Dissociated Representation of Binaural Cues in Single-Sided Deafness: Implications for Cochlear Implantation.

Congenital single-sided deafness (SSD) leads to an aural preference syndrome that is characterized by overrepresentation of the hearing ear in the auditory system. Cochlear implantation (CI) of the deaf ear is an effective treatment for SSD. However, the newly introduced auditory input in congenital SSD often does not reach expectations in late-implanted CI recipients with respect to binaural hearing and speech perception. In a previous study, a reduction of the interaural time difference (ITD) sensitivity has been shown in unilaterally congenitally deaf cats (uCDCs). In the present study, we focused on the interaural level difference (ILD) processing in the primary auditory cortex. The uCDC group was compared with hearing cats (HCs) and bilaterally congenitally deaf cats (CDCs). The ILD representation was reorganized, replacing the preference for the contralateral ear with a preference for the hearing ear, regardless of the cortical hemisphere. In accordance with the previous study, uCDCs were less sensitive to interaural time differences than HCs, resulting in unmodulated ITD responses, thus lacking directional information. Such incongruent ITDs and ILDs cannot be integrated for binaural sound source localization. In normal hearing, the predominant effect of each ear is excitation of the auditory cortex in the contralateral cortical hemisphere and inhibition in the ipsilateral hemisphere. In SSD, however, auditory pathways reorganized such that the hearing ear produced greater excitation in both cortical hemispheres and the deaf ear produced weaker excitation and preserved inhibition in both cortical hemispheres.

Congenital deafness reduces alpha-gamma cross-frequency coupling in the auditory cortex.

Neurons within a neuronal network can be grouped by bottom-up and top-down influences using synchrony in neuronal oscillations. This creates the representation of perceptual objects from sensory features. Oscillatory activity can be differentiated into stimulus-phase-locked (evoked) and non-phase-locked (induced). The former is mainly determined by sensory input, the latter by higher-level (cortical) processing. Effects of auditory deprivation on cortical oscillations have been studied in congenitally deaf cats (CDCs) using cochlear implant (CI) stimulation. CI-induced alpha, beta, and gamma activity were compromised in the auditory cortex of CDCs. Furthermore, top-down information flow between secondary and primary auditory areas in hearing cats, conveyed by induced alpha oscillations, was lost in CDCs. Here we used the matching pursuit algorithm to assess components of such oscillatory activity in local field potentials recorded in primary field A1. Additionally to the loss of induced alpha oscillations, we also found a loss of evoked theta activity in CDCs. The loss of theta and alpha activity in CDCs can be directly related to reduced high-frequency (gamma-band) activity due to cross-frequency coupling. Here we quantified such cross-frequency coupling in adult 1) hearing-experienced, acoustically stimulated cats (aHCs), 2) hearing-experienced cats following acute pharmacological deafening and subsequent CIs, thus in electrically stimulated cats (eHCs), and 3) electrically stimulated CDCs. We found significant cross-frequency coupling in all animal groups in > 70% of auditory-responsive sites. The predominant coupling in aHCs and eHCs was between theta/alpha phase and gamma power. In CDCs such coupling was lost and replaced by alpha oscillations coupling to delta/theta phase. Thus, alpha/theta oscillations synchronize high-frequency gamma activity only in hearing-experienced cats. The absence of induced alpha and theta oscillations contributes to the loss of induced gamma power in CDCs, thereby signifying impaired local network activity.

Multidimensional Alternating Kernel Method for cortical layer segmentation in 3D reconstructed histology.

