Perception and coding of interaural time differences with bilateral cochlear implants.

Hearing Research 322 (2015) 138e150

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Hearing Research journal homepage: www.elsevier.com/locate/heares

Review

Perception and coding of interaural time differences with bilateral cochlear implants Bernhard Laback*, Katharina Egger, Piotr Majdak Acoustics Research Institute, Austrian Academy of Sciences, Wohllebengasse 12-14, A-1040 Vienna, Austria

a r t i c l e i n f o

a b s t r a c t

Article history: Received 20 May 2014 Received in revised form 1 October 2014 Accepted 7 October 2014 Available online 19 October 2014

Bilateral cochlear implantation is increasingly becoming the standard in the clinical treatment of bilateral deafness. The main motivation is to provide users of bilateral cochlear implants (CIs) access to binaural cues essential for localizing sound sources and understanding speech in environments of interfering sounds. One of those cues, interaural level differences, can be perceived well by CI users to allow some basic left versus right localization. However, interaural time differences (ITDs) which are important for localization of low-frequency sounds and spatial release from masking are not adequately represented by clinical envelope-based CI systems. Here, we first review the basic ITD sensitivity of CI users, particularly their dependence on stimulation parameters like stimulation rate and place, modulation rate, and envelope shape in single-electrode stimulation, as well as stimulation level, electrode spacing, and monaural across-electrode timing in multiple-electrode stimulation. Then, we discuss factors involved in ITD perception in electric hearing including the match between highly phase-locked electric auditory nerve response properties and binaural cell properties, the restricted stimulation of apical tonotopic pathways, channel interactions in multiple-electrode stimulation, and the onset age of binaural auditory input. Finally, we present clinically available CI stimulation strategies and experimental strategies aiming at improving listeners' access to ITD cues. This article is part of a Special Issue entitled . © 2014 Elsevier B.V. All rights reserved.

1. Introduction Bilateral cochlear implantation is increasingly considered as standard approach in the clinical treatment of profound hearing loss or deafness. As nobody would nowadays postulate to supply only one eye with glasses, it has been more and more realized that there are reasons for having two ears and that providing a cochlear implant (CI) only on one ear prevents CI users from the advantages of binaural hearing experienced by normal-hearing (NH) listeners. In normal (acoustic) listening, binaural hearing allows for localizing sound sources along the left versus right dimension and facilitates the understanding of a target talker against a background of spatially separated interfering sounds (for reviews on binaural hearing in NH listeners see Blauert, 1997; Middlebrooks and Green, 1991; Stecker and Gallun, 2012; Yost and Hafter, 1987). Listening with bilateral CIs does not automatically imply fully functional binaural hearing as in acoustic hearing with both ears, where the

* Corresponding author. Tel.: þ43 1 51581 2514. E-mail address: [email protected] (B. Laback). http://dx.doi.org/10.1016/j.heares.2014.10.004 0378-5955/© 2014 Elsevier B.V. All rights reserved.

two ear signals are combined and processed at binaural stages in the auditory system. Fortunately, even without binaural processing, listening with bilateral CIs may provide advantages. For example, as a result of the acoustic head shadow, in many spatial configurations one of the CIs provides a better signal-to-noise ratio at certain instances of time, enabling the listener to pick out information about the target source from the momentarily “better” ear. As a result of this ability (so-called better-ear listening), bilateral CI listeners have been shown to gain a robust advantage from a second CI (for recent reviews see van Hoesel, 2012; Litovsky et al., 2012). In contrast, binaural hearing is more challenging because it requires the access of the listener to various binaural cues associated with a given auditory scene. Before addressing the situation with bilateral CIs, let us first describe the nature of binaural cues and their contribution to spatial tasks like sound localization and speech understanding in noise. Fig. 1(a) illustrates a spatial configuration with a sound source arriving from the side of a listener. This configuration results in interaural differences, i.e., differences between the signals arriving at the two ears. First, the acoustic head shadow attenuates the sound arriving at the right ear, resulting in an interaural level difference

B. Laback et al. / Hearing Research 322 (2015) 138e150

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Fig. 1. Binaural cues. (a) Schematic view of a sound source at the left side of a listener resulting in level and time differences between the signals arriving at the two ears. (b) Amplitude modulated signals arriving at both ears, containing ITD in the carrier (or temporal fine structure, ITDFS), ITD in the modulator (or envelope, ITDENV), and ILD. (c) Amplitude modulated, electric pulse trains, containing ITDFS, ITDENV, and ILD.

(ILD), which is most pronounced at high frequencies. Second, the longer sound propagation path to the right ear results in an interaural time difference (ITD). For an amplitude modulated sound as shown in Fig. 1(b), the ITD arises in different signal components: the carrier (or temporal fine structure), yielding ITDFS, the modulator (or ongoing envelope), yielding ITDENV, and the gating portions (onset and offset, not shown). For the sake of completeness, Fig. 1(c) shows the representation of such a stimulus in electric hearing. While all these types of binaural cues encode the temporal information on the lateral position of a sound source, their perceptual contribution is quite different. For sound-source localization, presuming sufficient amount of low-frequency content in the stimulus, ITD seems to be the most salient cue (Macpherson and Middlebrooks, 2002; Wightman and Kistler, 1992). In acoustic hearing, low-frequency ITDs manifest as ITDFS, suggesting its dominant role for this task (Smith et al., 2002). For speech understanding in the presence of interfering sounds, the improvement in performance due to binaural hearing, sometimes referred to as binaural squelch,1 can be attributed to at least two mechanisms: 1) Binaural unmasking, i.e., the improved target detection in the presence of an interfering sound under the assumptions of spatial separation between target and interferer and of a high degree of spectro-temporal overlap between target and interfering sounds (e.g., Bronkhorst and Plomp, 1988; Bronkhorst, 2000). This configuration usually involves a high degree of energetic masking. Binaural unmasking can therefore be understood in terms of a release from energetic masking (Kidd et al., 2008, 2010). The underlying effect is known as the so-called binaural masking level difference and can be best measured using deterministic stimuli presented via headphones. It refers to the reduction of the threshold of detecting a pure-tone target in the presence of a noise masker in conditions where the target and the masker differ in binaural cues as compared to conditions where target and masker have the same binaural cues (e.g., Durlach and Colburn, 1978). One particularly effective binaural cue is the phase inversion of the target or the masker at one ear, introducing frequency-dependent ITD. 2) Attention-driven spatial release from masking, i.e., the improved focus on a target sound, again assuming spatial separation between target and interferer (Kidd et al., 2008). This mechanism operates particularly in configurations involving a high degree of informational masking such as speech-on-speech

1 More precisely, binaural squelch is defined as the improvement in understanding speech in spatially separated, competing sounds due to combining information from both ears, including the one with the lower SNR and, thus, suppressing the competing sounds.

