Acoustic responses after total destruction of the cochlear receptor: brainstem and auditory cortex.

Acoustically evoked neural activity has been recorded from the brainstem and auditory cortex of guinea pigs after complete destruction of the organ of Corti by the aminoglycosidic antibiotic amikacin. These responses to sound differ in important respects from the evoked potentials normally recorded from the auditory pathways. At the brainstem level they resemble the potentials reported by others after stimulation of the vestibular nerve.

Auditory sensori-neural alterations induced by salicylate.

Early after the development of aspirin, almost 150 years ago, its auditory toxicity has been associated with high doses employed in the treatment of chronic inflammatory diseases. Tinnitus, loss of absolute acoustic sensitivity and alterations of perceived sounds are the three auditory alterations described by human subjects after ingestion of large doses of salicylate. They develop over the initials days of treatment but may then level off, fluctuate or decrease, and are reversible within a few days of cessation of treatment. They may also occur within hours of ingestion of an extremely large dose. Individual subjects vary notably as to their susceptibility to salicylate-induced auditory toxicity. Tinnitus may be the first subjective symptom, and is often described as a continuous high pitch sound of mild loudness. The hearing loss is slight to moderate, bilaterally symmetrical and affects all frequencies with often a predominance at the high frequencies. Alterations of perceived sounds include broadening of frequency filtering, alterations in temporal detection, deterioration of speech understanding and hypersensitivity to noise. Behavioral conditioning of animals provides evidence for mild and reversible hearing loss and tinnitus, similar to those observed in humans. Anatomical examinations revealed significant alterations only at outer hair cell lateral membrane. Electrophysiological investigations showed no change in endocochlear resting potential, and small changes in the compound sensory potentials, cochlear microphonic and summating potential, at low acoustic levels. Measures of cochlear mechanical responses to sounds indicated a clear loss of absolute sensitivity and an associated broadening of frequency filtering, both of a magnitude similar to audiometric alterations in humans, but at extremely high salicylate levels. Otoacoustic emissions demonstrated changes in the mechano-sensory functioning of the cochlea in the form of decrease of spontaneous emissions and reduced nonlinearities. In vitro measures of isolated outer hair cells showed reduction of their fast motile responses which are thought to be at the origin of cochlear absolute sensitivity and associated fine filtering. Acoustically evoked neural responses from the eighth nerve to the auditory cortex showed reversible and mild losses of absolute sensitivity and associated broadening of frequency filtering. There is no evidence of a direct alteration of cochlear efferent innervation. Evidence was obtained for decreases in cochlear blood supply under control of autonomous innervation. Spontaneous neural activity of the auditory nerve revealed increases in firings and/or in underlying temporal synchronies. Similar effects were found at the inferior colliculus, mostly at the external nucleus, and at the cortex, mostly at the anterior and less at the secondary auditory cortex but not at the primary auditory cortex. These changes in spontaneous activity might underlie tinnitus as they affect mostly neural elements coding high frequencies, can occur without a loss of sensitivity, are dose dependent, develop progressively, and are reversible. Biochemical cochlear alterations are poorly known. Modifications of oxydative phosphorylation does not seem to occur, involvement of inhibition of prostaglandin synthesis appears controversial but could underlie changes in blood supply. Other biochemical alterations certainly also occur at outer hair cells and at afferent nerve fibers but remain unknown.

Reversible hearing impairment induced by lithium in the guinea pig.

Lithium salts remain one of the most widely used treatments for depressive illness. The mechanisms involved probably include reduction in free inositol. Visual perceptive disturbances can be a side effect of the treatment. We report here for the first time that chronic lithium treatment in the guinea pig induces a predominantly low frequency hearing loss and, in the longer term, loss of sensitivity is observed across the whole audiogram. The changes are reversed when treatment is arrested. The observations could be accounted for, at least partially, by a lithium-induced perturbation of the phosphoinositide cascade within the inner ear.

Distortion products in early stage experimental hydrops in the guinea pig.

The swelling of the endolymphatic spaces in experimental hydrops is likely to induce mechanical changes all along the cochlea. The selective atrophy of short and middle stereocilia on the outer hair cell above the first cochlear turn is expected to alter micromechanics and transduction. Two tone stimuli were employed in the present study to investigate cochlear distortion products in hydropic ears. Despite a substantial low frequency sensitivity loss on the CAP audiogram, 2f1-f2 distortion products recorded in the RWCM and the CAP were similar in hydropic ears and normal control ears which reflect the probable common origin of these responses--the base of the cochlea where no threshold shifts can be detected. On the other hand this distortion product in the otoacoustic emissions was considerably reduced in hydropic cochleas when the primary tones lay within the pathological part of the audiogram. The reduction of CDT emissions cannot be accounted for by hair cell loss since at the early stage of hydrops described here there is only discrete hair cell loss which is restricted to the apex of the cochlea. On the other hand the reduction in the amplitude of the CDT might reflect disturbance in hair cell function and/or cochlear mechanics above the first cochlear turn.

