Auditory Nerve Brainstem Evoked Response Research Articles

Fluid stimulation elicits hearing in the absence of air and bone conduction—An animal study

Conclusion Cochlea can be directly excited by fluid (soft-tissue) stimulation. Objective To determine whether there is no difference in auditory-nerve-brainstem evoked response (ABR) thresholds to fluid stimulation between normal and animal models of post radical-mastoidectomy, as seen in a previous human study. Background It has been shown in humans that hearing can be elicited with stimulation to fluid in the external auditory meatus (EAM), and radical-mastoidectomy cavity. These groups differed in age, initial hearing, and drilling exposure. To overcome this difference, experiments were conducted in sand-rats, first intact, and after inducing a radical-mastoidectomy. Methods The EAM of five sand-rats was filled with 0.3 ml saline. ABR thresholds were determined in response to vibratory stimulation by a clinical bone-vibrator with a plastic rod, applied to the saline in the EAM. Then the tympanic membrane was removed, and malleus dislocated (radical-mastoidectomy model). The cavity was filled with 0.45 ml saline and the ABR threshold was determined in response to vibratory stimulation to the cavity fluid. Results There was no difference in ABR fluid thresholds to EAM and mastoidectomy cavity stimulation. Air-conduction stimulation from the bone-vibrator was not involved (conductive loss due to fluid). Bone-conduction stimulation was not involved (large difference in acoustic impedance between fluid and bone).

The mechanism of direct stimulation of the cochlea by vibrating the round window.

Active middle ear implants such as the vibrant sound bridge (VSB) have been placed on the round window (RW) in patients with conductive or mixed hearing loss, with satisfactory hearing results. Several observations show that the mechanism of RW stimulation is not completely understood. The purpose of the present study was to compare different coupling procedures between the transducer and the RW in order to contribute to an understanding of the mechanism of RW stimulation. Five fat sand rats underwent ablation of the left ear and opening of the right bulla, followed by baseline measurements of thresholds of auditory nerve brainstem evoked responses (ABR) to air and bone conduction click stimuli. Subsequently the malleus and incus were removed from the right middle ear, modeling a conductive hearing loss in which the VSB on the RW is indicated. In the next stage of the experiment, a rod attached to the bone vibrator was placed gently on the RW membrane and then on saline fluid applied to the RW niche. ABR thresholds were recorded following both placements. Mean baseline ABR threshold in response to air conduction stimuli was 48 ± 4 dB; mean ABR threshold when the rod was placed on the dry RW membrane was 99 ± 12 dB; mean ABR threshold when the rod was in the saline on RW niche was 79 ± 7 dB. ABR thresholds were better (lower) with stimulation of fluid on the RW membrane compared to direct stimulation of the RW, providing further evidence of a direct fluid pathway.

Air, bone and soft tissue excitation of the cochlea in the presence of severe impediments to ossicle and window mobility

Clinical conditions have been described in which one of the two cochlear windows is immobile (otosclerosis) or absent (round window atresia), but nevertheless bone conduction (BC) thresholds are relatively unaffected. To clarify this apparent paradox, experimental manipulations which would severely impede several of the classical osseous mechanisms of BC were induced in fat sand rats, including discontinuity or immobilization of the ossicular chain, coupled with window fixation. Effects of these manipulations were assessed by recording auditory nerve brainstem evoked response (ABR) thresholds to stimulation by air conduction (AC), by osseous BC and by non-osseous BC (also called soft tissue conduction-STC) in which the BC bone vibrator is applied to skin sites. Following the immobilization, discontinuity and window fixation, auditory stimulation was also delivered to cerebro-spinal fluid (CSF) and to saline applied to the middle ear cavity. While the manipulations (immobilization, discontinuity, window fixation) led to an elevation of AC thresholds, nevertheless, there was no change in osseous and non-osseous BC thresholds. On the other hand, ABR could be elicited in response to fluid pressure stimulation to CSF and middle ear saline, even in the presence of the severe restriction of ossicular chain and window mobility. The results of these experiments in which osseous and non-osseous BC thresholds remained unchanged in the presence of severe restriction of the classical middle ear mechanisms and in the absence of an efficient release window, while ABR could be recorded in response to fluid pressure auditory stimulation to fluid sites, indicate that it is possible that the inner ear may be activated at low sound intensities by fast fluid pressure stimulation. At higher sound intensities, a slower passive basilar membrane traveling wave may serve to excite the inner ear.

