Auditory Research publications

A modified auditory n-back task was used to examine the ability of young and older listeners to remember the content of spoken messages presented from different locations. The messages were sentences from the Coordinative Response Measure (CRM) corpus, and the task was to judge whether a target word on the current trial was the same as in the most recent presentation from the same location (left, center, or right). The number of trials between comparison items (the number back) was varied while keeping the number of items to be held in memory (the number of locations) constant. Three levels of stimulus uncertainty were evaluated. Low- and high-uncertainty conditions were created by holding the talker (voice) and nontarget words constant, or varying them unpredictably across trials. In a medium-uncertainty condition, each location was associated with a specific talker, thus increasing predictability and ecological validity. Older listeners performed slightly worse than younger listeners, but there was no significant difference in response times (RT) for the two groups. An effect of the number back (n) was seen for both PC and RT; PC decreased steadily with n, while RT was fairly constant after a significant increase from n = 1 to n = 2. Apart from the lower PC for the older group, there was no effect involving age for either PC or RT. There was an effect of target word location (faster RTs with a late-occurring target) and an effect of uncertainty (faster RTs with a constant talker-location mapping, relative to the high-uncertainty condition). A similar pattern of performance was observed with a group of elderly hearing-impaired listeners (with and without shaping to ensure audibility), but RTs were substantially slower and the effect of uncertainty was absent. Apart from the observed overall slowing of RTs, these results provide little evidence for an effect of age-related changes in cognitive abilities on this task.

Traveling waves in the inner ear exhibit an amplitude peak that shifts with frequency. The peaking is commonly believed to rely on motile processes that amplify the wave by inserting energy. We recorded the vibrations at adjacent positions on the basilar membrane in sensitive gerbil cochleae and tested the putative power amplification in two ways. First, we determined the energy flux of the traveling wave at its peak and compared it to the acoustic power entering the ear, thereby obtaining the net cochlear power gain. For soft sounds, the energy flux at the peak was 1 ± 0.6 dB less than the middle ear input power. For more intense sounds, increasingly smaller fractions of the acoustic power actually reached the peak region. Thus, we found no net power amplification of soft sounds and a strong net attenuation of intense sounds. Second, we analyzed local wave propagation on the basilar membrane. We found that the waves slowed down abruptly when approaching their peak, causing an energy densification that quantitatively matched the amplitude peaking, similar to the growth of sea waves approaching the beach. Thus, we found no local power amplification of soft sounds and strong local attenuation of intense sounds. The most parsimonious interpretation of these findings is that cochlear sensitivity is not realized by amplifying acoustic energy, but by spatially focusing it, and that dynamic compression is realized by adjusting the amount of dissipation to sound intensity.

Here we study links between aminoglycoside-induced mistranslation, protein misfolding and neuropathy. We demonstrate that aminoglycosides induce misreading in mammalian cells and assess endoplasmic reticulum (ER) stress and unfolded protein response (UPR) pathways. Genome-wide transcriptome and proteome analyses revealed upregulation of genes related to protein folding and degradation. Quantitative PCR confirmed induction of UPR markers including C/EBP homologous protein, glucose-regulated protein 94, binding immunoglobulin protein and X-box binding protein-1 (XBP1) mRNA splicing, which is crucial for UPR activation. We studied the effect of a compromised UPR on aminoglycoside ototoxicity in haploinsufficient XBP1 (XBP1 +/− ) mice. Intra-tympanic aminoglycoside treatment caused high-frequency hearing loss in XBP1 +/− mice but not in wild-type littermates. Densities of spiral ganglion cells and synaptic ribbons were decreased in gentamicin-treated XBP1 +/− mice, while sensory cells were preserved. Co-injection of the chemical chaperone tauroursodeoxycholic acid attenuated hearing loss. These results suggest that aminoglycoside-induced ER stress and cell death in spiral ganglion neurons is mitigated by XBP1, masking aminoglycoside neurotoxicity at the organismal level.

Congenital human cytomegalovirus (HCMV) occurs in 0.5-1% of live births and approximately 10% of infected infants develop hearing loss. The mechanism(s) of hearing loss remain unknown. We developed a murine model of CMV induced hearing loss in which murine cytomegalovirus (MCMV) infection of newborn mice leads to hematogenous spread of virus to the inner ear, induction of inflammatory responses, and hearing loss. Characteristics of the hearing loss described in infants with congenital HCMV infection were observed including, delayed onset, progressive hearing loss, and unilateral hearing loss in this model and, these characteristics were viral inoculum dependent. Viral antigens were present in the inner ear as were CD(3+) mononuclear cells in the spiral ganglion and stria vascularis. Spiral ganglion neuron density was decreased after infection, thus providing a mechanism for hearing loss. The lack of significant inner ear histopathology and persistence of inflammation in cochlea of mice with hearing loss raised the possibility that inflammation was a major component of the mechanism(s) of hearing loss in MCMV infected mice.

