Is Human Auditory Cortex Organization Compatible With the Monkey Model? Contrary Evidence From Ultra-High-Field Functional and Structural MRI.

It is commonly assumed that the human auditory cortex is organized similarly to that of macaque monkeys, where the primary region, or "core," is elongated parallel to the tonotopic axis (main direction of tonotopic gradients), and subdivided across this axis into up to 3 distinct areas (A1, R, and RT), with separate, mirror-symmetric tonotopic gradients. This assumption, however, has not been tested until now. Here, we used high-resolution ultra-high-field (7 T) magnetic resonance imaging (MRI) to delineate the human core and map tonotopy in 24 individual hemispheres. In each hemisphere, we assessed tonotopic gradients using principled, quantitative analysis methods, and delineated the core using 2 independent (functional and structural) MRI criteria. Our results indicate that, contrary to macaques, the human core is elongated perpendicular rather than parallel to the main tonotopic axis, and that this axis contains no more than 2 mirror-reversed gradients within the core region. Previously suggested homologies between these gradients and areas A1 and R in macaques were not supported. Our findings suggest fundamental differences in auditory cortex organization between humans and macaques.

Auditory Attention Causes Gain Enhancement and Frequency Sharpening at Successive Stages of Cortical Processing-Evidence from Human Electroencephalography.

Previous findings have suggested that auditory attention causes not only enhancement in neural processing gain, but also sharpening in neural frequency tuning in human auditory cortex. The current study was aimed to reexamine these findings. Specifically, we aimed to investigate whether attentional gain enhancement and frequency sharpening emerge at the same or different processing levels and whether they represent independent or cooperative effects. For that, we examined the pattern of attentional modulation effects on early, sensory-driven cortical auditory-evoked potentials occurring at different latencies. Attention was manipulated using a dichotic listening task and was thus not selectively directed to specific frequency values. Possible attention-related changes in frequency tuning selectivity were measured with an adaptation paradigm. Our results show marked disparities in attention effects between the earlier N1 deflection and the subsequent P2 deflection, with the N1 showing a strong gain enhancement effect, but no sharpening, and the P2 showing clear evidence of sharpening, but no independent gain effect. They suggest that gain enhancement and frequency sharpening represent successive stages of a cooperative attentional modulation mechanism that increases the representational bandwidth of attended versus unattended sounds.

The neural substrate for binaural masking level differences in the auditory cortex.

The binaural masking level difference (BMLD) is a phenomenon whereby a signal that is identical at each ear (S0), masked by a noise that is identical at each ear (N0), can be made 12-15 dB more detectable by inverting the waveform of either the tone or noise at one ear (Sπ, Nπ). Single-cell responses to BMLD stimuli were measured in the primary auditory cortex of urethane-anesthetized guinea pigs. Firing rate was measured as a function of signal level of a 500 Hz pure tone masked by low-passed white noise. Responses were similar to those reported in the inferior colliculus. At low signal levels, the response was dominated by the masker. At higher signal levels, firing rate either increased or decreased. Detection thresholds for each neuron were determined using signal detection theory. Few neurons yielded measurable detection thresholds for all stimulus conditions, with a wide range in thresholds. However, across the entire population, the lowest thresholds were consistent with human psychophysical BMLDs. As in the inferior colliculus, the shape of the firing-rate versus signal-level functions depended on the neurons' selectivity for interaural time difference. Our results suggest that, in cortex, BMLD signals are detected from increases or decreases in the firing rate, consistent with predictions of cross-correlation models of binaural processing and that the psychophysical detection threshold is based on the lowest neural thresholds across the population.

Parcellation of Human and Monkey Core Auditory Cortex with fMRI Pattern Classification and Objective Detection of Tonotopic Gradient Reversals.

Auditory cortex (AC) contains several primary-like, or "core," fields, which receive thalamic input and project to non-primary "belt" fields. In humans, the organization and layout of core and belt auditory fields are still poorly understood, and most auditory neuroimaging studies rely on macroanatomical criteria, rather than functional localization of distinct fields. A myeloarchitectonic method has been suggested recently for distinguishing between core and belt fields in humans (Dick F, Tierney AT, Lutti A, Josephs O, Sereno MI, Weiskopf N. 2012. In vivo functional and myeloarchitectonic mapping of human primary auditory areas. J Neurosci. 32:16095-16105). We propose a marker for core AC based directly on functional magnetic resonance imaging (fMRI) data and pattern classification. We show that a portion of AC in Heschl's gyrus classifies sound frequency more accurately than other regions in AC. Using fMRI data from macaques, we validate that the region where frequency classification performance is significantly above chance overlaps core auditory fields, predominantly A1. Within this region, we measure tonotopic gradients and estimate the locations of the human homologues of the core auditory subfields A1 and R. Our results provide a functional rather than anatomical localizer for core AC. We posit that inter-individual variability in the layout of core AC might explain disagreements between results from previous neuroimaging and cytological studies.

