Neural coding of dichotic pitches in auditory midbrain.

Dichotic pitches such as the Huggins pitch (HP) and the binaural edge pitch (BEP) are perceptual illusions whereby binaural noise that exhibits abrupt changes in interaural phase differences (IPDs) across frequency creates a tonelike pitch percept when presented to both ears, even though it does not produce a pitch when presented monaurally. At the perceptual and cortical levels, dichotic pitches behave as if an actual tone had been presented to the ears, yet investigations of neural correlates of dichotic pitch in single-unit responses at subcortical levels are lacking. We tested for cues to HP and BEP in the responses of binaural neurons in the auditory midbrain of anesthetized cats by varying the expected pitch frequency around each neuron's best frequency (BF). Neuronal firing rates showed specific features (peaks, troughs, or edges) when the pitch frequency crossed the BF, and the type of feature was consistent with a well-established model of binaural processing comprising frequency tuning, internal delays, and firing rates sensitive to interaural correlation. A Jeffress-like neural population model in which the behavior of individual neurons was governed by the cross-correlation model and the neurons were independently distributed along BF and best IPD predicted trends in human psychophysical HP detection but only when the model incorporated physiological BF and best IPD distributions. These results demonstrate the existence of a rate-place code for HP and BEP in the auditory midbrain and provide a firm physiological basis for models of dichotic pitches.NEW & NOTEWORTHY Dichotic pitches are perceptual illusions created centrally through binaural interactions that offer an opportunity to test theories of pitch and binaural hearing. Here we show that binaural neurons in auditory midbrain encode the frequency of two salient types of dichotic pitches via specific features in the pattern of firing rates along the tonotopic axis. This is the first combined single-unit and modeling study of responses of auditory neurons to stimuli evoking a dichotic pitch.

Chronic Bilateral Cochlear Implant Stimulation Partially Restores Neural Binaural Sensitivity in Neonatally-Deaf Rabbits.

Cochlear implant (CI) users with a prelingual onset of hearing loss show poor sensitivity to interaural time differences (ITDs), an important cue for sound localization and speech reception in noise. Similarly, neural ITD sensitivity in the inferior colliculus (IC) of neonatally-deafened animals is degraded compared with animals deafened as adults. Here, we show that chronic bilateral CI stimulation during development can partly reverse the effect of early-onset deafness on ITD sensitivity. The prevalence of ITD sensitive neurons was restored to the level of adult-deaf (AD) rabbits in the early-deaf rabbits of both sexes that received chronic stimulation and behavioral training with wearable bilateral sound processors during development. We also found a partial improvement in neural ITD sensitivity in the early-deaf and stimulated rabbits compared with unstimulated rabbits. In contrast, chronic CI stimulation did not improve temporal coding in early-deaf rabbits. The present study is the first report showing functional restoration of ITD sensitivity with CI stimulation in single neurons and highlights the importance of auditory experience during development on the maturation of binaural circuitry.SIGNIFICANCE STATEMENT Although cochlear implants (CI) are highly successful in providing speech reception in quiet for many profoundly deaf people, CI users still face difficulty in noisy everyday environment. This is partly because of their poor sensitivity to differences in the timing of sounds arriving at the two ears [interaural time differences (ITDs)], which help to identify where the sound is coming from. This problem is especially acute in those who lost hearing early in life. Here, we present the first report that sensitivity of auditory neurons to ITDs is restored by CI stimulation during development in an animal model of neonatal deafness. These findings highlight the importance of providing early binaural auditory experience with CIs in deaf children.

Rabbits use both spectral and temporal cues to discriminate the fundamental frequency of harmonic complexes with missing fundamentals.

