Auditory Research publications

Bilateral cochlear-implant (BiCI) users are less accurate at localizing free-field (FF) sound sources than normal-hearing (NH) listeners. This performance gap is not well understood but is likely due to a combination of compromises in acoustic signal representation by the two independent speech processors and neural degradation of auditory pathways associated with a patient’s hearing loss. To exclusively investigate the effect of CI speech encoding on horizontal-plane sound localization, the present study measured sound localization performance in NH subjects listening to vocoder processed and nonvocoded virtual acoustic space (VAS) stimuli. Various aspects of BiCI stimulation such as independently functioning devices, variable across-ear channel selection, and pulsatile stimulation were simulated using uncorrelated noise (N u ), correlated noise (N 0 ), or Gaussian-enveloped tone (GET) carriers during vocoder processing. Additionally, FF sound localization in BiCI users was measured in the same testing environment for comparison. Distinct response patterns across azimuthal locations were evident for both listener groups and were analyzed using a multilevel regression analysis. Simulated implant speech encoding, regardless of carrier, was detrimental to NH localization and the GET vocoder best simulated BiCI FF performance in NH listeners. Overall, the detrimental effect of vocoder processing on NH performance suggests that sound localization deficits may persist even for BiCI patients who have minimal neural degradation associated with their hearing loss and indicates that CI speech encoding plays a significant role in the sound localization deficits experienced by BiCI users.

While the barn owl has been extensively used as a model for sound localization and temporal coding, less is known about the mechanisms at its sensory organ, the basilar papilla (homologous to the mammalian cochlea). In this paper, we characterize, for the first time in the avian system, the auditory nerve fiber responses to broadband noise using reverse correlation. We use the derived impulse responses to study the processing of sounds in the cochlea of the barn owl. We characterize the frequency tuning, phase, instantaneous frequency, and relationship to input level of impulse responses. We show that, even features as complex as the phase dependence on input level, can still be consistent with simple linear filtering. Where possible, we compare our results with mammalian data. We identify salient differences between the barn owl and mammals, e.g., a much smaller frequency glide slope and a bimodal impulse response for the barn owl, and discuss what they might indicate about cochlear mechanics. While important for research on the avian auditory system, the results from this paper also allow us to examine hypotheses put forward for the mammalian cochlea.

This study describes two experiments that were conducted in search for a behavioral paradigm to test for tinnitus in guinea pigs. Conditioning paradigms are available to determine the presence of tinnitus in animals and are based on the assumption that tinnitus impairs their ability to detect silent intervals in continuous noise. Guinea pigs have not been subjected to these paradigms yet; therefore, we investigated whether guinea pigs could be conditioned in the two-way shuttle-box paradigm to respond to silent intervals in noise. Even though guinea pigs could be trained relatively easy to respond to the presence of a noise interval, training guinea pigs to silent intervals in noise was unsuccessful. Instead, it appeared that they became immobile when the continuous stimulus was suddenly stopped. This was confirmed by the next experiment, in which we subjected guinea pigs to alternating intervals of noise and silence with a random duration between 30 and 120 s. Indeed, guinea pigs were significantly longer immobile during silence compared to during noise. By interpreting immobility as a signature of perceiving silence, we hypothesized that the presence of tinnitus would reduce immobility in silence. Therefore, we unilaterally exposed one group of guinea pigs to an 11-kHz tone of 124 dB sound pressure level for 1 h. A subset of the exposed animals was significantly more active in silence, but also more active in noise, as compared to the control group. The increased mobility during silent intervals might represent tinnitus. However, the increased mobility in noise of this group implies that the observed behavior could have derived from, e.g., an overall increase in activity. Therefore, conducting validation experiments is very important before implementing this method as a new screening tool for tinnitus. Follow-up experiments are discussed to further elucidate the origin of the increased mobility in both silence and noise.

