Functional neuroimaging in hearing research and audiology.

The various methods of medical imaging are essential for many diagnostic issues in clinical routine, e.g., for the diagnostics and localisation of tumorous diseases, or for the clarification of other lesions in the central nervous system. In addition to these classical roles both positron emission tomography (PET) and magnetic resonance imaging (MRI) allow for the investigation of functional processes in the human brain, when used in a specific way. The last 25 years have seen great progress, especially with respect to functional MRI, in terms of the available experimental paradigms as well as the data analysis strategies, so that a directed investigation of neurophysiological correlates of psychoacoustic performance is possible. This covers fundamental measures of sound perception like loudness and pitch, specific audiological symptoms like tinnitus, which often accompanies hearing disorders, but it also includes experiments on speech perception or on virtual acoustic environments. One important aspect common to many auditory neuroimaging studies is the central question at what stage in the human auditory pathway the sensory coding of the incoming sound is transformed into a universal and context-dependent perceptual representation, which is the basis for what we hear. This overview summarises findings from the literature as well as a few studies from our lab, to discuss the possibilities and the limits of the adoption of functional neuroimaging methods in audiology. Up to this stage, most auditory neuroimaging studies have investigated basic processes in normal hearing listeners. However, the hitherto existing results suggest that the methods of auditory functional neuroimaging - possibly complemented by electrophysiological methods like EEG and MEG - have a great potential to contribute to a deeper understanding of the processes and the impact of hearing disorders.

Contextual effects on loudness judgments for sounds with continuous changes of intensity are reflected in nonauditory areas.

Psychoacoustic research suggests that judgments of perceived loudness change differ significantly between sounds with continuous increases and decreases of acoustic intensity, often referred to as "up-ramps" and "down-ramps." The magnitude and direction of this difference, in turn, appears to depend on focused attention and the specific task performed by the listeners. This has led to the suspicion that cognitive processes play an important role in the development of the observed context effects. The present study addressed this issue by exploring neural correlates of context-dependent loudness judgments. Normal hearing listeners continuously judged the loudness of complex-tone sequences which slowly changed in level over time while auditory fMRI was performed. Regression models that included information either about presented sound levels or about individual loudness judgments were used to predict activation throughout the brain. Our psychoacoustical data confirmed robust effects of the direction of intensity change on loudness judgments. Specifically, stimuli were judged softer when following a down-ramp, and louder in the context of an up-ramp. Levels and loudness estimates significantly predicted activation in several brain areas, including auditory cortex. However, only activation in nonauditory regions was more accurately predicted by context-dependent loudness estimates as compared with sound levels, particularly in the orbitofrontal cortex and medial temporal areas. These findings support the idea that cognitive aspects contribute to the generation of context effects with respect to continuous loudness judgments.

Activation in human auditory cortex in relation to the loudness and unpleasantness of low-frequency and infrasound stimuli.

Low frequency noise (LFS) and infrasound (IS) are controversially discussed as potential causes of annoyance and distress experienced by many people. However, the perception mechanisms for IS in the human auditory system are not completely understood yet. In the present study, sinusoids at 32 Hz (at the lower limit of melodic pitch for tonal stimulation), as well as 8 Hz (IS range) were presented to a group of 20 normal hearing subjects, using monaural stimulation via a loudspeaker sound source coupled to the ear canal by a long silicone rubber tube. Each participant attended two experimental sessions. In the first session, participants performed a categorical loudness scaling procedure as well as an unpleasantness rating task in a sound booth. In the second session, the loudness scaling procedure was repeated while brain activation was measured using functional magnetic resonance imaging (fMRI). Subsequently, activation data were collected for the respective stimuli presented at fixed levels adjusted to the individual loudness judgments. Silent trials were included as a baseline condition. Our results indicate that the brain regions involved in processing LFS and IS are similar to those for sounds in the typical audio frequency range, i.e., mainly primary and secondary auditory cortex (AC). In spite of large variation across listeners with respect to judgments of loudness and unpleasantness, neural correlates of these interindividual differences could not yet be identified. Still, for individual listeners, fMRI activation in the AC was more closely related to individual perception than to the physical stimulus level.

Searchlight Classification Informative Region Mixture Model (SCIM): Identification of Cortical Regions Showing Discriminable BOLD Patterns in Event-Related Auditory fMRI Data.

