Neural substrates of tinnitus in animal and human cortex : cortical correlates of tinnitus.

Animal models of tinnitus complement human findings and potentially deepen our insight into the neural substrates of tinnitus. The fact that animal data are largely based on recordings from the auditory system, in particular from subcortical structures, makes comparison with human electrophysiological data from predominantly cortical areas difficult. Electro/magnetoencephalography and imaging data extend beyond the auditory cortex. The most challenging link to be made is the one between the macroscopic data in humans and the microscopic (single neuron action potentials) and mesoscopic (local field potentials) results obtained in animal models. Since invasive recordings in humans are rare, a bridge needs to be built on the basis of changes in brain rhythms in animals with putative tinnitus.

Spontaneous firing rate changes in cat primary auditory cortex following long-term exposure to non-traumatic noise: tinnitus without hearing loss?

Changes of neural activity in animal models have been correlated with tinnitus in humans. For instance, increased spontaneous firing rates (SFR), increased spontaneous neural synchrony, and cortical tonotopic map reorganization may underlie this phantom auditory percept. The aim of this study is to quantify the changes in SFR activity in the cat primary auditory cortex, after long-term exposure to different types of non-traumatic acoustic environments. For that purpose, four different groups of adult cats were exposed to moderate-level (~70dB SPL), behaviorally irrelevant sounds for several weeks to months, and their SFRs were compared with those in control cats. The sounds consisted of random multi-frequency tone pip ensembles with various bandwidths (2-4kHz, 4-20kHz, and a pair of third-octave bands centered at 4 and 16kHz), as well as a "factory noise". Auditory brainstem response (ABR) thresholds, ABR wave 3 amplitudes at ~55 and 75dB SPL, and distortion product otoacoustic emission (DPOAE) amplitudes were unaffected by the exposure. However, we found that the SFR decreased within the exposure frequency range and increased outside the exposure range. This increased SFR for units with characteristic frequencies outside the exposure frequency range, which was slow to reverse after the exposure offset, suggests a mechanism for tinnitus in the absence of hearing loss.

Spectrotemporal receptive fields during spindling and non-spindling epochs in cat primary auditory cortex.

It was often thought that synchronized rhythmic epochs of spindle waves disconnect thalamo-cortical system from incoming sensory signals. The present study addresses this issue by simultaneous extracellular action potential and local field potential (LFP) recordings from primary auditory cortex of ketamine-anesthetized cats during spindling activity. We compared cortical spectrotemporal receptive fields (STRF) obtained during spindling and non-spindling epochs. The basic spectro-temporal parameters of "spindling" and "non-spindling" STRFs were similar. However, the peak-firing rate at the best frequency was significantly enhanced during spindling epochs. This enhancement was mainly caused by the increased probability of a stimulus to evoke spikes (effectiveness of stimuli) during spindling as compared with non-spindling epochs. Augmented LFPs associated with effective stimuli and increased single-unit pair correlations during spindling epochs suggested higher synchrony of thalamo-cortical inputs during spindling that resulted in increased effectiveness of stimuli presented during spindling activity. The neuronal firing rate, both stimulus-driven and spontaneous, was higher during spindling as compared with non-spindling epochs. Overall, our results suggests that thalamic cells during spindling respond to incoming stimuli-related inputs and, moreover, cause more powerful stimulus-related or spontaneous activation of the cortex.

Multi-frequency auditory stimulation disrupts spindling activity in anesthetized animals.

It is often implied that during the occurrence of spindle oscillations, thalamocortical neurons do not respond to signals from the outside world. Since recording of sound-evoked activity from cat auditory cortex is common during spindling this implies that sound stimulation changes the spindle-related brain state. Local field potentials and multi-unit activity recorded from cat primary auditory cortex under ketamine anesthesia during successive silence-stimulus-silence conditions were used to investigate the effect of sound on cortical spindle oscillations. Multi-frequency stimulation suppresses spindle waves, as shown by the decrease of spectral power within the spindle frequency range during stimulation as compared with the previous silent period. We show that the percentage suppression is independent of the power of the spindle waves during silence, and that the suppression of spindle power occurs very fast after stimulus onset. The global inter-spindle rhythm was not disturbed during stimulation. Spectrotemporal and correlation analysis revealed that beta waves (15-26 Hz), and to a lesser extent delta waves, were modulated by the same inter-spindle rhythm as spindle oscillations. The suppression of spindle power during stimulation had no effect on the spatial correlation of spindle waves. Firing rates increased under stimulation and spectro-temporal receptive fields could reliably be obtained. The possible mechanism of suppression of spindle waves is discussed and it is suggested that suppression likely occurs through activity of the specific auditory pathway.