The influence of cochlear spectral processing on the timing and amplitude of the speech-evoked auditory brain stem response.

The speech-evoked auditory brain stem response (speech ABR) is widely considered to provide an index of the quality of neural temporal encoding in the central auditory pathway. The aim of the present study was to evaluate the extent to which the speech ABR is shaped by spectral processing in the cochlea. High-pass noise masking was used to record speech ABRs from delimited octave-wide frequency bands between 0.5 and 8 kHz in normal-hearing young adults. The latency of the frequency-delimited responses decreased from the lowest to the highest frequency band by up to 3.6 ms. The observed frequency-latency function was compatible with model predictions based on wave V of the click ABR. The frequency-delimited speech ABR amplitude was largest in the 2- to 4-kHz frequency band and decreased toward both higher and lower frequency bands despite the predominance of low-frequency energy in the speech stimulus. We argue that the frequency dependence of speech ABR latency and amplitude results from the decrease in cochlear filter width with decreasing frequency. The results suggest that the amplitude and latency of the speech ABR may reflect interindividual differences in cochlear, as well as central, processing. The high-pass noise-masking technique provides a useful tool for differentiating between peripheral and central effects on the speech ABR. It can be used for further elucidating the neural basis of the perceptual speech deficits that have been associated with individual differences in speech ABR characteristics.

Neuroimaging paradigms for tonotopic mapping (I): the influence of sound stimulus type.

Although a consensus is emerging in the literature regarding the tonotopic organisation of auditory cortex in humans, previous studies employed a vast array of different neuroimaging protocols. In the present functional magnetic resonance imaging (fMRI) study, we made a systematic comparison between stimulus protocols involving jittered tone sequences with either a narrowband, broadband, or sweep character in order to evaluate their suitability for the purpose of tonotopic mapping. Data-driven analysis techniques were used to identify cortical maps related to sound-evoked activation and tonotopic frequency tuning. Principal component analysis (PCA) was used to extract the dominant response patterns in each of the three protocols separately, and generalised canonical correlation analysis (CCA) to assess the commonalities between protocols. Generally speaking, all three types of stimuli evoked similarly distributed response patterns and resulted in qualitatively similar tonotopic maps. However, quantitatively, we found that broadband stimuli are most efficient at evoking responses in auditory cortex, whereas narrowband and sweep stimuli offer the best sensitivity to differences in frequency tuning. Based on these results, we make several recommendations regarding optimal stimulus protocols, and conclude that an experimental design based on narrowband stimuli provides the best sensitivity to frequency-dependent responses to determine tonotopic maps. We forward that the resulting protocol is suitable to act as a localiser of tonotopic cortical fields in individuals, or to make quantitative comparisons between maps in dedicated tonotopic mapping studies.

Neuroimaging paradigms for tonotopic mapping (II): the influence of acquisition protocol.

Numerous studies on the tonotopic organisation of auditory cortex in humans have employed a wide range of neuroimaging protocols to assess cortical frequency tuning. In the present functional magnetic resonance imaging (fMRI) study, we made a systematic comparison between acquisition protocols with variable levels of interference from acoustic scanner noise. Using sweep stimuli to evoke travelling waves of activation, we measured sound-evoked response signals using sparse, clustered, and continuous imaging protocols that were characterised by inter-scan intervals of 8.8, 2.2, or 0.0 s, respectively. With regard to sensitivity to sound-evoked activation, the sparse and clustered protocols performed similarly, and both detected more activation than the continuous method. Qualitatively, tonotopic maps in activated areas proved highly similar, in the sense that the overall pattern of tonotopic gradients was reproducible across all three protocols. However, quantitatively, we observed substantial reductions in response amplitudes to moderately low stimulus frequencies that coincided with regions of strong energy in the scanner noise spectrum for the clustered and continuous protocols compared to the sparse protocol. At the same time, extreme frequencies became over-represented for these two protocols, and high best frequencies became relatively more abundant. Our results indicate that although all three scanning protocols are suitable to determine the layout of tonotopic fields, an exact quantitative assessment of the representation of various sound frequencies is substantially confounded by the presence of scanner noise. In addition, we noticed anomalous signal dynamics in response to our travelling wave paradigm that suggest that the assessment of frequency-dependent tuning is non-trivially influenced by time-dependent (hemo)dynamics when using sweep stimuli.