The investigation of abstract cognitive tasks, e.g., semantic processing of speech, requires the simultaneous use of a carefully selected stimulus design and sensitive tools for the analysis of corresponding neural activity that are comparable across different studies investigating similar research questions. Multi-voxel pattern analysis (MVPA) methods are commonly used in neuroimaging to investigate BOLD responses corresponding to neural activation associated with specific cognitive tasks. Regions of significant activation are identified by a thresholding operation during multivariate pattern analysis, the results of which are susceptible to the applied threshold value. Investigation of analysis approaches that are robust to a large extent with respect to thresholding, is thus an important goal pursued here. The present paper contributes a novel statistical analysis method for fMRI experiments, searchlight classification informative region mixture model (SCIM), that is based on the assumption that the whole brain volume can be subdivided into two groups of voxels: spatial voxel positions around which recorded BOLD activity does convey information about the present stimulus condition and those that do not. A generative statistical model is proposed that assigns a probability of being informative to each position in the brain, based on a combination of a support vector machine searchlight analysis and Gaussian mixture models. Results from an auditory fMRI study investigating cortical regions that are engaged in the semantic processing of speech indicate that the SCIM method identifies physiologically plausible brain regions as informative, similar to those from two standard methods as reference that we compare to, with two important differences. SCIM-identified regions are very robust to the choice of the threshold for significance, i.e., less "noisy," in contrast to, e.g., the binomial test whose results in the present experiment are highly dependent on the chosen significance threshold or random permutation tests that are additionally bound to very high computational costs. In group analyses, the SCIM method identifies a physiologically plausible pre-frontal region, anterior cingulate sulcus, to be involved in semantic processing that other methods succeed to identify only in single subject analyses.

Deductive development and validation of a questionnaire to assess sensitivity to very low and very high frequency sounds: SISUS-Q (Sensitivity to Infra-Sound and Ultra-Sound Questionnaire).

OBJECTIVE: Auditory research and complaints about environmental noise indicate that there exists a significant, small subgroup within the population which is sensitive towards infra- and low-frequency or ultra- and high-frequency sounds (ILF/UHF). This paper reports on the development, factorization and validation of measures of sensitivity towards frequencies outside the common hearing range. DESIGN: A multinational, cross-sectional survey study was run. Principal component analyses and exploratory factor analyses were conducted in a sample of 267 Europeans (from the UK, Slovenia, and Germany). RESULTS: The factor analyses suggested that ILF versus UHF sensitivity constitute different factors, each characterized by sensory perception, stress-responsivity, and behavioral avoidance. A third factor comprising beliefs of dangerousness of ILF and UHF emerged. The factors explained 72% of the variance. The factor-solution was replicated separately for the English (n = 98) and German (n = 169) versions of the questionnaire (Slovenians and UK residents filled out the English version). Acceptable to excellent reliability was found. ILF and UHF sensitivity were moderately related to noise sensitivity in the normal hearing range, suggesting the new measures are not redundant. Correlations with psychiatric and somatic symptoms were small to moderate. ILF sensitivity correlated with neuroticism (small effect) and daytime sleepiness (moderate effect). ILF and UHF sensitivity were related to agreeableness (small effects). Overall, the novel ILF and UHF sensitivity scales seems to provide a solid tool for conducting further research on the role of sensitivity concerning adverse effects of ILF and UHF sound (e.g. health outcomes, annoyance ratings). The questionnaire consortium recommends using the new scales in combination with established measures of normal hearing range sensitivity.

The representation of level and loudness in the central auditory system for unilateral stimulation.

