Cochlear Lesions Research Articles

Neural Hyperactivity of the Central Auditory System in Response to Peripheral Damage.

It is increasingly appreciated that cochlear pathology is accompanied by adaptive responses in the central auditory system. The cause of cochlear pathology varies widely, and it seems that few commonalities can be drawn. In fact, despite intricate internal neuroplasticity and diverse external symptoms, several classical injury models provide a feasible path to locate responses to different peripheral cochlear lesions. In these cases, hair cell damage may lead to considerable hyperactivity in the central auditory pathways, mediated by a reduction in inhibition, which may underlie some clinical symptoms associated with hearing loss, such as tinnitus. Homeostatic plasticity, the most discussed and acknowledged mechanism in recent years, is most likely responsible for excited central activity following cochlear damage.

Auditory brainstem response and late latency response in individuals with tinnitus having normal hearing.

Tinnitus is a commonly encountered complaint in routine audiology practice. The pathophysiology and exact generation site of tinnitus is not precisely established. Auditory brainstem response (ABR) and late latency response (LLR) findings in individuals with tinnitus show mixed results in the literature. Majority of studies have focused on individuals having tinnitus with peripheral hearing loss. The present study explores ABR and LLR characteristics among tinnitus patients with normal audiometric presentation; with no direct indication of any cochlear lesion. This study aims at characterizing the ABR and LLR findings in individuals with tinnitus having normal audiometric presentation. ABR and LLR waveform characteristics were recorded and compared between participants with tinnitus (Group 1) and those without tinnitus (Group 2). The ABR analysis indicated no significant differences in latency and amplitude between Groups 1 and 2. However, patients with tinnitus showed abnormally reduced absolute amplitudes of peaks I and V. LLR analysis indicated no significant differences in latency and amplitude between Groups 1 and 2 except enhanced amplitude of P1. The reduced amplitude of peaks I and V along with normal absolute latencies of peaks I, III and V indicate that the origin of tinnitus is possibly due to reduced excitation of auditory nerve fibres arising from a peripheral hearing loss beyond 8 kHz. The P1 amplitude enhancement could be attributed to mechanism explaining central gain model; which suggests that central auditory structures recalibrates the mean firing rate, considering the reduced output from sensory structures, generating neural noise perceived as tinnitus.

Establishment of a model of cochlear lesions in rats to study potential gene therapy for sensorineural hearing loss

IntroductionSensorineural hearing loss seriously influences a patient's daily life, and no effective treatments exist to date. Gene therapy is a potential treatment for regenerating hair cells to restore hearing. MethodsIn this study, we established a cochlear lesions model to study hair cell regeneration by co-administration of kanamycin and furosemide. After the injections, we assessed the survival of outer hair cells (OHC), inner hair cells (IHC), supporting cells (SC), spiral ganglion neurons (SGN) and peripheral axons. Moreover, we used two viral vectors to detect the transgene distribution. ResultsOur results showed at 12h post-treatment, numerous OHC were missing in the basal turn. At 24h post-treatment, all OHCs in basal half of the cochlea were lost, and by 48h, OHC loss had spread to the apical coil. Four days after the injections, all OHCs were absent. At 1mo post-treatment, the organ of Corti had collapsed. In contrast, most of the SC remained 4d after the injections. The loss of SGN and peripheral axons was consistent with this time course post-treatment. The results of transgene distribution suggested the correlative gene can be transferred into the organ of Corti using adenoviruses (AdV) vectors and lentiviruses (LV) vectors in our cochlear lesion model.Comparison with Existing Method(s): We assessed the details of HC death at more time point and chosen the time point for gene transfer in this model. ConclusionsWe conclude that this cochlear lesion model would be suitable for the study of hair cell regeneration.