Cortical tonotopic map reorganization and its implications for treatment of tinnitus.

CONCLUSION: There appears to be a definite link between reorganization of the cortical tonotopic map and increased spontaneous firing rates. The results have implications for the reduction of noise-induced hearing loss and in the prevention of noise-induced tinnitus in humans. OBJECTIVES: To review animal and human studies related to neural correlates of tinnitus. Among those are increased spontaneous firing rate, enhanced neural synchrony, and reorganization of the cortical frequency-place (tonotopic) map. MATERIALS AND METHODS: To separate these issues one would want to have a situation where hearing loss is present but without reorganization of the cortical frequency-place map. For that purpose, noise-exposed cats were placed, immediately after the trauma and for at least 3 weeks, either in a quiet or in a high-frequency or low-frequency enriched acoustic environment. RESULTS: In exposed cats that were placed in the quiet environment there was an increase in spontaneous firing rate and synchrony of neurons in primary auditory cortex. In contrast, exposed cats placed in the high-frequency-enriched acoustic environment did not show any significant difference in spontaneous firing rate or synchrony compared to the non-traumatized controls.

Neural correlates of an auditory afterimage in primary auditory cortex.

The Zwicker tone (ZT) is defined as an auditory negative afterimage, perceived after the presentation of an appropriate inducer. Typically, a notched noise (NN) with a notch width of 1/2 octave induces a ZT with a pitch falling in the frequency range of the notch. The aim of the present study was to find potential neural correlates of the ZT in the primary auditory cortex of ketamine-anesthetized cats. Responses of multiunits were recorded simultaneously with two 8-electrode arrays during 1 s and over 2 s after the presentation of a white noise (WN) and three NNs differing by the width of the notch, namely, 1/3 octave (NN1), 1/2 octave (NN2), and 2/3 octave (NN3). Both firing rate (FR) and peak cross-correlation coefficient (p) were evaluated for time windows of 500 ms. The cortical units were grouped according to whether their characteristic frequency (CF) was inside ("In" neurons) or outside ("Out" neurons) a 1-octave-wide frequency band centered on the notch center frequency. The ratios between the FRs and the rhos for each NN and the WN condition and for each group of neurons were then statistically evaluated. The ratios of FRs were significantly increased during and after the presentation of the NN for the "In" neurons. In contrast, the changes for the t" neurons were small and most often insignificant. The ratios of the p values differed significantly from 1 in the "In-In" and "In-Out" groups during stimulation as well as after it. We also found that the ps of "Out" neurons were dependent on the type of NN. Potentially, a combination of increased p and increased FR might be a neurophysiological correlate of the ZT.

Changes in spontaneous neural activity immediately after an acoustic trauma: implications for neural correlates of tinnitus.

Changes in spontaneous activity, recorded over 15-min periods before, immediately after and within hours after an acute acoustic trauma, were studied in primary auditory cortex of ketamine-anesthetized cats. We focused on the spontaneous firing rate (SFR), the peak cross-correlation coefficient (rho) and burst-firing activity. Multi-units (MUs) were grouped according to characteristic frequency (CF): MUs with a CF below the trauma-tone frequency (TF) were labeled as Be, those with a CF within 1 octave above the TF were labeled as Ab1 and those with a CF more than 1 octave above the TF were labeled as Ab2. Immediately after the trauma, the SFR was not significantly changed. The percentage of time that neurons were bursting, the mean burst duration, the number of spikes per burst and the mean inter-spike interval in a burst were enhanced. rho was locally increased in the Ab1-Ab2 and Ab2-Ab2 groups. A few hours post trauma, the SFR was increased in the Be and Ab2 groups, whereas burst-firing returned to pre-exposure levels. Moreover, rho was elevated in the Be-Ab2, Ab1-Ab2 and Ab2-Ab2 groups; this increase was significantly correlated to the changes in SFR. The results are discussed in the context of a neural correlate of tinnitus.

Between sound and perception: reviewing the search for a neural code.