The pitch of harmonic complex tones (HCTs) common in speech, music, and animal vocalizations plays a key role in the perceptual organization of sound. Unraveling the neural mechanisms of pitch perception requires animal models, but little is known about complex pitch perception by animals, and some species appear to use different pitch mechanisms than humans. Here, we tested rabbits' ability to discriminate the fundamental frequency (F0) of HCTs with missing fundamentals, using a behavioral paradigm inspired by foraging behavior in which rabbits learned to harness a spatial gradient in F0 to find the location of a virtual target within a room for a food reward. Rabbits were initially trained to discriminate HCTs with F0s in the range 400-800 Hz and with harmonics covering a wide frequency range (800-16,000 Hz) and then tested with stimuli differing in spectral composition to test the role of harmonic resolvability (experiment 1) or in F0 range (experiment 2) or in both F0 and spectral content (experiment 3). Together, these experiments show that rabbits can discriminate HCTs over a wide F0 range (200-1,600 Hz) encompassing the range of conspecific vocalizations and can use either the spectral pattern of harmonics resolved by the cochlea for higher F0s or temporal envelope cues resulting from interaction between unresolved harmonics for lower F0s. The qualitative similarity of these results to human performance supports the use of rabbits as an animal model for studies of pitch mechanisms, providing species differences in cochlear frequency selectivity and F0 range of vocalizations are taken into account.NEW & NOTEWORTHY Understanding the neural mechanisms of pitch perception requires experiments in animal models, but little is known about pitch perception by animals. Here we show that rabbits, a popular animal in auditory neuroscience, can discriminate complex sounds differing in pitch using either spectral cues or temporal cues. The results suggest that the role of spectral cues in pitch perception by animals may have been underestimated by predominantly testing low frequencies in the range of human voice.

Robust Rate-Place Coding of Resolved Components in Harmonic and Inharmonic Complex Tones in Auditory Midbrain.

Harmonic complex tones (HCTs) commonly occurring in speech and music evoke a strong pitch at their fundamental frequency (F0), especially when they contain harmonics individually resolved by the cochlea. When all frequency components of an HCT are shifted by the same amount, the pitch of the resulting inharmonic tone (IHCT) can also shift, although the envelope repetition rate is unchanged. A rate-place code, whereby resolved harmonics are represented by local maxima in firing rates along the tonotopic axis, has been characterized in the auditory nerve and primary auditory cortex, but little is known about intermediate processing stages. We recorded single-neuron responses to HCT and IHCT with varying F0 and sound level in the inferior colliculus (IC) of unanesthetized rabbits of both sexes. Many neurons showed peaks in firing rate when a low-numbered harmonic aligned with the neuron's characteristic frequency, demonstrating "rate-place" coding. The IC rate-place code was most prevalent for F0 > 800 Hz, was only moderately dependent on sound level over a 40 dB range, and was not sensitive to stimulus harmonicity. A spectral receptive-field model incorporating broadband inhibition better predicted the neural responses than a purely excitatory model, suggesting an enhancement of the rate-place representation by inhibition. Some IC neurons showed facilitation in response to HCT relative to pure tones, similar to cortical "harmonic template neurons" (Feng and Wang, 2017), but to a lesser degree. Our findings shed light on the transformation of rate-place coding of resolved harmonics along the auditory pathway.SIGNIFICANCE STATEMENT Harmonic complex tones are ubiquitous in speech and music and produce strong pitch percepts when they contain frequency components that are individually resolved by the cochlea. Here, we characterize a "rate-place" code for resolved harmonics in the auditory midbrain that is more robust across sound levels than the peripheral rate-place code and insensitive to the harmonic relationships among frequency components. We use a computational model to show that inhibition may play an important role in shaping the rate-place code. Our study fills a major gap in understanding the transformations in neural representations of resolved harmonics along the auditory pathway.

Pitch of harmonic complex tones: rate and temporal coding of envelope repetition rate in inferior colliculus of unanesthetized rabbits.

Harmonic complex tones (HCTs) found in speech, music, and animal vocalizations evoke strong pitch percepts at their fundamental frequencies. The strongest pitches are produced by HCTs that contain harmonics resolved by cochlear frequency analysis, but HCTs containing solely unresolved harmonics also evoke a weaker pitch at their envelope repetition rate (ERR). In the auditory periphery, neurons phase lock to the stimulus envelope, but this temporal representation of ERR degrades and gives way to rate codes along the ascending auditory pathway. To assess the role of the inferior colliculus (IC) in such transformations, we recorded IC neuron responses to HCT and sinusoidally modulated broadband noise (SAMN) with varying ERR from unanesthetized rabbits. Different interharmonic phase relationships of HCT were used to manipulate the temporal envelope without changing the power spectrum. Many IC neurons demonstrated band-pass rate tuning to ERR between 60 and 1,600 Hz for HCT and between 40 and 500 Hz for SAMN. The tuning was not related to the pure-tone best frequency of neurons but was dependent on the shape of the stimulus envelope, indicating a temporal rather than spectral origin. A phenomenological model suggests that the tuning may arise from peripheral temporal response patterns via synaptic inhibition. We also characterized temporal coding to ERR. Some IC neurons could phase lock to the stimulus envelope up to 900 Hz for either HCT or SAMN, but phase locking was weaker with SAMN. Together, the rate code and the temporal code represent a wide range of ERR, providing strong cues for the pitch of unresolved harmonics.NEW & NOTEWORTHY Envelope repetition rate (ERR) provides crucial cues for pitch perception of frequency components that are not individually resolved by the cochlea, but the neural representation of ERR for stimuli containing many harmonics is poorly characterized. Here we show that the pitch of stimuli with unresolved harmonics is represented by both a rate code and a temporal code for ERR in auditory midbrain neurons and propose possible underlying neural mechanisms with a computational model.

