The neural representation of an auditory spatial cue in the primate cortex.

Humans make use of small differences in the timing of sounds at the two ears-interaural time differences (ITDs)-to locate their sources. Despite extensive investigation, however, the neural representation of ITDs in the human brain is contentious, particularly the range of ITDs explicitly represented by dedicated neural detectors. Here, using magneto- and electro-encephalography (MEG and EEG), we demonstrate evidence of a sparse neural representation of ITDs in the human cortex. The magnitude of cortical activity to sounds presented via insert earphones oscillated as a function of increasing ITD-within and beyond auditory cortical regions-and listeners rated the perceptual quality of these sounds according to the same oscillating pattern. This pattern was accurately described by a population of model neurons with preferred ITDs constrained to the narrow, sound-frequency-dependent range evident in other mammalian species. When scaled for head size, the distribution of ITD detectors in the human cortex is remarkably like that recorded in vivo from the cortex of rhesus monkeys, another large primate that uses ITDs for source localization. The data solve a long-standing issue concerning the neural representation of ITDs in humans and suggest a representation that scales for head size and sound frequency in an optimal manner.

Simultaneous subcortical and cortical electrophysiological recordings of spectro-temporal processing in humans.

Objective assessment of auditory discrimination has often been measured using the Auditory Change Complex (ACC), which is a cortically generated potential elicited by a change occurring within an ongoing, long-duration auditory stimulus. In cochlear implant users, the electrically-evoked ACC has been used to measure electrode discrimination by changing the stimulating electrode during stimulus presentation. In addition to this cortical component, subcortical measures provide further information about early auditory processing in both normal hearing listeners and cochlear implant users. In particular, the frequency-following response (FFR) is thought to reflect the auditory encoding at the level of the brainstem. Interestingly, recent research suggests that it is possible to simultaneously measure both subcortical and cortical physiological activity. The aim of this research was twofold: first, to understand the scope for simultaneously recording both the FFR (subcortical) and ACC (cortical) responses in normal hearing adults. Second, to determine the best recording parameters for optimizing the simultaneous capture of both responses with clinical applications in mind. Electrophysiological responses were recorded in 10 normally-hearing adults while they listened to 16-second-long pure tone sequences. The carrier frequency of these sequences was either steady or alternating periodically throughout the sequence, generating an ACC response to each alternation-the alternating ACC paradigm. In the "alternating" sequences, both the alternating rate and the carrier frequency varied parametrically. We investigated three alternating rates (1, 2.5, and 6.5 Hz) and seven frequency pairs covering the low-, mid-, and high-frequency range, including narrow and wide frequency separations. Our results indicate that both the slowest (1 Hz) and medium (2.5 Hz) alternation rates led to significant FFR and ACC responses in most frequency ranges tested. Low carrier frequencies led to larger FFR amplitudes, larger P1 amplitudes, and N1-P2 amplitude difference at slow alternation rates. No significant relationship was found between subcortical and cortical response amplitudes, in line with different generators and processing levels across the auditory pathway. Overall, the alternating ACC paradigm can be used to measure sub-cortical and cortical responses as indicators of auditory early neural encoding (FFR) and sound discrimination (ACC) in the pathway, and these are best obtained at slow alternation rates (1 Hz) in the low-frequency range (300-1200 Hz).

Human cortical processing of interaural coherence.

Sounds reach the ears as a mixture of energy generated by different sources. Listeners extract cues that distinguish different sources from one another, including how similar sounds arrive at the two ears, the interaural coherence (IAC). Here, we find listeners cannot reliably distinguish two completely interaurally coherent sounds from a single sound with reduced IAC. Pairs of sounds heard toward the front were readily confused with single sounds with high IAC, whereas those heard to the sides were confused with single sounds with low IAC. Sounds that hold supra-ethological spatial cues are perceived as more diffuse than can be accounted for by their IAC, and this is accounted for by a computational model comprising a restricted, and sound-frequency dependent, distribution of auditory-spatial detectors. We observed elevated cortical hemodynamic responses for sounds with low IAC, suggesting that the ambiguity elicited by sounds with low interaural similarity imposes elevated cortical load.

Spike-Rate Adaptation in a Computational Model of Human-Shaped Spiral Ganglion Neurons.