This review investigates the roles of representation, transformation and coding as part of a hierarchical process between sound and perception. This is followed by a survey of how speech sounds and elements thereof are represented in the activity patterns along the auditory pathway. Then the evidence for a place representation of texture features of sound, comprising frequency, periodicity pitch, harmonicity in vowels, and direction and speed of frequency modulation, and for a temporal and synchrony representation of sound contours, comprising onsets, offsets, voice onset time, and low rate amplitude modulation, in auditory cortex is reviewed. Contours mark changes and transitions in sound and auditory cortex appears particularly sensitive to these dynamic aspects of sound. Texture determines which neurons, both cortical and subcortical, are activated by the sound whereas the contours modulate the activity of those neurons. Because contours are temporally represented in the majority of neurons activated by the texture aspects of sound, each of these neurons is part of an ensemble formed by the combination of contour and texture sensitivity. A multiplexed coding of complex sound is proposed whereby the contours set up widespread synchrony across those neurons in all auditory cortical areas that are activated by the texture of sound.

Spontaneous burst-firing in three auditory cortical fields: its relation to local field potentials and its effect on inter-area cross-correlations.

Burst-firing refers to epochs of sharply elevated neural discharge. It has been suggested that correlated firing in different cortical areas in anesthetized animals results from spontaneous burst-firing related to electroencephalogram spindling activity and state of drowsiness. To investigate this, simultaneous recordings of spontaneous firings of neurons in the primary (AI), secondary (AII) and anterior (AAF) fields of the auditory cortex in the lightly anaesthetized cat were obtained. This allowed a study of bursting behavior in the three cortical areas under exactly the same anesthetic state. Burst occurrences were detected using the Poisson-surprise method, and were typically highly synchronized with local field potentials (LFPs) and with burst-firing of other neurons recorded on the same electrode. Burst-firing occurred in 85% of 371 units studied, and in 48 (15%) thereof there were at least 100 bursts per 15 min. Neurons in Al were bursting at a significantly higher rate, but with fewer spikes per burst, than units in AII. The average percentage of the time that a spontaneously firing neuron is in the bursting state is only about 3% (range 0.004, 29%). The average peak cross-correlation coefficients between spikes and LFP triggers were largest for burst-onset spikes, followed by those between all burst spikes and LFP triggers, and smallest when all spikes of the single unit were used in the correlation. This was the case for within- and between-area conditions. Burst-onset times in different auditory fields were not correlated. Thus, the major cause of the observed correlation of spontaneous firing in different cortical areas is not synchronous burst-firing.

Of kittens and kids: altered cortical maturation following profound deafness and cochlear implant use.

Profoundly deaf children who use a cochlear implant (CI) provide a unique opportunity to investigate the effects of auditory sensory deprivation on the maturing human central nervous system. Previous results suggest that children fitted with a CI show evidence of altered auditory cortical maturation, based on evoked potentials. This altered maturation was characterized by both latency delays and morphological changes in the cortical auditory evoked potentials (AEPs). Based on prolonged P(1) latencies compared to age-matched normal-hearing (NH) peers, these data suggested a delayed maturation nearly equivalent to the period of deafness. However, rates of maturation for this AEP peak were essentially the same in NH and CI children. This suggests that, given enough time, the AEPs of CI children would assume the characteristic morphology found in older NH teens and NH adults. However, the data also indicated a substantial alteration of the typical set of obligatory P(1)-N(1b)-P(2) peaks, specifically related to the absence of the N(1) potential. Recent analyses of more extensive sets of longitudinal and cross-sectional data indicate that even after many years of implant use, the AEPs of CI users in their late teens remain very different from those of their NH peers. The P(1) peak latency remains prolonged and P(1) amplitude remains much larger in CI users than in age-matched NH teens. These findings suggested that age-related changes in the P(1) peak are completed by 12 years of age. In addition, the normal N(1b) peak fails to emerge in virtually all of the CI children tested in our laboratory. A major new interpretation of the abnormal maturation of AEP waveforms in CI children is presented. It is based on direct evidence showing that a persistent immaturity of the superficial layer axons has persistent negative effects on the generation of the N(1b) and, consequently, on the morphology of the AEPs. A comparison of scalp-recorded AEPs from implanted children with local field potentials measured from the cortical surface in deaf white kittens suggests the effects of deafness and CI use are similar across these mammalian species. For both species, a period of profound deafness followed by CI stimulation reveals a substantial immaturity in cortical activation even after a period of electrical stimulation by the CI.

Spontaneous firing activity of cortical neurons in adult cats with reorganized tonotopic map following pure-tone trauma.