The kinase Akt is a key downstream mediator of the phosphoinositide-3-kinase signaling pathway and participates in a variety of cellular processes. Akt comprises three isoforms each encoded by a separate gene. There is evidence to indicate that Akt is involved in the survival and protection of auditory hair cells in vitro. However, little is known about the physiological role of Akt in the inner ear-especially in the intact animal. To elucidate this issue, we first analyzed the mRNA expression of the three Akt isoforms in the inner ear of C57/BL6 mice by real-time PCR. Next, we tested the susceptibility to gentamicin-induced auditory hair cell loss in isoform-specific Akt knockout mice compared to wild-types (C57/BL6) in vitro. To analyze the effect of gene deletion in vivo, hearing and cochlear microanatomy were evaluated in Akt isoform knockout animals. In this study, we found that all three Akt isoforms are expressed in the cochlea. Our results further indicate that Akt2 and Akt3 enhance hair cell resistance to ototoxicity, while Akt1 does not. Finally, we determined that untreated Akt1 and Akt2/Akt3 double knockout mice display significant hearing loss, indicating a role for these isoforms in normal hearing. Taken together, our results indicate that each of the Akt isoforms plays a distinct role in the mammalian inner ear.

Background: Data on sex-specific differences in sound production, acoustic behaviour and hearing abilities in fishes are rare. Representatives of numerous catfish families are known to produce sounds in agonistic contexts (intraspecific aggression and interspecific disturbance situations) using their pectoral fins. The present study investigates differences in agonistic behaviour, sound production and hearing abilities in males and females of a callichthyid catfish. Methodology/principal findings: Eight males and nine females of the armoured catfish Megalechis thoracata were investigated. Agonistic behaviour displayed during male-male and female-female dyadic contests and sounds emitted were recorded, sound characteristics analysed and hearing thresholds measured using the auditory evoked potential (AEP) recording technique. Male pectoral spines were on average 1.7-fold longer than those of same-sized females. Visual and acoustic threat displays differed between sexes. Males produced low-frequency harmonic barks at longer distances and thumps at close distances, whereas females emitted broad-band pulsed crackles when close to each other. Female aggressive sounds were significantly shorter than those of males (167 ms versus 219 to 240 ms) and of higher dominant frequency (562 Hz versus 132 to 403 Hz). Sound duration and sound level were positively correlated with body and pectoral spine length, but dominant frequency was inversely correlated only to spine length. Both sexes showed a similar U-shaped hearing curve with lowest thresholds between 0.2 and 1 kHz and a drop in sensitivity above 1 kHz. The main energies of sounds were located at the most sensitive frequencies. Conclusions/significance: Current data demonstrate that both male and female M. thoracata produce aggressive sounds, but the behavioural contexts and sound characteristics differ between sexes. Sexes do not differ in hearing, but it remains to be clarified if this is a general pattern among fish. This is the first study to describe sex-specific differences in agonistic behaviour in fishes.

A significant challenge in tinnitus research lies in explaining how acoustic insult leads to tinnitus in some individuals, but not others. One possibility is genetic variability in the expression and function of neuromodulators - components of neural signaling that alter the balance of excitation and inhibition in neural circuits. An example is nitric oxide (NO) - a free radical and potent neuromodulator in the mammalian brain - that regulates plasticity via both pre-synaptic and postsynaptic mechanisms. Changes in NO have previously been implicated in tinnitus generation, specifically in the ventral cochlear nucleus (VCN). Here, we examined nitric oxide synthase (NOS) - the enzyme responsible for NO production - in the guinea pig VCN following acoustic trauma. NOS was present in most cell types - including spherical and globular bushy cells, small, medium, and large multipolar cells, and octopus cells - spanning the entire extent of the VCN. The staining pattern was symmetrical in control animals. Unilateral acoustic over-exposure (AOE) resulted in marked asymmetries between ipsilateral and contralateral sides of the VCN in terms of the distribution of NOS across the cochlear nuclei in animals with behavioral evidence of tinnitus: fewer NOS-positive cells and a reduced level of NOS staining was present across the whole extent of the contralateral VCN, relative to the ipsilateral VCN. The asymmetric pattern of NOS-containing cells was observed as early as 1 day after AOE and was also present in some animals at 3, 7, and 21 days after AOE. However, it was not until 8 weeks after AOE, when tinnitus had developed, that asymmetries were significant overall, compared with control animals. Asymmetrical NOS expression was not correlated with shifts in the threshold hearing levels. Variability in NOS expression between animals may represent one underlying difference that can be linked to whether or not tinnitus develops after noise exposure.

