Cochlear nerve acoustic envelope response detection is improved by the addition of random-phased tonal stimuli.

We test Lowenstein's dc bias hypothesis as an alternative mechanism for the phenomenon sometimes called 'stochastic resonance'. Probe stimuli consisting of paired phase-locked tones at frequencies f(1) and f(2) (where f(2)-f(1)=800 Hz, f(1)>4.5 kHz) and at equal intensity were used to generate synchronous 800 Hz cochlear nerve activity (envelope responses). When a background tone of the same intensity, with a frequency halfway between f(1) and f(2), is presented simultaneously with the probe stimulus, the envelope response amplitude typically decreases. Consistent with Lowenstein's hypothesis, however, when the intensities of the probe and background tone are near the detection threshold of the envelope response (approximately 0-20 dB sound pressure level), the simultaneous presence of the background tone often increases the amplitude of the envelope response. At these same intensity levels, when the background tone precedes the probe stimulus, it decreases the amplitude of the response to the probe stimulus. The effects of simultaneous presentation of the probe and the background tone are frequency-dependent, becoming less pronounced or reversing as the frequency of the background tone departs from those of the probe stimuli.

Low-frequency acoustic modulations generated by the high-frequency portion of the cochlea, noninvasively recorded from the scalp of mice (Mus musculus).

Vocalizations often contain low-frequency modulations of the envelope of a high-frequency sound. The high-frequency portion of the cochlear nerve of mice (Mus musculus) generates a robust phase-locked response to these low-frequency modulations, and it can be easily recorded from the surface of the scalp. The cochlea is most sensitive to envelope modulation frequencies of approximately 500 to 2000 Hz. These responses have detection thresholds that are approximately 10 dB more sensitive than auditory brainstem responses, and they are very sharply tuned. These measurements may provide a nontraumatic means of repeatedly assessing cochlear functions involved in sound localization and perception of vocalizations.

Essential roles of noise in neural coding and in studies of neural coding.

We present examples of results from our studies of auditory primary afferent nerve fibers and populations of such fibers in the frog and gerbil. We take advantage of the natural dithering effect of internal noise, where it is sufficient, to construct highly predictive descriptive models (based on the Wiener series with kernels derived from white-noise analysis). Where the internal noise is insufficient, we enhance dithering by applying external acoustic noise together with our stimuli. Using acoustic noise as a background sound, orthogonal to the stimulus waveform, we show that under some circumstances such background sound can enhance the ability of individual fibers and populations of fibers to encode the stimulus waveform.

Killer whale (Orcinus orca) hearing: auditory brainstem response and behavioral audiograms.

Killer whale (Orcinus orca) audiograms were measured using behavioral responses and auditory evoked potentials (AEPs) from two trained adult females. The mean auditory brainstem response (ABR) audiogram to tones between 1 and 100 kHz was 12 dB (re 1 mu Pa) less sensitive than behavioral audiograms from the same individuals (+/- 8 dB). The ABR and behavioral audiogram curves had shapes that were generally consistent and had the best threshold agreement (5 dB) in the most sensitive range 18-42 kHz, and the least (22 dB) at higher frequencies 60-100 kHz. The most sensitive frequency in the mean Orcinus audiogram was 20 kHz (36 dB), a frequency lower than many other odontocetes, but one that matches peak spectral energy reported for wild killer whale echolocation clicks. A previously reported audiogram of a male Orcinus had greatest sensitivity in this range (15 kHz, approximately 35 dB). Both whales reliably responded to 100-kHz tones (95 dB), and one whale to a 120-kHz tone, a variation from an earlier reported high-frequency limit of 32 kHz for a male Orcinus. Despite smaller amplitude ABRs than smaller delphinids, the results demonstrated that ABR audiometry can provide a useful suprathreshold estimate of hearing range in toothed whales.

Noise improves transfer of near-threshold, phase-locked activity of the cochlear nerve: evidence for stochastic resonance?

Stochastic resonance can be described as improved detection of weak periodic stimuli by a dynamic nonlinear system, resulting from the simultaneous presentation of a restricted dynamic range of low-intensity noise. This property has been reported in simple physical and biological activities. The present study describes data consistent with the interpretation that stochastic resonance can be observed in the response of cochlear neurons. These experiments utilized low levels (-5 to 25 dB SPL) of stimuli and noise (5 to 30 dB SPL). Stimuli consisted of simultaneously presented 8 kHz (F1) and 8.8 kHz (F2) tone bursts, which generated an 800 Hz F2-F1 cochlear nerve envelope ensemble response in the gerbil. The mean response threshold was approximately -3 dB SPL. Simultaneous presentation of a low-intensity wideband noise increased the amplitude of this response. This was observed with tonal stimuli having intensities of 0-5 dB SPL; responses to stimulus levels > 10 dB were attenuated by noise. Response amplitude was increased by noise levels of 10-15 dB; the amplitude was unaffected by lower levels of noise, and decreased in the presence of higher noise levels. These properties are compatible with those of stochastic resonance.