Evidence for pitch chroma mapping in human auditory cortex.

Some areas in auditory cortex respond preferentially to sounds that elicit pitch, such as musical sounds or voiced speech. This study used human electroencephalography (EEG) with an adaptation paradigm to investigate how pitch is represented within these areas and, in particular, whether the representation reflects the physical or perceptual dimensions of pitch. Physically, pitch corresponds to a single monotonic dimension: the repetition rate of the stimulus waveform. Perceptually, however, pitch has to be described with 2 dimensions, a monotonic, "pitch height," and a cyclical, "pitch chroma," dimension, to account for the similarity of the cycle of notes (c, d, e, etc.) across different octaves. The EEG adaptation effect mirrored the cyclicality of the pitch chroma dimension, suggesting that auditory cortex contains a representation of pitch chroma. Source analysis indicated that the centroid of this pitch chroma representation lies somewhat anterior and lateral to primary auditory cortex.

The specificity of stimulus-specific adaptation in human auditory cortex increases with repeated exposure to the adapting stimulus.

The neural response to a sensory stimulus tends to be more strongly reduced when the stimulus is preceded by the same, rather than a different, stimulus. This stimulus-specific adaptation (SSA) is ubiquitous across the senses. In hearing, SSA has been suggested to play a role in change detection as indexed by the mismatch negativity. This study sought to test whether SSA, measured in human auditory cortex, is caused by neural fatigue (reduction in neural responsiveness) or by sharpening of neural tuning to the adapting stimulus. For that, we measured event-related cortical potentials to pairs of pure tones with varying frequency separation and stimulus onset asynchrony (SOA). This enabled us to examine the relationship between the degree of specificity of adaptation as a function of frequency separation and the rate of decay of adaptation with increasing SOA. Using simulations of tonotopic neuron populations, we demonstrate that the fatigue model predicts independence of adaptation specificity and decay rate, whereas the sharpening model predicts interdependence. The data showed independence and thus supported the fatigue model. In a second experiment, we measured adaptation specificity after multiple presentations of the adapting stimulus. The multiple adapters produced more adaptation overall, but the effect was more specific to the adapting frequency. Within the context of the fatigue model, the observed increase in adaptation specificity could be explained by assuming a 2.5-fold increase in neural frequency selectivity. We discuss possible bottom-up and top-down mechanisms of this effect.

Mechanisms of adaptation in human auditory cortex.

This study investigates the temporal properties of adaptation in the late auditory-evoked potentials in humans. The results are used to make inferences about the mechanisms of adaptation in human auditory cortex. The first experiment measured adaptation by single adapters as a combined function of the adapter duration and the stimulus onset asynchrony (SOA) and interstimulus interval (ISI) between the adapter and the adapted sound ("probe"). The results showed recovery from adaptation with increasing ISI, as would be expected, but buildup of adaptation with increasing adapter duration and thus SOA. This suggests that adaptation in auditory cortex is caused by the ongoing, rather than the onset, response to the adapter. Quantitative modeling indicated that the rate of buildup of adaptation is almost an order of magnitude faster than the recovery rate of adaptation. The recovery rate suggests that cortical adaptation is caused by synaptic depression and slow afterhyperpolarization. The P2 was more strongly affected by adaptation than the N1, suggesting that the two deflections originate from different cortical generators. In the second experiment, the single adapters were replaced by trains of two or four identical adapters. The results indicated that adaptation decays faster after repeated presentation of the adapter. This increase in the recovery rate of adaptation might contribute to the elicitation of the auditory mismatch negativity response. It may be caused by top-down feedback or by local processes such as the buildup of residual Ca(2+) within presynaptic neurons.

Is overshoot caused by an efferent reduction in cochlear gain?

