Inner hair cell loss and steady-state potentials from the inferior colliculus and auditory cortex of the chinchilla

Steady-state evoked potentials were measured from unanesthetized chinchillas both before and after carboplatin-induced selective inner hair cell loss. Recordings were made from both the inferior colliculus (IC) and the auditory cortex (AC). The steady-state potential was measured in the form of the envelope following response (EFR), obtained by presenting a two-tone stimulus (f1 = 2000 Hz; f2 = 2020, 2040, 2080, 2160, or 2320 Hz), and measuring the magnitude of the Fourier coefficient at the f2-f1 difference frequency. From the IC, precarboplatin, EFR amplitude vs difference tone frequency showed a bandpass pattern, with maximum amplitude at either 160 or 80 Hz, depending upon stimulus level. Postcarboplatin, the preferred difference frequency was 80 Hz for all stimulus levels. From the AC, EFR amplitude versus difference tone frequency also showed a bandpass pattern, with the maximum amplitude at 80 Hz both pre- and postcarboplatin. EFR amplitude from the IC was decreased for some conditions postcarboplatin, while the amplitude from the AC showed no significant change.     

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.     

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.     

Age reduces response latency of mouse inferior colliculus neurons to AM sounds

Age and stimulus rise time (RT) effects on response latency were investigated for inferior colliculus (IC) neurons in young-adult and old CBA mice. Single-unit responses were recorded to unmodulated and sinusoidal amplitude modulated (SAM) broadband noise carriers, presented at 35 to 80 dB SPL. Data from 63 young-adult and 76 old phasic units were analyzed to identify the time interval between stimulus onset and driven-response onset (latency). When controlling for stimulus sound level and AM frequency, significant age-related changes in latency were identified. Absolute latency decreased with age at all stimulus AM frequencies, significantly so for equivalent rise times (RT) < or = 12.5 ms. The linear correlation of latency with AM stimulus RT was significant for both young-adult and old units, and increased significantly with age. It is likely that both the decrease in absolute latency and the increase in latency/RT correlation with age are consistent with a reduction of inhibitory drive with age in the IC. These latency changes will result in age-related timing variations in brainstem responses to stimulus onsets, and therefore affect the encoding of complex sounds.     

Cochlear nucleus, inferior colliculus, and medial geniculate responses during the behavioral detection of threshold-level auditory stimuli in the rabbit

Rabbits were conditioned to respond behaviorally to auditory stimuli by pairing a white-noise conditioned stimulus (CS) with a corneal airpuff unconditioned stimulus (US). The conditioned response (CR) was movement of the nictitating membrane (NM). After the subjects were responding at better than the 90% correct level, the intensity of the auditory stimulus was reduced to behavioral threshold using a staircase procedure. Simultaneous measurements of neural unit activity and behavioral NM responses were then made in rabbits performing at behavioral threshold. After the experiment was completed neural unit responses during behavioral detection trials were compared to neural responses made during nondetection trials. Neural unit responses to a constant intensity, white-noise stimulus at behavioral threshold were well defined and essentially identical on behavioral detection and nondetection trials in the ventral cochlear nucleus, the ventrolateral division of the central nucleus of the inferior colliculus, and the ventral division of the medial geniculate body. This suggests that an auditory stimulus can be neuronally "detected" without being behaviorally detected, and that the neural "decision" to respond behaviorally is not made in these nuclei. Responses recorded from the dorsomedial division of the central nucleus of the inferior colliculus, the pericentral nucleus of the inferior colliculus, and less commonly in the medial division of the medial geniculate body were also clearly present and nearly identical during the onset of the auditory stimulus, but were sometimes consistently different for detection and nondetection conditions during the latter part of the auditory stimulus. These brain regions appear to receive both auditory and nonauditory inputs, and show responses which are more highly correlated with detection behavior.     

Opioid modulation of GABA release in the rat inferior colliculus

Background  

The inferior colliculus, which receives almost all ascending and descending auditory signals, plays a crucial role in the processing of auditory information. While the majority of the recorded activities in the inferior colliculus are attributed to GABAergic and glutamatergic signalling, other neurotransmitter systems are expressed in this brain area including opiate peptides and their receptors which may play a modulatory role in neuronal communication.     

