Can auditory brain stem response accurately reflect the cochlear function?

Auditory brain stem response (ABR) and compound action potential (CAP) recordings have been used in animal research to determine hearing sensitivity. Because of the relative ease of testing, the ABR test has been more commonly used in assessing cochlear lesions than the CAP test. The purpose of this experiment is to examine the difference between these two methods in monitoring the dynamic changes in auditory function after cochlear damage and in detecting asymmetric hearing loss due to unilateral cochlear damage. ABR and CAP were measured in two models of cochlear damage: acoustic trauma induced by exposure to a narrowband noise centered at 4 kHz (2,800-5,600 Hz) at 105 dB sound pressure level for 5 h in chinchillas and unilateral cochlear damage induced by surgical destruction of one cochlea in guinea pigs. Cochlear hair cells were quantified after completing the evoked potential testing. In the noise-damaged model, we found different recovery patterns between ABR and CAP. At 1 day after noise exposure, the ABR and CAP assessment revealed a similar level of threshold shifts. However, at 30 days after noise exposure, ABR thresholds displayed an average of 20-dB recovery, whereas CAP thresholds showed no recovery. Notably, the CAP threshold signifies the actual condition of sensory cell pathogenesis in the cochlea because sensory cell death is known to be irreversible in mammals. After unilateral cochlear damage, we found that both CAP and ABR were affected by cross-hearing when testing the damaged ear with the testing stimuli delivered directly into the canal of the damaged ear. When cross-hearing occurred, ABR testing was not able to reveal the presence of cross-hearing because the ABR waveform generated by cross-stimulation was indistinguishable from that generated by the test ear (damaged ear), should the test ear be intact. However, CAP testing can provide a warning sign, since the typical CAP waveform became an ABR-like waveform when cross-hearing occurred. Our study demonstrates two advantages of the CAP test over the ABR test in assessing cochlear lesions: contributing evidence for the occurrence of cross-hearing when subjects have asymmetric hearing loss and providing a better assessment of the progression of cochlear pathogenesis.NEW & NOTEWORTHY Auditory brain stem response (ABR) is more commonly used to evaluate cochlear lesions than cochlear compound action potential (CAP). In a noise-induced cochlear damage model, we found that the reduced CAP and enhanced ABR caused the threshold difference. In a unilateral cochlear destruction model, a shadow curve of the ABR from the contralateral healthy ear masked the hearing loss in the destroyed ear.

Hidden hearing deficits in military service members with persistent post concussive symptoms.

INTRODUCTION: Individuals with persistent symptoms after mild traumatic brain injury (mTBI) often have auditory complaints. In this study, we used the auditory brainstem response (ABR) to determine whether cochlear synaptopathy could explain auditory symptoms. METHODS: 69 adult military service members with mTBI and 25 adults without brain injury (NCT01611194 and NCT01925963) completed pure-tone audiometry, ABR, and central auditory processing tests. All participants were male, ages 21-50. RESULTS: 37/69 mTBI participants had measurable hearing loss, while another 20%-30% had hearing complaints or tinnitus. While mTBI participants with measurable hearing loss had reduced wave I and III amplitude and decreased III-V interpeak latency, those with no measurable hearing loss did not significantly differ from controls on any ABR parameter. Those with measurable hearing loss were also more likely to have abnormal central auditory processing. mTBI participants with no measurable hearing loss but who reported hearing concerns had some ABR findings (III-V interpeak latency, I and V amplitudes, V/I amplitude ratio) more like the measurable hearing loss mTBI group than normative controls. CONCLUSION: Cochlear synaptopathy may have contributed to some of the auditory impairment in service members with mTBI with measurable hearing loss. However, these results are likely confounded by cochlear hair cell damage.

[Models of tinnitus development : From cochlea to cortex]. / Modelle der Tinnitusentstehung : Von der Cochlea zum Kortex.

The development of subjective tinnitus is still not mechanistically understood and existing models are controversially discussed. In this overview, the authors discuss three of the main models, all of which propose damage to the cochlea as the initial step in tinnitus development. Based on these models, a possible manifestation of tinnitus-related neuronal activity at the perceptually relevant level of the auditory pathway, the auditory cortex, is presented. Furthermore, it is demonstrated that one of the models offers a new view on the phenomenon, which could potentially help patients to better cope with their condition.

The Summating Potential Is a Reliable Marker of Electrode Position in Electrocochleography: Cochlear Implant as a Theragnostic Probe.