Under certain conditions, detection of a masked tone is improved by a preceding sound ("precursor"). This phenomenon is referred to as the "temporal effect" or "overshoot". A prevalent model of overshoot, referred to as the "gain reduction model", posits that overshoot is caused by efferent reduction in cochlear gain mediated by the medial olivocochlear (MOC) bundle. The model predicts that reduction in cochlear gain will reduce masking when masking is suppressive or when masking is excitatory and the signal-to-masker ratio is high. This study was aimed at testing the validity of these predictions. It consisted of two experiments. The first experiment investigated the relative contributions of suppressive versus excitatory masking to overshoot. The signal was a short 4-kHz tone pip, and the masker and precursor were limited to contain energy either only within (-on-frequency) or only outside (off-frequency) the cochlear filter around the signal frequency. The on-frequency masker would be expected to cause mainly excitatory masking, whereas masking by the off-frequency masker would be expected to be mainly suppressive. Only the off-frequency masker and precursor yielded -significant overshoot. This suggests that measurable overshoot requires suppressive masking. The second experiment sought to quantify the effect of a precursor on cochlear -suppression more directly by measuring the amount of suppression caused by a 4.75-kHz suppressor on a lower-frequency (4-kHz) suppressee with and without a precursor present. Suppression was measured using a forward-masking paradigm. While we found large suppression and large overshoot, we found no reduction in suppression by the precursor. This is contrary to the gain reduction model. Taken together, our results indicate that measurable overshoot requires off-frequency masking and that off-frequency overshoot must be caused by a mechanism other than MOC-mediated reduction in cochlear suppression.

Factors affecting the use of envelope interaural time differences in reverberation.

At high frequencies, interaural time differences (ITDs) are conveyed by the sound envelope. Sensitivity to envelope ITDs depends crucially on the envelope shape. Reverberation degrades the envelope shape, reducing the modulation depth of the envelope and the slope of its flanks. Reverberation also reduces the envelope interaural coherence (i.e., the similarity of the envelopes at two ears). The current study investigates the extent to which these changes affect sensitivity to envelope ITDs. The first experiment measured ITD discrimination thresholds at low and high frequencies in a simulated room. The stimulus was either a low-frequency narrowband noise or the same noise transposed to a higher frequency. The results suggest that the effect of reverberation on ITD thresholds was multiplicative. Given that the threshold without reverberation was larger for the transposed than for the low-frequency stimulus, this meant that, in absolute terms, the thresholds for the transposed stimulus showed a much greater increase due to reverberation than those for the low-frequency stimulus. Three further experiments indicated that the effect of reverberation on the envelope ITD thresholds was due to the combined effect of the reduction in the envelope modulation depth and slopes, as well as the decrease in the envelope interaural coherence.

What is the role of the medial olivocochlear system in speech-in-noise processing?

The medial olivocochlear (MOC) bundle reduces the gain of the cochlear amplifier through reflexive activation by sound. Physiological results indicate that MOC-induced reduction in cochlear gain can enhance the response to signals when presented in masking noise. Some previous studies suggest that this "antimasking" effect of the MOC system plays a role in speech-in-noise perception. The present study set out to reinvestigate this hypothesis by correlating measures of MOC activity and speech-in-noise processing across a group of normal-hearing participants. MOC activity was measured using contralateral suppression of otoacoustic emissions (OAEs), and speech-in-noise processing was measured by measuring the effect of noise masking on performance in a consonant-vowel (CV) discrimination task and on auditory brain stem responses evoked by a CV syllable. Whereas there was a significant correlation between OAE suppression and both measures of speech-in-noise processing, the direction of this correlation was opposite to that predicted by the antimasking hypothesis, in that individuals with stronger OAE suppression tended to show greater noise-masking effects on CV processing. The current results indicate that reflexive MOC activation is not always beneficial to speech-in-noise processing. We propose an alternative to the antimasking hypothesis, whereby the MOC system benefits speech-in-noise processing through dynamic (e.g., attention- and experience-dependent), rather than reflexive, control of cochlear gain.

Evidence for multisensory integration in the elicitation of prior entry by bimodal cues.

