耳蜗电图对耳蜗传入突触病变诊断意义的探讨

耳蜗传入突触病变在临床上可表现为听神经病、隐性听力损失、耳蜗死区病.目前除听神经病,另外两类疾病主要依据主观测试,尚无明确可用于诊断的客观方法.耳蜗电图可早期发现耳蜗传入突触病变,本文就其对耳蜗传入突触病变诊断意义进行综述,为耳蜗病变的诊断和精准治疗提供依据.     

Effects of noise exposure on auditory brainstem response and speech-in-noise tasks: a review of the literature

Abstract

Objective: Short-term noise exposure that induces transient changes in thresholds has induced permanent cochlear synaptopathy in multiple species. Here, the literature was reviewed to gain translational insight into the relationships between noise exposure, ABR metrics, speech-in-noise performance and TTS in humans.

Design: PubMed-based literature search, retrieval and review of full-text articles. Study Sample: Peer-reviewed literature identified using PubMed search.

Results: Permanent occupational noise-induced hearing loss (NIHL) is frequently accompanied by abnormal ABR amplitude and latency. In the absence of NIHL, there are mixed results for relationships between noise exposure and ABR metrics. Interpretation of speech-in-noise deficits is difficult as both cochlear synaptopathy and outer hair cell (OHC) loss can drive deficits. Reductions in Wave I amplitude during TTS may reflect temporary OHC pathology rather than cochlear synaptopathy. Use of diverse protocols across studies reduces the ability to compare outcomes across studies.

Conclusions: Longitudinal ABR and speech-in-noise data collected using consistent protocols are needed. Although speech-in-noise testing may not reflect cochlear synaptopathy, speech-in-noise testing should be completed as part of a comprehensive test battery to provide the objective measurement of patient difficulty.     

Age-Related Changes in Processing Simultaneous Amplitude Modulated Sounds Assessed Using Envelope Following Responses

Listening conditions in the real world involve segregating the stimuli of interest from competing auditory stimuli that differ in their sound level and spectral content. It is in these conditions of complex spectro-temporal processing that listeners with age-related hearing loss experience the most difficulties. Envelope following responses (EFRs) provide objective neurophysiological measures of auditory processing. EFRs were obtained to two simultaneous sinusoidally amplitude modulated (sAM) tones from young and aged Fischer-344 rats. One was held at a fixed suprathreshold sound level (sAM1_FL) while the second varied in sound level (sAM2_VL) and carrier frequency. EFR amplitudes to sAM1_FL in the young decreased with signal-to-noise ratio (SNR), and this reduction was more pronounced when the sAM2_VL carrier frequency was spectrally separated from sAM1_FL. Aged animals showed similar trends, while having decreased overall response amplitudes compared to the young. These results were replicated using an established computational model of the auditory nerve. The trends observed in the EFRs were shown to be due to the contributions of the low-frequency tails of high-frequency neurons, rather than neurons tuned to the sAM1_FL carrier frequency. Modeling changes in threshold and neural loss reproduced some of the changes seen with age, but accuracy improved when combined with an additional decrease representing synaptic loss of auditory nerve neurons. Sound segregation in this case derives primarily from peripheral processing, regardless of age. Contributions by more central neural mechanisms are likely to occur only at low SNRs.     

Age-Related Changes in the Relationship Between Auditory Brainstem Responses and Envelope-Following Responses

Hearing thresholds and wave amplitudes measured using auditory brainstem responses (ABRs) to brief sounds are the predominantly used clinical measures to objectively assess auditory function. However, frequency-following responses (FFRs) to tonal carriers and to the modulation envelope (envelope-following responses or EFRs) to longer and spectro-temporally modulated stimuli are rapidly gaining prominence as a measure of complex sound processing in the brainstem and midbrain. In spite of numerous studies reporting changes in hearing thresholds, ABR wave amplitudes, and the FFRs and EFRs under neurodegenerative conditions, including aging, the relationships between these metrics are not clearly understood. In this study, the relationships between ABR thresholds, ABR wave amplitudes, and EFRs are explored in a rodent model of aging. ABRs to broadband click stimuli and EFRs to sinusoidally amplitude-modulated noise carriers were measured in young (3–6 months) and aged (22–25 months) Fischer-344 rats. ABR thresholds and amplitudes of the different waves as well as phase-locking amplitudes of EFRs were calculated. Age-related differences were observed in all these measures, primarily as increases in ABR thresholds and decreases in ABR wave amplitudes and EFR phase-locking capacity. There were no observed correlations between the ABR thresholds and the ABR wave amplitudes. Significant correlations between the EFR amplitudes and ABR wave amplitudes were observed across a range of modulation frequencies in the young. However, no such significant correlations were found in the aged. The aged click ABR amplitudes were found to be lower than would be predicted using a linear regression model of the young, suggesting altered gain mechanisms in the relationship between ABRs and FFRs with age. These results suggest that ABR thresholds, ABR wave amplitudes, and EFRs measure complementary aspects of overlapping neurophysiological processes and the relationships between these measurements changes asymmetrically with age. Hence, measuring all three metrics provides a more complete assessment of auditory function, especially under pathological conditions like aging.     

