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PubMed2003

The ototoxic interaction of styrene and noise.

The interaction between noise and inhaled styrene on the structure and function of the auditory organ of the male Wistar rat was studied. The animals were exposed either to 600 ppm, 300 ppm or 100 ppm styrene (12 h/day, 5 days/week, for 4 weeks) alone or in combination with a simultaneous 100-105 dB industrial noise stimulant. Auditory sensitivity was tested by auditory brainstem audiometry at 1.0, 2.0, 4.0 and 8.0 kHz frequencies. Inner ear changes were studied by light microscopy. Exposure to 600 ppm styrene alone caused a 3 dB hearing loss only at the highest test frequency (8 kHz). Quantitative morphological analysis of cochlear hair cells (cytocochleograms) showed a severe outer hair cell (OHC) loss particularly in the third OHC row of the upper basal and lower middle coil. Exposure to noise alone caused only a mild hearing loss (2-9 dB), and only an occasional loss of OHCs (<1% missing). Exposure to the combination of noise and 600 ppm styrene caused a moderate flat hearing loss of 23-27 dB. The cytocochleograms showed a more severe damage of the OHCs than after exposure to 600 ppm styrene alone. The inner hair cells were found to be destroyed in some animals in the upper basal turn only after the combination exposure. Only in combination with noise exposure, the lower styrene concentrations (100 and 300 ppm) induced a hearing loss which was equivalent to that seen after exposure to noise alone. We conclude that: (1) There is an ototoxic interaction between styrene and noise. (2) Synergism is manifested only if styrene is applied in concentrations above the critical level (between 300 and 600 ppm in this study).

Animals↗
PubMed2003

Changes in spontaneous neural activity immediately after an acoustic trauma: implications for neural correlates of tinnitus.

Changes in spontaneous activity, recorded over 15-min periods before, immediately after and within hours after an acute acoustic trauma, were studied in primary auditory cortex of ketamine-anesthetized cats. We focused on the spontaneous firing rate (SFR), the peak cross-correlation coefficient (rho) and burst-firing activity. Multi-units (MUs) were grouped according to characteristic frequency (CF): MUs with a CF below the trauma-tone frequency (TF) were labeled as Be, those with a CF within 1 octave above the TF were labeled as Ab1 and those with a CF more than 1 octave above the TF were labeled as Ab2. Immediately after the trauma, the SFR was not significantly changed. The percentage of time that neurons were bursting, the mean burst duration, the number of spikes per burst and the mean inter-spike interval in a burst were enhanced. rho was locally increased in the Ab1-Ab2 and Ab2-Ab2 groups. A few hours post trauma, the SFR was increased in the Be and Ab2 groups, whereas burst-firing returned to pre-exposure levels. Moreover, rho was elevated in the Be-Ab2, Ab1-Ab2 and Ab2-Ab2 groups; this increase was significantly correlated to the changes in SFR. The results are discussed in the context of a neural correlate of tinnitus.

Animals↗
PubMed1996

Tonotopic organization of the sources of human auditory steady-state responses.

Steady-state responses (SSRs) or steady-state fields (SSFs) show maximum amplitude when tone pulses are presented at repetition rates near 40 Hz. This result has led to the hypothesis that the SSR/SSF consists of superimposed transient 'middle latency' responses which display wave periods near 40 Hz and summate with one another when phase locked by 40 Hz steady-state stimulation. We evaluated this hypothesis by comparing the cortical sources of the 40 Hz auditory SSF with sources of the middle latency Pa wave which is prominent in electrical and magnetic recordings, and with the cortical sources of the familiar N1 wave, at different carrier frequencies between 250 and 4000 Hz. SSF sources determined for the different carrier frequencies were found to display a 'medial' tendency tonotopy resembling that of the N1m (sources for the higher frequencies represented more deeply within the supratemporal sulcus), opposite the 'lateral' tendency tonotopy of the middle latency Pam (sources for the higher frequencies situated more laterally). A medial SSF tonotopy was observed in each of the subjects investigated, including three subjects for whom Pam and N1m maps were also available. These findings suggest that the 40 Hz SSF may not consist of summated or entrained middle latency responses, as has previously been proposed. Alternative mechanisms for the SSR are discussed.