Loudness is the perceptual correlate of the physical intensity of a sound. However, loudness judgments depend on a variety of other variables and can vary considerably between individual listeners. While functional magnetic resonance imaging (fMRI) has been extensively used to characterize the neural representation of physical sound intensity in the human auditory system, only few studies have also investigated brain activity in relation to individual loudness. The physiological correlate of loudness perception is not yet fully understood. The present study systematically explored the interrelation of sound pressure level, ear of entry, individual loudness judgments, and fMRI activation along different stages of the central auditory system and across hemispheres for a group of normal hearing listeners. 4-kHz-bandpass filtered noise stimuli were presented monaurally to each ear at levels from 37 to 97dB SPL. One diotic condition and a silence condition were included as control conditions. The participants completed a categorical loudness scaling procedure with similar stimuli before auditory fMRI was performed. The relationship between brain activity, as inferred from blood oxygenation level dependent (BOLD) contrasts, and both sound level and loudness estimates were analyzed by means of functional activation maps and linear mixed effects models for various anatomically defined regions of interest in the ascending auditory pathway and in the cortex. Our findings are overall in line with the notion that fMRI activation in several regions within auditory cortex as well as in certain stages of the ascending auditory pathway might be more a direct linear reflection of perceived loudness rather than of sound pressure level. The results indicate distinct functional differences between midbrain and cortical areas as well as between specific regions within auditory cortex, suggesting a systematic hierarchy in terms of lateralization and the representation of level and loudness.1.

Auditory fMRI of Sound Intensity and Loudness for Unilateral Stimulation.

We report a systematic exploration of the interrelation of sound intensity, ear of entry, individual loudness judgments, and brain activity across hemispheres, using auditory functional magnetic resonance imaging (fMRI). The stimuli employed were 4 kHz-bandpass filtered noise stimuli, presented monaurally to each ear at levels from 37 to 97 dB SPL. One diotic condition and a silence condition were included as control conditions. Normal hearing listeners completed a categorical loudness scaling procedure with similar stimuli before auditory fMRI was performed. The relationship between brain activity, as inferred from blood oxygenation level dependent (BOLD) contrasts, and both sound intensity and loudness estimates were analyzed by means of linear mixed effects models for various anatomically defined regions of interest in the ascending auditory pathway and in the cortex. The results indicate distinct functional differences between midbrain and cortical areas as well as between specific regions within auditory cortex, suggesting a systematic hierarchy in terms of lateralization and the representation of sensory stimulation and perception.

Locating Melody Processing Activity in Auditory Cortex with Magnetoencephalography.

This paper describes a technique for isolating the brain activity associated with melodic pitch processing. The magnetoencephalograhic (MEG) response to a four note, diatonic melody built of French horn notes, is contrasted with the response to a control sequence containing four identical, "tonic" notes. The transient response (TR) to the first note of each bar is dominated by energy-onset activity; the melody processing is observed by contrasting the TRs to the remaining melodic and tonic notes of the bar (2-4). They have uniform shape within a tonic or melodic sequence which makes it possible to fit a 4-dipole model and show that there are two sources in each hemisphere--a melody source in the anterior part of Heschl's gyrus (HG) and an onset source about 10 mm posterior to it, in planum temporale (PT). The N1m to the initial note has a short latency and the same magnitude for the tonic and the melodic sequences. The melody activity is distinguished by the relative sizes of the N1m and P2m components of the TRs to notes 2-4. In the anterior source a given note elicits a much larger N1m-P2m complex with a shorter latency when it is part of a melodic sequence. This study shows how to isolate the N1m, energy-onset response in PT, and produce a clean melody response in the anterior part of auditory cortex (HG).

Auditory functional magnetic resonance imaging in dogs--normalization and group analysis and the processing of pitch in the canine auditory pathways.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is an advanced and frequently used technique for studying brain functions in humans and increasingly so in animals. A key element of analyzing fMRI data is group analysis, for which valid spatial normalization is a prerequisite. In the current study we applied normalization and group analysis to a dataset from an auditory functional MRI experiment in anesthetized beagles. The stimulation paradigm used in the experiment was composed of simple Gaussian noise and regular interval sounds (RIS), which included a periodicity pitch as an additional sound feature. The results from the performed group analysis were compared with those from single animal analysis. In addition to this, the data were examined for brain regions showing an increased activation associated with the perception of pitch. RESULTS: With the group analysis, significant activations matching the position of the right superior olivary nucleus, lateral lemniscus and internal capsule were identified, which could not be detected in the single animal analysis. In addition, a large cluster of activated voxels in the auditory cortex was found. The contrast of the RIS condition (including pitch) with Gaussian noise (no pitch) showed a significant effect in a region matching the location of the left medial geniculate nucleus. CONCLUSION: By using group analysis additional activated areas along the canine auditory pathways could be identified in comparison to single animal analysis. It was possible to demonstrate a pitch-specific effect, indicating that group analysis is a suitable method for improving the results of auditory fMRI studies in dogs and extending our knowledge of canine neuroanatomy.