OBJECTIVES: The purpose of this study is to develop a biophysical model of human spiral ganglion neurons (SGNs) that includes voltage-gated hyperpolarization-activated cation (HCN) channels and low-threshold potassium voltage-gated, delayed-rectifier low-threshold potassium (KLT) channels, providing for a more complete simulation of spike-rate adaptation, a feature of most spiking neurons in which spiking activity is reduced in response to sustained stimulation. METHODS: Our model incorporates features of spike-rate adaptation reported from in vivo studies, whilst also displaying similar behaviour to existing models of human SGNs, including the dependence of electrically evoked thresholds on the polarity of electrical pulses. RESULTS: Hypothesizing that the mode of stimulation-intracellular or extracellular-predicts features of spike-rate adaptation similar to in vivo studies, including the influence of stimulus intensity and pulse-rate, we find that the mode of stimulation alters features of spike-rate adaptation. In particular, the reduction in spiking over time with sustained input was generally greater for extracellular, compared to intracellular, stimulation, when simulating a multi-compartment SGN with human morphological features. In contrast, time-constants of spike-rate adaption reported for in vivo data did not fit our predicted responses, highlighting the need for a more complete physiological understanding of the factors contributing to spike-rate adaptation in electrically stimulated human SGNs. CONCLUSION: Our model extends previous computational models of SGNs with human morphology with ionic channels accounting for features of spike-rate adaptation. SIGNIFICANCE: The significance of this work resides in the ability to improve the modeling of cochlear implant (CI) stimulation and its effects on neural responses. This will help develop novel, and perhaps personalised, stimulation strategies to reduce variability in CI user outcomes.

Characterizing Cochlear implant artefact removal from EEG recordings using a real human model.

Electroencephography (EEG) recordings from CI listeners are contaminated by electrical artefacts that make it difficult to extract neural responses. Previously, we have removed these artefacts by means of interpolation and spatial filtering. However, the extent to which this method can effectively reduce electrical artefacts has not been fully investigated. Here, we assessed the effectiveness of interpolation and spatial filtering to remove electrical artefacts using recordings from a human head specimen implanted with a CI.•Electrical artefacts were obtained using amplitude-modulated (AM'ed) pulse trains presented at several pulse rates (100-to-902 pps) or using high rate pulse trains (902 pps) in which either a pair of electrodes or AM frequencies alternated periodically at a rate of 1Hz.•By adding auditory change complex (ACC), auditory steady-state response (ASSR), or auditory change following response (AC-FR) template waveforms to the contaminated recordings, we show that interpolation allows for effective artefact removal for pulse rates below 400 pps whilst interpolation and spatial filtering are effective at higher pulse rates, with minimal distortions for ACC and AC-FR, and with a degree of amplitude- and phase-distortions for ASSR.•Recordings from CI listeners agreed with simulations, demonstrating that reliable responses can be recovered.

The influence of envelope shape on the lateralization of amplitude-modulated, low-frequency sound.

For abruptly gated sound, interaural time difference (ITD) cues at onset carry greater perceptual weight than those following. This research explored how envelope shape influences such carrier ITD weighting. Experiment 1 assessed the perceived lateralization of a tonal binaural beat that transitioned through ITD (diotic envelope, mean carrier frequency of 500 Hz). Listeners' left/right lateralization judgments were compared to those for static-ITD tones. For an 8 Hz sinusoidally amplitude-modulated envelope, ITD cues 24 ms after onset well-predicted reported sidedness. For an equivalent-duration "abrupt" envelope, which was unmodulated besides 20-ms onset/offset ramps, reported sidedness corresponded to ITDs near onset (e.g., 6 ms). However, unlike for sinusoidal amplitude modulation, ITDs toward offset seemingly also influenced perceived sidedness. Experiment 2 adjusted the duration of the offset ramp (25-75 ms) and found evidence for such offset weighting only for the most abrupt ramp tested. In experiment 3, an ITD was imposed on a brief segment of otherwise diotic filtered noise. Listeners discriminated right- from left-leading ITDs. In sinusoidal amplitude modulation, thresholds were lowest when the ITD segment occurred during rising amplitude. For the abrupt envelope, the lowest thresholds were observed when the segment occurred at either onset or offset. These experiments demonstrate the influence of envelope profile on carrier ITD sensitivity.