Assessment of inner ear bone vibrations during auditory stimulation by bone conduction and by soft tissue conduction

Soft tissue conduction (STC), a recently described mode of auditory stimulation elicited when the clinical bone vibrator is applied to skin sites over the head, neck, and thorax, complements air conduction (AC) and bone conduction (BC), elicited by the same vibrator. The study assessed skull bone vibrations induced during STC and BC stimulation. The experiments were conducted on fat sand rats. Thresholds of auditory nerve brainstem evoked responses (ABRs) were recorded and compared to the lowest-intensity sound stimuli that elicited vibrations at the bony vestibule of the inner ear detected by a laser Doppler vibrometer. Vibrations were detected during BC but not during STC stimulation. ABR was recorded to both STC and to BC stimulation. Low-intensity STC stimulation does not induce vibrations of the inner ear, showing that STC apparently does not involve mechanisms based on vibrations of bone.

Bone conduction activation through soft tissues following complete immobilization of the ossicular chain, stapes footplate and round window

Classically it has been thought that bone conduction activation at the mastoid leads to relative motion between the stapes footplate and the oval window due to inertial and to compression (distortion) mechanisms. However, several recent clinical findings and experimental manipulations may point to additional mechanisms. These manipulations were extended in the present study. In ten fat sand rats, following obliteration of one ear, auditory nerve brainstem evoked response (ABR) thresholds were recorded in response to broad band click stimuli, either air conducted (AC) through insert earphones or bone conducted (BC) delivered directly to the exposed skull bone. Following this, the entire ossicular chain, stapes footplate and round window were completely immobilized with super glue, leading to a mean AC threshold elevation of 44 dB, but to a mean BC threshold change (elevation) of only 3.5 dB. In this state of complete immobilization, the bone vibrator was applied to a pool of saline in the surgical area and ABR was elicited with a mean threshold which was not significantly different from that of the BC threshold. When the bone vibrator was then applied to the eye without touching the bone at the orbit, the resulting ABR threshold was about 20 dB greater than the BC threshold. In conclusion, BC stimulation can activate the cochlea without two mobile windows. Furthermore, the cochlea can be activated by a fluid pathway and by application of a bone vibrator to non-osseous sites (soft tissue conduction).

Several Mechanical Manipulations of the Wall of the Inner Ear Do Not Affect Air and Bone Conduction Auditory Thresholds

According to classic theories, auditory stimulation, whether air- or bone-conducted, has been thought to begin with sound-induced relative motion between the cochlear shell and the stapes footplate, producing a passive mechanical traveling wave along the basilar membrane. This study was designed to assess the effect of experimental mechanical manipulations of the cochlea on the auditory thresholds to air-conducted and bone-conducted stimulation. The left ear of Psammomys obesus (highest auditory sensitivity between 0.5 and 5.0 kHz) was initially ablated in all animals studied. After baseline recording of auditory nerve-brain stem evoked response (ABR) thresholds to air- and bone-conducted broadband click stimulation from the right ear, a hole was drilled in the vestibule of that ear in 3 animals. In 2 other animals, the round window of the animals was immobilized. In 3 additional animals, the round window was widely perforated. Repeat ABR thresholds were then determined. There was no change in ABR thresholds to both air- and bone-conducted stimulation following these manipulations. The ABR wave latency also did not change. It is likely that an alternative mode of cochlear excitation is possible.