The neocortex of the brain can be divided into six layers each with a distinct cell composition and connectivity pattern. Recently, sensory deprivation, including congenital deafness, has been shown to alter cortical structure (e.g. the cortical thickness) of the feline auditory cortex with variable and inconsistent results. Thus, understanding these complex changes will require further study of the constituent cortical layers in three-dimensional space. Further progress crucially depends on the use of objective computational techniques that can reliably characterize spatial properties of the complex cortical structure. Here a method for cortical laminar segmentation is derived and applied to the three-dimensional cortical areas reconstructed from a series of histological sections from four feline brains. In this approach, the Alternating Kernel Method was extended to fit a multi-variate Gaussian mixture model to a feature space consisting of both staining intensity and a biologically plausible equivolumetric depth map. This research method•Extends the Alternating Kernel Method to multi-dimensional feature spaces.•Uses it to segment the cortical layers in reconstructed histology volume. Segmentation features include staining intensity and a biologically plausible equivolumetric depth map.•Validates results in auditory cortical areas of feline brains, two with normal hearing and two with congenital deafness.

Processing of auditory information in forebrain regions after hearing loss in adulthood: Behavioral and electrophysiological studies in a rat model.

Background: Hearing loss was proposed as a factor affecting development of cognitive impairment in elderly. Deficits cannot be explained primarily by dysfunctional neuronal networks within the central auditory system. We here tested the impact of hearing loss in adult rats on motor, social, and cognitive function. Furthermore, potential changes in the neuronal activity in the medial prefrontal cortex (mPFC) and the inferior colliculus (IC) were evaluated. Materials and methods: In adult male Sprague Dawley rats hearing loss was induced under general anesthesia with intracochlear injection of neomycin. Sham-operated and naive rats served as controls. Postsurgical acoustically evoked auditory brainstem response (ABR)-measurements verified hearing loss after intracochlear neomycin-injection, respectively, intact hearing in sham-operated and naive controls. In intervals of 8 weeks and up to 12 months after surgery rats were tested for locomotor activity (open field) and coordination (Rotarod), for social interaction and preference, and for learning and memory (4-arms baited 8-arms radial maze test). In a final setting, electrophysiological recordings were performed in the mPFC and the IC. Results: Locomotor activity did not differ between deaf and control rats, whereas motor coordination on the Rotarod was disturbed in deaf rats (P < 0.05). Learning the concept of the radial maze test was initially disturbed in deaf rats (P < 0.05), whereas retesting every 8 weeks did not show long-term memory deficits. Social interaction and preference was also not affected by hearing loss. Final electrophysiological recordings in anesthetized rats revealed reduced firing rates, enhanced irregular firing, and reduced oscillatory theta band activity (4-8 Hz) in the mPFC of deaf rats as compared to controls (P < 0.05). In the IC, reduced oscillatory theta (4-8 Hz) and gamma (30-100 Hz) band activity was found in deaf rats (P < 0.05). Conclusion: Minor and transient behavioral deficits do not confirm direct impact of long-term hearing loss on cognitive function in rats. However, the altered neuronal activities in the mPFC and IC after hearing loss indicate effects on neuronal networks in and outside the central auditory system with potential consequences on cognitive function.

Deficient Recurrent Cortical Processing in Congenital Deafness.

The influence of sensory experience on cortical feedforward and feedback interactions has rarely been studied in the auditory cortex. Previous work has documented a dystrophic effect of deafness in deep cortical layers, and a reduction of interareal couplings between primary and secondary auditory areas in congenital deafness which was particularly pronounced in the top-down direction (from the secondary to the primary area). In the present study, we directly quantified the functional interaction between superficial (supragranular, I to III) and deep (infragranular, V and VI) layers of feline's primary auditory cortex A1, and also between superficial/deep layers of A1 and a secondary auditory cortex, namely the posterior auditory field (PAF). We compared adult hearing cats under acoustic stimulation and cochlear implant (CI) stimulation to adult congenitally deaf cats (CDC) under CI stimulation. Neuronal activity was recorded from auditory fields A1 and PAF simultaneously with two NeuroNexus electrode arrays. We quantified the spike field coherence (i.e., the statistical dependence of spike trains at one electrode with local field potentials on another electrode) using pairwise phase consistency (PPC). Both the magnitude as well as the preferred phase of synchronization was analyzed. The magnitude of PPC was significantly smaller in CDCs than in controls. Furthermore, controls showed no significant difference between the preferred phase of synchronization between supragranular and infragranular layers, both in acoustic and electric stimulation. In CDCs, however, there was a large difference in the preferred phase between supragranular and infragranular layers. These results demonstrate a loss of synchrony and for the first time directly document a functional decoupling of the interaction between supragranular and infragranular layers of the primary auditory cortex in congenital deafness. Since these are key for the influence of top-down to bottom-up computations, the results suggest a loss of recurrent cortical processing in congenital deafness and explain the outcomes of previous studies by deficits in intracolumnar microcircuitry.