Noise-induced damage to ribbon synapses without permanent threshold shifts in neonatal mice

Recently, ribbon synapses to the hair cells (HCs) in the cochlea have become a novel site of interest in the investigation of noise-induced cochlear lesions in adult rodents (Kujawa and Liberman, 2009; Lin et al., 2011; Liu et al., 2012; Shi et al., 2013). Permanent noise-induced damage to this type of synapse can result in subsequent degeneration of spiral ganglion neurons (SGNs) in the absence of permanent changes to hearing sensitivity. To verify whether noise exposure during an early developmental period produces a similar impact on ribbon synapses, the present study examined the damaging effects of noise exposure in neonatal Kunming mice. The animals received exposure to broadband noise at 105-decibel (dB) sound pressure level (SPL) for 2h on either postnatal day 10 (P10d) or postnatal day 14 (P14d), and then hearing function (based on the auditory brainstem response (ABR)) and cochlear morphology were evaluated during either postnatal weeks 3–4 (P4w) or postnatal weeks 7–8 (P8w). There were no significant differences in the hearing threshold between noise-exposed and control animals, which suggests that noise did not cause permanent loss of hearing sensitivity. However, noise exposure did produce a significant loss of ribbon synapses, particularly in P14d mice, which continued to increase from P4w to P8w. Additionally, a corresponding reduction in the amplitude of compound action potential (CAP) was observed in the noise-exposed groups at P4w and P8w, and the CAP latency was elongated, indicating a change in synaptic function.

LP9: Central post-stroke pain explored by laser-evoked potentials and quantitative sensory testing: a multiple case study

s of Poster Presentations / Clinical Neurophysiology 125, Supplement 1 (2014) S1–S339 S87 Results: Comparison of the auditory dysfunctions with the vestibular symptoms in patients with the unilateral hearing loss makes it possible to highlight the following regularities: 1.The patients suffered from MS with hearing loss always have retro cochlear lesion. 2. Patients with the unilateral hearing loss and brainstem vestibular symptoms, which indicate the damage of auditory and vestibular pathways in the brainstem, have plural plugs in the brainstem on MRI.3. In case of the unilateral hearing loss up to the deafness, which is not combined with the brainstem vestibular symptoms, the plugs of demyelization on MRI in the usual regime may be not revealed. However, the signs of the disturbances of afferentation specific for MS could be reviled by the EP data. Conclusion: The novelty of work consists in the complex use of objective methods of investigation the auditory and vestibular functions by EP and MRI in the regime of thin slices. LP9 Central post-stroke pain explored by laser-evoked potentials and quantitative sensory testing: a multiple case study E. Opsommer1, L. Stockinger2, G. Landmann2 1University of Applied Sciences and Arts Western Switzerland, Lausanne, Switzerland; 2Swiss Paraplegic Centre, Centre for Pain Medicine, Nottwil,

Effect of metabolic presbyacusis on cochlear responses: A simulation approach using a physiologically-based model

In the presented model, electrical, acoustical, and mechanical elements of the cochlea are explicitly integrated into a signal transmission line where these elements convey physiological interpretations of the human cochlear structures. As a result, this physiologically-motivated model enables simulation of specific cochlear lesions such as presbyacusis. The hypothesis is that high-frequency hearing loss in older adults may be due to metabolic presbyacusis whereby age-related cellular/chemical degenerations in the lateral wall of the cochlea cause a reduction in the endocochlear potential. The simulations quantitatively confirm this hypothesis and emphasize that even if the outer and inner hair cells are totally active and intact, metabolic presbyacusis alone can significantly deteriorate the cochlear functionality. Specifically, in the model, as the endocochlear potential decreases, the transduction mechanism produces less receptor current such that there is a reduction in the battery of the somatic motor. This leads to a drastic decrease in cochlear amplification and frequency sensitivity, as well as changes in position-frequency map (tuning pattern) of the cochlea. In addition, the simulations show that the age-related reduction of the endocochlear potential significantly inhibits the firing rate of the auditory nerve which might contribute to the decline of temporal resolution in the aging auditory system.

