Auditory Research publications

In the auditory system, early neural stations such as brain stem are characterized by strict tonotopy, which is used to deconstruct sounds to their basic frequencies. But higher along the auditory hierarchy, as early as primary auditory cortex (A1), tonotopy starts breaking down at local circuits. Here, we studied the response properties of both excitatory and inhibitory neurons in the auditory cortex of anesthetized mice. We used in vivo two photon-targeted cell-attached recordings from identified parvalbumin-positive neurons (PVNs) and their excitatory pyramidal neighbors (PyrNs). We show that PyrNs are locally heterogeneous as characterized by diverse best frequencies, pairwise signal correlations, and response timing. In marked contrast, neighboring PVNs exhibited homogenous response properties in pairwise signal correlations and temporal responses. The distinct physiological microarchitecture of different cell types is maintained qualitatively in response to natural sounds. Excitatory heterogeneity and inhibitory homogeneity within the same circuit suggest different roles for each population in coding natural stimuli.

Trimethyltin (TMT) is an occupational and environmental health hazard behaving as a potent neurotoxin known to affect the central nervous system as well as the peripheral auditory system. However, the mechanisms underlying TMT-induced ototoxicity are poorly understood. To elucidate the effects of TMT on the cochlea, a single injection of 4 or 8 mg/kg TMT was administered intraperitoneally to adult rats. The compound action potential (CAP) threshold was used to assess the functional status of the cochlea and histological techniques were used to assess the condition of the hair cells and auditory nerve fibers. TMT at 4 mg/kg produced a temporary CAP threshold elevation of 25-60 dB that recovered by 28 d post-treatment. Although there was no hair cell loss with the 4 mg/kg dose, there was a noticeable loss of auditory nerve fibers particularly beneath the inner hair cells. TMT at 8 mg/kg produced a large permanent CAP threshold shift that was greatest at the high frequencies. The CAP threshold shift was associated with the loss of outer hair cells and inner hair cells in the basal, high-frequency region of the cochlea, considerable loss of auditory nerve fibers and a significant loss of spiral ganglion neurons in the basal turn. Spiral ganglion neurons showed evidence of soma shrinkage and nuclear condensation and fragmentation, morphological features of apoptotic cell death. TMT-induced damage was greatest in the high-frequency, basal region of the cochlea and the nerve fibers beneath the inner hair cells were the most vulnerable structures.

Severe noise-induced damage to the inner ear leads to auditory nerve fiber degeneration thereby reducing the neural input to the cochlear nucleus (CN). Paradoxically, this leads to a significant increase in spontaneous activity in the CN which has been linked to tinnitus, hyperacusis and ear pain. The biological mechanisms that lead to an increased spontaneous activity are largely unknown, but could arise from changes in glutamatergic or GABAergic neurotransmission or neuroinflammation. To test this hypothesis, we unilaterally exposed rats for 2h to a 126dB SPL narrow band noise centered at 12kHz. Hearing loss measured by auditory brainstem responses exceeded 55dB from 6 to 32kHz. The mRNA from the exposed CN was harvested at 14 or 28days post-exposure and qRT-PCR analysis was performed on 168 genes involved in neural inflammation, neuropathic pain and glutamatergic or GABAergic neurotransmission. Expression levels of mRNA of Slc17a6 and Gabrg3, involved in excitation and inhibition respectively, were significantly increased at 28days post-exposure, suggesting a possible role in the CN spontaneous hyperactivity associated with tinnitus and hyperacusis. In the pain and inflammatory array, noise exposure upregulated mRNA expression levels of four pain/inflammatory genes, Tlr2, Oprd1, Kcnq3 and Ntrk1 and decreased mRNA expression levels of two more genes, Ccl12 and Il1β. Pain/inflammatory gene expression changes via Ntrk1 signaling may induce sterile inflammation, neuropathic pain, microglial activation and migration of nerve fibers from the trigeminal, cuneate and vestibular nuclei into the CN. These changes could contribute to somatic tinnitus, hyperacusis and otalgia.