Hearing disorder from music; a neglected dysfunction

Conclusion: Music-induced acute acoustic trauma is not inevitably linked to hearing dysfunction as validated by conventional pure tone audiometry. Tinnitus is often in combination with hyperacusis. Our results point at ‘silent hearing loss’ as the underlying pathology, having afferent nerve terminal damage rather than hair cell loss as the structural correlate.

Objectives: Exposure to loud music is one of the most common causes of acute acoustic trauma, which adolescents and teenagers experience by voluntary exposure to loud music of sound levels up to 110?dB(A).

Methods: The clinical and psychophysical data of 104 consecutive patients with music-induced hearing disorder (MIHD) were analyzed to construct individual hearing and tinnitus profiles. In all cases, tinnitus was the presenting symptom.

Results: Hearing abilities were normal in about two-thirds of the tinnitus patients. Tinnitus was experienced most often as a high-frequency tone (83%). The Tinnitus Handicap Inventory (THI) scores ranged from 0 to 94 with an average score of 43.1. Visual analog scales (VAS) were used to assess tinnitus loudness (average 42.4) and annoyance (average 54.2), and tinnitus awareness was estimated (average 60.3). All VAS values correlated strongly with the THI. Hyperacusis was present in 65% and 71% of the patients reported sleeping disorders.     

Subclinical hearing loss associated with aging

ObjectiveContribute to clarifying the existence of subclinical hearing deficits associated with aging.DesignIn this work, we study and compare the auditory perceptual and electrophysiological performance of normal-hearing young and adult subjects (tonal audiometry, high-frequency tone threshold, a triplet of digits in noise, and click-evoked auditory brainstem response).Study sample45 normal hearing volunteers were evaluated and divided into two groups according to age. 27 subjects were included in the “young group” (mean 22.1 years), and 18 subjects (mean 42.22 years) were included in the “adult group.”ResultsIn the perceptual tests, the adult group presented significantly worse tonal thresholds in the high frequencies (12 and 16 kHz) and worse performance in the digit triplet tests in noise. In the electrophysiological test using the auditory brainstem response technique, the adult group presented significantly lower I and V wave amplitudes and higher V wave latencies at the supra-threshold level. At the threshold level, we observed a significantly higher latency in wave V in the adult group. In addition, in the partial correlation analysis, controlling for the hearing level, we observed a relationship (negative) between age and speech in noise performance and high-frequency thresholds. No significant association was observed between age and the auditory brainstem response.ConclusionThe results are compatible with subclinical hearing loss associated with aging.     

Preventive Effects of Ginkgo-Extract EGb 761® on Noise Trauma-Induced Cochlear Synaptopathy

Noise trauma-induced loss of ribbon synapses at the inner hair cells (IHC) of the cochlea may lead to hearing loss (HL), resulting in tinnitus. We are convinced that a successful and sustainable therapy of tinnitus has to treat both symptom and cause. One of these causes may be the mentioned loss of ribbon synapses at the IHC of the cochlea. In this study, we investigated the possible preventive and curative effects of the Ginkgo biloba extract EGb 761^® on noise-induced synaptopathy, HL, and tinnitus development in Mongolian gerbils (Meriones unguiculatus). To this end, 37 male animals received EGb 761^® or placebo orally 3 weeks before (16 animals) or after (21 animals) a monaural acoustic noise trauma (2 kHz, 115 dB SPL, 75 min). Animals’ hearing thresholds were determined by auditory brainstem response (ABR) audiometry. A possible tinnitus percept was assessed by the gap prepulse inhibition acoustic startle reflex (GPIAS) response paradigm. Synaptopathy was quantified by cochlear immunofluorescence histology, counting the ribbon synapses of 15 IHCs at 11 different cochlear frequency locations per ear. We found a clear preventive effect of EGb 761^® on ribbon synapse numbers with the surprising result of a significant increase in synaptic innervation on the trauma side relative to placebo-treated animals. Consequently, animals treated with EGb 761^® before noise trauma did not develop a significant HL and were also less affected by tinnitus compared to placebo-treated animals. On the other hand, we did not see a curative effect (EGb 761^® treatment after noise trauma) of the extract on ribbon synapse numbers and, consequently, a significant HL and no difference in tinnitus development compared to the placebo-treated animals. Taken together, EGb 761^® prevented noise-induced HL and tinnitus by protecting from noise trauma-induced cochlear ribbon synapse loss; however, in our model, it did not restore lost ribbon synapses.     