There are two types of sensory cells in the mammalian cochlea, inner hair cells, which make synaptic contact with auditory-nerve afferent fibers, and outer hair cells that are innervated by crossed and uncrossed medial olivocochlear (MOC) efferent fibers. Contralateral acoustic stimulation activates the uncrossed efferent MOC fibers reducing cochlear neural responses, thus modifying the input to the central auditory system. The chinchilla, among all studied mammals, displays the lowest percentage of uncrossed MOC fibers raising questions about the strength and frequency distribution of the contralateral-sound effect in this species. On the other hand, MOC effects on cochlear sensitivity have been mainly studied in anesthetized animals and since the MOC-neuron activity depends on the level of anesthesia, it is important to assess the influence of anesthesia in the strength of efferent effects. Seven adult chinchillas (Chinchilla laniger) were chronically implanted with round-window electrodes in both cochleae. We compared the effect of contralateral sound in awake and anesthetized condition. Compound action potentials (CAP) and cochlear microphonics (CM) were measured in the ipsilateral cochlea in response to tones in absence and presence of contralateral sound. Control measurements performed after middle-ear muscles section in one animal discarded any possible middle-ear reflex activation. Contralateral sound produced CAP amplitude reductions in all chinchillas, with suppression effects greater by about 1-3 dB in awake than in anesthetized animals. In contrast, CM amplitude increases of up to 1.9 dB were found in only three awake chinchillas. In both conditions the strongest efferent effects were produced by contralateral tones at frequencies equal or close to those of ipsilateral tones. Contralateral CAP suppressions for 1-6 kHz ipsilateral tones corresponded to a span of uncrossed MOC fiber innervation reaching at least the central third of the chinchilla cochlea.

Chronic tinnitus, or "ringing of the ears", affects upwards of 15% of the adult population. Identifying a cost-effective and objective measure of tinnitus is needed due to legal concerns and disability issues, as well as for facilitating the effort to assess neural biomarkers. We developed a modified gap-in-noise (GIN) paradigm to assess tinnitus in mice using the auditory brainstem response (ABR). We then compared the commonly used acoustic startle reflex gap-prepulse inhibition (gap-PPI) and the ABR GIN paradigm in young adult CBA/CaJ mice before and after administrating sodium salicylate (SS), which is known to reliably induce a 16 kHz tinnitus percept in rodents. Post-SS, gap-PPI was significantly reduced at 12 and 16 kHz, consistent with previous studies demonstrating a tinnitus-induced gap-PPI reduction in this frequency range. ABR audiograms indicated thresholds were significantly elevated post-SS, also consistent with previous studies. There was a significant increase in the peak 2 (P2) to peak 1 (P1) and peak 4 (P4) to P1 amplitude ratios in the mid-frequency range, along with decreased latency of P4 at higher intensities. For the ABR GIN, peak amplitudes of the response to the second noise burst were calculated as a percentage of the first noise burst response amplitudes to quantify neural gap processing. A significant decrease in this ratio (i.e. recovery) was seen only at 16 kHz for P1, indicating the presence of tinnitus near this frequency. Thus, this study demonstrates that GIN ABRs can be used as an efficient, non-invasive, and objective method of identifying the approximate pitch and presence of tinnitus in a mouse model. This technique has the potential for application in human subjects and also indicates significant, albeit different, deficits in temporal processing in peripheral and brainstem circuits following drug induced tinnitus.