masking. Informational masking depends on factors such as attention, auditory grouping, and segregation, as well as memory and general processing capacity. Given the above, attention-driven spatial release from masking can be understood in terms of a release from informational masking (Kidd et al., 2010). For both binaural unmasking and attention-driven spatial release from masking, ITD has been shown to be the dominant cue. In more detail, binaural unmasking mostly relies on ITDFS (Durlach and Colburn, 1978; van der Heijden and Joris, 2010), to a smaller extent on ITDENV (van de Par and Kohlrausch, 1997), and to an even smaller extent on ILD (Van der Heijden and Joris, 2010). Attentiondriven spatial release from masking is stronger for low-frequency than for high-frequency stimuli, also suggesting an important role of ITDFS (Bremen and Middlebrooks, 2013; Kidd et al., 2010). One recent virtual-acoustics study, however, showed stronger spatial release from masking for ILD than for ITD (Glyde et al., 2013). Spatial cues, and particularly ITDFS, have been shown to be important for the segregation of temporally interleaved sequences of sounds (Middlebrooks and Onsan, 2012). Even though the amount of information received from sources separated only by ITDs appears to be low, in the absence of other segregation cues such as harmonicity, pitch, and onsets (Schwartz et al., 2012), a large spatial release from masking in such conditions has been found (Ihlefeld and Litovsky, 2012). In summary, there is strong evidence for a pivotal role of ITD, and particularly ITDFS, in various aspects of spatial hearing. When localizing a sound in reverberant environments, sound reflections from walls and other surfaces temporally overlap with the direct sound, resulting in spurious spatial information arriving at the listener's ears. Under such conditions, the ear-input signals become less interaurally coherent (Hartmann et al., 2005; Houtgast and Steeneken, 1973) and the instantaneous ITD fluctuates (Dietz et al., 2013). As compared to low-frequency temporal fine structure, highfrequency envelopes were reported to be less susceptible to the reduction of the interaural coherence caused by reverberation (Ruggles et al., 2012). Ruggles et al. (2012) concluded that, for younger adults, spatial hearing in reverberant settings relies more on highfrequency ITDENV cues than on low-frequency ITDFS cues. A potential role of high-frequency ITDENV cues in localization under reverberant conditions was also suggested in a recent study on CI listeners (Kerber and Seeber, 2013). Contrary to those findings, other studies testing NH listeners reported the sensitivity to ITDENV to be more impaired by reverberation than the sensitivity to ITDFS (Devore and Delgutte, 2010; Monaghan et al., 2013; Rakerd and Hartmann, 2010). Furthermore, reverberation was found to increase the relative perceptual contribution of high-frequency ILD cues (Devore and Delgutte, 2010).

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When applying these findings to binaural hearing with bilateral CIs, two main questions arise: 1) Are binaural difference cues preserved in the electric signals presented at the implant electrodes, after passing the signal-processing stages of clinical CI processors? 2) Are CI listeners sensitive to binaural difference cues at all, namely when controlled at the implant electrodes while bypassing the clinical CI processors. Generally, bilateral CI listeners using the widespread clinical stimulation strategies (see Section 4) have been shown to be able to discriminate left versus right locations of a single sound source (Grantham et al., 2008; Laback et al., 2004; Seeber and Fastl, 2008; Senn et al., 2005). So, obviously, both questions stated above seem to be answered positively. However, there is strong evidence that this ability is based on ILDs, not ITDs, directly re-addressing the two questions. Regarding the first question, most clinical stimulation strategies entirely discard ITDFS information, while the salience of the transmitted ITDENV cues depends critically on the properties of both the incoming sound and the stimulation strategy. Regarding the second question, even for direct, binaurally controlled stimulation, the CI listeners' sensitivity to ITDFS and ITDENV is overall reduced compared to NH listeners and depends critically on particular stimulation parameters (for details and references see below). Given the currently limited access of bilateral CI users to ITD cues and the high importance of these cues for localization and speech understanding in noise, this review article aims at providing an overview of the current knowledge on ITD perception with bilateral CIs. In Section 2, we address the basic psychophysical and physiological ITD sensitivity measured with direct stimulation of implant electrodes. Section 3 lists factors potentially accounting for the huge variability in ITD sensitivity observed in electric stimulation. Finally, Section 4 provides an overview of approaches to encode and enhance ITD cues with CI stimulation strategies.

2. General ITD sensitivity Experiments on the sensitivity to ITD with bilateral CIs require accurate control of electric stimulation sequences, stimulation place at each ear, and relative stimulation timing between the two ears. Therefore, in the experiments described in this section, computer-generated stimuli were transmitted to the implant electrodes via research interface systems while bypassing the clinical speech processors. CIs typically generate trains of biphasic, charge-balanced, electric pulses at a given electrode.2 For more details on the technical aspects of CIs, see, for example Zeng et al. (2008). The vast majority of experiments on ITD have been performed stimulating a single electrode at each ear (Section 2.1), referred to as single (interaural) electrode pair. Only recent investigations have included conditions of controlled stimulation at multipleelectrode pairs (Section 2.2). Usually, ITD sensitivity is measured by determining the listeners' thresholds for ITD-based left versus right discrimination of a target stimulus relative to a reference stimulus. The psychophysical data presented in this section were collected mostly in postlingually deafened, adult human listeners, with the exception of a few prelingually deafened listeners. The relevance of the onset of deafness is addressed in Section 3.2.

2 While early studies often used bipolar stimulation mode where two adjacent electrodes are paired as active and return, later studies most often used monopolar mode where the current flows from the active electrode to an extracochlear ground electrode.

