Spectrally specific temporal analyses of spike-train responses to complex sounds: A unifying framework.

Significant scientific and translational questions remain in auditory neuroscience surrounding the neural correlates of perception. Relating perceptual and neural data collected from humans can be useful; however, human-based neural data are typically limited to evoked far-field responses, which lack anatomical and physiological specificity. Laboratory-controlled preclinical animal models offer the advantage of comparing single-unit and evoked responses from the same animals. This ability provides opportunities to develop invaluable insight into proper interpretations of evoked responses, which benefits both basic-science studies of neural mechanisms and translational applications, e.g., diagnostic development. However, these comparisons have been limited by a disconnect between the types of spectrotemporal analyses used with single-unit spike trains and evoked responses, which results because these response types are fundamentally different (point-process versus continuous-valued signals) even though the responses themselves are related. Here, we describe a unifying framework to study temporal coding of complex sounds that allows spike-train and evoked-response data to be analyzed and compared using the same advanced signal-processing techniques. The framework uses a set of peristimulus-time histograms computed from single-unit spike trains in response to polarity-alternating stimuli to allow advanced spectral analyses of both slow (envelope) and rapid (temporal fine structure) response components. Demonstrated benefits include: (1) novel spectrally specific temporal-coding measures that are less confounded by distortions due to hair-cell transduction, synaptic rectification, and neural stochasticity compared to previous metrics, e.g., the correlogram peak-height, (2) spectrally specific analyses of spike-train modulation coding (magnitude and phase), which can be directly compared to modern perceptually based models of speech intelligibility (e.g., that depend on modulation filter banks), and (3) superior spectral resolution in analyzing the neural representation of nonstationary sounds, such as speech and music. This unifying framework significantly expands the potential of preclinical animal models to advance our understanding of the physiological correlates of perceptual deficits in real-world listening following sensorineural hearing loss.

The effect of fish and mealworm larvae meals as alternative dietary protein sources on nutrient digestibility and gastrointestinal function in Chinchilla lanigera.

Chinchillas are herbivores, but wild chinchillas may occasionally consume animal-based foods. The aim of this study was to determine the effect of fish meal (FM) and mealworm meal (MWM) included in complete pelleted diets on nutrient digestibility and gastrointestinal function in chinchillas. The experiment was performed on 24 male, divided into three groups, n=8. Control group (C) was fed a diet containing 10% soybean meal (SBM). In the experimental group FM, chinchillas received a diet containing 3% fish meal, and the diet administered to the experimental group MWM was supplemented with 4% dried mealworm larvae meal. The nutrient digestibility of diets was determined. At the end of the experiment animals were euthanized and their digestive tracts were removed to analyze gut activity. FM group animals were characterized by lower crude fat digestibility, whereas both alternative protein sources improved the digestibility of acid detergent fiber (ADF). A considerable increase in the activity of cecal intracellular and extracellular bacterial enzymes (in particular ß-glucosidase, ß-galactosidase and ß-xylosidase) was noted in the FM group, which however did not increase the concentrations of short-chain fatty acids (SCFA). The inclusion of MWM in chinchilla diets shifted the bacterial fermentation site from the cecum (lowest SCFA pool) to the colon (highest SCFA pool), thus enabling to derive additional energy from less digestible dietary components. In conclusion, chinchilla diets can be supplemented with small amounts of animal protein such as fish meal and dried mealworm larvae meal.

Between-ear sound frequency disparity modulates a brain stem biomarker of binaural hearing.

The auditory brain stem response (ABR) is an evoked potential that indexes a cascade of neural events elicited by sound. In the present study we evaluated the influence of sound frequency on a derived component of the ABR known as the binaural interaction component (BIC). Specifically, we evaluated the effect of acoustic interaural (between-ear) frequency mismatch on BIC amplitude. Goals were to 1) increase basic understanding of sound features that influence this long-studied auditory potential and 2) gain insight about the persistence of the BIC with interaural electrode mismatch in human users of bilateral cochlear implants, presently a limitation on the prospective utility of the BIC in audiological settings. Data were collected in an animal model that is audiometrically similar to humans, the chinchilla (Chinchilla lanigera; 6 females). Frequency disparities and amplitudes of acoustic stimuli were varied over broad ranges, and associated variation of BIC amplitude was quantified. Subsequently, responses were simulated with the use of established models of the brain stem pathway thought to underlie the BIC. Collectively, the data demonstrate that at high sound intensities (≥85 dB SPL), the acoustically elicited BIC persisted with interaurally disparate stimulation (click frequencies ≥1.5 octaves apart). However, sharper tuning emerged at moderate sound intensities (65 dB SPL), with the largest BIC occurring for stimulus frequencies within ~0.8 octaves, equivalent to ±1 mm in cochlear place. Such responses were consistent with simulated responses of the presumed brain stem generator of the BIC, the lateral superior olive. The data suggest that leveraging focused electrical stimulation strategies could improve BIC-based bilateral cochlear implant fitting outcomes.NEW & NOTEWORTHY Traditional hearing tests evaluate each ear independently. Diagnosis and treatment of binaural hearing dysfunction remains a basic challenge for hearing clinicians. We demonstrate in an animal model that the prospective utility of a noninvasive electrophysiological signature of binaural function, the binaural interaction component (BIC), depends strongly on the intensity of auditory stimulation. Data suggest that more informative BIC measurements could be obtained with clinical protocols leveraging stimuli restricted in effective bandwidth.