Mouse models are key tools for studying cochlear alterations in noise-induced hearing loss (NIHL) and for evaluating new therapies. Stimuli used to induce deafness in mice are usually white and octave band noises that include very low frequencies, considering the large mouse auditory range. We designed different sound stimuli, enriched in frequencies up to 20 kHz ("violet" noises) to examine their impact on hearing thresholds and cochlear cytoarchitecture after short exposure. In addition, we developed a cytocochleogram to quantitatively assess the ensuing structural degeneration and its functional correlation. Finally, we used this mouse model and cochleogram procedure to evaluate the potential therapeutic effect of transforming growth factor β1 (TGF-β1) inhibitors P17 and P144 on NIHL. CBA mice were exposed to violet swept-sine noise (VS) with different frequency ranges (2-20 or 9-13 kHz) and levels (105 or 120 dB SPL) for 30 min. Mice were evaluated by auditory brainstem response (ABR) and otoacoustic emission tests prior to and 2, 14 and 28 days after noise exposure. Cochlear pathology was assessed with gross histology; hair cell number was estimated by a stereological counting method. Our results indicate that functional and morphological changes induced by VS depend on the sound level and frequency composition. Partial hearing recovery followed the exposure to 105 dB SPL, whereas permanent cochlear damage resulted from the exposure to 120 dB SPL. Exposure to 9-13 kHz noise caused an auditory threshold shift (TS) in those frequencies that correlated with hair cell loss in the corresponding areas of the cochlea that were spotted on the cytocochleogram. In summary, we present mouse models of NIHL, which depending on the sound properties of the noise, cause different degrees of cochlear damage, and could therefore be used to study molecules which are potential players in hearing loss protection and repair.

Electromotile activity in auditory outer hair cells (OHCs) is essential for sound amplification. It relies on the highly specialized membrane motor protein prestin, and its interactions with the cytoskeleton. It is believed that the expression of prestin and related molecules involved in OHC electromotility may be dynamically regulated by signals from the acoustic environment. However little is known about the nature of such signals and how they affect the expression of molecules involved in electromotility in OHCs. We show evidence that prestin oligomerization is regulated, both at short and relatively long term, by acoustic input and descending efferent activity originating in the cortex, likely acting in concert. Unilateral removal of the middle ear ossicular chain reduces levels of trimeric prestin, particularly in the cochlea from the side of the lesion, whereas monomeric and dimeric forms are maintained or even increased in particular in the contralateral side, as shown in Western blots. Unilateral removal of the auditory cortex (AC), which likely causes an imbalance in descending efferent activity on the cochlea, also reduces levels of trimeric and tetrameric forms of prestin in the side ipsilateral to the lesion, whereas in the contralateral side prestin remains unaffected, or even increased in the case of trimeric and tetrameric forms. As far as efferent inputs are concerned, unilateral ablation of the AC up-regulates the expression of α10 nicotinic Ach receptor (nAChR) transcripts in the cochlea, as shown by RT-Quantitative real-time PCR (qPCR). This suggests that homeostatic synaptic scaling mechanisms may be involved in dynamically regulating OHC electromotility by medial olivocochlear efferents. Limited, unbalanced efferent activity after unilateral AC removal, also affects prestin and β-actin mRNA levels. These findings support that the concerted action of acoustic and efferent inputs to the cochlea is needed to regulate the expression of major molecules involved in OHC electromotility, both at the transcriptional and posttranscriptional levels.

Spatial hearing evolved independently in mammals and birds and is thought to adapt to altered developmental input in different ways. We found, however, that ferrets possess multiple forms of plasticity that are expressed according to which spatial cues are available, suggesting that the basis for adaptation may be similar across species. Our results also provide insight into the way sound source location is represented by populations of cortical neurons.

The most common reason for sensorineural deafness is death of hair cells (HCs). Heat shock proteins (HSPs) are molecular chaperones that participate in folding, targeting, and degrading proteins. HSP expression is increased in response to various environmental stresses to protect cells from damage. Here, we tested whether viral-mediated overexpression of HSP70 can protect HCs and hearing from severe ototoxicity (kanamycin and furosemide) in guinea pigs. Adenovirus-HSP70 mCherry (Ad.HSP70-mCherry) was injected to experimental animals and adenovirus-mCherry to controls, 4 days before the ototoxic insult. Hearing thresholds were measured by auditory brainstem response before the insult and again before sacrificing the animals, 14 days after the insult. Epi-fluorescence immunocytochemistry showed that injection of Ad.HSP70-mCherry resulted in mCherry fluorescence in nonsensory cells of the organ of Corti. The ototoxic insult eliminated both outer HCs and inner HCs throughout most of the cochlea of control (adenovirus-mCherry-injected) ears and contralateral (uninjected) ears. Ad.HSP70-mCherry-injected ears exhibited a significant preservation of inner HCs compared to control and contralateral ears, but outer HCs were not protected. Auditory brainstem response thresholds were significantly better in Ad.HSP70-mCherry-injected ears than in control and contralateral ears. Our data show that HSP70 augmentation may represent a potential therapy attenuating ototoxic inner HC loss.