Acoustic responses recorded from the saccular bundle on the eighth nerve of the guinea pig.

Previous studies have demonstrated the existence of acoustic responses from the saccule in guinea pigs for stimulus intensities above 75 dB SPL. It is well known that the saccule receives a double afferent innervation: a bundle of the superior branch of the eighth nerve reaches its anterior part and another bundle of the inferior branch innervates its posterior part. These two bundles join just at the exit of the internal auditory meatus. An electrophysiological experiment was performed to investigate whether saccular acoustic responses could be similarly recorded from both bundles. Recordings from an electrode tip of 0.2 mm diameter were obtained in normal animals and also in animals with a complete and selective destruction of the cochlear sensory epithelium induced by treatment with an ototoxic antibiotic combined with a loop diuretic. In both normal and treated animals acoustic responses with the peculiar very short latency were specifically recorded in the area of the junction of the two bundles, they were of maximal amplitude on the bundle of the inferior branch. These data confirm in a more direct way the saccular origin of the short latency acoustic responses and indicate that they are probably conveyed in both saccular nerve bundles but mostly in that of the inferior branch of the eighth nerve. Finally these data show unequivocally that saccular acoustic responses exist in normal guinea pig ears.

Alterations of CAP audiogram by increased endolymphatic pressure and its relation to hydrops.

Most current theories regarding the inner ear pathology of Menières disease assume that there is an augmentation of the endolymphatic pressure due to the presence of hydrops. In this study normal hearing pigmented guinea pigs were employed to investigate the effect of increased endolymphatic pressure on the compound action potential (CAP) audiogram. All animals were implanted with an electrode on the round window and the CAP audiogram was determined prior to further surgery. The endolymphatic canal was then visualised by a posterior fossa intra-dural surgical approach. A hole was pierced in the canal and a cannula inserted. The CAP audiogram was again determined before, and at frequent intervals after, the application of hydrostatic pressure (0.5-1 cm Hg). A similar sequence of CAP sensitivity losses was observed within 2 h for 0.5 cm Hg or 15 min for 1 cm Hg. There was at first a very high frequency loss, followed by a very low frequency loss and finally a mid frequency sensitivity loss rendered the audiogram flat and lying around 50 dB sound pressure level. Given that the first characteristic index for experimental hydrops is a low frequency loss the present data suggest that an increase in endolymphatic pressure, as in these experiments, is likely to be a rather late pathological feature of hydrops. Indeed we have shown that a high frequency loss develops at a second phase during the evolution of hydrops.

Evidence for potassium-induced motility in type I vestibular hair cells in the guinea pig.

In higher vertebrates, vestibular epithelia contain two types of hair cells, type I and type II cells. Physiological properties of single nerve units have been correlated to the corresponding hair cell type and a better knowledge of the hair cell static and dynamic properties should help in understanding transduction and coding in the vestibular system. For the auditory system, isolated outer cochlear hair cells (OHCs) have provided a useful approach for electrophysiological studies and for observations of motile processes involved in the active control of cochlear micromechanics. The present study tests the hypothesis of motile properties in guinea-pig vestibular hair cells, using stimuli known to elicit motile events in OHCs. After exposure to a medium containing a high concentration in potassium (125 mM or 80 mM KCl), 19 of 26 type I hair cells showed an irreversible tilt of the neck region often accompanied by an obvious swelling of the cell body. In contrast, no shape changes were detected in type II cells. In response to extracellular electrical stimulation, no motility was observed in either type I or type II cells.

Rapidly fluctuating thresholds at the onset of experimentally-induced hydrops in the guinea pig.

Pigmented guinea pigs were chronically implanted bilaterally with a platinum electrode on each round window. After recovery the endolymphatic sac was destroyed and the duct blocked on one side only; the other side was employed as a control. The round window response thresholds on both sides were recorded several times per week over a three month period. There were three main results. A sensitivity loss of up to 20 dB was observed for frequencies between 250 Hz and 6.4 kHz within two weeks post-op. At the end of three months the threshold elevation for these frequencies was as much as 50 dB. On the other hand the thresholds for frequencies between 8 and 16 kHz remained within 10 dB of their pre-operative value for at least two months. The thresholds fluctuated with a shift of as much as 25 dB within 24 h. The threshold elevation was associated with a decrease in the latency, at threshold, of the round window AP response which at frequencies between 250 Hz and 6.4 kHz was as short as that for 8 kHz. This observation suggested that it was the base, only, of the cochlea which responded. The present study has indicated that experimentally induced endolymphatic hydrops in the guinea pig mimics well the progressive and fluctuating hearing loss characteristic of Ménière's disease.