OBJECTIVE: For the increasing number of cochlear implantations in subjects with residual hearing, hearing preservation, and thus the prevention of implantation trauma, is crucial. A method for monitoring the intracochlear position of a cochlear implant (CI) and early indication of imminent cochlear trauma would help to assist the surgeon to achieve this goal. The aim of this study was to evaluate the reliability of the different electric components recorded by an intracochlear electrocochleography (ECochG) as markers for the cochleotopic position of a CI. The measurements were made directly from the CI, combining intrasurgical diagnostics with the therapeutical use of the CI, thus, turning the CI into a "theragnostic probe." DESIGN: Intracochlear ECochGs were measured in 10 Dunkin Hartley guinea pigs of either sex, with normal auditory brainstem response thresholds. All subjects were fully implanted (4 to 5 mm) with a custom six contact CI. The ECochG was recorded simultaneously from all six contacts with monopolar configuration (retroauricular reference electrode). The gross ECochG signal was filtered off-line to separate three of its main components: compound action potential, cochlear microphonic, and summating potential (SP). Additionally, five cochleae were harvested and histologically processed to access the spatial position of the CI contacts. Both ECochG data and histological reconstructions of the electrode position were fitted with the Greenwood function to verify the reliability of the deduced cochleotopic position of the CI. RESULTS: SPs could be used as suitable markers for the frequency position of the recording electrode with an accuracy of ±1/4 octave in the functioning cochlea, verified by histology. Cochlear microphonics showed a dependency on electrode position but were less reliable as positional markers. Compound action potentials were not suitable for CI position information but were sensitive to "cochlear health" (e.g., insertion trauma). CONCLUSIONS: SPs directly recorded from the contacts of a CI during surgery can be used to access the intracochlear frequency position of the CI. Using SP monitoring, implantation may be stopped before penetrating functioning cochlear regions. If the technique was similarly effective in humans, it could prevent implantation trauma and increase hearing preservation during CI surgery. Diagnostic hardware and software for recording biological signals with a CI without filter limitations might be a valuable add-on to the portfolios of CI manufacturers.

Distorted Tonotopic Coding of Temporal Envelope and Fine Structure with Noise-Induced Hearing Loss.

People with cochlear hearing loss have substantial difficulty understanding speech in real-world listening environments (e.g., restaurants), even with amplification from a modern digital hearing aid. Unfortunately, a disconnect remains between human perceptual studies implicating diminished sensitivity to fast acoustic temporal fine structure (TFS) and animal studies showing minimal changes in neural coding of TFS or slower envelope (ENV) structure. Here, we used general system-identification (Wiener kernel) analyses of chinchilla auditory nerve fiber responses to Gaussian noise to reveal pronounced distortions in tonotopic coding of TFS and ENV following permanent, noise-induced hearing loss. In basal fibers with characteristic frequencies (CFs) >1.5 kHz, hearing loss introduced robust nontonotopic coding (i.e., at the wrong cochlear place) of low-frequency TFS, while ENV responses typically remained at CF. As a consequence, the highest dominant frequency of TFS coding in response to Gaussian noise was 2.4 kHz in noise-overexposed fibers compared with 4.5 kHz in control fibers. Coding of ENV also became nontonotopic in more pronounced cases of cochlear damage. In apical fibers, more classical hearing-loss effects were observed, i.e., broadened tuning without a significant shift in best frequency. Because these distortions and dissociations of TFS/ENV disrupt tonotopicity, a fundamental principle of auditory processing necessary for robust signal coding in background noise, these results have important implications for understanding communication difficulties faced by people with hearing loss. Further, hearing aids may benefit from distinct amplification strategies for apical and basal cochlear regions to address fundamentally different coding deficits. SIGNIFICANCE STATEMENT: Speech-perception problems associated with noise overexposure are pervasive in today's society, even with modern digital hearing aids. Unfortunately, the underlying physiological deficits in neural coding remain unclear. Here, we used innovative system-identification analyses of auditory nerve fiber responses to Gaussian noise to uncover pronounced distortions in coding of rapidly varying acoustic temporal fine structure and slower envelope cues following noise trauma. Because these distortions degrade and diminish the tonotopic representation of temporal acoustic features, a fundamental principle of auditory processing, the results represent a critical advancement in our understanding of the physiological bases of communication disorders. The detailed knowledge provided by this work will help guide the design of signal-processing strategies aimed at alleviating everyday communication problems for people with hearing loss.

Effects of Implantation and Reimplantation of Cochlear Implant Electrodes in an In Vivo Animal Experimental Model (Macaca fascicularis).

