Correction: Modeling and MEG evidence of early consonance processing in auditory cortex.

[This corrects the article DOI: 10.1371/journal.pcbi.1006820.].

Auditory cortex activity measured using functional near-infrared spectroscopy (fNIRS) appears to be susceptible to masking by cortical blood stealing.

To validate the use of functional near-infrared spectroscopy (fNIRS) in auditory perception experiments, combined fNIRS and electroencephalography (EEG) data were obtained from normal-hearing subjects passively listening to speech-like stimuli without linguistic content. The fNIRS oxy-haemoglobin (HbO) results were found to be inconsistent with the deoxy-haemoglobin (HbR) and EEG data, as they were dominated by increasingly more negative responses along a diagonal axis running in posterior-superior to anterior-inferior direction. This large-scale bilateral gradient in the HbO data masked the right-lateralised neural activity in the auditory cortex that was clearly evident in the HbR data and EEG source reconstructions and is most likely due to cerebral blood stealing. When the subjects were subsequently split into subgroups with more positive or more negative HbO responses in the right auditory cortex, the former group surprisingly showed smaller event-related potentials and increased EEG alpha power, indicating reduced attention and vigilance. These findings thus suggest that positive HbO responses in the auditory cortex may not necessarily be a favourable result when investigating auditory perception using fNIRS. More generally, the results show that the interpretation of fNIRS HbO signals can be misleading and demonstrate the benefits of combined fNIRS-EEG analyses.

Modeling and MEG evidence of early consonance processing in auditory cortex.

Pitch is a fundamental attribute of auditory perception. The interaction of concurrent pitches gives rise to a sensation that can be characterized by its degree of consonance or dissonance. In this work, we propose that human auditory cortex (AC) processes pitch and consonance through a common neural network mechanism operating at early cortical levels. First, we developed a new model of neural ensembles incorporating realistic neuronal and synaptic parameters to assess pitch processing mechanisms at early stages of AC. Next, we designed a magnetoencephalography (MEG) experiment to measure the neuromagnetic activity evoked by dyads with varying degrees of consonance or dissonance. MEG results show that dissonant dyads evoke a pitch onset response (POR) with a latency up to 36 ms longer than consonant dyads. Additionally, we used the model to predict the processing time of concurrent pitches; here, consonant pitch combinations were decoded faster than dissonant combinations, in line with the experimental observations. Specifically, we found a striking match between the predicted and the observed latency of the POR as elicited by the dyads. These novel results suggest that consonance processing starts early in human auditory cortex and may share the network mechanisms that are responsible for (single) pitch processing.

Lateralization and Binaural Interaction of Middle-Latency and Late-Brainstem Components of the Auditory Evoked Response.

We used magnetoencephalography to examine lateralization and binaural interaction of the middle-latency and late-brainstem components of the auditory evoked response (the MLR and SN10, respectively). Click stimuli were presented either monaurally, or binaurally with left- or right-leading interaural time differences (ITDs). While early MLR components, including the N19 and P30, were larger for monaural stimuli presented contralaterally (by approximately 30 and 36 % in the left and right hemispheres, respectively), later components, including the N40 and P50, were larger ipsilaterally. In contrast, MLRs elicited by binaural clicks with left- or right-leading ITDs did not differ. Depending on filter settings, weak binaural interaction could be observed as early as the P13 but was clearly much larger for later components, beginning at the P30, indicating some degree of binaural linearity up to early stages of cortical processing. The SN10, an obscure late-brainstem component, was observed consistently in individuals and showed linear binaural additivity. The results indicate that while the MLR is lateralized in response to monaural stimuli-and not ITDs-this lateralization reverses from primarily contralateral to primarily ipsilateral as early as 40 ms post stimulus and is never as large as that seen with fMRI.

Electrophysiological and psychophysical asymmetries in sensitivity to interaural correlation gaps and implications for binaural integration time.