Background: The cochlea is the sensory organ of hearing. In the cochlea, the organ of Corti houses sensory cells that are susceptible to pathological insults. While the organ of Corti lacks immune cells, it does have the capacity for immune activity. We hypothesized that resident cells in the organ of Corti were responsible for the stress-induced immune response of the organ of Corti. This study profiled the molecular composition of the immune system in the organ of Corti and examined the immune response of non-immune epithelial cells to acoustic overstimulation. Methods: Using high-throughput RNA-sequencing and qRT-PCR arrays, we identified immune- and inflammation-related genes in both the cochlear sensory epithelium and the organ of Corti. Using bioinformatics analyses, we cataloged the immune genes expressed. We then examined the response of these genes to acoustic overstimulation and determined how changes in immune gene expression were related to sensory cell damage. Results: The RNA-sequencing analysis reveals robust expression of immune-related genes in the cochlear sensory epithelium. The qRT-PCR array analysis confirms that many of these genes are constitutively expressed in the resident cells of the organ of Corti. Bioinformatics analyses reveal that the genes expressed are linked to the Toll-like receptor signaling pathway. We demonstrate that expression of Toll-like receptor signaling genes is predominantly from the supporting cells in the organ of Corti cells. Importantly, our data demonstrate that these Toll-like receptor pathway genes are able to respond to acoustic trauma and that their expression changes are associated with sensory cell damage. Conclusion: The cochlear resident cells in the organ of Corti have immune capacity and participate in the cochlear immune response to acoustic overstimulation.

Conductive hearing loss causes a progressive decline in cochlear activity that may result in functional and structural modifications in auditory neurons. However, whether these activity-dependent changes are accompanied by a glial response involving microglia, astrocytes, or both has not yet been fully elucidated. Accordingly, the present study was designed to determine the involvement of glial related mechanisms in the anteroventral cochlear nucleus (AVCN) of adult rats at 1, 4, 7, and 15 d after removing middle ear ossicles. Quantitative immunohistochemistry analyses at light microscopy with specific markers of microglia or astroglia along with immunocytochemistry at the electron microscopy level were used. Also, in order to test whether trophic support by neurotrophins is modulated in glial cells by auditory activity, the expression and distribution of neurotrophin-3 (NT-3) and its colocalization with microglial or astroglial markers was investigated. Diminished cochlear activity after middle ear ossicle removal leads to a significant ipsilateral increase in the mean gray levels and stained area of microglial cells but not astrocytes in the AVCN at 1 and 4 d post-lesion as compared to the contralateral side and control animals. These results suggest that microglial cells but not astrocytes may act as dynamic modulators of synaptic transmission in the cochlear nucleus immediately following unilateral hearing loss. On the other hand, NT-3 immunostaining was localized mainly in neuronal cell bodies and axons and was upregulated at 1, 4 and 7 d post-lesion. Very few glial cells expressed this neurotrophin in both control and experimental rats, suggesting that NT-3 is primarily activated in neurons and not as much in glia after limiting auditory activity in the AVCN by conductive hearing loss.

Objective: The inferior colliculus (IC) is the primary processing center of auditory information in the midbrain and is one site of tinnitus-related activity. One potential option for suppressing the tinnitus percept is through deep brain stimulation via the auditory midbrain implant (AMI), which is designed for hearing restoration and is already being implanted in deaf patients who also have tinnitus. However, to assess the feasibility of AMI stimulation for tinnitus treatment we first need to characterize the functional connectivity within the IC. Previous studies have suggested modulatory projections from the dorsal cortex of the IC (ICD) to the central nucleus of the IC (ICC), though the functional properties of these projections need to be determined. Approach: In this study, we investigated the effects of electrical stimulation of the ICD on acoustic-driven activity within the ICC in ketamine-anesthetized guinea pigs. Main results: We observed ICD stimulation induces both suppressive and facilitatory changes across ICC that can occur immediately during stimulation and remain after stimulation. Additionally, ICD stimulation paired with broadband noise stimulation at a specific delay can induce greater suppressive than facilitatory effects, especially when stimulating in more rostral and medial ICD locations. Significance: These findings demonstrate that ICD stimulation can induce specific types of plastic changes in ICC activity, which may be relevant for treating tinnitus. By using the AMI with electrode sites positioned with the ICD and the ICC, the modulatory effects of ICD stimulation can be tested directly in tinnitus patients.

Mounting evidence suggests that auditory attention tasks may modulate the sensitivity of the cochlea by way of the corticofugal and the medial olivocochlear ( MOC ) efferent pathways. Here, we studied the extent to which a separate efferent tract, the ‘uncrossed’ MOC , which functionally connects the two ears, mediates inter‐aural selective attention. We compared distortion product otoacoustic emissions ( DPOAE s) in one ear with binaurally presented primaries, using an intermodal target detection task in which participants were instructed to report the occurrence of brief target events (visual changes, tones). Three tasks were compared under identical physical stimulation: (i) report brief tones in the ear in which DPOAE responses were recorded; (ii) report brief tones presented to the contralateral, non‐recorded ear; and (iii) report brief phase shifts of a visual grating at fixation. Effects of attention were observed as parallel shifts in overall DPOAE contour level, with DPOAE s relatively higher in overall level when subjects ignored the auditory stimuli and attended to the visual stimulus, compared with both of the auditory‐attending conditions. Importantly, DPOAE levels were statistically lowest when attention was directed to the ipsilateral ear in which the DPOAE recordings were made. These data corroborate notions that top‐down mechanisms, via the corticofugal and medial efferent pathways, mediate cochlear responses during intermodal attention. New findings show attending to one ear can significantly alter the physiological response of the contralateral, unattended ear, probably through the uncrossed‐medial olivocochlear efferent fibers connecting the two ears.