The robust representation of the environment from unreliable sensory cues is vital for the efficient function of the brain. However, how the neural processing captures the most reliable cues is unknown. The interaural time difference (ITD) is the primary cue to localize sound in horizontal space. ITD is encoded in the firing rate of neurons that detect interaural phase difference (IPD). Due to the filtering effect of the head, IPD for a given location varies depending on the environmental context. We found that, in barn owls, at each location there is a frequency range where the head filtering yields the most reliable IPDs across contexts. Remarkably, the frequency tuning of space-specific neurons in the owl's midbrain varies with their preferred sound location, matching the range that carries the most reliable IPD. Thus, frequency tuning in the owl's space-specific neurons reflects a higher-order feature of the code that captures cue reliability.

Music perception builds on expectancy in harmony, melody, and rhythm. Neural responses to the violations of such expectations are observed in event-related potentials (ERPs) measured using electroencephalography. Most previous ERP studies demonstrating sensitivity to musical violations used stimuli that were temporally regular and musically structured, with less-frequent deviant events that differed from a specific expectation in some feature such as pitch, harmony, or rhythm. Here, we asked whether expectancies about Western musical scale are strong enough to elicit ERP deviance components. Specifically, we explored whether pitches inconsistent with an established scale context elicit deviant components even though equally rare pitches that fit into the established context do not, and even when their timing is unpredictable. We used Markov chains to create temporally irregular pseudo-random sequences of notes chosen from one of two diatonic scales. The Markov pitch-transition probabilities resulted in sequences that favored notes within the scale, but that lacked clear melodic, harmonic, or rhythmic structure. At the random positions, the sequence contained probe tones that were either within the established scale or were out of key. Our subjects ignored the note sequences, watching a self-selected silent movie with subtitles. Compared to the in-key probes, the out-of-key probes elicited a significantly larger P2 ERP component. Results show that random note sequences establish expectations of the "first-order" statistical property of musical key, even in listeners not actively monitoring the sequences.

Biases such as the preference of a particular response for no obvious reason, are an integral part of psychophysics. Such biases have been reported in the common two-alternative forced choice (2AFC) experiments, where participants are instructed to compare two consecutively presented stimuli. However, the principles underlying these biases are largely unknown and previous studies have typically used ad-hoc explanations to account for them. Here we consider human performance in the 2AFC tone frequency discrimination task, utilizing two standard protocols. In both protocols, each trial contains a reference stimulus. In one (Reference-Lower protocol), the frequency of the reference stimulus is always lower than that of the comparison stimulus, whereas in the other (Reference protocol), the frequency of the reference stimulus is either lower or higher than that of the comparison stimulus. We find substantial interval biases. Namely, participants perform better when the reference is in a specific interval. Surprisingly, the biases in the two experiments are opposite: performance is better when the reference is in the first interval in the Reference protocol, but is better when the reference is second in the Reference-Lower protocol. This inconsistency refutes previous accounts of the interval bias, and is resolved when experiments statistics is considered. Viewing perception as incorporation of sensory input with prior knowledge accumulated during the experiment accounts for the seemingly contradictory biases both qualitatively and quantitatively. The success of this account implies that even simple discriminations reflect a combination of sensory limitations, memory limitations, and the ability to utilize stimuli statistics.

Sodium salicylate (SS) is a widely used medication with side effects on hearing. In order to understand these side effects, we recorded sound-driven local-field potentials in a neural structure, the dorsal cortex of the inferior colliculus (ICd). Using a microiontophoretic technique, we applied SS at sites of recording and studied how auditory responses were affected by the drug. Furthermore, we studied how the responses were affected by combined local application of SS and an agonists/antagonist of the type-A or type-B γ-aminobutyric acid receptor (GABAA or GABAB receptor). Results revealed that SS applied alone enhanced auditory responses in the ICd, indicating that the drug had local targets in the structure. Simultaneous application of the drug and a GABAergic receptor antagonist synergistically enhanced amplitudes of responses. The synergistic interaction between SS and a GABAA receptor antagonist had a relatively early start in reference to the onset of acoustic stimulation and the duration of this interaction was independent of sound intensity. The interaction between SS and a GABAB receptor antagonist had a relatively late start, and the duration of this interaction was dependent on sound intensity. Simultaneous application of the drug and a GABAergic receptor agonist produced an effect different from the sum of effects produced by the two drugs released individually. These differences between simultaneous and individual drug applications suggest that SS modified GABAergic inhibition in the ICd. Our results indicate that SS can affect sound-driven activity in the ICd by modulating local GABAergic inhibition.

