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Polygenic Risk Score-Based Association Analysis Identifies Genetic Comorbidities Associated with Age-Related Hearing Difficulty in Two Independent Samples. 基于多基因风险评分的关联分析在两个独立样本中发现了与年龄相关听力障碍有关的遗传合并症。
IF 2.4 3区 医学 Q3 NEUROSCIENCES Pub Date : 2024-08-01 Epub Date: 2024-05-23 DOI: 10.1007/s10162-024-00947-0
Ishan Sunilkumar Bhatt, Juan Antonio Raygoza Garay, Srividya Grama Bhagavan, Valerie Ingalls, Raquel Dias, Ali Torkamani
<p><strong>Purpose: </strong>Age-related hearing loss is the most common form of permanent hearing loss that is associated with various health traits, including Alzheimer's disease, cognitive decline, and depression. The present study aims to identify genetic comorbidities of age-related hearing loss. Past genome-wide association studies identified multiple genomic loci involved in common adult-onset health traits. Polygenic risk scores (PRS) could summarize the polygenic inheritance and quantify the genetic susceptibility of complex traits independent of trait expression. The present study conducted a PRS-based association analysis of age-related hearing difficulty in the UK Biobank sample (N = 425,240), followed by a replication analysis using hearing thresholds (HTs) and distortion-product otoacoustic emissions (DPOAEs) in 242 young adults with self-reported normal hearing. We hypothesized that young adults with genetic comorbidities associated with age-related hearing difficulty would exhibit subclinical decline in HTs and DPOAEs in both ears.</p><p><strong>Methods: </strong>A total of 111,243 participants reported age-related hearing difficulty in the UK Biobank sample (> 40 years). The PRS models were derived from the polygenic risk score catalog to obtain 2627 PRS predictors across the health spectrum. HTs (0.25-16 kHz) and DPOAEs (1-16 kHz, L1/L2 = 65/55 dB SPL, F2/F1 = 1.22) were measured on 242 young adults. Saliva-derived DNA samples were subjected to low-pass whole genome sequencing, followed by genome-wide imputation and PRS calculation. The logistic regression analyses were performed to identify PRS predictors of age-related hearing difficulty in the UK Biobank cohort. The linear mixed model analyses were performed to identify PRS predictors of HTs and DPOAEs.</p><p><strong>Results: </strong>The PRS-based association analysis identified 977 PRS predictors across the health spectrum associated with age-related hearing difficulty. Hearing difficulty and hearing aid use PRS predictors revealed the strongest association with the age-related hearing difficulty phenotype. Youth with a higher genetic predisposition to hearing difficulty revealed a subclinical elevation in HTs and a decline in DPOAEs in both ears. PRS predictors associated with age-related hearing difficulty were enriched for mental health, lifestyle, metabolic, sleep, reproductive, digestive, respiratory, hematopoietic, and immune traits. Fifty PRS predictors belonging to various trait categories were replicated for HTs and DPOAEs in both ears.</p><p><strong>Conclusion: </strong>The study identified genetic comorbidities associated with age-related hearing loss across the health spectrum. Youth with a high genetic predisposition to age-related hearing difficulty and other related complex traits could exhibit sub-clinical decline in HTs and DPOAEs decades before clinically meaningful age-related hearing loss is observed. We posit that effective communication of genetic risk
目的:老年性听力损失是最常见的永久性听力损失,与各种健康特征相关,包括阿尔茨海默病、认知能力下降和抑郁症。本研究旨在确定老年性听力损失的遗传合并症。过去的全基因组关联研究发现了多个基因组位点与常见的成人发病健康特征有关。多基因风险评分(PRS)可以总结多基因遗传,并量化复杂性状的遗传易感性,而不受性状表达的影响。本研究对英国生物库样本(N = 425,240 )中与年龄相关的听力困难进行了基于多基因风险评分的关联分析,随后使用听阈(HTs)和失真产物耳声发射(DPOAEs)对 242 名自我报告听力正常的年轻人进行了重复分析。我们假设,患有与年龄相关的听力困难遗传合并症的年轻人会表现出双耳听阈和 DPOAEs 的亚临床下降:在英国生物库样本中,共有 111,243 名参与者报告了与年龄相关的听力障碍(大于 40 岁)。PRS模型来自多基因风险评分目录,获得了2627个健康范围内的PRS预测因子。对 242 名年轻成年人进行了 HTs(0.25-16 kHz)和 DPOAEs(1-16 kHz,L1/L2 = 65/55 dB SPL,F2/F1 = 1.22)测量。对唾液中的 DNA 样本进行了低通滤波全基因组测序,然后进行了全基因组归因和 PRS 计算。通过逻辑回归分析,确定了英国生物库队列中年龄相关听力障碍的 PRS 预测因子。进行线性混合模型分析以确定PRS预测HTs和DPOAEs的因素:基于 PRS 的关联分析确定了 977 个与年龄相关听力困难有关的健康范围内的 PRS 预测因子。听力困难和助听器使用 PRS 预测因子与年龄相关听力困难表型的关联性最强。听力困难遗传易感性较高的青少年的双耳 HTs 出现亚临床升高,DPOAEs 出现下降。与年龄相关听力障碍相关的 PRS 预测因子富含心理健康、生活方式、代谢、睡眠、生殖、消化、呼吸、造血和免疫特征。属于不同性状类别的 50 个 PRS 预测因子在双耳 HTs 和 DPOAEs 中得到了重复:结论:这项研究发现了与年龄相关性听力损失有关的遗传合并症。对老年性听力障碍和其他相关复杂特征具有高度遗传易感性的青少年,可能会在临床上观察到有意义的老年性听力损失之前几十年,就出现 HTs 和 DPOAEs 的亚临床衰退。我们认为,有效传达遗传风险信息、提倡健康的生活方式以及在年轻时减少接触环境风险因素,有助于预防或推迟老年性听力障碍的发生。
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引用次数: 0
SVPath: A Deep Learning Tool for Analysis of Stria Vascularis from Histology Slides. SVPath:从组织学切片分析血管结构的深度学习工具
IF 2.4 3区 医学 Q3 NEUROSCIENCES Pub Date : 2024-08-01 Epub Date: 2024-05-17 DOI: 10.1007/s10162-024-00948-z
Aseem Jain, Dianela Perdomo, Nimesh Nagururu, Jintong Alice Li, Bryan K Ward, Amanda M Lauer, Francis X Creighton

