On the Tonotopy of the Low-Frequency Region of the Cochlea.

It is generally assumed that frequency selectivity varies along the cochlea. For example, at the base of the cochlea, which is a region sensitive to high-frequency sounds, the best frequency of a cochlear location increases toward the most basal end, that is, near the stapes. Response phases also vary along cochlear locations. At any given frequency, there is a decrease in phase lag toward the stapes. This tonotopic arrangement in the cochlea was originally described by Georg von Békésy in a seminal series of experiments on human cadavers and has been confirmed in more recent works on live laboratory animals. Nonetheless, our knowledge of tonotopy at the apex of the cochlea remains incomplete in animals with low-frequency hearing, which is relevant to human speech. The results of our experiments on guinea pig, gerbil, and chinchilla cochleas, regardless of the sex of the animal, show that responses to sound differ at locations across the apex in a pattern consistent with previous studies of the base of the cochlea.SIGNIFICANCE STATEMENT Tonotopy is an important property of the auditory system that has been shown to exist in many auditory centers. In fact, most auditory implants work on the assumption of its existence by assigning different frequencies to different stimulating electrodes based on their location. At the level of the basilar membrane in the cochlea, a tonotopic arrangement implies that high-frequency stimuli evoke largest displacements at the base, near the ossicles, and low-frequency sounds have their greatest effects at the apex. Although tonotopy has been confirmed at the base of the cochlea on live animals at the apex of the cochlea, however, it has been less studied. Here, we show that a tonotopic arrangement does exist at the apex of the cochlea.

Information Processing by Onset Neurons in the Cat Auditory Brainstem.

Octopus cells in the ventral cochlear nucleus (VCN) have been difficult to study because of the very features that distinguish them from other VCN neurons. We performed in vivo recordings in cats on well-isolated units, some of which were intracellularly labeled and histologically reconstructed. We found that responses to low-frequency tones with frequencies < 1 kHz reveal higher levels of neural synchrony and entrainment to the stimulus than the auditory nerve. In responses to higher frequency tones, the neural discharges occur mostly near the stimulus onset. These neurons also respond in a unique way to 100 % amplitude-modulated (AM) tones with discharges exhibiting a bandpass tuning. Responses to frequency-modulated sounds (FM) are unusual: Octopus cells react more vigorously during the ascending than the descending parts of the FM stimulus. We examined responses of neurons in the ventral nucleus of the lateral lemniscus (VNLL) whose discharges to tones and AM sounds are similar to octopus cells. Repeated stimulation with short tone pips of VCN and VNLL onset neurons evokes trains of action potentials with gradual shifts toward later times in their first spike latency. This behavior parallels short-term post-synaptic depression observed by other authors in in vitro VCN recordings of octopus cells. VCN and VNLL onset units in cats respond to frozen noise stimuli with gaps as narrow as 1 ms with a robust discharge near the stimulus onset following the gap. This finding suggests that VCN and VNLL onset cells play a role in gap detection, which is of great importance to speech perception.

Unusual mechanical processing of sounds at the apex of the Guinea pig cochlea.

One of the tenets of mammalian auditory physiology is that the frequency selectivity at the cochlear base decreases as a function of stimulus level. Changes in frequency selectivity have been shown to be accompanied by changes in response phases as a function of stimulus level. The existence of such nonlinear properties has been revealed by the analysis of either direct or indirect recordings of mechanical vibrations of the cochlea. Direct measurements of cochlear mechanical vibrations, however, have been carried out with success primarily in cochlear regions that are tuned to frequencies >7 kHz, but not in regions sensitive to lower frequencies. In this paper we continue to analyze recently published data from measurements of sound-induced vibrations at four locations near the apex of the intact guinea pig cochlea, in a region encompassing approximately 25% of its total length. Analysis of the responses at all locations reveal level-dependent phase properties that are rather different from those usually reported at the base of the cochlea of laboratory animals such as the chinchilla. Cochlear group delays, for example, increase or remain constant with increasing stimulus. Similarly, frequency selectivity at all the regions increases as a function of stimulus level.

Mechanical tuning and amplification within the apex of the guinea pig cochlea.

