Neural ITD coding with bilateral cochlear implants: effect of binaurally coherent jitter

We investigated the role of GABAergic inhibition on the responses of inferior colliculus (IC) neurons sensitive to interaural time differences (ITDs) in anesthetized guinea pigs. Responses to static and dynamic ITDs were obtained before, during, and after recovery from ionotophoretic application of GABA, or antagonists to the GABA(A) receptor gabazine and bicuculline. For most neurons, a linear relationship was observed between discharge rates evoked by a particular ITD during drug application and control discharge rates. Blocking GABAergic inhibition, or adding exogenous GABA, scaled IC discharge rates in a multiplicative (divisive) and/or additive (subtractive) manner. When the influence of iontophoresed GABA antagonists or exogenous GABA on discharge rates was accounted for, GABAergic inhibition was found to have no effect on the ITD tuning properties of IC neurons. The tuning sharpness of ITD functions, the ITD that evoked 50% response magnitude, and the relative symmetry of ITD functions around their peak response were unaffected by blockade of inhibition or addition of tonic inhibition. However, the ability of neurons to discriminate between ITDs by virtue of differences in their discharge rate was altered by blocking or adding GABA. We propose that inhibition in the IC is involved in the control of the neural gain of the output of IC neurons rather than the regulation of ITD tuning. This gain control appears to arise from a combination of additive and multiplicative processes, and may involve mechanisms such as shunting inhibition or changes in the efficacy of inhibitory and excitatory inputs.

Responses of a population model of low‐frequency inferior colliculus (IC) neurons to a pair of broadband clicks were evaluated. IC inputs came from Hodgkin‐Huxley models of medial superior olive (MSO) and cochlear nucleus bushy cells driven by a stochastic auditory nerve model. Each IC cell received converging inputs that were excitatory from ipsilateral MSO and inhibitory from contralateral MSO. Convergence of multiple excitatory, ipsilateral MSO inputs with similar interaural time difference (ITD) tuning improved ITD sensitivity and reduced the influence of MSO onset responses caused by monaural, rather than binaural, coincidences. Inhibition that lasted over several milliseconds suppressed IC responses to the lagging click. The effect of the inhibition depended on the ITD tuning of the excitation and inhibition converging on a given IC neuron. With appropriate convergence, the IC population showed no response to the lagging click at short delays, and responded to the lagging click but did not encode its ITD at intermediate delays. Only at longer inter‐click delays did IC responses show sensitivity to the lagging click ITD, consistent with the perceptual phenomenon of the precedence effect. [Work supported by NSF and NIH].

Sensitivity to interaural time differences (ITDs) in high-frequency bandpass-filtered periodic and aperiodic (jittered) pulse trains was tested at a nominal pulse rate of 600 pulses per second (pps). It was found that random binaurally-synchronized jitter of the pulse timing significantly increases ITD sensitivity. A second experiment studied the effects of rate and place. ITD sensitivity for jittered 1200-pps pulse trains was significantly higher than for periodic 600-pps pulse trains, and there was a relatively small effect of place. Furthermore, it could be concluded from this experiment that listeners were not solely benefiting from the longest interpulse intervals (IPIs) and the instances of reduced rate by adding jitter, because the two types of pulse trains had the same longest IPI. The effect of jitter was studied using a physiologically-based model of auditory nerve and brainstem (medial superior olive neurons). It was found that the random timing of the jittered pulses increased firing synchrony in the auditory periphery, which caused an improved rate-ITD tuning for the 600-pps pulse trains. These results suggest that a recovery from binaural adaptation induced by temporal jitter is possibly related to changes in the temporal firing pattern, not spectral changes.

Both the performance of cochlear implant (CI) listeners and the responses of auditory neurons show limits in temporal processing at high frequencies. However, the upper limit of temporal coding of pulse-train stimuli in the inferior colliculus (IC) of anesthetized animals appears to be lower than that observed in corresponding perceptual tasks. We hypothesize that the neural rate limits have been underestimated due to the effect of anesthesia. To test this hypothesis, we developed a chronic, awake rabbit preparation for recording responses of single IC neurons to CI stimulation without the confound of anesthesia and compared these data with earlier recordings from the IC of anesthetized cats. Stimuli were periodic trains of biphasic pulses with rates varying from 20 to 1,280 pulses per second (pps). We found that the maximum pulse rates that elicited sustained firing and phase-locked responses were 2-3 times higher in the IC of awake rabbits than in anesthetized cats. Moreover, about 25 % of IC neurons in awake rabbit showed sustained responses to periodic pulse trains at much higher pulse rates (>1,000 pps) than observed in anesthetized animals. Similar differences were observed in single units whose responses to pulse trains were monitored while the animal was given an injection of an ultrashort-acting anesthetic. In general, the physiological rate limits of IC neurons in awake rabbit are more consistent with the psychophysical limits in human CI subjects compared to the data from anesthetized animals.