2.1. Single interaural electrode pair The normal auditory system is most sensitive to binaural information if the binaural stimulus is tonotopically place-matched between the two ears (Henning, 1974; Scharf et al., 1976). Therefore, studies on binaural sensitivity in CI listeners mostly attempted to present stimuli at interaurally place-matched electrodes (for details on methods see, e.g., Laback et al., 2007; Majdak et al., 2006; for a discussion of place matching see Section 3.2). In addition, given that binaural sensitivity is best for stimuli perceived at a centered position along the left versus right dimension (Hafter et al., 1975), the stimulation levels at the two ears are usually adjusted to elicit a centered auditory image. 2.1.1. ITDFS Fig. 2(a) shows ITDFS thresholds for an unmodulated pulse train. The thresholds were compiled from 14 studies (total of 100 CI listeners; Best et al., 2011; Egger et al., 2014; Van Hoesel and Tyler, 2003; Van Hoesel, 2007; Van Hoesel et al., 2009; Van Hoesel, 2004; Van Hoesel and Clark, 1997; Kan et al., 2013a; Laback et al., 2007, 2011; Litovsky et al., 2010, 2012; Noel and Eddington, 2013; Poon et al., 2009). Only data for low pulse rates showing best ITD sensitivity (100 pulses per second, pps) were considered. For more details on the pulse rate limitation see below. The goal of this representation is to show the best performance which can be achieved with ITDFS across listeners and studies. Furthermore, in cases of several thresholds available for the same listener, the interaural electrode pair revealing the lowest threshold was chosen.3 Fig. 2(b) shows the same thresholds pooled across the corresponding studies. The median threshold was 144 ms. As a comparison, thresholds of NH listeners were compiled from five studies (Fig. 2(c), total of 22 NH listeners; Brughera et al., 2013; Hawkins et al., 1978; Klumpp and Eady, 1956; Yost, 1974; Zwislocki and Feldman, 1956) in which pure tone stimuli were used. Also here, the best thresholds across frequencies were chosen from each study, forming an acrossstudy median threshold of 11.5 ms. These results show that, compared to NH listeners, CI listeners show a larger range of performance, with best thresholds approaching those of NH listeners and worst thresholds exceeding the range of natural ITDs (approximately 800 ms). The clearly larger median threshold in electric hearing illustrates the current situation on ITD perception with bilateral CIs as a group. The near overlap of a few individual thresholds between the two listener groups indicates that, at least under optimal conditions, electric stimulation can provide ITD sensitivity similar to that in NH listeners. In Section 3, we discuss various factors potentially affecting the ITD sensitivity in electric hearing. Fig. 3 shows the effect of pulse rate on ITDFS thresholds for unmodulated pulse trains. Thresholds were compiled from six studies (Egger et al., 2014; Van Hoesel and Tyler, 2003; Van Hoesel, 2007; Van Hoesel et al., 2009; Van Hoesel and Clark, 1997; Laback et al., 2007).4 Note that listeners with low performance at low

3 For Van Hoesel (2007), only data measured with a stimulation level fixed at approximately 80 % of the dynamic range for a 400-pps pulse train (denoted in the paper as “80 % DR400”) were included. For Laback et al. (2007), only data for listeners fulfilling the selection criterion prior to the experiment were included. For Litovsky et al. (2010), the thresholds correspond to half the thresholds as stated in the paper to obtain better comparability to the other studies. For Laback et al. (2011), the threshold of one listener was determinable but extremely large (>4500 ms), presumably due to a non-fused auditory image and, thus, plotted as not defined (ND). Note that some listeners took part in more than one study shown in the plot. 4 For Van Hoesel (2007), only data measured with a stimulation level fixed at approximately 80 % of the dynamic range for a 400-pps pulse train (denoted in the paper as “80 % DR400”) were included. Note that some listeners took part in more than one study shown in the plot.


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Fig. 2. (a) Individual ITD thresholds (small symbols) and average statistics for each study (box-and-whisker plots, for studies with more than three individual thresholds). The boxes range from the lower to the upper quartile with the horizontal line as the median; whiskers indicate the lowest and highest occurring response within the 1.5-interquartile range of the lower and higher quartile, respectively. Arithmetic averages are shown with large symbols. (b) Thresholds pooled across all considered CI studies (total of 100 CI listeners). (c) Average thresholds and average statistics (box-and-whisker plot) for five NH studies (total of 22 NH listeners; Brughera et al., 2013; Hawkins et al., 1978; Klumpp and Eady, 1956; Yost, 1974; Zwislocki and Feldman, 1956).

rates were intentionally included in order to show the variance across the listeners found in various studies. Fig. 3(a) shows the individual listeners' thresholds and Fig. 3(b) shows the median of the threshold normalized to each listener's thresholds for the lowest pulse rate tested. For rates exceeding 100 pps, the vast majority of CI listeners shows a deterioration of ITD sensitivity, with thresholds becoming unmeasurable for rates exceeding approximately 400e800 pps. There are, however, some listeners showing measurable ITD sensitivity up to 800 to 1000 pps. While this can be partly attributed to onset ITD cues, it appears that some exceptional listeners are able to use ITDFS at such high rates (Van Hoesel et al., 2009; Laback et al., 2007). The pattern of thresholds as a function of

Fig. 3. (a) Individual ITD thresholds and (b) median of the normalized ITD thresholds across all listeners per study as a function of pulse rate. Only listeners considered showing measurable performance for at least two different pulse rates.

pulse rate has some similarities with ITDENV thresholds as a function of modulation rate in NH listeners (Bernstein and Trahiotis, 2002; Majdak and Laback, 2009). The pattern also shares some similarity with monaural rate discrimination thresholds as a function of reference pulse rate in electric hearing, although it is not clear yet whether the underlying limiting mechanism is the same (Carlyon et al., 2008; Van Hoesel, 2007). In any case, the low ITD sensitivity at higher pulse rates appears to represent a severe limitation in encoding ITD cues with CIs. The development of approaches to improve ITD sensitivity at higher rates is still subject of investigation. Random but interaurally-synchronized variation of the interpulse interval (IPI), referred to as binaurally-synchronized jitter, has been found to enhance ITDFS sensitivity at rates 800 pps (Laback and Majdak, 2008). While the original motivation for introducing jitter was to induce binaural restarting as observed in acoustic hearing when introducing irregular intervals in acoustic pulse trains (Hafter and Buell, 1990), it has been argued that the jitter effect in electric hearing may be due to effectively introducing low-rate cues, either by means of long instantaneous IPIs or as a consequence of modulation of the responses of integrating neural circuits in the auditory system (Van Hoesel, 2008, 2012). Recent physiological measurements suggest that spikes are triggered primarily by short rather than long IPIs in jittered pulse trains (Hancock et al., 2012), thereby indicating the potential role of temporal summation of short IPI pulses to produce sufficiently rapid increases in neural membrane potential. 2.1.2. ITDENV At high carrier frequencies (>2 kHz), NH listeners are not sensitive to ITDFS; nevertheless, they can perceive ITDs at those frequencies via ongoing envelope modulation, i.e., ITDENV (Henning, 1974). Generally, CI listeners are also sensitive to ITDENV cues (Van Hoesel et al., 2009; Laback et al., 2011; Majdak et al., 2006; Noel and Eddington, 2013). Interestingly, when using very high carrier rates (>4000 pps) and 100-Hz sinusoidally amplitudemodulated (SAM) tones, ITDENV sensitivity was found to be almost as good as ITDFS sensitivity for unmodulated pulse trains with 100 pps (Van Hoesel et al., 2009; Noel and Eddington, 2013). With a 1000-pps pulse rate, the ITD sensitivity has been found to be best at 100-Hz modulation frequency and to decline towards both lower and higher modulation frequencies (Van Hoesel et al., 2009; Noel and Eddington, 2013). Physiological data show also decreasing ITDENV sensitivity towards low modulation frequencies but do not reveal decreasing sensitivity towards the highest modulation