Neural coding and perception of auditory motion direction based on interaural time differences.

While motion is important for parsing a complex auditory scene into perceptual objects, how it is encoded in the auditory system is unclear. Perceptual studies suggest that the ability to identify the direction of motion is limited by the duration of the moving sound, yet we can detect changes in interaural differences at even shorter durations. To understand the source of these distinct temporal limits, we recorded from single units in the inferior colliculus (IC) of unanesthetized rabbits in response to noise stimuli containing a brief segment with linearly time-varying interaural time difference ("ITD sweep") temporally embedded in interaurally uncorrelated noise. We also tested the ability of human listeners to either detect the ITD sweeps or identify the motion direction. Using a point-process model to separate the contributions of stimulus dependence and spiking history to single-neuron responses, we found that the neurons respond primarily by following the instantaneous ITD rather than exhibiting true direction selectivity. Furthermore, using an optimal classifier to decode the single-neuron responses, we found that neural threshold durations of ITD sweeps for both direction identification and detection overlapped with human threshold durations even though the average response of the neurons could track the instantaneous ITD beyond psychophysical limits. Our results suggest that the IC does not explicitly encode motion direction, but internal neural noise may limit the speed at which we can identify the direction of motion.NEW & NOTEWORTHY Recognizing motion and identifying an object's trajectory are important for parsing a complex auditory scene, but how we do so is unclear. We show that neurons in the auditory midbrain do not exhibit direction selectivity as found in the visual system but instead follow the trajectory of the motion in their temporal firing patterns. Our results suggest that the inherent variability in neural firings may limit our ability to identify motion direction at short durations.

Pitch of Harmonic Complex Tones: Rate Coding of Envelope Repetition Rate in the Auditory Midbrain.

Envelope repetition rate (ERR) is an important cue for the pitch of harmonic complex tones (HCT), especially when the tone consists entirely of unresolved harmonics. Neural synchronization to the stimulus envelope provides a prominent cue for ERR in the auditory periphery, but this temporal code becomes degraded and gives way to rate codes in higher centers. The inferior colliculus (IC) likely plays a key role in this temporal-to-rate code transformation. Here we recorded single IC neuron responses to HCT at varying fundamental frequencies (F 0). ERR was manipulated by applying different inter-harmonic phase relationships. We identified a subset of neurons that showed a 'non-tonotopic' rate tuning to ERR between 160 and 1500 Hz. A comparison of neural responses to HCT and sinusoidally amplitude modulated (SAM) noise suggests that this tuning is dependent on the shape of stimulus envelope. A phenomenological model is able to reproduce the non-tonotopic tuning to ERR, and suggests it arises in the IC via synaptic inhibition.

Neural Coding of Interaural Time Differences with Bilateral Cochlear Implants in Unanesthetized Rabbits.