The localization of low-frequency sounds (less than 3 kHz) along the azimuth involves comparing the ongoing difference in the time of arrival of a sound at the two ears. Information about interaural time differences (ITDs) is derived from an initial comparison performed in the superior olivary complex. However, little is known about which aspects of this information are transformed as it ascends the brainstem. To address this issue, we compared the ITD sensitivity of neurons in the inferior colliculus (IC) and auditory thalamus, successive stations in the auditory pathway. We found ITD sensitivity in the IC and thalamus to be similar in several respects. At both levels, the large majority of neurons responded maximally to ITDs within the range that a rabbit would normally encounter (+/- 300 microseconds) and preferred ipsilateral delays, delays that would be created by sounds in the contralateral sound field. The range of frequencies over which ITD sensitivity was expressed was also similar in the midbrain and thalamus. Several differences were also apparent. In comparison to IC neurons, neurons in the thalamus responded over more restricted ranges of ITD, responded at lower rates, and, in response to monaural stimulation, showed an increased influence of inhibition. Finally, a greater proportion of thalamic units had characteristic delays corresponding to intermediate discharge rates. The preservation of a bias for ipsilateral delays from IC to thalamus suggests that a representation of contralateral azimuths is present at both levels. Similarities between the two levels suggest that information about ITDs is faithfully transmitted from midbrain to thalamus. Differences in ITD sensitivity, such as the sharper tuning for ITDs, suggest that the thalamus is not a simple relay. Enhanced sensitivity to ITDs should translate to better-defined azimuthal receptive fields, and therefore may be a step toward achieving an optimal representation of azimuth within the auditory pathway.

With the exception of low‐frequency characteristic frequency (CF) units, the ipsilaterally evoked discharge of the majority of S‐segment cells can be inhibited with simultaneous stimulation of the contralateral ear. The contralateral inhibitory CF is usually identical to the ipsilateral excitatory CF. The width of the contralateral inhibitory tuning curve is similar to the width of the ipsilateral excitatory tuning curve. Partial inhibition of the ipsilaterally evoked discharge increases the interspike intervals and increases the variability of the discharge. Inhibition, like excitation, is tonically acting. The contralateral inhibitory input with equally intense tones (measured in terms of decibels above threshold) is either about as effective as the excitatory input or less effective, rarely more effective. The primary factor determining the spike output from S‐segment cells is not the absolute intensity level of the stimulus but rather the relative intensity difference of the stimulus at the two ears. [Work supported in part by National Institutes of Health, U. S. Department of Health, Education, and Welfare.]

Bilateral collicular interaction: Modulation of auditory signal processing in frequency domain

A major cue for the localization of sound in space is the interaural time difference (ITD). We examined the role of inhibition in the shaping of ITD responses in the inferior colliculus (IC) by iontophoretically ejecting gamma-aminobutyric acid (GABA) antagonists and GABA itself using a multibarrel pipette. The GABA antagonists block inhibition, whereas the applied GABA provides a constant level of inhibition. The effects on ITD responses were evaluated before, during and after the application of the drugs. If GABA-mediated inhibition is involved in shaping ITD tuning in IC neurons, then applying additional amounts of this inhibitory transmitter should alter ITD tuning. Indeed, for almost all neurons tested, applying GABA reduced the firing rate and consequently sharpened ITD tuning. Conversely, blocking GABA-mediated inhibition increased the activity of IC neurons, often reduced the signal-to-noise ratio and often broadened ITD tuning. Blocking GABA could also alter the shape of the ITD function and shift its peak suggesting that the role of inhibition is multifaceted. These effects indicate that GABAergic inhibition at the level of the IC is important for ITD coding.