Brief deviations of interaural correlation (IAC) can provide valuable cues for detection, segregation and localization of acoustic signals. This study investigated the processing of such "binaural gaps" in continuously running noise (100-2000 Hz), in comparison to silent "monaural gaps", by measuring late auditory evoked potentials (LAEPs) and perceptual thresholds with novel, iteratively optimized stimuli. Mean perceptual binaural gap duration thresholds exhibited a major asymmetry: they were substantially shorter for uncorrelated gaps in correlated and anticorrelated reference noise (1.75 ms and 4.1 ms) than for correlated and anticorrelated gaps in uncorrelated reference noise (26.5 ms and 39.0 ms). The thresholds also showed a minor asymmetry: they were shorter in the positive than in the negative IAC range. The mean behavioral threshold for monaural gaps was 5.5 ms. For all five gap types, the amplitude of LAEP components N1 and P2 increased linearly with the logarithm of gap duration. While perceptual and electrophysiological thresholds matched for monaural gaps, LAEP thresholds were about twice as long as perceptual thresholds for uncorrelated gaps, but half as long for correlated and anticorrelated gaps. Nevertheless, LAEP thresholds showed the same asymmetries as perceptual thresholds. For gap durations below 30 ms, LAEPs were dominated by the processing of the leading edge of a gap. For longer gap durations, in contrast, both the leading and the lagging edge of a gap contributed to the evoked response. Formulae for the equivalent rectangular duration (ERD) of the binaural system's temporal window were derived for three common window shapes. The psychophysical ERD was 68 ms for diotic and about 40 ms for anti- and uncorrelated noise. After a nonlinear Z-transform of the stimulus IAC prior to temporal integration, ERDs were about 10 ms for reference correlations of ±1 and 80 ms for uncorrelated reference. Hence, a physiologically motivated peripheral nonlinearity changed the rank order of ERDs across experimental conditions in a plausible manner.

Ipsi- and contralateral interaction in the 40 Hz auditory steady state responses (ASSRs) with two carriers at 60 dB SPL.

OBJECTIVE: Auditory steady state responses have been suggested for simultaneous threshold assessment using the multiple ASSR (MASSR) technique. However, at least at high stimulation levels, strong interactions reduce response amplitudes. The present study investigates ASSR interaction at a moderate stimulus level. DESIGN: Sinusoidal carriers modulated at rates near 40 Hz were used as probe. Unmodulated and modulated interferers were presented ipsi- or contralaterally. STUDY SAMPLE: Twenty normal-hearing subjects participated. RESULTS: Unmodulated interferers did not significantly change ASSR amplitudes. Modulated interferers, presented ipsilaterally or contralaterally, both significantly reduced the ASSR SNR by 13% and 8%, respectively. CONCLUSIONS: To compensate for the average SNR reduction would require a 32% and 18% longer measurement time for ipsi- and contralateral interferers, respectively, far less than the doubling of measurement time for two single measurements, emphasizing the MASSR technique advantage. However, the largest reduction for a single subject was 22% for the amplitude and 28% for the SNR, almost completely undoing the benefit in measurement time in MASSR. The individually varying interaction effects even at 60 dB SPL clearly limits the advantage of using the MASSR for modulation rates near 40 Hz over corresponding single ASSR measurements, at least for two simultaneous carriers.

Electrophysiological and psychophysical asymmetries in sensitivity to interaural correlation steps.

The binaural auditory system's sensitivity to changes in the interaural cross correlation (IAC), as an indicator for the perceived spatial diffuseness of a sound, is of major importance for the ability to distinguish concurrent sound sources. In this article, we present electroencephalographical and corresponding psychophysical experiments with stepwise transitions of the IAC in continuously running noise. Both the transient and sustained brain response, display electrophysiological correlates of specific binaural processing in humans. The transient late auditory evoked potentials (LAEP) systematically depend on the size of the IAC transition, the reference correlation preceding the transition, the direction of the transition and on unspecific context information from the stimulus sequence. The psychophysical and electrophysiological data are characterized by two asymmetries. (1) Major asymmetry: for reference correlations of +1 and -1, psychoacoustical thresholds are comparatively lower, and the peak-to-peak-amplitudes of LAEP are larger than for a reference correlation of zero. (2) Minor asymmetry: for IAC transitions in the positive parameter range, perceptual thresholds are slightly better and peak-to-peak amplitudes are larger than in the negative range. In all experimental conditions, LAEP amplitudes are linearly related to the dB scaled power ratio of correlated (N(0)) versus anticorrelated (N(pi)) signal components. The voltage gain of LAEP per dB(N(0)/N(pi)) closely corresponds to a constant perceptual distance between two correlations. We therefore suggest that activity in the auditory cortex and perceptual IAC sensitivity are better represented by the dB-scaled N(0)/N(pi) power ratio than by the normalized IAC itself.

The influence of externalization and spatial cues on the generation of auditory brainstem responses and middle latency responses.

