The cochlear microphonic potential does not reflect the passive basilar membrane traveling wave.

OBJECTIVE: Understanding the cochlear microphonic potential (CM) can contribute to its clinical usefulness, e.g. in auditory neuropathy where the CM is present, while auditory evoked neural potentials are absent. The space-time pattern of the basilar membrane traveling wave in the cochlea is thought to be responsible for generation of the CM and its pattern along the cochlea. This relationship was studied in two experiments. EXPERIMENT I: METHODS: The threshold of the CM was measured in animals before and after drilling a hole in the wall of the inner ear vestibule. Such a hole likely reduces the magnitude of the basilar membrane traveling wave. RESULTS: The hole did not cause a change in CM threshold. CONCLUSION: This is evidence that the passive basilar membrane traveling wave described by von Bekesy in cadavers in response to high intensity stimulation may not be the trigger for cochlear activation and CM generation at low intensities. EXPERIMENT II: METHODS: A saline filled tube provided fluid coupling between the cochlea of one animal and that of a second through the perforated round windows of their cochleae. RESULTS: In response to sound stimulation of animal 1, CM (and ABR) could be recorded in animal 2, even when animal 1 was no longer living. CONCLUSION: It is highly unlikely that a basilar membrane traveling wave could have been induced in cochlea 2 in these conditions. SIGNIFICANCE: It is therefore suggested that at low sound intensities, the initial event activating the cochlea in general and the CM in particular is the fluid pressures (condensations/rarefactions) induced in the cochlear fluids by sound-induced stapes footplate vibrations.

Somatosensory function in boys with ADHD and tactile defensiveness.

In this study, we tested for deficits in somatosensory function in boys with Attention Deficit Hyperactivity Disorder (ADHD) and tactile defensiveness (TD). The subjects were 67 boys with ADHD, sub-typed as TD (ADHD+TD+) or non TD (ADHD+TD-), matched with 60 "typical" children in the control group. Sixty nine percent of the boys with ADHD were categorized as TD. The groups were compared on three measures: (a) performance scores on subtests of the Sensory Integration and Praxis Test, (b) measurements of the Somatosensory Evoked Potential (SEP) and (c) ratings of the children's affective responses during tactile stimulation. Both ADHD groups differed from the control group on most study measures. No significant differences were found between the two ADHD subgroups on threshold and perceptual tests scores, except for Finger Identification. However, the TD+ group demonstrated significantly higher central SEP amplitudes than did the TD- group. Together, the results support claims that TD is related to central processing of somatosensory information, but not to anomalous tactile perception, with the exception of Finger Identification.

The contribution of the time locking of EEG waves to the generation of the auditory P300.

OBJECTIVES: To study the time locking of the 'natural' (delta, theta, slow alpha, fast alpha and beta) EEG waves during the generation of the P300 in passive (P300a) and active (P300b) auditory oddball paradigms in order to obtain insights into the generation of the P300 and into the transitions between background and evoked activity. METHODS: Tone burst stimuli (standard and deviant) were delivered to normal young adult subjects in passive and active oddball paradigms. The time distributions of EEG waves were analyzed in several frequency bands during background and post-stimulus periods. RESULTS: The ongoing background activity was modified by the deviant stimulus, producing the time locking of the positive delta, theta and alpha EEG deflections in the time range of the P300. This involved prolongation of the positive component of negative-positive wave complexes so that the positive wave was delayed into the time period of the P300. The time locking effects were more prominent in the delta and theta ranges, and differed in frequency components and scalp topography between the two paradigms. Not all deviant stimulus trials contributed deflections to the P300. The contributing trials can be selected, providing the basis for single trial analysis. CONCLUSIONS: The study of the time locking of the EEG waves in different frequency bands provides improved analysis of the P300 and an approach to single deviant stimulus trial analysis, that in turn can enhance signal-to-noise ratios. The results show that the time reorganization of EEG can be considered in the generation of P300 separately from the amplitude factor. SIGNIFICANCE: This can lead to improved analysis of normal and abnormal brain function in individual subjects.

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.

A new technique for the analysis of background and evoked EEG activity: time and amplitude distributions of the EEG deflections.

