Electrical stimulation activates two different sites within the guinea pig cochlea

This study investigates whether auditory brainstem responses (ABRs) can be used to assess the functioning of electrically stimulated cochleas. Electrically evoked auditory brainstem responses (EABRs) were recorded in guinea pigs with normal hearing and guinea pigs deafened by amikacin, a powerful ototoxic antibiotic, combined with diuretic aminooxyacetic acid (AOAA). Two different types of EABRs were observed in normal animals, depending on the electrical pulse intensity applied to the round window: long-latency brainstem responses were evoked by low stimulation intensities, short-latency brainstem responses by high intensities. The absence of effect of strychnine applied intracochlearly ruled out the possibility of medial efferents being involved in these responses. Conversely, an intracochlear application of tetrodotoxin (TTX), an Na⁺-channel blocker, resulted in the disappearance of both types of responses, attesting that the sites activated by the electrical stimulation were located within the cochlea. In AOAA/ amikacin poisoned cochleas, in which most of the hair cells were missing with apparently normal ganglion neurons, the long-latency brainstem responses evoked by low intensities were completely lacking. These findings suggest that low currents applied to the round window of the guinea pig cochlea primarily activate the hair cells, the neurons being directly excited at higher intensities.     

Electrophysiological measures of auditory function in the neurofilament-deficient mutant quail (Quv)

Auditory pathway electrophysiological studies were performed on the mutant quail 'Quv'. This mutation is known to result in neurofilament deficiencies of both the peripheral and central nervous systems. Auditory evoked brainstem responses (ABRs), electrocochleograms (EcochGs) and middle latency responses (MLRs) were evaluated. ABRs in Quv quails demonstrated markedly altered waveforms exhibiting longer latencies, absence of the later peaks and lower amplitudes. The EcochG showed normal cochlear microphonics with no obvious abnormalities in amplitude or latency and normal latencies for peak N1. Quv quails had a mild threshold elevation with a normal latency for the first peak of the ABR (P1). The Quv MLRs showed no significant differences in amplitude but they revealed a latency prolongation for peaks N0, Pa and Na relative to the controls. We have discovered abnormal findings of auditory evoked potentials in the neurofilament-deficient quail (Quv). We suggest that the smaller axonal size and axonal hypotrophy due to altered neurofilament expression underlies these abnormal auditory evoked potential responses.     

Otoakustische Emissionen, Hirnstammpotentiale, Tonschwellengehör und Sprachverständlichkeit bei auditorischer Neuropathie

The combined findings of "normal evoked otoacoustic emissions (EOAE) and absent or markedly disturbed auditory evoked potentials from the brainstem and/or cortex" has been named auditory neuropathy in the English literature. The pure tone thresholds in these patients range from mild to severe loss. The loss of speech comprehension is out of proportion in comparison to the pure tone threshold elevation. This combination of findings suggests that cochlear function and in particular outer hair cell function, is normal in these patients but also suggests that the inner hair cell / VIII nerve functional unit is abnormal. Disruption in neural synchrony has previously been postulated as a reasonable explanation for the absent auditory brainstem response while otoacoustic emissions are preserved. Because the long-latency auditory evoked potentials, not having the stringent synchrony requirements of the ABR, may also be missing, the term synchrony - disruption may be somewhat misleading. The literature about auditory neuropathy is reviewed here: We now know that a set of salient features distinguishes these patients from the majority of patients with sensorineural hearing loss or other described syndromes. The symptoms defining auditory neuropathy are mild, moderate or severe elevation of auditory thresholds to pure tone stimuli by air and bone conduction, absent to severely abnormal ABRs to high level stimuli, present otoacoustic emissions (that do not suppress with contralateral noise), word recognition ability poorer than expected from the pure tone hearing loss configuration (in cases with mild to moderate hearing threshold elevation) and absent acoustic reflexes to both ipsilateral and contralateral tones. The entire set of findings, consistently seen in these patients, supports the importance of the crosscheck principle in diagnostic evaluation especially in children with delayed and/or impaired language acquisition. It is of ponderous importance that this disorder is not being confused with sensory hearing loss.     