Ototoxic Model of Oxaliplatin and Protection from Nicotinamide Adenine Dinucleotide

Oxaliplatin, an anticancer drug commonly used to treat colorectal cancer and other tumors, has a number of serious side effects, most notably neuropathy and ototoxicity. To gain insights into its ototoxic profile, oxaliplatin was applied to rat cochlear organ cultures. Consistent with it neurotoxic propensity, oxaliplatin selectively damaged nerve fibers at a very low dose 1 μM. In contrast, the dose required to damage hair cells and spiral ganglion neurons was 50 fold higher (50 μM). Oxailiplatin-induced cochlear lesions initially increased with dose, but unexpectedly decreased at very high doses. This non-linear dose response could be related to depressed oxaliplatin uptake via active transport mechanisms. Previous studies have demonstrated that axonal degeneration involves biologically active processes which can be greatly attenuated by nicotinamide adenine dinucleotide (NAD+). To determine if NAD+ would protect spiral ganglion axons and the hair cells from oxaliplatin damage, cochlear cultures were treated with oxaliplatin alone at doses of 10 μM or 50 μM respectively as controls or combined with 20mM NAD+. Treatment with 10 μM oxaliplatin for 48hours resulted in minor damage to auditory nerve fibers, but spared cochlear hair cells. However, when cochlear cultures were treated with 10 μM oxaliplatin plus 20mM NAD+, most auditory nerve fibers were intact. 50 μM oxaliplatin destroyed most of spiral ganglion neurons and cochlear hair cells with apoptotic characteristics of cell fragmentations. However, 50 μM oxaliplatin plus 20mM NAD+ treatment greatly reduced neuronal degenerations and hair cell missing. The results suggested that NAD+ provides significant protection against oxaliplatin-induced neurotoxicity and ototoxicity, which may be due to its actions of antioxidant, antiapoptosis, and energy supply.

Comparison of Cochlear Cell Death Caused by Cisplatin, Alone and in Combination with Furosemide

Establishment of appropriate animal models is an important step in exploring the mechanisms of drug-induced ototoxicity. In the present study, using guinea pigs we compared cochlear lesions induced by cisplatin administered in two regimens: consecutive application alone and in combination with furosemide. The effects of furosemide alone were also evaluated; it was found to cause temporary hearing loss and reversible damage to the stria vascularis. Consecutive application of cisplatin alone appeared to be disadvantageous because it resulted in progressive body weight loss and higher mortality compared to the combined regimen, which used a smaller cisplatin dose. The combined regimen resulted in comparable hearing loss and hair cell loss but a markedly lower mortality. However, their coadministration failed to cause similar damage to spiral ganglion neurons (SGN), as seen in animals that received cisplatin alone. This difference suggests that the combined regimen did not mimic the damage to cochlear neuronal innervation caused by the clinical application of cisplatin. The difference also suggests that the SGN lesion is not caused by cisplatin entering the cochlea via the stria vascularis.

Cochlear Cell Death Induced Via Cisplatin or Gentamycin in Combination with Furosemide in Rodents

Ototoxic models of animal represent an elemental tool in basic otological research. In the present study, using guinea pigs we compared cochlear lesions mediated via cisplatin applied in terms of two regimens: consecutive application alone and in combination with furosemide. The influences of furosemide alone were also assessed; it was observed to result in temporary hearing loss and reversible damage to the stria vascularis. Consecutive administration of cisplatin alone tended to be disadvantageous because it bred progressive body weight loss and higher mortality compared with the combined regimen, which utilized a smaller cisplatin dose. The combined regimen brought about remarkable hair cell loss without corresponding lesion of spiral ganglion neurons. This difference suggests that the co-administered regimen did not mimic the damage to cochlear neuronal innervation caused by clinical application of cisplatin. In the meantime, we spread this method to the ototoxic model build in mice. Coadministration of gentamicin and furosemide caused marked hair cell loss as well as less mortality compared with consecutive application of gentamicin in mice. Due to different pharmacokinetics between cisplatin in guinea pigs and gentamicin in mice, the injection regimens of co-administration of furosemide - cisplatin in guinea pigs and gentamicin – furosemide in mice were varied. Overall, the methods of co-administration of cisplatin/gentacimin and furosemide in rodents facilitate ototoxic model build.

