Auditory Research publications

Objective. The temporal spacing or distribution of stimulation pulses in therapeutic neurostimulation waveforms—referred to here as the Temporal Pattern (TP)—has emerged as an important parameter for tuning the response to deep-brain stimulation and intracortical microstimulation (ICMS). While it has long been assumed that modulating the TP of ICMS may be effective by altering the rate coding of the neural response, it is unclear how it alters the neural response at the network level. The present study is designed to elucidate the neural response to TP at the network level. Approach . We use in vivo two-photon imaging of mice expressing the calcium sensor Thy1 -GCaMP or the glutamate sensor hSyn -iGluSnFr to examine the layer II/III neural response to ICMS with different TPs. We study the neuronal calcium and glutamate response to TPs with the same average frequency (10 Hz) and same total charge injection, but varying degrees of bursting. We also investigate one control pattern with an average frequency of 100 Hz and 10X the charge injection. Main Results . Stimulation trains with the same average frequency and same total charge injection but distinct TPs recruit distinct sets of neurons. More than half (60% of 309 cells) of neurons prefer one TP over the other. Despite their distinct spatial recruitment patterns, cells exhibit similar ability to follow 30 s trains of both TPs without failing, and they exhibit similar levels of glutamate release during stimulation. Both neuronal calcium and glutamate release entrain to the bursting TP pattern, with a ∼21-fold increase in relative power at the frequency of bursting. Bursting also results in a statistically significant elevation in the correlation between somatic calcium activity and neuropil activity, which we explore as a metric for inhibitory-excitatory tone. Interestingly, soma-neuropil correlation during the bursting pattern is a statistically significant predictor of cell preference for TP, which exposes a key link between TP and inhibitory-excitatory tone. Finally, using mesoscale imaging, we show that both TPs result in distal inhibition during stimulation, which reveals complex spatial and temporal interactions between TP and inhibitory-excitatory tone in ICMS. Significance . Our results may ultimately suggest that TP is a valuable parameter space to modulate inhibitory-excitatory tone and to recruit distinct network activity in ICMS. This presents a broader mechanism of action than rate coding, as previously thought. By implicating these additional mechanisms, TP may have broader utility in the clinic and should be pursued to expand the efficacy of ICMS therapies.

The latency of the auditory steady-state response (ASSR) may provide valuable information regarding the integrity of the auditory system, as it could potentially reveal the presence of multiple intracerebral sources. To estimate multiple latencies from high-order ASSRs, we propose a novel two-stage procedure that consists of a nonparametric estimation method, called apparent latency from phase coherence (ALPC), followed by a heuristic sequential forward selection algorithm (SFS). Compared with existing methods, ALPC-SFS requires few prior assumptions, and is straightforward to implement for higher-order nonlinear responses to multi-cosine sound complexes with their initial phases set to zero. It systematically evaluates the nonlinear components of the ASSRs by estimating multiple latencies, automatically identifies involved ASSR components, and reports a latency consistency index. To verify the proposed method, we performed simulations for several scenarios: two nonlinear subsystems with different or overlapping outputs. We compared the results from our method with predictions from existing, parametric methods. We also recorded the EEG from ten normal-hearing adults by bilaterally presenting superimposed tones with four frequencies that evoke a unique set of ASSRs. From these ASSRs, two major latencies were found to be stable across subjects on repeated measurement days. The two latencies are dominated by low-frequency (LF) (near 40 Hz, at around 41–52 ms) and high-frequency (HF) (> 80 Hz, at around 21–27 ms) ASSR components. The frontal-central brain region showed longer latencies on LF components, but shorter latencies on HF components, when compared with temporal-lobe regions. In conclusion, the proposed nonparametric ALPC-SFS method, applied to zero-phase, multi-cosine sound complexes is more suitable for evaluating embedded nonlinear systems underlying ASSRs than existing methods. It may therefore be a promising objective measure for hearing performance and auditory cortex (dys)function.