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frequency tested (Smith and Delgutte, 2008). This discrepancy may be due to the limited range of tested modulation frequencies. For very high pulse rates (4640 pps), ITDENV sensitivity was found to be good even for modulation frequencies beyond 100 Hz (Noel and Eddington, 2013), likely due to better envelope sampling. Remarkably, ITDENV sensitivity measured in Noel and Eddington (2013) was poorest for modulation frequencies in the range of the most-prominent modulation frequencies of speech signals (around 4 Hz). Given the above-described strong effect of modulation frequency on ITDENV sensitivity, the question arises which aspects of the envelope shape are important for perception. As for the modulation depth, some listeners show a steady improvement in ITDENV sensitivity from 0 % to 100 % of modulation depth, while others do not improve beyond a modulation depth of 20 % (Van Hoesel and Tyler, 2003; Ihlefeld et al., 2014). The changes in the modulation depth have a global impact on the envelope shape. Thus, Laback et al. (2011) studied the independent contribution of various envelope-shape parameters like the off time (silent interval in each modulation cycle) and the envelope slope to the ITDENV sensitivity. 1515-pps pulse trains with a trapezoidal envelope and modulation frequency of 27 Hz were used. Increasing the off time improved sensitivity (up to 20 ms), but changing the slope did not show any systematic effect. Given their restriction to 100 % modulation depth, shallow slopes were not tested although more shallow slopes should decrease the sensitivity at some point. Indeed, an experiment with very low rate (4 Hz) SAM pulse trains, thus with were shallow slopes, showed the expected effect of the slope (Noel and Eddington, 2013). This is in agreement with results found in physiological measurements in animals, which revealed significant effects of both the off time and the slope for various modulation rates (Hancock et al., 2014). Noel and Eddington (2013) found that the above-described decline of ITDENV sensitivity towards low modulation frequencies (from 50 down to 4 Hz) is related to the slope becoming more shallow. By contrast, the number of modulation cycles had a minimal effect. Note that for such low modulation frequencies the off times are implicitly large, so it is unlikely that their variation produced a confounding effect (Laback et al., 2011). Finally, for constant slope, off time, and modulation frequency, the amplitude peak level had a significant effect on ITD sensitivity (Laback et al., 2011). The increasing sensitivity with increasing peak level was attributed to the recruitment of additional neurons having higher thresholds.

the perceptual contributions of onset and subsequent pulses were similar, suggesting that each pulse was treated as a separate onset (Van Hoesel, 2008; Laback et al., 2007). The dominance of ITD in the onset pulse at higher rates was further demonstrated in terms of ITD thresholds and in terms of an observer weighting paradigm for pulse rates exceeding 300 pps (Van Hoesel, 2007, 2008). Consequently, onset ramps were found to affect ITD sensitivity: For unmodulated (600 pps) or SAM (600 Hz) pulse trains with onset ramps, the ITD sensitivity largely deteriorated for the majority of listeners compared to that for corresponding stimuli without ramps (Van Hoesel et al., 2009). Interestingly, for 100-Hz SAM pulse trains only a mild effect of ramping was found (Ihlefeld et al., 2014). Together with the above-described results, this suggests that CI listeners are sensitive to ongoing ITDENV (beyond the gating onset) at low (100 Hz) but not at high (600 Hz) modulation frequencies.

2.1.3. Waveform ITD: coherent ITD in the envelope and carrier Even for amplitude modulated pulse trains, the sensitivity to ITDFS depends on the carrier pulse rate (Laback and Majdak, 2008; Majdak et al., 2006; Noel and Eddington, 2013). ITDFS contributes strongly at low rates (400 pps), to a smaller extent around 800 pps, and only marginally at even higher rates. For SAM pulse trains at 1000 pps, the sensitivity to ITDENV is similar to the sensitivity to waveform ITD (Noel and Eddington, 2013), being consistent with the lack of a contribution of ITDFS cues at such high rates.

2.1.5. Place effect In NH listeners, the tonotopic place of stimulation is pivotal for ITD sensitivity. While frequencies below approximately 1.5 kHz activate neural structures sensitive to temporal fine structure and, thus, involve ITDFS coding, ITDENV is the only cue for higher frequencies. In CI listeners, the choice of electrode directly determines the place of stimulation and the auditory nerve (AN) can be stimulated with exactly the same stimulus at different places. Given the different binaural cell properties for low-frequency fine structure channels and high-frequency envelope channels (Colburn et al., 2009), one might hypothesize some place-dependence of ITD sensitivity when using the same stimuli at different electrodes. Fig. 4 shows the effect of tonotopic place of stimulation, i.e., ITD thresholds as a function of distance from the round window for unmodulated low-rate pulse trains (100 pps). Thresholds were compiled from six studies (Best et al., 2011; Egger et al., 2014; Van Hoesel et al., 2009; Kan et al., 2013a; Litovsky et al., 2010, 2012).5 Note that the distance from the round window was calculated assuming full insertion depth of the electrode array as specified by the manufacturer, resulting in a stimulation range from approximately 8 to 23.8 mm for Cochlear Nucleus devices and a stimulation range from 3.9 to 30.3 mm for MED-EL devices with standard electrode length (Baumann and Nobbe, 2004). Within the tonotopic range tested in all the studies (up to approximately 23 mm), the thresholds are overall consistent in showing no systematic place effect. One study (Kan et al., 2013a) was exceptional in showing generally higher thresholds with a dramatic deterioration of sensitivity towards the apical-most place, for which the reasons are yet unclear. For places more apical than 25 mm, ITD sensitivity deteriorated compared to more basal places (Best et al., 2011; Egger et al., 2014). A potential reason for the worse sensitivity at apical-most electrodes might be the worse electrode coupling due to less selective stimulation of neural structures (Briaire and Frijns, 2006). Another reason might be that only the apical-most electrodes stimulate neural structures which are normally tuned to ITDFS coding, and that electrical stimulation properties are not well-matched with those structures. For further

2.1.4. Gating onset ITD The auditory system is particularly sensitive to binaural information at a signal's onset, likely in order to reduce interference from reverberant energy and, thus, to enhance its robustness (Litovsky et al., 1999; Stecker and Hafter, 2002). There are several indications that also CI listeners put more perceptual weight on binaural information and, particularly, on ITD at the signal's gating onset. At higher pulse rates (400 pps), the thresholds for stimuli containing ITD information only in the first pulse of a four-pulse train were similar to those containing ITD information in all four pulses (Laback et al., 2007). In contrast, at low pulse rates (100 pps),

5 For Litovsky et al. (2010), the thresholds correspond to half the thresholds as stated in the paper to obtain better comparability to the other studies. For Litovsky et al. (2012), the place of stimulation data were provided through personal communication with the authors. For two listeners in Litovsky et al. (2012) (where no precise information was available), the places of stimulation, apex, middle, and base, were set to electrode numbers 2, 11, and 21 (electrode numbers from apex to base in ascending order); for Kan et al. (2013a), the places, apex, mid-apex, mid, mid-base, and base, were set to electrode numbers 2, 7, 11, 16, and 21, respectively. For Kan et al. (2013a), the thresholds for apex and mid-apex place of stimulation of one listener were determinable but were exceeding 2500 ms and, thus, are plotted as ND and are included in the median. Note that some listeners took part in more than one study shown in the plot.


