神经分离。相比之下，MH独有的连接趋势揭示了涉及高阶视觉处理的网络，可能反映了与超听觉相关的过程。这些发现提供了恐音症和听觉亢进之间精细的神经生物学分离，并强调了在研究和临床环境中仔细诊断分离的重要性。通过分离恐音症相关的大脑网络，我们的研究结果为开发精确的神经科学干预措施提供了可行的见解。特别是，他们支持以心理学为基础的治疗方法，以突出和控制回路的功能失调连接为目标，治疗恐音症。

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引用次数: 0

Application of tensile load at the tympanic membrane by an eardrum-contact transducer 鼓膜接触式换能器对鼓膜施加拉伸载荷

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-02-01 Epub Date: 2026-01-01 DOI: 10.1016/j.heares.2025.109524

Michael Martin , Stepan Kempa , Katharina Bader , Bernhard Hirt , Volker Steenhoff , Florian Strobl , Ernst Dalhoff

Safety of hearing devices attached to the tympanic membrane depends on applied forces and resulting movements of the ossicles when pulling off the device. A robotized temporal bone measurement setup was designed to apply and measure defined pull-off forces and as well as the corresponding displacements of the round-window membrane via Laser-Doppler-vibrometry. Here, we investigate in five temporal bones the pull-off dynamics of the Vibrosonic Hearing Contact Lens® the silicone membrane of which being formed to match the tympanic-membrane shape of individual temporal bones. The devices were pulled off with a linear stage actuator in a defined manner. We here show that the time courses of stapes displacement and pull-off force follow a consistent characteristic. Mean geometrical maximum stapes displacements were determined to be 5.4 µm ± 6.9 dB, and the geometrical mean maximum force 0.14 N ± 3.8 dB. The acoustical middle-ear transfer function of the temporal bones, expressed as stapes head displacement vs. ear-canal sound pressure, did not change significantly over up to 7 repeated pull-off procedures, as assessed by a low-frequency displacement average. Based on these results, the detachment of the hearing contact lens appears to be tolerable.

附着在鼓膜上的助听器的安全性取决于在拔出助听器时所施加的力和听骨的运动。设计了一种机器人颞骨测量装置，通过激光多普勒振动仪应用和测量定义的拉离力以及圆窗膜的相应位移。在这里，我们研究了在五块颞骨中振动超声听力隐形眼镜®的拉脱动力学，硅胶膜的形成与个体颞骨的鼓膜形状相匹配。这些装置以确定的方式用线性级执行器拉离。结果表明，镫骨位移和拉脱力的时间过程具有一致的特征。平均几何最大镫骨位移为5.4µm±6.9 dB，几何平均最大力为0.14 N±3.8 dB。颞骨的声学中耳传递函数，表示为镫骨头位移与耳道声压，在多达7次重复拔离手术中没有显著变化，通过低频位移平均评估。根据这些结果，听力隐形眼镜的脱落似乎是可以容忍的。

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引用次数: 0

A robust DeepLabCut-based pipeline for the multi-dimensional quantification of vestibular dysfunction in mice 基于deeplabcut的强大管道用于小鼠前庭功能障碍的多维量化。

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1016/j.heares.2026.109528

Mingwei Xu , Qiong Wu , Tianyu Gong , Yuan Yao , Qin Zhang , Qianqian Zhang , Ting Han , Yong Gu , Qing Zhang

Accurate quantification of behavioral deficits is critical for investigating vestibular disorders, yet current assessment methods often fail to capture complex kinematic features like rotational asymmetry. This study aimed to develop a cost-effective, high-precision automated analysis pipeline using the pose estimation tool DeepLabCut to quantify fine-grained behavioral phenotypes in a mouse model of Bilateral Vestibular Dysfunction (BVD). We established the BVD model via bilateral intratympanic gentamicin injection and monitored locomotor function using the Open Field Test over a 7-day post-operative period. By tracking anatomical landmarks (nose, head, and tail) with DeepLabCut and utilizing a custom Python analysis framework, we quantified total locomotor distance, central zone exploration, and specific rotational metrics. The analysis revealed a distinct biphasic behavioral progression: an acute phase (Days 1–2) characterized by significant hypokinesia and thigmotaxis, indicative of severe spatial disorientation, followed by a chronic phase (Days 5–7) marked by a transition to profound hyperactivity and pathological, stereotypic circling. Crucially, the pipeline detected early onset rotational tendencies that traditional metrics overlooked. This study demonstrates that the proposed DeepLabCut-based methodology provides a sensitive, objective, and accessible tool for the multi-dimensional assessment of vestibular dysfunction, offering a robust paradigm for evaluating functional recovery and therapeutic interventions.