KEY POINTS: A popular conception of mammalian cochlear physiology is that tuned mechanical vibration of the basilar membrane defines the frequency response of the innervating auditory nerve fibres However, the data supporting these concepts come from vibratory measurements at cochlear locations tuned to high frequencies (>7 kHz). Here, we measured the travelling wave in regions of the guinea pig cochlea that respond to low frequencies (<2 kHz) and found that mechanical tuning was broad and did not match auditory nerve tuning characteristics. Non-linear amplification of the travelling wave functioned over a broad frequency range and did not substantially sharpen frequency tuning. Thus, the neural encoding of low-frequency sounds, which includes most of the information conveyed by human speech, is not principally determined by basilar membrane mechanics. ABSTRACT: The popular notion of mammalian cochlear function is that auditory nerves are tuned to respond best to different sound frequencies because basilar membrane vibration is mechanically tuned to different frequencies along its length. However, this concept has only been demonstrated in regions of the cochlea tuned to frequencies >7 kHz, not in regions sensitive to lower frequencies where human speech is encoded. Here, we overcame historical technical limitations and non-invasively measured sound-induced vibrations at four locations distributed over the apical two turns of the guinea pig cochlea. In turn 3, the responses demonstrated low-pass filter characteristics. In turn 2, the responses were low-pass-like, in that they occasionally did have a slight peak near the corner frequency. The corner frequencies of the responses were tonotopically tuned and ranged from 384 to 668 Hz. Non-linear gain, or amplification of the vibrations in response to low-intensity stimuli, was found both below and above the corner frequencies. Post mortem, cochlear gain disappeared. The non-linear gain was typically 10-30 dB and was broad-band rather than sharply tuned. However, the gain did reach nearly 50 dB in turn 2 for higher stimulus frequencies, nearly the amount of gain found in basal cochlear regions. Thus, our data prove that mechanical responses do not match neural responses and that cochlear amplification does not appreciably sharpen frequency tuning for cochlear regions that respond to frequencies <2 kHz. These data indicate that the non-linear processing of sound performed by the guinea pig cochlea varies substantially between the cochlear apex and base.

Fast Waves at the Base of the Cochlea.

Georg von Békésy observed that the onset times of responses to brief-duration stimuli vary as a function of distance from the stapes, with basal regions starting to move earlier than apical ones. He noticed that the speed of signal propagation along the cochlea is slow when compared with the speed of sound in water. Fast traveling waves have been recorded in the cochlea, but their existence is interpreted as the result of an experiment artifact. Accounts of the timing of vibration onsets at the base of the cochlea generally agree with Békésy's results. Some authors, however, have argued that the measured delays are too short for consistency with Békésy's theory. To investigate the speed of the traveling wave at the base of the cochlea, we analyzed basilar membrane (BM) responses to clicks recorded at several locations in the base of the chinchilla cochlea. The initial component of the BM response matches remarkably well the initial component of the stapes response, after a 4-µs delay of the latter. A similar conclusion is reached by analyzing onset times of time-domain gain functions, which correspond to BM click responses normalized by middle-ear input. Our results suggest that BM responses to clicks arise from a combination of fast and slow traveling waves.

Temporal properties of responses to sound in the ventral nucleus of the lateral lemniscus.

Besides the rapid fluctuations in pressure that constitute the "fine structure" of a sound stimulus, slower fluctuations in the sound's envelope represent an important temporal feature. At various stages in the auditory system, neurons exhibit tuning to envelope frequency and have been described as modulation filters. We examine such tuning in the ventral nucleus of the lateral lemniscus (VNLL) of the pentobarbital-anesthetized cat. The VNLL is a large but poorly accessible auditory structure that provides a massive inhibitory input to the inferior colliculus. We test whether envelope filtering effectively applies to the envelope spectrum when multiple envelope components are simultaneously present. We find two broad classes of response with often complementary properties. The firing rate of onset neurons is tuned to a band of modulation frequencies, over which they also synchronize strongly to the envelope waveform. Although most sustained neurons show little firing rate dependence on modulation frequency, some of them are weakly tuned. The latter neurons are usually band-pass or low-pass tuned in synchronization, and a reverse-correlation approach demonstrates that their modulation tuning is preserved to nonperiodic, noisy envelope modulations of a tonal carrier. Modulation tuning to this type of stimulus is weaker for onset neurons. In response to broadband noise, sustained and onset neurons tend to filter out envelope components over a frequency range consistent with their modulation tuning to periodically modulated tones. The results support a role for VNLL in providing temporal reference signals to the auditory midbrain.

Masking of sounds by a background noise--cochlear mechanical correlates.