1. Interaural level differences (ILDs), created by the head and pinna, have long been known to be the dominant acoustic cue for azimuthal localization of high-frequency tones. However, psychophysical experiments have demonstrated that human subjects can also lateralize complex high-frequency sounds on the basis of interaural time differences (ITDs) of the signal envelope. The lateral superior olive (LSO) is one of two pairs of binaural nuclei where the primary extraction of binaural cues for sound source location occurs. "IE" cells in LSO are inhibited by stimuli to the contralateral and excited by stimuli to the ipsilateral ear, and their response rate is therefore dependent on ILD. Anatomic specializations in the afferent pathways to the LSO suggest that this circuit also has a function in the detection of timing cues. We hypothesized that, besides ILD sensitivity, the IE property also conveys a sensitivity to ITDs of amplitude-modulated (AM) tones and could provide the physiological substrate for the psychophysical effect mentioned above. 2. In extracellular recordings from binaural LSO cells in barbiturate-anesthetized cats, response rate was a periodic function of ITDs of AM stimuli, i.e., all cells displayed ITD sensitivity. Binaural responses were smaller than responses to stimulation of the ipsilateral ear alone and were minimal when the envelopes in both ears were in-phase or nearly so. There was good correspondence between responses to ITDs and to dynamic interaural phase differences (IPDs), created by a difference in the envelope frequency to the two ears. Qualitatively, the responses were consistent with the outcome of an IE operation on temporally structured inputs. 3. To compare the relative importance of ILD and ITD, responses to combinations of the two cues were obtained. Despite robust ITD sensitivity in all binaural LSO cells encountered, the changes in response rate that would occur in response to naturally occurring ITDs were small in comparison with the changes expected for naturally occurring ILDs. The main limitation on ITD sensitivity was a steep decline in average discharge rate as the modulation frequency exceeded several hundred Hertz. 4. ITD sensitivity was also present to broadband stimuli, again with minimal rates occurring near 0 ITD. The sensitivity depended in a predictable fashion on the passband of filtered noise and was absent to binaurally uncorrelated noise bands. In response to clicks, ILDs interacted with ITD in a complicated fashion involving amplitude and latency effects. 5. Three low-characteristic frequency (CF) LSO cells were encountered that were IE and showed ITD sensitivity to the fine structure of low-frequency stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuronal sensitivity to the interaural time difference of the sound envelope in the mouse inferior colliculus

Altered voltage-gated calcium channels in rat inferior colliculus neurons contribute to alcohol withdrawal seizures

Presentation rate of stimulus modulates neuronal responses to frequency modulated sweeps in the mouse inferior colliculus

Bilateral cochlear implant (CI) listeners currently use stimulation strategies which encode interaural time differences (ITD) in the temporal envelope but which do not transmit ITD in the fine structure, due to the constant phase in the electric pulse train. To determine the utility of encoding ITD in the fine structure, ITD-based lateralization was investigated with four CI listeners and four normal hearing (NH) subjects listening to a simulation of electric stimulation. Lateralization discrimination was tested at different pulse rates for various combinations of independently controlled fine structure ITD and envelope ITD. Results for electric hearing show that the fine structure ITD had the strongest impact on lateralization at lower pulse rates, with significant effects for pulse rates up to 800 pulses per second. At higher pulse rates, lateralization discrimination depended solely on the envelope ITD. The data suggest that bilateral CI listeners benefit from transmitting fine structure ITD at lower pulse rates. However, there were strong interindividual differences: the better performing CI listeners performed comparably to the NH listeners.

Interaural time differences (ITDs) are the dominant cue for the localization of low-frequency sounds. While much is known about the processing of ITDs in the auditory brainstem and midbrain, there have been relatively few studies of ITD processing in auditory cortex. In this study, we compared the neural representation of ITDs in the inferior colliculus (IC) and primary auditory cortex (A1) of gerbils. Our IC results were largely consistent with previous studies, with most cells responding maximally to ITDs that correspond to the contralateral edge of the physiological range. In A1, however, we found that preferred ITDs were distributed evenly throughout the physiological range without any contralateral bias. This difference in the distribution of preferred ITDs in IC and A1 had a major impact on the coding of ITDs at the population level: while a labeled-line decoder that considered the tuning of individual cells performed well on both IC and A1 responses, a two-channel decoder based on the overall activity in each hemisphere performed poorly on A1 responses relative to either labeled-line decoding of A1 responses or two-channel decoding of IC responses. These results suggest that the neural representation of ITDs in gerbils is transformed from IC to A1 and have important implications for how spatial location may be combined with other acoustic features for the analysis of complex auditory scenes.

1. Encoding of temporal stimulus parameters by inferior collicular (IC) neurons of Eptesicus fuscus was studied by recording their responses to a wide range of repetition rates (RRs) and durations at several stimulus intensities under free field stimulus conditions. 2. The response properties of 424 IC neurons recorded were similar to those reported in previous studies of this species. 3. IC neurons were classified as low-pass, band-pass, and high-pass according to their preference for RRs and/or durations characteristic of, respectively, search, approach, or terminal phases of echolocation. These neurons selectively process stimuli characteristic of the various phases of hunting. 4. Best RRs and best durations were not correlated with either the BFs or recording depths This suggests that each isofrequency lamina is capable of processing RRs and durations of all hunting phases. 5. Responses of one half of IC neurons studied were correlated with the stimulus duty cycle. These neurons may preferentially process terminal phase information when the bat's pulse emission duty cycle increases. 6. While the stimulus RR affected the dynamic range and overall profile of the intensity rate function, only little effect was observed with different stimulus durations.