Introduction: The stria vascularis (SV) may have a significant role in various otologic pathologies. Currently, researchers manually segment and analyze the stria vascularis to measure structural atrophy. Our group developed a tool, SVPath, that uses deep learning to extract and analyze the stria vascularis and its associated capillary bed from whole temporal bone histopathology slides (TBS).

Methods: This study used an internal dataset of 203 digitized hematoxylin and eosin-stained sections from a normal macaque ear and a separate external validation set of 10 sections from another normal macaque ear. SVPath employed deep learning methods YOLOv8 and nnUnet to detect and segment the SV features from TBS, respectively. The results from this process were analyzed with the SV Analysis Tool (SVAT) to measure SV capillaries and features related to SV morphology, including width, area, and cell count. Once the model was developed, both YOLOv8 and nnUnet were validated on external and internal datasets.

Results: YOLOv8 implementation achieved over 90% accuracy for cochlea and SV detection. nnUnet SV segmentation achieved a DICE score of 0.84-0.95; the capillary bed DICE score was 0.75-0.88. SVAT was applied to compare both the ears used in the study. There was no statistical difference in SV width, SV area, and average area of capillary between the two ears. There was a statistical difference between the two ears for the cell count per SV.

Conclusion: The proposed method accurately and efficiently analyzes the SV from temporal histopathology bone slides, creating a platform for researchers to understand the function of the SV further.

导言血管横纹(SV)可能在各种耳科病症中起着重要作用。目前,研究人员通过手动分割和分析血管纹来测量结构性萎缩。我们的研究小组开发了一种工具 SVPath,利用深度学习从整个颞骨组织病理学切片(TBS)中提取和分析血管横纹及其相关的毛细血管床:这项研究使用了一个内部数据集,其中包括 203 个来自正常猕猴耳朵的数字化苏木精和伊红染色切片,以及一个单独的外部验证集,其中包括来自另一个正常猕猴耳朵的 10 个切片。SVPath 采用深度学习方法 YOLOv8 和 nnUnet 分别检测和分割 TBS 的 SV 特征。利用 SV 分析工具(SVAT)对这一过程的结果进行分析,以测量 SV 毛细血管以及与 SV 形态相关的特征,包括宽度、面积和细胞数。模型开发完成后,YOLOv8 和 nnUnet 在外部和内部数据集上进行了验证:nnUnet SV 分割的 DICE 得分为 0.84-0.95;毛细血管床的 DICE 得分为 0.75-0.88。SVAT 用于比较研究中使用的两只耳朵。两只耳朵的 SV 宽度、SV 面积和毛细血管平均面积没有统计学差异。结论:结论:所提出的方法能准确、高效地分析颞组织病理学骨切片中的 SV,为研究人员进一步了解 SV 的功能提供了一个平台。
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引用次数: 0
Optimal Scale-Invariant Wavelet Representation and Filtering of Human Otoacoustic Emissions. 人体声发射的最佳尺度不变小波表示和滤波。
IF 2.4 3区 医学 Q3 NEUROSCIENCES Pub Date : 2024-08-01 Epub Date: 2024-05-24 DOI: 10.1007/s10162-024-00943-4
Arturo Moleti