Otoacoustic emissions and brainstem evoked potentials in compound carriers of connexin 26 mutations

This study compares the effects of mutations in the gap junction protein connexin 26 (Cx26), on outer hair cells (OHCs), inner hair cells (IHCs) and auditory nerve/brainstem among carriers of these mutations. One hundred and twenty eight individuals, from a village with widespread consanguinity and congenital deafness, due to three Cx26 mutations, were selected among relatives of deaf persons, and divided into non-carriers, carriers of one mutation, homozygous to one mutation, or compound heterozygous carriers of two different mutations. Distortion product otoacoustic emissions (DPOAEs), auditory brainstem responses (ABRs) and audiometric evaluation were compared in these genetic groups. Hearing loss among homozygotes and compound heterozygotes was comparable and ranged from mild to profound. Most ABRs from these groups showed no responses or partial responses (peaks III, V) with prolonged latencies, but some individuals had all peaks at normal latencies. DPOAEs were absent, except sporadic responses. Carriers of one mutation had significantly smaller DPOAEs compared to non-carriers, although normal pure tone audiograms and ABRs were found in these groups. In conclusion, based on DPOAEs, Cx26 mutations may impact OHC function among carriers of one or two Cx26 mutations. IHC/nerve impairment among homozygotes and compound heterozygotes is variable. OHCs may be more susceptible to Cx26 mutations compared to IHCs and the auditory nerve and brainstem pathway activated by them.     

Vestibular evoked myogenic potentials in acoustic tumor patients with normal auditory brainstem responses

In order to clarify the utility of the vestibular evoked myogenic potential (VEMP) in detecting acoustic tumors, we report two patients who were found to have normal auditory brainstem responses (ABRs) and abnormal VEMPs. To record VEMPs, electromyographic responses to brief loud clicks (0.1 ms at 95 dBnHL) were amplified and averaged on the sternocleidomastoid muscle ipsilateral to the stimulated side. The stimulation rate was 5 Hz and the analysis time 50 ms. The first case was a 54-year-old woman in whom VEMPs were absent on the affected side while caloric tests and ABRs were normal. The second case was a 58-year-old woman whose VEMPs were absent on the affected side while caloric tests revealed a 22% canal paresis and normal ABRs. These results and previous studies suggested that the VEMP could reflect a function different from those evaluated by the ABR or the caloric test. We concluded that the VEMP can provide useful information in diagnosing acoustic tumors. Received: 17 March 1998 / Accepted: 29 July 1998     

Psychophysical measures of central auditory dysfunction in multiple sclerosis: neurophysiological and neuroanatomical correlates

Central auditory function was assessed in 15 patients with multiple sclerosis (MS) to determine whether the demyelinating lesions resulted in disruption of temporal processing. Auditory evoked potential (AEP) recordings included all three latency regions: Auditory brain stem responses (ABRs), midlatency responses (MLRs), and long-latency responses (LLRs). Two psychophysical tasks thought to involve temporal processing were used: a monaural-processing task (gap-detection) and a binaural-processing task (masking level difference; MLD). Further, AEP abnormalities and psychophysical performance deficits were related to lesion location, based on magnetic resonance imaging (MRI) scans. Reduced MLDs were seen in six MS subjects. Abnormal MLDs were always accompanied by abnormal ABRs and MLRs, and compared to subjects with normal MLDs, the subjects with abnormal MLDs were more likely to have bilateral abnormalities in the AEPs. Further, MLR indices of abnormal binaural interaction appeared to be specifically related to the psychophysical measure of binaural processing. The MRI data of these patients indicated widespread involvement of the auditory pathway. MS subjects with abnormal MRI signals restricted to levels caudal to the lateral lemniscus did not have abnormal MLDs. Gap-detection thresholds were more resistant to the effects of the demyelinating lesions; only two subjects had abnormal gap-detection thresholds. These subjects had extensive AEP abnormalities (bilaterally, in all three latency regions). The gap-detection thresholds were most specifically related to abnormalities of the LLRs. In addition, the subjects with elevated gap-detection thresholds were the only ones with a prolonged interval between the ABRs and MLRs. Thus, efficient neural conduction between the upper brain stem and auditory cortex appears to be crucial for normal monaural temporal processing. The results indicate that demyelinating lesions can cause deficits in temporal processing in the central auditory pathway. However, auditory temporal processing is not a unitary phenomenon since abnormalities at different levels of the auditory system disrupt different types of temporal processing. Finally, abnormal psychophysical performance was not seen in all subjects with AEP and MRI evidence of involvement of the auditory pathway; rather, these psychophysical measures appeared to be sensitive to disruption only in specific portions of the auditory system.     