Fig. 4. (a) Individual ITD thresholds and (b) median ITD thresholds as a function of tonotopic place of stimulation for various studies. The place of stimulation is given as distance from the round window (in mm), averaged across ears for each electrode pair. Only listeners considered showing measurable performance for at least two different places of stimulation. The small arrows point to the individual data of the prelingually deafened listener from Egger et al. (2014) (see Section 3.2).

discussion on the potential effect of a mismatch between AN input patterns and binaural cell properties see Section 3.1. 2.2. Multiple interaural electrode pairs In practical listening with CIs, multiple electrodes are activated at each ear. Therefore, the perception of ITD information presented at multiple interaural electrode pairs is an important issue. Multiple-electrode ITD perception has recently become a very active field of research, but there are only few conclusions available on that topic yet. In the following, we describe some recent developments and results, distinguishing between configurations with consistent ITD cues and inconsistent ITD cues across electrode pairs. 2.2.1. Consistent ITD across electrodes Presenting consistent ITD at multiple-electrode pairs might lead to a variety of outcomes. First, ITD sensitivity might improve compared to that provided by the better single pair because of the integration of ITD information presented at independent peripheral auditory channels, as occurring in the NH auditory system (e.g., Buell and Hafter, 1991; Buell and Trahiotis, 1993). Second, ITD sensitivity might be similar to that provided by the better single pair because the listener might be able to “ignore” the pair providing the worse sensitivity. Third, ITD sensitivity might deteriorate compared to that provided by the better single pair because of peripheral neural population interactions as a result of electrical current spread along the cochlea (Chatterjee et al., 2006). A few studies compared ITDFS sensitivity obtained with unmodulated, 100-pps pulse trains presented at pitch-matched single

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interaural electrode pairs with ITDFS sensitivity obtained when combining such pairs while keeping the stimulation levels constant across conditions (Egger et al., 2014; Jones et al., 2007, 2009, 2013). For combinations of two pairs (double pairs) with wide tonotopic spacings between electrodes, improved sensitivity relative to the better-performing single pairs was observed, suggesting integration of ITD information (Egger et al., 2014). For various combinations of three or five pairs with different amounts of electrode spacing and in different tonotopic regions, performance did not change in a consistent pattern across listeners relative to the better-performing single pairs (Jones et al., 2013). In addition, an analysis of those data revealed suboptimal integration of information. For more narrowly spaced double pairs, the ITD sensitivity was similar to that for the respective single pairs (Egger et al., 2014). For a pulse train with double rate (200 pps), representing infinitely narrow electrode spacing, thresholds were found to be larger than for the narrowly spaced double-pair condition driven at 100 pps, further supporting the importance of tonotopic spacing (Egger et al., 2014). In the same study, when the levels of the double pairs were matched in loudness to those for single pairs, no ITD integration was found for any tonotopic spacing. A further comparison of data collected at various levels revealed a strong overall level effect for both, single and double pairs, showing improving performance with increasing level (Egger et al., 2014). A few studies also investigated multiple-electrode ITDENV sensitivity for high-rate carriers (Ihlefeld et al., 2014; Jones et al., 2013; Lenssen, 2013). For 100-Hz SAM pulse trains presented at either single pairs or double pairs with wide spacing and the same level across conditions, listeners did not perform worse for the double pairs compared to the respective better pairs in most conditions (Ihlefeld et al., 2014). The large asymmetries in performance between the two single pairs found in that study did not allow to differentiate between an explanation in terms of either ignoring the worse pair or integrating ITD information. Jones et al. (2013) observed a trend for improved sensitivity for multiple-pair conditions relative to the better-performing single pairs, although an analysis revealed only suboptimal integration of information. Lenssen (2013) measured ITDENV thresholds for transposed SAM tones either at a single pair in the middle of the electrode array, or at loudness-matched combinations of three pairs. No attempt was made to match the pair members in pitch. The monaural temporal offset between the individual pulses of the multiple-pair trains was varied. For multiple-electrode conditions involving a large offset (2.5 ms), ITD sensitivity was worse relative to the single-pair conditions. For a small offset (71 ms, i.e., quasi-synchronous pulse trains), the sensitivity was either similar or even better relative to the single-pair conditions. This is consistent with results from Jones et al. (2009), who reported better ITDFS sensitivity for an offset of 60 ms compared to an offset of half the IPI (5 ms). Lenssen (2013) attributed the better performance for the shorter offset to the longer effective off time in the across-channel excitation patterns, an effect shown with respect to ITDENV sensitivity in single-electrode stimulation (Laback et al., 2011). Taken together, the currently available data on the perception of consistent ITD cues at multiple electrodes suggest the influence of a multitude of stimulation parameters. It appears that ITD sensitivity is best for high stimulus levels, large tonotopic spacings, and short temporal offsets between individual pulse trains in a multipleelectrode stimulus. However, practical multiple-electrode stimulation in clinical CI systems involves restrictions on overall loudness and on the maximum spacing between stimulation electrodes. Given these restrictions, it might be possible to, at best, maintain the ITD sensitivity of the better-performing single pair.

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2.2.2. Inconsistent ITD across electrodes Listening in the real world often involves the simultaneous occurrence of multiple sound sources arriving from different directions. As this involves the reception of different (inconsistent) ITD cues at the same time, the question arises how CI listeners perceptually combine these cues. In acoustic hearing, the sensitivity to a binaural cue of a narrow-band target is reduced by the presence of a simultaneous narrow-band interferer with a deviant binaural cue in a remote frequency region. This effect is referred to as binaural interference (Best et al., 2007; Heller and Richards, 2010). Binaural interference tends to occur when monaural grouping cues promote perceptual integration of the target and interferer. Translated to electric hearing, electrical pulse trains presented simultaneously at different electrodes with different binaural cues are an example of a stimulus potentially promoting binaural interference due to simultaneous grouping. Such a stimulus configuration was studied by presenting a target, i.e., a pulse train at a tonotopically centered electrode pair, with various ITDFS, while simultaneously presenting an interferer, i.e., a pulse train with ITDFS of zero, at variable electrode pair positions relative to the target (Jones et al., 2007, 2009). Both target and interferer were unmodulated, 100-pps pulse trains. ITD sensitivity mostly degraded in conditions with an inconsistent-ITD interferer and, notably, the degradation was stronger than in conditions with consistent-ITD interferers. This result seems to be consistent with the binaural interference effect in NH listeners. There was no clear effect of electrode spacing between interferer and target. Best et al. (2011) used the same type of stimuli but attempted to minimize the influence of peripheral channel interactions by presenting target and interferer at widely spaced interaural electrode pairs. The listeners' task was to judge the lateral position of the target. Consistent with the expectation of binaural interference in NH listeners, also in CI listeners the extent of lateralization decreased with the addition of the interferer. In a condition with an ongoing stream of interferers, a recovery from interference was observed, similar to findings in acoustic hearing (Best et al., 2007; Darwin and Hukin, 1997, 1998; Hukin and Darwin, 1995). These results suggest that the interference effect was at least partly centrally mediated and not dominated by peripheral channel interactions. Further, they indicate that the recovery from interference was relying on monaural sequential grouping, showing evidence for the operation of both simultaneous and sequential grouping mechanisms in electric hearing. These conclusions are further supported by similar results observed in their other conditions where 1) ITD cues were replaced by ILD cues and 2) the potential influence of peripheral temporal interference between electrodes on the extent of lateralization was reduced. Remarkably, Jones et al. (2009) observed deteriorated ITD sensitivity when the monaural temporal offset between the target and the interferer increased from 60 ms to 5 ms. On the one hand, this is consistent with an interpretation in terms of a shorter off time in the effective across-channel excitation patterns. On the other hand, a larger offset might have reduced simultaneous grouping and, consequently, binaural interference. As indicated by Best et al. (2011), the 5-ms offset might be not sufficient to cause a robust segregation between the target and interferer. This is consistent with monaural grouping experiments in electric hearing, showing weak segregation for very similar stimuli (Carlyon et al., 2007). In summary, the available results suggest that the perception of ITDs presented at one electrode pair is largely impaired by the simultaneous presentation of conflicting ITDs at another electrode pair. This effect appears to be due to centrally-mediated binaural