Acoustic Stimulation↗
PubMed1997

Rate and adaptation effects on the auditory evoked brainstem response in human newborns and adults.

Auditory evoked brainstem response (ABR) latencies increased and amplitudes decreased with increasing stimulus repetition rate for human newborns and adults. The wave V latency increases were larger for newborns than adults. The wave V amplitude decreases were smaller for newborns than adults. These differences could not be explained by developmental differences in frequency responsivity. The transition from the unadapted to the fully adapted response was less rapid in newborns than adults at short (= 10 ms) inter stimulus intervals (ISIs). At longer ISIs (= 20 ms) there were no developmental differences in the transition to the fully adapted response. The newborn transition occurred in a two stage process. The rapid initial stage observed in adults and newborns was complete by about 40 ms. A second slower stage was observed only in newborns although it has been observed in adults in other studies (Weatherby and Hecox, 1982; Lightfoot, 1991; Lasky et al., 1996). These effects were replicated at different stimulus intensities. After the termination of stimulation the return to the wave V unadapted response took nearly 500 ms in newborns. Neither the newborn nor the adult data can be explained by forward masking of one click on the next click. These results indicate human developmental differences in adaptation to repetitive auditory stimulation at the level of the brainstem.

Acoustic Stimulation↗
PubMed1998

Nonlinear functional modeling of scalp recorded auditory evoked responses to maximum length sequences.

The purpose of this study was to model the adult human's scalp recorded evoked response to auditory pulses separated by varying inter pulse intervals (IPIs). The responses modeled probably reflect auditory nerve and brainstem generators. The subjects were 10 young adult humans with normal hearing. They were presented pseudo random sequences of pulses (maximum length sequences, MLSs) in order to characterize their system response. For the stimuli and the responses modeled accounting for temporal nonlinearities (interactions among the pulses) improved model performance only marginally. Nonlinear contributions to the models decreased with increasing interval between the input pulses. Increasing the memory of the model beyond 20 ms did not increase modeled performance dramatically. Model performance varied as a function of minimum IPI (MIPI) of the MLSs. At the shortest MIPI overall model performance deteriorated (due, in part, to a decrease in SNR), but nonlinear effects became relatively more important. At the longest MIPI performance also deteriorated, possibly due to the increasing influence of longer latency, more variable evoked potential components. Modeled performance generalized to responses recorded in the same recording session to the same and different MLSs. This study confirms the similarity between MLS linear kernels and conventionally averaged evoked responses--both are adapted responses reflecting the IPIs of the evoking stimuli.

Acoustic Stimulation↗
PubMed1999

Effects of a hair cell transcription factor, Brn-3.1, gene deletion on homozygous and heterozygous mouse cochleas in adulthood and aging.

The transcription factor Brn-3.1, is expressed in the inner ear hair cells throughout life and is necessary for the development of these cells. Mutant mice in which the Brn-3.1 encoding region has been deleted have no identifiable hair cells, greatly reduced numbers of spiral ganglion cells and are deaf. A mutation in the human homologue of this gene has been shown to be related to adult onset, sensorineural hearing loss (Vahava et al., 1998). The question whether haploinsufficiency in the mutant Brn-3.1 mouse with a mixed C57BL6/129Sv genetic background could affect the adult or aged cochlea was tested, therefore, by measuring the auditory brainstem responses and examining the cochlea's histologically at 2, 18 and 24 months of age. The heterozygotes had a comparable hearing to the wild-type animals and similar patterns of cochlear degeneration. Both groups showed an about 30 dB hearing loss beginning at 18 months of age, outer hair cell degeneration and loss of spiral ganglion neurons in the basal turn. There appeared to be no effect of Brn-3.1 haploinsufficiency on the mouse cochlea, implying that one intact copy of the gene is sufficient to maintain a normal cochlea.