A Dominantly Inherited Progressive Deafness Affecting Distal Auditory Nerve and Hair Cells

We have studied 72 members belonging to a large kindred with a hearing disorder inherited in an autosomal dominant pattern. We used audiological, physiological, and psychoacoustic measures to characterize the hearing disorders. The initial phenotypic features of the hearing loss are of an auditory neuropathy (AN) with abnormal auditory nerve and brainstem responses (ABRs) and normal outer hair cell functions [otoacoustic emissions (OAEs) and cochlear microphonics (CMs)]. Psychoacoustic studies revealed profound abnormalities of auditory temporal processes (gap detection, amplitude modulation detection, speech discrimination) and frequency processes (difference limens) beyond that seen in hearing impairment accompanying cochlear sensory disorders. The hearing loss progresses over 10–20 years to also involve outer hair cells, producing a profound sensorineural hearing loss with absent ABRs and OAEs. Affected family members do not have evidence of other cranial or peripheral neuropathies. There was a marked improvement of auditory functions in three affected family members studied after cochlear implantation with return of electrically evoked auditory brainstem responses (EABRs), auditory temporal processes, and speech recognition. These findings are compatible with a distal auditory nerve disorder affecting one or all of the components in the auditory periphery including terminal auditory nerve dendrites, inner hair cells, and the synapses between inner hair cells and auditory nerve. There is relative sparing of auditory ganglion cells and their axons.     

On the relationship between speech- and nonspeech-evoked auditory brainstem responses

Auditory brainstem response (ABR) reflects activation of the neural generators along the ascending auditory pathway when a sound is heard. In this study, we explored the relationship between brainstem encoding of click and speech signals in normal-learning children and in those with language-based learning problems. To that end, ABR was recorded from both types of stimuli. We found that the normal pattern of correlation between click- and speech-evoked ABRs was disrupted when speech-evoked ABRs were delayed. Thus, delayed responses to speech were not indicative of clinically abnormal responses to clicks. We conclude that these two responses reflect largely separate neural processes and that only processes involved in encoding complex signals such as speech are impaired in children with learning problems.     

Detailed Analysis of Auditory Brainstem Responses in Patients with Noise-induced Tinnitus

The role of the auditory brainstem in tinnitus is questionable. This study aimed comprehensively to assess auditory brainstem responses (ABRs) in patients suffering from noise-induced tinnitus (NIT). ABRs were recorded from 13 chronic NIT patients (21 ears) and 11 (21 ears) age and hearing matched control subjects without tinnitus. ABRs were recorded with scalp electrodes placed ipsilateral and contralateral to the stimulated ear, and in three orthonormal differential configurations. The ABRs were analyzed as a function of time, frequency and voltage space. A significantly enhanced ipsilaterally recorded, time domain wave III amplitude was observed for the tinnitus patients. This finding was not confirmed by any of the other ABR measures, which were indistinguishable between subject groups. Although this may be a spurious result, it nonetheless may point to an alteration in the functioning of the putative wave III auditory brainstem generator, which deserves further study.     

Auditory brainstem responses and usefulness of hearing aids in hearing impaired children with Cornelia de Lange syndrome

OBJECTIVE: To examine auditory brainstem evoked responses (ABRs) of children with Cornelia de Lange syndrome (CDLS) to evaluate hearing and the utility of hearing aids in hearing impaired cases. SUBJECTS AND METHODS: Thirteen Japanese infants and children with CDLS were studied. Behavioral observation audiometry and ABR were used to evaluate hearing. RESULT: Four different ABR patterns at 85 dB clicks were observed: no response in either ear (6 patients); clear ABRs in both ears (2 patients); no response in one ear but ABRs recorded in the other ear (3 patients); and no peaks after wave III in one ear and ABRs recorded in the other ear (2 patients). However, in 2 patients with no response in either ear at the first measurement, ABRs were recorded in one ear within 2 years. Three out of 13 patients exhibited better responses to sound through the use of hearing aids and auditory training. CONCLUSIONS: The fitting of hearing aids and early consistent training have a significant effect on auditory development in CDLS children in terms of making them aware of sound localization and the different types of environmental sound.     

Auditory brainstem responses, electrocochleograms, and cochlear microphonics in the myelin deficient mutant hamster 'bt'.

Electrophysiological studies of the auditory pathway were performed on the mutant hamster 'bt' which is known to have myelin deficiencies in the central nervous system. Auditory brainstem responses (ABRs), electrocochleograms (EcochGs), and cochlear microphonics (CMs) were recorded. ABRs in 'bt' demonstrated markedly transformed waveforms with significantly prolonged latencies. EcochG in 'bt' showed significantly prolonged N1 latencies of the compound action potentials (CAPs) while 'bt' showed normal CMs. The myelin deficient mutant hamster 'bt' may have myelin deficiencies not only in the brainstem auditory pathway but also in the cochlear nerve.     