UNLABELLED: Although bilateral cochlear implants (CIs) provide improvements in sound localization and speech perception in noise over unilateral CIs, bilateral CI users' sensitivity to interaural time differences (ITDs) is still poorer than normal. In particular, ITD sensitivity of most CI users degrades with increasing stimulation rate and is lacking at the high carrier pulse rates used in CI processors to deliver speech information. To gain a better understanding of the neural basis for this degradation, we characterized ITD tuning of single neurons in the inferior colliculus (IC) for pulse train stimuli in an unanesthetized rabbit model of bilateral CIs. Approximately 73% of IC neurons showed significant ITD sensitivity in their overall firing rates. On average, ITD sensitivity was best for pulse rates near 80-160 pulses per second (pps) and degraded for both lower and higher pulse rates. The degradation in ITD sensitivity at low pulse rates was caused by strong, unsynchronized background activity that masked stimulus-driven responses in many neurons. Selecting synchronized responses by temporal windowing revealed ITD sensitivity in these neurons. With temporal windowing, both the fraction of ITD-sensitive neurons and the degree of ITD sensitivity decreased monotonically with increasing pulse rate. To compare neural ITD sensitivity to human performance in ITD discrimination, neural just-noticeable differences (JNDs) in ITD were computed using signal detection theory. Using temporal windowing at lower pulse rates, and overall firing rate at higher pulse rates, neural ITD JNDs were within the range of perceptual JNDs in human CI users over a wide range of pulse rates. SIGNIFICANCE STATEMENT: Many profoundly deaf people wearing cochlear implants (CIs) still face challenges in everyday situations, such as understanding conversations in noise. Even with CIs in both ears, they have difficulty making full use of subtle differences in the sounds reaching the two ears [interaural time difference (ITD)] to identify where the sound is coming from. This problem is especially acute at the high stimulation rates used in clinical CI processors. This study provides a better understanding of ITD processing with bilateral CIs and shows a parallel between human performance in ITD discrimination and neural responses in the auditory midbrain. The present study is the first report on binaural properties of auditory neurons with CIs in unanesthetized animals.

Neural coding of time-varying interaural time differences and time-varying amplitude in the inferior colliculus.

Binaural cues occurring in natural environments are frequently time varying, either from the motion of a sound source or through interactions between the cues produced by multiple sources. Yet, a broad understanding of how the auditory system processes dynamic binaural cues is still lacking. In the current study, we directly compared neural responses in the inferior colliculus (IC) of unanesthetized rabbits to broadband noise with time-varying interaural time differences (ITD) with responses to noise with sinusoidal amplitude modulation (SAM) over a wide range of modulation frequencies. On the basis of prior research, we hypothesized that the IC, one of the first stages to exhibit tuning of firing rate to modulation frequency, might use a common mechanism to encode time-varying information in general. Instead, we found weaker temporal coding for dynamic ITD compared with amplitude modulation and stronger effects of adaptation for amplitude modulation. The differences in temporal coding of dynamic ITD compared with SAM at the single-neuron level could be a neural correlate of "binaural sluggishness," the inability to perceive fluctuations in time-varying binaural cues at high modulation frequencies, for which a physiological explanation has so far remained elusive. At ITD-variation frequencies of 64 Hz and above, where a temporal code was less effective, noise with a dynamic ITD could still be distinguished from noise with a constant ITD through differences in average firing rate in many neurons, suggesting a frequency-dependent tradeoff between rate and temporal coding of time-varying binaural information.NEW & NOTEWORTHY Humans use time-varying binaural cues to parse auditory scenes comprising multiple sound sources and reverberation. However, the neural mechanisms for doing so are poorly understood. Our results demonstrate a potential neural correlate for the reduced detectability of fluctuations in time-varying binaural information at high speeds, as occurs in reverberation. The results also suggest that the neural mechanisms for processing time-varying binaural and monaural cues are largely distinct.

Neural coding of sound envelope in reverberant environments.

Speech reception depends critically on temporal modulations in the amplitude envelope of the speech signal. Reverberation encountered in everyday environments can substantially attenuate these modulations. To assess the effect of reverberation on the neural coding of amplitude envelope, we recorded from single units in the inferior colliculus (IC) of unanesthetized rabbit using sinusoidally amplitude modulated (AM) broadband noise stimuli presented in simulated anechoic and reverberant environments. Although reverberation degraded both rate and temporal coding of AM in IC neurons, in most neurons, the degradation in temporal coding was smaller than the AM attenuation in the stimulus. This compensation could largely be accounted for by the compressive shape of the modulation input-output function (MIOF), which describes the nonlinear transformation of modulation depth from acoustic stimuli into neural responses. Additionally, in a subset of neurons, the temporal coding of AM was better for reverberant stimuli than for anechoic stimuli having the same modulation depth at the ear. Using hybrid anechoic stimuli that selectively possess certain properties of reverberant sounds, we show that this reverberant advantage is not caused by envelope distortion, static interaural decorrelation, or spectral coloration. Overall, our results suggest that the auditory system may possess dual mechanisms that make the coding of amplitude envelope relatively robust in reverberation: one general mechanism operating for all stimuli with small modulation depths, and another mechanism dependent on very specific properties of reverberant stimuli, possibly the periodic fluctuations in interaural correlation at the modulation frequency.