Neural encoding of spectro-temporal cues at slow and near speech-rate in cochlear implant users.

The ability to process rapid modulations in the spectro-temporal structure of sounds is critical for speech comprehension. For users of cochlear implants (CIs), spectral cues in speech are conveyed by differential stimulation of electrode contacts along the cochlea, and temporal cues in terms of the amplitude of stimulating electrical pulses, which track the amplitude-modulated (AM'ed) envelope of speech sounds. Whilst survival of inner-ear neurons and spread of electrical current are known factors that limit the representation of speech information in CI listeners, limitations in the neural representation of dynamic spectro-temporal cues common to speech are also likely to play a role. We assessed the ability of CI listeners to process spectro-temporal cues varying at rates typically present in human speech. Employing an auditory change complex (ACC) paradigm, and a slow (0.5Hz) alternating rate between stimulating electrodes, or different AM frequencies, to evoke a transient cortical ACC, we demonstrate that CI listeners-like normal-hearing listeners-are sensitive to transitions in the spectral- and temporal-domain. However, CI listeners showed impaired cortical responses when either spectral or temporal cues were alternated at faster, speech-like (6-7Hz), rates. Specifically, auditory change following responses-reliably obtained in normal-hearing listeners-were small or absent in CI users, indicating that cortical adaptation to alternating cues at speech-like rates is stronger under electrical stimulation. In CI listeners, temporal processing was also influenced by the polarity-behaviourally-and rate of presentation of electrical pulses-both neurally and behaviorally. Limitations in the ability to process dynamic spectro-temporal cues will likely impact speech comprehension in CI users.

Development of electrophysiological and behavioural measures of electrode discrimination in adult cochlear implant users.

The plasticity of the auditory system enables it to adjust to electrical stimulation from cochlear implants (CI). Whilst speech perception may develop for many years after implant activation, very little is known about the changes in auditory processing that underpin these improvements. Such an understanding could help guide interventions that improve hearing performance. In this longitudinal study, we examine how electrode discrimination ability changes over time in newly implanted adult CI users. Electrode discrimination was measured with a behavioural task as well as the spatial auditory change complex (ACC), which is a cortical response to a change in place of stimulation. We show that there was significant improvement in electrode discrimination ability over time, though in certain individuals the process of accommodation was slower and more limited. We found a strong relationship between objective and behavioural measures of electrode discrimination using pass-fail rules. In several cases, the development of the spatial ACC preceded accurate behavioural discrimination. These data provide evidence for plasticity of auditory processing in adult CI users. Behavioural electrode discrimination score but not spatial ACC amplitude was found to be a significant predictor of speech perception. We suggest that it would be beneficial to measure electrode discrimination in CI users and that interventions that exploit the plastic capacity of the auditory system to improve basic auditory processing, could be used to optimize performance in CI users.

Electrophysiological and Behavioral Evidence of Reduced Binaural Temporal Processing in the Aging and Hearing Impaired Human Auditory System.

A person's ability to process temporal fine structure information is indispensable for speech understanding. As speech understanding typically deteriorates throughout adult life, this study aimed to disentangle age and hearing impairment (HI)-related changes in binaural temporal processing. This was achieved by examining neural and behavioral processing of interaural phase differences (IPDs). Neural IPD processing was studied electrophysiologically through steady-state activity in the electroencephalogram evoked by periodic changes in IPDs over time, embedded in the temporal fine structure of acoustic stimulation. In addition, behavioral IPD discrimination thresholds were determined for the same stimuli. To disentangle potential effects of age from those of HI, both measures were applied to six participant groups: young, middle-aged, and older persons, with either normal hearing or sensorineural HI. All participants passed a cognitive screening, and stimulus audibility was controlled for in participants with HI. The results demonstrated that HI changes neural processing of binaural temporal information for all age-groups included in this study. These outcomes were revealed, superimposed on age-related changes that emerge between young adulthood and middle age. Poorer neural outcomes were also associated with poorer behavioral performance, even though the behavioral IPD discrimination thresholds were affected by age rather than by HI. The neural outcomes of this study are the first to evidence and disentangle the dual load of age and HI on binaural temporal processing. These results could be a valuable first step toward future research on rehabilitation.