Average spectrum of cochlear activity: a possible synchronized firing, its olivo-cochlear feedback and alterations under anesthesia.

Average spectrum of electrophysiological cochlear activity (ASECA) recorded from the cochlea or the eighth nerve is related to firing of auditory neurons and has been used recently in search of an objective measure of tinnitus both in animal models and in humans. Little is known about neuro-sensory processes underlying the spectral features of ASECA. The present study used awake and/or anesthetized animals and investigated effects of various sounds presented contralaterally and ipsilaterally. Contralateral stimulation with noise bands at frequencies above about 8 kHz and below acoustic interaural cross-talk decreased the amplitude of the 1 kHz peak of ASECA. When presented ipsilaterally noises produced either an increase or a decrease of this spectral peak when the acoustic bandwidth was respectively above or below 1.5 kHz. Pure tones when presented contralaterally had no detectable effect. When presented ipsilaterally pure tones with frequencies higher than about 4 kHz decreased the 1 kHz peak of ASECA. The detailed time course of sound-induced variations of the 1 kHz peak was measured by time averaging. The resulting response patterns resemble PST histograms of the auditory nerve. Sedation and anesthesia deepened the 500 Hz trough of ASECA and shifted it towards 400 Hz. Sedation induced a diminution and anesthesia an almost complete suppression of the decrease of the 1 kHz peak induced by contralateral noise. Overall these data indicate that ASECA would reflect synchronized firings and they provide evidence for an influence of olivo-cochlear feedback sensitive to the state of awakeness.

Atrophy of middle and short stereocilia on outer hair cells of guinea pig cochleas with experimentally induced hydrops.

Scanning electron microscopy was employed to investigate hair cell morphology at different stages in the development of experimentally induced hydrops in the guinea pig. A particular form of morpho-pathology, never before described, was identified as characteristic of hydropic cochleas. The pathology was characteristically identified as atrophy of the short and middle stereocilia on the outer hair cells while the inner hair cell stereocilia did not have such a pathology. The atrophy was restricted to the upper cochlear turns in remarkable correspondence with the low/middle frequency sensitivity loss and was detected only at the end of the period of fluctuating thresholds. These stereocilia perturbations appear therefore to be linked with the threshold fluctuations and represent the first evidence for a clear correlation between hair cell morphology and physiology in the experimental model of endolymphatic hydrops. Such a morphopathology might also be expected to occur in cochleas of Menière's patients but may have been overlooked in the past because of the discrete nature of the pathology.

Alterations of auditory nerve responses by hypoxia in normal and hydropic ears of awake guinea pigs.

Total interruption of blood or oxygen supply to the inner ear produces very rapid and drastic effects, whereas moderate decreases can be well tolerated by normal ears. In experimental endolymphatic hydrops some moderate alterations of cochlear vasculature have been described which might affect cochlear adaptation to moderate blood or oxygen deficiencies. In order to test this hypothesis an hypoxia at 5% oxygen was imposed for 30 min in normal and hydropic ears of awake guinea pigs and cochlear function was monitored with an electrode at the round window. Electrophysiological recordings used measures of compound action potential (CAP) amplitudes evoked by high-intensity tones, and of CAP thresholds. In normal ears hypoxia induced threshold elevations at all frequencies and decreases of CAP amplitude only for high frequencies. Hydropic ears presented similar or smaller threshold elevations but showed CAP amplitude decreases extending to lower frequencies and showed a much slower recovery both for CAP thresholds and amplitudes. The data indicate that hypoxia had different effects on auditory nerve responses evoked by high versus low intensity tones. The deleterious effects of hypoxia were increased in hydropic ears. Hypoxia-induced alterations were measured twice at one week intervals during which an anti-ischemic drug was administered to the animals; some beneficial effects of the drug treatment were observed on normal but not on hydropic ears.

Periodicity of long-term context can influence gap detection.