The high prevalence of noise-induced and age-related hearing loss in the general population has warranted the use of animal models to study the etiology of these pathologies. Quick and accurate auditory threshold determination is a prerequisite for experimental manipulations targeting hearing loss in animal models. The standard auditory brainstem response (ABR) measurement is fairly quick and translational across species, but is limited by the need for anesthesia and a lack of perceptual assessment. The goal of this study was to develop a new method of hearing assessment utilizing prepulse inhibition (PPI) of the acoustic startle reflex, a commonly used tool that measures detection thresholds in awake animals, and can be performed on multiple animals simultaneously. We found that in control mice PPI audiometric functions are similar to both ABR and traditional operant conditioning audiograms. The hearing thresholds assessed with PPI audiometry in sound exposed mice were also similar to those detected by ABR thresholds one day after exposure. However, three months after exposure PPI threshold shifts were still evident at and near the frequency of exposure whereas ABR thresholds recovered to the pre-exposed level. In contrast, PPI audiometry and ABR wave one amplitudes detected similar losses. PPI audiometry provides a high throughput automated behavioral screening tool of hearing in awake animals. Overall, PPI audiometry and ABR assessments of the auditory system are robust techniques with distinct advantages and limitations, which when combined, can provide ample information about the functionality of the auditory system.

Sensory processing in the lower auditory pathway is generally considered to be rigid and thus less subject to modulation than central processing. However, in addition to the powerful bottom-up excitation by auditory nerve fibers, the ventral cochlear nucleus also receives efferent cholinergic innervation from both auditory and nonauditory top–down sources. We thus tested the influence of cholinergic modulation on highly precise time-coding neurons in the cochlear nucleus of the Mongolian gerbil. By combining electrophysiological recordings with pharmacological application in vitro and in vivo , we found 55–72% of spherical bushy cells (SBCs) to be depolarized by carbachol on two time scales, ranging from hundreds of milliseconds to minutes. These effects were mediated by nicotinic and muscarinic acetylcholine receptors, respectively. Pharmacological block of muscarinic receptors hyperpolarized the resting membrane potential, suggesting a novel mechanism of setting the resting membrane potential for SBC. The cholinergic depolarization led to an increase of spike probability in SBCs without compromising the temporal precision of the SBC output in vitro . In vivo , iontophoretic application of carbachol resulted in an increase in spontaneous SBC activity. The inclusion of cholinergic modulation in an SBC model predicted an expansion of the dynamic range of sound responses and increased temporal acuity. Our results thus suggest of a top–down modulatory system mediated by acetylcholine which influences temporally precise information processing in the lower auditory pathway.

Objective: This study examined the effect of microphone placement on the interaural level differences (ILDs) available to bilateral cochlear implant (BiCI) users, and the subsequent effects on horizontal-plane sound localization. Design: Virtual acoustic stimuli for sound localization testing were created individually for eight BiCI users by making acoustic transfer function measurements for microphones placed in the ear (ITE), behind the ear (BTE), and on the shoulders (SHD). The ILDs across source locations were calculated for each placement to analyze their effect on sound localization performance. Sound localization was tested using a repeated-measures, within-participant design for the three microphone placements. Results: The ITE microphone placement provided significantly larger ILDs compared to BTE and SHD placements, which correlated with overall localization errors. However, differences in localization errors across the microphone conditions were small. Conclusions: The BTE microphones worn by many BiCI users in everyday life do not capture the full range of acoustic ILDs available, and also reduce the change in cue magnitudes for sound sources across the horizontal plane. Acute testing with an ITE placement reduced sound localization errors along the horizontal plane compared to the other placements in some patients. Larger improvements may be observed if patients had more experience with the new ILD cues provided by an ITE placement.

Mice often produce ultrasonic vocalizations (USVs) that sweep upwards in frequency from around 60 to around 80 kHz and downwards in frequency from 80 to 60 kHz. Whether or not these USVs are used for communication purposes is still unknown. Here, mice were trained and tested using operant conditioning procedures and positive reinforcement to discriminate between synthetic upsweeps and downsweeps. The stimuli varied in bandwidth, duration, and direction of sweep. The mice performed significantly worse when discriminating between background and test stimuli when the stimuli all occupied the same bandwidths. Further, the mice's discrimination performance became much worse for stimuli that had durations similar to those natural vocalizations of the mice. Sweeps composed of different frequency ranges and longer durations had improved discrimination. These results collected using artificial stimuli created to mimic natural USVs indicate that the bandwidth of the vocalizations may be much more important for communication than the frequency contours of the vocalizations.