Leupeptin reduces impulse noise induced hearing loss

BackgroundExposure to continuous and impulse noise can induce a hearing loss. Leupeptin is an inhibitor of the calpains, a family of calcium-activated proteases which promote cell death. The objective of this study is to assess whether Leupeptin could reduce the hearing loss resulting from rifle impulse noise.MethodsA polyethelene tube was implanted into middle ear cavities of eight fat sand rats (16 ears). Following determination of auditory nerve brainstem evoked response (ABR) threshold in each ear, the animals were exposed to the noise of 10 M16 rifle shots. Immediately after the exposure, saline was then applied to one (control) ear and non-toxic concentrations of leupeptin determined in the first phase of the study were applied to the other ear, for four consecutive days.ResultsEight days after the exposure, the threshold shift (ABR) in the control ears was significantly greater (44 dB) than in the leupeptin ears (27 dB).ConclusionLeupeptin applied to the middle ear cavity can reduce the hearing loss resulting from exposure to impulse noise.

Uniform comparison of several drugs which provide protection from noise induced hearing loss

BackgroundThe ability of drugs to reduce noise induced hearing loss (NIHL) has been evaluated in diverse experimental conditions (animal species, noise intensities, durations, assessment techniques, etc), making it difficult to assess their relative efficacy. The present study was designed to provide more uniform comparisons and to allow to a better understanding of the mechanism of the NIHL. Methods: The drugs studied included furosemide (loop diuretic) and the antioxidants N Acetyl-L-Cysteine, vitamins A, C, E with the vasodilator magnesium. Mice were exposed to a continuous broadband noise (113 dB SPL for 3.5 hours) and the NIHL was assessed in all animals before noise exposure and 1 week after with auditory nerve brainstem evoked responses (ABR) to broadband clicks and to 8 kHz tone bursts.ResultsEach of the drugs alone and in combination led to similar reductions in NIHL.ConclusionsThe loop diuretic furosemide, by reducing the magnitude of the endocochlear potential in scala media, probably depressed active vibrations of the outer hair cells and basilar membrane, resulting in reduction of free radical formation during the noise exposure. The antioxidants N Acetyl-L-Cysteine and vitamins A, C, E with the vasodilator magnesium presumably counteract the free radicals. Thus, the administration of the antioxidants to animals in which free radical formation had already been reduced by previous injection of furosemide did not have an additional protective effect on the NIHL.

How are the Inner Hair Cells and Auditory Nerve Fibers Activated without the Mediation of the Outer Hair Cells and the Cochlear Amplifier?

The present study was designed to assess whether, in the presence of a depression of the cochlear amplifier i.e. a sensorineural hearing loss (SNHL), the inner hair cells (IHCs) require the presence of a normal endocochlear potential for transduction. An SNHL was induced by injecting salicylic acid (which binds to the motor protein prestin in the outer hair cells), and then furosemide (which depresses the endocochlear potential) was injected. Furosemide did not cause an additional elevation of the threshold of the auditory nerve brainstem evoked response (ABR) over that induced by the salicylic acid injection. Exposure to noise was also used to induce a SNHL in other mice, and then furosemide was injected. Here too furosemide did not cause an additional ABR threshold elevation over that induced by the noise. These results show that the IHCs (and the auditory nerve) can be excited in the presence of a SNHL (i.e. without the cochlear amplifier) and in the absence of an endocochlear potential. Possible mechanisms of excitation in such a state are discussed.

Occluding the Round Window Causes No Change in Threshold, but an Increase in Hearing Loss Following Noise Exposure

