Lateralization of interaural time differences with mixed rates of stimulation in bilateral cochlear implant listeners.

While listeners with bilateral cochlear implants (BiCIs) are able to access information in both ears, they still struggle to perform well on spatial hearing tasks when compared to normal hearing listeners. This performance gap could be attributed to the high stimulation rates used for speech representation in clinical processors. Prior work has shown that spatial cues, such as interaural time differences (ITDs), are best conveyed at low rates. Further, BiCI listeners are sensitive to ITDs with a mixture of high and low rates. However, it remains unclear whether mixed-rate stimuli are perceived as unitary percepts and spatially mapped to intracranial locations. Here, electrical pulse trains were presented on five, interaurally pitch-matched electrode pairs using research processors, at either uniformly high rates, low rates, or mixed rates. Eight post-lingually deafened adults were tested on perceived intracranial lateralization of ITDs ranging from 50 to 1600 µs. Extent of lateralization depended on the location of low-rate stimulation along the electrode array: greatest in the low- and mixed-rate configurations, and smallest in the high-rate configuration. All but one listener perceived a unitary auditory object. These findings suggest that a mixed-rate processing strategy can result in good lateralization and convey a unitary auditory object with ITDs.

Lateralization of binaural envelope cues measured with a mobile cochlear-implant research processora).

Bilateral cochlear implant (BICI) listeners do not have full access to the binaural cues that normal hearing (NH) listeners use for spatial hearing tasks such as localization. When using their unsynchronized everyday processors, BICI listeners demonstrate sensitivity to interaural level differences (ILDs) in the envelopes of sounds, but interaural time differences (ITDs) are less reliably available. It is unclear how BICI listeners use combinations of ILDs and envelope ITDs, and how much each cue contributes to perceived sound location. The CCi-MOBILE is a bilaterally synchronized research processor with the untested potential to provide spatial cues to BICI listeners. In the present study, the CCi-MOBILE was used to measure the ability of BICI listeners to perceive lateralized sound sources when single pairs of electrodes were presented amplitude-modulated stimuli with combinations of ILDs and envelope ITDs. Young NH listeners were also tested using amplitude-modulated high-frequency tones. A cue weighting analysis with six BICI and ten NH listeners revealed that ILDs contributed more than envelope ITDs to lateralization for both groups. Moreover, envelope ITDs contributed to lateralization for NH listeners but had negligible contribution for BICI listeners. These results suggest that the CCi-MOBILE is suitable for binaural testing and developing bilateral processing strategies.

The Impact of Synchronized Cochlear Implant Sampling and Stimulation on Free-Field Spatial Hearing Outcomes: Comparing the ciPDA Research Processor to Clinical Processors.

OBJECTIVES: Bilateral cochlear implant (BiCI) listeners use independent processors in each ear. This independence and lack of shared hardware prevents control of the timing of sampling and stimulation across ears, which precludes the development of bilaterally-coordinated signal processing strategies. As a result, these devices potentially reduce access to binaural cues and introduce disruptive artifacts. For example, measurements from two clinical processors demonstrate that independently-running processors introduce interaural incoherence. These issues are typically avoided in the laboratory by using research processors with bilaterally-synchronized hardware. However, these research processors do not typically run in real-time and are difficult to take out into the real-world due to their benchtop nature. Hence, the question of whether just applying hardware synchronization to reduce bilateral stimulation artifacts (and thereby potentially improve functional spatial hearing performance) has been difficult to answer. The CI personal digital assistant (ciPDA) research processor, which uses one clock to drive two processors, presented an opportunity to examine whether synchronization of hardware can have an impact on spatial hearing performance. DESIGN: Free-field sound localization and spatial release from masking (SRM) were assessed in 10 BiCI listeners using both their clinical processors and the synchronized ciPDA processor. For sound localization, localization accuracy was compared within-subject for the two processor types. For SRM, speech reception thresholds were compared for spatially separated and co-located configurations, and the amount of unmasking was compared for synchronized and unsynchronized hardware. There were no deliberate changes of the sound processing strategy on the ciPDA to restore or improve binaural cues. RESULTS: There was no significant difference in localization accuracy between unsynchronized and synchronized hardware (p = 0.62). Speech reception thresholds were higher with the ciPDA. In addition, although five of eight participants demonstrated improved SRM with synchronized hardware, there was no significant difference in the amount of unmasking due to spatial separation between synchronized and unsynchronized hardware (p = 0.21). CONCLUSIONS: Using processors with synchronized hardware did not yield an improvement in sound localization or SRM for all individuals, suggesting that mere synchronization of hardware is not sufficient for improving spatial hearing outcomes. Further work is needed to improve sound coding strategies to facilitate access to spatial hearing cues. This study provides a benchmark for spatial hearing performance with real-time, bilaterally-synchronized research processors.