Cochlear tuning in the gerbil: a comparison of responses to sinusoidal amplitude modulation and difference tone stimuli.

Vocalizations often have periodic variations of their acoustic waveform envelope. Two simultaneously presented frequencies have an envelope fluctuation with a frequency equal to their difference tone (DT = F2-F1). Sinusoidal amplitude modulation (SAM) of a carrier frequency also produces an envelope fluctuation. Electrical ensemble responses to DT and SAM stimuli were recorded from the gerbil's round window. The predominant frequency of the response to the DT stimuli is F2-F1; to the SAM stimuli, it is the modulation frequency. Both responses are spectrally, temporally, and dynamically non-linear. Forward masking of a low-frequency DT response produced a tuning curve (TC) with a tip at the high-stimulus frequency. Forward masker TCs of a low-frequency SAM ensemble response had tips at the high frequency of the carrier. Tip thresholds and sharpness of tuning of DT and SAM TCs are quite similar, with cochlear neurons having high characteristic frequencies providing sharply tuned information about low frequency acoustic envelope periodicities.

Temporal factors associated with cochlear nerve tuning to dual and single tones: a qualitative study.

The simultaneous presentation of a 10- and 10.86-kHz tone produces an 860-Hz cochlear nerve difference tone (DT) response in the gerbil which persists for the duration of the stimulus. Forward masking shows this response is generated by neurons sharply tuned to the stimulus frequencies. When compared with the DT response, the cochlear nerve compound action potential (CAP) to a single tone is smaller in amplitude, has a higher nonmasked threshold, and produces a less sensitive tuning curve (TC). Forward maskers can also produce amplitude enhancement of the CAP, but this was not observed for the onset portion of the DT response. The CAP TC is as sharply tuned as the TC of either the DT onset response or the entire DT response. A comparison was made of tuning of the DT response to the onset, the first half and second half of the 23-ms duration probe stimulus, using either a 5- or 15-ms masker-probe interval. An increase of the tip threshold of the TC to all three portions of the stimulus occurred as the interval was increased between the end of the masker and the midpoint of the portion of the stimulus under question. The 15-ms masker-probe interval produced sharper TCs.

Sharply tuned cochlear nerve ensemble periodicity responses to sonic and ultrasonic frequencies.

Vertebrates are able to perceive the pitch of a series of harmonics, even when the fundamental frequency has been removed from the acoustic stimulus. Neural periodicity responses corresponding to the "missing fundamental" frequency of sonic stimuli have been observed in the auditory system of several animal species, including our own. This paper examines periodic cochlear neural responses of the gerbil. Periodicity responses to both sonic and ultrasonic stimuli originate within the cochlea of this animal. Acoustic stimuli, consisting of 2-12 successive harmonic frequencies, were used to generate an ensemble cochlear nerve periodicity response that was recorded from the round window of the cochlea. This response had a frequency equal to that of the missing fundamental, and not to those of the harmonic stimuli. Forward masking of the stimuli used to produce the periodicity response was used to generate sharp tuning curves, with tip frequencies corresponding to the harmonics and not to the periodicities. The sharpness of these functions increased as the frequencies of the harmonics increased, up to at least 38 kHz. This property could be related to reception of ultrasonic vocalizations utilized by many rodent species.

Auditory nerve neurophonic tuning curves produced by masking of round window responses.

In response to low-intensity, low-frequency, phase-locked tonal stimuli with non-alternating polarity, the time-average round window (RW) response of the gerbil is a mixture of the auditory nerve neurophonic (ANN) and cochlear microphonic (CM), with the former often being of equal or greater magnitude than the latter. Forward masking (using a conservative 25% amplitude reduction criterion) can be used to generate ANN tuning curves (TC). Most of these TCs are sharply tuned V-shaped functions. Harmonic distortion is often present in the ANN, especially in response to the lower-frequency (< or = 1 kz) or higher-intensity (> or = 50 dB) stimuli. The TCs created by forward masking of the harmonics are similar in appearance to those generated by masking the fundamental frequency of the ANN. When lower-frequency probe stimuli (< or = approximately equal to 1 kHz) are used, the frequency of the TC tip tends to be higher than that of the probe; with higher probe frequencies, the tip tends to be lower. Regardless of the frequency of the probe, the TC tip threshold occurs at an intensity level lower than that of the probe. The sharpness of these TCs generally increases as a function of the frequency of the probe stimulus and the values of Q10dB are comparable to those of FTCs of cochlear nerve fibers of the gerbil. The amplitude of the ANN is often enhanced in response to a limited intensity range of forward maskers over a restricted range of frequencies that are outside the high-frequency boundary of the forward masker TC. By alternating the polarity of the probe stimulus, the CM can be canceled, allowing the effects of simultaneous maskers to be evaluated.