Otoacoustic emissions (OAEs) are generated in the cochlea and recorded in the ear canal either as a time domain waveform or as a collection of complex responses to tones in the frequency domain (Probst et al. J Account Soc Am 89:2027-2067, 1991). They are typically represented either in their original acquisition domain or in its Fourier-conjugated domain. Round-trip excursions to the conjugated domain are often used to perform filtering operations in the computationally simplest way, exploiting the convolution theorem. OAE signals consist of the superposition of backward waves generated in different cochlear regions by different generation mechanisms, over a wide frequency range. The cochlear scaling symmetry (cochlear physics is the same at all frequency scales), which approximately holds in the human cochlea, leaves its fingerprints in the mathematical properties of OAE signals. According to a generally accepted taxonomy (Sher and Guinan Jr, J Acoust Soc Am 105:782-798, 1999), OAEs are generated either by wave-fixed sources, moving with frequency according with the cochlear scaling (as in nonlinear distortion) or by place-fixed sources (as in coherent reflection by roughness). If scaling symmetry holds, the two generation mechanisms yield OAEs with different phase gradient delay: almost null for wave-fixed sources, and long (and scaling as 1/f) for place-fixed sources. Thus, the most effective representation of OAE signals is often that respecting the cochlear scale-invariance, such as the time-frequency domain representation provided by the wavelet transform. In the time-frequency domain, the elaborate spectra or waveforms yielded by the superposition of OAE components from different generation mechanisms assume a much clearer 2-D pattern, with each component localized in a specific and predictable region. The wavelet representation of OAE signals is optimal both for visualization purposes and for designing filters that effectively separate different OAE components, improving both the specificity and the sensitivity of OAE-based applications. Indeed, different OAE components have different physiological meanings, and filtering dramatically improves the signal-to-noise ratio.

耳声发射 (OAE) 在耳蜗中产生,并在耳道中记录为时域波形或频域中对音调的复杂响应集合(Probst et al. J Account Soc Am 89:2027-2067, 1991)。它们通常以原始采集域或傅立叶共轭域表示。共轭域的往返偏移通常用于利用卷积定理,以最简单的计算方式执行滤波操作。OAE 信号由不同耳蜗区域通过不同产生机制产生的后向波在宽频率范围内的叠加组成。耳蜗的比例对称性(耳蜗物理学在所有频率范围内都是相同的)在人类耳蜗中大致成立,它在 OAE 信号的数学特性中留下了自己的痕迹。根据普遍接受的分类法(Sher 和 Guinan Jr,J Acoust Soc Am 105:782-798,1999),OAE 要么由固定波源产生,随耳蜗缩放频率移动(如非线性失真),要么由固定位置源产生(如粗糙度的相干反射)。如果缩放对称性成立,这两种产生机制会产生具有不同相位梯度延迟的 OAE:波固定源几乎为空,而位置固定源则较长(且缩放为 1/f)。因此,OAE 信号最有效的表示方法通常是尊重耳蜗尺度不变性的表示方法,如小波变换提供的时频域表示方法。在时频域中,来自不同产生机制的 OAE 分量叠加产生的复杂频谱或波形呈现出更清晰的二维模式,每个分量都定位在特定的可预测区域。OAE 信号的小波表示法是可视化和设计滤波器的最佳选择,可有效分离不同的 OAE 成分,提高基于 OAE 的应用的特异性和灵敏度。事实上,不同的 OAE 成分具有不同的生理意义,而滤波可显著提高信噪比。
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引用次数: 0
Electron Microscopic Mapping of Mitochondrial Morphology in the Cochlear Nerve Fibers. 电子显微镜绘制耳蜗神经纤维线粒体形态图
IF 2.4 3区 医学 Q3 NEUROSCIENCES Pub Date : 2024-08-01 Epub Date: 2024-06-27 DOI: 10.1007/s10162-024-00957-y
Yan Lu, Yi Jiang, Fangfang Wang, Hao Wu, Yunfeng Hua

To enable nervous system function, neurons are powered in a use-dependent manner by mitochondria undergoing morphological-functional adaptation. In a well-studied model system-the mammalian cochlea, auditory nerve fibers (ANFs) display distinct electrophysiological properties, which is essential for collectively sampling acoustic information of a large dynamic range. How exactly the associated mitochondrial networks are deployed in functionally differentiated ANFs remains scarcely interrogated. Here, we leverage volume electron microscopy and machine-learning-assisted image analysis to phenotype mitochondrial morphology and distribution along ANFs of full-length in the mouse cochlea inner spiral bundle. This reveals greater variance in mitochondrial size with increased ANF habenula to terminal path length. Particularly, we analyzed the ANF terminal-residing mitochondria, which are critical for local calcium uptake during sustained afferent activities. Our results suggest that terminal-specific enrichment of mitochondria, in addition to terminal size and overall mitochondrial abundance of the ANF, correlates with heterogenous mitochondrial contents of the terminal.

