Synchronous auditory nerve activity in the carboplatin-chinchilla model of auditory neuropathy.

Two hallmark features of auditory neuropathy (AN) are normal outer hair cell function in the presence of an absent/abnormal auditory brainstem response (ABR). Studies of human AN patients are unable to determine whether disruption of the ABR is the result of a reduction of neural input, a loss of auditory nerve fiber (ANF) synchrony, or both. Neurophysiological data from the carboplatin model of AN reveal intact neural synchrony in the auditory nerve and inferior colliculus, despite significant reductions in neural input. These data suggest that (1), intact neural synchrony is available to support an ABR following carboplatin treatment and, (2), impaired spike timing intrinsic to neurons is required for the disruption of the ABR observed in human AN.

Characteristics of patients with gaze-evoked tinnitus.

OBJECTIVE: The authors describe symptoms and population characteristics in subjects who can modulate the loudness and/or pitch of their tinnitus by eye movements. STUDY DESIGN: Data were obtained by questionnaire. SETTING: The study was conducted at a university center and a tertiary care center. PATIENTS: Respondents had the self-reported ability to modulate their tinnitus with eye movements. RESULTS: Ninety-one subjects reported having gaze-evoked tinnitus after posterior fossa surgery involving the eighth nerve. Eighty-seven of them underwent removal of a vestibular schwannoma (acoustic neuroma), two had bilateral eighth nerve tumors (one underwent bilateral tumor removal; the other unilateral tumor removal), one underwent removal of a cholesteatoma, and one underwent removal of a glomus jugulare tumor. Seventeen subjects who had never had posterior fossa surgery reported gaze-evoked tinnitus. Of those with vestibular schwannomas, tumor size ranged from small (<2 cm) to large (>4 cm). The gender distribution was 48.3% male and 51.7% female. In 77% of patients, the gaze-evoked tinnitus was localized to the surgical ear or side of head; 21.8% had bilateral tinnitus that was louder in the surgical ear or side of head. In 86 of 87 subjects, loudness of tinnitus changed with eye movement. Eye movement away from the central (eyes centered) position increased the loudness of tinnitus in all 86 subjects who responded to this question. Seventy-three of 85 (85.9%) patients indicated that pitch changed with eye movement, with pitch increasing in 64/72 (88.9%) of them. Eighty-three of 87 (95.4%) patients reported total loss of hearing in the surgical ear. Seventy of 83 (84.3%) patients reported facial nerve problems immediately after surgery, 52 of 87 (60%) reported persistent facial weakness, and 16 of 87 (18.4%) patients reported persistent double vision. In those 17 subjects with gaze-evoked tinnitus and no posterior fossa surgery, the majority of respondents (14/17, 82.4%) were male. CONCLUSIONS: Gaze-evoked tinnitus after cerebellar pontine angle surgery is more common than was previously believed. In addition, posterior fossa surgery is not a prerequisite for the development of gaze-evoked tinnitus. It is likely that gaze-evoked tinnitus is a manifestation of functional reorganization. Gaze-evoked tinnitus could result from an unmasking of brain regions that respond to multiple stimulus/response modalities, and/or from anomalous cross-modality interactions, perhaps caused by collateral sprouting.

Sensitivity of unanesthetized chinchilla auditory system to noise burst onset, and the effects of carboplatin.

The gross near-field responses of the auditory nerve and inferior colliculus to noise burst stimuli were recorded through intracranially implanted electrodes in six unanesthetized chinchillas. Responses were studied as a function of stimulus plateau amplitude and rise time, both before and after a systemic dose of 75 mg/kg of carboplatin. Both recording sites showed sensitivity to stimulus level and rise time. Increases in stimulus level and decreases in stimulus rise time each produced increases in the response magnitude, and decreases in response latency. When the stimuli were re-specified as rate of pressure change at sound onset (Pa/s), the amplitude and latency of responses at each site were found to be a direct function of rate of sound pressure change. These data provide the first confirmation in unanesthetized animals of previous single unit observations in barbiturate-anesthetized cats. Carboplatin treatment resulted in a 20-80% loss of inner hair cells, a modest threshold elevation, and a 50-75% reduction in peak response amplitudes. The general patterns of sensitivity to stimulus level and rise time were not markedly affected by carboplatin, nor was the fashion in which response parameters (amplitude and latency) were ruled by rate of pressure change at sound onset.