Pure word deafness with auditory object agnosia after bilateral lesion of the superior temporal sulcus.

Based on results from functional imaging, cortex along the superior temporal sulcus (STS) has been suggested to subserve phoneme and pre-lexical speech perception. For vowel classification, both superior temporal plane (STP) and STS areas have been suggested relevant. Lesion of bilateral STS may conversely be expected to cause pure word deafness and possibly also impaired vowel classification. Here we studied a patient with bilateral STS lesions caused by ischemic strokes and relatively intact medial STPs to characterize the behavioral consequences of STS loss. The patient showed severe deficits in auditory speech perception, whereas his speech production was fluent and communication by written speech was grossly intact. Auditory-evoked fields in the STP were within normal limits on both sides, suggesting that major parts of the auditory cortex were functionally intact. Further studies showed that the patient had normal hearing thresholds and only mild disability in tests for telencephalic hearing disorder. Prominent deficits were discovered in an auditory-object classification task, where the patient performed four standard deviations below the control group. In marked contrast, performance in a vowel-classification task was intact. Auditory evoked fields showed enhanced responses for vowels compared to matched non-vowels within normal limits. Our results are consistent with the notion that cortex along STS is important for auditory speech perception, although it does not appear to be entirely speech specific. Formant analysis and single vowel classification, however, appear to be already implemented in auditory cortex on the STP.

Human auditory neuroimaging of intensity and loudness.

The physical intensity of a sound, usually expressed in dB on a logarithmic ratio scale, can easily be measured using technical equipment. Loudness is the perceptual correlate of sound intensity, and is usually determined by means of some sort of psychophysical scaling procedure. The interrelation of sound intensity and perceived loudness is still a matter of debate, and the physiological correlate of loudness perception in the human auditory pathway is not completely understood. Various studies indicate that the activation in human auditory cortex is more a representation of loudness sensation rather than of physical sound pressure level. This raises the questions (1), at what stage or stages in the ascending auditory pathway is the transformation of the physical stimulus into its perceptual correlate completed, and (2), to what extent other factors affecting individual loudness judgements might modulate the brain activation as registered by auditory neuroimaging. An overview is given about recent studies on the effects of sound intensity, duration, bandwidth and individual hearing status on the activation in the human auditory system, as measured by various approaches in auditory neuroimaging. This article is part of a Special Issue entitled Human Auditory Neuroimaging.

Functional magnetic resonance imaging of the ascending stages of the auditory system in dogs.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is a technique able to localize neural activity in the brain by detecting associated changes in blood flow. It is an essential tool for studying human functional neuroanatomy including the auditory system. There are only a few studies, however, using fMRI to study canine brain functions. In the current study ten anesthetized dogs were scanned during auditory stimulation. Two functional sequences, each in combination with a suitable stimulation paradigm, were used in each subject. Sequence 1 provided periods of silence during which acoustic stimuli could be presented unmasked by scanner noise (sparse temporal sampling) whereas in sequence 2 the scanner noise was present throughout the entire session (continuous imaging). The results obtained with the two different functional sequences were compared. RESULTS: This study shows that with the proper experimental setup it is possible to detect neural activity in the auditory system of dogs. In contrast to human fMRI studies the strongest activity was found in the subcortical parts of the auditory pathways. Especially sequence 1 showed a high reliability in detecting activated voxels in brain regions associated with the auditory system. CONCLUSION: These results indicate that fMRI is applicable for studying the canine auditory system and could become an additional method for the clinical evaluation of the auditory function of dogs. Additionally, fMRI is an interesting technique for future studies concerned with canine functional neuroanatomy.

Pitch-induced responses in the right auditory cortex correlate with musical ability in normal listeners.

Previous work compellingly shows the existence of functional and structural differences in human auditory cortex related to superior musical abilities observed in professional musicians. In this study, we investigated the relationship between musical abilities and auditory cortex activity in normal listeners who had not received a professional musical education. We used functional MRI to measure auditory cortex responses related to auditory stimulation per se and the processing of pitch and pitch changes, which represents a prerequisite for the perception of musical sequences. Pitch-evoked responses in the right lateral portion of Heschl's gyrus were correlated positively with the listeners' musical abilities, which were assessed using a musical aptitude test. In contrast, no significant relationship was found for noise stimuli, lacking any musical information, and for responses induced by pitch changes. Our results suggest that superior musical abilities in normal listeners are reflected by enhanced neural encoding of pitch information in the auditory system.