Tinnitus is often identified in animal models by using the gap prepulse inhibition of acoustic startle. Impaired gap detection following acoustic over-exposure (AOE) is thought to be caused by tinnitus "filling in" the gap, thus, reducing its salience. This presumably involves altered perception, and could conceivably be caused by changes at the level of the neocortex, i.e., cortical reorganization. Alternatively, reduced gap detection ability might reflect poorer temporal processing in the brainstem, caused by AOE; in which case, impaired gap detection would not be a reliable indicator of tinnitus. We tested the latter hypothesis by examining gap detection in inferior colliculus (IC) neurons following AOE. Seven of nine unilaterally noise-exposed guinea pigs exhibited behavioral evidence of tinnitus. In these tinnitus animals, neural gap detection thresholds (GDTs) in the IC significantly increased in response to broadband noise stimuli, but not to pure tones or narrow-band noise. In addition, when IC neurons were sub-divided according to temporal response profile (onset vs. sustained firing patterns), we found a significant increase in the proportion of onset-type responses after AOE. Importantly, however, GDTs were still considerably shorter than gap durations commonly used in objective behavioral tests for tinnitus. These data indicate that the neural changes observed in the IC are insufficient to explain deficits in behavioral gap detection that are commonly attributed to tinnitus. The subtle changes in IC neuron response profiles following AOE warrant further investigation.

Sensory information undergoes ordered and coordinated processing across cortical layers. Whereas cortical layer (L) 4 faithfully acquires thalamic information, the superficial layers appear well staged for more refined processing of L4-relayed signals to generate corticocortical outputs. However, the specific role of superficial layer processing and how it is specified by local synaptic circuits remains not well understood. Here, in the mouse primary auditory cortex, we showed that upper L2/3 circuits play a crucial role in refining functional selectivity of excitatory neurons by sharpening auditory tonal receptive fields and enhancing contrast of frequency representation. This refinement is mediated by synaptic inhibition being more broadly recruited than excitation, with the inhibition predominantly originating from interneurons in the same cortical layer. By comparing the onsets of synaptic inputs as well as of spiking responses of different types of neuron, we found that the broadly tuned, fast responding inhibition observed in excitatory cells can be primarily attributed to feedforward inhibition originating from parvalbumin (PV)-positive neurons, whereas somatostatin (SOM)-positive interneurons respond much later compared with the onset of inhibitory inputs to excitatory neurons. We propose that the feedforward circuit-mediated inhibition from PV neurons, which has an analogous function to lateral inhibition, enables upper L2/3 excitatory neurons to rapidly refine auditory representation.

The mechanism of loss of consciousness (LOC) under anesthesia is unknown. Because consciousness depends on activity in the cortico-thalamic network, anesthetic actions on this network are likely critical for LOC. Competing theories stress the importance of anesthetic actions on bottom-up "core" thalamo-cortical (TC) vs. top-down cortico-cortical (CC) and matrix TC connections. We tested these models using laminar recordings in rat auditory cortex in vivo and murine brain slices. We selectively activated bottom-up vs. top-down afferent pathways using sensory stimuli in vivo and electrical stimulation in brain slices, and compared effects of isoflurane on responses evoked via the two pathways. Auditory stimuli in vivo and core TC afferent stimulation in brain slices evoked short latency current sinks in middle layers, consistent with activation of core TC afferents. By contrast, visual stimuli in vivo and stimulation of CC and matrix TC afferents in brain slices evoked responses mainly in superficial and deep layers, consistent with projection patterns of top-down afferents that carry visual information to auditory cortex. Responses to auditory stimuli in vivo and core TC afferents in brain slices were significantly less affected by isoflurane compared to responses triggered by visual stimuli in vivo and CC/matrix TC afferents in slices. At a just-hypnotic dose in vivo, auditory responses were enhanced by isoflurane, whereas visual responses were dramatically reduced. At a comparable concentration in slices, isoflurane suppressed both core TC and CC/matrix TC responses, but the effect on the latter responses was far greater than on core TC responses, indicating that at least part of the differential effects observed in vivo were due to local actions of isoflurane in auditory cortex. These data support a model in which disruption of top-down connectivity contributes to anesthesia-induced LOC, and have implications for understanding the neural basis of consciousness.