Aging↗
PubMed2000

Inner hair cell loss leads to enhanced response amplitudes in auditory cortex of unanesthetized chinchillas: evidence for increased system gain.

Carboplatin preferentially destroys inner hair cells (IHCs) in the chinchilla inner ear, while retaining a near-normal outer hair cell (OHC) population. The present study investigated the functional consequences of IHC loss on the compound action potential (CAP), inferior colliculus potential (ICP) and auditory cortex potential (ACP) recorded from chronically implanted electrodes. IHC loss led to a reduction in CAP amplitude that was roughly proportional to IHC loss. The ICP amplitude was typically reduced by IHC loss, but the magnitude of this reduction was generally less than that observed for the CAP. In contrast to the CAP and ICP, ACP amplitudes were generally not reduced following IHC loss. In some animals, the ACP amplitude remained at pre-carboplatin values despite substantial IHC loss. However, in other animals, IHC loss led to an increase ('enhancement') of ACP amplitude. ACP enhancement was greatest at 1-2 weeks post-carboplatin, returning towards baseline amplitudes at 5 weeks post-carboplatin. In other animals, the ACP remained enhanced up to 5 weeks post-carboplatin. We interpret the transient and sustained enhancement of ACP amplitude following partial IHC loss as evidence of functional reorganization occurring at or below the level of the auditory cortex. These results suggest that the gain of the central auditory pathway increases following IHC loss to compensate for the reduced input from the cochlea.

Action Potentials↗
PubMed2000

Pattern of degeneration of the spiral ganglion cell and its processes in the C57BL/6J mouse.

Although degeneration of spiral ganglion cells has been described as a histopathologic correlate of hearing loss both in animals and humans, the pattern and sequence of this degeneration remain controversial. Degeneration of hair cells and of spiral ganglion cells and their dendritic processes was evaluated in the C57BL/6J mouse, in which there is a genetically determined progressive sensorineural loss starting in the high frequencies that is similar to the pattern commonly seen in the human. Auditory function was evaluated by brainstem evoked responses, and degeneration of hair cells, ganglion cells and their dendrites was evaluated histologically at 3, 8, 12 and 18 months of age. Progressive loss of auditory sensitivity was correlated with the loss of outer and inner hair cells and spiral ganglion cells and their dendritic processes. In addition, dendritic counts were consistently lower at a distal location in the osseous spiral lamina (i.e. near the organ of Corti) than at a proximal location (i.e. near the spiral ganglion), and the difference between the number of distal dendrites and the number of proximal dendrites tended to be greater with advancing age. These observations suggest an age-related progressive retrograde degeneration of spiral ganglion cells. Thus, in degenerating cochleas, some remaining spiral ganglion cells may have no distal dendritic processes near the organ of Corti. This may have implications for successful stimulation of the cochlear neuron in cochlear implantation.

Age Factors↗
PubMed2001

Pharmacological antagonism of the slow-activating delayed rectifying potassium channel (I(Ks)) has no effect on cochlear structure and function in vivo.

The experimental class III antiarrhythmic drug, L-768673, prolongs the refractory period of cardiac myocytes by selectively blocking the slow-activating delayed rectifying potassium (I(Ks)) channel. The I(Ks) channel has also been identified in vestibular dark cells and in the marginal cells of the stria vascularis. In the stria vascularis, the I(Ks) channel plays an important role in cochlear homeostasis. Genetic null deletion of the I(Ks) channel in mice and man results in profound hearing loss and cochlear pathology. Therefore, the purpose of the present study was to investigate the effect of L-768673 on the auditory function and cochlear morphology in rats using auditory brainstem-evoked response and light microscopy. Auditory testing was performed one week prior to dosing, following 14 days of administration and 28 days after the completion of dosing. L-768673 (50 or 250 mg/kg/day for 14 days), had no significant effects on auditory function or cochlear morphology. The results of this study suggest that high doses of L-768673 are not toxic to the inner ear of adult rats treated for 14 consecutive days, and that the ototoxic potential of orally administered L-768673 and similar I(Ks)-selective compounds is unlikely at doses within the therapeutic range.