The functional anatomy of gaze-evoked tinnitus and sustained lateral gaze.

OBJECTIVE: To identify neural sites associated with gaze-evoked tinnitus (GET), an unusual condition that may follow cerebellar-pontine angle surgery. METHODS: The authors examined eight patients with GET and used PET to map the neural sites activated by lateral gaze in them and seven age- and sex-matched control subjects. RESULTS: In patients with GET, tinnitus loudness and pitch increased with lateral gaze and, to a lesser extent, up and down gaze. Evidence for neural activity related to GET was seen in the auditory lateral pontine tegmentum or auditory cortex. GET-associated nystagmus appears to activate the cuneus and cerebellar vermis. These sites were found in addition to an extensive network that included frontal eye fields and other sites in frontal, parietal, and temporal cortex that were activated by lateral gaze in seven control subjects and the patients. The unilateral deafness in patients with GET was associated with expansion of auditory cortical areas responsive to tones delivered to the good ear. In addition to GET, unilateral deafness, end-gaze nystagmus, and facial nerve dysfunction were common. CONCLUSIONS: Patients with GET have plastic changes in multiple neural systems that allow neural activity associated with eye movement, including those associated with the neural integrator, to stimulate the auditory system. Anomalous auditory activation is enhanced by the failure of cross-modal inhibition to suppress auditory cortical activity. The time course for the development of GET suggests that it may be due to multiple mechanisms.

The human auditory brainstem response to high click rates: aging effects.

In 1999 J. Walton, M. Orlando, & R. Burkard (Hearing Research, 127, 86-94) investigated aging effects on auditory brainstem response (ABR) wave V latency using a tone-on-toneburst forward-masking paradigm. They found that at short forward-masking intervals, wave V latency shift was greater in normal-hearing older adults than in normal-hearing young adults for moderate level, high-frequency toneburst maskers and probes. It was not possible to evaluate wave I latency because stimulation and recording procedures did not produce a consistently observable wave I. In order to optimize the recording of wave I, the present study used a high-level (115 dB pSPL) click stimulus, combined with a tympanic membrane inverting electrode, and investigated the latencies and amplitudes of waves I and V across click rate. Young adults had hearing thresholds within normal limits, whereas older adults had normal hearing or mild threshold elevation. All data were collected and analyzed with a Nicolet Bravo. Using conventional recording procedures, ABRs were obtained at click rates of 11, 25, 50, and 75 Hz. Using maximum length sequences (MLSs), ABRs were obtained at 100, 200, 300, 400, and 500 Hz. Results across age groups were very similar. With increasing click rate, peak latencies increased, the I-V interval increased and peak amplitudes decreased. The most notable difference between age groups was that wave I amplitude was substantially smaller in the older subjects. It appears that changes in the ABR with increasing rate are remarkably similar in young and older adults when audiometric thresholds are normal or near-normal in both age groups.

Cochlear microphonics and otoacoustic emissions in chronically de-efferented chinchilla.