Impaired hippocampal Ca homeostasis and concomitant K channel dysfunction in a mouse model of rett syndrome during anoxia

Methyl-CpG-binding protein 2 (MeCP2) deficiency causes Rett syndrome (RTT), a neurodevelopmental disorder characterized by severe cognitive impairment, synaptic dysfunction, and hyperexcitability. Previously we reported that the hippocampus of MeCP2-deficient mice (Mecp2^−/y), a mouse model for RTT, is more susceptible to hypoxia. To identify the underlying mechanisms we now focused on the anoxic responses of wildtype (WT) and Mecp2^−/y CA1 neurons in acute hippocampal slices. Intracellular recordings revealed that Mecp2^−/y neurons show only reduced or no hyperpolarizations early during cyanide-induced anoxia, suggesting potassium channel (K⁺ channel) dysfunction. Blocking adenosine-5′-triphosphate-sensitive K⁺ channels (K_ATP-) and big-conductance Ca²⁺-activated K⁺ channels (BK-channels) did not affect the early anoxic hyperpolarization in either genotype. However, blocking Ca²⁺ release from the endoplasmic reticulum almost abolished the anoxic hyperpolarizations in Mecp2^−/y neurons. Single-channel recordings confirmed that neither K_ATP- nor BK-channels are the sole mediators of the early anoxic hyperpolarization. Instead, anoxia Ca²⁺-dependently activated various small/intermediate-conductance K⁺ channels in WT neurons, which was less evident in Mecp2^−/y neurons. Yet, pharmacologically increasing the Ca²⁺ sensitivity of small/intermediate-conductance K_Ca channels fully restored the anoxic hyperpolarization in Mecp2^−/y neurons. Furthermore, Ca²⁺ imaging unveiled lower intracellular Ca²⁺ levels in resting Mecp2^−/y neurons and reduced anoxic Ca²⁺ transients with diminished Ca²⁺ release from intracellular stores. In conclusion, the enhanced hypoxia susceptibility of Mecp2^−/y hippocampus is primarily associated with disturbed Ca²⁺ homeostasis and diminished Ca²⁺ rises during anoxia. This secondarily attenuates the activation of K_Ca channels and thereby increases the hypoxia susceptibility of Mecp2^−/y neuronal networks. Since cytosolic Ca²⁺ levels also determine neuronal excitability and synaptic plasticity, Ca²⁺ homeostasis may constitute a promising target for pharmacotherapy in RTT.     

Current concepts in cochlear ribbon synapse formation

In mammals, hair cells and spiral ganglion neurons (SGNs) in the cochlea together are sophisticated “sensorineural” structures that transduce auditory information from the outside world into the brain. Hair cells and SGNs are joined by glutamatergic ribbon‐type synapses composed of a molecular machinery rivaling in complexity the mechanoelectric transduction components found at the apical side of the hair cell. The cochlear hair cell ribbon synapse has received much attention lately because of recent and important findings related to its damage (sometimes termed “synaptopathy”) as a result of noise overexposure. During development, ribbon synapses between type I SGNs and inner hair cells form in the time window between birth and hearing onset and is a process coordinated with type I SGN myelination, spontaneous activity, synaptic pruning, and innervation by efferents. In this review, we highlight new findings regarding the diversity of type I SGNs and inner hair cell synapses, and the molecular mechanisms of selective hair cell targeting. Also discussed are cell adhesion molecules and protein constituents of the ribbon synapse, and how these factors participate in ribbon synapse formation. We also note interesting new insights into the morphological development of type II SGNs, and the potential for cochlear macrophages as important players in protecting SGNs. We also address recent studies demonstrating that the structural and physiological profiles of the type I SGNs do not reach full maturity until weeks after hearing onset, suggesting a protracted development that is likely modulated by activity.