To assess the effects of occluding the round window on the degree of hearing loss following exposure to broad band noise. Following opening of the middle ear bulla in both ears of ten sand rats, auditory nerve-brainstem evoked response (ABR) thresholds were determined in each ear separately using an insert earphone. The round window of one ear was then occluded with super-glue. The opposite ear was sham-operated. ABR thresholds were again assessed immediately. The animals were then exposed to 113 dB SPL broad band noise for 12 hours. 24 hours after the round window was occluded, which was 8-10 hours after the end of the noise exposure, ABR thresholds were again determined in each ear. In four control animals, the round window was blocked, but they were not exposed to noise. Following the noise exposure, the mean ABR threshold elevation in the round window blocked ears (54.5 +/- 5.5 dB) was significantly (p < 0.004) greater than that in the sham-operated ear (40.5 +/- 8.6 dB). In the four control ears, there was no change in ABR threshold 24 hours after the round window was occluded. Occluding the round window was not accompanied by a threshold elevation, but following noise exposure, the noise induced hearing loss was increased, probably by reducing the efficacy of an inherent protective mechanical mechanism.

Prior Heat Acclimation Confers Protection against Noise-Induced Hearing Loss

Exposure to intense noise stress can cause a permanent noise-induced hearing loss which is thought to be due to elevation of reactive oxygen species in excess of the inherent antioxidant mechanisms of the cell. However, preconditioning to low levels of stress of one type can activate cellular mechanisms leading to the elevation of antioxidant levels so that the cell is then better able to tolerate subsequent severe stress of a different type. This has been called cross-tolerance. Here, we tested this hypothesis by acclimating rats to a moderate heat stress (30 days at 34°C). The rats were exposed to 113 dB SPL noise for 3 days (12 h/day) in three different groups: heat acclimated then noise exposed; noise exposed and then heat acclimated; heat acclimated, then noise exposed and then heat acclimated again. Permanent changes in auditory function – auditory nerve brainstem evoked responses (ABR) and distortion product otoacoustic emissions (DPOAEs) – were evaluated in each of these animals and compared with those in rats exposed to noise only and in control groups of rats. Statistical evaluation of the results showed that when assessed with ABR, each of the heat-acclimated, noise-exposed groups was protected from the noise, even the group that was heat-acclimated after the noise exposure. When assessed with DPOAE, protection was statistically apparent only in the group that was heat acclimated, then exposed to noise, and not in the other groups. Thus, heat acclimation provides protection against permanent noise-induced hearing loss.

Effect of an initial noise induced hearing loss on subsequent noise induced hearing loss

The effect of previous noise induced hearing loss (NIHL) on subsequent NIHL was studied in rats. Three groups of animals were initially exposed to different durations of 113 dB SPL broad band noise (21 days, 3 days or 0 days – unexposed). Their permanent threshold shifts (PTS) from this exposure (PTS1) were evaluated using auditory nerve-brainstem evoked responses (ABR). All the animals were then noise-exposed for an additional 12 days, and the incremental PTS following this exposure (PTS2) was also assessed. The 21 day group showed the greater PTS1 [mean ± SD: 27.03 ± 6.78 dB, compared with 11.67 ± 10.47 dB (3 day group)] and the lowest PTS2 [9.84 ± 8.19 dB, compared with 13.33 ± 14.60 dB (3 day group) and 24.04 ± 12.4 dB (0 day group)]. This group also showed the highest total PTS and lowest SD following the two noise exposures [36.88 ± 6.29 dB, compared with 25.00 ± 12.68 dB (3 day group) and 26.35 ± 11.93 dB (0 day group)]. The results may be explained by the lower effective intensity of the second noise exposure for the animals with a large PTS1 compared to those with little or no NIHL from the first noise exposure.

The Neonate Has a Temporary Conductive Hearing Loss due to Fluid in the Middle Ear

Postnatal functional changes in the activity of the ear and auditory pathway in neonatal guinea pigs [from day of birth (postnatal day, PND = 0), PNDs 1–4, 7 and then weekly up to 7 weeks] were studied as a model of maturation of hearing in human neonates. On the day of birth there were signs of a conductive hearing loss: negative middle ear pressure, auditory nerve brainstem evoked response (ABR) threshold elevation, ABR wave 1 latency prolongation and low amplitude otoacoustic emissions. The conductive hearing loss is probably a result of the (amniotic) fluid found in the neonatal middle-ear cavity. Over the next PNDs, this conductive hearing loss was resolved. In order to confirm this neonatal conductive hearing loss and its resolution, saline was instilled into the middle ear of guinea pigs. This induced signs of a conductive hearing loss similar to those seen in the neonatal guinea pigs which disappeared with clearance of this fluid. Therefore it may be concluded that most of the changes in auditory function seen over the first PNDs are due to absorption of amniotic fluid from the middle-ear cavity.