Acetamides↗
PubMed1993

Representation of acoustic events in the primary auditory cortex.

One approach to the problem of specifying the contribution of the primary auditory cortex to auditory perception has been based on single-neuron recording techniques in animals. These experiments measure the response rates of individual neural elements to parametric variations in 1 or more stimulus dimensions. The patterns of response rates and response failures revealed by these manipulations are quantitative descriptions of the form and fidelity of the cortex's representation of those stimulus dimensions. This strategy has been used to advantage in studies of the cortical representation of the spectral content of auditory events, the spatial location of a sound, and the time structure of sounds. The data constitute new links between neural coding and behavioral performance in normal and impaired listeners.

Animals↗
PubMed1987

The effect of stimulus repetition rate on the auditory brainstem response in tumor and nontumor patients.

Auditory brainstem responses were recorded in two groups of adult subjects with asymmetric sensorineural hearing loss. Clicks were presented at repetition rates of 9.7, 39.7, 49.7, and 59.7/s. One group was composed of 20 patients with no known otoneurologic lesion (cochlear group), and one group was composed of 8 patients with a surgically confirmed acoustic neuroma in the ear with poorer hearing sensitivity (retrocochlear group). Detection of wave V at different repetition rates was not significantly different between the two groups. Average wave-V latency shift was not significantly different between the two groups as repetition rate increased from 9.7/s to 39.7/s but was significantly greater for the retrocochlear group as repetition rate increased from 9.7/s to 49.7/s and 59.7/s. However, the wave-V latency shift showed no improvement over the slow-rate interaural wave-V latency difference in discriminating between the two groups of patients. No significant correlation between the amount of wave-V latency shift and hearing loss at 2000 Hz or 4000 Hz was found for the ears with poorer hearing sensitivity.

Acoustic Stimulation↗
PubMed2002

Simultaneous intracerebral EEG recordings of early auditory thalamic and cortical activity in human.

We describe documented simultaneous intracerebral auditory evoked potentials from the auditory cortex and medial geniculate body (MGB) of a human patient. The MGB response lasted > 300 ms, with an initial negativity at 13.5 ms (N13), two positive peaks P21 and P29, and two broader negativities N50 and N200. P21 and N50 amplitudes were strongest for lowest tone frequencies, suggesting possible MGB tonotopic organization. Thalamic peaks were strongly interlaced with cortical activities recorded in Heschl's gyri before 30 ms: N13 preceded the first cortical component by 3.5 ms, then P21 and P29 preceded and lagged, respectively, the following two cortical polarity reversals by 1.5-2 ms. This study provides new functional data on the human MGB, and supports a more complex than simply relay-like role of the thalamus in sound perception.

Acoustic Stimulation↗
PubMedDate not supplied

[Hearing screening using acoustically evoked brain stem potentials in newborn infants and infants].

Reported failure rates of hearing screening using the conventional brainstem auditory evoked response (BAER) audiometry range from 5% to 60% with about 30% of the babies having normal hearing sensitivity on follow-up. Testing an automated infant screener using advanced evoked response technology the results of this new system are compared to a conventional evoked response system operated by skilled personal. 50 neonates (100 ears) were tested at a gestational age of 40-42 weeks. Normal results were obtained in all 25 neonates (50 ears) of the control group using both testing procedures. Out of 25 neonates (50 ears) at risk for congenital, peri- or postnatal hearing disorder abnormal results were seen with either one or both methods in 8 patients. In 4 out of 100 investigated ears (4%) results of the BAER infant screener were false positive and in 2 cases (2%) false negative. The possibilities and limits of this hearing screener are evaluated and its validity for newborn-screening compared to known follow-up studies are discussed.