Deafness Weakens Interareal Couplings in the Auditory Cortex.

The function of the cerebral cortex essentially depends on the ability to form functional assemblies across different cortical areas serving different functions. Here we investigated how developmental hearing experience affects functional and effective interareal connectivity in the auditory cortex in an animal model with years-long and complete auditory deprivation (deafness) from birth, the congenitally deaf cat (CDC). Using intracortical multielectrode arrays, neuronal activity of adult hearing controls and CDCs was registered in the primary auditory cortex and the secondary posterior auditory field (PAF). Ongoing activity as well as responses to acoustic stimulation (in adult hearing controls) and electric stimulation applied via cochlear implants (in adult hearing controls and CDCs) were analyzed. As functional connectivity measures pairwise phase consistency and Granger causality were used. While the number of coupled sites was nearly identical between controls and CDCs, a reduced coupling strength between the primary and the higher order field was found in CDCs under auditory stimulation. Such stimulus-related decoupling was particularly pronounced in the alpha band and in top-down direction. Ongoing connectivity did not show such a decoupling. These findings suggest that developmental experience is essential for functional interareal interactions during sensory processing. The outcomes demonstrate that corticocortical couplings, particularly top-down connectivity, are compromised following congenital sensory deprivation.

Categorical processing of fast temporal sequences in the guinea pig auditory brainstem.

Discrimination of temporal sequences is crucial for auditory object recognition, phoneme categorization and speech understanding. The present study shows that auditory brainstem responses (ABR) to pairs of noise bursts separated by a short gap can be classified into two distinct groups based on the ratio of gap duration to initial noise burst duration in guinea pigs. If this ratio was smaller than 0.5, the ABR to the trailing noise burst was strongly suppressed. On the other hand, if the initial noise burst duration was short compared to the gap duration (a ratio greater than 0.5), a release from suppression and/or enhancement of the trailing ABR was observed. Consequently, initial noise bursts of shorter duration caused a faster transition between response classes than initial noise bursts of longer duration. We propose that the described findings represent a neural correlate of subcortical categorical preprocessing of temporal sequences in the auditory system.

Stem Cell Based Drug Delivery for Protection of Auditory Neurons in a Guinea Pig Model of Cochlear Implantation.