interference, at least for wide electrode spacings. Monaural grouping cues such as sequential grouping appear to be important to promote perceptual segregation between interfering electrode pairs and to allow for the perception of distinct sound sources corresponding to the different ITDs. 3. Factors potentially affecting ITD sensitivity of CI listeners 3.1. Factors related to specific properties of electric stimulation Electric stimulation of the AN differs in various aspects from acoustic stimulation of the healthy cochlea. In this section, we focus on some of the differences between electric and acoustic stimulation which appear to be important for the perception of ITD cues. AN responses to electric stimulation at low stimulation rates (500e800 Hz) show stronger phase locking compared to acoustic stimulation, as reflected by higher temporal precision of firing within and across fibers and higher probability of discharging on every stimulus cycle (Hartmann et al., 1984; Van den Honert and Stypulkowski, 1987). With increasing stimulation rate, the neural responses remain entrained up to higher rates than in acoustic stimulation (Dynes and Delgutte, 1992), but neural refractoriness prevents the fibers from discharging on every cycle at some point. The combination of exaggerated synchrony, excessively high discharge rates, and refractoriness leads to unnatural responses, as seen, e.g., in the response to 1000-pps pulse trains which alternates between strong and weak responses to each pulse (Wilson et al., 1997). Despite their unnaturalness, these AN response properties intuitively do not appear to be disadvantageous for accurate ITD coding in electric stimulation. Indeed, ITD tuning in a majority of neurons of acutely deafened and bilaterally implanted cats was found to be comparable to acoustically stimulated cats (Smith and Delgutte, 2007), even though in electric hearing the tuning was restricted to a narrow dynamic range and to low pulse rates (4500 ms), presumably due to a non-fused auditory image and, thus, plotted as not defined (ND). Note that some listeners took part in more than one study shown in the plot.

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Fig. 5. Individual ITD thresholds as a function of listener's age at onset of profound binaural hearing loss for various studies.

2010, 2012).8 Given that audiological measurements from early childhood are not available for those listeners, we conjecture that the lack of residual hearing in early childhood was the cause for their lack of ITD sensitivity. In summary, while there is some evidence from animal and human studies that the lack of binaural auditory input in the first few years of life prevents the development of ITD sensitivity, the postlingual age at onset of profound binaural hearing loss does not seem to be a critical factor. Very early binaural CI hearing experience might provide the binaural circuits with sufficient binaural information to develop good ITD sensitivity, at least under optimal circumstances. Much more evidence is required for definite conclusions on this and other listener-specific factors.

4. Stimulation strategies for encoding ITD 4.1. Envelope-based strategies The stimulation strategy has a large influence on the performance achievable with a CI. While early CIs used only a single channel for stimulation (Tyler, 1988), nowadays all stimulation strategies use multi-channel, pulsatile stimulation (Wilson et al., 1991). The reason for using pulses instead of continuous stimulation is the broad excitation spread of electric stimulation in the cochlea. Simultaneous stimulation on more than one electrode results in an uncontrolled interaction through summation of the electric fields from each of the electrodes (De Balthasar et al., 2003; Pelizzone et al., 1999). This is avoided by stimulating one electrode at a time. Present pulsatile stimulation strategies include the continuous interleaved sampling (CIS; Wilson et al., 1991) and the “n-of-m” (corresponding to selection of n among m channels) strategies spectral peak (SPEAK; Skinner et al., 1994) and advanced combination encoder (ACE; Kiefer et al., 2001).

8 Note that the listeners tested in Litovsky et al. (2010) were also included in Litovsky et al. (2012) and data points from both studies might refer to the same listener. More precisely, two data points (at the ages at onset of profound binaural hearing loss of zero and three) showing no ITD sensitivity in both studies refer to the same two prelingually deafened listeners. One listener with an age at onset of binaural hearing loss at birth showed no sensitivity in Litovsky et al. (2010) but the same listener corresponds to the threshold of 593 ms in Litovsky et al. (2012). This improvement in sensitivity might result from ongoing ITD sensitivity training and the fact that in Litovsky et al. (2010) ITD thresholds were not measured directly in an ITD discrimination task but were computed from ITD lateralization data.

