感音神经性聋患者听觉皮层BOLD-fMRI研究

目的利用血氧水平依赖的功能磁共振成像（blood oxygenation level dependent functional magnetic resonance imaging,BOLD—fMRI）技术观察感音神经性聋患者纯音刺激时大脑听觉皮层激活情况,探讨感音神经性聋的中枢客观检查方法。方法对22例单侧中重度感音神经性聋患者（耳聋组）和15例健康志愿者（对照组）行听觉刺激BOLD-fMRI检查,比较两组纯音刺激时听觉皮层激活的体积和信号强度。结果对照组纯音刺激单耳时,对侧听觉皮层激活体积和信号强度明显大于同侧（P〈0．01）,表现为对侧半球传导优势;耳聋组刺激健侧时健侧听觉皮层激活体积和信号强度大于患侧,但差异无统计学意义（P〉0．05）。结论感音神经性聋患者纯音刺激健耳时对侧听觉半球传导优势消失,其听觉皮层可能发生了结构重塑。     

年龄相关性听力损失小鼠听皮层神经元凋亡及听功能变化

目的探讨年龄相关性听力损失C57BL/6J小鼠初级听皮层神经元凋亡及听功能变化。方法选取年轻组（2月龄）和老年组（10月龄）C57BL/6J小鼠为研究对象,通过听性脑干反应（ABR）检测并比较年轻组与老年组小鼠听力变化;用HE染色法、Tunel-POD法观察并比较两组小鼠初级听皮层神经元大体形态及凋亡比例的差异。结果老年组小鼠较年轻组小鼠听阈明显提高。老年组C57BL/6J小鼠初级听皮层神经元凋亡比例较年轻组增多。结论初级听皮层神经元的凋亡与C57BL/6J小鼠年龄相关性听力损失密切相关。     

Effects of Noise-Induced Hearing Loss at Young Age on Voice Onset Time and Gap-in-Noise Representations in Adult Cat Primary Auditory Cortex

Here we show that mild hearing loss induced by noise exposure in early age causes a decrease in neural temporal resolution when measured in adulthood. We investigated the effect of this chronic hearing loss on the representation of a voice onset time (VOT) and a gap-duration continuum in primary auditory cortex (AI) in cats, which were exposed at the age of 6 weeks to a 120-dB SPL, 5-kHz 1/3 octave noise band for 2 h. The resulting hearing loss measured using auditory brainstem responses and cortical multiunit thresholds at 4–6 months of age was 20–40 dB between 1 and 32 kHz. Multiple single-unit activity was recorded in seven noise-exposed cats and nine control cats related to the presentation of a/ba/–/pa/ continuum in which VOT was varied in 5-ms step from 0 to 70 ms. We also obtained data for noise bursts with gaps, of duration equal to the VOT, embedded in noise 5 ms after the onset. Both stimuli were presented at 65 dB SPL. Minimum VOT and early-gap duration were defined as the lowest value in which an on-response, significantly above the spontaneous activity, to both the leading and trailing noise bursts or vowel was obtained. The mild chronic noise-induced hearing loss increased the minimum detectable VOT and gap duration by 10 ms. We also analyzed the maximum firing rate (FR_max) and the latency of the responses as a function of VOT and gap duration and found a significant reduction in the FR_max to the trailing noise burst for gap durations above 50 ms. This suggests that mild hearing loss acquired in early age may affect cortical temporal processing in adulthood.     

突发性聋患者急性期听皮层代谢~1H-MRS研究

目的利用氢质子磁共振波谱(hydrogen proton magnetic resonance spectroscopy,1 H-MRS)技术观察突发性聋患者急性期听皮层代谢变化。方法选取单侧突发性聋患者20例(右侧12例,左侧8例)和10例正常志愿者行1 H-MRS检测,测定双侧颞横回N-乙酰天门冬氨酸(NAA)、肌酸(Cr)、胆碱(Cho)、谷氨酰胺和谷氨复合物(Glx)的峰下面积并计算NAA/Cr、Cho/Cr、Glx/Cr比值,分析突聋组和对照组之间听皮层代谢的差异。结果突聋组与对照组比较,两侧听皮层NAA/Cr、Cho/Cr比值差异均无统计学意义(P>0.05));突聋组耳聋侧听皮层Glx/Cr比值与对照组比较差异无统计学意义(P>0.05),但聋耳对侧听皮层Glx/Cr比值高于对照组,差异有统计学意义(P<0.05)。结论 1 H-MRS可以在活体状态下检测听觉中枢组织代谢变化,突聋患者聋耳对侧听皮层存在谷氨酸代谢异常。     

Public Health Perspectives on Hearing Loss and Aging Outcomes: Age-Related Hearing Loss and the Development of Cognitive Impairment and Late-Life Depression: A Scoping Overview