The latency of auditory nerve brainstem evoked responses to air- and bone-conducted stimuli

The auditory nerve brainstem evoked responses (ABRs) to bone conduction (BC) stimuli are longer in latency than those to air conduction (AC). In order to study the mechanism of this difference, ABR wave I was recorded in experimental animals in response to low intensity (0–20 dB above their threshold) logon stimuli delivered by BC and by using the same bone vibrator to generate the air-conducted stimulus. The BC stimuli were delivered to skull bone, and directly to the contents of the cranial cavity (brain and cerebrospinal fluid) through a craniotomy. ABR wave I in response to BC stimuli delivered to skull bone was significantly longer in latency than that to BC delivered on the brain, while there was no latency difference between AC stimuli and BC to the brain. Furthermore, the vibration (measured with an accelerometer) recorded on the brain during BC stimulation of skull bone was always delayed compared to that measured on the skull. Thus there is a delay in the transfer of vibratory energy from the skull bone to the underlying contents of the cranial cavity. From there, the delayed vibrations of the contents of the cranial cavity are transmitted to the inner ear. This is probably the mechanism of the longer latency BC response compared to the AC response.

Use of evoked potentials to objectively differentiate between selective vulnerability of cochlear and vestibular end organ function.

Auditory nerve brainstem evoked responses (ABR) have been used for several decades to investigate cochlear function. Recently techniques have been developed to elicit similar recordings from the vestibular end organs - short latency vestibular evoked potentials (VsEPs). Both ABR and VsEP reflect appropriate end organ function and may therefore be used to investigate the vulnerability of these end organs to various experimental insults, such as noise exposure and ototoxic drugs.

Bone conduction experiments in animals – evidence for a non-osseous mechanism

Bone conducted stimuli are used to differentiate between conductive and sensori-neural hearing loss. It has been thought that the main route for the transfer of vibratory energy from the point of application of the bone vibrator on the skull to the inner ear is completely osseous. An additional mechanism may play a prominent role. In rats, a bone vibrator was applied to the skull and also directly on the brain, after removing bone (a craniotomy), exposing the brain. Auditory nerve-brainstem evoked response (ABR) could be elicited not only with the vibrator on bone, but also with the vibrator directly on the brain. Similar results were obtained in guinea-pigs and fat sand rats. Noise masked this ABR. Extensive removal of skull bone did not alter the ABR to bone-conducted stimuli delivered to the exposed brain. Experimental elimination of the ossicular chain inertial mechanism and of the occlusion effect did not greatly alter the bone conduction response. A reduction in the fluid volume of the cranial cavity induced threshold elevations of the bone conducted ABR but not of the air conducted ABR. These findings can be interpreted as evidence that the ‘classical’ bone conduction mechanisms should be modified to include a major pathway for cochlear excitation which is non-osseous: when a bone vibrator is applied to the skull, the bone vibrations may induce audio-frequency sound pressures in the skull contents (brain and cerebro-spinal fluid) which are then communicated by fluid channels to the fluids of the inner ear.