Background: The success of a cochlear implant (CI), which is the standard therapy for patients suffering from severe to profound sensorineural hearing loss, depends on the number and excitability of spiral ganglion neurons (SGNs). Brain-derived neurotrophic factor (BDNF) has a protective effect on SGNs but should be applied chronically to guarantee their lifelong survival. Long-term administration of BDNF could be achieved using genetically modified mesenchymal stem cells (MSCs), but these cells should be protected - by ultra-high viscous (UHV-) alginate ('alginate-MSCs') - from the recipient immune system and from uncontrolled migration. Methods: Brain-derived neurotrophic factor-producing MSCs were encapsulated in UHV-alginate. Four experimental groups were investigated using guinea pigs as an animal model. Three of them were systemically deafened and (unilaterally) received one of the following: (I) a CI; (II) an alginate-MSC-coated CI; (III) an injection of alginate-embedded MSCs into the scala tympani followed by CI insertion and alginate polymerization. Group IV was normal hearing, with CI insertion in both ears and a unilateral injection of alginate-MSCs. Using acoustically evoked auditory brainstem response measurements, hearing thresholds were determined before implantation and before sacrificing the animals. Electrode impedance was measured weekly. Four weeks after implantation, the animals were sacrificed and the SGN density and degree of fibrosis were evaluated. Results: The MSCs survived being implanted for 4 weeks in vivo. Neither the alginate-MSC injection nor the coating affected electrode impedance or fibrosis. CI insertion with and without previous alginate injection in normal-hearing animals resulted in increased hearing thresholds within the high-frequency range. Low-frequency hearing loss was additionally observed in the alginate-injected and implanted cochleae, but not in those treated only with a CI. In deafened animals, the alginate-MSC coating of the CI significantly prevented SGN from degeneration, but the injection of alginate-MSCs did not. Conclusion: Brain-derived neurotrophic factor-producing MSCs encapsulated in UHV-alginate prevent SGNs from degeneration in the form of coating on the CI surface, but not in the form of an injection. No increase in fibrosis or impedance was detected. Further research and development aimed at verifying long-term mechanical and biological properties of coated electrodes in vitro and in vivo, in combination with chronic electrical stimulation, is needed before the current concept can be tested in clinical trials.

Induced cortical responses require developmental sensory experience.

Sensory areas of the cerebral cortex integrate the sensory inputs with the ongoing activity. We studied how complete absence of auditory experience affects this process in a higher mammal model of complete sensory deprivation, the congenitally deaf cat. Cortical responses were elicited by intracochlear electric stimulation using cochlear implants in adult hearing controls and deaf cats. Additionally, in hearing controls, acoustic stimuli were used to assess the effect of stimulus mode (electric versus acoustic) on the cortical responses. We evaluated time-frequency representations of local field potential recorded simultaneously in the primary auditory cortex and a higher-order area, the posterior auditory field, known to be differentially involved in cross-modal (visual) reorganization in deaf cats. The results showed the appearance of evoked (phase-locked) responses at early latencies (<100 ms post-stimulus) and more abundant induced (non-phase-locked) responses at later latencies (>150 ms post-stimulus). In deaf cats, substantially reduced induced responses were observed in overall power as well as duration in both investigated fields. Additionally, a reduction of ongoing alpha band activity was found in the posterior auditory field (but not in primary auditory cortex) of deaf cats. The present study demonstrates that induced activity requires developmental experience and suggests that higher-order areas involved in the cross-modal reorganization show more auditory deficits than primary areas.

Intracortical microstimulation differentially activates cortical layers based on stimulation depth.

BACKGROUND: Intracortical microstimulation is one of the most common techniques to causally interfere with neuronal processing, but neuronal recordings spanning the whole cortical depth during stimulation are exceptionally rare. OBJECTIVE/HYPOTHESIS: Here we combined layer-specific intracortical microstimulation with extracellular recordings on the same shank of a linear multi-electrode array to study the effects of electrical stimulation in different cortical depths on intracortical processing in the auditory cortex in vivo. METHODS: Population responses (local field potentials and multi-unit activity) were recorded from the auditory cortex of 8 guinea pigs under ketamine/xylazine anesthesia while single current pulses (charge-balanced, biphasic, square-wave, 0.1-45 µA, 200 µs/phase) were delivered in different cortical depths. RESULTS: The cortical responses differed with a change in the stimulation parameters, with significant factors being the stimulating current (p < 0.0001), stimulation depth (p = 0.03) and the recording depth (p = 0.002) considering the local field potential amplitude. A cross-correlation analysis between responses evoked by intracortical microstimulation and physiological auditory stimuli revealed the closest match when stimulating the middle granular layer (p < 0.05). CONCLUSION: Intracortical response profiles to low-current intracortical microstimulation were layer specific. The most natural cortical response was achieved by stimulation in the thalamo-recipient layer. These findings contribute to a basis for designing cortical neuroprosthetics.

Cross-Modal Plasticity in Higher-Order Auditory Cortex of Congenitally Deaf Cats Does Not Limit Auditory Responsiveness to Cochlear Implants.