Age-related hearing loss (ARHL) has been connected to both cognitive decline and late-life depression. Several mechanisms have been offered to explain both individual links. Causal and common mechanisms have been theorized for the relationship between ARHL and impaired cognition, including dementia. The causal mechanisms include increased cognitive load, social isolation, and structural brain changes. Common mechanisms include neurovascular disease as well as other known or as-yet undiscovered neuropathologic processes. Behavioral mechanisms have been used to explain the potentially causal association of ARHL with depression. Behavioral mechanisms include social isolation, loneliness, as well as decreased mobility and impairments of activities of daily living, all of which can increase the risk of depression. The mechanisms underlying the associations between hearing loss and impaired cognition, as well as hearing loss and depression, are likely not mutually exclusive. ARHL may contribute to both impaired cognition and depression through overlapping mechanisms. Furthermore, ARHL may contribute to impaired cognition which may, in turn, contribute to depression. Because ARHL is highly prevalent and greatly undertreated, targeting this condition is an appealing and potentially influential strategy to reduce the risk of developing two potentially devastating diseases of later life. However, further studies are necessary to elucidate the mechanistic relationship between ARHL, depression, and impaired cognition.     

A Chromosome 17 Locus Engenders Frequency-Specific Non-Progressive Hearing Loss that Contributes to Age-Related Hearing Loss in Mice

The 129S6/SvEvTac (129S6) inbred mouse is known for its resistance to noise-induced hearing loss (NIHL). However, less is understood of its unique age-related hearing loss (AHL) phenotype and its potential relationship with the resistance to NIHL. Here, we studied the physiological characteristics of hearing loss in 129S6 and asked if noise resistance (NR) and AHL are genetically linked to the same chromosomal region. We used auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to examine hearing sensitivity between 1 and 13 months of age of recombinant-inbred (congenic) mice with an NR phenotype. We identified a region of proximal chromosome (Chr) 17 (D17Mit143-D17Mit100) that contributes to a sensory, non-progressive hearing loss (NPHL) affecting exclusively the high-frequencies (>24 kHz) and maps to the nr1 locus on Chr 17. ABR experiments showed that 129S6 and CBA/CaJ F1 (CBACa) hybrid mice exhibit normal hearing, indicating that the hearing loss in 129S6 mice is inherited recessively. An allelic complementation test between the 129S6 and 101/H (101H) strains did not rescue hearing loss, suggesting genetic allelism between the nphl and phl1 loci of these strains, respectively. The hybrids had a milder hearing loss than either parental strain, which indicate a possible interaction with other genes in the mouse background or a digenic interaction between different genes that reside in the same genomic region. Our study defines a locus for nphl on Chr 17 affecting frequencies greater than 24 kHz.     

Hearing and Age-Related Changes in the Gray Mouse Lemur

In order to examine auditory thresholds and hearing sensitivity during aging in the gray mouse lemur (Microcebus murinus), suggested to represent a model for early primate evolution and Alzheimer research, we applied brainstem-evoked response audiometry (BERA), traditionally used for screening hearing sensitivity in human babies. To assess the effect of age, we determined auditory thresholds in two age groups of adult mouse lemurs (young adults, 1–5 years; old adults, ≥7 years) using clicks and tone pips. Auditory thresholds indicated frequency sensitivity from 800 Hz to almost 50 kHz, covering the species tonal communication range with fundamentals from about 8 to 40 kHz. The frequency of best hearing at 7.9 kHz was slightly lower than that and coincided with the dominant frequencies of communication signals of a predator. Aging shifted auditory thresholds in the range between 2 and 50.4 kHz significantly by 12–27 dB. This mild presbyacusis, expressed in a drop of amplitudes of BERA signals, but not discernible in latencies of responses, suggests a metabolic age-related decrease potentially combined with an accompanying degeneration of the cochlear nerve. Our findings on hearing range of this species support the hypothesis that predation was a driving factor for the evolution of hearing in small ancestral primates. Likewise, results provide the empirical basis for future approaches trying to differentiate peripheral from central factors when studying Alzheimer’s disease-like pathologies in the aging brain.     

Clinical investigation of hearing loss in the elderly*

The prevalence of hearing loss increases with age. Epidemiological and histopathological studies relating hearing loss to age are reviewed and clinical evidence presented suggesting that hearing loss is due not only to age but also to disease processes known to be associated with hearing threshold deterioration. 80 elderly patients presenting with a hearing problem at hospital have been studied and compared with 287 ‘non-complainers’. 83% of the study group were found to have factors, additional to age, contributing to their hearing loss; 50% had a medical condition previously unrecognized; 30% were taking potentially ototoxic drugs. Audiometric measurements indicate that hearing thresholds of the elderly are influenced by numerous disease processes. Patients attending hospital with hearing impairment are at greater risk of having a vascular or biochemical abnormality than a group of elderly ‘non-complainers’. Elderly patients presenting with hearing loss should therefore be adequately investigated before being labelled as having presbyacusis.     