In the search for cochlear correlates of auditory masking by noise stimuli, we recorded basilar membrane (BM) vibrations evoked by either tone or click signals in the presence of varying levels of background noise. The BM vibrations were recorded from basal regions in healthy cochleae of anaesthetized chinchilla and gerbil. Non-linear interactions that could underpin various aspects of psychophysical masking data, including both compression and suppression at the BM level, were observed. The suppression effects, whereby the amplitude of the responses to each stimulus component could be reduced, depended on the relative intensities of the noise and the tones or clicks. Only stimulus components whose frequencies fell inside the non-linear region of the recording site, i.e. around its characteristic frequency (CF), were affected by presentation of the 'suppressing' stimulus (which could be either the tone or the noise). Mutual suppression, the simultaneous reduction of the responses to both tones and noise components, was observed under some conditions, but overall reductions of BM vibration were rarely observed. Moderate- to high-intensity tones suppressed BM responses to low-intensity Gaussian stimuli, including both broadband and narrowband noise. Suppression effects were larger for spectral components of the noise response that were closer to the CF. In this regime, the tone and noise stimuli became the suppressor and probe signals, respectively. This study provides the first detailed observations of cochlear mechanical correlates of the masking effects of noise. Mechanical detection thresholds for tone signals, which were arbitrarily defined using three criteria, are shown to increase in almost direct proportion to the noise level for low and moderately high noise levels, in a manner that resembles the findings of numerous psychophysical observations.

Enhancement and distortion in the temporal representation of sounds in the ventral cochlear nucleus of chinchillas and cats.

A subset of neurons in the cochlear nucleus (CN) of the auditory brainstem has the ability to enhance the auditory nerve's temporal representation of stimulating sounds. These neurons reside in the ventral region of the CN (VCN) and are usually known as highly synchronized, or high-sync, neurons. Most published reports about the existence and properties of high-sync neurons are based on recordings performed on a VCN output tract--not the VCN itself--of cats. In other species, comprehensive studies detailing the properties of high-sync neurons, or even acknowledging their existence, are missing.Examination of the responses of a population of VCN neurons in chinchillas revealed that a subset of those neurons have temporal properties similar to high-sync neurons in the cat. Phase locking and entrainment--the ability of a neuron to fire action potentials at a certain stimulus phase and at almost every stimulus period, respectively--have similar maximum values in cats and chinchillas. Ranges of characteristic frequencies for high-sync neurons in chinchillas and cats extend up to 600 and 1000 Hz, respectively. Enhancement of temporal processing relative to auditory nerve fibers (ANFs), which has been shown previously in cats using tonal and white-noise stimuli, is also demonstrated here in the responses of VCN neurons to synthetic and spoken vowel sounds.Along with the large amount of phase locking displayed by some VCN neurons there occurs a deterioration in the spectral representation of the stimuli (tones or vowels). High-sync neurons exhibit a greater distortion in their responses to tones or vowels than do other types of VCN neurons and auditory nerve fibers.Standard deviations of first-spike latency measured in responses of high-sync neurons are lower than similar values measured in ANFs' responses. This might indicate a role of high-sync neurons in other tasks beyond sound localization.

Traveling waves on the organ of corti of the chinchilla cochlea: spatial trajectories of inner hair cell depolarization inferred from responses of auditory-nerve fibers.

Spatial magnitude and phase profiles for inner hair cell (IHC) depolarization throughout the chinchilla cochlea were inferred from responses of auditory-nerve fibers (ANFs) to threshold- and moderate-level tones and tone complexes. Firing-rate profiles for frequencies ≤2 kHz are bimodal, with the major peak at the characteristic place and a secondary peak at 3-5 mm from the extreme base. Response-phase trajectories are synchronous with peak outward stapes displacement at the extreme cochlear base and accumulate 1.5 period lags at the characteristic places. High-frequency phase trajectories are very similar to the trajectories of basilar-membrane peak velocity toward scala tympani. Low-frequency phase trajectories undergo a polarity flip in a region, 6.5-9 mm from the cochlear base, where traveling-wave phase velocity attains a local minimum and a local maximum and where the onset latencies of near-threshold impulse responses computed from responses to near-threshold white noise exhibit a local minimum. That region is the same where frequency-threshold tuning curves of ANFs undergo a shape transition. Since depolarization of IHCs presumably indicates the mechanical stimulus to their stereocilia, the present results suggest that distinct low-frequency forward waves of organ of Corti vibration are launched simultaneously at the extreme base of the cochlea and at the 6.5-9 mm transition region, from where antiphasic reflections arise.

Basilar-membrane responses to broadband noise modeled using linear filters with rational transfer functions.