Auditory nerve neurophonic produced by the frequency difference of two simultaneously presented tones.

When two phase-locked sinusoidal stimuli having frequencies of F1 and F2 are simultaneously introduced to the ear of the gerbil, a difference tone (DT) can be observed (DT = F2-F1, where F2 > F1) in the time-averaged electrical response recorded from the cochlear round window (RW). Tetrodotoxin (TTX), which blocks the axonal firing of the cochlear nerve fiber, greatly attenuates this DT response, suggesting it is primarily neural in origin. Alternating the polarity of a single phase-locked tone cancels out the RW cochlear microphonic (CM) from the time-averaged response, leaving a residual auditory nerve neurophonic (ANN) response if the stimulus frequency is low enough to result in phase-locked firing of cochlear nerve axons. Simultaneous presentation of 1 kHz (F1) and 2 kHz (F2) tones, each being phase-locked with alternating polarity, produces a small ANN in response to the original tones and a large time-averaged ANN in response to the DT. Even when the frequency of the individual tones is too high to support phase-locking, a large DT-ANN can also be measured in response to simultaneously presented tones. A robust time-averaged DT-ANN can be measured when the temporal and intensity relationships between F1 and F2 are varied widely, with the latency (but not amplitude) of the response following the stimulus envelope. The DT-ANN produced by pairs of tones having frequencies ranging from 500 Hz to 3.5 kHz is largest in response to a DT of approximately 700-1100 Hz. This is in contrast to the ANN generated in response to a single tone, which decreases in magnitude as the stimulus frequency increases from 500 to 1500 Hz. Robust DT-ANNs can be measured from the gerbil even when the F2 frequency is greater than 30 kHz.

Tuning curves of the difference tone auditory nerve neurophonic.

When a pair of tonal stimuli of different frequencies (F1 and F2, where F2 > F1) are simultaneously presented to the ear, an electrical response with a frequency of F2-F1 can be recorded from the round window (RW) of the gerbil's cochlea. By using phase-locked tones of alternating polarity, the cochlear microphonics are canceled, leaving a time-averaged difference tone-auditory nerve neurophonic (DT-ANN). When the F1 frequency ranges from 1.25 to 30 kHz and F2-F1 approximately 900 Hz, a DT-ANN audiogram can be constructed which parallels (but is at least 10 dB more sensitive than) the compound action potential (CAP) audiogram. In addition to this DT response, a smaller magnitude, higher threshold response having a frequency of 2 DT can often be measured. Both the DT-ANN and the 2 DT-ANN show non-monotonic amplitude input-output functions. The DT- and 2 DT-ANN responses can be forward masked. Masking of low level (e.g., 30 dB SPL) probe stimuli results in DT- and 2 DT-ANN V-shaped tuning curves (TC) with low tip thresholds (approximately 20-30 dB SPL) and a tip frequency close to that of F1 and F2. The Q10 dB values of the forward masked DT-ANN TCs ranges from 1.54 to 20.0 for F1 frequencies varying from 2 to 20 kHz, respectively. The V-shaped DT-ANN TCs generated with simultaneous maskers are often flanked, outside their high- and low-frequency slopes, by frequency-intensity domains where the masker enhances the amplitude of the DT-ANN response. These data (1) provide evidence that, in response to low-intensity tones, the DT-ANN is generated by a restricted population of neurons that have characteristic frequencies close to F1 and F2, and (2) provide evidence for sharply tuned, phase-locked activity occurring in response to low-intensity stimuli, by cochlear axons having characteristic frequencies as high as 20 kHz.

Nonlinear effects of noise on phase-locked cochlear-nerve responses to sinusoidal stimuli.