Simultaneous 3D imaging of sound-induced motions of the tympanic membrane and middle ear ossicles.

Efficient transfer of sound by the middle ear ossicles is essential for hearing. Various pathologies can impede the transmission of sound and thereby cause conductive hearing loss. Differential diagnosis of ossicular disorders can be challenging since the ossicles are normally hidden behind the tympanic membrane (TM). Here we describe the use of a technique termed optical coherence tomography (OCT) vibrography to view the sound-induced motion of the TM and ossicles simultaneously. With this method, we were able to capture three-dimensional motion of the intact TM and ossicles of the chinchilla ear with nanometer-scale sensitivity at sound frequencies from 0.5 to 5 kHz. The vibration patterns of the TM were complex and highly frequency dependent with mean amplitudes of 70-120 nm at 100 dB sound pressure level. The TM motion was only marginally sensitive to stapes fixation and incus-stapes joint interruption; however, when additional information derived from the simultaneous measurement of ossicular motion was added, it was possible to clearly distinguish these different simulated pathologies. The technique may be applicable to clinical diagnosis in Otology and to basic research in audition and acoustics.

Postnatal maturation of contralateral DPOAE suppression in a precocious animal model (chinchilla) of the human neonate.

CONCLUSION: In the neonatal chinchilla, the degree of contralateral distortion product otoacoustic emission (DPOAE) suppression and the latency and time constants of suppression are immature for 40-60 days. This suggests that olivocochlear efferent innervation of outer hair cells is not fully mature at birth in this animal model, and this may also be the case for human neonates. OBJECTIVES: To track postnatal changes in the dynamics of the olivocochlear efferent system in an animal model with cochlear development at birth similar to that in humans. METHODS: Real-time measurements of contralateral DPOAE suppression were made in 79 ears of anaesthetized chinchillas, ranging in age from 1 day to 70 days. An adult control group (13 ears) was also tested. DPOAE (2f1-f2; f2 = 4.4 kHz; f2/f1 = 1.22) input/output functions were measured. Dynamics of contralateral broadband noise suppression were measured, including latency and suppression time constants. RESULTS: DPOAE amplitude input/output functions are immature until 20-30 days postnatally. The maturation period for contralateral suppression amplitude is about 30 days. Latency of onset suppression was 40 ms at birth reducing to adult values (23 ms) at 40 days. The DPOAE suppression time constant was about 350 ms at birth and mature (230 ms) at 60 days.

Third-window vibroplasty with an active middle ear implant: assessment of physiologic responses in a model of stapes fixation in Chinchilla lanigera.

HYPOTHESIS: Mechanical stimulation through a cochlear third window into the scala tympani in a chinchilla model with normal and fixed stapes can generate cochlear responses equivalent to acoustic stimuli. BACKGROUND: Cochlear stimulation via the round window (RW) using active middle ear implants (AMEIs) can produce physiologic responses similar to acoustic stimulation including in a model of stapes fixation. However, pathologic conditions, such as advanced otosclerosis, can preclude delivery of sound energy to the cochlea through the oval window and/or the RW. METHODS: Cochlear microphonic (CM) and laser Doppler vibrometer measurements of stapes and RW velocities were performed in 6 ears of 4 chinchillas. Baseline measurements to acoustic sinusoidal stimuli (0.25-8 kHz) were made. Measurements were repeated with an AMEI driving the RW or a third window to the scala tympani before and after stapes fixation. RESULTS: AMEI stimulation of the third window produced CM waveforms with morphologies similar to acoustic stimuli. CM thresholds with RW and third-window stimulation were frequency dependent but ranged from 0.25 to 10 and 0.5 to 40 mV, respectively. Stapes fixation, confirmed by laser Doppler vibrometer measurements, resulted in a significant frequency dependent impairment in CM thresholds up to 13 dB (at <3 kHz) for RW stimulation and a nonsignificant frequency-dependent improvement of up to 10 dB (at >3 kHz) via third-window stimulation. CONCLUSION: AMEI mechanical stimulation through a third window into the scala tympani produces physiologic responses nearly identical to acoustic stimulation including in a model of stapes fixation with decreased efficiency.