A Bayesian adaptive procedure, the quick-auditory-filter (qAF) procedure, was used to estimate auditory-filter shapes that were asymmetric about their peaks. In three experiments, listeners who were naive to psychoacoustic experiments detected a fixed-level, pure-tone target presented with a spectrally notched noise masker. The qAF procedure adaptively manipulated the masker spectrum level and the position of the masker notch, which was optimized for the efficient estimation of the five parameters of an auditory-filter model. Experiment I demonstrated that the qAF procedure provided a convergent estimate of the auditory-filter shape at 2 kHz within 150 to 200 trials (approximately 15 min to complete) and, for a majority of listeners, excellent test-retest reliability. In experiment II, asymmetric auditory filters were estimated for target frequencies of 1 and 4 kHz and target levels of 30 and 50 dB sound pressure level. The estimated filter shapes were generally consistent with published norms, especially at the low target level. It is known that the auditory-filter estimates are narrower for forward masking than simultaneous masking due to peripheral suppression, a result replicated in experiment III using fewer than 200 qAF trials.

The Hybrid cochlear implant (CI), also known as Electro-Acoustic Stimulation (EAS), is a new type of CI that preserves residual acoustic hearing and enables combined cochlear implant and hearing aid use in the same ear. However, 30-55% of patients experience acoustic hearing loss within days to months after activation, suggesting that both surgical trauma and electrical stimulation may cause hearing loss. The goals of this study were to: 1) determine the contributions of both implantation surgery and EAS to hearing loss in a normal-hearing guinea pig model; 2) determine which cochlear structural changes are associated with hearing loss after surgery and EAS. Two groups of animals were implanted (n = 6 per group), with one group receiving chronic acoustic and electric stimulation for 10 weeks, and the other group receiving no direct acoustic or electric stimulation during this time frame. A third group (n = 6) was not implanted, but received chronic acoustic stimulation. Auditory brainstem response thresholds were followed over time at 1, 2, 6, and 16 kHz. At the end of the study, the following cochlear measures were quantified: hair cells, spiral ganglion neuron density, fibrous tissue density, and stria vascularis blood vessel density; the presence or absence of ossification around the electrode entry was also noted. After surgery, implanted animals experienced a range of 0-55 dB of threshold shifts in the vicinity of the electrode at 6 and 16 kHz. The degree of hearing loss was significantly correlated with reduced stria vascularis vessel density and with the presence of ossification, but not with hair cell counts, spiral ganglion neuron density, or fibrosis area. After 10 weeks of stimulation, 67% of implanted, stimulated animals had more than 10 dB of additional threshold shift at 1 kHz, compared to 17% of implanted, non-stimulated animals and 0% of non-implanted animals. This 1-kHz hearing loss was not associated with changes in any of the cochlear measures quantified in this study. The variation in hearing loss after surgery and electrical stimulation in this animal model is consistent with the variation in human patients. Further, these findings illustrate an advantage of a normal-hearing animal model for quantification of hearing loss and damage to cochlear structures without the confounding effects of chemical- or noise-induced hearing loss. Finally, this study is the first to suggest a role of the stria vascularis and damage to the lateral wall in implantation-induced hearing loss. Further work is needed to determine the mechanisms of implantation- and electrical-stimulation-induced hearing loss.

There are three main acoustical cues to sound location, each attributable to space- and frequency-dependent filtering of the propagating sound waves by the outer ears, head, and torso: Interaural differences in time (ITD) and level (ILD) as well as monaural spectral shape cues. While the guinea pig has been a common model for studying the anatomy, physiology, and behavior of binaural and spatial hearing, extensive measurements of their available acoustical cues are lacking. Here, these cues were determined from directional transfer functions (DTFs), the directional components of the head-related transfer functions, for 11 adult guinea pigs. In the frontal hemisphere, monaural spectral notches were present for frequencies from ∼10 to 20 kHz; in general, the notch frequency increased with increasing sound source elevation and in azimuth toward the contralateral ear. The maximum ITDs calculated from low-pass filtered (2 kHz cutoff frequency) DTFs were ∼250 μs, whereas the maximum ITD measured with low-frequency tone pips was over 320 μs. A spherical head model underestimates ITD magnitude under normal conditions, but closely approximates values when the pinnae were removed. Interaural level differences (ILDs) strongly depended on location and frequency; maximum ILDs were <10 dB for frequencies <4 kHz and were as large as 40 dB for frequencies >10 kHz. Removal of the pinna reduced the depth and sharpness of spectral notches, altered the acoustical axis, and reduced the acoustical gain, ITDs, and ILDs; however, spectral shape features and acoustical gain were not completely eliminated, suggesting a substantial contribution of the head and torso in altering the sounds present at the tympanic membrane.