Previous research with speech and non-speech stimuli suggested that in audiovisual perception, visual information starting prior to the onset of corresponding sound can provide visual cues, and form a prediction about the upcoming auditory sound. This prediction leads to audiovisual (AV) interaction. Auditory and visual perception interact and induce suppression and speeding up of the early auditory event-related potentials (ERPs) such as N1 and P2. To investigate AV interaction, previous research examined N1 and P2 amplitudes and latencies in response to audio only (AO), video only (VO), audiovisual, and control (CO) stimuli, and compared AV with auditory perception based on four AV interaction models (AV vs. AO+VO, AV-VO vs. AO, AV-VO vs. AO-CO, AV vs. AO). The current study addresses how different models of AV interaction express N1 and P2 suppression in music perception. Furthermore, the current study took one step further and examined whether previous musical experience, which can potentially lead to higher N1 and P2 amplitudes in auditory perception, influenced AV interaction in different models. Musicians and non-musicians were presented the recordings (AO, AV, VO) of a keyboard /C4/ key being played, as well as CO stimuli. Results showed that AV interaction models differ in their expression of N1 and P2 amplitude and latency suppression. The calculation of model (AV-VO vs. AO) and (AV-VO vs. AO-CO) has consequences for the resulting N1 and P2 difference waves. Furthermore, while musicians, compared to non-musicians, showed higher N1 amplitude in auditory perception, suppression of amplitudes and latencies for N1 and P2 was similar for the two groups across the AV models. Collectively, these results suggest that when visual cues from finger and hand movements predict the upcoming sound in AV music perception, suppression of early ERPs is similar for musicians and non-musicians. Notably, the calculation differences across models do not lead to the same pattern of results for N1 and P2, demonstrating that the four models are not interchangeable and are not directly comparable.

Purpose This article aimed to document longitudinal changes in auditory function, including measures of temporal processing, and to examine the associations between observed changes in auditory and cognitive function in middle-aged and older adults. Method This was a prospective longitudinal study of 98 adults (66 women) with baseline ages ranging from 40 to 85 years. The mean interval between T1 baseline and T2 follow-up measurements was 8.8 years with a range of 7–11 years. Measures of hearing threshold, gap detection, and auditory temporal-order identification were completed at T1 and T2. Cognitive measures completed at T1 and T2 were the 13 scales of the Wechsler Adult Intelligence Scale–Third Edition. Three approaches were taken to analyze these data: (a) examination of changes over time in group performance, (b) correlations and slopes between auditory and cognitive measures to examine concomitant rates of decline over the 9-year T1-to-T2 period, and (c) regression analyses examining associations between auditory performance at T1 and cognitive performance 9 years later at T2. Results For the group data, there were significant declines in hearing loss, gap-detection thresholds at one frequency, and process-type measures of cognitive function from T1 to T2 matching the trends in the baseline cross-sectional data. Regression analyses of the longitudinal data revealed the strongest connection between auditory temporal-order processing and cognitive processing typically explaining 10%–15% of the variance. Conclusions A significant amount of variance in rates of cognitive decline, T1 to T2, and subsequent cognitive performance (T2) was explained by measures of auditory function. Although hearing loss occasionally emerged as a significant factor, auditory temporal-order identification emerged much more frequently as the auditory measure most strongly associated with cognitive function.

Studies of acoustic communication often focus on the categories and units of vocalizations, but subtle variation also occurs in how these signals are uttered. In human speech, it is not only phonemes and words that carry information but also the timbre, intonation, and stress of how speech sounds are delivered (often referred to as “paralinguistic content”). In non-human animals, variation across utterances of vocal signals also carries behaviorally relevant information across taxa. However, the discriminability of these cues has been rarely tested in a psychophysical paradigm. Here, we focus on acoustic communication in the zebra finch ( Taeniopygia guttata ), a songbird species in which the male produces a single stereotyped motif repeatedly in song bouts. These motif renditions, like the song repetitions of many birds, sound very similar to the casual human listener. In this study, we show that zebra finches can easily discriminate between the renditions, even at the level of single song syllables, much as humans can discriminate renditions of speech sounds. These results support the notion that sensitivity to fine acoustic details may be a primary channel of information in zebra finch song, as well as a shared, foundational property of vocal communication systems across species.

Core auditory cortex (AC) neurons encode slow fluctuations of acoustic stimuli with temporally patterned activity. However, whether temporal encoding is necessary to explain auditory perceptual skills remains uncertain. Here, we recorded from gerbil AC neurons while they discriminated between a 4-Hz amplitude modulation (AM) broadband noise and AM rates >4 Hz. We found a proportion of neurons possessed neural thresholds based on spike pattern or spike count that were better than the recorded session’s behavioral threshold, suggesting that spike count could provide sufficient information for this perceptual task. A population decoder that relied on temporal information outperformed a decoder that relied on spike count alone, but the spike count decoder still remained sufficient to explain average behavioral performance. This leaves open the possibility that more demanding perceptual judgments require temporal information. Thus, we asked whether accurate classification of different AM rates between 4 and 12 Hz required the information contained in AC temporal discharge patterns. Indeed, accurate classification of these AM stimuli depended on the inclusion of temporal information rather than spike count alone. Overall, our results compare two different representations of time-varying acoustic features that can be accessed by downstream circuits required for perceptual judgments.