Temporal gap detection in bands of noise is a basic paradigm to investigate auditory temporal resolution. This study further examined the role of the long-term temporal organization for gap detection. Our experiments aimed at determining whether a gap superimposed on an amplitude-modulated noise was easier to detect when the amplitude modulation was regular--or periodic--than when it was not. Care was taken to ensure that the stimulus portion, where the gap was inserted, was exactly the same for both periodic and aperiodic conditions. Results show that gap detection in periodically modulated white noise (125 Hz fundamental frequency, or 8 ms duration from peak to peak) is easier (with a threshold 4.7 ms lower) than in an aperiodically modulated noise (modulation randomly varied from 5 to 18 ms). This effect is observed for variations of the modulation frequency from 125 to 1000 Hz. These results indicate that the regularity of long-term temporal organization of amplitude modulations in noise can improve the detection of a gap.

Eighth nerve auditory evoked responses recorded at the base of the vestibular nucleus in the guinea pig.

Anatomical and physiological studies of brainstem acoustic nuclei involving the classical ascending auditory pathway or the cerebellar and reticular pathways imply that all afferents from the cochlea terminate in the cochlear nucleus. In the experimental pathology of complete and selective destruction of the cochlea in the guinea pig acoustic responses still evoked at mid and high intensities, demonstrated to come from the saccule, show a pattern of far field evoked brainstem potentials quite different from that of normal animals. Intracranial electrophysiological investigations of the brainstem were undertaken in such pathological animals and in normal guinea pigs for comparison. In both cases acoustic responses were recorded at the base of the vestibular nucleus, showing a first peak corresponding to an eighth nerve projection and after a synaptic delay a second peak of local activation. In normal animals acoustic responses from the vestibular nucleus showing normal threshold and tuning curves may represent a direct projection from the cochlea.

Threshold elevation at high frequencies of the auditory nerve action potentials in acute versus chronic recordings in guinea pigs.

Thresholds of the auditory nerve compound action potential (CAP) responses to filtered clicks from 0.5 to 40 kHz, defining a CAP frequency threshold curve, have been determined in the same guinea pigs: (1) in acute conditions, the animal still anesthetized at the end of the operation for permanent implantation of a round-window electrode, and (2) several days later in the implanted awake and unrestrained animal. The results show higher CAP thresholds for high frequencies in acute conditions as compared to chronic recordings. This difference appears above about 12.5 kHz and increases progressively to around 40 dB at 40 kHz. Similar effects, although somewhat less pronounced, were observed during anesthesia alone in already implanted guinea pigs. Thes observations could explain the discrepancies which appear between electrophysiological thresholds, acutely recorded either from single fibers or whole-nerve responses, and behavioral audiograms. Moreover, in the accurate evaluation of the cochlea, slight impairments may be masked by this phenomenon as illustrated in guinea pigs treated with low doses of ototoxic antibiotic.

Intensity difference thresholds assessed with eighth nerve and auditory cortex potentials: compared values from cochlear and vascular responses.

In normal guinea pigs the eighth nerve compound action potential shows a latency of about 1 ms and the evoked early potential at the auditory cortex occurs after about 10 ms. Determination of auditory sensitivity with both responses using tone-bursts of variable rise/fall time and plateau duration showed they are responses to the onset of the stimulus since the existence of a plateau has no effect. Increases in stimulus rise time diminish the synchrony of both responses, the limits were found to be 2 ms for eighth nerve responses and 10 ms for cortical potentials. Amplitude modulation of continuous tones using these time values evokes clear responses at levels which apparently correspond to intensity difference thresholds measured behaviorally by other authors. Similar measures were performed on saccular acoustic responses, using the model of selective cochlear destruction. Evoked responses could also be observed at levels of amplitude modulation similar to those of normal animals. This fine sensitivity reinforces the idea of a functionality of the saccular acoustic reception.

Acute effects of noradrenalin related vasoactive agents on the ototoxicity of aspirin: an experimental study in the guinea pig.

Aspirin is known to be ototoxic when administered at high doses. Its mode of action is unknown but an alteration of the vascular function has been suspected. To further document this hypothesis, acute effects of some vasoactive agents on the ototoxicity of aspirin were tested in experiments on the guinea pig using sensori-neural electrophysiological responses and morphometry of the vessels of the stria and the spiral lamina. Electrophysiological measures showed no modification of sensory responses but neural responses revealed clear changes after administration of noradrenalin related agents, limited modifications after a drug acting partly as a serotonin antagonist, and no change after a dopaminergic agent. Morphometric studies showed no modification of the strial but some effect on the spiral vessels. The results are compatible with the hypothesis of a vascular involvement in the ototoxicity of aspirin and they point toward an interaction with the noradrenergic sympathetic cochlear system in the spiral lamina.

Plastic changes in ipsi-contralateral differences of auditory cortex and inferior colliculus evoked potentials after injury to one ear in the adult guinea pig.