The Speech Intelligibility Index (SII) assumes additivity of the importance of acoustically independent bands of speech. To further evaluate this assumption, open-set speech recognition was measured for words and sentences, in quiet and in noise, when the speech stimuli were presented to the listener in selected frequency bands. The filter passbands were constructed from various combinations of 20 bands having equivalent (0.05) importance in the SII framework. This permitted the construction of a variety of equal-SII band patterns that were then evaluated by nine different groups of young adults with normal hearing. For monosyllabic words, a similar dependence on band pattern was observed for SII values of 0.4, 0.5, and 0.6 in both quiet and noise conditions. Specifically, band patterns concentrated toward the lower and upper frequency range tended to yield significantly lower scores than those more evenly sampling a broader frequency range. For all stimuli and test conditions, equal SII values did not yield equal performance. Because the spectral distortions of speech evaluated here may not commonly occur in everyday listening conditions, this finding does not necessarily represent a serious deficit for the application of the SII. These findings, however, challenge the band-independence assumption of the theory underlying the SII.

Objectives: The binaural interaction component (BIC) is the residual auditory brainstem response (ABR) obtained after subtracting the sum of monaurally evoked from binaurally evoked ABRs. The DN1 peak—the first negative peak of the BIC—has been postulated to have diagnostic value as a biomarker for binaural hearing abilities. Indeed, not only do DN1 amplitudes depend systematically upon binaural cues to location (interaural time and level differences), but they are also predictive of central hearing deficits in humans. A prominent issue in using BIC measures as a diagnostic biomarker is that DN1 amplitudes not only exhibit considerable variability across subjects, but also within subjects across different measurement sessions. Design: In this study, the authors investigate the DN1 amplitude measurement reliability by conducting repeated measurements on different days in eight adult guinea pigs. Results: Despite consistent ABR thresholds, ABR and DN1 amplitudes varied between and within subjects across recording sessions. However, the study analysis reveals that DN1 amplitudes varied proportionally with parent monaural ABR amplitudes, suggesting that common experimental factors likely account for the variability in both waveforms. Despite this variability, the authors show that the shape of the dependence between DN1 amplitude and interaural time difference is preserved. The authors then provide a BIC normalization strategy using monaural ABR amplitude that reduces the variability of DN1 peak measurements. Finally, the authors evaluate this normalization strategy in the context of detecting changes of the DN1 amplitude-to-interaural time difference relationship. Conclusions: The study results indicate that the BIC measurement variability can be reduced by a factor of two by performing a simple and objective normalization operation. The authors discuss the potential for this normalized BIC measure as a biomarker for binaural hearing.

Contralateral suppression of otoacoustic emissions (OAEs) is frequently used to assess the medial olivocochlear (MOC) efferent system, and may have clinical utility. However, OAEs are weak or absent in hearing-impaired ears, so little is known about MOC function in the presence of hearing loss. A potential alternative measure is contralateral suppression of the auditory steady-state response (ASSR) because ASSRs are measurable in many hearing-impaired ears. This study compared contralateral suppression of both transient-evoked otoacoustic emissions (TEOAEs) and ASSRs in a group of ten primarily older adults with either normal hearing or mild sensorineural hearing loss. Responses were elicited using 75-dB peak sound pressure level clicks. The MOC was activated using contralateral broadband noise at 60 dB sound pressure level. Measurements were made concurrently to ensure a consistent attentional state between the two measures. The magnitude of contralateral suppression of ASSRs was significantly larger than contralateral suppression of TEOAEs. Both measures usually exhibited high test–retest reliability within a session. However, there was no significant correlation between the magnitude of contralateral suppression of TEOAEs and of ASSRs. Further work is needed to understand the role of the MOC in contralateral suppression of ASSRs.