The effects of eliminating the olivocochlear bundle (OCB) on cochlear electromechanical properties were examined by measuring cochlear microphonics (CM) and distortion product otoacoustic emissions (DPOAEs) in chronically de-efferented chinchillas. The OCB fibers to the right ears were successfully sectioned in six out of 15 adult chinchillas via a posterior paraflocular fossa approach. At the end of the experiment, these ears were histologically verified as being deprived of both lateral and medial OCB fibers. The opposite (left) ears from the animals served as controls. Following de-efferentation, changes of the inter-modulation distortion components (2f(1)-f(2), f(2)-f(1), 3f(1)-2f(2), 3f(2)-2f(1)) varied, depending on the frequencies and levels of the stimuli. DPOAE amplitudes to low-level stimuli were within the 95% confidence intervals around mean DPOAE amplitudes of the control ears at all the frequencies (1-8 kHz). At high stimulus levels, DPOAE amplitudes increased by 5-20 dB at 1 and 2 kHz while remaining in the normal range at 4 and 8 kHz. In contrast, the CM input/output functions to stimuli from 1 to 8 kHz were significantly reduced by approximately 40-50% at all input levels. The results suggest that the OCB may play a role in modulating electrical properties of the outer hair cells and in reducing the magnitude of cochlear distortion to high-level stimuli.

Studies of interaural attenuation to investigate the validity of a dichotic difference tone response recorded from the inferior colliculus in the chinchilla.

In a previous paper (Arnold and Burkard, 1998) a dichotic f2-f1 difference tone (DT) auditory evoked potential from the chinchilla inferior colliculus (IC) was measured while presenting f1 (2000 Hz) to one ear and f2 (2100 Hz) to the other ear. This measurement paradigm could be used as a means to study binaural processing in an unanesthetized animal model. However, it is possible that this response is actually generated peripherally, as a result of acoustic crossover. The purpose of the present set of experiments was to investigate whether the dichotic DT is a true binaural phenomenon. Recordings were made from chronically implanted IC electrodes in unanesthetized, monaural chinchillas (left cochlea destroyed). In experiment 1, interaural attenuation (IA) was measured in two ways. First, IA was measured by comparing IC evoked potential thresholds obtained when stimulating the normal right ear and the dead left ear, using tone bursts (0.5-8 kHz). Mean values of interaural attenuation ranged from 50-65 dB across frequency (55 dB at 2000 Hz). Next, the DT was measured monaurally using f1 = 2000 and f2 = 2100 (L1 = L2). By comparing the mean DT input/output functions for monaural stimulation of the right and left ears, a mean value of IA for the tonal pair was estimated (approximately 69 dB). In experiment 2, the DT was measured with right monaural stimulation, while varying the relative levels of the primaries. A small DT could be seen with primary levels up to 30 dB apart, but not for greater level differences. Differences substantially greater than 30 dB would be expected in the crossover situation based upon IA. In experiment 3, the stimuli were presented dichotically (f1 to right ear, f2 to left ear and vice versa, L1 = L2) to determine whether acoustic crosstalk to the normal right ear would generate a DT. No DT was reliably observed in this condition. Taken together, these results suggest that the dichotic DT is a true binaural phenomenon, and not simply attributable to acoustic crossover.

Effects of background noise on audiometric thresholds during positron emission tomography: passive and active noise-reduction.

Position emission tomography (PET) is used to assess the functional activity of the human auditory brain; however, the activity detected by PET could be affected by ambient acoustic noise from the PET equipment. To evaluate these effects, we compared behavioural thresholds in the PET camera with those measured in an audiometric sound booth. Thresholds were measured with: (i) ER2 earphones, (ii) ER2 earphones + Cabot earmuffs, (iii) ER2 earphones + Bose Series II Aviation Headset with active noise-reduction off, and (iv) ER2 earphones + Bose Series II Aviation Headset with active noise-reduction on. Overall ambient noise level in the camera was 73 dB SPL and the maximum octave-band SPL was 68 dB SPL at 250 Hz. Threshold elevations in the PET camera were greatest with ER2 (17 dB, 125 Hz) earphones and lowest with ER2 earphones + Bose Series II Aviation Headset (8 dB at 250 Hz) with active noise-reduction. Thus, PET scanner noise had little or no effect on threshold when stimuli were presented through ER2 earphones covered with an activated Bose Series II Aviation Headset.