Cortical representation of the combination of monaural and binaural unmasking.

The audibility of a target tone is improved by introducing either -amplitude modulations that are coherent across different frequency channels of the masker (comodulation masking release, CMR) or interaural phase differences that are -different for target and masker (binaural masking-level difference, BMLD). Although the two effects are likely to be based on different processing strategies, they both result in improved figure-background decomposition for a target-in-noise situation. In this study, we analyzed the combination of CMR and BMLD for a -target tone in a masker with six 48-Hz-wide noise bands, distributed over a wide frequency range from 216 Hz to 2.78 kHz. Psychoacoustical detection thresholds for the tones in noise were determined for two masker conditions (comodulated or unmodulated bands) and two interaural phase differences of the target tone (0 or 180°). The mean results indicate that the effects of unmasking add independently. The lowest thresholds are found for the dichotic signal embedded in a -modulated masker with an overall threshold difference of about 16 dB compared to the -unmodulated condition with no binaural cues. Based on the psychoacoustic results, a set of 12 signal-masker configurations was selected individually to explore the representation of the audibility of the test tone in brain activation maps by means of auditory functional MR imaging. The comparison of the results for the combination of CMR and BMLD with the results for the separate effects indicates a large overlap of the activated brain regions, where a largely extended area is activated, covering primary auditory cortex and adjacent regions. The result is in agreement with previous fMRI studies on auditory masking, identifying specific regions in the auditory cortex representing a change of the audibility of a target tone in a noise masker, irrespective of the overall sound pressure level of the stimulus.

Neural coding of sound intensity and loudness in the human auditory system.

Inter-individual differences in loudness sensation of 45 young normal-hearing participants were employed to investigate how and at what stage of the auditory pathway perceived loudness, the perceptual correlate of sound intensity, is transformed into neural activation. Loudness sensation was assessed by categorical loudness scaling, a psychoacoustical scaling procedure, whereas neural activation in the auditory cortex, inferior colliculi, and medial geniculate bodies was investigated with functional magnetic resonance imaging (fMRI). We observed an almost linear increase of perceived loudness and percent signal change from baseline (PSC) in all examined stages of the upper auditory pathway. Across individuals, the slope of the underlying growth function for perceived loudness was significantly correlated with the slope of the growth function for the PSC in the auditory cortex, but not in subcortical structures. In conclusion, the fMRI correlate of neural activity in the auditory cortex as measured by the blood oxygen level-dependent effect appears to be more a linear reflection of subjective loudness sensation rather than a display of physical sound pressure level, as measured using a sound-level meter.

Sustained responses for pitch and vowels map to similar sites in human auditory cortex.

Several studies have shown enhancement of auditory evoked sustained responses for periodic over non-periodic sounds and for vowels over non-vowels. Here, we directly compared pitch and vowels using synthesized speech with a "damped" amplitude modulation. These stimuli were parametrically varied to yield four classes of matched stimuli: (1) periodic vowels (2) non-periodic vowels, (3) periodic non-vowels, and (4) non-periodic non-vowels. 12 listeners were studied with combined MEG and EEG. Sustained responses were reliably enhanced for vowels and periodicity. Dipole source analysis revealed that a vowel contrast (vowel-non-vowel) and the periodicity-pitch contrast (periodic-non-periodic) mapped to the same site in antero-lateral Heschl's gyrus. In contrast, the non-periodic, non-vowel condition mapped to a more medial and posterior site. The sustained enhancement for vowels was significantly more prominent when the vowel identity was varied, compared to a condition where only one vowel was repeated, indicating selective adaptation of the response. These results render it unlikely that there are spatially distinct fields for vowel and pitch processing in the auditory cortex. However, the common processing of vowels and pitch raises the possibility that there is an early speech-specific field in Heschl's gyrus.

Spectral loudness summation takes place in the primary auditory cortex.