准确量化行为缺陷对于研究前庭疾病至关重要，但目前的评估方法往往无法捕捉复杂的运动学特征，如旋转不对称。本研究旨在开发一种成本效益高、高精度的自动化分析管道，使用姿势估计工具DeepLabCut来量化双侧前庭功能障碍（BVD）小鼠模型的细粒度行为表型。我们通过双侧鼓室内注射庆大霉素建立BVD模型，并在术后7天内使用开放野试验监测运动功能。通过使用DeepLabCut跟踪解剖标志（鼻子，头部和尾部）并利用自定义Python分析框架，我们量化了总运动距离，中心区域勘探和特定旋转指标。分析显示了明显的双相行为进展：急性期（1-2天）以明显的运动障碍和震颤为特征，表明严重的空间定向障碍，随后是慢性期（5-7天），以过渡到深度多动和病理性、刻板的打圈为特征。至关重要的是，管道检测到传统指标忽略的早期旋转趋势。本研究表明，提出的基于deeplabcut的方法为前庭功能障碍的多维评估提供了一个敏感、客观和可访问的工具，为评估功能恢复和治疗干预提供了一个强大的范式。

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引用次数: 0

Furosemide prevents noise-induced hearing loss and enhances the preventive effect of N-acetylcysteine 速尿可预防噪声性听力损失，增强n -乙酰半胱氨酸的预防作用

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-02-01 Epub Date: 2026-01-09 DOI: 10.1016/j.heares.2026.109537

Hongguo Su , Fan Wu , Khujista Haque , Su-Hua Sha

Disruption of reactive oxygen species (ROS) homeostasis is a key mechanism underlying noise-induced sensory hair cell damage. Antioxidant treatments such as N-acetylcysteine (NAC) have been shown to attenuate noise-induced hearing loss (NIHL), supporting the role of ROS accumulation. However, no FDA-approved pharmaceutical therapy currently exists for the prevention or treatment of NIHL, likely due to the complexity of the damaging mechanisms and the presence of the blood-labyrinth barrier (BLB), which limits drug permeability and prevents therapeutic compounds from reaching effective concentrations via systemic administration.

Furosemide (FRS) has demonstrated potential to reduce NIHL and facilitate drug delivery into inner ear by transiently opening the BLB. In this study, we investigated the mechanisms by which FRS pretreatment prevents NIHL. A single dose of 200 mg/kg FRS administered immediately before noise exposure significantly reduced NIHL in FVB/NJ mice. One hour after FRS treatment, the endocochlear potential (EP) was temporarily reduced without altering cochlear sensitivity (ABR thresholds), outer hair cell function (DPOAE amplitudes), or synaptic transmission integrity between hair cells and auditory nerve fibers (suprathreshold ABR wave I amplitudes).

Furthermore, this dose of FRS selectively increased stria vascularis permeability to small molecules but not to large protein-bound tracers. Combined treatment with FRS and NAC enhanced NAC's antioxidant effect and additively prevented noise-induced outer hair cell (OHC) loss and NIHL, with OHC loss almost entirely prevented. These findings provide important insight into future strategies for the prevention and treatment of NIHL.