Objective assessment of electrode discrimination with the auditory change complex in adult cochlear implant users.

The spatial auditory change complex (ACC) is a cortical response elicited by a change in place of stimulation. There is growing evidence that it provides a useful objective measure of electrode discrimination in cochlear implant (CI) users. To date, the spatial ACC has only been measured in relatively experienced CI users with one type of device. Early assessment of electrode discrimination could allow auditory stimulation to be optimized during a potentially sensitive period of auditory rehabilitation. In this study we used a direct stimulation paradigm to measure the spatial ACC in both pre- and post-lingually deafened adults. We show that it is feasible to measure the spatial ACC in different CI devices and as early as 1 week after CI switch-on. The spatial ACC has a strong relationship with performance on a behavioural discrimination task and in some cases provides information over and above behavioural testing. We suggest that it may be useful to measure the spatial ACC to guide auditory rehabilitation and improve hearing performance in CI users.

Spatial Selectivity in Cochlear Implants: Effects of Asymmetric Waveforms and Development of a Single-Point Measure.

Three experiments studied the extent to which cochlear implant users' spatial selectivity can be manipulated using asymmetric waveforms and tested an efficient method for comparing spatial selectivity produced by different stimuli. Experiment 1 measured forward-masked psychophysical tuning curves (PTCs) for a partial tripolar (pTP) probe. Maskers were presented on bipolar pairs separated by one unused electrode; waveforms were either symmetric biphasic ("SYM") or pseudomonophasic with the short high-amplitude phase being either anodic ("PSA") or cathodic ("PSC") on the more apical electrode. For the SYM masker, several subjects showed PTCs consistent with a bimodal excitation pattern, with discrete excitation peaks on each electrode of the bipolar masker pair. Most subjects showed significant differences between the PSA and PSC maskers consistent with greater masking by the electrode where the high-amplitude phase was anodic, but the pattern differed markedly across subjects. Experiment 2 measured masked excitation patterns for a pTP probe and either a monopolar symmetric biphasic masker ("MP_SYM") or pTP pseudomonophasic maskers where the short high-amplitude phase was either anodic ("TP_PSA") or cathodic ("TP_PSC") on the masker's central electrode. Four of the five subjects showed significant differences between the masker types, but again the pattern varied markedly across subjects. Because the levels of the maskers were chosen to produce the same masking of a probe on the same channel as the masker, it was correctly predicted that maskers that produce broader masking patterns would sound louder. Experiment 3 exploited this finding by using a single-point measure of spread of excitation to reveal significantly better spatial selectivity for TP_PSA compared to TP_PSC maskers.

Neural Representation of Interaural Time Differences in Humans-an Objective Measure that Matches Behavioural Performance.

Humans, and many other species, exploit small differences in the timing of sounds at the two ears (interaural time difference, ITD) to locate their source and to enhance their detection in background noise. Despite their importance in everyday listening tasks, however, the neural representation of ITDs in human listeners remains poorly understood, and few studies have assessed ITD sensitivity to a similar resolution to that reported perceptually. Here, we report an objective measure of ITD sensitivity in electroencephalography (EEG) signals to abrupt modulations in the interaural phase of amplitude-modulated low-frequency tones. Specifically, we measured following responses to amplitude-modulated sinusoidal signals (520-Hz carrier) in which the stimulus phase at each ear was manipulated to produce discrete interaural phase modulations at minima in the modulation cycle-interaural phase modulation following responses (IPM-FRs). The depth of the interaural phase modulation (IPM) was defined by the sign and the magnitude of the interaural phase difference (IPD) transition which was symmetric around zero. Seven IPM depths were assessed over the range of ±22 ° to ±157 °, corresponding to ITDs largely within the range experienced by human listeners under natural listening conditions (120 to 841 µs). The magnitude of the IPM-FR was maximal for IPM depths in the range of ±67.6 ° to ±112.6 ° and correlated well with performance in a behavioural experiment in which listeners were required to discriminate sounds containing IPMs from those with only static IPDs. The IPM-FR provides a sensitive measure of binaural processing in the human brain and has a potential to assess temporal binaural processing.

Objective Measures of Neural Processing of Interaural Time Differences.