It is well known that, in a cochlear afferent axon with background spike activity, a sinusoidal stimulus (tone) of sufficiently low frequency will produce periodic modulation of the instantaneous spike rate, the alternating half cycles of which comprise excursions above and below the mean background spike rate. It also is known that if the amplitude of the stimulus is sufficiently small, the instantaneous spike rate follows very nearly a sinusoidal trajectory through these positive and negative excursions. For such cases, we define the AC responsiveness of a primary auditory afferent axon to be the amplitude of sinusoidal modulation of the instantaneous spike rate divided by the amplitude of the tone producing that modulation. In the experiments described in this paper, changes in AC responsiveness were followed during and after sudden changes in the background noise level. When the amplitude of the tone was sufficiently small relative to that of the noise, we found that the AC responsiveness can be strongly dependent on the time elapsed since the last change in noise level, while being nearly independent of the amplitude of the tone itself. Under those circumstances, after transitions between noise levels 20 dB apart, we observed changes in AC responsiveness that consistently followed time courses similar to those of the short-term mean (background) spike rate (approximating the adapting response to the noise alone), unfolding over several milliseconds or tens of milliseconds. At the time of the transition between noise levels, there was another change in AC responsiveness, which appeared to be instantaneous; as the noise level increased, the AC responsiveness immediately increased with it. This seemingly paradoxical effect and the similarity of the time courses of AC responsiveness and short-term mean spike rate both are consistent with a simple, descriptive model of spike generation involving the shifting of threshold along a bell curve.

Auditory nerve neurophonic recorded from the round window of the Mongolian gerbil.

In the Mongolian gerbil, round window (RW) recordings of averaged responses to phase-locked acoustic stimuli which are not alternated in polarity can include both the cochlear mirophonic (CM) and auditory nerve neurophonic (ANN). The ANN can dominate the recordings when the RW electrode is referenced to some portion of the body that allows the two electrodes to straddle the auditory nerve. Concentric bipolar RW electrodes are biased in favor of the CM. When there is a substantial ANN component in the RW response, as the sinusoidal stimulus intensity increases there is a non-monotonic increase of amplitude and a pronounced change of phase of the response. When the phase-locked stimuli are alternated in polarity in order to cancel the CM, a residual response is often observed. This residual response has twice the frequency of the stimulus and is decreased in amplitude by forward masking. It also shows a pattern of amplitude decrement following the stimulus onset, resembling adaptation of the firing rate of cochlear nerve axons. Tetrodotoxin (TTX) eliminates the non-monotonic RW amplitude input-output (I/O) function, reduces the phase changes of the response as the stimulus intensity is increased, eliminates the residual non-canceled response to alternated stimuli, and the time-limited amplitude decrements which resemble adaptation. Following application of TTX, the RW response of the gerbil to stimuli with non-alternated polarity much more closely resembles the CM responses of other animals. It is concluded that the gerbil's residual response following cancellation of the CM is the ANN, and that the RW of the gerbil is a convenient site for recording measures of phase-locked cochlear axonal activity.

Dynamic changes in tuning in the gerbil cochlea.

Afferent axons of the gerbil cochlear nerve were studied with reverse correlation analyses carried out with movable time windows and with noise that was modulated with a 10-Hz trapezoidal envelope that switched the noise amplitude between two levels, 20 dB apart. At the time of switching, the attributes of the axonal tuning curves derived in this manner switched very rapidly (e.g., within 10 ms) from those characteristic of lower-level stimuli to those characteristic of higher-level stimuli and vice versa. As previous investigators have shown, the attributes of tuning curves at higher levels include broader bandwidth and an accentuated low-frequency hump. Characteristic frequencies (CFs) of gerbil axons used in this study ranged from approximately 500 Hz to approximately 5 kHz. Over this range, the low-frequency hump was most pronounced in our studies for units with higher CFs, each of which showed a sharp high-frequency peak and a distinctly separate, broad low-frequency hump (reminiscent of the tip and tail of a conventional frequency-threshold tuning curve). The amplitude of the peak relative to that of the hump, and the breadth of the peak, both changed rapidly and reversibly following sudden change of noise level. Observation of such rapid changes of tuning would be difficult to achieve with conventional frequency-threshold tuning curves, derived from tonal stimuli.

Amplitude enhancement is seen in the cochlear nerve but not at, or before, the afferent synapse.