UNLABELLED: Congenital sensory deprivation can lead to reorganization of the deprived cortical regions by another sensory system. Such cross-modal reorganization may either compete with or complement the "original" inputs to the deprived area after sensory restoration and can thus be either adverse or beneficial for sensory restoration. In congenital deafness, a previous inactivation study documented that supranormal visual behavior was mediated by higher-order auditory fields in congenitally deaf cats (CDCs). However, both the auditory responsiveness of "deaf" higher-order fields and interactions between the reorganized and the original sensory input remain unknown. Here, we studied a higher-order auditory field responsible for the supranormal visual function in CDCs, the auditory dorsal zone (DZ). Hearing cats and visual cortical areas served as a control. Using mapping with microelectrode arrays, we demonstrate spatially scattered visual (cross-modal) responsiveness in the DZ, but show that this did not interfere substantially with robust auditory responsiveness elicited through cochlear implants. Visually responsive and auditory-responsive neurons in the deaf auditory cortex formed two distinct populations that did not show bimodal interactions. Therefore, cross-modal plasticity in the deaf higher-order auditory cortex had limited effects on auditory inputs. The moderate number of scattered cross-modally responsive neurons could be the consequence of exuberant connections formed during development that were not pruned postnatally in deaf cats. Although juvenile brain circuits are modified extensively by experience, the main driving input to the cross-modally (visually) reorganized higher-order auditory cortex remained auditory in congenital deafness. SIGNIFICANCE STATEMENT: In a common view, the "unused" auditory cortex of deaf individuals is reorganized to a compensatory sensory function during development. According to this view, cross-modal plasticity takes over the unused cortex and reassigns it to the remaining senses. Therefore, cross-modal plasticity might conflict with restoration of auditory function with cochlear implants. It is unclear whether the cross-modally reorganized auditory areas lose auditory responsiveness. We show that the presence of cross-modal plasticity in a higher-order auditory area does not reduce auditory responsiveness of that area. Visual reorganization was moderate, spatially scattered and there were no interactions between cross-modally reorganized visual and auditory inputs. These results indicate that cross-modal reorganization is less detrimental for neurosensory restoration than previously thought.

Monaural Congenital Deafness Affects Aural Dominance and Degrades Binaural Processing.

Cortical development extensively depends on sensory experience. Effects of congenital monaural and binaural deafness on cortical aural dominance and representation of binaural cues were investigated in the present study. We used an animal model that precisely mimics the clinical scenario of unilateral cochlear implantation in an individual with single-sided congenital deafness. Multiunit responses in cortical field A1 to cochlear implant stimulation were studied in normal-hearing cats, bilaterally congenitally deaf cats (CDCs), and unilaterally deaf cats (uCDCs). Binaural deafness reduced cortical responsiveness and decreased response thresholds and dynamic range. In contrast to CDCs, in uCDCs, cortical responsiveness was not reduced, but hemispheric-specific reorganization of aural dominance and binaural interactions were observed. Deafness led to a substantial drop in binaural facilitation in CDCs and uCDCs, demonstrating the inevitable role of experience for a binaural benefit. Sensitivity to interaural time differences was more reduced in uCDCs than in CDCs, particularly at the hemisphere ipsilateral to the hearing ear. Compared with binaural deafness, unilateral hearing prevented nonspecific reduction in cortical responsiveness, but extensively reorganized aural dominance and binaural responses. The deaf ear remained coupled with the cortex in uCDCs, demonstrating a significant difference to deprivation amblyopia in the visual system.

Strengthening of hearing ear representation reduces binaural sensitivity in early single-sided deafness.

Single-sided deafness initiates extensive adaptations in the central auditory system, with the consequence that a stronger and a weaker ear representation develops in the auditory brain. Animal studies demonstrated that the effects are substantially stronger if the condition starts early in development. Sequential binaural cochlear implantations with longer interimplant delays demonstrate that the speech comprehension at the weaker ear is substantially compromised. A pronounced loss of the ability to extract and represent binaural localisation cues accompanies this condition, as shown in animal models.