We hypothesized that moderate sensorineural hearing loss resulting from acoustic trauma would cause (i) a change in the cortical tonotopic map, (ii) an increase in spontaneous activity in the reorganized region and (iii) increased inter-neuronal synchrony within the reorganized part of the cortex. Five kittens were exposed to a 126 dB sound pressure limit tone of 6 kHz for 1 h at both 5 and 6 weeks of age. Recordings were performed 7-16 weeks after the exposure. Auditory brainstem response thresholds for frequencies above 12 kHz were increased by 30 dB on average relative to those in normal cats. Tonotopic maps in the primary auditory cortex were reorganized in such a way that the area normally tuned to frequencies of 10-40 kHz was now entirely tuned to 10 kHz. Spontaneous firing rates were significantly higher in reorganized areas than in normal areas. In order to test for changes in inter-neuronal synchrony, cross-correlation analysis was done on 225 single-unit pairs recorded in the traumatized cats. For the single- and dual-electrode pairs there was no significant difference in peak cross-correlation coefficients for the firings of simultaneously recorded cells between normal and reorganized areas. However, the percentage of correlations that differed significantly from zero was higher in the reorganized area than in the normal area. This suggests a potential correlation between cortical reorganization, increased spontaneous firing rate and inter-neuronal synchrony that might be related to tinnitus found in high-frequency hearing loss induced by acoustic trauma.

Neuronal responses in cat primary auditory cortex to natural and altered species-specific calls.

We investigated how natural and morphed cat vocalizations are represented in primary auditory cortex (AI). About 40% of the neurons showed time-locked responses to major peaks in the vocalization envelope, 60% only responded at the onset. Simultaneously recorded multi-unit (MU) activity of these peak-tracking neurons on separate electrodes was significantly more synchronous during stimulation than under silence. Thus, the representation of the vocalizations is likely synchronously distributed across the cortex. The sum of the responses to the low and high frequency part of the meow, with the boundary at 2.5 kHz, was larger than the neuronal response to the natural meow itself, suggesting that strong lateral inhibition is shaping the response to the natural meow. In this sense, the neurons are combination-sensitive. The frequency-tuning properties and the response to amplitude-modulated tones of the MU recordings can explain the responses to natural, and temporally and spectrally altered vocalizations. Analysis of the mutual information in the firing rate suggests that the activity of at least 95 recording sites in AI would be needed to reliably distinguish between the nine different vocalizations. This suggests that a distributed representation based on temporal stimulus aspects may be more efficient than one based on firing rate.

Neural responses in primary auditory cortex mimic psychophysical, across-frequency-channel, gap-detection thresholds.

Responses of single- and multi-units in primary auditory cortex were recorded for gap-in-noise stimuli for different durations of the leading noise burst. Both firing rate and inter-spike interval representations were evaluated. The minimum detectable gap decreased in exponential fashion with the duration of the leading burst to reach an asymptote for durations of 100 ms. Despite the fact that leading and trailing noise bursts had the same frequency content, the dependence on leading burst duration was correlated with psychophysical estimates of across frequency channel (different frequency content of leading and trailing burst) gap thresholds in humans. The duration of the leading burst plus that of the gap was represented in the all-order inter-spike interval histograms for cortical neurons. The recovery functions for cortical neurons could be modeled on basis of fast synaptic depression and after-hyperpolarization produced by the onset response to the leading noise burst. This suggests that the minimum gap representation in the firing pattern of neurons in primary auditory cortex, and minimum gap detection in behavioral tasks is largely determined by properties intrinsic to those, or potentially subcortical, cells.

Maturation of the mismatch negativity: effects of profound deafness and cochlear implant use.

The use of cochlear implants to restore auditory sensation in deaf children is increasing, with a trend toward earlier implantation. However, little is known about how auditory deprivation and subsequent cochlear implant use affect the maturing human central auditory system. Our previous studies have demonstrated that the obligatory auditory evoked potentials (AEPs) of implanted children are very different from those of normal-hearing children. Unlike the obligatory potentials, which primarily reflect neural responses to stimulus onset, the mismatch negativity (MMN) provides a neurophysiological measure of auditory short-term memory and discrimination processes. The purpose of this investigation is to review our studies of the effects of auditory deprivation due to profound deafness and cochlear implant use on the maturation of the MMN in children, placed in the context of overall age-related changes in the AEPs. The development and application of a statistical technique to assess the MMN in individuals is also reviewed. Results show that although the morphology of the obligatory AEPs is substantially altered by the absence of a normal N(1) peak, the MMN is robustly present in a group of implanted children who have good spoken language perception through their device. Differences exist in the scalp distribution of the MMN between implanted and normal-hearing children. Specifically, the MMN appears to be more symmetrical in amplitude over both hemispheres, whereas it is initially much larger over the contralateral hemisphere in normal-hearing children. These findings suggest that, compared to N(1), the MMN is a better measure of basic auditory processes necessary for the development of spoken language perception skills in profoundly deaf children and adults who use a cochlear implant.