Asymmetric temporal envelope sensitivity: Within- and across-ear envelope comparisons in listeners with bilateral cochlear implants.

For listeners with bilateral cochlear implants (BiCIs), patient-specific differences in the interface between cochlear implant (CI) electrodes and the auditory nerve can lead to degraded temporal envelope information, compromising the ability to distinguish between targets of interest and background noise. It is unclear how comparisons of degraded temporal envelope information across spectral channels (i.e., electrodes) affect the ability to detect differences in the temporal envelope, specifically amplitude modulation (AM) rate. In this study, two pulse trains were presented simultaneously via pairs of electrodes in different places of stimulation, within and/or across ears, with identical or differing AM rates. Results from 11 adults with BiCIs indicated that sensitivity to differences in AM rate was greatest when stimuli were paired between different places of stimulation in the same ear. Sensitivity from pairs of electrodes was predicted by the poorer electrode in the pair or the difference in fidelity between both electrodes in the pair. These findings suggest that electrodes yielding poorer temporal fidelity act as a bottleneck to comparisons of temporal information across frequency and ears, limiting access to the cues used to segregate sounds, which has important implications for device programming and optimizing patient outcomes with CIs.

Temporal dynamics and uncertainty in binaural hearing revealed by anticipatory eye movements.

Accurate perception of binaural cues is essential for left-right sound localization. Much literature focuses on threshold measures of perceptual acuity and accuracy. This study focused on supra-threshold perception using an anticipatory eye movement (AEM) paradigm designed to capture subtle aspects of perception that might not emerge in behavioral-motor responses, such as the accumulation of certainty, and rapid revisions in decision-making. Participants heard interaural timing differences (ITDs) or interaural level differences in correlated or uncorrelated narrowband noises, respectively. A cartoon ball moved behind an occluder and then emerged from the left or right side, consistent with the binaural cue. Participants anticipated the correct answer (before it appeared) by looking where the ball would emerge. Results showed quicker and more steadfast gaze fixations for stimuli with larger cue magnitudes. More difficult stimuli elicited a wider distribution of saccade times and greater number of corrective saccades before final judgment, implying perceptual uncertainty or competition. Cue levels above threshold elicited some wrong-way saccades that were quickly corrected. Saccades to ITDs were earlier and more reliable for low-frequency noises. The AEM paradigm reveals the time course of uncertainty and changes in perceptual decision-making for supra-threshold binaural stimuli even when behavioral responses are consistently correct.

Effect of channel separation and interaural mismatch on fusion and lateralization in normal-hearing and cochlear-implant listeners.