CIS is the most straight-forward envelope-based strategy and, apart from differences in pulse rates used, can be considered as a basis for SPEAK, ACE, and other “n-of-m” strategies. The preprocessed microphone signal is converted to a digital audio stream and then split into frequency channels by a bandpass filter bank. In each channel, the envelope is detected by rectification of the signal followed by low-pass filtering or by means of the Hilbert transform. The envelope detector usually has a low-pass cut-off frequency of 200e400 Hz, i.e., above the fundamental frequency of voiced speech as well as above the rate of rapid transitions of consonants and in the region of the upper limit for temporal pitch discrimination for most CI users (Shannon, 1983; Zeng, 2002). The envelope is then mapped to fit the electric stimulation range and the outcome is used to modulate a pulse train. The resulting modulated pulse train steers a current source connected to an electrode. Across different channels, the pulse trains are interleaved to avoid simultaneous stimulation and to separate the electric fields along the tonotopy. The rate of the pulse trains must be at least twice the cutoff frequency of the envelope detector to avoid aliasing effects. Nevertheless, results from recordings of AN responses indicate that the pulse rate should be even higher to achieve a good neural representation of the modulation waveform (Wilson, 1997). CIS processors use pulse rates of 1000 pps or higher for each electrode. Envelope-based, standard clinical strategies can achieve high performance in terms of speech perception in quiet as supported by numerous studies. However, all these strategies have been designed for monaural stimulation, because at the time of development, bilateral stimulation was not the main focus of interest. The ITD sensitivity found with users of those strategies is rather poor (Grantham et al., 2008; Laback et al., 2004), being closely related to the access to ITDENV only. Thus, it is not surprising that, compared to NH listeners, CI users show deficits in processes relying on ITD perception like sound lateralization (Laback et al., 2004), minimum audible angle (Litovsky et al., 2006; Senn et al., 2005), sound localization (Aronoff et al., 2010; Grantham et al., 2007; Grieco-Calub and Litovsky, 2010; Van Hoesel et al., 2002; Majdak et al., 2011; Seeber and Fastl, 2008; Verschuur et al., 2005; Zheng et al., 2011), sound localization in reverberation (Kerber and Seeber, 2013; Zheng et al., 2011), and speech perception in noise (Culling et al., 2012). Given the lack of salient ITD cues, CI users rely primarily on ILDs (e.g., Seeber and Fastl, 2008). Given the success of envelope-based strategies for speech understanding, various modifications have been proposed considering a re-shaping of the envelope to enhance the salience of envelope ITD cues (Laback et al., 2011, 2013; Wouters et al., 2011).


Envelope parameters like onset slope and off-time offer room for improvements of ITDENV sensitivity with envelope-based stimulation strategies (Laback et al., 2013; Noel and Eddington, 2013). An approach aiming at enhancing envelope ITD cues particularly in reverberation, which was implemented as an acoustic CI simulation, showed improved envelope ITD thresholds in NH listeners (Monaghan and Seeber, 2011). Further, there is some potential for future developments aiming to improve the match between the modulation frequency range within which CI listeners are most sensitive to ITDENV and the modulation frequency range of speech (see Section 2.1.2.). Note that very high pulse rates (>2000 pps) were considered for stimulation strategies which may allow for more natural neural discharge patterns (Litvak et al., 2003; Rubinstein et al., 1999), provide a larger dynamic range (Kreft et al., 2004), and provide a better representation of ITDENV cues (see Section 2.1.2.). Still, given potential limitations in modulation processing at very high pulse rates (Middlebrooks, 2004, 2008), the future of very high-rate stimulation for a clinical strategy is yet unclear. 4.2. Strategies encoding the temporal fine structure Envelope-based strategies share the disadvantage of discarding the temporal fine structure information, namely, the pulse trains are generated in a predefined scheme, entirely discarding the temporal fine structure in the acoustic signal. Given the importance of the fine structure for monaural auditory functions, most importantly those relying on pitch information (Moore, 2008; Smith et al., 2002), there have been attempts to encode fine structure information in CIs by means of the electric pulse timing (Dillier et al., 1993; Nie et al., 2005; Skinner et al., 1991). One of the first strategies considering the temporal fine structure of the signal to explicitly improve the perception of ITDFS cues was the peakderived timing (PDT) strategy (Van Hoesel and Tyler, 2003). The PDT strategy was mainly investigated with respect to binaural effects by taking into consideration the fine structure of acoustic signals and providing the ITD in both fine structure and envelope. In the PDT strategy, the temporal position of an acoustic peak in a frequency channel is determined and an electric pulse is applied at the corresponding electrode at the corresponding time. As a consequence, the pulse rate varies according to the temporal properties of the acoustic signal at each channel and is limited to a maximum of 1400 pps. Interestingly, with respect to the performance in sound localization and speech perception in noise, no clear difference between the PDT strategy and the standard clinical envelope-based strategy was found (Van Hoesel and Tyler, 2003; Van Hoesel, 2008). The comparison in Van Hoesel and Tyler (2003) was potentially confounded by differences in the experimental setup such as automatic gain control, dynamic range, and number of electrodes. Van Hoesel et al. (2008) controlled for those differences, suggesting that the high stimulation pulse rate (700 pps, on average) and channel interactions were reasons for the lack of a benefit from ITDFS coding in the PDT strategy (see Section 2.1.1.). Even though PDT remained an experimental strategy, it can be considered as a first major step towards encoding of the temporal fine-structure in a stimulation strategy. A few years later, the fine-structure processing (FSP) strategy was developed and made clinically available (Hochmair et al., 2006). The FSP strategy considers the fine structure in the signal in two to three of the apical-most electrodes by stimulating at the zero-crossings of the corresponding bandpass-filtered signals (Hochmair et al., 2006). The FSP-driven electrodes stimulate at a low pulse rate derived from the signal timing, and the other electrodes are driven according to the CIS strategy. While preliminary results on speech and music perception appeared to be

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encouraging (Arnoldner et al., 2007), it is not clear yet whether the improvements relative to purely envelope-based strategies are due to the extended low-frequency range of FSP (Kleine Punte et al., 2014; Riss et al., 2011) or due to the encoding of the temporal fine structure. Also, the impact on binaural cue sensitivity and spatial release from masking is still unclear. While the FSP strategy restricts the accuracy of the stimulation pulse timing and thereby potentially limits the transmission of precise ITD information to the auditory system, further developments of FSP consider more accurate timing of the pulses (a strategy called FS4, Riss et al., 2014) and simultaneous stimulation of multiple electrodes (FS4-p, Bahmer and Baumann, 2013). Both FS4 and FS4-p seem to be promising candidates for clinical strategies providing temporal fine structure cues. Another recent development is the fundamental asynchronous stimulus timing (FAST) strategy, which, similarly to PDT and FS4, places the pulses according to the fine-structure in a corresponding frequency channel. In contrast to FS4, FAST synchronizes pulses to the local maxima of the temporal envelope in each frequency channel. While preliminary results showed improved ITD sensitivity (Smith, 2010) and ITD-based spatial release from masking (Smith, 2013), more extensive evaluations are still missing. The FS4 and FAST strategies share the advantage of using low pulse rates, which is advantageous for ITD perception (see Section 2.1.1.). The requirement for low pulse rates in ITD perception is, nonetheless, in conflict with demands for speech perception. Speech reception performance appears to be better with processors that use pulse rates of at least 500 pps (Arora et al., 2009; Loizou et al., 2000). Therefore, methods are required for overcoming the degradation in ITD sensitivity at such high pulse rates. One method is to introduce binaurally-synchronized jitter in the stimulation timing of the pulses (Laback and Majdak, 2008). Jittered pulse trains were shown to yield large improvements in ITD sensitivity as compared to regular pulse trains, even for pulse rates up to 1515 pps (see Section 2.1.1.). Thus, the application of binaurallysynchronized jitter in a stimulation strategy might be advantageous. The exploitation of this effect in a stimulation strategy might be simplified given recent evidence that using two pulses within a short interval may be as effective as binaurally-synchronized jitter (Hancock et al., 2012). An important and often raised issue with respect to encoding ITD cues with CIs concerns the question whether explicit coordination of stimulation timing between the two ears is required. Here, different aspects have to be distinguished. The encoding of ITDFS cues does not require explicit interaural coordination because, like in normal hearing, the fine structure is implicitly coordinated between the two ears via the sound waves arriving at the two ears. PDT, FSP, and FAST are examples of strategies relying on such an implicit coordination. The precision of the ITDFS cues with such systems is determined by the precision of the temporal processing of each of the CI processors. Nevertheless, some type of coordination of the automatic gain control units at the two ears is required to avoid uncontrolled effects on ILD coding (Wiggins and Seeber, 2012). An implementation of approaches like the abovedescribed binaurally-synchronized jitter or two pulses within a short interval, however, would require an explicit interaural coordination. While systems like the Neurelec Digisonic SP (Bonnard et al., 2013) allow for explicit interaural coordination of stimulation timing, clinical stimulation strategies exploiting that option to encode ITDFS cues are not available for that device, yet. While potentially promising, fine-structure coding strategies have to be extensively tested, focusing on multiple-electrode stimulation in spatial hearing tasks. The success of those strategies will also depend on their ability to properly encode other grouping cues such as loudness, pitch, or harmonicity.