Auditory functional magnetic resonance imaging (fMRI) was used to assess neural activation in the human auditory brainstem (AB) and cortex (AC) as a function of bandwidth (BW). We recorded brain activation of 22 normal hearing listeners induced by band pass filtered pink noise stimuli with equal sound pressure level of 70 dB SPL. Tested bandwidths were 50, 500, 1,500, 3,000, 6,000, and 8,000 Hz. The center frequency was 4,000 Hz. Categorical loudness scaling had been performed in a silent booth with all of these stimuli. Loudness as a function of bandwidth followed a concave-shaped curve which reflected the influence of spectral loudness summation (SLS) for higher BW and the influence of large amplitude fluctuations for very low BW, which itself could be explained by peak-listening. While neural activation of the AB, as measured by the percent signal change from baseline (PSC), was tuned to the physical BW of the stimuli in a straight linear fashion, the trend of perceived loudness as a function of BW was reflected in several aspects by corresponding neural activation in the primary auditory cortex (PAC). Finally, from the absolute differences of the PSC between PAC and AB, gains in perceived loudness associated with SLS and the effect of large amplitude fluctuations could be predicted with an accuracy of 1-2 dB for the whole group of participants.

An auditory fMRI correlate of impulsivity.

Impulsivity and serotonergic neurotransmission have previously been shown to be linked to the intensity dependence of auditory evoked potentials. The present study investigates whether impulsivity in normal healthy subjects has a similar influence on the neuronal correlates of the coding of sound intensity using functional magnetic resonance imaging (fMRI). Forty-four participants completed Cloninger's Tridimensional Personality Questionnaire (TPQ). The dependence of fMRI activation on sound intensity was examined using continuous pink noise with varying intensity as acoustic stimuli. Imaging data were analyzed for the volume of activation sensitive to sound intensity. Impulsivity has a significant effect on the volume of activation sensitive to sound intensity. Persons with high impulsivity scores on the TPQ scale show approximately twice the volume of activation when compared with persons with low impulsivity scores. The neuronal correlate of impulsivity as revealed by fMRI gives strong evidence of a link between impulsive behavior and neural activity evoked by auditory stimulation. This link may prove useful for measuring central serotonergic neurotransmission in a clinical setting.

Dichotic pitch activates pitch processing centre in Heschl's gyrus.

Although several neuroimaging studies have reported pitch-evoked activations at the lateral end of Heschl's gyrus, it is still under debate whether these findings truly represent activity in relation to the perception of pitch or merely stimulus-related features of pitch-evoking sounds. We investigated this issue in a functional magnetic resonance imaging (fMRI) experiment using pure tones in noise and dichotic pitch sequences, which either contained a melody or a fixed pitch. Dichotic pitch evokes a sensation of pitch only in binaural listening conditions, while the monaural signal cannot be distinguished from random noise. Our data show similar neural activations for both tones in noise and dichotic pitch, which are perceptually similar, but physically different. Pitch-related activation was found at the lateral end of Heschl's gyrus in both hemispheres, providing new evidence for a general involvement of this region in pitch processing. In line with prior studies, we found melody-related activation in Planum temporale and Planum polare, but not in primary auditory areas. These results support the view of a general representation of pitch in auditory cortex, irrespective of the physical attributes of the pitch-evoking sound.

Cortical representation of release from auditory masking.

The aim of the present study was to find a functional MRI correlate in human auditory cortex of the psychoacoustical effect of release from masking, using amplitude-modulated noise stimuli. A sinusoidal target signal was embedded in a band-limited white noise, which was either unmodulated or (co)modulated. Psychoacoustical thresholds were measured for the target signals in both types of masking noise, using an adaptive procedure. The mean threshold difference between the unmodulated and the comodulated condition, i.e., the release from masking, was 15 dB. The same listeners then participated in an fMRI experiment, recording activation of auditory cortex in response to tones in the presence of modulated and unmodulated noise maskers at five different signal-to-noise ratios. In general, a spatial dissociation of changes of overall level and signal-to-noise ratio in auditory cortex was found, replicating a previous fMRI study on pure-tone masking. The comparison of the fMRI activation maps for a signal presented in modulated and in unmodulated noise reveals that those regions in the antero-lateral part of Heschl's gyrus previously shown to represent the audibility of a tonal target (rather than overall level) exhibit a stronger activation for the modulated than for the unmodulated conditions. This result is interpreted as a physiological correlate of the psychoacoustical effect of comodulation masking release at the level of the auditory cortex.