OBJECTIVES: The EEG during background activity and that evoked in response to sensory stimuli (evoked potential, EP) has traditionally been studied by averaging and by frequency analysis. These obscure trial to trial variability. A new analysis technique is presented here which leads to single trial analysis and to insight into the mechanisms of EP generation. METHODS: This technique is based on the identification of the EEG deflections recorded on the scalp before (background) and immediately after visual stimuli. A statistical description of the time and amplitude distributions of these deflections is defined and leads to the differentiation between background and evoked activity. RESULTS: In response to stimuli, the time and amplitude of ongoing deflections (background) are re-organized (time locking) and amplified, generating the EP. Not all stimulus trials are accompanied by an appropriate response. Separate analysis of those single trials that do contain a response deflection provides information on the exact timing, variability, amplitude, etc., of those EEG deflections which contribute to the EP. CONCLUSIONS: New EEG analysis techniques are described which provide single trial EP analysis and insight into mechanisms of EP generation.

The pathway for the transmission of external sounds into the fetal inner ear.

After at least 20 weeks gestation, the human fetus in utero is able to hear and respond to external and internal (maternal) sounds. The external sounds are attenuated by maternal tissues and fluids - higher frequencies by about 20 dB, and lower frequencies are only slightly reduced. The sounds in the amniotic fluid, which completely envelops the fetus, then reach the fetal inner ear by bone conduction. The sound pressure in the amniotic fluid induces skull vibrations which are transmitted directly into the contents of the cranial cavity (brain and CSF) and from there, presumably by fluid channels connecting them, into the cochlear fluids. A further stage of conductive attenuation is probably involved in this transmission. Since the fetus in utero receives oxygen by placental diffusion (less efficient than pulmonary diffusion), the fetal inner ear is hypoxic compared to that following birth (pulmonary oxygen diffusion). This leads to a reduction in the magnitude of the endocochlear potential, to a depression of cochlear transduction and amplification, and thus to an additional sensorineural component of threshold elevation in the fetus. Upon birth, these conductive and sensorineural attenuations are removed.

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.

The pathway enabling external sounds to reach and excite the fetal inner ear.

The human fetus in utero is able to respond to sounds in the amniotic fluid enveloping the fetus after about 20 weeks gestation. The pathway by which sound reaches and activates the fetal inner ear is not entirely known. It has been suggested that in this total fluid environment, the tympanic membrane and the round window membrane become 'transparent' to the sound field, enabling the sounds to reach the inner ear directly through the tympanic membrane and the round window membrane. It is also possible that sounds reach the inner ear by means of tympanic membrane--ossicular chain--stapes footplate conduction (as in normal air conduction). There is also evidence that sounds reach the fetal inner ear by bone conduction. Several animal and human models of the fetus in utero were studied here in order to investigate the pathway enabling sounds to reach and activate the fetal inner ear. This included studying the auditory responses to sound stimuli of animals and humans under water. It was clearly shown in all the models that the dominant mechanism was bone conduction, with little if any contribution from the external and middle ears. Based on earlier experiments on the mechanism and pathway of bone conduction, the results of this study lead to the suggestion that the skull bone vibrations induced by the sound field in the amniotic fluid enveloping the fetus probably give rise to a sound field within the fetal cranial cavity (brain and CSF) which reaches the fetal inner ear through fluid communication channels connecting the cranial cavity and the inner ear.

Objective method for differentiating between drug-induced vestibulotoxicity and cochleotoxicity.

HYPOTHESIS: An objective direct method is proposed to differentiate between drug-induced functional vestibulotoxicity and cochleotoxicity. BACKGROUND: Many substances are ototoxic. Although there are objective methods to directly evaluate functional cochlear toxicity (auditory nerve brainstem responses [ABR]), it is more difficult to assess direct functional ototoxicity to the various vestibular end organs. METHODS: Short-latency vestibular evoked potentials (VsEP) from different vestibular end organs and ABR, were used to assess functional impairment of the vestibular and cochlear end organs caused by daily injections of the aminoglycoside amikacin (known to be preferentially cochleotoxic) in guinea pigs. RESULTS: There was no significant change in the various VsEPs. whereas ABR thresholds were elevated, confirming the selective functional cochleotoxicity previously reported, as evaluated by other (mainly nondirect) methods. CONCLUSION: This study demonstrates the feasibility in general of using short-latency evoked potentials to evaluate functional cochleotoxicity and vestibulotoxicity of ototoxic drugs and to differentiate between them.