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.

Cu/Zn SOD deficiency potentiates hearing loss and cochlear pathology in aged 129,CD-1 mice.

Copper/zinc superoxide dismutase (Cu/Zn SOD) is a first-line defense against free radical damage in the cochlea and other tissues. To determine whether deficiencies in Cu/Zn SOD increase age-related hearing loss and cochlear pathology, we collected auditory brainstem responses (ABRs) and determined cochlear hair cell loss in 13-month-old 129/CD-1 mice with (a) no measurable Cu/Zn SOD activity (homozygous knockout mice), (b) 50% reduction of Cu/Zn SOD (heterozygous knockout mice), and (c) normal levels of Cu/Zn SOD (wild-type mice). ABRs were obtained by using 4-, 8-, 16-, and 32-kHz tone bursts. Cochleas were harvested immediately after testing, and separate counts were made of inner and outer hair cells. Compared with wild-type mice, homozygous and heterozygous knockout mice exhibited significant threshold elevations and greater hair cell loss. Phenotypic variability was higher among heterozygous knockout mice than among wild-type or homozygous knockout mice. Separate groups of wild-type and homozygous knockout mice were examined for loss of spiral ganglion cells and eighth nerve fibers. At 13 months of age, both wild-type and knockout mice had significantly fewer nerve fibers than did 2-month-old wild-type mice, with significantly greater loss in aged knockout mice than in aged wild-type mice. Thirteen-month-old knockout mice also had a significant loss of spiral ganglion cells compared with 2-month-old wild-type mice. The results indicate that Cu/Zn SOD deficiencies increase the vulnerability of the cochlea to damage associated with normal aging, presumably through metabolic pathways involving the superoxide radical.

Near-field responses from the round window, inferior colliculus, and auditory cortex of the unanesthetized chinchilla: manipulations of noiseburst level and rate.

Few studies have compared the response properties of near-field potentials from multiple levels of the auditory nervous system of unanesthetized animals. The purpose of this study was to investigate the effects of brief-duration noisebursts on neural responses recorded from electrodes chronically implanted at the round window, inferior colliculus and auditory cortex of chinchillas. Responses were obtained from seven unanesthetized chinchillas to a noiseburst-level and noiseburst-rate series. For the noiseburst-rate series, a 70 dB pSPL noiseburst was varied in rate from 10 to 100 Hz using conventional averaging procedures, and from 100 to 500 Hz using pseudorandom pulse trains called maximum length sequences (MLSs). Response thresholds were similar for the compound action potential (CAP), inferior colliculus potential (ICP) and auditory cortex potential (ACP). With decreasing noiseburst level, there were decreases in the amplitudes and increases in the latencies of the CAP, ICP and ACP. The shapes of the mean normalized amplitude input/output (I/O) functions were similar for the ICP and ACP, while the normalized I/O functions for the first positive peak (P1) and first negative peak (N1) of the CAP differed from each other and from the ICP and ACP. The slopes of the latency/intensity functions were shallowest for the CAP, intermediate for the ICP, and steepest for the ACP. With increasing rate, the latency shift was least for the CAP, intermediate for the ICP and greatest for the ACP. The amplitude of P1 of the CAP varied little with rate. All other potentials showed a pronounced decrease in amplitude at high stimulation rates. Excluding CAP P1, proportional amplitude decrease with rate was greatest for the ACP, intermediate for N1 of the CAP and least for the ICP. Responses were present in most animals at all recording sites, even for the highest rate (500 Hz) used in this study. For all potentials, the MLS procedure allowed the collection of a response at rates well above those where sequential responses would have overlapped using conventional averaging procedures.

Response magnitude and timing of auditory response initiation in the inferior colliculus of the awake chinchilla.