Classifying Human Audiometric Phenotypes of Age-Related Hearing Loss from Animal Models

Age-related hearing loss (presbyacusis) has a complex etiology. Results from animal models detailing the effects of specific cochlear injuries on audiometric profiles may be used to understand the mechanisms underlying hearing loss in older humans and predict cochlear pathologies associated with certain audiometric configurations (“audiometric phenotypes”). Patterns of hearing loss associated with cochlear pathology in animal models were used to define schematic boundaries of human audiograms. Pathologies included evidence for metabolic, sensory, and a mixed metabolic + sensory phenotype; an older normal phenotype without threshold elevation was also defined. Audiograms from a large sample of older adults were then searched by a human expert for “exemplars” (best examples) of these phenotypes, without knowledge of the human subject demographic information. Mean thresholds and slopes of higher frequency thresholds of the audiograms assigned to the four phenotypes were consistent with the predefined schematic boundaries and differed significantly from each other. Significant differences in age, gender, and noise exposure history provided external validity for the four phenotypes. Three supervised machine learning classifiers were then used to assess reliability of the exemplar training set to estimate the probability that newly obtained audiograms exhibited one of the four phenotypes. These procedures classified the exemplars with a high degree of accuracy; classifications of the remaining cases were consistent with the exemplars with respect to average thresholds and demographic information. These results suggest that animal models of age-related hearing loss can be used to predict human cochlear pathology by classifying audiograms into phenotypic classifications that reflect probable etiologies for hearing loss in older humans.     

Genome-Wide Association Study for Age-Related Hearing Loss (AHL) in the Mouse: A Meta-Analysis

Age-related hearing loss (AHL) is characterized by a symmetric sensorineural hearing loss primarily in high frequencies and individuals have different levels of susceptibility to AHL. Heritability studies have shown that the sources of this variance are both genetic and environmental, with approximately half of the variance attributable to hereditary factors as reported by Huag and Tang (Eur Arch Otorhinolaryngol 267(8):1179–1191, 2010). Only a limited number of large-scale association studies for AHL have been undertaken in humans, to date. An alternate and complementary approach to these human studies is through the use of mouse models. Advantages of mouse models include that the environment can be more carefully controlled, measurements can be replicated in genetically identical animals, and the proportion of the variability explained by genetic variation is increased. Complex traits in mouse strains have been shown to have higher heritability and genetic loci often have stronger effects on the trait compared to humans. Motivated by these advantages, we have performed the first genome-wide association study of its kind in the mouse by combining several data sets in a meta-analysis to identify loci associated with age-related hearing loss. We identified five genome-wide significant loci (<10⁻⁶). One of these loci confirmed a previously identified locus (ahl8) on distal chromosome 11 and greatly narrowed the candidate region. Specifically, the most significant associated SNP is located 450 kb upstream of Fscn2. These data confirm the utility of this approach and provide new high-resolution mapping information about variation within the mouse genome associated with hearing loss.     

Idiopathic Intracranial Hypertension Presenting as Auditory Neuropathy Hearing Disorder in a Child

Otologic manifestations are known to occur in patients with idiopathic intracranial hypertension (IIH), but the occurrence of sensorineural hearing loss, especially in pediatric populations, has been addressed in only a few reports. Here, we describe a pediatric patient who presented with IIH and severe bilateral hearing loss. The patient's hearing loss was diagnosed as a form of auditory neuropathy (AN) and resolved after prompt treatment of the increased intracranial pressure. This case points to a possible association between IIH and AN and suggests that IIH may potentially be a reversible cause of AN spectrum disorder. Laryngoscope, 129:E407–E411, 2019     

听皮层认知功能障碍与听力损失相关性的探讨

听力损失(hearing loss,HL)和认知功能(cognitive function,CF)有着密切的关系.耳蜗是听觉信息传入和传出的重要结构,即中枢听觉系统接收和反馈听觉信息的重要窗口.耳蜗精细结构就具有言语编码的功能,耳蜗的基底膜(basal membrane,BM)和毛细胞(hair cells,HCs)从...     