Bilateral cochlear implantation has provided access to some of the benefits of binaural hearing enjoyed by normal-hearing (NH) listeners. However, a gap in performance still exists between the two populations. Single-channel stimulation studies have shown that interaural place-of-stimulation mismatch (IPM) due to differences in implantation depth leads to decreased binaural fusion and lateralization of interaural time and level differences (ITDs and ILDs, respectively). While single-channel studies are informative, multi-channel stimulation is needed for good speech understanding with cochlear implants (CIs). Some multi-channel studies have shown that channel interaction due to current spread can affect ITD sensitivity. In this work, we studied the effect of IPM and channel spacing, along with their potential interaction, on binaural fusion and ITD/ILD lateralization. Experiments were conducted in adult NH listeners and CI listeners with a history of acoustic hearing. Results showed that IPM reduced the range of lateralization for ITDs but not ILDs. CI listeners were more likely to report a fused percept in the presence of IPM with multi-channel stimulation than NH listeners. However, no effect of channel spacing was found. These results suggest that IPM should be accounted for in clinical mapping practices in order to maximize bilateral CI benefits.

Asymmetric temporal envelope encoding: Implications for within- and across-ear envelope comparison.

Separating sound sources in acoustic environments relies on making ongoing, highly accurate spectro-temporal comparisons. However, listeners with hearing impairment may have varying quality of temporal encoding within or across ears, which may limit the listeners' ability to make spectro-temporal comparisons between places-of-stimulation. In this study in normal hearing listeners, depth of amplitude modulation (AM) for sinusoidally amplitude modulated (SAM) tones was manipulated in an effort to reduce the coding of periodicity in the auditory nerve. The ability to judge differences in AM rates was studied for stimuli presented to different cochlear places-of-stimulation, within- or across-ears. It was hypothesized that if temporal encoding was poorer for one tone in a pair, then sensitivity to differences in AM rate of the pair would decrease. Results indicated that when the depth of AM was reduced from 50% to 20% for one SAM tone in a pair, sensitivity to differences in AM rate decreased. Sensitivity was greatest for AM rates near 90 Hz and depended upon the places-of-stimulation being compared. These results suggest that degraded temporal representations in the auditory nerve for one place-of-stimulation could lead to deficits comparing that temporal information with other places-of-stimulation.

Auditory motion tracking ability of adults with normal hearing and with bilateral cochlear implants.

Adults with bilateral cochlear implants (BiCIs) receive benefits in localizing stationary sounds when listening with two implants compared with one; however, sound localization ability is significantly poorer when compared to normal hearing (NH) listeners. Little is known about localizing sound sources in motion, which occurs in typical everyday listening situations. The authors considered the possibility that sound motion may improve sound localization in BiCI users by providing multiple places of information. Alternatively, the ability to compare multiple spatial locations may be compromised in BiCI users due to degradation of binaural cues, and thus result in poorer performance relative to NH adults. In this study, the authors assessed listeners' abilities to distinguish between sounds that appear to be moving vs stationary, and track the angular range and direction of moving sounds. Stimuli were bandpass-filtered (150-6000 Hz) noise bursts of different durations, panned over an array of loudspeakers. Overall, the results showed that BiCI users were poorer than NH adults in (i) distinguishing between a moving vs stationary sound, (ii) correctly identifying the direction of movement, and (iii) tracking the range of movement. These findings suggest that conventional cochlear implant processors are not able to fully provide the cues necessary for perceiving auditory motion correctly.

Comparative effectiveness of beta-interferons and glatiramer acetate for relapsing-remitting multiple sclerosis: systematic review and network meta-analysis of trials including recommended dosages.