Auditory feedback modulates development of kitten vocalizations.

Effects of hearing loss on vocal behavior are species-specific. To study the impact of auditory feedback on feline vocal behavior, vocalizations of normal-hearing, hearing-impaired (white) and congenitally deaf (white) cats were analyzed at around weaning age. Eleven animals were placed in a soundproof booth for 30 min at different ages, from the first to the beginning of the fourth postnatal month, every 2 weeks of life. In total, 13,874 vocalizations were analyzed using an automated procedure. Firstly, vocalizations were detected and segmented, with voiced and unvoiced vocalizations being differentiated. The voiced isolation calls ('meow') were further analyzed. These vocalizations showed developmental changes affecting several parameters in hearing controls, whereas the developmental sequence was delayed in congenitally deaf cats. In hearing-impaired and deaf animals, we observed differences both in vocal behavior (loudness and duration) and in the calls' acoustic structure (fundamental frequency and higher harmonics). The fundamental frequency decreased with age in all groups, most likely due to maturation of the vocal apparatus. In deaf cats, however, other aspects of the acoustic structure of the vocalizations did not fully mature. The harmonic ratio (i.e., frequency of first harmonic divided by fundamental frequency) was higher and more variable in deaf cats than in the other study groups. Auditory feedback thus affects the acoustic structure of vocalizations and their ontogenetic development. The study suggests that both the vocal apparatus and its neuronal motor control are subject to maturational processes, whereas the latter is additionally dependent on auditory feedback in cats.

Hearing and age-related changes in the gray mouse lemur.

In order to examine auditory thresholds and hearing sensitivity during aging in the gray mouse lemur (Microcebus murinus), suggested to represent a model for early primate evolution and Alzheimer research, we applied brainstem-evoked response audiometry (BERA), traditionally used for screening hearing sensitivity in human babies. To assess the effect of age, we determined auditory thresholds in two age groups of adult mouse lemurs (young adults, 1-5 years; old adults, ≥7 years) using clicks and tone pips. Auditory thresholds indicated frequency sensitivity from 800 Hz to almost 50 kHz, covering the species tonal communication range with fundamentals from about 8 to 40 kHz. The frequency of best hearing at 7.9 kHz was slightly lower than that and coincided with the dominant frequencies of communication signals of a predator. Aging shifted auditory thresholds in the range between 2 and 50.4 kHz significantly by 12-27 dB. This mild presbyacusis, expressed in a drop of amplitudes of BERA signals, but not discernible in latencies of responses, suggests a metabolic age-related decrease potentially combined with an accompanying degeneration of the cochlear nerve. Our findings on hearing range of this species support the hypothesis that predation was a driving factor for the evolution of hearing in small ancestral primates. Likewise, results provide the empirical basis for future approaches trying to differentiate peripheral from central factors when studying Alzheimer's disease-like pathologies in the aging brain.

Unilateral hearing during development: hemispheric specificity in plastic reorganizations.

The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing (unilateral deafness). The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved.

Neural representation in the auditory midbrain of the envelope of vocalizations based on a peripheral ear model.