Neural population encoding and decoding of sound source location across sound level in the rabbit inferior colliculus.

At lower levels of sensory processing, the representation of a stimulus feature in the response of a neural population can vary in complex ways across different stimulus intensities, potentially changing the amount of feature-relevant information in the response. How higher-level neural circuits could implement feature decoding computations that compensate for these intensity-dependent variations remains unclear. Here we focused on neurons in the inferior colliculus (IC) of unanesthetized rabbits, whose firing rates are sensitive to both the azimuthal position of a sound source and its sound level. We found that the azimuth tuning curves of an IC neuron at different sound levels tend to be linear transformations of each other. These transformations could either increase or decrease the mutual information between source azimuth and spike count with increasing level for individual neurons, yet population azimuthal information remained constant across the absolute sound levels tested (35, 50, and 65 dB SPL), as inferred from the performance of a maximum-likelihood neural population decoder. We harnessed evidence of level-dependent linear transformations to reduce the number of free parameters in the creation of an accurate cross-level population decoder of azimuth. Interestingly, this decoder predicts monotonic azimuth tuning curves, broadly sensitive to contralateral azimuths, in neurons at higher levels in the auditory pathway.

Coding of electric pulse trains presented through cochlear implants in the auditory midbrain of awake rabbit: comparison with anesthetized preparations.

Cochlear implant (CI) listeners show limits at high frequencies in tasks involving temporal processing such as rate pitch and interaural time difference discrimination. Similar limits have been observed in neural responses to electric stimulation in animals with CI; however, the upper limit of temporal coding of electric pulse train stimuli in the inferior colliculus (IC) of anesthetized animals is lower than the perceptual limit. We hypothesize that the upper limit of temporal neural coding has been underestimated in previous studies due to the confound of anesthesia. To test this hypothesis, we developed a chronic, awake rabbit preparation for single-unit studies of IC neurons with electric stimulation through CI. Stimuli were periodic trains of biphasic pulses with rates varying from 20 to 1280 pulses per second. We found that IC neurons in awake rabbits showed higher spontaneous activity and greater sustained responses, both excitatory and suppressive, at high pulse rates. Maximum pulse rates that elicited synchronized responses were approximately two times higher in awake rabbits than in earlier studies with anesthetized animals. Here, we demonstrate directly that anesthesia is a major factor underlying these differences by monitoring the responses of single units in one rabbit before and after injection of an ultra-short-acting barbiturate. In general, the physiological rate limits of IC neurons in the awake rabbit are more consistent with the psychophysical limits in human CI subjects compared with limits from anesthetized animals.

Decoding sound source location and separation using neural population activity patterns.

The strategies by which the central nervous system decodes the properties of sensory stimuli, such as sound source location, from the responses of a population of neurons are a matter of debate. We show, using the average firing rates of neurons in the inferior colliculus (IC) of awake rabbits, that prevailing decoding models of sound localization (summed population activity and the population vector) fail to localize sources accurately due to heterogeneity in azimuth tuning across the population. In contrast, a maximum-likelihood decoder operating on the pattern of activity across the population of neurons in one IC accurately localized sound sources in the contralateral hemifield, consistent with lesion studies, and did so with a precision consistent with rabbit psychophysical performance. The pattern decoder also predicts behavior in response to incongruent localization cues consistent with the long-standing "duplex" theory of sound localization. We further show that the pattern decoder accurately distinguishes two concurrent, spatially separated sources from a single source, consistent with human behavior. Decoder detection of small amounts of source separation directly in front is due to neural sensitivity to the interaural decorrelation of sound, at both low and high frequencies. The distinct patterns of IC activity between single and separated sound sources thereby provide a neural correlate for the ability to segregate and localize sources in everyday, multisource environments.

Dual sensitivity of inferior colliculus neurons to ITD in the envelopes of high-frequency sounds: experimental and modeling study.