The effect of various durations of noise exposure on auditory brainstem response, distortion product otoacoustic emissions and transient evoked otoacoustic emissions in rats.

This study was designed to investigate the effect of various durations of noise exposure in animals on physiological responses from the cochlea which are also used clinically in humans: auditory brainstem response (ABR), transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs). Rats were exposed to 113 dB SPL broad-band noise (12 h on/12 h off) for durations of 3, 6, 9, 12, 15 and 21 days, and tested 24 h after cessation of the noise and again after a period of 6 weeks. ABR threshold to click stimuli and to a 2-kHz tone burst (TB), TEOAE energy content and DPOAE amplitude in the exposed rats were compared to those in a group of control rats not exposed to noise. ABR thresholds (click and TB) were significantly elevated in all exposure duration groups compared to control rats. DPOAE amplitudes and TEOAE energy content were significantly reduced. The mean ABR thresholds following 21 days exposure were significantly greater (click = 100 dB pe SPL; TB = 115 dB pe SPL) than those following 3 days exposure (click = 86 dB pe SPL; TB = 91 dB pe SPL). Linear regression analysis between recorded responses and duration of noise exposure (days) showed a significant increase in ABR thresholds of approximately 0.8-- 1.4 dB/day. TEOAE and DPOAE responses showed no such dependence on noise duration and were already maximally reduced after only 3 days of exposure. This can be explained by the possibility that short noise exposures may cause damage to the early, more active stages of cochlear transduction (as shown by TEOAEs and DPOAEs). As the noise exposure continues, further damage may be induced at additional, later stages of the cochlear transduction cascade (as shown by ABR). Thus, ABR seems more sensitive to noise duration than OAE measures.

Vestibular end-organ impairment in an animal model of type 2 diabetes mellitus.

OBJECTIVES/HYPOTHESIS: To define and assess the functional impairment of the vestibular part of the inner ear in a diabetic state, using a direct and objective test for evaluating the vestibular end-organ and an animal model for diet-induced type 2 diabetes mellitus. STUDY DESIGN: Prospective controlled animal study. METHODS: Two groups of sand rats (Psammomys obesus) were maintained on two different diets. The experimental group received a specially designed high-energy diet known to induce a diabetic state, and the control group a low-energy diet maintaining these animals in a normal metabolic state. After 1 month of documented hyperglycemia in the experimental group, recordings of vestibular evoked potentials (VsEPs) and recordings of auditory brainstem response (ABR) were conducted in all animals. The latency and the amplitude of the first wave of both responses, shown to reflect end-organ activity, were compared between the two groups. RESULTS: The mean latency of the first wave of the VsEPs was significantly (P = .002) prolonged and the amplitude was significantly (P = .005) decreased in the diabetic group in comparison to the control group. The latency of the first wave of ABR was significantly (P = .02) prolonged, the amplitude was not significantly decreased, and threshold was significantly elevated (P = .01) in the diabetic group. CONCLUSION: For the first time, using an objective assessment test, functional impairment of the vestibular part of the inner ear has been demonstrated in the diabetic metabolic state. Despite this being an animal study, these findings would seem to indicate that the vestibular-end-organ should be added to the long list of organs and tissues adversely affected by diabetes.

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.

Vestibular and cochlear ototoxicity of topical antiseptics assessed by evoked potentials.

