Eric Javel

Electrical stimulation of the auditory nerve. III. Response initiation sites and temporal fine structure.

Latency, temporal dispersion and input-output characteristics of auditory nerve fiber responses to electrical pulse trains in normal and chronically deafened cat ears were classified and tentatively associated with sites where activity is initiated. Spikes occurred in one or more of four discrete time ranges whose endpoints overlapped partially. A responses had latencies <0.44 ms, exhibited asymptotic temporal dispersion of 8-12 micros and possessed an average dynamic range of 1.2 dB for 200 pulses/s (pps) pulse trains. They likely originated from central processes of spiral ganglion cells. B(1) and B(2) responses (0.45-0.9 ms, 25-40 micros, 1.9 dB) likely stemmed from activity at myelinated and unmyelinated peripheral processes, respectively. C100 micros) likely originated from direct stimulation of inner hair cells, and D8 dB) arose from propagating traveling waves possibly caused by electrically induced motion of outer hair cells. C and D responses were recorded only in acoustically responsive ears. Mean latencies of spikes in all time ranges usually decreased with intensity, and activity at two or even three discrete latencies was often observed in the same spike train. Latency shifts from one discrete time range to another often occurred as intensity increased. Some shifts could be attributed to responses to the opposite-polarity phase of the biphasic pulse. In these cases, temporal dispersion and dynamic range were approximately equal for activity at each latency. A second type of latency shift was also often observed, in which responses at each latency exhibited dissimilar temporal dispersion and dynamic range. This behavior was attributed to a centralward shift in the spike initiation site and it occurred for monophasic as well as biphasic signals. Several fibers exhibited dual latency activity with a 40-90 micros time difference between response peaks. This may have stemmed from spike initiation at nodes on either side of the cell body. Increasing the stimulus pulse rate to 800-1000 pps produced small increases in temporal dispersion and proportionate increases in asymptotic discharge rate and dynamic range, but thresholds did not improve and slopes of rate-intensity functions (in spikes/s/dB) did not change. Responses to high-rate stimuli also exhibited discrete latency increases when discharge rates exceeded 300-400 spikes/s. Spike by spike latencies in these cases depended strongly on the discharge history. Implications for high-rate speech processing strategies are discussed.

Coding of AM tones in the chinchilla auditory nerve: Implications for the pitch of complex tones

Responses to sinusoidally amplitude modulated (AM) tones were recorded in single auditory nerve fibers of anesthetized chinchillas. The tones chosen were of a class which, in humans, gives rise to a percept of low subjective pitch. It was found that, for high-frequency stimuli, neurons tuned to high frequencies signaled waveform envolope periodicity when the stimulus was of sufficient intensity. Neurons tuned to low frequencies responded to low-frequency AM tones in an orderly manner which ranged, as overall intensity was raised, from signaling all frequency components to signaling only the component to which the neuron was most sensitive. This result was interpreted to indicate the presence of two-tone suppression. Variation of modulation frequency and modulation depth produced response patterns which were generally predictable based on the relative effectiveness of each of the component frequencies in eliciting discharges. Neurons tuned to low frequencies did not respond at low and moderate intensities to higher-frequency AM tones, even though the subjective pitch of the tones corresponded to frequencies to which the neuron was sensitive. At high intensities, distortion products locked in-phase to the frequency of the subjective pitch were observed. Responses to a single AM tone recorded from different neurons in the same animal displayed considerable diversity in their responses. Response diversity was correlated with neuronal tuning characteristics, stimulus intensiry, and intrinsic factors such as suppression. Neurons retained stimulus finestructure information in the temporal patterns of their discharges as stimulus components were varied from a harmonic relationship to an inharmonic relationship. The data indicate that responses of auditory nerve fibers contain sufficient information for extraction of the subjective pitch of AM tones by a central auditory processor which operates on temporal features of the responses.

Two‐tone suppression in auditory nerve of the cat: Rate‐intensity and temporal analyses

Responses to two-tone stimuli were recorded from auditory-nerve fibers in anesthetized cats. One tone, the suppressor, was set at a frequency above characteristic frequency and was fixed in intensity. A second tone was set at an excitatory frequency and was varied in intensity. The suppressor tone, when set at a sufficient level, always reduced the response to the excitatory tone by an amount equivalent to a fixed number of decibels, regardless of the excitatory tones intensity. Estimates of suppression magnitude were derived from shifts in rate-intensity function obtained when the suppressor tone was present relative to the functions obtained for the excitatory tone alone. When suppressor-tone intensity was increased, suppression magnitude likewise increased. When the two tones were increasingly separated in frequency, either by varying the excitor or by varying the suppressor, suppression magnitude decreased monotonically. Suppression behaved in the same manner regardless of whether suppresor tone was excitatory or nonexcitatory. When frequency separation was small enough and when both tones were above the neurons characteristic frequency, responses synchronized to low-order combination tones could be elicited. These responses usually possessed different rate-intensity characteristics and resulted in estimates of suppression magnitude which were spuriously low. When frequency separation is normalized with regard to position of traveling wave maxima within the cochlear duct, the magnitude of two-tone suppression for a given suppressor-tone intensity is seen to be frequency independent.