Detecting the direction of frequency modulation (FM) is essential for vocal communication in both animals and humans. Direction-selective firing of neurons in the primary auditory cortex (A1) has been classically attributed to temporal offsets between feedforward excitatory and inhibitory inputs. However, it remains unclear how cortical recurrent circuitry contributes to this computation. Here, we used two-photon calcium imaging and whole-cell recordings in awake mice to demonstrate that direction selectivity is not caused by temporal offsets between synaptic currents, but by an asymmetry in total synaptic charge between preferred and non-preferred directions. Inactivation of cortical somatostatin-expressing interneurons (SOM cells) reduced direction selectivity, revealing its cortical contribution. Our theoretical models showed that charge asymmetry arises due to broad spatial topography of SOM cell-mediated inhibition which regulates signal amplification in strongly recurrent circuitry. Together, our findings reveal a major contribution of recurrent network dynamics in shaping cortical tuning to behaviorally relevant complex sounds.

Spatial hearing in cochlear implant (CI) patients remains a major challenge, with many early deaf users reported to have no measurable sensitivity to interaural time differences (ITDs). Deprivation of binaural experience during an early critical period is often hypothesized to be the cause of this shortcoming. However, we show that neonatally deafened (ND) rats provided with precisely synchronized CI stimulation in adulthood can be trained to lateralize ITDs with essentially normal behavioral thresholds near 50 μs. Furthermore, comparable ND rats show high physiological sensitivity to ITDs immediately after binaural implantation in adulthood. Our result that ND-CI rats achieved very good behavioral ITD thresholds, while prelingually deaf human CI patients often fail to develop a useful sensitivity to ITD raises urgent questions concerning the possibility that shortcomings in technology or treatment, rather than missing input during early development, may be behind the usually poor binaural outcomes for current CI patients.

Introduction A defect in the cochlear afferent synapse between the inner hair cells and spiral ganglion neurons, after noise exposure, without changes in the hearing threshold has been reported. Animal studies on auditory evoked potentials demonstrated changes in the auditory brainstem response (ABR) measurements of peak I amplitude and the loss of synapses, which affect the temporal resolution of complex sounds. Human studies of auditory evoked potential have reported ambiguous results regarding the relationship between peak I amplitude and noise exposure. Paired click stimuli have been used to investigate the temporal processing abilities of humans and animals. In this study, we investigated the utility of measuring auditory evoked potentials in response to paired click stimuli to assess the temporal processing function of ribbon synapses in noise-induced cochlear synaptopathy. Materials and Methods Twenty-two Sprague Dawley rats were used in this study, and synaptopathy was induced by narrow-band noise exposure (16 kHz with 1 kHz bandwidth, 105 dB sound pressure level for 2 h). ABRs to tone and paired click stimuli were measured before and 1, 3, 7, and 14 days after noise exposure. For histological analyses, hair cells and ribbon synapses were immunostained and the synapses quantified. The relationships among ABR peak I amplitude, number of synapses, and ABR to paired click stimuli were examined. Results Our results showed that ABR thresholds increase 1 day after noise exposure but fully recover to baseline levels after 14 days. Further, we demonstrated test frequency-dependent decreases in peak I amplitude and the number of synapses after noise exposure. These decreases were statistically significant at frequencies of 16 and 32 kHz. However, the ABR recovery threshold to paired click stimuli increased, which represent deterioration in the ability of temporal auditory processing. Our results indicate that the ABR recovery threshold is highly correlated with ABR peak I amplitude after noise exposure. We also established a direct correlation between the ABR recovery threshold and histological findings. Conclusion The result from this study suggests that in animal studies, the ABR to paired click stimuli along with peak I amplitude has potential as an assessment tool for hidden hearing loss.