为使神经系统发挥功能,神经元通过线粒体进行形态-功能适应,以依赖使用的方式提供动力。在一个研究得很透彻的模型系统--哺乳动物耳蜗中,听觉神经纤维(ANFs)显示出独特的电生理特性,这对于集体采样大动态范围的声学信息至关重要。在功能分化的听觉神经纤维中,相关线粒体网络究竟是如何部署的,目前仍鲜有研究。在这里,我们利用体视电子显微镜和机器学习辅助图像分析,对小鼠耳蜗内螺旋束全长 ANF 的线粒体形态和分布进行了表型分析。结果表明,线粒体的大小随ANF habenula到末端路径长度的增加而变化较大。我们特别分析了ANF末端驻留的线粒体,这些线粒体对持续传入活动中的局部钙吸收至关重要。我们的研究结果表明,除了ANF末端的大小和线粒体的总体丰度外,末端特异性线粒体的富集还与末端线粒体含量的异质性有关。
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引用次数: 0
The Origin Along the Cochlea of Otoacoustic Emissions Evoked by Mid-Frequency Tone Pips. 中频音点诱发耳蜗声发射的起源
IF 2.4 3区 医学 Q3 NEUROSCIENCES Pub Date : 2024-08-01 Epub Date: 2024-06-27 DOI: 10.1007/s10162-024-00955-0
Shawn S Goodman, Shannon M Lefler, Choongheon Lee, John J Guinan, Jeffery T Lichtenhan

Purpose: Tone-pip-evoked otoacoustic emissions (PEOAEs) are transient-evoked otoacoustic emissions (OAEs) that are hypothesized to originate from reflection of energy near the best-frequency (BF) cochlear place of the stimulus frequency. However, individual PEOAEs have energy with a wide range of delays. We sought to determine whether some PEOAE energy is consistent with having been generated far from BF.

Methods: PEOAEs from 35 and 47 dB SPL tone pips were obtained by removing pip-stimulus energy by subtracting the ear-canal sound pressure from scaled-down 59 dB SPL tone pips (which evoke relatively small OAEs). PEOAE delays were measured at each peak in the PEOAE absolute-value waveforms. While measuring PEOAEs and auditory-nerve compound action potentials (CAPs), amplification was blocked sequentially from apex to base by cochlear salicylate perfusion. The perfusion time when a CAP was reduced identified when the perfusion reached the tone-pip BF place. The perfusion times when each PEOAE peak was reduced identified where along the cochlea it received cochlear amplification. PEOAEs and CAPs were measured simultaneously using one pip frequency in each ear (1.4 to 4 kHz across 16 ears).

Results: Most PEOAE peaks received amplification primarily between the BF place and 1-2 octaves basal of the BF place. PEOAE peaks with short delays received amplification basal of BF place. PEOAE peaks with longer delays sometimes received amplification apical of BF place, consistent with previous stimulus-frequency-OAE results.

Conclusion: PEOAEs provide information about cochlear amplification primarily within ~ 1.5 octave of the tone-pip BF place, not about regions > 3 octaves basal of BF.