Recent single-unit studies in anesthetized cats have revealed that the latency and strength of transient responses to tone burst stimuli are determined largely by stimulus events in the first few ms of the signal. The present study sought to extend these findings by studying the inferior colliculus potential (ICP) in unanesthetized chinchillas. The ICP magnitude and latency were studied as a function of the plateau amplitude and rise time of noise burst stimuli. ICP amplitude increased with stimulus amplitude and decreased with stimulus rise time. ICP latency decreased with stimulus amplitude and increased with stimulus rise time. The absolute values of the ICP latencies confirmed that it is only the first few ms of the stimulus which determine the timing of response initiation, and therefore, that it is not the plateau level of the stimulus that directly determines the latent period. These data constitute a direct link between earlier single-unit studies in anesthetized animals and brainstem-evoked potential data in animals and man.

The functional anatomy of the normal human auditory system: responses to 0.5 and 4.0 kHz tones at varied intensities.

Most functional imaging studies of the auditory system have employed complex stimuli. We used positron emission tomography to map neural responses to 0.5 and 4.0 kHz sine-wave tones presented to the right ear at 30, 50, 70 and 90 dB HL and found activation in a complex neural network of elements traditionally associated with the auditory system as well as non-traditional sites such as the posterior cingulate cortex. Cingulate activity was maximal at low stimulus intensities, suggesting that it may function as a gain control center. In the right temporal lobe, the location of the maximal response varied with the intensity, but not with the frequency of the stimuli. In the left temporal lobe, there was evidence for tonotopic organization: a site lateral to the left primary auditory cortex was activated equally by both tones while a second site in primary auditory cortex was more responsive to the higher frequency. Infratentorial activations were contralateral to the stimulated ear and included the lateral cerebellum, the lateral pontine tegmentum, the midbrain and the medial geniculate. Contrary to predictions based on cochlear membrane mechanics, at each intensity, 4.0 kHz stimuli were more potent activators of the brain than the 0.5 kHz stimuli.

Auditory brainstem response forward-masking recovery functions in older humans with normal hearing.

We investigated the auditory brainstem response (ABR) recovery from forward masking using toneburst maskers and probes. Two subject groups matched for hearing thresholds were evaluated: normal-hearing young adults (21-40 years) and older subjects (63-77 years) with normal audiometric thresholds. Stimuli consisted of 1, 4 and 8 kHz tonebursts, with 2-4 cycle rise/fall time and no plateau. Forward maskers were tonebursts of the same frequency, with a 5 ms rise/fall time and a 20 ms plateau time. Probes were presented at 40 dB above threshold, and the forward masker was adjusted to a level that just eliminated the ABR to the 40 dB sensation level toneburst when the probe onset occurred at masker offset. Forward-masker intervals varied from 2 to 64 ms. ABR wave V latencies were similar for the young and old age groups regardless of toneburst frequency. Under forward-masking conditions, wave V latency was prolonged for the shorter intervals, and recovered to baseline latency by 64 ms. The forward-masker recovery functions were nearly identical for the two age groups for the 1 kHz toneburst. In contrast, there were clear differences in the recovery functions for the two age groups for the 4 and 8 kHz tonebursts. Specifically, the mean latency shift was greater for the aged group for forward-masker intervals of 16 ms or less. The two age groups showed identical latency shifts for longer forward-masker intervals. These data demonstrate prolonged recovery from forward masking in older human subjects. As these subjects had audiometric thresholds within normal limits, one plausible interpretation of this finding is that the prolonged recovery time is a manifestation of an aging effect on the central auditory nervous system rather than the periphery.

Neuroanatomy of tinnitus.

We tested the hypothesis that tinnitus was due to excessive spontaneous activity in the central auditory system by seeking cerebral blood flow (CBF) changes that paralleled changes in the loudness of tinnitus in patients able to alter the loudness of their tinnitus. We found CBF changes in the left temporal lobe in patients with right ear tinnitus, in contrast to bilateral temporal lobe activity associated with stimulation of the right ear. The tones activated more extensive portions of the brain in patients than controls. We conclude that tinnitus is not cochlear in origin and associated with plastic transformations of the central auditory system. We suggest that tinnitus arises as a consequence of these aberrant new pathways and may be the auditory system analog to phantom limb sensations in amputees.