Recently, application of stem cell therapy in regenerative medicine has become an active field of study. Mesenchymal stem cells (MSCs) are known to have a strong ability for homing. MSCs labeled with superparamagnetic iron oxide nanoparticles (SPIONs) exhibit enhanced homing due to magnetic attraction. We have designed a SPION that has a cluster core of iron oxide-based nanoparticles coated with PLGA-Cy5.5. We optimized the nanoparticles for internalization to enable the transport of PCS nanoparticles through endocytosis into MSCs. The migration of magnetized MSCs with SPION by static magnets was seen in vitro. The auditory hair cells do not regenerate once damaged, ototoxic mouse model was generated by administration of kanamycin and furosemide. SPION labeled MSC's were administered through different injection routes in the ototoxic animal model. As result, the intratympanic administration group with magnet had the highest number of cells in the brain followed by the liver, cochlea, and kidney as compared to those in the control groups. The synthesized PCS (poly clustered superparamagnetic iron oxide) nanoparticles, together with MSCs, by magnetic attraction, could synergistically enhance stem cell delivery. The poly clustered superparamagnetic iron oxide nanoparticle labeled in the mesenchymal stem cells have increased the efficacy of homing of the MSC's to the target area by synergetic effect of magnetic attraction and chemotaxis (SDF-1/CXCR4 axis). This technique allows delivery of the stem cells to the areas with limited vasculatures. The nanoparticle in the biomedicine allows drug delivery, thus, the combination of nanomedicince together with the regenerative medicine will provide highly effective therapy.

Cisplatin, a potent chemotherapeutic drug, induces ototoxicity, which limits its clinical utility. Cisplatin-induced oxidative stress plays a causal role in cochlear apoptosis while the consequent nitrative stress leads to the nitration of LIM domain only 4 (LMO4), a transcriptional regulator, and decreases its cochlear expression levels. Here, we show a direct link between cochlear LMO4 and cisplatin-induced hearing loss by employing a Lmo4 conditional knockout mouse model (Lmo4lox/lox; Gfi1Cre/+). Hair cell-specific deletion of Lmo4 did not alter cochlear morphology or affect hearing thresholds and otoacoustic emissions, in the absence of apoptotic stimuli. Cisplatin treatment significantly elevated the auditory brainstem response thresholds of conditional knockouts, across all frequencies. Moreover, deletion of Lmo4 compromised the activation of STAT3, a downstream target that regulates anti-apoptotic machinery. Immunostaining indicated that the expression of phosphorylated STAT3 was significantly decreased while the expression of activated caspase 3 was significantly increased in Lmo4 deficient hair cells, post-cisplatin treatment. These findings suggest an otoprotective role of LMO4 as cisplatin-induced decrease in cochlear LMO4 could compromise the LMO4/STAT3 cellular defense mechanism to induce ototoxicity.

Oxidative stress is the key determinant in the pathogenesis of noise-induced hearing loss (NIHL). Given that cellular defense against oxidative stress is an energy-consuming process, the aim of the present study was to investigate whether increasing energy availability by glucose supplementation protects cochlear hair cells against oxidative stress and attenuates NIHL. Our results revealed that glucose supplementation reduced the noise-induced formation of reactive oxygen species (ROS) and consequently attenuated noise-induced loss of outer hair cells, inner hair cell synaptic ribbons, and NIHL in CBA/J mice. In cochlear explants, glucose supplementation increased the levels of ATP and NADPH, as well as attenuating H2O2-induced ROS production and cytotoxicity. Moreover, pharmacological inhibition of glucose transporter type 1 activity abolished the protective effects of glucose against oxidative stress in HEI-OC1 cells. These findings suggest that energy availability is crucial for oxidative stress resistance and glucose supplementation offers a simple and effective approach for the protection of cochlear hair cells against oxidative stress and NIHL.

Tinnitus, the phantom perception of sound, often occurs as a clinical sequela of auditory traumas. In an effort to develop an objective test and therapeutic approach for tinnitus, the present study was performed in blast-exposed rats and focused on measurements of auditory brainstem responses (ABRs), prepulse inhibition of the acoustic startle response, and presynaptic ribbon densities on cochlear inner hair cells (IHCs). Although the exact mechanism is unknown, the “central gain theory” posits that tinnitus is a perceptual indicator of abnormal increases in the gain (or neural amplification) of the central auditory system to compensate for peripheral loss of sensory input from the cochlea. Our data from vehicle-treated rats supports this rationale; namely, blast-induced cochlear synaptopathy correlated with imbalanced elevations in the ratio of centrally-derived ABR wave V amplitudes to peripherally-derived wave I amplitudes, resulting in behavioral evidence of tinnitus. Logistic regression modeling demonstrated that the ABR wave V/I amplitude ratio served as a reliable metric for objectively identifying tinnitus. Furthermore, histopathological examinations in blast-exposed rats revealed tinnitus-related changes in the expression patterns of key plasticity factors in the central auditory pathway, including chronic loss of Arc/Arg3.1 mobilization. Using a formulation of N -acetylcysteine (NAC) and disodium 2,4-disulfophenyl- N -tert-butylnitrone (HPN-07) as a therapeutic for addressing blast-induced neurodegeneration, we measured a significant treatment effect on preservation or restoration of IHC ribbon synapses, normalization of ABR wave V/I amplitude ratios, and reduced behavioral evidence of tinnitus in blast-exposed rats, all of which accorded with mitigated histopathological evidence of tinnitus-related neuropathy and maladaptive neuroplasticity.