Sound pressure transformations by the head and pinnae of the adult Chinchilla (Chinchilla lanigera).

There are three main cues to sound location: the interaural differences in time (ITD) and level (ILD) as well as the monaural spectral shape cues. These cues are generated by the spatial- and frequency-dependent filtering of propagating sound waves by the head and external ears. Although the chinchilla has been used for decades to study the anatomy, physiology, and psychophysics of audition, including binaural and spatial hearing, little is actually known about the sound pressure transformations by the head and pinnae and the resulting sound localization cues available to them. Here, we measured the directional transfer functions (DTFs), the directional components of the head-related transfer functions, for 9 adult chinchillas. The resulting localization cues were computed from the DTFs. In the frontal hemisphere, spectral notch cues were present for frequencies from ∼6-18 kHz. In general, the frequency corresponding to the notch increased with increases in source elevation as well as in azimuth towards the ipsilateral ear. The ILDs demonstrated a strong correlation with source azimuth and frequency. The maximum ILDs were <10 dB for frequencies <5 kHz, and ranged from 10-30 dB for the frequencies >5 kHz. The maximum ITDs were dependent on frequency, yielding 236 µs at 4 kHz and 336 µs at 250 Hz. Removal of the pinnae eliminated the spectral notch cues, reduced the acoustic gain and the ILDs, altered the acoustic axis, and reduced the ITDs.

A physiological frequency-position map of the chinchilla cochlea.

Accumulating evidence indicates that mammalian cochlear frequency-position maps (location of maximum vibration of the basilar membrane as a function of frequency) depend on the physiological condition of the inner ear. Cochlear damage desensitizes the ear, after the damage the original location of maximum vibration is tuned to a lower sound frequency. This suggests that frequency-position maps, derived from such desensitized ears, are shifted to lower frequencies, corresponding to a shift of the basilar membrane vibration pattern towards the base for a given stimulus frequency. To test this hypothesis, we re-mapped the cochlear frequency-position map in the chinchilla. We collected frequency-position data from chinchillas in normal physiological condition ("physiological map") and compared these to data previously established from sound overexposed ears ("anatomical map"). The characteristic frequency (CF) of neurons in the cochlear nucleus was determined. Horse-radish peroxidase (HRP) or biocytin (BCT) were injected iontophoretically to trace auditory nerve fibers towards their innervation site in the organ of Corti. The relationship between distance from the base (d, percent) and frequency (f, kHz) was described best by a simple exponential function: d = 61.2 - 42.2 x log(f). The slope of the function was 2.55 mm/octave. Compared to the "anatomical map", the "physiological map" was shifted by about 0.3 octaves to higher frequencies corresponding to a shift of the basilar membrane vibration pattern of 0.8 mm towards the apex for a given stimulus frequency. Our findings affirm that frequency-position maps in the mammalian cochlea depend on the condition of the inner ear. Damage-induced desensitization in mammalian inner ears results in similar shifts of CF (about 0.5 octaves) but different shifts of the maximum of the vibration pattern towards the base at given frequencies, dependent on the mapping constant of the species, longer basilar membranes showing a larger basal shift. Furthermore, the results substantiate the notion that "crowding" at lower frequencies appears to be a specialization rather than a general feature.

A superior semicircular canal dehiscence-induced air-bone gap in chinchilla.