This study reports an experiment investigating the relative effects of intramodal, crossmodal and bimodal cues on visual and auditory temporal order judgements. Pairs of visual or auditory targets, separated by varying stimulus onset asynchronies, were presented to either side of a central fixation (±45°), and participants were asked to identify the target that had occurred first. In some of the trials, one of the targets was preceded by a short, non-predictive visual, auditory or audiovisual cue stimulus. The cue and target stimuli were presented at the exact same locations in space. The point of subjective simultaneity revealed a consistent spatiotemporal bias towards targets at the cued location. For the visual targets, the intramodal cue elicited the largest, and the crossmodal cue the smallest, bias. The bias elicited by the bimodal cue fell between the intramodal and crossmodal cue biases, with significant differences between all cue types. The pattern for the auditory targets was similar apart from a scaling factor and greater variance, so the differences between the cue conditions did not reach significance. These results provide evidence for multisensory integration in exogenous attentional cueing. The magnitude of the bimodal cueing effect was equivalent to the average of the facilitation elicited by the intramodal and crossmodal cues. Under the assumption that the visual and auditory cues were equally informative, this is consistent with the notion that exogenous attention, like perception, integrates multimodal information in an optimal way.

Could Tailored Chirp Stimuli Benefit Measurement of the Supra-threshold Auditory Brainstem Wave-I Response?

Auditory brainstem responses (ABRs) to broadband clicks are strongly affected by dyssynchrony, or "latency dispersion", of their frequency-specific cochlear contributions. Optimized chirp stimuli, designed to compensate for cochlear dispersion, can afford substantial increase in broadband ABR amplitudes, particularly for the prominent wave-V deflection. Reports on the smaller wave I, however, which may be useful for measuring cochlear synaptopathy, have been mixed. This study aimed to test previous claims that ABR latency dispersion differs between waves I and V, and between males and females, and thus that using wave- and/or sex-tailored chirps may provide more reliable wave-I benefit. Using the derived-band technique, we measured responses from frequency-restricted (one-octave-wide) cochlear regions to energy-matched click and chirp stimuli. The derived-band responses' latencies were used to assess any wave- and/or sex-related dispersion differences across bands, and their amplitudes, to evaluate any within-band dispersion differences. Our results suggest that sex-related dispersion difference within the lowest-frequency cochlear regions (< 1 kHz), where dispersion is generally greatest, may be a predominant driver of the often-reported sex difference in broadband ABR amplitude. At the same time, they showed no systematic dispersion difference between waves I and V. Instead, they suggest that reduced chirp benefit on wave I may arise as a result of chirp-induced desynchronization of on- and off-frequency responses generated at the same cochlear places, and resultant reduction in response contributions from higher-frequency cochlear regions, to which wave I is thought to be particularly sensitive.

Evidence for opponent-channel coding of interaural time differences in human auditory cortex.

In humans, horizontal sound localization of low-frequency sounds is mainly based on interaural time differences (ITDs). Traditionally, it was assumed that ITDs are converted into a topographic (or rate-place) code, supported by an array of neurons with parametric tuning to ITDs within the behaviorally relevant range. Although this topographic model has been confirmed in owls, its applicability to mammals has been challenged by recent physiological results suggesting that, at least in small-headed species, ITDs are represented by a nontopographic population rate code, which involves only two opponent (left and right) channels, broadly tuned to ITDs from the two auditory hemifields. The current study investigates which of these two models of ITD processing is more likely to apply to humans. For that, evoked responses to abrupt changes in the ITDs of otherwise continuous sounds were measured with electroencephalography. The ITD change was either away from ("outward" change) or toward the midline ("inward" change). According to the opponent-channel model, the response to an outward ITD change should be larger than the response to the corresponding inward change, whereas the topographic model would predict similar response sizes for both conditions. The measured response sizes were highly consistent with the predictions of the opponent-channel model and contravened the predictions of the topographic model, suggesting that, in humans, ITDs are coded nontopographically. The hemispheric distributions of the ITD change responses suggest that the majority of ITD-sensitive neurons in each hemisphere are tuned to ITDs from the contralateral hemifield.

Evidence for early specialized processing of speech formant information in anterior and posterior human auditory cortex.

Many speech sounds, such as vowels, exhibit a characteristic pattern of spectral peaks, referred to as formants, the frequency positions of which depend both on the phonological identity of the sound (e.g. vowel type) and on the vocal-tract length of the speaker. This study investigates the processing of formant information relating to vowel type and vocal-tract length in human auditory cortex by measuring electroencephalographic (EEG) responses to synthetic unvoiced vowels and spectrally matched noises. The results revealed specific sensitivity to vowel formant information in both anterior (planum polare) and posterior (planum temporale) regions of auditory cortex. The vowel-specific responses in these two areas appeared to have different temporal dynamics; the anterior source produced a sustained response for as long as the incoming sound was a vowel, whereas the posterior source responded transiently when the sound changed from a noise to a vowel, or when there was a change in vowel type. Moreover, the posterior source appeared to be largely invariant to changes in vocal-tract length. The current findings indicate that the initial extraction of vowel type from formant information is complete by the level of non-primary auditory cortex, suggesting that speech-specific processing may involve primary auditory cortex, or even subcortical structures. This challenges the view that specific sensitivity to speech emerges only beyond unimodal auditory cortex.