Hyperexcitability of inferior colliculus neurons caused by acute noise exposure

Noise exposure is one of the most common causes of hearing loss. Recent studies found that noise exposure-induced cochlear damage may change the excitability and tonotopic organization of the central auditory system (CAS). This plasticity was suspected to be related to tinnitus and hyperacusis. However, how cochlear damage affects CAS function and causes these neurologic diseases is still not clear. CAS function is activity dependent, so we hypothesize that a restricted cochlear lesion might disrupt the balance of excitation and inhibition in the CAS and thereby affect its neural activity. To test this hypothesis, we studied the effects of narrow-band noise exposure on the firing properties of neurons in the inferior colliculus (IC), which has complex neural circuits and plays an important role in sound processing. We found that noise exposure (20 kHz, 105 dB SPL, 30 min) caused a dramatic decrease of the characteristic frequency in about two-thirds of high-frequency neurons with/without causing a significant threshold shift. The noise exposure also caused an increase in firing rate of the low-frequency neurons at suprathreshold levels, whereas it dramatically decreased the firing rate of the high-frequency neurons. Our results suggest that acute high-frequency noise exposure may increase low-frequency responsiveness by causing hyperexcitability of low-frequency neurons. The functional change of the low-frequency neurons may be related to the disruption of side-band inhibition at the noise exposure frequencies caused by cochlear damage.

Neuromagnetic index of hemispheric asymmetry predicting long-term outcome in sudden hearing loss

The neuromagnetic index of hemispheric asymmetry in terms of ipsilateral/contralateral ratio at acute stage was previously revealed to prognosticate the 1-month hearing outcome of acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL), showing a dynamic relationship between top- and down-levels of auditory pathway. However, the prognostic effect of reorganization pattern for the long-term results remained elusive. This study aimed to probe the prognosticating relevance of hemispheric asymmetry to the hearing at chronic stage of ISSNHL. Using magnetoencephalography (MEG), inter-hemispheric differences in peak dipole of N100m responses to monaural tones were evaluated in 21 controls and 21 ISSNHL patients at initial and final (12 months later) stages. Predictive value of hemispheric asymmetry was assessed by correlating hearing level and ipsilateral/contralateral ratio (I/C) of N100m latency and amplitude. Healthy-side dominance of N100m was observed in ISSNHL initially, and remained in three final prognostic subgroups (complete, partial, and no recovery) of ISSNHL. The initial I/C(amplitude) on affected-ear stimulation strongly correlated with the hearing level of final stage in ISSNHL. However, there was no prognostic effect of hemispheric asymmetry pattern for the 12-month hearing improvement. The heterogeneity between neuromagnetic index and hearing levels possibly echoed different pathogeneses of ISSNHL. Since a restored hearing status did not necessarily lead toward a normal functional organization, the dynamics of hemispheric asymmetry could actually index a central resilient reorganization in the brain for sound processing in ISSNHL. Our finding showed not only a clinically relevant measure to predict final hearing of ISSNHL, but also a linkage between central plasticity and cochlear lesion. This finding suggests a new perspective, and perhaps new interventions, to diagnose and treat unilateral ISSNHL.

Downregulation of N-methyl-d-aspartate receptor ζ1 subunit (GluN1) gene in inferior colliculus with aging