Evaluation of inner hair cell and nerve fiber loss as sufficient pathologies underlying auditory neuropathy

Auditory neuropathy is a hearing disorder characterized by normal function of outer hair cells, evidenced by intact cochlear microphonic (CM) potentials and otoacoustic emissions (OAEs), with absent or severely dys-synchronized auditory brainstem responses (ABRs). To determine if selective lesions of inner hair cells (IHCs) and auditory nerve fibers (ANFs) can account for these primary clinical features of auditory neuropathy, we measured physiological responses from chinchillas with large lesions of ANFs (about 85%) and IHCs (45% loss in the apical half of the cochlea; 73% in the basal half). Distortion product OAEs and CM potentials were significantly enhanced, whereas summating potentials and compound action potentials (CAPs) were significantly reduced. CAP threshold was elevated by 7.5 dB, but response synchrony was well preserved down to threshold levels of stimulation. Similarly, ABR threshold was elevated by 5.6 dB, but all waves were present and well synchronized down to threshold levels in all animals. Thus, large lesions of IHCs and ANFs reduced response amplitudes but did not abolish or severely dys-synchronize CAPs or ABRs. Pathologies other than or in addition to ANF and IHC loss are likely to account for the evoked potential dys-synchrony that is a clinical hallmark of auditory neuropathy in humans.     

Electrocochleography in auditory neuropathy

Auditory neuropathy (AN) is a disorder characterized by the absence or the severe impairment of the auditory brainstem responses (ABRs) together with the preservation of otoacoustic emissions and/or cochlear microphonic (CM). We recorded transtympanic electrocochleography (ECohG) evoked by 0.1 ms clicks in one young adult and in four children having distortion product otoacoustic emissions and absent ABRs. In all but one patient CM and summating potential (SP) were present with normal threshold, and their amplitudes appeared comparable to or higher than the values obtained from subjects with normal hearing. The compound action potential (CAP) was absent in two patients while in one subject CM and SP were followed by a highly desynchronized neural activity. A broad CAP was found in two children and the threshold appeared clearly elevated in one of them, while it showed only a mild elevation in the other. No correlation was found between CAP and behavioral thresholds. These results suggest that ECohG can be useful in AN diagnoses since it is the only reliable tool in evaluating the auditory peripheral function in the presence of a desynchronized ABR.     

Progressive hearing loss in an infant in a neonatal intensive care unit as revealed by auditory evoked brainstem responses

We herein report a case of a 14-month-old infant who revealed a progressive hearing loss by repeated auditory evoked brainstem responses (ABR) during his 1 year stay in the neonatal intensive care unit (NICU). He was born prematurely with asphyxia, hyperbilirubinemia and respiratory distress. During his 1 year stay in the NICU he was under constant mechanical ventilation. Repeated ABRs over this year initially showed normal waves but subsequently demonstrated progressive hearing impairment (HI) leading finally to no responses. Possible causes of this progressive deafness (PF) include the multiple problems of asphyxia, hyperbilirubinemia and pulmonary disorders.     

Auditory brain stem responses of kernicterus infants

Auditory brainstem evoked responses (ABRs) and behavioral audiometry in 25 infants with kernicterus were studied to determine the level of the lesion causing their hearing disorders. ABR thresholds, peak latencies of wave I and V, and interwave latency of wave V-I were measured; behavioral audiometric thresholds were determined through conditioned orientation reflex audiometry (COR).Eighty-eight per cent of infants with kernicterus who showed ABR threshold elevation with respect to age-matched normals, were found to show ABR abnormalities associated with peripheral hearing loss, and 84% of these were found to have COR threshold elevation.The ABR abnormalities were threshold elevation of wave V, prolonged latency of wave I and V, and the absence of ABRs. However, no brainstem lesion pattern was found in our cases.Our results suggested that at least some lesions which produce hearing disorders in kernicterus occur in the cochlea or auditory nerve.     