Audiometry, Evoked Response↗
PubMed2005

A comparison of the mismatch negativity and a differential waveform response.

A mismatch negativity response (MMN) and a new differential waveform were derived in an effort to evaluate a neural refractory or recovery effect in adult listeners. The MMN was elicited using oddball test runs in which the standard and deviant stimuli differed in frequency To derive the differential waveform, the same standard and deviant stimuli were presented alone. MMN responses were obtained by subtracting the averaged responses to standards from the deviants. The differential waveforms were obtained by subtracting the averaged responses to standards presented alone from deviants presented alone. Scalp topography for the MMN and differential waveforms were similar. A significant (p <.05) positive and negative correlation was found between the earlier and later components of the bimodal MMN and the NI and P2 component of the differential waveform, respectively. Further, N1 and P2 of the differential waveform were significant (p <.05) predictor variables of early and late peak amplitudes of the MMN. These results suggest that refractory effects may overlay/modify the morphology of the MMN waveform.

Acoustic Impedance Tests↗
PubMed1999

ABR evaluation of ototoxicity in cancer patients receiving cisplatin or carboplatin.

The development of ototoxicity was evaluated using auditory brainstem response (ABR) in cancer patients randomized to receive a cisplatin-based chemotherapy (cisplatin dose: 70 mg/m2) or a carboplatin-based chemotherapy (carboplatin dose: 250 mg/m2). The ABR measurements were performed in a sound-treated room using 2000 clicks of alternating polarity at an intensity of 100 dB PESPL presented to the patients at a rate of 21 clicks per second. Of 59 patients, 21 (9 in the cisplatin group and 12 in the carboplatin group) met our pre-established criteria and were included in the ototoxicity study. Two patients of the cisplatin group developed evidence of clinically occult ototoxicity after two cycles of chemotherapy; the latency of wave V of the ABR increased significantly from 5.874 to 6.336 msec and from 5.826 to 6.458 msec in both patients; these patients had a hearing loss detected by conventional audiometry (125 to 8,000 Hz) after five and six cycles of chemotherapy, respectively. None of the 12 examined carboplatin patients developed ABR-measured ototoxicity or abnormal audiograms during treatment. Our results suggest that ABR might prove to be useful in detecting early hearing deterioration from cisplatin.

Aged↗
PubMed2002

A case study of pure word deafness: modularity in auditory processing?

AL, a woman with an acquired disturbance of auditory processing beginning in the second decade, was originally diagnosed as having pure word deafness. Recent analysis with a wide range of stimuli suggests that her comprehension deficit also extends to a subset of musical and non-verbal environmental sounds. The perceptual demands of the different auditory stimuli appear to account for part of the apparent material specificity. Additionally, over the years, the presumed temporal lobe cortical pathology has been supplemented by a mild to moderate, peripheral low-frequency hearing loss and evidence of dysfunction in lower level auditory processing pathways. The current peripheral dysfunction closely resembles cases recently labeled as auditory neuropathy. The diagnosis of pure word deafness should not be based on a limited set of auditory stimuli; additionally, a careful assessment using modern audiological techniques should be performed to evaluate peripheral auditory functions.

Achievement↗
PubMedDate not supplied

Brainstem responses to tone pip and click stimuli.

Brainstem auditory-evoked responses to tone pips at 1000, 2000, and 4000 Hz and clicks were evaluated for 17 normal-hearing adults. Wave V consistently emerged as the best indicator of auditory sensitivity, whereas waves II, III, and IV generally were not identifiable at lower intensities. An inverse relationship existed between wave V latency and intensity and between wave V latency and stimulus frequency. Large ranges were noted for the levels at which the various components became identifiable. Even though some frequency specificity may have occurred, the range of wave V latencies for 1000- and 4000-Hz tone pips demonstrated considerable overlap.

Adult↗