The temporal order discrimination of target tone pairs is hindered by the presence of flanker tones but is improved when the flanker tones are captured by a separate stream of tones that match the flankers in frequency [Bregman and Rudnicky (1975). J. Exp. Psychol. 1, 263–267]. In an event-related potential (ERP) study with these stimuli, listeners' mismatch negativity (MMN) responses were temporally linked to the position of the changing target tones, irrespective of streaming. In contrast, N1 response latency varied as a function of the perceived grouping of flanker tones established by previous behavioral studies, providing a neurophysiological index of auditory stream segregation.

Background: In ectothermal animals such as fish, -temperature affects physiological and metabolic processes. This includes sensory organs such as the auditory system. The reported effects of temperature on hearing in eurythermal otophysines are contradictory. We therefore investigated the effect on the auditory system in species representing two different orders. Methodology/principal findings: Hearing sensitivity was determined using the auditory evoked potentials (AEP) recording technique. Auditory sensitivity and latency in response to clicks were measured in the common carp Cyprinus carpio (order Cypriniformes) and the Wels catfish Silurus glanis (order Siluriformes) after acclimating fish for at least three weeks to two different water temperatures (15°C, 25°C and again 15°C). Hearing sensitivity increased with temperature in both species. Best hearing was detected between 0.3 and 1 kHz at both temperatures. The maximum increase occurred at 0.8 kHz (7.8 dB) in C. carpio and at 0.5 kHz (10.3 dB) in S. glanis. The improvement differed between species and was in particular more pronounced in the catfish at 4 kHz. The latency in response to single clicks was measured from the onset of the sound stimulus to the most constant positive peak of the AEP. The latency decreased at the higher temperature in both species by 0.37 ms on average. Conclusions/significance: The current study shows that higher temperature improves hearing (lower thresholds, shorter latencies) in eurythermal species from different orders of otophysines. Differences in threshold shifts between eurythermal species seem to reflect differences in absolute sensitivity at higher frequencies and they furthermore indicate differences to stenothermal (tropical) species.

Williams-Beuren Syndrome (WBS) is a rare genetic condition caused by a hemizygous deletion involving up to 28 genes within chromosome 7q11.23. Among the spectrum of physical and neurological defects in WBS, it is common to find a distinctive response to sound stimuli that includes extreme adverse reactions to loud, or sudden sounds and a fascination with certain sounds that may manifest as strengths in musical ability. However, hearing tests indicate that sensorineural hearing loss (SNHL) is frequently found in WBS patients. The functional and genetic basis of this unusual auditory phenotype is currently unknown. Here, we investigated the potential involvement of GTF2IRD1, a transcription factor encoded by a gene located within the WBS deletion that has been implicated as a contributor to the WBS assorted neurocognitive profile and craniofacial abnormalities. Using Gtf2ird1 knockout mice, we have analysed the expression of the gene in the inner ear and examined hearing capacity by evaluating the auditory brainstem response (ABR) and the distortion product of otoacoustic emissions (DPOAE). Our results show that Gtf2ird1 is expressed in a number of cell types within the cochlea, and Gtf2ird1 null mice showed higher auditory thresholds (hypoacusis) in both ABR and DPOAE hearing assessments. These data indicate that the principal hearing deficit in the mice can be traced to impairments in the amplification process mediated by the outer hair cells and suggests that similar mechanisms may underpin the SNHL experienced by WBS patients.