We assessed neural sensitivity to interaural time differences (ITDs) conveyed in the temporal fine structure (TFS) of low-frequency sounds and ITDs conveyed in the temporal envelope of amplitude-modulated (AM'ed) high-frequency sounds. Using electroencephalography (EEG), we recorded brain activity to sounds in which the interaural phase difference (IPD) of the TFS (or the modulated temporal envelope) was repeatedly switched between leading in one ear or the other. When the amplitude of the tones is modulated equally in the two ears at 41 Hz, the interaural phase modulation (IPM) evokes an IPM following-response (IPM-FR) in the EEG signal. For low-frequency signals, IPM-FRs were reliably obtained, and largest for an IPM rate of 6.8 Hz and when IPD switches (around 0°) were in the range 45-90°. IPDs conveyed in envelope of high-frequency tones also generated IPM-FRs; response maxima occurred for IPDs switched between 0° and 180° IPD. This is consistent with the interpretation that distinct binaural mechanisms generate the IPM-FR at low and high frequencies, and with the reported physiological responses of medial superior olive (MSO) and lateral superior olive (LSO) neurons in other mammals. Low-frequency binaural neurons in the MSO are considered maximally activated by IPDs in the range 45-90°, consistent with their reception of excitatory inputs from both ears. High-frequency neurons in the LSO receive excitatory and inhibitory input from the two ears receptively--as such maximum activity occurs when the sounds at the two ears are presented out of phase.

A Comparison of Two Objective Measures of Binaural Processing: The Interaural Phase Modulation Following Response and the Binaural Interaction Component.

There has been continued interest in clinical objective measures of binaural processing. One commonly proposed measure is the binaural interaction component (BIC), which is obtained typically by recording auditory brainstem responses (ABRs)-the BIC reflects the difference between the binaural ABR and the sum of the monaural ABRs (i.e., binaural - (left + right)). We have recently developed an alternative, direct measure of sensitivity to interaural time differences, namely, a following response to modulations in interaural phase difference (the interaural phase modulation following response; IPM-FR). To obtain this measure, an ongoing diotically amplitude-modulated signal is presented, and the interaural phase difference of the carrier is switched periodically at minima in the modulation cycle. Such periodic modulations to interaural phase difference can evoke a steady state following response. BIC and IPM-FR measurements were compared from 10 normal-hearing subjects using a 16-channel electroencephalographic system. Both ABRs and IPM-FRs were observed most clearly from similar electrode locations-differential recordings taken from electrodes near the ear (e.g., mastoid) in reference to a vertex electrode (Cz). Although all subjects displayed clear ABRs, the BIC was not reliably observed. In contrast, the IPM-FR typically elicited a robust and significant response. In addition, the IPM-FR measure required a considerably shorter recording session. As the IPM-FR magnitude varied with interaural phase difference modulation depth, it could potentially serve as a correlate of perceptual salience. Overall, the IPM-FR appears a more suitable clinical measure than the BIC.

The polarity sensitivity of the electrically stimulated human auditory nerve measured at the level of the brainstem.

Recent behavioral studies have suggested that the human auditory nerve of cochlear implant (CI) users is mainly excited by the positive (anodic) polarity. Those findings were only obtained using asymmetric pseudomonophasic (PS) pulses where the effect of one phase was measured in the presence of a counteracting phase of opposite polarity, longer duration, and lower amplitude than the former phase. It was assumed that only the short high-amplitude phase was responsible for the excitation. Similarly, it has been shown that electrically evoked compound action potentials could only be obtained in response to the anodic phases of asymmetric pulses. Here, experiment 1 measured electrically evoked auditory brainstem responses to standard symmetric, PS, reversed pseudomonophasic, and reversed pseudomonophasic with inter-phase gap (6 ms) pulses presented for both polarities. Responses were time locked to the short high-amplitude phase of asymmetric pulses and were smaller, but still measurable, when that phase was cathodic than when it was anodic. This provides the first evidence that cathodic stimulation can excite the auditory system of human CI listeners and confirms that this stimulation is nevertheless less effective than for the anodic polarity. A second experiment studied the polarity sensitivity at different intensities by means of a loudness balancing task between pseudomonophasic anodic (PSA) and pseudomonophasic cathodic (PSC) stimuli. Previous studies had demonstrated greater sensitivity to anodic stimulation only for stimuli producing loud percepts. The results showed that PSC stimuli required higher amplitudes than PSA stimuli to reach the same loudness and that this held for current levels ranging from 10 to 100% of the dynamic range.