目的:音调-嗓音诱发的耳声发射(PEOAEs)是一种瞬时诱发的耳声发射(OAEs),据推测其起源于刺激频率的最佳频率(BF)耳蜗位置附近的能量反射。然而,单个 PEOAEs 的能量延迟范围很广。我们试图确定某些 PEOAE 能量是否与远离最佳频率(BF)产生的能量一致:方法:通过减去按比例缩小的 59 dB SPL 音调点(可诱发相对较小的 OAE)的耳道声压,去除点刺激能量,从而获得来自 35 和 47 dB SPL 音调点的 PEOAE。在 PEOAE 绝对值波形的每个峰值处测量 PEOAE 延迟。在测量 PEOAEs 和听觉神经复合动作电位(CAPs)时,通过耳蜗水杨酸盐灌注从顶部到底部依次阻断放大。当灌注到达音点 BF 处时,确定 CAP 降低的灌注时间。每个 PEOAE 峰值降低时的灌注时间可确定其在耳蜗的哪个位置接受耳蜗放大。PEOAE 和 CAP 同时测量,每只耳朵使用一个音点频率(16 只耳朵的频率为 1.4 至 4 kHz):大多数 PEOAE 峰值主要在 BF 位置和 BF 位置基底 1-2 个八度之间得到放大。延迟时间较短的 PEOAE 峰值在 BF 位置基底处得到放大。延迟时间较长的 PEOAE 峰有时会在 BF 位置的顶端得到放大,这与之前的刺激频率-OAE 结果一致:结论:PEOAE 提供的耳蜗放大信息主要集中在音点 BF 位置 ~ 1.5 个八度音程的范围内,而不是 BF 基底 3 个八度音程以上的区域。
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引用次数: 0
The Rapid Decline in Interaural-Time-Difference Sensitivity for Pure Tones Can Be Explained by Peripheral Filtering. 外周滤波可解释纯音调耳内时差灵敏度的迅速下降
IF 2.4 3区 医学 Q3 NEUROSCIENCES Pub Date : 2024-08-01 Epub Date: 2024-05-20 DOI: 10.1007/s10162-024-00949-y
Matthew J Goupell, G Christopher Stecker, Brittany T Williams, Anhelina Bilokon, Daniel J Tollin

Purpose: The interaural time difference (ITD) is a primary horizontal-plane sound localization cue computed in the auditory brainstem. ITDs are accessible in the temporal fine structure of pure tones with a frequency of no higher than about 1400 Hz. How listeners' ITD sensitivity transitions from very best sensitivity near 700 Hz to impossible to detect within 1 octave currently lacks a fully compelling physiological explanation. Here, it was hypothesized that the rapid decline in ITD sensitivity is dictated not by a central neural limitation but by initial peripheral sound encoding, specifically, the low-frequency (apical) portion of the cochlear excitation pattern produced by a pure tone.

Methods: ITD sensitivity was measured in 16 normal-hearing listeners as a joint function of frequency (900-1500 Hz) and level (10-50 dB sensation level).

Results: Performance decreased with increasing frequency and decreasing sound level. The slope of performance decline was 90 dB/octave, consistent with the low-frequency slope of the cochlear excitation pattern.

Conclusion: Fine-structure ITD sensitivity near 1400 Hz may be conveyed primarily by "off-frequency" activation of neurons tuned to lower frequencies near 700 Hz. Physiologically, this could be realized by having neurons sensitive to fine-structure ITD up to only about 700 Hz. A more extreme model would have only a single narrow channel near 700 Hz that conveys fine-structure ITDs. Such a model is a major simplification and departure from the classic formulation of the binaural display, which consists of a matrix of neurons tuned to a wide range of relevant frequencies and ITDs.

目的:耳间时差(ITD)是在听觉脑干中计算的主要水平面声音定位线索。在频率不高于约 1400 Hz 的纯音的时间精细结构中可以获得 ITD。听者的 ITD 灵敏度是如何从 700 Hz 附近的最佳灵敏度过渡到 1 个倍频程内无法检测到的,目前还缺乏令人信服的生理学解释。在此,我们假设 ITD 灵敏度的快速下降不是由中枢神经限制决定的,而是由最初的外周声音编码决定的,特别是由纯音产生的耳蜗激励模式的低频(耳尖)部分:方法:对 16 名听力正常的听者的 ITD 灵敏度进行了测量,并将其作为频率(900-1500 Hz)和电平(10-50 dB 感觉电平)的联合函数:结果:灵敏度随频率增加和声级降低而降低。听力下降的斜率为 90 dB/倍频程,与耳蜗激励模式的低频斜率一致:结论:1400 Hz 附近的精细结构 ITD 灵敏度可能主要通过 "非频率 "激活调谐到 700 Hz 附近低频的神经元来传达。在生理学上,这可以通过神经元对精细结构 ITD 的敏感度仅达到约 700 Hz 来实现。一个更极端的模型是在 700 Hz 附近只有一个狭窄通道传递细结构 ITD。这种模式是对双耳显示经典模式的重大简化和偏离,因为双耳显示是由神经元矩阵组成的,而神经元矩阵可对各种相关频率和 ITD 进行调谐。
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引用次数: 0
Tinnitus in Children. 儿童耳鸣
IF 2.4 3区 医学 Q3 NEUROSCIENCES Pub Date : 2024-06-01 Epub Date: 2024-05-06 DOI: 10.1007/s10162-024-00944-3
Derek J Hoare, Harriet Smith, Veronica Kennedy, Kathryn Fackrell