Basilar-membrane responses to white Gaussian noise were recorded using laser velocimetry at basal sites of the chinchilla cochlea with characteristic frequencies near 10 kHz and first-order Wiener kernels were computed by cross correlation of the stimuli and the responses. The presence or absence of minimum-phase behavior was explored by fitting the kernels with discrete linear filters with rational transfer functions. Excellent fits to the kernels were obtained with filters with transfer functions including zeroes located outside the unit circle, implying nonminimum-phase behavior. These filters accurately predicted basilar-membrane responses to other noise stimuli presented at the same level as the stimulus for the kernel computation. Fits with all-pole and other minimum-phase discrete filters were inferior to fits with nonminimum-phase filters. Minimum-phase functions predicted from the amplitude functions of the Wiener kernels by Hilbert transforms were different from the measured phase curves. These results, which suggest that basilar-membrane responses do not have the minimum-phase property, challenge the validity of models of cochlear processing, which incorporate minimum-phase behavior.

Timing of cochlear responses inferred from frequency-threshold tuning curves of auditory-nerve fibers.

Links between frequency tuning and timing were explored in the responses to sound of auditory-nerve fibers. Synthetic transfer functions were constructed by combining filter functions, derived via minimum-phase computations from average frequency-threshold tuning curves of chinchilla auditory-nerve fibers with high spontaneous activity (Temchin et al., 2008), and signal-front delays specified by the latencies of basilar-membrane and auditory-nerve fiber responses to intense clicks (Temchin et al., 2005). The transfer functions predict several features of the phase-frequency curves of cochlear responses to tones, including their shape transitions in the regions with characteristic frequencies of 1 kHz and 3-4 kHz (Temchin and Ruggero, 2010). The transfer functions also predict the shapes of cochlear impulse responses, including the polarities of their frequency sweeps and their transition at characteristic frequencies around 1 kHz. Predictions are especially accurate for characteristic frequencies <1 kHz.

Response properties of cochlear nucleus neurons in monkeys.

Much of what is known about how the cochlear nuclei participate in mammalian hearing comes from studies of non-primate mammalian species. To determine to what extent the cochlear nuclei of primates resemble those of other mammalian orders, we have recorded responses to sound in three primate species: marmosets, cynomolgus macaques, and squirrel monkeys. These recordings show that the same types of temporal firing patterns are found in primates that have been described in other mammals. Responses to tones of neurons in the ventral cochlear nucleus have similar tuning, latencies, post-stimulus time and interspike interval histograms as those recorded in non-primate cochlear nucleus neurons. In the dorsal cochlear nucleus, too, responses were similar. From these results it is evident that insights gained from non-primate studies can be applied to the peripheral auditory system of primates.

Basilar membrane responses to noise at a basal site of the chinchilla cochlea: quasi-linear filtering.

Basilar membrane responses to clicks and to white noise were recorded using laser velocimetry at basal sites of the chinchilla cochlea with characteristic frequencies near 10 kHz. Responses to noise grew at compressive rates and their instantaneous frequencies decreased with increasing stimulus level. First-order Wiener kernels were computed by cross-correlation of the noise stimuli and the responses. For linear systems, first-order Wiener kernels are identical to unit impulse responses. In the case of basilar membrane responses, first-order Wiener kernels and responses to clicks measured at the same sites were similar but not identical. Both consisted of transient oscillations with onset frequencies which increased rapidly, over about 0.5 ms, from 4-5 kHz to the characteristic frequency. Both first-order Wiener kernels and responses to clicks were more highly damped, exhibited slower frequency modulation, and grew at compressive rates with increasing stimulus levels. Responses to clicks had longer durations than the Wiener kernels. The statistical distribution of basilar membrane responses to Gaussian white noise is also Gaussian and the envelopes of the responses are Rayleigh distributed, as they should be for Gaussian noise passing through a linear band-pass filter. Accordingly, basilar membrane responses were accurately predicted by linear filters specified by the first-order Wiener kernels of responses to noise presented at the same level. Overall, the results indicate that cochlear nonlinearity is not instantaneous and resembles automatic gain control.

Analysis of responses to noise in the ventral cochlear nucleus using Wiener kernels.

Responses to noise were recorded in ventral cochlear nucleus (VCN) neurons of anesthetized chinchillas and cats, then analyzed using Wiener-kernel theory. First-order kernels, which are proportional to reverse-correlation functions, of primary-like (PL) and primary-like with notch (PLN) neurons having low characteristic frequency (CF) are similar to those obtained in auditory nerve fibers (ANFs). Such kernels consist of lightly damped transient oscillations with frequency equal to the neuron's CF. The first-order kernel of high-CF PL and PLN neurons displays no evidence of tuning to CF. Second-order kernels of the aforementioned VCN neuron types also resemble those in the nerve, irrespective of CF. In general, first- and second-order Wiener kernels of chopper neurons are similar to those obtained in high-CF ANFs. This is likely the consequence of the poor phase-locking capabilities to near-CF tones exhibited by chopper neurons. By analyzing second-order kernels using singular-value decomposition, it was possible to estimate group delays for the entire neuronal population, regardless of the neuron's type or CF. This was done by analyzing the highest-ranking singular vector (FSV). Amplitude values of FSVs in chopper neurons in the cat are substantially larger than in high-spontaneous ANFs.