An SCD is a pathologic hole (or dehiscence) in the bone separating the superior semicircular canal from the cranial cavity that has been associated with a conductive hearing loss in patients with SCD syndrome. The conductive loss is defined by an audiometrically determined air-bone gap that results from the combination of a decrease in sensitivity to air-conducted sound and an increase in sensitivity to bone-conducted sound. Our goal is to demonstrate, through physiological measurements in an animal model, that mechanically altering the superior semicircular canal (SC) by introducing a hole (dehiscence) is sufficient to cause such an air-bone gap. We surgically introduced holes into the SC of chinchilla ears and evaluated auditory sensitivity (cochlear potential) in response to both air- and bone-conducted stimuli. The introduction of the SC hole led to a low-frequency (<2000 Hz) decrease in sensitivity to air-conducted stimuli and a low-frequency (<1000 Hz) increase in sensitivity to bone-conducted stimuli resulting in an air-bone gap. This result was consistent and reversible. The air-bone gaps in the animal results are qualitatively consistent with findings in patients with SCD syndrome.

Middle-ear pressure gain and cochlear partition differential pressure in chinchilla.

An important step to describe the effects of inner-ear impedance and pathologies on middle- and inner-ear mechanics is to quantify middle- and inner-ear function in the normal ear. We present middle-ear pressure gain G(MEP) and trans-cochlear-partition differential sound pressure DeltaP(CP) in chinchilla from 100 Hz to 30 kHz derived from measurements of intracochlear sound pressures in scala vestibuli P(SV) and scala tympani P(ST) and ear-canal sound pressure near the tympanic membrane P(TM). These measurements span the chinchilla's auditory range. G(MEP) had constant magnitude of about 20 dB between 300 Hz and 20 kHz and phase that implies a 40-micros delay, values with some similarities to previous measurements in chinchilla and other species. DeltaP(CP) was similar to G(MEP) below about 10 kHz and lower in magnitude at higher frequencies, decreasing to 0 dB at 20 kHz. The high-frequency rolloff correlates with the audiogram and supports the idea that middle-ear transmission limits high-frequency hearing, providing a stronger link between inner-ear macromechanics and hearing. We estimate the cochlear partition impedance Z(CP) from these and previous data. The chinchilla may be a useful animal model for exploring the effects of non-acoustic inner-ear stimulation such as "bone conduction" on cochlear mechanics.

Responses of neurons in chinchilla auditory cortex to frequency-modulated tones.

Frequency-modulated (FM) stimuli have been used to explore the behavior of neurons in the auditory cortex of several animal models; however, the properties of FM-sensitive auditory cortical neurons in the chinchilla are still unknown. Single-unit responses to FM stimulation were obtained from the auditory cortex of anesthetized adult chinchillas (Chinchilla laniger). Upward and downward linear FM sweeps spanning frequencies from 0.1 to 20 kHz were presented at speeds of 0.05 to 0.82 kHz/ms. Results indicated that >90% of sampled neurons were responsive to FM sweeps. The population preference was for upward FM sweeps and for medium to fast speeds (> or =0.3 kHz/ms). Few units (3%) were selective for downward FM sweeps, whereas <22% of units preferred slow speeds (< or =0.1 kHz/ms). Velocity preference and direction sensitivity were positively correlated for upward sweeps only (r = 0.40, P = 0.0021, t-test). Three types of firing rate patterns were observed in the FM response peristimulus time histograms: a single peak at sweep onset/offset ("onset") and a single peak ("late") or multiple peaks ("burst") during the sweep. "Late" units expressed the highest mean values for direction sensitivity and speed selectivity; "onset" units were selective only for direction and "burst" units were not selective for either direction or speed. The robust responsiveness of these neurons to FM sweeps suggests a functional role for FM detection such as the identification of FM sweeps present in vocalizations of other organisms within the chinchilla's natural environment.

Threshold tuning curves of chinchilla auditory-nerve fibers. I. Dependence on characteristic frequency and relation to the magnitudes of cochlear vibrations.

Frequency-threshold tuning curves were recorded in thousands of auditory-nerve fibers (ANFs) in chinchilla. Synthetic tuning curves with 21 characteristic frequencies (187 Hz to 19.04 kHz, spaced every 1/3 octave) were constructed by averaging individual tuning curves within 2/3-octave frequency bands. Tuning curves undergo a gradual transition in symmetry at characteristic frequencies (CFs) of 1 kHz and an abrupt change in shape at CFs of 3-4 kHz. For CFs < or = 3 kHz, the lower limbs of tuning curves have similar slopes, about -18 dB/octave, but the upper limbs have slopes that become increasingly steep with increasing frequency and CF. For CFs >4 kHz, tuning curves normalized to the CF are nearly identical and consist of three segments. A tip segment, within 30-40 dB of CF threshold, has lower- and upper-limb slopes of -60 and +120 dB/octave, respectively, and is flanked by a low-frequency ("tail") segment, with shallow slope, and a terminal high-frequency segment with very steep slope (several hundreds of dB/octave). The tuning curves of fibers innervating basal cochlear sites closely resemble basilar-membrane tuning curves computed with low isovelocity criteria. At the apex of the chinchilla cochlea, frequency tuning is substantially sharper for ANFs than for available recordings of organ of Corti vibrations.