This perspective reviews the current state of the art and literature on tinnitus in children, prevalence and risk factors, clinical management, and future priorities for healthcare provision and research. Most research in the field to date appears to be prevalence studies, which have reached dramatically different estimates; this reflects the lack of a standard language when asking about the presence of tinnitus, or how bothersome, distressing, or negatively impacting it is for the child. Estimates are also likely affected by a lack of awareness of tinnitus amongst children and parents. Children are less likely to spontaneously report tinnitus than adults, and parents are often unaware their child could even develop tinnitus, considering it a disease of older age for example. It is critical that children are asked and learn about tinnitus. In hearing clinics, clinicians should routinely ask about all children about tinnitus and offer tinnitus care and settings that are child- and family-friendly. As well as asking directly, clinicians should be alert to soft signs of tinnitus such as unexplained listening, speech perception, concentration difficulties, worry or anxiety, or difficulties completing hearing tests or using hearing aids. The recently developed impact of Tinnitus in Children Questionnaire (iTICQ) can then be used to assess problems that are most commonly core to children's experience of tinnitus. Clinical guidelines for tinnitus in children are few but provide recommendations for additional paediatric questionnaires and alternative assessments and for a range of treatment options. Of note, however, is the lack of clinical trials and, therefore, evidence of the effectiveness of any treatment for tinnitus in children. Significant and concerted work is therefore needed to raise awareness of tinnitus in children, understand the scale of clinical need, and standardise and evaluate clinical management options.

本视角回顾了有关儿童耳鸣、发病率和风险因素、临床管理以及未来医疗服务和研究重点的技术和文献现状。迄今为止,该领域的大多数研究似乎都是流行率研究,但得出的估计结果却大相径庭;这反映出在询问是否存在耳鸣或耳鸣对儿童造成的困扰、苦恼或负面影响时缺乏标准语言。儿童和家长对耳鸣缺乏认识也可能影响估计值。与成人相比,儿童自发报告耳鸣的可能性较低,而家长往往不知道自己的孩子可能会患上耳鸣,认为耳鸣是一种老年疾病。因此,向儿童询问和了解有关耳鸣的知识至关重要。在听力诊所,临床医生应定期询问所有儿童有关耳鸣的情况,并提供适合儿童和家庭的耳鸣护理和环境。除了直接询问外,临床医生还应警惕耳鸣的轻微征兆,如不明原因的倾听、言语感知、注意力难以集中、担心或焦虑,或难以完成听力测试或使用助听器。最近开发的 "儿童耳鸣影响问卷"(iTICQ)可用于评估儿童耳鸣最常见的核心问题。针对儿童耳鸣的临床指南很少,但提供了关于其他儿科问卷和替代性评估以及一系列治疗方案的建议。但值得注意的是,目前还缺乏临床试验,因此也就缺乏治疗儿童耳鸣有效性的证据。因此,我们需要共同努力,提高人们对儿童耳鸣的认识,了解临床需求的规模,并对临床治疗方案进行标准化和评估。
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引用次数: 0
Tinnitus: Clinical Insights in Its Pathophysiology-A Perspective. 耳鸣:病理生理学的临床见解--透视。
IF 2.4 3区 医学 Q3 NEUROSCIENCES Pub Date : 2024-06-01 Epub Date: 2024-03-26 DOI: 10.1007/s10162-024-00939-0
Berthold Langguth, Dirk de Ridder, Winfried Schlee, Tobias Kleinjung

Tinnitus, the perception of sound without a corresponding external sound source, and tinnitus disorder, which is tinnitus with associated suffering, present a multifaceted clinical challenge due to its heterogeneity and its incompletely understood pathophysiology and especially due to the limited therapeutic options. In this narrative review, we give an overview on various clinical aspects of tinnitus including its heterogeneity, contributing factors, comorbidities and therapeutic pathways with a specific emphasis on the implications for its pathophysiology and future research directions. Tinnitus exhibits high perceptual variability between affected individuals (heterogeneity) and within affected individuals (temporal variability). Hearing loss emerges as predominant risk factor and the perceived pitch corresponds to areas of hearing loss, supporting the compensatory response theory. Whereas most people who have tinnitus can live a normal life, in 10-20% tinnitus interferes severely with quality of life. These patients suffer frequently from comorbidities such as anxiety, depression or insomnia, acting as both risk factors and consequences. Accordingly, neuroimaging studies demonstrate shared brain networks between tinnitus and stress-related disorders shedding light on the intricate interplay of mental health and tinnitus. The challenge lies in deciphering causative relationships and shared pathophysiological mechanisms. Stress, external sounds, time of day, head movements, distraction, and sleep quality can impact tinnitus perception. Understanding these factors provides insights into the interplay with autonomic, sensory, motor, and cognitive processes. Counselling and cognitive-behavioural therapy demonstrate efficacy in reducing suffering, supporting the involvement of stress and anxiety-related networks. Hearing improvement, especially through cochlear implants, reduces tinnitus and thus indirectly validates the compensatory nature of tinnitus. Brain stimulation techniques can modulate the suffering of tinnitus, presumably by alteration of stress-related brain networks. Continued research is crucial for unravelling the complexities of tinnitus. Progress in management hinges on decoding diverse manifestations, identifying treatment-responsive subtypes, and advancing targeted therapeutic approaches.