The effect of externalization and spatial cues on the generation of auditory brainstem responses (ABRs) and middle latency responses (MLRs) was investigated in this study. Most previous evoked potential studies used click stimuli with variations of interaural time (ITDs) and interaural level differences (ILDs) which merely led to a lateralization of sound inside the subject's head. In contrast, in the present study potentials were elicited by a virtual acoustics stimulus paradigm with 'natural' spatial cues and compared to responses to a diotic, non-externalized reference stimulus. Spatial sound directions were situated on the horizontal plane (corresponding to variations in ITD, ILD, and spectral cues) or the midsagittal plane (variation of spectral cues only). An optimized chirp was used which had proven to be advantageous over the click since it compensates for basilar membrane dispersion. ABRs and MLRs were recorded from 32 scalp electrodes and both binaural potentials (B) and binaural difference potentials (BD, i.e., the difference between binaural and summed monaural responses) were investigated. The amplitudes of B and BD to spatial stimuli were not higher than those to the diotic reference. ABR amplitudes decreased and latencies increased with increasing laterality of the sound source. A rotating dipole source exhibited characteristic patterns in dependence on the stimulus laterality. For the MLR data, stimulus laterality was reflected in the latency of component N(a). In addition, dipole source analysis revealed a systematic magnitude increase for the dipole contralateral to the azimuthal position of the sound source. For the variation of elevation, the right dipole source showed a stronger activation for stimuli away from the horizontal plane. The results indicate that at the level of the brainstem and primary auditory cortex binaural interaction is mostly affected by interaural cues (ITD, ILD). Potentials evoked by stimuli with natural combinations of ITD, ILD, and spectral cues were not larger than those elicited by diotic chirps.

Interaural delay-dependent changes in the binaural difference potential of the human auditory brain stem response.

Binaural difference potentials (BDs) are thought to be generated by neural units in the brain stem responding specifically to binaural stimulation. They are computed by subtracting the sum of monaural responses from the binaural response, BD = B - (L + R). BDs in dependency on the interaural time difference (ITD) have been measured and compared to the Jeffress model in a number of studies with conflicting results. The classical Jeffress model assuming binaural coincidence detector cells innervated by bilateral excitatory cells via two delay lines predicts a BD latency increase of ITD/2. A modification of the model using only a single delay line as found in birds yields a BD latency increase of ITD. The objective of this study is to measure BDs with a high signal-to-noise ratio for a large range of ITDs and to compare the data with the predictions of some models in the literature including that of Jeffress. Chirp evoked BDs were recorded for 17 ITDs in the range from 0 to 2 ms at a level of 40 dB nHL for four channels (A1, A2, PO9, PO10) from 11 normal hearing subjects. For each binaural condition 10,000 epochs were collected while 40,000 epochs were recorded for each of the two monaural conditions. Significant BD components are observed for ITDs up to 2 ms. The peak-to-peak amplitude of the first components of the BD, DP1-DN1, is monotonically decreasing with ITD. This is in contrast with click studies which reported a constant BD-amplitude for ITDs up to 1 ms. The latency of the BD-component DN1 is monotonically, but nonlinearly increasing with ITD. In the current study, DN1 latency is found to increase faster than ITD/2 but slower than ITD incompatible with either variant of the Jeffress model. To describe BD waveforms, the computational model proposed by Ungan et al. [Hearing Research 106, 66-82, 1997] using ipsilateral excitatory and contralateral inhibitory inputs to the binaural cells was implemented with only four parameters and successfully fitted to the BD data. Despite its simplicity the model predicts features which can be physiologically tested: the inhibitory input must arrive slightly before the excitatory input, and the duration of the inhibition must be considerably longer than the standard deviations of excitatory and inhibitory arrival times to the binaural cells. With these characteristics, the model can accurately describe BD amplitude and latency as a function of the ITD.

Neural correlates of the precedence effect in auditory evoked potentials.

The precedence effect in subjective localization tasks reflects the dominance of directional information of a direct sound (lead) over the information provided by one or several reflections (lags) for short delays. By collecting data of both psychoacoustical measurements and auditory evoked potentials the current study aims at neurophysiological correlates for the precedence effect in humans. In order to investigate whether the stimulus features or the perception of the stimulus is reflected on the ascending stages of the human auditory pathway, auditory brainstem responses (ABRs) as well as cortical auditory evoked potentials (CAEPs) using double click-pairs were recorded. Potentials were related to the results of the psychoacoustical data. ABRs to double click-pairs with lead-lag delays from 0 to 20 ms and interaural time differences (ITDs) in the lag click of 0 and 300 micros show an emerging second wave V for lead-lag delays larger than 2 ms. The amplitudes of the first and second wave V are the same for a lead-lag delay of about 5 ms. For the lag-ITD stimuli the latency of the second wave V was prolonged by approximately ITD/2 compared to the stimuli without lag-ITD. As the amplitudes of the second wave V were not decreased for a lead-lag delay around 5 ms as could be expected from psychoacoustical measurements of the precedence effect, ABRs reflect stimulus features rather than the perceptive qualities of the stimulus. The mismatch negativity (MMN) component of the CAEP for double click-pairs was determined using a diotic standard and a deviant with an ITD of 800 micros in the lag click. The comparison between the MMN components and the psychoacoustical data shows that the MMN is related to the perception of the stimulus, i.e., to the precedence effect. Generally, the findings of the present study suggest that the precedence effect is not a result of a poor sensitivity of the peripheral bottom-up processing. Rather, the precedence effect seems to be reflected by the MMN, i.e., cognitive processes on higher stages of the auditory pathway.