Effect of hypoxemia and ethacrynic acid on ABR and distortion product emission thresholds

Various studies have shown that induction of hypoxemia in animals such that arterial blood oxygen tensions reach 20–30 mm Hg is accompanied by reversible threshold elevations of the auditory nerve-brain-stem evoked response (ABR). In this state, the endocochlear potential (EP) is depressed, causing a smaller potential difference across the hair cells and/or reduced activity of the cochlear amplifier of the outer hair cells. In order to test these possibilities, ABR threshold (an expression of the overall sensitivity of the cochlea) and changes in threshold of the cubic (2f 1 − f 2) distortion product emissions (DPE) (an expression of activity of the cochlear amplifier) were measured in the same cats while the EP was depressed by hypoxemia or by ethacrynic acid. During the episodes of hypoxemia, DPE thresholds were elevated by 10 dB while ABR thresholds were elevated by 22.8 dB. Therefore, it seems that a normal EP is necessary both for normal cochlear transduction (inner hair cells) and for normal cochlear amplification (outer hair cells). The human fetus in utero is relatively hypoxic and there is evidence that its auditory threshold is also similarly elevated. Therefore the threshold elevation in the fetus in utero, estimated to be about 20 dB, is a consequence of both reduced transduction current through the inner hair cells (about 10 dB) and an additional 10 dB reduction in the activity of the cochlear amplifier of the outer hair cells.

ABR interpeak latencies in rats are shorter at low click intensities.

There are conflicting findings concerning whether auditory nerve-brainstem evoked response (ABR) interpeak latencies (e.g. brainstem transmission time - BTT) are constant in response to different stimulus intensities. In order to study the effects of click intensity on the BTT, and to try to determine the mechanism of such an effect, ABR was recorded from 10 adult white Sabra rats in response to different click intensities. The stimulus intensity was reduced from the highest intensity generated by the equipment until no responses could be obtained. Band-reject (notched) noise was presented simultaneously with the clicks in order to restrict the region of basilar membrane activation. BTT decreased with decreasing click intensity and this was accompanied by a prolongation of the latency of wave I to a greater extent than that of wave IV. At high and intermediate intensities, wave I appeared as two split peaks. These effects were not abolished by the restricting notched noise. Possible mechanisms of these latency changes are considered.

Development of hearing in neonatal rats: Air and bone conducted ABR thresholds

While the human full-term neonate can hear at birth, in the rat the onset of auditory function as monitored by recording auditory nerve-brainstem evoked responses (ABR) has been reported to begin on post-natal day (PND) 12–14 and reaches adult thresholds at about 22 days. In order to determine the factors involved in this late onset and then rapid threshold improvement in rats, the ABR to both air conducted (AC) and bone-conducted (BC) auditory stimulation was determined in neonatal rats. ABR to maximal intensity BC stimuli (55 dB above adult rat ABR threshold — 55 dB HL∗) could be recorded from PND 7–8 while AC responses to 80 dB HL∗ stimuli, only from PND 11. The air-bone gap (a measure of conductive immaturities only) disappeared on PND 15. This shows that there are both conductive (external and middle ear — Air-bone gap) and sensori-neural (inner ear — BC threshold) immaturities in the neonatal rat; the conductive factors are resolved by PND 15 while the sensori-neural continue after that. With respect to conductive factors, it seems that the state of the ear canal is not important while the chief conductive factors involved probably include mesenchyme resorption and/or ossicular ossification. The chief sensori-neural factor may be the development of the endocochlear potential. It is likely that the human fetus in-utero undergoes similar stages of development.

Thyroid hormone induces earlier onset of auditory function in neonatal rats

The effect of thyroid hormone injection on the development of auditory function in neonatal rats was evaluated using auditory nerve-brainstem evoked responses (ABR). The hormone induced earlier onset of auditory function. In order to differentiate between conductive and sensorineural factors, both air-conducted (AC) and bone-conducted (BC) ABR responses were recorded. Neonatal rats were injected with thyroxine (T4), or with saline (control animals), from day of birth (post-natal day-PND-0), daily, until PND 9. AC- and BC-ABRs were recorded from PND 6 up to PND 20. It was found that both AC- and BC-ABR thresholds were lower in the T4-injected rats up to PND 15, after which no difference was found between the two groups. This indicated earlier maturity of both conductive (external and middle ears) and sensorineural (inner ear) factors and is probably due to the earlier appearance in the blood of higher T4 levels, following injection, than that occurring naturally during the neonatal period in these animals.