耳鸣是指在没有相应外部声源的情况下对声音的感知,耳鸣症是指伴有痛苦的耳鸣,由于其异质性和病理生理学尚未完全清楚,特别是由于治疗方法有限,耳鸣症带来了多方面的临床挑战。在这篇叙述性综述中,我们概述了耳鸣的各种临床问题,包括其异质性、诱因、并发症和治疗途径,并特别强调了耳鸣的病理生理学意义和未来的研究方向。耳鸣在患者之间(异质性)和患者内部(时变性)表现出高度的知觉变异性。听力损失是主要的风险因素,感知到的音高与听力损失的区域相对应,支持补偿反应理论。虽然大多数耳鸣患者可以正常生活,但有 10-20% 的耳鸣患者的生活质量会受到严重影响。这些患者经常伴有焦虑、抑郁或失眠等并发症,这既是风险因素,也是后果。因此,神经影像学研究表明,耳鸣与压力相关疾病之间存在共同的大脑网络,揭示了心理健康与耳鸣之间错综复杂的相互作用。目前面临的挑战在于如何破译因果关系和共同的病理生理机制。压力、外部声音、一天中的时间、头部运动、注意力分散和睡眠质量都会影响耳鸣感知。了解这些因素有助于深入了解自律神经、感觉、运动和认知过程之间的相互作用。心理咨询和认知行为疗法在减轻患者痛苦方面具有一定的疗效,证明了压力和焦虑相关网络的参与。改善听力,特别是通过人工耳蜗植入,可减少耳鸣,从而间接验证耳鸣的代偿性质。大脑刺激技术可以调节耳鸣的痛苦,这可能是通过改变与压力相关的大脑网络实现的。持续的研究对于揭示耳鸣的复杂性至关重要。管理方面的进展取决于对各种表现的解码、确定对治疗有反应的亚型以及推进有针对性的治疗方法。
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引用次数: 0
Mechanical Effects of Medical Device Attachment to Human Tympanic Membrane. 医疗器械附着在人体鼓膜上的机械效应。
IF 2.4 3区 医学 Q1 Medicine Pub Date : 2024-06-01 Epub Date: 2024-04-01 DOI: 10.1007/s10162-024-00942-5
Arash Ebrahimian, Hossein Mohammadi, Nima Maftoon

Purpose: Several treatment methods for hearing disorders rely on attaching medical devices to the tympanic membrane. This study aims to systematically analyze the effects of the material and geometrical properties and location of the medical devices attached to the tympanic membrane on middle-ear vibrations.

Methods: A finite-element model of the human middle ear was employed to simulate the effects of attachment of medical devices. Various types of material and geometrical properties, locations, and modeling scenarios were investigated for the medical device.

Results: The attachment of the device magnifies the effects of anti-resonances of the middle ear. Additionally, the variations of the material properties of the device significantly alter the middle-ear resonance frequency while changes in the umbo and stapes footplate motions are negligible at frequencies above 5 kHz. Furthermore, modeling the device as a point mass cannot accurately represent the implanted middle-ear behavior. The variations of the diameter and height of the medical device have negligible effects on the middle-ear vibrations at frequencies below 200 Hz but can have considerable impacts at higher frequencies. The effects of changing the device height were negligible at frequencies above 2 kHz. We also discuss the effects of medical device attachment on the vibration patterns of the tympanic membrane as well as the impacts of the variations of the location of the device on the stapes footplate responses.

Conclusion: The findings of our study aid the development and optimization of new therapeutic devices, attached to the tympanic membrane, to have the least adverse effects on middle-ear vibrations.