The auditory midbrain implant (AMI) consists of a single shank array (20 sites) for stimulation along the tonotopic axis of the central nucleus of the inferior colliculus (ICC) and has been safely implanted in deaf patients who cannot benefit from a cochlear implant (CI). The AMI improves lip-reading abilities and environmental awareness in the implanted patients. However, the AMI cannot achieve the high levels of speech perception possible with the CI. It appears the AMI can transmit sufficient spectral cues but with limited temporal cues required for speech understanding. Currently, the AMI uses a CI-based strategy, which was originally designed to stimulate each frequency region along the cochlea with amplitude-modulated pulse trains matching the envelope of the bandpass-filtered sound components. However, it is unclear if this type of stimulation with only a single site within each frequency lamina of the ICC can elicit sufficient temporal cues for speech perception. At least speech understanding in quiet is still possible with envelope cues as low as 50 Hz. Therefore, we investigated how ICC neurons follow the bandpass-filtered envelope structure of natural stimuli in ketamine-anesthetized guinea pigs. We identified a subset of ICC neurons that could closely follow the envelope structure (up to ~100 Hz) of a diverse set of species-specific calls, which was revealed by using a peripheral ear model to estimate the true bandpass-filtered envelopes observed by the brain. Although previous studies have suggested a complex neural transformation from the auditory nerve to the ICC, our data suggest that the brain maintains a robust temporal code in a subset of ICC neurons matching the envelope structure of natural stimuli. Clinically, these findings suggest that a CI-based strategy may still be effective for the AMI if the appropriate neurons are entrained to the envelope of the acoustic stimulus and can transmit sufficient temporal cues to higher centers.

Single-sided deafness leads to unilateral aural preference within an early sensitive period.

Unilateral deafness has a high incidence in children. In addition to children who are born without hearing in one ear, children with bilateral deafness are frequently equipped only with one cochlear implant, leaving the other ear deaf. The present study investigates the effects of such single-sided deafness during development in the congenitally deaf cat. The investigated animals were either born with unilateral deafness or received a cochlear implant in one ear and were subjected to chronic monaural stimulation. In chronically stimulated animals, implantation ages were at the following three critical developmental points: 'early' during the peak of functional cortical synaptogenesis in deaf animals; 'intermediate' at the age when synaptic activity in the deaf cats dropped to the level of hearing control cats and finally, 'late' at the age when the evoked synaptic activity fell below the level of hearing control cats. After periods of unilateral hearing, local field potentials were recorded from the cortical surface using a microelectrode at ∼100 recording positions. Stimulation was with cochlear implants at both ears. The measures evaluated were dependent only on the symmetry of aural input: paired differences of onset latencies and paired relations of peak amplitudes of local field potentials. A massive reorganization of aural preference in favour of the hearing ear was found in these measures if the onset of unilateral hearing was early (before or around the peak of functional synaptogenesis). The effect was reduced if onset of unilateral hearing was in the intermediate period, and it disappeared if the onset was late. In early onset of unilateral deafness, the used ear became functionally dominant with respect to local field potential onset latency and amplitude. This explains the inferior outcome of implantations at the second-implanted ear compared with first-implanted ear in children. However, despite a central disadvantage for the deaf ear, it still remained capable of activating the auditory cortex. Appropriate training may thus help to improve the performance at the second-implanted ear. In conclusion, periods of monaural stimulation should be kept as short as possible, and training focused on the deaf ear should be introduced after delayed second implantation in children.

Fast propagating waves within the rodent auditory cortex.

Central processing of acoustic signals is assumed to take place in a stereotypical spatial and temporal pattern involving different fields of auditory cortex. So far, cortical propagating waves representing such patterns have mainly been demonstrated by optical imaging, repeatedly in the visual and somatosensory cortex. In this study, the surface of rat auditory cortex was mapped by recording local field potentials (LFPs) in response to a broadband acoustic stimulus. From the peak amplitudes of LFPs, cortical activation maps were constructed over 4 cortical auditory fields. Whereas response onset had same latencies across primary auditory field (A1), anterior auditory field (AAF), and ventral auditory field and longer latencies in posterior auditory field, activation maps revealed a reproducible wavelike pattern of activity propagating for ∼45 ms poststimulus through all cortical fields. The movement observed started with 2 waves within the primary auditory fields A1 and AAF moving from ventral to dorsal followed by a motion from rostral to caudal, passing continuously through higher-order fields. The pattern of propagating waves was well reproducible and showed only minor changes if different anesthetics were used. The results question the classical "hierarchical" model of cortical areas and demonstrate that the different fields process incoming information as a functional unit.