Interaural time sensitivity of high-frequency neurons in the inferior colliculus

Recent psychoacoustic experiments have shown that interaural time differences provide adequate cues for lateralizing high-frequency sounds, provided the stimuli are complex and not pure tones. We present here physiological evidence in support of these findings. Neurons of high best frequency in the cat inferior colliculus respond to interaural phase differences of amplitude modulated waveforms, and this response depends upon preservation of phase information of the modulating signal. Interaural phase differences were introduced in two ways: by interaural delays of the entire waveform and by binaural beats in which there was an interaural frequency difference in the modulating waveform. Results obtained with these two methods are similar. Our results show that high-frequency cells can respond to interaural time differences of amplitude modulated signals and that they do so by a sensitivity to interaural phase differences of the modulating waveform.     

Synchronized discharge rate representation of voice-onset time in the chinchilla auditory nerve

Responses of chinchilla auditory nerve fibers to synthesized stop consonant syllables differing in voice-onset time (VOT) were obtained. The syllables, heard as /ga/-/ka/ or /da/-/ta/, were similar to those previously used by others in psychophysical experiments with human and chinchilla subjects. Synchronized discharge rates of neurons tuned to frequencies near the first formant increased at the onset of voicing for VOTs longer than 20 ms. Stimulus components near the formant or the neuron's characteristic frequency accounted for the increase. In these neurons, synchronized response changes were closely related to the same neuron's average discharge rates [D. G. Sinex and L. P. McDonald, J. Acoust. Soc. Am. 83, 1817-1827 (1988)]. Neurons tuned to frequency regions near the second and third formants usually responded to components near the second formant prior to the onset of voicing. These neurons' synchronized discharges could be captured by the first formant at the onset of voicing or with a latency of 50-60 ms, whichever was later. Since these neurons' average rate responses were unaffected by the onset of voicing, the latency of the synchronized response did provide as much additional neural cue to VOT. Overall, however, discharge synchrony did not provide as much information about VOT as was provided by the best average rate responses. The results are compared to other measurements of the peripheral encoding of speech sounds and to aspects of VOT perception.     

Psychophysical tuning curves and auditory thresholds after hair cell damage in the chinchilla

Chinchillas were treated with kanamycin sulfate (150--200 mg/kg/day) to produce high-frequency hearing loss extending to about 4.0 kHz. Thresholds and psychophysical tuning curves (PTCs) were obtained before and after treatment, utilizing a shuttlebox avoidance procedure, and cochlear hair cells were evaluated under phase contrast microscopy. Hair cell loss resulting from kanamycin treatment varied from restricted lesions of the outer hair cells (OHCs) in the cochlear base, with no loss of inner hair cells (IHCs), to more extensive lesions involving both OHCs and IHCs. Threshold shift of at least 40 dB was always associated with OHC loss. PTCs obtained from frequency regions exhibiting 40--50 dB of threshold shift were normal in shape. With threshold shift in excess of 50 dB, PTCs were progressively distorted, with truncation of the tip segment and in some cases increased sensitivity of the tail segment. The results suggest that the threshold of optimally functional IHCs after kanamycin-induced OHC loss is about 40 dB higher than normal. Threshold shift in excess of 40 dB may represent IHC damage. IHCs are capable of transducing the fine-frequency information necessary for generating normally sharp PTCs in the absence of OHCs. However, with threshold shift in excess of approximately 50 dB, this frequency resolution is increasingly compromised.     