BACKGROUND: We systematically reviewed the comparative effectiveness of injectable beta-interferons (IFN-ß) and glatiramer acetate (GA) on annualised relapse rate (ARR), progression and discontinuation due to adverse events (AEs) in RRMS, using evidence from within the drugs' recommended dosages. METHODS: We updated prior comprehensive reviews, checked references of included studies, contacted experts in the field, and screened websites for relevant publications to locate randomised trials of IFN-ß and GA with recommended dosages in RRMS populations, compared against placebo or other recommended dosages. Abstracts were screened and assessed for inclusion in duplicate and independently. Studies were appraised using the Cochrane risk of bias tool. Rate ratios for ARR, hazard ratios for time to progression, and risk ratios for discontinuation due to AEs were synthesised in separate models using random effects network meta-analysis. RESULTS: We identified 24 studies reported in 42 publications. Most studies were at high risk of bias in at least one domain. All drugs had a beneficial effect on ARR as compared to placebo, but not compared to each other, and findings were robust to sensitivity analysis. We considered time to progression confirmed at 3 months and confirmed at 6 months in separate models; while both models suggested that the included drugs were effective, findings were not consistent between models. Discontinuation due to AEs did not appear to be different between drugs. CONCLUSIONS: Meta-analyses confirmed that IFN-ß and GA reduce ARR and generally delay progression as defined in these trials, though there was no clear 'winner' across outcomes. Findings are additionally tempered by the high risk of bias across studies, and the use of an impairment/mobility scale to measure disease progression. Future research should consider more relevant measures of disability and, given that most trials have been short-term, consider a longitudinal approach to comparative effectiveness. REVIEW REGISTRATION: PROSPERO CRD42016043278 .

The Effect of Simulated Interaural Frequency Mismatch on Speech Understanding and Spatial Release From Masking.

OBJECTIVE: The binaural-hearing system interaurally compares inputs, which underlies the ability to localize sound sources and to better understand speech in complex acoustic environments. Cochlear implants (CIs) are provided in both ears to increase binaural-hearing benefits; however, bilateral CI users continue to struggle with understanding speech in the presence of interfering sounds and do not achieve the same level of spatial release from masking (SRM) as normal-hearing listeners. One reason for diminished SRM in CI users could be that the electrode arrays are inserted at different depths in each ear, which would cause an interaural frequency mismatch. Because interaural frequency mismatch diminishes the salience of interaural differences for relatively simple stimuli, it may also diminish binaural benefits for spectral-temporally complex stimuli like speech. This study evaluated the effect of simulated frequency-to-place mismatch on speech understanding and SRM. DESIGN: Eleven normal-hearing listeners were tested on a speech understanding task. There was a female target talker who spoke five-word sentences from a closed set of words. There were two interfering male talkers who spoke unrelated sentences. Nonindividualized head-related transfer functions were used to simulate a virtual auditory space. The target was presented from the front (0°), and the interfering speech was either presented from the front (colocated) or from 90° to the right (spatially separated). Stimuli were then processed by an eight-channel vocoder with tonal carriers to simulate aspects of listening through a CI. Frequency-to-place mismatch ("shift") was introduced by increasing the center frequency of the synthesis filters compared with the corresponding analysis filters. Speech understanding was measured for different shifts (0, 3, 4.5, and 6 mm) and target-to-masker ratios (TMRs: +10 to -10 dB). SRM was calculated as the difference in the percentage of correct words for the colocated and separated conditions. Two types of shifts were tested: (1) bilateral shifts that had the same frequency-to-place mismatch in both ears, but no interaural frequency mismatch, and (2) unilateral shifts that produced an interaural frequency mismatch. RESULTS: For the bilateral shift conditions, speech understanding decreased with increasing shift and with decreasing TMR, for both colocated and separate conditions. There was, however, no interaction between shift and spatial configuration; in other words, SRM was not affected by shift. For the unilateral shift conditions, speech understanding decreased with increasing interaural mismatch and with decreasing TMR for both the colocated and spatially separated conditions. Critically, there was a significant interaction between the amount of shift and spatial configuration; in other words, SRM decreased for increasing interaural mismatch. CONCLUSIONS: A frequency-to-place mismatch in one or both ears resulted in decreased speech understanding. SRM, however, was only affected in conditions with unilateral shifts and interaural frequency mismatch. Therefore, matching frequency information between the ears provides listeners with larger binaural-hearing benefits, for example, improved speech understanding in the presence of interfering talkers. A clinical procedure to reduce interaural frequency mismatch when programming bilateral CIs may improve benefits in speech segregation that are due to binaural-hearing abilities.