Presbycusis is the impairment of auditory function associated with aging, which stems from peripheral cochlear lesions and degeneration of the central auditory process. The effect of age-induced peripheral hearing loss on the central auditory process is not fully understood. C57Bl/6 (C57) mice present accelerated peripheral hearing loss, which is well developed by middle-age and mimics the human presbycusis pattern. The aim of this study was to elucidate the molecular effects of peripheral hearing loss in the inferior colliculus (IC) with age between young and middle-aged C57 mice using cDNA microarray. Glutamate receptor ionotropic NMDA ζ1 (GluN1) exhibited the greatest decrease in the middle-aged group as determined using cDNA microarray and by further assessment using real-time PCR (qPCR). Histological assessment with in situ hybridization of GluN1 showed significantly decreased expression in all IC subdivisions of the middle-aged group. GluN1 is a receptor for excitatory neurotransmission, and significant downregulation of this gene may be subsequent to the decline of afferent input from the cochlea in aging C57 mice. Consequently, using the combination of microarray, qPCR, and in situ hybridization, we showed that the decline of GluN1 in the IC of aging animals might have a key role in the pathogenesis of presbycusis.

Comparison of various treatment modalities for acute tinnitus

Because in most cases the development of tinnitus is triggered by cochlear damage, there exists the opportunity to eliminate tinnitus while the cochlear lesion is still reversible. Therefore, we evaluated the therapeutic effects of various treatment modalities on acute subjective idiopathic tinnitus (SIT) and investigated prognostic factors affecting the treatment outcome. Prospective, controlled, double-blind trial. A total 107 patients who underwent treatment for unilateral SIT that had developed within the previous 3 months completed the study. The patients were randomly assigned into three groups according to the treatment modality: group I (n = 32), alprazolam orally for 3 months; group II (n = 35), as for group I plus four intratympanic dexamethasone (ITD) injections; and group III (n = 40), as for group II plus four intravenous injections of lipo-prostaglandin E(1) . The improvement rate of group II (75.8%) was significantly higher than that of group I (40.3%; P < .05), and there was no significant difference in the improvement rate of group III (50.0%) compared with groups I and II (P > .05). The cure rates of group II (25.8%) and group III (20.0%) were significantly higher than that of group I (9.8%; P < .05). There was a significant correlation between the cure rate and duration of symptoms. The results of the present study indicate that ITD injection plus alprazolam medication is the best treatment choice for acute SIT within 3 months of development.

Ototoxic destruction by co-administration of kanamycin and ethacrynic acid in rats

It is well known that ethacrynic acid (EA) can potentiate the ototoxicity of aminoglycoside antibiotics (AmAn) such as kanamycin (KM), if they were applied at the same time. Currently, to create the model of EA-KM-induced cochlear lesion in rats, adult rats received a single injection of EA (75 mg/kg, intravenous injection), or followed immediately by KM (500 mg/kg, intramuscular injection). The hearing function was assessed by auditory brainstem response (ABR) measurement in response to click and/or tone bursts at 4, 8, 12, 16, 20, 24, and 32 kHz. The static microcirculation status in the stria vascularis after a single EA injection was evaluated with eosin staining. The pathological changes in cochlear and vestibular hair cells were also quantified after co-administration of EA and KM. After a single EA injection, blood flow in vessels supplying the stria vascularis rapidly diminished. However, the blood supply to the cochlear lateral wall partially recovered 5 h after EA treatment. Threshold changes in ABR were basically parallel to the microcirculation changes in stria vascularis after single EA treatment. Importantly, disposable co-administration of EA and KM resulted in a permanent hearing loss and severe damage to the cochlear hair cells, but spared the vestibular hair cells. Since the cochlear lateral wall is the important part of the blood-cochlea barrier, EA-induced anoxic damage to the epithelium of stria vascularis may enhance the entry of KM to the cochlea. Thus, experimental animal model of selective cochlear damage with normal vestibular systems can be reliably created through co-administration of EA and KM.