Hearing impairment is the most common sensory disorder in humans. So far, rehabilitation of profoundly deaf subjects relies on direct stimulation of the auditory nerve through cochlear implants. However, in some forms of genetic hearing impairment, the organ of Corti is structurally intact and therapeutic replacement of the mutated gene could potentially restore near natural hearing. In the case of defects of the otoferlin gene ( OTOF ), such gene therapy is hindered by the size of the coding sequence (~6 kb) exceeding the cargo capacity (<5 kb) of the preferred viral vector, adeno-associated virus (AAV). Recently, a dual-AAV approach was used to partially restore hearing in deaf otoferlin knock-out ( Otof- KO) mice. Here, we employed in vitro and in vivo approaches to assess the gene-therapeutic potential of naturally-occurring and newly-developed synthetic AAVs overloaded with the full-length Otof coding sequence. Upon early postnatal injection into the cochlea of Otof- KO mice, overloaded AAVs drove specific expression of otoferlin in ~30% of all IHCs, as demonstrated by immunofluorescence labeling and polymerase chain reaction. Recordings of auditory brainstem responses and a behavioral assay demonstrated partial restoration of hearing. Together, our results suggest that viral gene therapy of DFNB9—using a single overloaded AAV vector—is indeed feasible, reducing the complexity of gene transfer compared to dual-AAV approaches.

Auditory Residual Inhibition (ARI) is a temporary suppression of tinnitus that occurs in some people following the presentation of masking sounds. Differences in neural response to ARI stimuli may enable classification of tinnitus and a tailored approach to intervention in the future. In an exploratory study, we investigated the use of a brain-inspired artificial neural network to examine the effects of ARI on electroencephalographic function, as well as the predictive ability of the model. Ten tinnitus patients underwent two auditory stimulation conditions (constant and amplitude modulated broadband noise) at two time points and were then characterised as responders or non-responders, based on whether they experienced ARI or not. Using a spiking neural network model, we evaluated concurrent neural patterns generated across space and time from features of electroencephalographic data, capturing the neural dynamic changes before and after stimulation. Results indicated that the model may be used to predict the effect of auditory stimulation on tinnitus on an individual basis. This approach may aid in the development of predictive models for treatment selection.

Inner hair cell (IHC) ribbon synapses are the first synapse in the auditory system and can be degenerated by noise and aging, thereby leading to hidden hearing loss (HHL) and other hearing disorders. However, the mechanism underlying this cochlear synaptopathy remains unclear. Here, we report that elevation of extracellular K + , which is a consequence of noise exposure, could cause IHC ribbon synapse degeneration and swelling. Like intensity dependence in noise-induced cochlear synaptopathy, the K + -induced degeneration was dose-dependent, and could be attenuated by BK channel blockers. However, application of glutamate receptor (GluR) agonists caused ribbon swelling but not degeneration. In addition, consistent with synaptopathy in HHL, both K + and noise exposure only caused IHC but not outer hair cell ribbon synapse degeneration. These data reveal that K + excitotoxicity can degenerate IHC ribbon synapses in HHL, and suggest that BK channel may be a potential target for prevention and treatment of HHL.