OBJECTIVES/HYPOTHESIS: To evaluate and compare the effect of chlorhexidine gluconate, povidoneiodine, and alcohol-three antiseptics used before ear surgery-on the function of the vestibular and cochlear parts of the sand rat's inner ear. The assessment of damage is based on the recording of vestibular evoked potentials (VsEPs) and auditory brainstem response (ABR). STUDY DESIGN: Prospective controlled animal study. METHODS: Fat sand rats were randomly assigned to five different groups, each receiving topical application of a different agent: saline (control), gentamicin (ototoxic control), chlorhexidine, povidone-iodine, and alcohol. Right-side total labyrinthectomy was performed, and a polyethylene tube was inserted into the left (contralateral) middle ear. After baseline recordings were taken of VsEPs and ABR, each animal received five consecutive daily applications of the specific agent into the left middle ear. Three days after the fifth application, evoked potential recordings (VsEPs and ABRs) were repeated and compared with baseline measurements. RESULTS: Administration of saline affected neither VsEPs nor ABR. In contrast, as expected, neither of these responses could be recorded after gentamicin application. After application of chlorhexidine all waves disappeared in all sand rats. Alcohol caused the waves to disappear in some of the animals only. Povidone-iodine did not affect VsEP recordings and had only a small effect on ABR. CONCLUSIONS: Chlorhexidine and alcohol had a clear toxic effect on the vestibular and cochlear function of the inner ear of the sand rat, whereas povidone-iodine did not. Thus, taking into consideration that this is an animal study, it appears that povidone-iodine might be preferable to the other agents tested in disinfecting ears with a perforated tympanic membrane.

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.

Bone conduction experiments in humans - a fluid pathway from bone to ear.

Animal experiments in this laboratory have led to the suggestion that a major pathway in bone conduction stimulation to the inner ear is via the skull contents (brain and CSF). This hypothesis was now tested in humans. Auditory nerve brainstem evoked responses could be recorded in neonates to bone conduction stimulation over the fontanelle and audiometric responses were obtained in neurosurgical patients with the bone vibrator on the skin over a craniotomy. There were no differences in threshold between these responses and those obtained to bone conduction stimulation over skull bone in the same subjects. Audiometric thresholds in response to bone vibrator stimulation of the eye (a 'natural craniotomy') were no different from those to bone stimulation delivered to several sites on the head. Thus there is no need to vibrate bone in order to obtain 'bone conduction' responses. Bone vibrator thresholds to stimulation at the head region with thinnest bone (temporal) were better than those to stimulation at the forehead region which has much thicker bone, implying that the vibrations penetrate the skull at the site of the vibrator. In addition, the magnitude of vibration (acceleration) measured at various sites around the head in response to bone vibrator stimulation at a fixed point on the forehead generally decreased with distance from the point of vibration. Therefore it seems that the vibrations produced by a bone vibrator at a point on the head are also able to penetrate the skull, setting up audio-frequency pressures in the CSF which spread by fluid communications to the inner ear fluids, exciting the ear.

Effect of high-dose cisplatin on auditory brainstem responses and otoacoustic emissions in laboratory animals.

OBJECTIVE: The role of transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE) as early indicators of cisplatin-induced ototoxicity in three different rodent species--the guinea pig. the albino rat, and the fat sand rat (Psammomys obesus)--was investigated. In addition, an attempt was made to determine which of the three rodent species is most susceptible to cisplatin-induced ototoxicity as measured by auditory brainstem responses (ABR), BACKGROUND: There have been numerous clinical and experimental reports on cisplatin-induced ototoxicity, but to the authors' best knowledge, there has been no comparative report on the short-term effects of cisplatin on OAE measured with commercially available equipment between different rodent species. METHODS: Cisplatin was systemically administered as a single high dose (12 mg/kg intraperitoneally) to all three species, and the ototoxic effects were measured before and 3 days after the injection of cisplatin in the same animals, using ABR, TEOAE, and DPOAE. RESULTS: The ABR thresholds were significantly elevated in the guinea pigs and the albino rats but not in the sand rats. Significant depression of TEOAE energy and DPOAE amplitude occurred only in the guinea pigs. The depression of the DPOAE was greater than that of the TEOAE. The guinea pigs showed the greatest degree of ototoxicity (depression of ABR and OAE). CONCLUSIONS: Among the three rodent species, the guinea pig has the potential to be used as a sensitive animal model in studies of cisplatin ototoxicity. The study also showed that the recordings of TEOAE and DPOAE, in addition to ABR, are sensitive techniques for the assessment of cisplatin-induced ototoxicity.

Assessment of vestibular ototoxicity of ear drops by recording of vestibular evoked potentials to acceleration impulses.