Amplitude modulation of DPOAEs by acoustic stimulation of the contralateral ear.

CONCLUSION: Otoacoustic emissions generated by outer hair cells (OHCs) are influenced by stimulation of the contralateral ear via a neural pathway involving the olivo-cochlear efferent system. This is often referred to as a contralateral 'suppression reflex', but we suggest that such a term is inappropriate since distortion product otoacoustic emissions (DPOAEs) can be both enhanced and suppressed, and there is continuous modulation with no threshold effects. OBJECTIVE: To characterize the continuous amplitude modulation of DPOAEs by contralateral sound stimulation. MATERIALS AND METHODS: In an animal model (chinchilla), DPOAEs were recorded in real time from one ear during presentation of acoustic stimuli to the opposite ear. RESULTS: DPOAE amplitude is suppressed by an increase in contralateral stimulation, and enhanced by a decrease in same, i.e. the emissions are continuously modulated by activity in the opposite ear. The input-output function shows a linear relationship to this system over a 40-50 dB range of contralateral stimulus levels. After a neural delay time of approximately 25 ms, DPOAE amplitude closely follows contralateral amplitude signals up to modulation frequencies of approximately 20 Hz. Thus, stimuli to one ear continually modulate the OHC system (and therefore the biomechanical amplification) of the contralateral cochlea.

Structures that contribute to middle-ear admittance in chinchilla.

We describe measurements of middle-ear input admittance in chinchillas (Chinchilla lanigera) before and after various manipulations that define the contributions of different middle-ear components to function. The chinchilla's middle-ear air spaces have a large effect on the low-frequency compliance of the middle ear, and removing the influences of these spaces reveals a highly admittant tympanic membrane and ossicular chain. Measurements of the admittance of the air spaces reveal that the high-degree of segmentation of these spaces has only a small effect on the admittance. Draining the cochlea further increases the middle-ear admittance at low frequencies and removes a low-frequency (less than 300 Hz) level dependence in the admittance. Spontaneous or sound-driven contractions of the middle-ear muscles in deeply anesthetized animals were associated with significant changes in middle-ear admittance.

Wideband reflectance tympanometry in chinchillas and human.

Wideband reflectance tympanometry was performed on twelve chinchillas ears. The complex input impedance of the middle ear, multifrequency admittance tympanograms, reflectance patterns (reflectance versus frequency), and reflectance tympanograms (reflectance versus ear-canal air pressure) were analyzed and compared to human data. The complex impedance of the chinchilla ear has a lower stiffness reactance at low frequencies, a higher mass reactance at high frequencies, and a lower resistance compared to the human. Multifrequency admittance tympanograms from chinchillas follow the same sequence of patterns as humans for low frequencies (<2 kHz). At higher frequencies tympanograms from both species are poorly organized and do not follow a consistent sequence of patterns. Reflectance patterns of chinchillas and humans are different. However, both species show high reflectance at low frequencies, regions of lower reflectance in mid-frequencies (2-6 kHz), and high reflectance at high frequencies (>8 kHz). Reflectance tympanograms for the two species show a single, centrally located minimum at low frequencies (<2 kHz) and are substantially different at higher frequencies. Results are shown for two animals that underwent eustachian tube obstruction. Reflectance patterns obtained with different ear-canal air pressures are substantially different. Reflectance results at any single ear-canal pressure (including ambient pressure) do not completely characterize the effects of middle-ear pathology.

Responses of ventral cochlear nucleus units in the chinchilla to amplitude modulation by low-frequency, two-tone complexes.