Sound-induced synchronization of neural activity between and within three auditory cortical areas.

Neural synchrony within and between auditory cortical fields is evaluated with respect to its potential role in feature binding and in the coding of tone and noise sound pressure level. Simultaneous recordings were made in 24 cats with either two electrodes in primary auditory cortex (AI) and one in anterior auditory field (AAF) or one electrode each in AI, AAF, and secondary auditory cortex. Cross-correlograms (CCHs) for 1-ms binwidth were calculated for tone pips, noise bursts, and silence (i.e., poststimulus) as a function of intensity level. Across stimuli and intensity levels the total percentage of significant stimulus onset CCHs was 62% and that of significant poststimulus CCHs was 58% of 1,868 pairs calculated for each condition. The cross-correlation coefficient to stimulus onsets was higher for single-electrode pairs than for dual-electrode pairs and higher for noise bursts compared with tone pips. The onset correlation for single-electrode pairs was only marginally larger than the poststimulus correlation. For pairs from electrodes across area boundaries, the onset correlations were a factor 3-4 higher than the poststimulus correlations. The within-AI dual-electrode peak correlation was higher than that across areas, especially for spontaneous conditions. Correlation strengths for between area pairs were independent of the difference in characteristic frequency (CF), thereby providing a mechanism of feature binding for broadband sounds. For noise-burst stimulation, the onset correlation for between area pairs was independent of stimulus intensity regardless the difference in CF. In contrast, for tone-pip stimulation a significant dependence on intensity level of the peak correlation strength was found for pairs involving AI and/or AAF with CF difference less than one octave. Across all areas, driven rate, between-area peak correlation strength, or a combination of the two did not predict stimulus intensity. However, between-area peak correlation strength performs better than firing rate to decide if a stimulus is present or absent.

Moderate noise trauma in juvenile cats results in profound cortical topographic map changes in adulthood.

Cortical topographic map changes have been reported after profound drug-induced hearing loss in neonates, after progressive high-frequency hearing loss, and after mechanically induced lesions in the cochlea of adult animals. The present study demonstrates that exposure of 5-week-old kittens to a loud 6 kHz tone, producing mild to moderate high-frequency hearing loss, induces a profound reorganization of the frequency map in auditory cortex. In the reorganized cortical region, the frequency-tuning curves were of normal sharpness with near normal thresholds. Inhibitory tuning curve bandwidths were similar to those in control animals. Spontaneous activity in the reorganized part of the cortex was significantly increased. In contrast, the strength of the cross-correlation of the spontaneous activity of units recorded on different electrodes was the same in the normal and reorganized part. Minimum first-spike latency was significantly increased in trauma cats, largely for units at the dorsal side of the sampled region. Because most other neural response properties are normal in the reorganized part of cortex, sub-cortical topographic map changes are likely involved in producing the altered cortical topographic maps.

Noise suppression of transient-evoked otoacoustic emissions. I. A comparison with the non-linear method.

A new method to record transient-evoked otoacoustic emissions (TEOAEs) is introduced. Click stimuli were presented both with and without a simultaneously presented wide-band noise burst. Subtraction of the recorded signal evoked by the noise burst plus click from the signal evoked by the click alone, cancelled the eardrum reflection components of the response and resulted in a measure of the emission. This was used to obtain the TEOAEs from 21 subjects for peak click stimulus levels of 48-66 dB SPL. The root-mean-square (RMS) level of the noise burst was set 10 dB higher than the peak click level, and resulted in suppression of the TEOAE by up to 20 dB. The TEOAE waveforms obtained by the new method were compared to those obtained with Kemp's non-linear method, and were indistinguishable in 20 of the 21 subjects. On basis of the emission spectra, they were indistinguishable in 18 out of 21 subjects. The latencies of narrow-band filtered components from the TEOAEs obtained with the two methods were also similar. This suggests that this noise-suppression method produces similar results as Kemp's non-linear method with the advantage that emission components with very short latencies can be obtained.