Suppression of auditory nerve responses I: Temporal analysis, intensity effects and suppression contours

Two-tone suppression was studied in response patterns of single auditory nerve fibers in anesthetized cats. Utilizing suppression of discharge synchronization in response to low- and moderate-frequency tones as an index, it was found that (a) suppression behaves in the same manner when the suppressor tone presented alone is strongly excitatory as when it is ineffective in altering discharge rate; (b) suppression exists throughout an auditory nerve fibers response area; (c) for fixed-intensity suppressors, suppression is maximal at a fibers characteristic frequency; and (d) suppression magnitude over a wide intensity range depends only upon the parameters of the suppressor tone and not of the tone being suppressed. The data are in general agreement with previously published reports of suppression behavior, and they support the concept that suppression is generated primarily as a result of interactions occurring within hair cells or in the subtectorial space.

Long-term adaptation in cat auditory-nerve fiber responses.

Driven responses of cat auditory-nerve fibers to long-duration characteristic-frequency (CF) tones could decrease substantially over time periods ranging from seconds to minutes. In extreme cases, the discharge rate could fall before the pre-stimulation spontaneous rate (SR). Reductions in response were characterized by two processes, each of which followed a decaying exponential function. long-term adaptation affects the discharge rate in the first several seconds following stimulus onset. The average amount in high-SR fibers was 42.5% for tones at 20-40 dB SL, and the mean time constant was 3.65 s. Long-term adaptation increased significantly with sensation level (SL, or level above threshold), decreased with SR, and was not significantly correlated with CF or fiber response threshold. Time constants did not depend on CF, SR, or SL. Very-long-term adaptation refers to further, smaller reductions in the discharge rate that accumulate over a period of minutes. Fiber responses formed two groups. The larger group adapted with a mean time constant of 45.22 s for CF tones at 20-40 dB SL, and the smaller group did not adapt over very long terms. Considerable variability in amounts of long-term and very-long-term effects do not arise from cochlear mechanics or middle ear muscle activity. No long-term effects were observed in responses of fibers directly stimulated by high-intensity electrical pulses present at rates up to 500/s through a cochlear implant. This suggests that the effects do not arise from fundamental differences in spike-generating properties of spiral ganglion cells. The data suggest that long-term adaptation may occur either when neurotransmitter utilization at inner hair cell synapses exceeds the rate at which it is replenished from global stores or uptake mechanisms, or which metabolic resources influencing neurotransmitter release become depleted. The neural data are related to perceptual findings in human listeners, in which unusually large amounts of tone decay may be observed at high frequencies, and they indicate that the perceptual effects originate peripherally.

The effects of stimulus duration on ABR and behavioral thresholds

ABR and behavioral thresholds were estimated as a function of stimulus duration for three normal and two hearing-impaired subjects. Stimuli were 2000-Hz tone bursts with 0.5-ms rise/fall times and durations ranging from 1 to 256 or 512 ms. For both groups of subjects, ABR thresholds were independent of stimulus duration. Normal subjects showed greater improvement in behavioral thresholds as a function of duration than did subjects with hearing losses. Thus, it appeared that ABR and behavioral thresholds were affected differently by changes in stimulus duration and that the magnitude of these differences could depend upon the presence of hearing loss. These data indicate that temporal integration may be one factor which makes comparisons between ABR and behavioral thresholds complicated. In the present study, the magnitude of hearing loss, measured by the ABR, would have been underestimated if normal behavioral thresholds for short-duration stimuli were used as the reference.