The amplitude of the cochlear nerve compound action potential (CAP) produced by a moderate intensity tonal stimulus (S2) can be enhanced when S2 is preceded by a low intensity S1 of the same frequency. The presence of S1 had no observable influence on the threshold of the CAP to S2. Enhancement was not observed in the cochlear microphonics or summating potentials. Deactivation of the contralateral olivocochlear bundle did not influence enhancement. Tetrodotoxin (TTX) was applied to the round window to block cochlear nerve spike activity, resulting in a residual EPSP-like potential, as described in the guinea pig by Dolan et al. (1989). Kainic acid, in turn, eliminated this EPSP-like response. Even though some differences were found in the responses of the gerbil and their guinea pig preparation to TTX and kainic acid, enhancement was not observed in this residual potential. When enhancement was observed at the level of the CAP, it was observed at brainstem levels. It is suggested that enhancement originates within the cochlear nerve axons.

Albino and pigmented gerbil auditory function: influence of genotype and gentamicin.

Auditory function of albino and pigmented gerbils was examined before and after treatment with the ototoxic aminoglycoside antibiotic gentamicin. Auditory brainstem responses (ABRs) and cochlear nerve compound action potentials (CAPs) were measured in response to pure tones having frequencies between 2 and 32 kHz. Age-matched albinos had significantly lower CAP, but not ABR, thresholds than pigmented gerbils. Gentamicin treatment elevated CAP and ABR thresholds in both genotypes, but pigmented gerbils were less severely affected. Compared to the ABR, the CAP is a more sensitive measure of ototoxicity and pigmentation differences. CAP tuning curves (TCs) were another sensitive measure of genotypic differences in susceptibility to ototoxicity. TC tip thresholds from pigmented animals given gentamicin were not as elevated as the TC tip thresholds of albinos.

One-tone suppression in the cochlear nerve of the gerbil.

One-tone rate suppression has been reported several times for auditory nerve fibers of mammalian and non-mammalian vertebrates. Because its properties are very similar to those of two-tone rate suppression, the possibility exists that one-tone rate suppression is the result of an interaction within the inner ear of the suppressing tonal stimulus and some ongoing extraneous acoustic stimulus. For this reason, reports of one-tone rate suppression often elicit suspicions that the investigators were not sufficiently careful in controlling leaks in their acoustic barriers or in the electrical pathways to their acoustic drivers. Recent reports of one-tone rate suppression in pigeon basilar-papillar fibers and goldfish saccular fibers were accompanied by descriptions of measures taken to avoid such leaks. In this paper, we describe one-tone rate suppression in a mammal, the Mongolian gerbil; and we demonstrate that the background spike activity being suppressed is not driven by either external sounds coming from outside the acoustic isolation test chamber or by non-stimulus electrical inputs to the acoustic driver. The suppressed background spike activity evidently arises from sources within the animal. These sources may be non-acoustic, associated with spontaneous pre- or post-synaptic ion-channel activity; or they may be acoustic sources--internal sound or vibration generators.

Derived and enhanced compound action potentials at near-threshold levels: forward masking increases sensitivity of audiograms and tuning curves.

The amplitude of a cochlear nerve compound action potential (CAP) can be increased by forward maskers having levels close to the visual detection threshold of the CAP. This effect, termed enhancement, varies as a function of the frequency of the masker and probe stimulus, and is nonmonotonic with respect to the level of the masker. Other studies using the derived CAP have used a subtraction technique to evaluate the ability of simultaneous maskers having levels near the CAP visual detection threshold to influence the CAP produced by an above threshold tone. The present paper compares audiograms produced by the conventional nonmasked CAP visual detection threshold technique with audiograms produced by both forward masked derived CAPs and forward masked enhanced CAPs. In response to low and middle frequency stimuli, both masked CAP measures produce more sensitive audiograms than does the conventional nonmasking method. Forward masked amplitude tuning curves (TCs) were also produced, comparing the conventional 50% amplitude reduction and 20 microV amplitude reduction methods with TCs obtained with derived and enhanced CAPs. When the same criteria are used, both masked CAP measures result in sharply tuned amplitude TCs that are approximately 60 dB more sensitive than the conventional CAP technique. At near-threshold levels, the properties of forward masked enhanced and derived CAPs appear to be similar.

Modulation of cochlear nerve spike rate by cardiac activity in the gerbil.

Among primary auditory axons with characteristic frequencies (CFs) below 2500 Hz, a substantial subpopulation was found in which spike activity was driven by cardiac events. The presence of cardiac-driven activity was inferred from cycle histograms triggered on the peak of the electrocardiogram (ECG). This driven activity was either like a simple onset response (often followed by a reduction of spike activity to below background level), or as a longer lasting series of peaks and troughs. In two axons with high CFs (7 kHz and 12.5 kHz), cardiac-driven suppression was observed. Recordings made by a probe microphone revealed the presence of heart-related sound in the external ear canal. The onset of that sound coincided with the onset of cardiac-driven spike activity (and suppression).