Prevention of hearing loss in experimental pneumococcal meningitis by administration of dexamethasone and ketorolac.

Pneumococcal meningitis remains a significant cause of morbidity, particularly sensorineural hearing loss. Recent literature has suggested that a vigorous host immune response to Streptococcus [corrected] pneumoniae is responsible for much of the neurologic sequelae, including deafness, after bacterial meningitis. This study used a rabbit model of hearing loss in experimental pneumococcal meningitis to evaluate the therapeutic effect of two anti-inflammatory agents, dexamethasone and ketorolac, coadministered with ampicillin. Both adjunctive drugs minimized or prevented sensorineural hearing loss compared with placebo. Dexamethasone, administered 10 min before ampicillin, was particularly effective in minimizing mean hearing threshold change compared with placebo for both clicks (dexamethasone: 6.7-dB sound pressure level [SPL] vs. placebo: 33. 4-dB SPL, P=.0078) and 10-kHz tone bursts (dexamethasone: 8.4-dB SPL vs. placebo: 53.4-dB SPL, P=.0003). These findings support the beneficial role of anti-inflammatory agents in reducing the incidence of hearing loss from pneumococcal meningitis, especially if therapy is instituted early in the course of infection.

Modulation of tinnitus by voluntary jaw movements.

OBJECTIVE: The authors describe symptoms and population characteristics in patients with tinnitus who report the ability to control the loudness of their tinnitus by performing voluntary movements. DESIGN: The authors used a questionnaire. SETTING: The study was conducted at a tertiary care center. PATIENTS: Respondents have the self-reported ability to control the loudness of their tinnitus by performing voluntary movements. RESULTS: The authors describe symptoms and population characteristics in 93 patients with tinnitus (83% men, 17% women) who report the ability to control the loudness of their tinnitus by performing voluntary movements: 85% of these report jaw movements and 9% report eye movements affect their tinnitus. In the jaw-movement group, tinnitus loudness increased in 90%. Jaw movement affected the pitch in 51% with an increase in pitch reported by 90%. Other maneuvers, such as pressure applied to the head, affected tinnitus in many subjects. Tinnitus had a major impact on the lives of the authors' respondents: 27% registered mild to moderate depression and 8% moderate to severe depression as shown by the Beck Depression Inventory. CONCLUSIONS: The ability to modulate tinnitus by performing voluntary somatosensory or motor acts is likely the result of plastic changes in the brains of these patients with the development of aberrant connections between the auditory and sensory-motor systems. The strong predominance of men in the sample suggests the presence of a gender-specific factor that mediates these changes.

The auditory evoked potential difference tone and cubic difference tone measured from the inferior colliculus of the chinchilla.

The auditory evoked potential f2-f1 difference tone (DT) and the 2 f1-f2 cubic difference tone (CDT) were recorded from electrodes implanted in the inferior colliculus in a group of chinchillas. The purpose of this study was to measure normative aspects of AEP distortion products in awake chinchillas, by comparing the DT and CDT under a variety of stimulus conditions. For experiment 1, f1 was held constant at 1998 Hz, while the f2/f1 ratio was varied from 1.05 to 1.50. Input-output functions were measured over a range of primary tone levels up to 80 dB SPL. The amplitude of the DT was greatest for the smallest f2/f1 ratio, and decreased systematically as f2/f1 ratio increased. DT amplitude was greater than CDT amplitude for all primary tone pairs. Experiment 2 was conducted to determine the effect of f1 frequency upon the DT and CDT for a constant f1-f2 difference frequency of 102 Hz (f1-999, 1998, 4999, and 9998 Hz). The DT input-output functions were overlapping for all f1 frequencies. For the CDT, amplitude decreased with increasing f1 frequency, which corresponded to an increase in CDT frequency. In experiment 3, the relationship between ear of stimulation and inferior colliculus recorded from was investigated. DT input-output functions (f1 = 1998 Hz, DT = 102 Hz) were measured for monaural contralateral, monaural ipsilateral, and dichotic stimulus conditions. DT amplitude was largest for the contralateral condition, followed by the ipsilateral condition. A smaller, dichotic component to the DT was observed as well.