Conservation of endocochlear potential in mice with profound hearing loss induced by co-administration of kanamycin and furosemide

Research in mammalian hair cell regeneration is hampered by a lack of in vivo model of adult mouse inner ear injury. In the present study we investigated the effects of a combination of a single dose of aminoglycoside followed by a loop diuretic in adult mice. The auditory brainstem response threshold shift, extent and defining characteristics of the cochlear lesion were assessed and verified at different time points post-treatment. Our data indicated that this drug combination caused the rapid and extensive death of outer hair cells (OHCs). OHC death presented throughout the cochlea that commenced in the basal turn by 24 h and progressed apically. In contrast, inner hair cell (IHC) loss was delayed and mild. Terminal deoxynucleotidyl transferase dUTP nick end labelling-positive nuclei demonstrated that the majority of OHCs died via an apoptotic pathway. Auditory threshold shifts of up to 90 dB SPL indicated a profound hearing loss. In addition, the endocochlear potential (EP) in the drug-treated animals displayed a significant decline at 12 h post-treatment followed by recovery by 48 h post-treatment. Despite this recovery, there was a significant and progressive decrease in strial vascularis thickness, which was predominantly due to atrophy of marginal cells. The present study reproduced an adult mouse model of aminoglycoside-induced hearing loss. The mechanism underlying the recovered EP in the model with extensive hair cell death is discussed.

Musical hallucination associated with hearing loss

In spite of the fact that musical hallucination have a significant impact on patients' lives, they have received very little attention of experts. Some researchers agree on a combination of peripheral and central dysfunctions as the mechanism that causes hallucination. The most accepted physiopathology of musical hallucination associated to hearing loss (caused by cochlear lesion, cochlear nerve lesion or by interruption of mesencephalon or pontine auditory information) is the disinhibition of auditory memory circuits due to sensory deprivation. Concerning the cortical area involved in musical hallucination, there is evidence that the excitatory mechanism of the superior temporal gyrus, as in epilepsies, is responsible for musical hallucination. In musical release hallucination there is also activation of the auditory association cortex. Finally, considering the laterality, functional studies with musical perception and imagery in normal individuals showed that songs with words cause bilateral temporal activation and melodies activate only the right lobe. The effect of hearing aids on the improvement of musical hallucination as a result of the hearing loss improvement is well documented. It happens because auditory hallucination may be influenced by the external acoustical environment. Neuroleptics, antidepressants and anticonvulsants have been used in the treatment of musical hallucination. Cases of improvement with the administration of carbamazepine, meclobemide and donepezil were reported, but the results obtained were not consistent.

Noise-induced tinnitus: A comparison between four clinical groups without apparent hearing loss

The number of people with normal hearing thresholds seeking medical help for tinnitus and other hearing problems is increasing. For diagnostic purposes, existence/nonexistence of lesions or combinations of lesions in the inner ear not reflected in the audiogram was evaluated with advanced hearing tests applied to tinnitus patients with certain backgrounds, including noise exposure. For forty-six patients with pronounced tinnitus, and other symptoms, tentative diagnoses were established, including judgments of the influence of four causative factors: (1) acoustic trauma, (2) music, (3) suspected hereditary, and (4) nonauditory, for example, stress or muscular tension. They were analyzed with a test battery sensitive to lesions involving the outer hair cells, damage from impulse noise, and dysfunction of the efferent system. There were significant differences in test results between groups with individuals with the same most likely causative factor. Most patients claiming acoustic trauma had a specific type of result, 'hyper-PMTF' (psychoacoustical modulation transfer function), and abnormal test results of the efferent system. Everyone in the hereditary group had dysfunction of the efferent system. All patients working with music, except one, had some abnormality, but without specific pattern. The nonauditory group mostly had normal test results. The investigation shows that it is possible to diagnose minor cochlear lesions as well as dysfunction of the efferent system, which might be causing the tinnitus. Those abnormalities could not be detected with routine audiological tests. Malfunctioning caused by impulse noise is an obvious example of this. These findings facilitate choice of treatment, rehabilitation programs, and medicolegal decisions.