Average discharge rate representation of voice onset time in the chinchilla auditory nerve

Responses of chinchilla auditory-nerve fibers to synthesized stop consonants differing in voice onset time (VOT) were obtained. The syllables, heard as /ga/-/ka/ or /da/-/ta/, were similar to those previously used by others in psychophysical experiments with human and with chinchilla subjects. Average discharge rates of neurons tuned to the frequency region near the first formant generally increased at the onset of voicing, for VOTs longer than 20 ms. These rate increases were closely related to spectral amplitude changes associated with the onset of voicing and with the activation of the first formant; as a result, they provided accurate information about VOT. Neurons tuned to frequency regions near the second and third formants did not encode VOT in their average discharge rates. Modulations in the average rates of these neurons reflected spectral variations that were independent of VOT. The results are compared to other measurements of the peripheral encoding of speech sounds and to psychophysical observations suggesting that syllables with large variations in VOT are heard as belonging to one of only two phonemic categories.     

Complex tone processing in primary auditory cortex of the awake monkey. I. Neural ensemble correlates of roughness

Previous physiological studies [e.g., Bieser and Muller-Preuss, Exp. Brain Res. 108, 273-284 (1996); Schulze and Langner, J. Comp. Physiol. A 181, 651-663 (1997); Steinschneider et al., J. Acoust. Soc. Am. 104, 2935-2955 (1998)] have suggested that neural activity in primary auditory cortex (A1) phase-locked to the waveform envelope of complex sounds with low (<300 Hz) periodicities may represent a neural correlate of roughness perception. However, a correspondence between these temporal response patterns and human psychophysical boundaries of roughness has not yet been demonstrated. The present study examined whether the degree of synchronized phase-locked activity of neuronal ensembles in A1 of the awake monkey evoked by complex tones parallels human psychoacoustic data defining the existence region and frequency dependence of roughness. Stimuli consisted of three consecutive harmonics of fundamental frequencies (f(0)s) ranging from 25 to 4000 Hz. The center frequency of the complex tones was fixed at the best frequency (BF) of the cortical sites, which ranged from 0.3 to 10 kHz. Neural ensemble activity in the thalamorecipient zone (lower lamina III) and supragranular cortical laminae (upper lamina III and lamina II) was measured using multiunit activity and current source density techniques and the degree of phase-locking to the f0 was quantified by spectral analysis. In the thalamorecipient zone, the stimulus f0 at which phase-locking was maximal increased with BF and reached an upper limit between 75 and 150 Hz for BFs greater than about 3 kHz. Estimates of limiting phase-locking rates also increased with BF and approximated psychoacoustic values for the disappearance of roughness. These physiological relationships parallel human perceptual data and therefore support the relevance of phase-locked activity of neuronal ensembles in A1 for the physiological representation of roughness.     

Complex tone processing in primary auditory cortex of the awake monkey. II. Pitch versus critical band representation

Noninvasive neurophysiological studies in humans support the existence of an orthogonal spatial representation of pure tone frequency and complex tone pitch in auditory cortex [Langner et al., J. Comp. Physiol. A 181, 665-676 (1997)]. However, since this topographic organization is based on neuromagnetic responses evoked by wideband harmonic complexes (HCs) of variable fundamental frequency (f0), and thus interharmonic frequency separation (deltaF), critical band filtering effects due to differential resolvability of harmonics may have contributed to shaping these responses. To test this hypothesis, the present study examined responses evoked by three-component HCs of variable f0 in primary auditory cortex (A1) of the awake monkey. The center frequency of the HCs was fixed at the best frequency (BF) of the cortical site. Auditory evoked potential (AEP), multiunit activity, and current source density techniques were used to evaluate A1 responses as a function of f0 (=deltaF). Generally, amplitudes of nearly all response components increased with f0, such that maximal responses were evoked by HCs comprised of low-order resolved harmonics. Statistically significant increases in response amplitude typically occurred at deltaFs between 10% and 20% of center frequency, suggestive of critical bandlike behavior. Complex tone response amplitudes also reflected nonlinear summation in that they could not be predicted by the pure tone frequency sensitivity curves of the cortical sites. A mechanism accounting for the observed results is proposed which involves mutual lateral inhibitory interactions between responses evoked by stimulus components lying within the same critical band. As intracortical AEP components likely to be propagated to the scalp were also strongly modulated by deltaF, these findings indicate that noninvasive recordings of responses to complex sounds may require a consideration of critical band effects in their interpretation.     