The transgenic P23H line 1 (P23H-1) rat expresses a variant of rhodopsin with a mutation that leads to loss of visual function. This rat strain is an experimental model usually employed to study photoreceptor degeneration. Although the mutated protein should not interfere with other sensory functions, observing severe loss of auditory reflexes in response to natural sounds led us to study auditory brain response (ABR) recording. Animals were separated into different hearing levels following the response to natural stimuli (hand clapping and kissing sounds). Of all the analyzed animals, 25.9% presented auditory loss before 50 days of age (P50) and 45% were totally deaf by P200. ABR recordings showed that all the rats had a higher hearing threshold than the control Sprague-Dawley (SD) rats, which was also higher than any other rat strains. The integrity of the central and peripheral auditory pathway was analyzed by histology and immunocytochemistry. In the cochlear nucleus (CN), statistical differences were found between SD and P23H-1 rats in VGluT1 distribution, but none were found when labeling all the CN synapses with anti-Syntaxin. This finding suggests anatomical and/or molecular abnormalities in the auditory downstream pathway. The inner ear of the hypoacusic P23H-1 rats showed several anatomical defects, including loss and disruption of hair cells and spiral ganglion neurons. All these results can explain, at least in part, how hearing impairment can occur in a high percentage of P23H-1 rats. P23H-1 rats may be considered an experimental model with visual and auditory dysfunctions in future research.

Speech production requires the precise control of vocal tract movements to generate individual speech sounds (phonemes) which, in turn, are rapidly organized into complex sequences. Multiple productions of the same phoneme can exhibit substantial variability, some of which is inherent to control of the vocal tract and its biomechanics, and some of which reflects the contextual effects of surrounding phonemes ("coarticulation"). The role of the CNS in these aspects of speech motor control is not well understood. To address these issues, we recorded multielectrode cortical activity directly from human ventral sensory-motor cortex (vSMC) during the production of consonant-vowel syllables. We analyzed the relationship between the acoustic parameters of vowels (pitch and formants) and cortical activity on a single-trial level. We found that vSMC activity robustly predicted acoustic parameters across vowel categories (up to 80% of variance), as well as different renditions of the same vowel (up to 25% of variance). Furthermore, we observed significant contextual effects on vSMC representations of produced phonemes that suggest active control of coarticulation: vSMC representations for vowels were biased toward the representations of the preceding consonant, and conversely, representations for consonants were biased toward upcoming vowels. These results reveal that vSMC activity for phonemes are not invariant and provide insight into the cortical mechanisms of coarticulation.

Aminoglycoside-induced cochlear ototoxicity causes hair cell (HC) loss and results in hearing impairment in patients. Previous studies have developed the concept of an ototoxicity-sensitive period during which the cochleae of young mice are more vulnerable to auditory trauma than adults. Here, we compared neomycin-induced ototoxicity at the following four developmental ages in mice: postnatal day (P)1-P7, P8-P14, P15-P21, and P60-P66. We found that when neomycin was administered between P8 and P14, the auditory brainstem response threshold increase was significantly higher at low frequencies and HC loss was significantly greater in the apical turn of the cochlea compared to neomycin administration during the other age ranges. Quantitative real-time PCR (qPCR) data revealed that the expression of apoptotic markers, including Casp3 and Casp9, was significantly higher when neomycin was injected from P8 to P14, while the expression of the X-linked inhibitor of apoptosis protein (XIAP) gene was significantly higher when neomycin was injected from P60 to P66. Because XIAP expression was low during the neomycin-sensitive period, we overexpressed XIAP in mice and found that it could protect against neomycin-induced hearing loss at low frequencies and HC loss in the apical turn of the cochlea. Altogether, our findings demonstrate a protective role for XIAP against neomycin-induced hearing loss and HC loss in the apical turn of the cochlea during the ototoxic-sensitive period, and suggest that apoptotic factors mediate the effect of neomycin during the ototoxic-sensitive period.

Our understanding of the large-scale population dynamics of neural activity is limited, in part, by our inability to record simultaneously from large regions of the cortex. Here, we validated the use of a large-scale active microelectrode array that simultaneously records 196 multiplexed micro-electrocortigraphical (μECoG) signals from the cortical surface at a very high density (1,600 electrodes/cm 2 ). We compared μECoG measurements in auditory cortex using a custom “active” electrode array to those recorded using a conventional “passive” μECoG array. Both of these array responses were also compared with data recorded via intrinsic optical imaging, which is a standard methodology for recording sound-evoked cortical activity. Custom active μECoG arrays generated more veridical representations of the tonotopic organization of the auditory cortex than current commercially available passive μECoG arrays. Furthermore, the cortical representation could be measured efficiently with the active arrays, requiring as little as 13.5 s of neural data acquisition. Next, we generated spectrotemporal receptive fields from the recorded neural activity on the active μECoG array and identified functional organizational principles comparable to those observed using intrinsic metabolic imaging and single-neuron recordings. This new electrode array technology has the potential for large-scale, temporally precise monitoring and mapping of the cortex, without the use of invasive penetrating electrodes.