Envelope Coding in Auditory Nerve Fibers Following Noise-Induced Hearing Loss

Recent perceptual studies suggest that listeners with sensorineural hearing loss (SNHL) have a reduced ability to use temporal fine-structure cues, whereas the effects of SNHL on temporal envelope cues are generally thought to be minimal. Several perceptual studies suggest that envelope coding may actually be enhanced following SNHL and that this effect may actually degrade listening in modulated maskers (e.g., competing talkers). The present study examined physiological effects of SNHL on envelope coding in auditory nerve (AN) fibers in relation to fine-structure coding. Responses were compared between anesthetized chinchillas with normal hearing and those with a mild–moderate noise-induced hearing loss. Temporal envelope coding of narrowband-modulated stimuli (sinusoidally amplitude-modulated tones and single-formant stimuli) was quantified with several neural metrics. The relative strength of envelope and fine-structure coding was compared using shuffled correlogram analyses. On average, the strength of envelope coding was enhanced in noise-exposed AN fibers. A high degree of enhanced envelope coding was observed in AN fibers with high thresholds and very steep rate-level functions, which were likely associated with severe outer and inner hair cell damage. Degradation in fine-structure coding was observed in that the transition between AN fibers coding primarily fine structure or envelope occurred at lower characteristic frequencies following SNHL. This relative fine-structure degradation occurred despite no degradation in the fundamental ability of AN fibers to encode fine structure and did not depend on reduced frequency selectivity. Overall, these data suggest the need to consider the relative effects of SNHL on envelope and fine-structure coding in evaluating perceptual deficits in temporal processing of complex stimuli.     

Towards a Unifying Basis of Auditory Thresholds: The Effects of Hearing Loss on Temporal Integration Reconsidered

For signal detection and identification, the auditory system needs to integrate sound over time. It is frequently assumed that the quantity ultimately integrated is sound intensity and that the integrator is located centrally. However, we have recently shown that absolute thresholds are much better specified as the temporal integral of the pressure envelope than of intensity, and we proposed that the integrator resides in the auditory pathways first synapse. We also suggested a physiologically plausible mechanism for its operation, which was ultimately derived from the specific rate of temporal integration, i.e., the decrease of threshold sound pressure levels with increasing duration. In listeners with sensorineural hearing losses, that rate seems reduced, but it is not fully understood why. Here we propose that in such listeners there may be an elevation in the baseline above which sound pressure is effective in driving the system, in addition to a reduction in sensitivity. We test this simple model using thresholds of cats to stimuli of differently shaped temporal envelopes and durations obtained before and after hearing loss. We show that thresholds, specified as the temporal integral of the effective pressure envelope, i.e., the envelope of the pressure exceeding the elevated baseline, behave almost exactly as the lower thresholds, specified as the temporal integral of the total pressure envelope before hearing loss. Thus, the mechanism of temporal integration is likely unchanged after hearing loss, but the effective portion of the stimulus is. Our model constitutes a successful alternative to the model currently favored to account for altered temporal integration in listeners with sensorineural hearing losses, viz., reduced peripheral compression. Our model does not seem to be at variance with physiological observations and it also qualitatively accounts for a number of phenomena observed in such listeners with suprathreshold stimuli.     

老年性聋听觉认知障碍的研究进展

随着人口老龄化现象日趋显著,老年性聋伴随认知障碍发生率增加,二者的相关性及其深层的发病机制是近年来听觉认知领域的研究热点和临床关注的焦点.本文对近年来国内外关于老年性聋听觉认知障碍的相关研究文献进行了详细梳理,阐述老年性聋对认知障碍的发生机制上潜在的联系,并就两者深入研究的重点方向提出观点.     

Epidemiology of Hearing Loss

Epidemiology no longer concerns itself only with infectious diseases. Now it deals with the commoner non-infectious diseases in a population. In epidemiology, we deal with populations and this is the centre of the problem.

Data on more than 30 000 cases of hearing loss were statistically analysed for the period 1966–1971. The number of males was higher than that of females in spite of the fact that, in the population, there is an inverse ration. The ratio of males to females increased as a function of age.

The most frequent diseases were presbyacusis noise-induced hearing loss, sensorineural hearing loss of unknown origin, the different forms of chronic otitis and the consequence of these (cicatrisation, adhesive process, tympanosclerosis).

The grades of hearing loss were determined in the different pathological processes and the distribution of these grades was calculated according to age.

As regards sensorineural hearing loss, it was found that, among the patients older than 40 years, not only did the number of cases increase but the severity of the loss also.

The number of hearing losses due to chronic otitis increased only up to the age group of 20–30 years. The number of cicatrisations, adhesions and tympanosclerosis increased among the older patients also.

The grade of hearing loss caused by different conductive hearing increased with age. This was also observed in cases of tympanosclerosis in spite of the fact that these were clinically healed processes.

The majority of the hearing levels in cases of sensorineural hearing loss remained stationary. Amongst the treated cases, improvement was noted in 8%.

Most cases of sudden hearing loss occurred amongst the older patients (47% improved; 11.7% deteriorated; 41.3% remained unchanged).

Among the cases of sensorineural hearing loss caused by bacterial or viral agents, there was a greater chance for children and for the aged to sustain total deafness.