Sound recognition relies not only on spectral cues, but also on temporal cues, as demonstrated by the profound impact of time reversals on perception of common sounds. To address the coding principles underlying such auditory asymmetries, we recorded a large sample of auditory cortex neurons using two-photon calcium imaging in awake mice, while playing sounds ramping up or down in intensity. We observed clear asymmetries in cortical population responses, including stronger cortical activity for up-ramping sounds, which matches perceptual saliency assessments in mice and previous measures in humans. Analysis of cortical activity patterns revealed that auditory cortex implements a map of spatially clustered neuronal ensembles, detecting specific combinations of spectral and intensity modulation features. Comparing different models, we show that cortical responses result from multi-layered nonlinearities, which, contrary to standard receptive field models of auditory cortex function, build divergent representations of sounds with similar spectral content, but different temporal structure.

Just-noticeable differences (JNDs) in interaural time delay (ITD), interaural level difference (ILD), and interaural cross-correlation (ICC) were measured with low- and high-frequency noise bands over multiple sessions for 10 normal-hearing (NH) and 11 hearing-impaired (HI) listeners. Individual subject thresholds tended to improve with training then stabilize. Measured JNDs varied over these experienced listeners, for both subject groups and all tasks. Group JNDs were seldom predictable from hearing level. Individual listeners' JNDs were highly correlated across frequency for each task and group, except for ICC in the HI listeners. Further, ITD JNDs almost always significantly correlated with ILD JNDs within a group. Finally, although the ICC JNDs always significantly correlated with the ITD or ILD JNDs for the NH listeners, they often did not for the HI listeners. These findings suggest that little information about binaural sensitivity is added for NH listeners with multiple ITD, ILD, and ICC measures. For HI listeners, however, while ITD and ILD measures are well correlated, information is added with ICC measures. In general, the results suggest that less information is added with JND measures for NH listeners (15 significant correlations) than for HI listeners (six significant correlations).

Neurons at higher stages of sensory processing can partially compensate for a sudden drop in peripheral input through a homeostatic plasticity process that increases the gain on weak afferent inputs. Even after a profound unilateral auditory neuropathy where >95% of afferent synapses between auditory nerve fibers and inner hair cells have been eliminated with ouabain, central gain can restore cortical processing and perceptual detection of basic sounds delivered to the denervated ear. In this model of profound auditory neuropathy, auditory cortex (ACtx) processing and perception recover despite the absence of an auditory brainstem response (ABR) or brainstem acoustic reflexes, and only a partial recovery of sound processing at the level of the inferior colliculus (IC), an auditory midbrain nucleus. In this study, we induced a profound cochlear neuropathy with ouabain and asked whether central gain enabled a compensatory plasticity in the auditory thalamus comparable to the full recovery of function previously observed in the ACtx, the partial recovery observed in the IC, or something different entirely. Unilateral ouabain treatment in adult mice effectively eliminated the ABR, yet robust sound-evoked activity persisted in a minority of units recorded from the contralateral medial geniculate body (MGB) of awake mice. Sound driven MGB units could decode moderate and high-intensity sounds with accuracies comparable to sham-treated control mice, but low-intensity classification was near chance. Pure tone receptive fields and synchronization to broadband pulse trains also persisted, albeit with significantly reduced quality and precision, respectively. MGB decoding of temporally modulated pulse trains and speech tokens were both greatly impaired in ouabain-treated mice. Taken together, the absence of an ABR belied a persistent auditory processing at the level of the MGB that was likely enabled through increased central gain. Compensatory plasticity at the level of the auditory thalamus was less robust overall than previous observations in cortex or midbrain. Hierarchical differences in compensatory plasticity following sensorineural hearing loss may reflect differences in GABA circuit organization within the MGB, as compared to the ACtx or IC.