Dipole source analysis of auditory brain stem responses evoked by lateralized clicks.

The objective of this paper was to elucidate the relation between psychophysical lateralization and the neural generators of the corresponding auditory evoked potentials. Auditory brain stem responses to binaural click stimuli with different interaural time- and level differences were obtained in 12 subjects by means of multi-channel EEG recording. Data were modeled by equivalent current dipoles representing the generating sources in the brain. A generalized maximum-likelihood method was used to solve the inverse problem, taking into account the noise covariance matrix of the data. The quality of the fit was assessed by computing the goodness-of-fit as the outcome of a chi 2-test. This measure was advantageous compared to the conventionally employed residual variance. At the latency of Jewett wave V, there was a systematic variation of the moment of a rotating dipole with the lateralization of the stimulus. Dipole moment trajectories of stimuli with similar lateralization were similar. A sign reversal of the interaural differences resulted in a mirrored trajectory. Centrally-perceived stimuli corresponded to dipoles with the largest vertical components. With increasing lateralization, the vertical component of the moment decreased, while the horizontal components increased. The similarity of trajectories inducted by the same lateralization show that interaural time- and level differences are not processed independently. The present data support the notion that directional information is already extracted and represented at the level of the brain stem.

Comparison of binaural auditory brainstem responses and the binaural difference potential evoked by chirps and clicks.

Rising chirps that compensate for the dispersion of the travelling wave on the basilar membrane evoke larger monaural brainstem responses than clicks. In order to test if a similar effect applies for the early processing stages of binaural information, monaurally and binaurally evoked auditory brainstem responses were recorded for clicks and chirps for levels from 10 to 60 dB nHL in steps of 10 dB. Ten thousand sweeps were collected for every stimulus condition from 10 normal hearing subjects. Wave V amplitudes are significantly larger for chirps than for clicks for all conditions. The amplitude of the binaural difference potential, DP1-DN1, is significantly larger for chirps at the levels 30 and 40 dB nHL. Both the binaurally evoked potential and the binaural difference potential exhibit steeper growth functions for chirps than for clicks for levels up to 40 dB nHL. For higher stimulation levels the chirp responses saturate approaching the click evoked amplitude. For both stimuli the latency of DP1 is shorter than the latency of the binaural wave V, which in turn is shorter than the latency of DN1. The amplitude ratio of the binaural difference potential to the binaural response is independent of stimulus level for clicks and chirps. A possible interpretation is that with click stimulation predominantly binaural interaction from high frequency regions is seen which is compatible with a processing by contralateral inhibitory and ipsilateral excitatory (IE) cells. Contributions from low frequencies are negligible since the responses from low frequencies are not synchronized for clicks. The improved synchronization at lower frequencies using chirp stimuli yields contributions from both low and high frequency neurons enlarging the amplitudes of the binaural responses as well as the binaural difference potential. Since the constant amplitude ratio of the binaural difference potential to the binaural response makes contralateral and ipsilateral excitatory interaction improbable, binaural interaction at low frequencies is presumably also of the IE type. Another conclusion of this study is that the chirp stimuli employed here are better suited for auditory brainstem responses and binaural difference potentials than click stimuli since they exhibit higher amplitudes and a better signal-to-noise ratio.

Auditory brain stem responses evoked by lateralized clicks: is lateralization extracted in the human brain stem?

The dependence of binaurally evoked auditory brain stem responses and the binaural difference potential on simultaneously presented interaural time and level differences is investigated in order to assess the representation of stimulus lateralization in the brain stem. Auditory brain stem responses to binaural click stimuli with all combinations of three interaural time and three interaural level differences were recorded from 12 subjects and 4 channels. The latency of Jewett wave V is shortest for zero interaural time difference and longest for the trading stimuli. The amplitude of wave V is largest for centrally perceived stimuli, i.e., the diotic and trading stimuli, and smallest for the most laterally perceived stimuli. The latency of the most prominent peak of the binaural difference potential DN1 mainly depends on the interaural time difference. The amplitude of the components of the binaural difference potential, DP1-DN1, depends similarly on stimulus conditions as wave V amplitude in the case of the binaural stimuli: smallest amplitudes are found for the most lateral stimuli and largest amplitudes for central stimuli. The results demonstrate that interaural level and time differences are not processed independently. This supports the hypothesis that directional information in humans is already extracted and represented at the level of the brain stem.