It is generally thought that background noise can mask auditory information. However, how the noise specifically transforms neuronal auditory processing in a level-dependent manner remains to be carefully determined. Here, with in vivo loose-patch cell-attached recordings in layer 4 of the rat primary auditory cortex (A1), we systematically examined how continuous wideband noise of different levels affected receptive field properties of individual neurons. We found that the background noise, when above a certain critical/effective level, resulted in an elevation of intensity threshold for tone-evoked responses. This increase of threshold was linearly dependent on the noise intensity above the critical level. As such, the tonal receptive field (TRF) of individual neurons was translated upward as an entirety toward high intensities along the intensity domain. This resulted in preserved preferred characteristic frequency (CF) and the overall shape of TRF, but reduced frequency responding range and an enhanced frequency selectivity for the same stimulus intensity. Such translational effects on intensity threshold were observed in both excitatory and fast-spiking inhibitory neurons, as well as in both monotonic and nonmonotonic (intensity-tuned) A1 neurons. Our results suggest that in a noise background, fundamental auditory representations are modulated through a background level-dependent linear shifting along intensity domain, which is equivalent to reducing stimulus intensity.

Noise exposure causes damage of multiple cochlear cell types producing permanent hearing loss with important social consequences. In mammals, no regeneration of either damaged hair cells or auditory neurons has been observed and no successful treatment is available to achieve a functional recovery. Loads of evidence indicate adipose-derived stem cells (ASCs) as promising tools in diversified regenerative medicine applications, due to the high degree of plasticity and trophic features. This study was aimed at identifying the path of in vivo cell migration and expression of trophic growth factors, upon ASCs transplantation into the cochlea, following noise-induced injury. ASCs were isolated in primary culture from the adipose tissue of a guinea pig, transduced using a viral vector to express the green fluorescent protein, and implanted into the scala tympani of deafened animals. Auditory function was assessed 3 and 7 days after surgery. The expression of trophic growth factors was comparatively analyzed using real-time PCR in control and noise-injured cochlear tissues. Immunofluorescence was used to assess the in vivo localization and expression of trophic growth factors in ASCs and cochleae, 3 and 7 days following homologous implantation. ASC implantation did not modify auditory function. ASCs migrated from the perilymphatic to the endolymphatic compartment, during the analyzed time course. Upon noise exposure, the expression of chemokine ligands and receptors related to the PDGF, VEGF, and TGFbeta pathways, increased in the cochlear tissues, possibly guiding in vivo cell migration. Immunofluorescence confirmed the increased expression, which appeared to be further strengthened by ASCs' implantation. These results indicated that ASCs are able to migrate at the site of tissue damage and express trophic factors, upon intracochlear implantation, providing an original proof of principle, which could pave the way for further developments of ASC-based treatments of deafness.

Bilateral cochlear-implant (BiCI) users are less accurate at localizing free-field (FF) sound sources than normal-hearing (NH) listeners. This performance gap is not well understood but is likely due to a combination of compromises in acoustic signal representation by the two independent speech processors and neural degradation of auditory pathways associated with a patient’s hearing loss. To exclusively investigate the effect of CI speech encoding on horizontal-plane sound localization, the present study measured sound localization performance in NH subjects listening to vocoder processed and nonvocoded virtual acoustic space (VAS) stimuli. Various aspects of BiCI stimulation such as independently functioning devices, variable across-ear channel selection, and pulsatile stimulation were simulated using uncorrelated noise (N u ), correlated noise (N 0 ), or Gaussian-enveloped tone (GET) carriers during vocoder processing. Additionally, FF sound localization in BiCI users was measured in the same testing environment for comparison. Distinct response patterns across azimuthal locations were evident for both listener groups and were analyzed using a multilevel regression analysis. Simulated implant speech encoding, regardless of carrier, was detrimental to NH localization and the GET vocoder best simulated BiCI FF performance in NH listeners. Overall, the detrimental effect of vocoder processing on NH performance suggests that sound localization deficits may persist even for BiCI patients who have minimal neural degradation associated with their hearing loss and indicates that CI speech encoding plays a significant role in the sound localization deficits experienced by BiCI users.