Objective . Electrocorticography (ECoG) has become an important tool in human neuroscience and has tremendous potential for emerging applications in neural interface technology. Electrode array design parameters are outstanding issues for both research and clinical applications, and these parameters depend critically on the nature of the neural signals to be recorded. Here, we investigate the functional spatial resolution of neural signals recorded at the human cortical surface. We empirically derive spatial spread functions to quantify the shared neural activity for each frequency band of the electrocorticogram. Approach . Five subjects with high-density (4 mm center-to-center spacing) ECoG grid implants participated in speech perception and production tasks while neural activity was recorded from the speech cortex, including superior temporal gyrus, precentral gyrus, and postcentral gyrus. The cortical surface field potential was decomposed into traditional EEG frequency bands. Signal similarity between electrode pairs for each frequency band was quantified using a Pearson correlation coefficient. Main results . The correlation of neural activity between electrode pairs was inversely related to the distance between the electrodes; this relationship was used to quantify spatial falloff functions for cortical subdomains. As expected, lower frequencies remained correlated over larger distances than higher frequencies. However, both the envelope and phase of gamma and high gamma frequencies (30–150 Hz) are largely uncorrelated (<90%) at 4 mm, the smallest spacing of the high-density arrays. Thus, ECoG arrays smaller than 4 mm have significant promise for increasing signal resolution at high frequencies, whereas less additional gain is achieved for lower frequencies. Significance. Our findings quantitatively demonstrate the dependence of ECoG spatial resolution on the neural frequency of interest. We demonstrate that this relationship is consistent across patients and across cortical areas during activity.

Dietary folic acid deficiency induced early hearing loss in C57BL/6J mice after 2-months, corroborates the epidemiological association previously described between vitamin deficiency and this sensory impairment. However, this strain is prone to early hearing loss, and hence we decided to analyze whether the effects exerted by folate deprivation follow the same pattern in a mouse strain such as CBA/Ca, which is resistant to hearing impairment. Here, we show results of a long-term study on hearing carried out on CBA/Ca mice subjected to dietary folate deprivation. Systemic changes included decreased serum folate levels, hyperhomocysteinemia and signs of anemia in the group fed with folate-deficient (FD) diet. Initial signs of hearing loss were detected in this strain after 8-months of vitamin deficiency, and correlated with histological damage in the cochleae. In conclusion, the data presented reinforce the importance of adequate folic acid levels for the auditory system and suggest that the impact of dietary deficiencies may depend on the genetic background.

Unlabelled: Neuroplastin (Nptn) is a member of the Ig superfamily and is expressed in two isoforms, Np55 and Np65. Np65 regulates synaptic transmission but the function of Np55 is unknown. In an N-ethyl-N-nitrosaurea mutagenesis screen, we have now generated a mouse line with an Nptn mutation that causes deafness. We show that Np55 is expressed in stereocilia of outer hair cells (OHCs) but not inner hair cells and affects interactions of stereocilia with the tectorial membrane. In vivo vibrometry demonstrates that cochlear amplification is absent in Nptn mutant mice, which is consistent with the failure of OHC stereocilia to maintain stable interactions with the tectorial membrane. Hair bundles show morphological defects as the mutant mice age and while mechanotransduction currents can be evoked in early postnatal hair cells, cochlea microphonics recordings indicate that mechanontransduction is affected as the mutant mice age. We thus conclude that differential splicing leads to functional diversification of Nptn, where Np55 is essential for OHC function, while Np65 is implicated in the regulation of synaptic function. Significance statement: Amplification of input sound signals, which is needed for the auditory sense organ to detect sounds over a wide intensity range, depends on mechanical coupling of outer hair cells to the tectorial membrane. The current study shows that neuroplastin, a member of the Ig superfamily, which has previously been linked to the regulation of synaptic plasticity, is critical to maintain a stable mechanical link of outer hair cells with the tectorial membrane. In vivo recordings demonstrate that neuroplastin is essential for sound amplification and that mutation in neuroplastin leads to auditory impairment in mice.