INTRODUCTION: The cochlear ototoxicity of several ear drops is well documented in the literature, but very few studies exist on the vestibular ototoxicity of these topical drugs. GOAL OF STUDY: To develop an animal model for the assessment of the vestibular ototoxicity of ear drops. MATERIALS AND METHODS: Two animal groups, consisting of five fat sand rats (FSRs) each, underwent unilateral labyrinthectomy. Normal saline was topically applied into the middle ear cavity of rats in the first group for 7 days (control group). Rats in the second group were treated in the same way by topical gentamicin solution. Cochlear function was assessed by the recording of auditory evoked potential (ABPs) thresholds, and vestibular function was assessed by the recording of vestibular evoked potentials (VsEPs) to angular accelerations. RESULTS: In the control group, except for the amplitude of the first wave, there was no significant difference in the VsEPs recorded before and after topical application. In the gentamicin group, VsEPs could not be recorded after 7 days, and ABPs were recorded in one case only, with a threshold of 100 dB sound pressure level (SPL). CONCLUSION: VsEPs seem to be a reliable measure for evaluating the vestibular ototoxicity of topical ear drops.

Basic and clinical physiology of the inner ear receptors and their neural pathways in the brain.

The six receptors of the inner ear (cochlea, two otolith organs and three semicircular canals) share a common transduction unit made up of a sensory hair cell, a first order sensory neuron and the synapse between them. Displacement of the stereocilia in a particular direction leads to excitation of the hair cell and activation of the neuron. Electrical and mechanical reflections of these stages of transduction can be recorded non-invasively in humans and in animals. These include cochlear microphonic potentials, otoacoustic emissions, auditory and vestibular evoked potentials. The ability to record these activities can be used to track the development of inner ear function in the fetus and neonate and to study the effects of various ototoxic agents (e.g. noise) and drugs.

Development of short latency vestibular evoked potentials in the neonatal rat.

The development of short latency vestibular evoked potentials (VsEPs) was investigated in the neonatal rat. Using the appropriate stimulus (linear or angular acceleration impulses) and head orientation, responses elicited in various vestibular end-organs (utricle: x-VsEP; saccule: z-VsEP; lateral semi-circular canal: a-VsEP) were measured in rat pups at various ages between post-natal days (PND) 5 and 30, and compared to those recorded from adult animals. It was found that the VsEPs initially appeared on PND 6 (x-VsEPs and z-VsEPs) or 7 (a-VsEPs), and that by PND 8 the three responses could be recorded in all animals. The first wave of the responses, generated in the primary sensory nerve and reflecting end-organ activity, reached adult latencies and amplitudes by PND 10, showing rapid maturity of the responses. Auditory responses, on the other hand, develop at a later stage (from PND 11). The possible mechanisms involved in this differential maturation between vestibular and auditory activity are discussed.

The effect of head orientation on the vestibular evoked potentials to linear acceleration impulses in rats.

OBJECTIVE: To investigate the influence of linear acceleration impulses delivered when the head is held in different static head orientations, on the first wave of the short latency vestibular evoked potential (VsEP). The first wave is the compound action potential of the primary vestibular neurons synchronously activated. BACKGROUND: It has been shown previously that the VsEP elicited in response to linear acceleration is initiated mainly in the otolith organs. These organs are responsive to both dynamic and static linear forces, including gravity. METHODS: VsEPs to linear acceleration stimuli (4g) were recorded when the rats head was oriented so that a) the plane of the utricular macula was aligned with the plane of the stimulus, b) in supine position and c) with the head pitched up and down in various angles with respect to gravity (stimulus-head spatial relation remained constant) as compared to a reference position. RESULTS: With the stimulus aligned with the plane of the utricular macula, the amplitude of the first wave of the L-VsEPs was significantly larger than in the reference position. In the supine position, the amplitude of the first wave was significantly larger and the latency was significantly shorter. The amplitude of the first VsEP wave tended to be larger in the "head up" orientations as compared to the "head down" orientations (not statistically significant). CONCLUSIONS: These results demonstrate the influence of head position and gravity on the VsEPs to linear acceleration impulses, which is in accordance with their otolithic origin.