Envelope following responses (EFRs) may be a useful tool for evaluating the audibility of speech sounds in infants. The present study aimed to evaluate the characteristics of speech-evoked EFRs in infants with normal hearing, relative to adults, and identify age-dependent changes in EFR characteristics during infancy. In 42 infants and 21 young adults, EFRs were elicited by the first (F1) and the second and higher formants (F2+) of the vowels /u/, /a/, and /i/, dominant in low and mid frequencies, respectively, and by amplitude-modulated fricatives /s/ and /∫/, dominant in high frequencies. In a subset of 20 infants, the in-ear stimulus level was adjusted to match that of an average adult ear (65 dB sound pressure level [SPL]). We found that (a) adult–infant differences in EFR amplitude, signal-to-noise ratio, and intertrial phase coherence were larger and spread across the frequency range when in-ear stimulus level was adjusted in infants, (b) adult–infant differences in EFR characteristics were the largest for low-frequency stimuli, (c) infants demonstrated adult-like phase coherence when they received a higher (i.e., unadjusted) stimulus level, and (d) EFR phase coherence and signal-to-noise ratio changed with age in the first year of life for a few F2+ vowel stimuli in a level-specific manner. Together, our findings reveal that development-related changes in EFRs during infancy likely vary by stimulus frequency, with low-frequency stimuli demonstrating the largest adult–infant differences. Consistent with previous research, our findings emphasize the significant role of stimulus level calibration methods while investigating developmental trends in EFRs.

A sequential dual-task design was used to assess the impacts of spoken sentence context and cognitive load on listening effort. Young adults with normal hearing listened to sentences masked by multitalker babble in which sentence-final words were either predictable or unpredictable. Each trial began with visual presentation of a short (low-load) or long (high-load) sequence of to-be-remembered digits. Words were identified more quickly and accurately in predictable than unpredictable sentence contexts. In addition, digits were recalled more quickly and accurately on trials on which the sentence was predictable, indicating reduced listening effort for predictable compared to unpredictable sentences. For word and digit recall response time but not for digit recall accuracy, the effect of predictability remained significant after exclusion of trials with incorrect word responses and was thus independent of speech intelligibility. In addition, under high cognitive load, words were identified more slowly and digits were recalled more slowly and less accurately than under low load. Participants’ working memory and vocabulary were not correlated with the sentence context benefit in either word recognition or digit recall. Results indicate that listening effort is reduced when sentences are predictable and that cognitive load affects the processing of spoken words in sentence contexts.

This work examines how sounds are held in auditory working memory (AWM) in humans by examining oscillatory local field potentials (LFPs) in candidate brain regions. Previous fMRI studies by our group demonstrated blood oxygenation level-dependent (BOLD) response increases during maintenance in auditory cortex, inferior frontal cortex and the hippocampus using a paradigm with a delay period greater than 10s. The relationship between such BOLD changes and ensemble activity in different frequency bands is complex, and the long delay period raised the possibility that long-term memory mechanisms were engaged. Here we assessed LFPs in different frequency bands in six subjects with recordings from all candidate brain regions using a paradigm with a short delay period of 3 s. Sustained delay activity was demonstrated in all areas, with different patterns in the different areas. Enhancement in low frequency (delta) power and suppression across higher frequencies (beta/gamma) were demonstrated in primary auditory cortex in medial Heschl's gyrus (HG) whilst non-primary cortex showed patterns of enhancement and suppression that altered at different levels of the auditory hierarchy from lateral HG to superior- and middle-temporal gyrus. Inferior frontal cortex showed increasing suppression with increasing frequency. The hippocampus and parahippocampal gyrus showed low frequency increases and high frequency decreases in oscillatory activity. This work demonstrates sustained activity patterns during AWM maintenance, with prominent low-frequency increases in medial temporal lobe regions.

The difference in binaural benefit between bilateral cochlear implant (CI) users and normal hearing (NH) listeners has typically been attributed to CI sound coding strategies not encoding the acoustic fine structure (FS) interaural time differences (ITD). The Temporal Limits Encoder (TLE) strategy is proposed as a potential way of improving binaural hearing benefits for CI users in noisy situations. TLE works by downward-transposition of mid-frequency band-limited channel information and can theoretically provide FS-ITD cues. In this work, the effect of choice of lower limit of the modulator in TLE was examined by measuring performance on a word recognition task and computing the magnitude of binaural benefit in bilateral CI users. Performance listening with the TLE strategy was compared with the commonly used Advanced Combinational Encoder (ACE) CI sound coding strategy. Results showed that setting the lower limit to ≥200 Hz maintained word recognition performance comparable to that of ACE. While most CI listeners exhibited a large binaural benefit (≥6 dB) in at least one of the conditions tested, there was no systematic relationship between the lower limit of the modulator and performance. These results indicate that the TLE strategy has potential to improve binaural hearing abilities in CI users but further work is needed to understand how binaural benefit can be maximized.