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5. Summary Interaural time differences (ITDs) provide essential cues for the localization of sound sources and for the understanding of speech in environments with interfering sounds. Most bilateral CI listeners perform worse than NH listeners in ITD-based spatial-hearing tasks because of 1) the suboptimal transmission of ITDs with envelopebased stimulation strategies and 2) the generally worse ITD sensitivity even with direct, binaurally controlled stimulation and even when applying the currently known optimal parameters. The ITD sensitivity varies dramatically across bilateral CI listeners and depends critically on parameters like pulse rate, temporal modulation rate, envelope shape in single-electrode stimulation, and stimulation level, electrode spacing, as well as monaural across-electrode timing in multiple-electrode stimulation. Approaches for improving listeners' access to ITDs include the enhancement of fine-structure ITD cues by controlling the pulse timing, the enhancement of envelope ITD cues by manipulating the envelope shape, and the reduction of channel interactions. Factors appearing to be beneficial for ITD perception in electric hearing include: 1) the match between temporal properties of AN response to electric stimulation and corresponding properties of binaural neurons, 2) the stimulation of neural pathways having high temporal acuity like those with a low characteristic frequency in acoustic hearing, 3) a low degree of channel interactions due to electric current spread, 4) the interaural match in the place of electric stimulation, and 5) receiving binaural auditory input in the first years of life (acoustical or electrical). The primary goal of future research will be the better understanding and control of these and other factors affecting ITD perception in electric hearing. Enhanced access to salient ITD cues is expected to improve the performance of CI listeners in sound localization and speech understanding in noise. Acknowledgments We thank all our listeners for their participation in various studies. We thank the Austrian Academy of Sciences for long-term funding research on spatial hearing with CIs. We thank the Institute of Ion Physics and Applied Physics, Leopold-Franzens-University of Innsbruck, Austria for providing the equipment for direct electric stimulation. We thank Ruth Litovsky, Matt Goupell, and Alan Kan for kindly providing supplementary information on their CI listeners' etiologies and experimental results. We thank Fan-Gang Zeng and two anonymous reviewers for helpful comments on an earlier version of this manuscript. Financial support was partially provided by MED-EL Corporation. References Arnoldner, C., Riss, D., Brunner, M., Durisin, M., Baumgartner, W.-D., Hamzavi, J.-S., 2007. Speech and music perception with the new fine structure speech coding strategy: preliminary results. Acta Otolaryngol. 127, 1298e1303. Aronoff, J.M., Yoon, Y.-S., Freed, D.J., Vermiglio, A.J., Pal, I., Soli, S.D., 2010. The use of interaural time and level difference cues by bilateral cochlear implant users. J. Acoust. Soc. Am. 127, EL87e92. Arora, K., Dawson, P., Dowell, R., Vandali, A., 2009. Electrical stimulation rate effects on speech perception in cochlear implants. Int. J. Audiol. 48, 561e567. Bahmer, A., Baumann, U., 2013. New parallel stimulation strategies revisited: effect of synchronous multi electrode stimulation on rate discrimination in cochlear implant users. Cochlear Implants Int. 14, 142e149. €x, C., Cosendai, G., Valentini, G., Sigrist, A., Pelizzone, M., 2003. De Balthasar, C., Boe Channel interactions with high-rate biphasic electrical stimulation in cochlear implant subjects. Hear. Res. 182, 77e87. Baumann, U., Nobbe, A., 2004. Pitch ranking with deeply inserted electrode arrays. Ear. Hear. 25, 275e283. Bernstein, L.R., Trahiotis, C., 2002. Enhancing sensitivity to interaural delays at high frequencies by using ‘transposed stimuli,’. J. Acoust. Soc. Am. 112, 1026e1036.

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

Perception of Interaural Phase Differences With Envelope and Fine Structure Coding Strategies in Bilateral Cochlear Implant Users.

Comparison of Interaural Electrode Pairing Methods for Bilateral Cochlear Implants.

Bilateral Loudness Balancing and Distorted Spatial Perception in Recipients of Bilateral Cochlear Implants.

Language and speech perception of young children with bimodal fitting or bilateral cochlear implants.

Neuroelectrical imaging study of music perception by children with unilateral and bilateral cochlear implants.

Different perception of musical stimuli in patients with monolateral and bilateral cochlear implants.

Long-term improvement of speech perception with the fine structure processing coding strategy in cochlear implants.

Interaural level differences and sound source localization for bilateral cochlear implant patients.

Effect of multi-electrode configuration on sensitivity to interaural timing differences in bilateral cochlear-implant users.

Modulation enhancement in the electrical signal improves perception of interaural time differences with bimodal stimulation.

Bilateral cochlear implants in children: Effects of auditory experience and deprivation on auditory perception.

Emotional perception of music in children with unilateral cochlear implants.

A circuit for coding interaural time differences in the chick brainstem.

A longitudinal study in adults with sequential bilateral cochlear implants: time course for individual ear and bilateral performance.

Auditory Model-Based Sound Direction Estimation With Bilateral Cochlear Implants.

Speech perception with F0mod, a cochlear implant pitch coding strategy.

Deep electrode insertion and sound coding in cochlear implants.

A longitudinal study of the bilateral benefit in children with bilateral cochlear implants.

Detecting interaural time differences and remodeling their representation.

Reverberation time influences musical enjoyment with cochlear implants.

Sensitivity to Envelope Interaural Time Differences at High Modulation Rates.

Relationships between bilateral differences in body perception and bilateral differences in skin conductance levels.

Sensitivity to interaural envelope correlation changes in bilateral cochlear-implant users.