Spread of excitation varies for different electrical pulse shapes and stimulation modes in cochlear implants.

In cochlear implants (CI) bipolar (BP) electrical stimulation has been suggested as a method to reduce the spread of current along the cochlea. However, behavioral measurements in BP mode have shown either similar or worse performance than in monopolar (MP) mode. This could be explained by a bimodal excitation pattern, with two main excitation peaks at the sites of the stimulating electrodes. We measured the spread of excitation (SOE) by means of the electrically evoked compound action potential (ECAP), obtained using the forward-masked paradigm. The aim was to measure the bimodality of the excitation and to determine whether it could be reduced by using asymmetric pulses. Three types of maskers shapes were used: symmetric (SYM), pseudomonophasic (PS), and symmetric with a long inter-phase gap (SYM-IPG) pulses. Maskers were presented in BP + 9 (wide), BP + 3 (narrow) and MP (only SYM) mode on fixed electrodes. The SOE obtained with the MP masker showed a main excitation peak close to the masker electrode. Wide SYM maskers produced bimodal excitation patterns showing two peaks close to the electrodes of the masker channel, whereas SYM-IPG maskers showed a single main peak near the electrode for which the masker's second phase (responsible for most of the masking) was anodic. Narrow SYM maskers showed complex and wider excitation patterns than asymmetric stimuli consistent with the overlap of the patterns produced by each channel's electrodes. The masking produced by narrow SYM-IPG and PS stimuli was more pronounced close to the masker electrode for which the effective phase was anodic. These results showed that the anodic polarity is the most effective one in BP mode and that the bimodal patterns produced by SYM maskers could be partially reduced by using asymmetric pulses.

Evaluating the noise in electrically evoked compound action potential measurements in cochlear implants.

Electrically evoked compound action potentials (ECAPs) are widely used to study the excitability of the auditory nerve and stimulation properties in cochlear implant (CI) users. However, ECAP detection can be difficult and very subjective at near-threshold stimulation levels or in spread of excitation measurements. In this study, we evaluated the statistical properties of the background noise (BN) and the postaverage residual noise (RN) in ECAP measurements in order to determine an objective detection criterion. For the estimation of the BN and the RN, a method currently used in auditory brainstem response measurements was applied. The potential benefit of using weighted (Bayesian) averages was also examined. All estimations were performed with a set of approximately 360 ECAP measurements recorded from five human CI users of the CII or HiRes90K device (advanced bionics). Results demonstrated that the BN was normally distributed and the RN decreased according to the square root of the number of averages. No additional benefit was observed by using weighted averaging. The noise was not significantly different either at different stimulation intensities or across recording electrodes along the cochlea. The analysis of the statistical properties of the noise indicated that a signal-to-noise ratio of 1.7 dB as a detection criterion corresponds to a false positive detection rate of 1% with the used measurement setup.

Polarity effects on neural responses of the electrically stimulated auditory nerve at different cochlear sites.

Three experiments studied the effect of stimulus polarity on the Electrically Evoked Compound Action Potential (ECAP) obtained with the masker-probe paradigm on different sites along the cochlea in cochlear implant users. Experiment 1 used a biphasic cathodic-1st (BIC) masker and showed that ECAP N(1) peak latencies were longer for BIC than for biphasic anodic-1st (BIA) probes on all electrodes under test. Both the latency of each probe as well as the latency difference between BIA and BIC probes increased when the phase width (PW) of the masker and probe were increased together. Experiment 2 used maskers with long inter-phase gaps (IPGs), and, by manipulating the polarity of the second phase (closest in time to the biphasic probe), showed that only an anodic phase could mask the probe response. Experiment 3 used maskers and probes with long IPGs and measured ECAPs to the first phase of the probe; ECAPs could be measured when both this phase and the second phase of the masker were anodic, but not when they were cathodic. Our results extend those of a previous study, showing that the auditory nerve in humans is preferentially activated by anodic stimulation, to different sites along the cochlea.