The occurrence of tinnitus can be linked to hearing loss in the majority of cases, but there is nevertheless a large degree of unexplained heterogeneity in the relation between hearing loss and tinnitus. Part of the problem might be that hearing loss is usually quantified in terms of increased hearing thresholds, which only provides limited information about the underlying cochlear damage. Moreover, noise exposure that does not cause hearing threshold loss can still lead to "hidden hearing loss" (HHL), i.e., functional deafferentation of auditory nerve fibers (ANFs) through loss of synaptic ribbons in inner hair cells. While it is known that increased hearing thresholds can trigger increases in spontaneous neural activity in the central auditory system, i.e., a putative neural correlate of tinnitus, the central effects of HHL have not yet been investigated. Here, we exposed mice to octave-band noise at 100 and 105 dB SPL to generate HHL and permanent increases of hearing thresholds, respectively. Deafferentation of ANFs was confirmed through measurement of auditory brainstem responses and cochlear immunohistochemistry. Acute extracellular recordings from the auditory midbrain (inferior colliculus) demonstrated increases in spontaneous neuronal activity (a putative neural correlate of tinnitus) in both groups. Surprisingly, the increase in spontaneous activity was most pronounced in the mice with HHL, suggesting that the relation between hearing loss and neuronal hyperactivity might be more complex than currently understood. Our computational model indicated that these differences in neuronal hyperactivity could arise from different degrees of deafferentation of low-threshold ANFs in the two exposure groups. Our results demonstrate that HHL is sufficient to induce changes in central auditory processing, and they also indicate a non-monotonic relationship between cochlear damage and neuronal hyperactivity, suggesting an explanation for why tinnitus might occur without obvious hearing loss and conversely why hearing loss does not always lead to tinnitus.

The ear is the organ that is most sensitive to blast overpressure and ear damage is most frequently seen after blast exposure. Blast overpressure to the ear results in sensorineural hearing loss, which is untreatable and is often associated with a decline in the quality of life. In this study, we used a rat model to demonstrate the pathophysiological and structural changes in the inner ear that replicate pure sensorineural hearing loss associated with blast injury using laser-induced shock wave (LISW) without any conductive hearing loss. Our results indicate that threshold elevation of the auditory brainstem response (ABR) after blast exposure was primarily caused by outer hair cell dysfunction induced by stereociliary bundle disruption. The bundle disruption pattern was unique; disturbed stereocilia were mostly observed in the outermost row, whereas those in the inner and middle rows stereocilia remained intact. In addition, the ABR examination showed a reduction in wave I amplitude without elevation of the threshold in the lower energy exposure group. This phenomenon was caused by loss of the synaptic ribbon. This type of hearing dysfunction has recently been described as hidden hearing loss caused by cochlear neuropathy, which is associated with tinnitus or hyperacusis.

Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has been proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus-like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and 129sv) for pre-pulse inhibition (PPI) and gap detection with varying interstimulus intervals (ISI) and found that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in the presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, 129sv and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32-kHz narrow band noise gap carrier in GLAST knockout (KO) mice when compared to their wild-type (WT) littermates. Auditory brainstem responses (ABR) and distortion-product otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in WT mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the mechanisms of tinnitus.

Objects and events in the sensory environment are generally predictable, making most of the energy impinging upon sensory transducers redundant. Given this fact, efficient sensory systems should detect, extract, and exploit predictability in order to optimize sensitivity to less predictable inputs that are, by definition, more informative. Not only are perceptual systems sensitive to changes in physical stimulus properties, but growing evidence reveals sensitivity both to relative predictability of stimuli and to co-occurrence of stimulus attributes within stimuli. Recent results revealed that auditory perception rapidly reorganizes to efficiently capture covariance among stimulus attributes. Acoustic properties per se were perceptually abandoned, and sounds were instead processed relative to patterns of co-occurrence. Here, we show that listeners' ability to distinguish sounds from one another is driven primarily by the extent to which they are consistent or inconsistent with patterns of covariation among stimulus attributes and, to a lesser extent, whether they are heard frequently or infrequently. When sounds were heard frequently and deviated minimally from the prevailing pattern of covariance among attributes, they were poorly discriminated from one another. In stark contrast, when sounds were heard rarely and markedly violated the pattern of covariance, they became hyperdiscriminable with discrimination performance beyond apparent limits of the auditory system. Plausible cortical candidates underlying these dramatic changes in perceptual organization are discussed. These findings support efficient coding of stimulus statistical structure as a model for both perceptual and neural organization.