Comparative study of middle-latency responses and auditory brainstem responses in elderly subjects

Auditory senescence is studied through an electrophysiological investigation of the brainstem, midbrain and thalamocortical tracts of auditory pathways. For this purpose, comparative electrophysiologic studies were carried out by recording middle-latency responses (MLR) and auditory brainstem responses (ABR) in elderly subjects in the 7th-8th and 9th decades of life and in a control group consisting of young subjects in the 3rd decade of life. All these subjects were free of otological, neurological, vascular and metabolic pathologic states. In elderly subjects, the statistical analysis of the results, especially of MLRs, showed a deterioration in the progression of information from the periphery to the center due to changes in morphology, increased latency, reduced amplitude and poorer reproducibility. Furthermore, a different behavior was noticed in females versus males. Indeed, the shorter latency of evoked potentials in the female control group was remarkably reduced in the elderly subjects. MLRs scan a wide tract of auditory pathways and give evident results even by adopting a juxtaliminal stimulation; therefore, they are a more complete and sensitive test than ABRs for the study of involutional processes.     

言语诱发听性脑干反应的潜伏期特性分析

目的探讨不同刺激强度下健康成人言语诱发听性脑干反应（speech evoked auditory brainstem response,speech-ABR）的潜伏期特性及其在脑干神经元编码言语信息中的意义。方法记录32例健康成人32耳在4种刺激强度（20、40、60、80dBSPL）、11.1次/s速率下的speech-ABR,分析不同强度条件下speech-ABR的潜伏期和相关性。结果 speech-ABR由一系列主波组成,分为起始部分（包括V和A波）、过渡部分（C波）、频率跟随部分（D-E-F波）和终止部分（O波）。随着强度的降低,各主波潜伏期逐渐延长,差异有统计学意义（P〈0.05）。强度降低20dBSPL级差时,潜伏期的平均延长值表现为V、A、C、O波接近,D、E、F波接近。不同强度下,V-A-C波潜伏期之间、D-E波潜伏期、E-F波潜伏期的相关性均有统计学意义,且相关系数大于0.40,其中V-A波潜伏期的相关系数大于0.80;强度降低时,潜伏期间的相关性有统计学意义的主波逐渐增多。结论健康成人speech-ABR各主波的潜伏期随着刺激强度降低而显著延长;起始反应和频率跟随反应的潜伏期及其显著相关性具有不同的变化特点。言语强度降低时,speech-ABR主波潜伏期的显著延长以及主波潜伏期间相关性的改变可能与言语的不易被识别有关。     

Lateral asymmetry in the ABR of neonates: evidence and mechanisms

Lateralized processing of auditory stimuli occurs at the level of the auditory cortex but differences in function between the left and right sides are not clear at lower levels of the auditory system. The current study is designed to (1) investigate asymmetric auditory function at the ear and brainstem in human infants and (2) investigate possible mechanisms for asymmetry at these levels. Study 1 evaluated auditory brainstem responses (ABRs) in response to high and low-level clicks presented to the right and left ears of neonates. Wave V was significantly larger in amplitude and waves III and V were shorter in latency when the ABR was generated in the right ear. Study 2 investigated two possible mechanisms of such asymmetry by (a) using contralateral white noise masking to activate the medial olivocochlear system and (b) increasing stimulus rate to reveal neural conduction and synaptic mechanisms. ABR wave V, evoked by clicks to the left ear, showed a greater reduction in amplitude with contralateral noise than the response evoked from the right ear. No systematic asymmetries in ABR latencies or amplitudes were found with increased stimulus rate. We conclude that (1) the click-evoked ABR in neonates demonstrates asymmetric auditory function with a small but significant right ear advantage and (2) asymmetric activation of the medial olivocochlear system, specifically greater contralateral suppression of ABR produced by the left ear, is a possible mechanism for asymmetry.     

Hearing threshold investigations in infants and children

The influence of age on the auditory brainstem responses (ABRs) of 39 normal infants (aged less than 6-18 months) and children (aged 19 months to 3.5 years) was investigated. While the ABR threshold of infants (mean value: 9.3 dB nHL) is still slightly higher than that of normal-hearing adults, children show a distribution which corresponds approximately to that of adults. The mean I-V interpeak interval of the ABRs of these children is slightly longer (4.1 ms) compared with a normal value in the range of 3.95 ms. Furthermore, a comparison was made between the threshold values measured by brainstem-evoked response audiometry and conditioned orientation reflex audiometry in 115 children of between 6 months and 3.5 years of age who were suspected to be hearing impaired. In the case of normally configurated ABRs there was an 86% agreement of thresholds (within the limits of +/- 10 dB) while it amounted to 66% in the case of ABR changes, which indicates brainstem lesions.