Human listeners are sensitive to interaural time differences (ITDs) in the envelopes of sounds, which can serve as a cue for sound localization. Many high-frequency neurons in the mammalian inferior colliculus (IC) are sensitive to envelope-ITDs of sinusoidally amplitude-modulated (SAM) sounds. Typically, envelope-ITD-sensitive IC neurons exhibit either peak-type sensitivity, discharging maximally at the same delay across frequencies, or trough-type sensitivity, discharging minimally at the same delay across frequencies, consistent with responses observed at the primary site of binaural interaction in the medial and lateral superior olives (MSO and LSO), respectively. However, some high-frequency IC neurons exhibit dual types of envelope-ITD sensitivity in their responses to SAM tones, that is, they exhibit peak-type sensitivity at some modulation frequencies and trough-type sensitivity at other frequencies. Here we show that high-frequency IC neurons in the unanesthetized rabbit can also exhibit dual types of envelope-ITD sensitivity in their responses to SAM noise. Such complex responses to SAM stimuli could be achieved by convergent inputs from MSO and LSO onto single IC neurons. We test this hypothesis by implementing a physiologically explicit, computational model of the binaural pathway. Specifically, we examined envelope-ITD sensitivity of a simple model IC neuron that receives convergent inputs from MSO and LSO model neurons. We show that dual envelope-ITD sensitivity emerges in the IC when convergent MSO and LSO inputs are differentially tuned for modulation frequency.

Neural correlates of the perception of sound source separation.

As two sound sources become spatially separated in the horizontal plane, the binaural cues used for sound localization become distorted from their values for each sound in isolation. Because firing rates of most neurons in the inferior colliculus (IC) are sensitive to these binaural cues, we hypothesized that these neurons would be sensitive to source separation. We examined changes in the target azimuth tuning functions of IC neurons in unanesthetized rabbits caused by the concurrent presentation of an interferer at a fixed spatial location. Both target and interferer were broadband noise bursts, uncorrelated with each other. Signal detection analysis of firing rates of individual IC neurons shows that responses are correlated with psychophysical performance on segregation of spatially separated sources. The analysis also highlights the role of neural sensitivity to interaural time differences of cochlea-induced envelopes in performing this task. Psychophysical performance on source segregation was also compared to the performance of two contrasting ­maximum-likelihood classifiers operating on the firing rates of the population of IC ­neurons. The "population-pattern" classifier had access to the firing rates of every neuron in the population, while the "two-channel" classifier operated on the summed firing rates from each side of the brain. Unlike the two-channel classifier, the ­population-pattern classifier could segregate the sources accurately, suggesting that some of the information contained in the heterogeneity of azimuth tuning functions across IC neurons is used to segregate sources.

Better temporal neural coding with cochlear implants in awake animals.

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.

Effect of Reverberation on Neural Responses to Natural Speech in Rabbit Auditory Midbrain: No Evidence for a Neural Dereverberation Mechanism.

Reverberation is ubiquitous in everyday acoustic environments. It degrades both binaural cues and the envelope modulations of sounds and thus can impair speech perception. Still, both humans and animals can accurately perceive reverberant stimuli in most everyday settings. Previous neurophysiological and perceptual studies have suggested the existence of neural mechanisms that partially compensate for the effects of reverberation. However, these studies were limited by their use of either highly simplified stimuli or rudimentary reverberation simulations. To further characterize how reverberant stimuli are processed by the auditory system, we recorded single-unit (SU) and multiunit (MU) activity from the inferior colliculus (IC) of unanesthetized rabbits in response to natural speech utterances presented with no reverberation ("dry") and in various degrees of simulated reverberation (direct-to-reverberant energy ratios (DRRs) ranging from 9.4 to -8.2 dB). Linear stimulus reconstruction techniques (Mesgarani et al., 2009) were used to quantify the amount of speech information available in the responses of neural ensembles. We found that high-quality spectrogram reconstructions could be obtained for dry speech and in moderate reverberation from ensembles of 25 units. However, spectrogram reconstruction quality deteriorated in severe reverberation for both MUs and SUs such that the neural degradation paralleled the degradation in the stimulus spectrogram. Furthermore, spectrograms reconstructed from responses to reverberant stimuli resembled spectrograms of reverberant speech better than spectrograms of dry speech. Overall, the results provide no evidence for a dereverberation mechanism in neural responses from the rabbit IC when studied with linear reconstruction techniques.

Sensitivity of cochlear nucleus neurons to spatio-temporal changes in auditory nerve activity.