Identification of gene expression profiles in rat ears with cDNA microarrays

The physiological processes of hearing implicate thousands of molecules acting in harmony; however, their identities are only partially understood. We used cDNA microarrays containing 1,176 genes to identify >150 genes expressed in rat middle and inner ear tissue. Expressed genes covered several gene families and biological pathways, many of which have previously not been described. Transcription factor genes that were expressed included inhibitors of DNA binding protein (Id). These were localized to the spiral ganglion, organ of Corti and stria vascularis, and they are possibly involved in neurogenesis and angiogenesis. Transcriptional factors that were highly expressed included Gax (homeobox) and I-kappaB, which inhibit cellular proliferation. Their presence suggests that inhibitory programs for cell proliferation are enforced in the ear. Ion channel genes that were expressed included voltage-dependent L-type calcium channels (LTCC) and proton-gated cation channels (PGCC). Genes involved in neurotransmitter production and release included glutamic acid decarboxylase (GAD1). Genes involved in postsynaptic inhibition included neuropeptide Y5 receptors (NPY5) and GAD1. Due to the existence of receptors and/or enzymes involved in their biochemical synthesis, neurotransmitters associated with these might include serotonin, glutamide, acetylcholine, gamma-aminobutyric acid (GABA), neurotensin, and dopamine.

ABR measurements in the cat using a forward‐masking paradigm

Probe-elicited wave V amplitudes of the auditory brainstem response (ABR) were measured using a forward-masking paradigm. Subjects were anesthetized cats. For individual experiments, probe frequency and intensity were fixed and masker frequencies and intensities were varied. For each masker frequency, the extent to which the probe-elicited wave V amplitude was reduced by the preceding masker was plotted as a function of masker intensity. The rising segments of the masking functions were fitted with straight lines, using a least-squares procedure, to obtain estimates of their slopes. Masking grew most rapidly for masker frequencies below probe frequency, becoming progressively less steep as masker frequency increased. ABR tuning curves were constructed by using the linear fits to define the masker intensity that caused a 50% reduction in probe-elicited wave V amplitude. The shapes of these tuning curves were comparable to whole-nerve action potential (AP) tuning curves obtained under similar stimulus conditions. These results indicate that ABR amplitude measurements in a forward-masking paradigm can be used to estimate the growth of response to masking stimuli and frequency selectivity in a manner similar to AP amplitude measurements.

Shapes of cat auditory nerve fiber tuning curves

Tuning curves of auditory nerve fibers in normal-hearing cats were fitted by a computational model comprising four processes. One process accounts for sensitivity in tuning curve tails and consists of an approximation to bandpass filtering by extracochlear structures. The second and third processes describe passive and active components of basilar membrane (BM) mechanics, respectively. The former consists of a lowpass filter function, which provides baseline threshold sensitivity and filtering above characteristic frequency (CF), and the latter consists of a Gaussian that accounts for sharp tuning and high sensitivity around CF. A fourth process, modeled as a high-pass filter, was needed in many fits to account for breaks and plateaus in threshold sensitivity at frequencies above CF. The latter three processes operated on cochlear spatial coordinates rather than stimulus frequency. The four-process description closely accounted for shapes of most tuning curves. Tuning curve tails possessed minima at 40-80 dB SPL, and minima increased with fiber CF. High-frequency cutoffs of tail filters tended to increase with CF, but low-frequency cutoffs were generally constant across CF. Functions describing tails varied from ear to ear but behaved in a similar manner for fibers from a single ear. Passive components of BM resonances possessed baselines with sensitivities that decreased with CF and cutoff slopes that increased with CF. The magnitude of the active component increased smoothly with CF over an 80 + dB range, and its spatial extent was essentially constant at 1.5 mm or 6% of cochlear length regardless of gain magnitude, fiber CF, or threshold sensitivity. Tuning curves from fibers with high and medium spontaneous rates (SRs) and similar CFs had nearly identical shapes, with the sole difference being essentially constant differences in sensitivity across the entire excitatory frequency range. Tuning curve shapes from fibers with low SRs were more variable. These could either resemble those obtained from similarly-tuned fibers with higher SRs, or they could exhibit lower tip-to-tail ratios and reduced active component magnitudes. The latter were typically associated with low maximum discharge rates.

Two‐tone suppression in the auditory nerve of the cat: Suppression thresholds and rate of growth

Our previous work has been directed at elucidating the behavior of the two‐tone suppression phenomena when both tones are excitatory. Analyzing the phase‐locked response of fibers possessing low characteristic frequency (CF), we have shown [E. Javel, J. Acoust. Soc. Am. Suppl. 1 65, S83(A) (1979)] that suppression exists throughout an auditory nerve fibers response area and that the ability of an excitatory tone to suppress the response to another excitatory tone is similar to a nonexcitatory tones ability to suppress. For a given suppressor‐tone intensity, suppression is maximal when the suppressor tone lies near fiber CF, and suppression magnitude is reduced on either side of CF. The contours relating suppression magnitude to frequency are similar in shape, but not in extent, to the isointensity response contours observed in determinations of response area. The “threshold” for suppression is systematically related to fiber sensitivity at the suppressor‐tone frequency, but it is always greater or equal...