Auditory midbrain and nerve responses to sinusoidal variations in interaural correlation.

The human sensitivity to interaural temporal differences in the acoustic waveforms to the two ears shows remarkable acuity but is also very sluggish. Fast changes in binaural parameters are not detectable, and this inability contrasts sharply with the excellent temporal resolution of the monaural auditory system. We studied the response of binaural neurons in the inferior colliculus of the cat to sinusoidal changes in the interaural correlation of broadband noise. Responses to the same waveforms were also obtained from auditory nerve fibers and further analyzed with a coincidence analysis. Overall, the auditory nerve and inferior colliculus showed a similar ability to code changes in interaural correlation. This ability extended to modulation frequencies an order of magnitude higher than the highest frequencies detected binaurally in humans. We conclude that binaural sluggishness is not caused by a lack of temporal encoding of fast binaural changes at the level of the midbrain. We hypothesize that there is no neural substrate at the level of the midbrain or higher to read out this temporal code and that this constitutes a low-pass "sluggishness" filter.

Delays of stimulus-frequency otoacoustic emissions and cochlear vibrations contradict the theory of coherent reflection filtering.

When stimulated by tones, the ear appears to emit tones of its own, stimulus-frequency otoacoustic emissions (SFOAEs). SFOAEs were measured in 17 chinchillas and their group delays were compared with a place map of basilar-membrane vibration group delays measured at the characteristic frequency. The map is based on Wiener-kernel analysis of responses to noise of auditory-nerve fibers corroborated by measurements of vibrations at several basilar-membrane sites. SFOAE group delays were similar to, or shorter than, basilar-membrane group delays for frequencies >4 kHz and <4 kHz, respectively. Such short delays contradict the generally accepted "theory of coherent reflection filtering" [Zweig and Shera, J. Acoust. Soc. Am. 98, 2018-2047 (1995)], which predicts that the group delays of SFOAEs evoked by low-level tones approximately equal twice the basilar-membrane group delays. The results for frequencies higher than 4 kHz are compatible with hypotheses of SFOAE propagation to the stapes via acoustic waves or fluid coupling, or via reverse basilar membrane traveling waves with speeds corresponding to the signal-front delays, rather than the group delays, of the forward waves. The results for frequencies lower than 4 kHz cannot be explained by hypotheses based on waves propagating to and from their characteristic places in the cochlea.

Wiener kernels of chinchilla auditory-nerve fibers: verification using responses to tones, clicks, and noise and comparison with basilar-membrane vibrations.

Responses to tones, clicks, and noise were recorded from chinchilla auditory-nerve fibers (ANFs). The responses to noise were analyzed by computing the zeroth-, first-, and second-order Wiener kernels (h0, h1, and h2). The h1s correctly predicted the frequency tuning and phases of responses to tones of ANFs with low characteristic frequency (CF). The h2s correctly predicted the frequency tuning and phases of responses to tones of all ANFs, regardless of CF. Also regardless of CF, the kernels jointly predicted about 77% of the features of ANF responses to "frozen" samples of noise. Near-CF group delays of kernels and signal-front delays of responses to intense rarefaction clicks exceeded by 1 ms the corresponding basilar-membrane delays at both apical and basal sites of the chinchilla cochlea. This result, confirming that synaptic and neural processes amount to 1 ms regardless of CF, permitted drawing a map of basilar-membrane delay as a function of position for the entire length of the chinchilla cochlea, a first for amniotic species.

Wiener-kernel analysis of responses to noise of chinchilla auditory-nerve fibers.

Responses to broadband Gaussian white noise were recorded in auditory-nerve fibers of deeply anesthetized chinchillas and analyzed by computation of zeroth-, first-, and second-order Wiener kernels. The first-order kernels (similar to reverse correlations or "revcors") of fibers with characteristic frequency (CF) <2 kHz consisted of lightly damped transient oscillations with frequency equal to CF. Because of the decay of phase locking strength as a function of frequency, the signal-to-noise ratio of first-order kernels of fibers with CFs >2 kHz decreased with increasing CF at a rate of about -18 dB per octave. However, residual first-order kernels could be detected in fibers with CF as high as 12 kHz. Second-order kernels, 2-dimensional matrices, reveal prominent periodicity at the CF frequency, regardless of CF. Thus onset delays, frequency glides, and near-CF group delays could be estimated for auditory-nerve fibers innervating the entire length of the chinchilla cochlea.