The spatio-temporal pattern of auditory nerve (AN) activity, representing the relative timing of spikes across the tonotopic axis, contains cues to perceptual features of sounds such as pitch, loudness, timbre, and spatial location. These spatio-temporal cues may be extracted by neurons in the cochlear nucleus (CN) that are sensitive to relative timing of inputs from AN fibers innervating different cochlear regions. One possible mechanism for this extraction is "cross-frequency" coincidence detection (CD), in which a central neuron converts the degree of coincidence across the tonotopic axis into a rate code by preferentially firing when its AN inputs discharge in synchrony. We used Huffman stimuli (Carney LH. J Neurophysiol 64: 437-456, 1990), which have a flat power spectrum but differ in their phase spectra, to systematically manipulate relative timing of spikes across tonotopically neighboring AN fibers without changing overall firing rates. We compared responses of CN units to Huffman stimuli with responses of model CD cells operating on spatio-temporal patterns of AN activity derived from measured responses of AN fibers with the principle of cochlear scaling invariance. We used the maximum likelihood method to determine the CD model cell parameters most likely to produce the measured CN unit responses, and thereby could distinguish units behaving like cross-frequency CD cells from those consistent with same-frequency CD (in which all inputs would originate from the same tonotopic location). We find that certain CN unit types, especially those associated with globular bushy cells, have responses consistent with cross-frequency CD cells. A possible functional role of a cross-frequency CD mechanism in these CN units is to increase the dynamic range of binaural neurons that process cues for sound localization.

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

Poor sensitivity to the interaural time difference (ITD) constrains the ability of human bilateral cochlear implant users to listen in everyday noisy acoustic environments. ITD sensitivity to periodic pulse trains degrades sharply with increasing pulse rate but can be restored at high pulse rates by jittering the interpulse intervals in a binaurally coherent manner (Laback and Majdak. Binaural jitter improves interaural time-difference sensitivity of cochlear implantees at high pulse rates. Proc Natl Acad Sci USA 105: 814-817, 2008). We investigated the neural basis of the jitter effect by recording from single inferior colliculus (IC) neurons in bilaterally implanted, anesthetized cats. Neural responses to trains of biphasic pulses were measured as a function of pulse rate, jitter, and ITD. An effect of jitter on neural responses was most prominent for pulse rates above 300 pulses/s. High-rate periodic trains evoked only an onset response in most IC neurons, but introducing jitter increased ongoing firing rates in about half of these neurons. Neurons that had sustained responses to jittered high-rate pulse trains showed ITD tuning comparable with that produced by low-rate periodic pulse trains. Thus, jitter appears to improve neural ITD sensitivity by restoring sustained firing in many IC neurons. The effect of jitter on IC responses is qualitatively consistent with human psychophysics. Action potentials tended to occur reproducibly at sparse, preferred times across repeated presentations of high-rate jittered pulse trains. Spike triggered averaging of responses to jittered pulse trains revealed that firing was triggered by very short interpulse intervals. This suggests it may be possible to restore ITD sensitivity to periodic carriers by simply inserting short interpulse intervals at select times.

Time course of dynamic range adaptation in the auditory nerve.

Auditory adaptation to sound-level statistics occurs as early as in the auditory nerve (AN), the first stage of neural auditory processing. In addition to firing rate adaptation characterized by a rate decrement dependent on previous spike activity, AN fibers show dynamic range adaptation, which is characterized by a shift of the rate-level function or dynamic range toward the most frequently occurring levels in a dynamic stimulus, thereby improving the precision of coding of the most common sound levels (Wen B, Wang GI, Dean I, Delgutte B. J Neurosci 29: 13797-13808, 2009). We investigated the time course of dynamic range adaptation by recording from AN fibers with a stimulus in which the sound levels periodically switch from one nonuniform level distribution to another (Dean I, Robinson BL, Harper NS, McAlpine D. J Neurosci 28: 6430-6438, 2008). Dynamic range adaptation occurred rapidly, but its exact time course was difficult to determine directly from the data because of the concomitant firing rate adaptation. To characterize the time course of dynamic range adaptation without the confound of firing rate adaptation, we developed a phenomenological "dual adaptation" model that accounts for both forms of AN adaptation. When fitted to the data, the model predicts that dynamic range adaptation occurs as rapidly as firing rate adaptation, over 100-400 ms, and the time constants of the two forms of adaptation are correlated. These findings suggest that adaptive processing in the auditory periphery in response to changes in mean sound level occurs rapidly enough to have significant impact on the coding of natural sounds.