Responses of chopper units in the ventral cochlear nucleus of the anaesthetised guinea pig to clicks-in-noise and click trains.

Auditory brainstem responses (ABRs) have been measured with clicks, clicks masked by noise, click trains and pseudorandom maximum length sequences (MLS) of clicks. To investigate the neuronal populations contributing to the ABR under these stimulation conditions, we measured the extracellular responses of ventral cochlear nucleus (VCN) units in the urethane-anaesthetised guinea pig. We studied 23 chopper, 7 primary-like and 7 onset units. This report focuses on the responses from chopper units. The probability of discharge for chopper units increased with increasing click level reaching nearly 100% in many units, over a range of about 20-30 dB. Following each response to a click there was a 5-10 ms suppression of the spontaneous or noise evoked activity. As the level of the noise was increased over a range of 20-30 dB, the response to the clicks gradually decreased leading to a complete abolition of the click response at high noise levels. In a few units, low level noise produced a facilitation of the response to single clicks. In response to constant level equally spaced click trains, discharge probability increased with increasing minimum pulse interval (MPI), approaching 100% for MPIs of 4-8 ms in some units. The recovery afforded by the gaps in the MLS train often resulted in higher discharge probability for MLS than click trains with the same MPI, while response probabilities for MLS and click trains were similar when compared at equivalent average click rates. At short MPIs (0.5 and 1.0 ms), peri stimulus time histograms in response to click trains resembled those to best frequency (BF) tones and noisebursts, with chopping peaks unrelated to unit BF. VCN units show highly synchronised and reliable responses to click trains, MLS trains and clicks masked by noise. The decrease in discharge rate and increase in latency of chopper units with decreasing click level, increasing click rate and increasing masker level parallel the peak amplitude and latency changes observed in the auditory brainstem response.

The effects of click level, click rate, and level of background masking noise on the inferior colliculus potential (ICP) in the normal and carboplatin-treated chinchilla.

Carboplatin produces a selective loss of inner hair cells in chinchilla, substantially reducing the amplitude of the compound action potential. A key question that arises from these experiments is: What effect does a reduction in IHC-eighth-nerve fiber input have on the central auditory nervous system? This investigation evaluated the inferior colliculus potential (ICP) in chinchillas treated with carboplatin. The left ear was surgically destroyed and a recording electrode was placed in the left inferior colliculus. Following thirteen days of recovery time, the ICP was recorded in the awake animal. Click level was varied from 10-20 to 80 dB pSPL. Click rate was varied from 10 to 1000 Hz using both conventional averaging and a cross-correlation procedure. Broadband masking noise was varied from 30 to 70 dB SPL with click level held constant at 80 dB pSPL. The dependent variables were the positive peak latency and peak-to-following trough amplitude of the evoked potential. Following baseline studies, the animals were administered carboplatin (50 mg/kg IP) and retested two weeks later. Prior to carboplatin administration, there was an increase in ICP latency and a decrease in ICP amplitude with decreasing stimulus level, increasing rate and increasing noise level. Mean ICP threshold was 30 dB pSPL. Following carboplatin administration, there was little change in threshold or peak latencies. In contrast, the amplitude of the ICP was reduced on average by one-third, although this effect varied considerably across animals. The magnitude of this amplitude decrement was not strongly dependent on click level, click rate, or the level of background noise.