In normal adult guinea pigs, evoked potentials recorded at the ipsilateral auditory cortex to monaural high-frequency acoustic stimuli present higher thresholds and lower amplitudes than at the contralateral cortex; in the inferior colliculus, such ipsi-contralateral differences (ICDs) are smaller than in the auditory cortex. Changes in the ICDs were studied after opposite ear injury. Following quasi-complete hair cell destruction induced by sisomicin injection into the contralateral inner ear, threshold ICDs almost disappeared after about two to six days and ipsilateral amplitudes progressively increased in two to three weeks. The occurrence of ICDs at higher auditory centers revealed in this study, indicates peculiar processing of high frequency stimuli in normal guinea pigs. The alteration of ICDs after opposite ear impairment provides a new possibility to study the auditory plasticity in adult animals.

Onset overmasking of a brief amplitude increment in a pure tone and sensorineural hearing impairment.

HYPOTHESIS: The goal of this investigation was to determine, in patients with sensorineural hearing loss who may show an audiologic alteration in onset overmasking, whether different pathologic conditions differ in this respect, and whether patients with a vestibular neurotomy damaging the cochlear efferents will be affected. BACKGROUND: Auditory detection of brief signals, when presented at the beginning of a simultaneous long masking sound, may require a higher acoustic level than when presented after several hundred milliseconds. The proposed explanation, in terms of auditory nerve fibers adaptation has been based on the observation of a proportionally smaller increase of firing in response to an amplitude increment at the onset of a stimulus. However, this may not explain all the data, and other underlying processes are certainly involved. The degree or type of sensorineural pathologic condition may be a contributing factor. In addition, the cochlear efferent system, which exhibits a time course and a high-frequency predominance compatible with that of onset overmasking, could be involved. METHODS: Onset overmasking of a brief amplitude increment in one pure tone was examined in 6 normal subjects, 12 patients who had undergone vestibular neurotomy, 8 subjects with Meniere's-like symptoms, 5 subjects with presbyacusis, and 3 patients with a small neuroma. Both ears of all subjects were tested. Detection thresholds, amount of onset overmasking, and differences between the two ears were examined. RESULTS: All results from subjects with presbyacusis and neuroma were within the range observed in the group of normal subjects. In the group of eight Ménière's syndrome patients, four had results outside the normal range, three had deteriorated detection, and one had better detection. Among the 12 subjects who had undergone neurotomy, 2 had better detection in the unoperated ear. CONCLUSIONS: The results from Ménière's patients indicate that, in addition to the previously reported improved detection threshold for short onset delay, a deterioration of detection thresholds may occur in some subjects. Overall, the results from neurotomized ears do not provide evidence for an involvement of cochlear efferents in this tested psychoacoustic task.

Contribution of increased endolymphatic pressure to hearing loss in experimental hydrops.

After the induction of experimental hydrops there follows a strict sequence of compound action potential (CAP) audiogram changes. Within days a low-frequency loss (below 8 kHz) is detected; within weeks a very high-frequency loss (above 8 kHz) develops; and finally within months the 8-kHz region is also affected. Following the application of excess pressure, presumably to the endolymphatic spaces, via a cannula placed in the endolymphatic duct, a sequence of CAP audiogram changes occurs that is not similar to that observed with hydrops. There is first a very high-frequency loss (above 4 kHz), then a very low-frequency loss (below 4 kHz), and finally the 4 kHz region is also affected and thresholds for all frequencies become even more raised. The data thus suggest that a slow accumulation of endolymph as induced by blockage of the endolymphatic duct does not produce the same disorder as a rapid onset of a high pressure applied at the base of the cochlea. In addition the data suggest that raised endolymphatic pressure is not likely to be significant in early stages of hydrops, but could contribute to the later high-frequency sensitivity losses.

Indication of a relation between speech perception and temporal resolution for cochlear implantees.

In order to better understand the reasons for success or failure of a cochlear implant system for various patients, it appears necessary to analyze the patients' basic psychophysical capacities in relation to speech perception. Five patients with intracochlear multichannel Ineraid implants were studied in terms of their performance on temporal analysis in relation to their perception of consonants. For temporal analysis we measured the detection of a silent gap in noise and of an interval between two clicks. For consonant perception we established a confusion matrix based on 12 consonants presented in a vowel-consonant-vowel context using the vowel /a/. The results showed a correlation between temporal resolution for two successive clicks at the most basal cochlear electrode used, and the perception of place of articulation of consonants. This finding indicates that delivering fine temporal coding can be crucial for the success of an implant and that for a given subject, optimal capacity for temporal resolution may serve as a criterion for choosing a basal electrode.