目的:几种治疗听力障碍的方法都依赖于在鼓膜上安装医疗器械。本研究旨在系统分析附着在鼓膜上的医疗器械的材料和几何特性以及位置对中耳振动的影响:方法:采用人体中耳有限元模型模拟附着医疗器械的影响。研究了医疗设备的各种材料和几何特性、位置和建模方案:结果:医疗设备的附着会放大中耳的反共振效应。此外,设备材料特性的变化会显著改变中耳共振频率,而在频率高于 5 kHz 时,umbo 和镫骨脚板运动的变化可以忽略不计。此外,将该装置建模为点状质量并不能准确表示植入中耳的行为。在频率低于 200 赫兹时,医疗设备直径和高度的变化对中耳振动的影响可以忽略不计,但在频率较高时则会产生相当大的影响。在频率高于 2 kHz 时,改变设备高度的影响可以忽略不计。我们还讨论了医疗设备附件对鼓膜振动模式的影响,以及设备位置变化对镫骨脚板响应的影响:我们的研究结果有助于开发和优化附着在鼓膜上的新型治疗设备,使其对中耳振动的不利影响最小。
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引用次数: 0
Tinnitus: A Dimensionally Segregated, yet Perceptually Integrated Heterogeneous Disorder. 耳鸣:一种维度分割但知觉整合的异质性疾病。
IF 2.4 3区 医学 Q1 Medicine Pub Date : 2024-04-01 Epub Date: 2024-01-18 DOI: 10.1007/s10162-023-00923-0
Anusha Yasoda-Mohan, Katherine Adcock, Sook Ling Leong, Emma Meade, Berthold Langguth, Martin Schecklmann, Hubert Lim, Sven Vanneste

Objectives: Tinnitus subtypes are proposed to lie on a continuum of different symptom dimensions rather than be categorical. However, there is no comprehensive empirical data showing this complex relationship between different tinnitus symptoms. The objective of this study is to provide empirical evidence for the dimensional nature of tinnitus and how different auditory and non-auditory symptoms interact with each other through complex interactions. We do this using graph theory, a mathematical tool that empirically maps this complex interaction. This way, graph theory can be utilised to highlight a new and possibly important outlook on how we can understand the heterogeneous nature of tinnitus.

Design: In the current study, we use the screening databases of the Treatment Evaluation of Neuromodulation for Tinnitus-Stage A1 (TENT-A1) and A2 (TENT-A2) randomised trials to delineate the dimensional relationship between different clinical measures of tinnitus as a secondary data analysis. We first calculate the empirical relationship by computing the partial correlation. Following this, we use different measures of centrality to describe the contribution of different clinical measures to the overall network. We also calculate the stability of the network and compare the similarity and differences between TENT-A1 and TENT-A2.

Results: Components of the auditory subnetwork (loudness discomfort level, sound sensitivity, average hearing loss and high frequency hearing loss) are highly inter-connected in both networks with sound sensitivity and loudness discomfort level being highly influential with high measures of centrality. Furthermore, the relationship between the densely connected auditory subnetwork with tinnitus-related distress seems to vary at different levels of distress, hearing loss, duration and age of the participants.

Conclusion: Our findings provide first-time evidence for tinnitus varying in a dimensional fashion illustrating the heterogeneity of this phantom percept and its ability to be perceptually integrated, yet behaviourally segregated on different symptomatic dimensions.

目的:耳鸣亚型被认为是不同症状维度的连续体,而不是分类的。然而,目前还没有全面的实证数据显示不同耳鸣症状之间的复杂关系。本研究旨在为耳鸣的维度性质以及不同听觉和非听觉症状如何通过复杂的相互作用相互影响提供实证证据。我们使用图论来实现这一目标,图论是一种数学工具,可根据经验映射出这种复杂的相互作用。通过这种方式,图论可以为我们理解耳鸣的异质性提供一个全新的、可能非常重要的视角:在本研究中,我们利用耳鸣神经调控治疗评估 A1 阶段(TENT-A1)和 A2 阶段(TENT-A2)随机试验的筛选数据库,划定耳鸣不同临床测量指标之间的维度关系,作为二次数据分析。我们首先通过计算部分相关性来计算经验关系。然后,我们使用不同的中心度量来描述不同临床指标对整个网络的贡献。我们还计算了网络的稳定性,并比较了 TENT-A1 和 TENT-A2 之间的异同:结果:听觉子网络(响度不适水平、声音灵敏度、平均听力损失和高频听力损失)的各组成部分在两个网络中都具有高度的相互联系,其中声音灵敏度和响度不适水平具有高度影响力,中心度较高。此外,连接密集的听觉子网络与耳鸣相关困扰之间的关系似乎因不同程度的困扰、听力损失、持续时间和参与者的年龄而异:我们的研究结果首次提供了耳鸣以维度方式变化的证据,说明了这种幻觉的异质性及其在感知上的整合能力,以及在不同症状维度上的行为分离能力。
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引用次数: 0
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Jaro-Journal of the Association for Research in Otolaryngology
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