Increased BrdU incorporation reflecting DNA repair, neuronal de-differentiation or possible neurogenesis in the adult cochlear nucleus following bilateral cochlear lesions in the rat

Neurogenesis is known to occur in response to injury in the brain, for example, as a result of neurodegenerative diseases. However, there have been few investigations into how the brain responds to damage to peripheral sensory nerves, in other areas such as the brainstem. Here, we report that bilateral surgical lesions of the cochlea result in increased incorporation of the DNA replication marker, bromodeoxyuridine (BrdU), in cells of the brainstem cochlear nucleus (CN) of the adult rat, suggesting either cell proliferation or DNA repair. Some of the BrdU-labelled cells colabelled for the mature neuron marker, NeuN and the GABAergic enzyme GAD-65, suggesting the possibility that neurogenesis might have occurred and resulted in the generation of new neurons with a GABAergic phenotype. However, some of the mature neurons also re-expressed immature neuronal intermediate filament and microtuble-associated proteins, without apoptotic neuronal death, which suggests that the colabelling of BrdU with NeuN and GAD-65 may not be a true reflection of neurogenesis, but injury-stimulated neuronal dedifferentiation. These results suggest the possibility that DNA repair, neuronal de-differentiation or possible neurogenesis occurs in the cochlear nucleus, in response to damage to the peripheral auditory system.

Histopathologic Changes of the Ear in Canine Models of Mucopolysaccharidosis Types I and VII

Mucopolysaccharidosis (MPS) types I and VII are inborn errors of metabolism caused by mutation of enzymes involved in glycosaminoglycan catabolism, which leads to intralysosomal accumulation of glycosaminoglycans. In children, severe forms of MPS I and VII are characterized by somatic and neurologic manifestations, including a poorly understood hearing loss. The purpose of this study is to describe the age-related histopathologic changes of the ear in spontaneous canine models of MPS I and VII. Pathologic changes in the ear were assessed in MPS I and VII dogs ranging from 1.6 to 9.3 months of age. Paraffin-embedded sections of the whole ear and Epon-embedded semithin sections of the cochlea were examined. The following lesions were blindly scored in the middle and inner ear: inflammation, cells vacuolization, thickening of osseous and membranous structures, perivascular vacuolated macrophages infiltration, and bone resorption. All dogs had lysosomal storage within cells of tympanic membrane, ossicles, tympanic bone and mucosa, cochlear bone, spiral ligament, limbus, and stria vascularis. The MPS I dogs mainly had progressive cochlear lesions. The MPS VII dogs had severe and early middle ear lesions, including chronic otitis media and bone resorption. The MPS I dog only partially recapitulates the pathology seen in humans; specifically, the dog model lacks inflammatory middle ear disease. In contrast, the MPS VII dog has severe inflammatory middle ear disease similar to that reported in the human. In conclusion, the canine MPS VII model appears to be a good model to study MPS VII-related deafness.

Severe and extensive neonatal hearing loss in cats results in auditory cortex plasticity that differentiates into two regions

We examined the response characteristics of primary auditory cortex (A1) neurons in adult cats partially but extensively deafened by ototoxic drugs 2-8 days after birth. The damage evoked extensive A1 topographic map reorganization as also found by others, but a novel finding was that in the majority of cats with low-frequency edges to the cochlear lesion, the area of reorganization segregated into two areas expressing the same novel frequency inputs but differentiated by neuronal sensitivity and responsiveness. Immediately adjacent to normal A1 is an approximately 1.2-mm-wide area of reorganization in which sensitivity and responsiveness to sound are similar to that in normal A1 in the same animals and in unlesioned adult animals. Extending further into deprived A1 is a more extensive area of reorganization where neurons have poorer sensitivity and responsiveness to new inputs. These two areas did not differ in response-area bandwidth and response latency. We interpret these novel changes as the cortical consequences of severe receptor organ lesions extending to low-frequency cochlear regions. We speculate that the two areas of A1 reorganization may reflect differences in the transcortical spatial distribution of thalamo-cortical and horizontal intracortical connections. Qualitatively similar changes in response properties have been seen after retinal lesions producing large areas of visual cortical reorganization, suggesting they might be a general consequence of receptor lesions that deprive large regions of cortex of normal input. These effects may have perceptual implications for the use of cochlear implants in patients with residual low-frequency hearing.