活性氧（ROS）稳态的破坏是噪声诱导感觉毛细胞损伤的关键机制。抗氧化处理如n -乙酰半胱氨酸（NAC）已被证明可以减轻噪声性听力损失（NIHL），支持ROS积累的作用。然而，目前还没有fda批准的药物疗法用于预防或治疗NIHL，这可能是由于损伤机制的复杂性和血液迷宫屏障（BLB）的存在，这限制了药物的渗透性，并阻止治疗性化合物通过全身给药达到有效浓度。呋塞米（FRS）已被证明有可能减少NIHL，并通过瞬间打开BLB促进药物进入内耳。在本研究中，我们探讨了FRS预处理预防NIHL的机制。在噪声暴露前立即单次给药200 mg/kg FRS可显著降低FVB/NJ小鼠的NIHL。FRS治疗1小时后，耳蜗内电位（EP）暂时降低，但不改变耳蜗敏感性（ABR阈值）、外毛细胞功能（DPOAE振幅）或毛细胞与听神经纤维之间的突触传递完整性（阈上ABR波I振幅）。此外，该剂量的FRS选择性地增加了血管纹对小分子的渗透性，而不是对大蛋白结合示踪剂的渗透性。FRS和NAC联合处理可增强NAC的抗氧化作用，并能有效预防噪声引起的外毛细胞（OHC）损失和NIHL，几乎完全防止OHC损失。这些发现为未来NIHL的预防和治疗策略提供了重要的见解。

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引用次数: 0

Effects of early childhood otitis media–related conductive hearing loss on speech perception, neural processing, and working memory 早期儿童中耳炎相关传导性听力损失对言语感知、神经加工和工作记忆的影响。

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-02-01 Epub Date: 2026-01-10 DOI: 10.1016/j.heares.2026.109540

Anadel Khalaila-Zbidat , Arie Gordin , Hanin Karawani

Otitis media with effusion (OME) is a common childhood ear disease that can cause temporary conductive hearing loss during a critical period of auditory development. This condition is hypothesized to be related to deficits in neural, perceptual, and cognitive abilities. This study examined the relation between conductive hearing loss due to OME in early childhood and its effects on neural and perceptual speech processing, as well as working memory (WM) function in early school-aged children.

A total of 21 children aged 6–8 years with normal hearing who had a history of OME in early childhood were included in the OME group. In addition, a matched control group of 34 children with no history of ear disease was used for comparison. Perceptual and neural speech-in-noise (SiN) processing were evaluated and compared between the two groups using both electrophysiological and behavioral measures. Specifically, frequency-following responses (FFRs) to the speech syllable /da/ were recorded in quiet and in noise conditions, and latency and amplitude components analyzed. For the perceptual assessment, participants completed a sentence-perception task at three signal-to-noise ratios: +3 dB, 0 dB, and -3 dB. In addition, all participants completed forward and backward digit-span WM tasks.

In the quiet condition, the OME group exhibited lower peak amplitudes compared to the control group, whereas in the noise condition, they showed earlier peak latencies, indicating a more resilient neural response to noise. Perceptually, both groups performed similarly on the SiN perception and WM tasks. However, within the OME group, better SiN perception was associated with stronger performance on both forward and backward WM tasks, while in the control group this association was observed only for the forward WM task.

School-age children with a history of early OME may exhibit neural and cognitive adaptations that support speech perception in noise. Specifically, enhanced neural encoding and increased reliance on WM may serve as compensatory mechanisms, helping these children maintain performance levels comparable to peers without a history of OME.

渗出性中耳炎（OME）是一种常见的儿童耳部疾病，可在听觉发育的关键时期引起暂时性传导性听力丧失。这种情况被认为与神经、知觉和认知能力的缺陷有关。本研究探讨了早期儿童期OME导致的传导性听力损失与其对早期学龄儿童神经和知觉言语加工以及工作记忆（WM）功能的影响。研究对象为21例6 ~ 8岁、听力正常、早期有OME病史的儿童。另外，34名无耳部疾病史的儿童作为对照组进行比较。使用电生理和行为测量来评估和比较两组之间的感知和神经语音噪声处理。具体来说，在安静和噪音条件下记录语音音节/da/的频率跟随反应（FFRs），并分析潜伏期和振幅成分。对于感知评估，参与者在三种信噪比下完成句子感知任务：+3 dB， 0 dB和-3 dB。此外，所有参与者都完成了向前和向后数字跨度的WM任务。在安静条件下，OME组表现出比对照组更低的峰值振幅，而在噪音条件下，他们表现出更早的峰值潜伏期，表明对噪音的神经反应更有弹性。在感知上，两组在SiN感知和WM任务上的表现相似。然而，在OME组中，更好的SiN感知与前向和后向WM任务的更强表现相关，而在对照组中，这种关联仅在前向WM任务中观察到。有早期OME病史的学龄儿童可能表现出支持噪音中言语感知的神经和认知适应。具体来说，增强的神经编码和对WM的依赖可能是一种代偿机制，帮助这些儿童保持与没有OME病史的同龄人相当的表现水平。