Understanding pitch perception as a hierarchical process with top-down modulation.

Pitch is one of the most important features of natural sounds, underlying the perception of melody in music and prosody in speech. However, the temporal dynamics of pitch processing are still poorly understood. Previous studies suggest that the auditory system uses a wide range of time scales to integrate pitch-related information and that the effective integration time is both task- and stimulus-dependent. None of the existing models of pitch processing can account for such task- and stimulus-dependent variations in processing time scales. This study presents an idealized neurocomputational model, which provides a unified account of the multiple time scales observed in pitch perception. The model is evaluated using a range of perceptual studies, which have not previously been accounted for by a single model, and new results from a neurophysiological experiment. In contrast to other approaches, the current model contains a hierarchy of integration stages and uses feedback to adapt the effective time scales of processing at each stage in response to changes in the input stimulus. The model has features in common with a hierarchical generative process and suggests a key role for efferent connections from central to sub-cortical areas in controlling the temporal dynamics of pitch processing.

Noise-Induced Changes of the Auditory Brainstem Response to Speech-a Measure of Neural Desynchronisation?

It is commonly assumed that difficulty in listening to speech in noise is at least partly due to deficits in neural temporal processing. Given that noise reduces the temporal fidelity of the auditory brainstem response (ABR) to speech, it has been suggested that the speech ABR may serve as an index of such neural deficits. However, the temporal fidelity of ABRs, to both speech and non-speech sounds, is also known to be influenced by the cochlear origin of the response, as responses from higher-frequency cochlear regions are faster and more synchronous than responses from lower-frequency regions. Thus, if noise caused a reweighting of response contributions from higher- to lower-frequency cochlear regions, the temporal fidelity of the aggregate response should be reduced even in the absence of any changes in neural processing. This 'place mechanism' has been demonstrated for non-speech ABRs. The aim of this study was to test whether it also applies to speech ABRs. We used the so-called 'derived-band' method to isolate response contributions from frequency-limited cochlear regions. Broadband and derived-band speech ABRs were measured both in quiet and in noise. Whilst the noise caused significant changes to the temporal properties of the broadband response, its effects on the derived-band responses were mostly restricted to the response amplitudes. Importantly, the amplitudes of the higher-frequency derived-band responses were much more strongly affected than those of the lower-frequency responses, suggesting that the noise indeed caused a reweighting effect. Our results indicate that, as for non-speech ABRs, the cochlear place mechanism can represent a potentially substantial confound to speech-ABR-in-noise measurements.

Automated extraction of auditory brainstem response latencies and amplitudes by means of non-linear curve registration.

BACKGROUND AND OBJECTIVES: Animal results have suggested that auditory brainstem responses (ABRs) to transient sounds presented at supra-threshold levels may be useful for measuring hearing damage that is hidden to current audiometric tests. Evaluating such ABRs requires extracting the latencies and amplitudes of relevant deflections, or "waves". Currently, this is mostly done by human observers manually picking the waves' peaks and troughs in each individual response - a process that is both time-consuming and requiring of expert experience. Here, we propose a highly automated procedure for extracting individual ABR wave latencies and amplitudes based on the well-established methodology of non-linear curve registration. METHODS: First, the to-be-analysed individual ABRs are temporally aligned - either with one another or, if available, with a pre-existing template - by locally compressing or stretching their time axes with smooth and invertible time warping functions. Then, the individual latencies and amplitudes of relevant ABR waves are obtained by picking the latencies of the waves' peaks and troughs on the common (aligned) time axis and combining these with the individual aligned responses and inverse time warping functions. RESULTS: Using an example ABR data set with a wide range of response latencies and signal-to-noise ratios (SNRs), we test different choices for fitting the time warping functions. We cross-validate the warping results using independent response replicates and compare automatically and manually extracted latencies and amplitudes for ABR waves I and V. Using a Bayesian approach, we show that, for the best registration condition, automatic and manual data were statistically similar. CONCLUSIONS: Non-linear curve registration can be used to temporally align individual ABRs and extract their wave latencies and amplitudes in a way that closely matches results from manual picking.