Noise suppression of transient-evoked otoacoustic emissions. II. Derived narrow-band contributions.

Transient-evoked otoacoustic emissions (TEOAEs) were decomposed into cochlear place specific components using high-pass noise suppression. This was performed using high-pass filtered noise with cut-off frequencies between 0.7 and 5.6 kHz in 0.5-octave steps. Subtraction of the TEOAEs obtained in the presence of two high-pass noise suppressors with 0.5-octave difference in their cut-off frequencies, f(A) and f(B), should theoretically result in TEOAE components with frequencies between f(A) and f(B). The reconstructed wide-band emission power spectrum obtained by summing the narrow-band emission power spectra, was nearly identical to the power spectrum of the original wide-band emission. This suggests that no phase-cancellation occurs and that the individual narrow-band TEOAEs are uncorrelated, and thus that their generators are potentially independent. About 66% of the derived narrow-band emissions had spectral components that extended below the cut-off frequency of the lower high-pass noise filter. These tail components were interpreted as resulting from high-frequency side suppression of the high-pass noise on the click emission and potentially distortion product components from the TEOAE.

Maturation of human central auditory system activity: evidence from multi-channel evoked potentials.

OBJECTIVE: The purpose of this study was to evaluate central auditory system maturation based on detailed data from multi-electrode recordings of long-latency auditory evoked potentials (AEPs). METHODS: AEPs were measured at 30 scalp-electrode locations from 118 subjects between 5 and 20 years of age. Analyses focused on age-related latency and amplitude changes in the P1, N1b, P2, and N2 peaks of the AEPs generated by a brief train of clicks presented to the left ear. RESULTS: Substantial and unexpected changes that extend well into adolescence were found for both the amplitude and latency of the AEP components. While the maturational changes in latency followed a pattern of gradual change, amplitude changes tended to be more abrupt and step-like. Age-related latency decreases were largest for the P1 and N1b peaks. In contrast, P2 latency did not change significantly and the N2 peak increased in latency as a function of age. Abrupt changes in P1, P1-N1b, and N2 peak amplitude (also RMS amplitude) were observed around age 10 at the lateral electrode locations C3 and C4, but not at the midline electrodes Cz and Fz. These changes in amplitude coincided with a sharp increase and plateau in AEP peak and RMS amplitude variability from 9 to 11 years of age. CONCLUSIONS: These analyses demonstrated that the observed pattern of AEP maturation depends on the scalp location at which the responses are recorded. The distinct maturational time courses observed for individual AEP peaks support a model of AEP generation in which activity originates from two or more at least partly independent central nervous system pathways. A striking parallel was observed between previously reported maturational changes in auditory cortex synaptic density and, in particular, the age-related changes in P1 amplitude. The results indicate that some areas of the brain activated by sound stimulation have a maturational time course that extends into adolescence. Maturation of certain auditory processing skills such as speech recognition in noise also has a prolonged time course. This raises the possibility that the emergence of adult-like auditory processing skills may be governed by the same maturing neural processes that affect AEP latency and amplitude.

Effects of acute pure tone induced hearing loss on response properties in three auditory cortical fields in cat.

In this study, we assessed the changes in spontaneous activity and frequency tuning by simultaneous recording of multi-units and local field potentials in primary auditory cortex (AI), anterior auditory field (AAF) and secondary auditory cortex (AII) of cats before and immediately after 30 min exposure to a loud (93 123 dB SPL) pure tone. The average difference of the pure tone and the characteristic frequency (CF) was less than one octave for 70% of the recordings. We found that the mean threshold at CF increased significantly in AI and in AAF but not in AII. The mean CF for units in AI decreased significantly, whereas no significant effect was noted in AAF and AII. The mean frequency-tuning curve bandwidth decreased significantly in AII. Spontaneous activity increased significantly in AI, did not change in AAF, and decreased significantly in AII. Inter-area neural synchrony was not affected. Multi-unit response areas were usually similarly affected as local field potentials based response areas because the 'damaged area', defined as the response surface before minus the surface after the trauma, was very similar. This suggests that the damage reflects peripheral activity changes. Enhancement of frequency response areas around CF, but at least one octave below the frequency of the traumatizing tone, was found most frequently in AAF and suggests a reduction of inhibition likely as a result of the peripheral hearing loss.