Salicylate-induced changes in spontaneous activity of single units in the inferior colliculus of the guinea pig

Changes in spontaneous neuronal activity of the inferior colliculus in albino guinea pigs before and after administration of sodium salicylate were analyzed. Animals were anesthetized with pentobarbital, and two microelectrodes separated by a few hundred microns were driven through the inferior colliculus. After collecting a sufficiently large sample of cells, sodium salicylate (450 mg/kg) was injected i.p. and recordings again made 2 h after the injection. Comparison of spontaneous activity recorded before and after salicylate administration revealed highly statistically significant differences (p less than 0.001). After salicylate, the mean rate of the cell population increased from 29 to 83 Hz and the median from 26 to 74 Hz. Control experiments in which sodium salicylate was replaced by saline injection revealed no statistically significant differences in cell discharges. Recordings made during the same experiments from lobulus V of the cerebellar vermis revealed no changes in response to salicylate. The observed changes in single-unit activity due to salicylate administration may represent the first systematic evidence of a tinnituslike phenomenon in animals.     

Age effects on discrimination of timing in auditory sequences

The experiments examined age-related changes in temporal sensitivity to increments in the interonset intervals (IOI) of components in tonal sequences. Discrimination was examined using reference sequences consisting of five 50-ms tones separated by silent intervals; tone frequencies were either fixed at 4 kHz or varied within a 2-4-kHz range to produce spectrally complex patterns. The tonal IOIs within the reference sequences were either equal (200 or 600 ms) or varied individually with an average value of 200 or 600 ms to produce temporally complex patterns. The difference limen (DL) for increments of IOI was measured. Comparison sequences featured either equal increments in all tonal IOIs or increments in a single target IOI, with the sequential location of the target changing randomly across trials. Four groups of younger and older adults with and without sensorineural hearing loss participated. Results indicated that DLs for uniform changes of sequence rate were smaller than DLs for single target intervals, with the largest DLs observed for single targets embedded within temporally complex sequences. Older listeners performed more poorly than younger listeners in all conditions, but the largest age-related differences were observed for temporally complex stimulus conditions. No systematic effects of hearing loss were observed.     

Neural mechanisms of interstimulus interval-dependent responses in the primary auditory cortex of awake cats

Background  

Primary auditory cortex (AI) neurons show qualitatively distinct response features to successive acoustic signals depending on the inter-stimulus intervals (ISI). Such ISI-dependent AI responses are believed to underlie, at least partially, categorical perception of click trains (elemental vs. fused quality) and stop consonant-vowel syllables (eg.,/da/-/ta/continuum).     

Middle-ear response in the chinchilla and its relationship to mechanics at the base of the cochlea

The responses of the malleus and the stapes to sinusoidal acoustic stimulation have been measured in the middle ears of anesthetized chinchillas using the M?ssbauer technique. With "intact" bullas (i.e., closed except for venting via capillary tubing), the vibrations of the tip of the malleus reach a maximal peak velocity of about 2 mm/s in responses to 100-dB SPL tones in the frequency range 500-6000 Hz; vibration velocity diminishes toward lower frequencies with a slope of about 6 dB/oct. Opening the bulla widely increases the responses to low-frequency stimuli by as much as 16 dB. At low frequencies, malleus response sensitivity with either open or intact bullas far exceeds all previous measurements in cats and matches or exceeds such measurements in guinea pigs. Whether measured in open or intact bullas, phase-versus-frequency curves closely approximate those predicted from the magnitude-versus-frequency curves by minimum phase theory. The stapes responses are similar to those of the malleus, except that stapes response magnitude is lower, on the average, by 7.5 dB at frequencies below 2 kHz and 10.7 dB at 2 kHz and above. Comparison of the responses of the middle ear with those of the basilar membrane at a site 3.5 mm from the stapes indicates that, at frequencies below 150 Hz, the basilar membrane displacement is proportional to stapes acceleration. At frequencies between 150 and 2000 Hz, basilar membrane displacement is proportional to stapes velocity.