For a tone that is amplitude modulated by two tones (fmod1 and fmod2), neither the stimulus waveform nor the half-wave rectified waveform has spectral energy at the envelope beat frequency (fmod2-fmod1). The response of ventral cochlear nucleus units in the chinchilla were recorded for best frequency tones that were amplitude modulated by low-frequency, two-tone complexes. Fourier analysis of poststimulus time histograms shows spectral peaks at fmod2-fmod1 in addition to the peaks at fmod1 and fmod2. The peaks in the neural spectra arise from compressive nonlinearities in the auditory system. The magnitudes of these spectral peaks are measures of synchrony at each frequency component. For all units, synchrony at fmod1 and fmod2 is greater than the synchrony at fmod2-fmod1. For a given unit, synchrony at fmod1 and fmod2 remains relatively constant as a function of overall level, whereas synchrony at fmod2-fmod1 decreases as the level increases. Synchrony was quantified in terms of the Rayleigh statistic (z), which is a measure of the statistical significance of the phase locking. In terms of z, phase locking at fmod1 and fmod2 is largest in chopper units, whereas onset-chopper units and primarylike units having sloping saturation in their rate-level functions show the smallest amount of phase locking. Phase locking at fmod2-fmod1 is also largest in chopper units, and smallest in onset-chopper units and primarylike units with sloping saturation.

Sound localization in chinchillas. I: Left/right discriminations.

The ability of chinchillas to localize sound was examined behaviorally using a conditioned avoidance procedure in which the animals were trained to discriminate left from right sound sources. Their minimum audible angle was 15.6 degrees for 100-ms broadband noise making them one of the more accurate rodents, although they are not as accurate as primates and carnivores. Thresholds obtained for filtered noise stimuli demonstrated that chinchillas are equally accurate in localizing either low- or high-frequency noise. Further, they are able to use both interaural phase-difference and interaural intensity-difference cues as demonstrated by their ability to localize both low- and high-frequency pure tones. Finally, analysis of the chinchilla retina supports the hypothesis that the role of auditory localization in directing the eyes to sound sources played a role in the evolution of auditory spatial perception.

Detection of bandlimited noise masked by wideband noise in the chinchilla.

Six chinchillas were trained to detect a 1 s bandlimited noise signal in the presence of a continuous, wideband noise masker. As the bandwidth of the noise signal increased, there was a decrease in detection threshold. Threshold signal-to-noise ratios for the bandlimited noise signal were independent of the level of the noise masker. The slope of the bandwidth function obtained for the chinchilla is similar to the slopes reported for human subjects, approximating the predicted slope of the ideal energy detector.

Neural correlates of gap detection in auditory nerve fibers of the chinchilla.

The neural correlates of gap detection were examined in a population of single auditory nerve fibers in the chinchilla. Acoustic stimuli consisted of 120 ms noise bursts (30-80 dB SPL) which contained silent intervals (gaps: 1, 2, 3, 4,5, 6 and 10 ms) at the midpoint. The neural response to the gap was quantified by the modulation index, (MAX-MIN)/AVE, which accounts for the steady state discharge rate before the gap (AVE), the minimum firing rate during the gap (MIN), and the maximum firing rate after the gap (MAX). In general, the modulation index increased as a function of gap width and stimulus level. Furthermore, there was a positive correlation between the modulation index and the characteristic frequency of the fiber. To estimate how detection could be based on the neuronal response, a criterion-free measure, analogous to d'. was calculated using z-scores obtained from the distributions of modulation index values collected before and during the gap and used to predict percent correct values for chinchilla psychophysical studies. The values increased with gap duration in a sigmoidal manner much like the psychometric functions in the chinchilla. In general, the neural gap thresholds obtained approximated those obtained psychophysically, although they were less affected by stimulus level.

The relation among hearing loss, sensory cell loss and tuning characteristics in the chinchilla.

Evoked-potential tuning curves were obtained on over 150 chinchillas before and after acoustic overstimulation in order to relate the effects of changes in frequency selectivity to sensory cell loss over a wide range of hearing loss. Pre- and post-exposure measures of auditory thresholds and masked thresholds (simultaneous tone-on-tone paradigm) were obtained in each animal at 0.5, 1.0, 2.0, 4.0, 8.0 and 11.2 kHz, using the auditory evoked potential recorded from the inferior colliculus. Three tuning curve variables (Q10dB, low-frequency slope and high-frequency slope) were compared to the amount of noise-induced permanent threshold shift and to the percent sensory cell loss produced by a variety of noise exposures. Based upon large sample averages, frequencies showing permanent threshold shifts in excess of 10 dB also showed statistically significant differences between pre- and post-exposure measures of all three tuning curve variables. Shifts of less than 10 dB were not accompanied by statistically significant changes in the tuning curve variables. The percentage of outer hair cell loss, and percentage change in tuning curve characteristics showed systematic and parallel increases as threshold shifts increased at all probe tone frequencies except 8.0 and 11.2 kHz. In general, the results were consistent in showing that there is a systematic change in the variables which define the quality of tuning as hearing loss progressively increases and that these changes are clearly related to outer hair cell losses.