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引用次数: 0

Anxiety-like behavior in deaf Ebf1 conditional knockout mice 耳聋Ebf1条件敲除小鼠的焦虑样行为。

IF 2.5 2区医学 Q1 AUDIOLOGY & SPEECH-LANGUAGE PATHOLOGY

Hearing Research

Pub Date : 2026-01-01 Epub Date: 2025-12-16 DOI: 10.1016/j.heares.2025.109510

Ashton N. Baxter , Sarah E. Hunter , Rachel D. Penrod , Brent A. Wilkerson

Introduction

Hearing is critical for communication and clinical evidence suggests that hearing loss can lead to poorer mental well-being including social isolation, anxiety, depression, and cognitive decline. Deaf animal models offer opportunities to investigate the impact of hearing loss on behavioral correlates of mental health while controlling for genetic variability and shared etiological factors such as environmental stressors, aging, and metabolic diseases. We previously showed that conditional deletion of Ebf1 in the inner ear causes deafness. We hypothesize that otic-specific Ebf1 knockout (KO) mice recapitulate neurobehavioral alterations experienced in congenital deafness.

Methods

Slc26a9P2A-Cre and Ebf1 floxed mice were crossed previously to generate the otic-specific Ebf1 conditional KO. We measured auditory brainstem response and behavior in groups of otic-specific Ebf1 conditional KO mice and Cre-negative littermate controls (WT). We performed behavioral tests including elevated plus maze, acoustic startle, locomotor activity, forced swim, and Y-maze.

Results

We found that the KO mice spend significantly less time than WT mice in the open arms of the elevated plus maze. KO mice also show significantly increased latency to enter the open arms. Acoustic startle response was decreased in KO mice vs. WT controls and pre-pulse inhibition was also reduced in the KO, consistent with elevated hearing thresholds. We found no significant differences in exploratory behavior, forced swim immobility time, or other behavioral measures examined.

Conclusions

Our findings demonstrate that deaf otic-specific KO mice are indeed a model for the study of effects of hearing loss on clinically relevant behavioral correlates. Our results provide new empirical evidence that hearing loss contributes to anxiety, which is consistent with clinical evidence that anxiety is associated with hearing loss in older adults.

听力对沟通至关重要，临床证据表明，听力损失会导致心理健康状况恶化，包括社会孤立、焦虑、抑郁和认知能力下降。聋人动物模型为研究听力损失对心理健康行为相关因素的影响提供了机会，同时控制遗传变异和共同的病因因素，如环境压力源、衰老和代谢疾病。我们之前的研究表明，内耳Ebf1的条件缺失会导致耳聋。我们假设光特异性Ebf1敲除（KO）小鼠再现先天性耳聋所经历的神经行为改变。方法：预先将Slc26a9P2A-Cre与Ebf1固定小鼠杂交，产生光特异性Ebf1条件KO。我们测量了听觉特异性Ebf1条件KO小鼠组和cre阴性的同窝对照组（WT）的听觉脑干反应和行为。我们进行了行为学测试，包括高架+迷宫、声惊吓、运动活动、强迫游泳和y形迷宫。结果：我们发现KO小鼠在高架+迷宫中张开双臂的时间明显少于WT小鼠。KO小鼠进入张开双臂的潜伏期也明显增加。与WT对照组相比，KO小鼠的声惊吓反应降低，脉冲前抑制也减少，这与听力阈值升高一致。我们发现探索性行为、强迫游泳静止时间或其他行为测量没有显著差异。结论：我们的研究结果表明，聋哑听觉特异性KO小鼠确实是研究听力损失对临床相关行为影响的模型。我们的研究结果提供了新的经验证据，证明听力损失会导致焦虑，这与临床证据一致，即焦虑与老年人听力损失有关。

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引用次数: 0