OBJECTIVES: The objectives of this study were to evaluate the effect of reimplanting a cochlear implant electrode in animal normal-hearing cochlea to propose measures that may prevent cochlear injury and, given its close phylogenetic proximity to humans, to evaluate the macaque as a model for electroacoustic stimulation. DESIGN: Simultaneous, bilateral surgical procedures in a group of 5 normal-hearing specimens (Macaca fascicularis) took place in a total of 10 ears. Periodic bilateral auditory testing (distortion product otoacoustic emissions and auditory brainstem evoked responses [ABR]) took place during a 6-month follow-up period. Subsequently, unilateral explantation and reimplantation was performed. Auditory follow-up continued up to 12 months, after which animals were sacrificed and both temporal bones extracted for histological analysis. RESULTS: Implantation and reimplantation surgeries were performed without complications in 9 of 10 cases. Full insertion depth was achieved at reimplantation in four of five ears. Auditory evaluation: Statistically significant differences between implanted and reimplanted were observed for the frequencies 2000 and 11,000 Hz, the remaining frequencies showed no differences for distortion product otoacoustic emission. Before the procedure, average thresholds with click-stimuli ABR of the five animals were 40 dB SPL (implanted group) and 40 dB SPL (reimplanted group). One week after first implantation, average thresholds were 55 dB SPL and 60 dB, respectively. After 12 months of follow-up, the average thresholds were 72.5 dB SPL (implanted group) and 65 dB SPL (reimplanted group). Hearing loss appeared during the first weeks after the first implantation and no deterioration was observed thereafter. Differences for ABR under click stimulus were not significant between the two ear groups. Similar results were observed with tone-burst ABR. A 15 dB shift was observed for the implanted group preoperatively versus 1-week post surgery and an additional 17.5 dB shift was seen after 12-month follow-up. For the reimplanted group, a 20 dB shift was observed within the first week post reimplantation surgery and an additional 5 dB after 6 months follow-up. Statistical analysis revealed significant differences between the implanted and reimplanted ear groups for frequencies 4000 Hz (p = 0.034), 12000 Hz (p = 0.031), and 16,000 Hz (p = 0.031). The histological analysis revealed that the electrode insertion was minimally traumatic for the cochlea, mainly indicating rupture of the basilar membrane in the transition area between the basal turn and the first cochlear turn only in Mf1 left ear. CONCLUSIONS: With application of minimally traumatic surgical techniques, it is possible to maintain high rates of hearing preservation after implantation and even after reimplantation. Partial impairment of auditory thresholds may occur during the first weeks after surgery, which remains stable. Considering the tonotopic distribution of the cochlea, we found a correlation between the histological lesions sites and the auditory findings, suggesting that a rupture of the basilar membrane may impact hearing levels. The macaque was observed to be a functionally and anatomically an excellent animal model for cochlear implantation.

Three-Dimensional Force Profile During Cochlear Implantation Depends on Individual Geometry and Insertion Trauma.

OBJECTIVES: To preserve the acoustic hearing, cochlear implantation has to be as atraumatic as possible. Therefore, understanding the impact of the cochlear geometry on insertion forces and intracochlear trauma might help to adapt and improve the electrode insertion and reduce the probability of intracochlear trauma. DESIGN: The study was conducted on 10 fresh-frozen human temporal bones. The inner ear was removed from the temporal bone. The bony capsule covering the scala vestibuli was removed and the dissected inner ear was mounted on the three-dimensional (3D) force measurement system (Agilent technologies, Nano UTM, Santa Clare, CA). A lateral wall electrode array was inserted, and the forces were recorded in three dimensions with a sensitivity of 2 µN. Afterwards, the bones were scanned using a Skyscan 1173 micro-computed tomography (micro-CT). The obtained 3D force profiles were correlated with the videos of the insertions recorded through the microscope, and the micro-CT images. RESULTS: A correlation was found between intracochlear force profiles measured in three different directions with intracochlear trauma detected with micro-CT imaging. The angle of insertion and the cochlear geometry had a significant impact on the electrode array insertion forces and possible insertion trauma. Intracochlear trauma occurred frequently within the first 180° from the round window, where buckling of the proximal part of the electrode carrier inside the cochlea, and rupturing of the spiral ligament was observed. CONCLUSIONS: The combination of the 3D force measurement system and micro-CT can be used to characterize the mechanical behavior of a CI electrode array and some forms of insertion trauma. Intracochlear trauma does not always correlate with higher force amplitudes, but rather with an abrupt change of force directions.

Role of cysteinyl leukotriene signaling in a mouse model of noise-induced cochlear injury.

Noise-induced hearing loss is one of the most common types of sensorineural hearing loss. In this study, we examined the expression and localization of leukotriene receptors and their respective changes in the cochlea after hazardous noise exposure. We found that the expression of cysteinyl leukotriene type 1 receptor (CysLTR1) was increased until 3 d after noise exposure and enhanced CysLTR1 expression was mainly observed in the spiral ligament and the organ of Corti. Expression of 5-lipoxygenase was increased similar to that of CysLTR1, and there was an accompanying elevation of CysLT concentration. Posttreatment with leukotriene receptor antagonist (LTRA), montelukast, for 4 consecutive days after noise exposure significantly decreased the permanent threshold shift and also reduced the hair cell death in the cochlea. Using RNA-sequencing, we found that the expression of matrix metalloproteinase-3 (MMP-3) was up-regulated after noise exposure, and it was significantly inhibited by montelukast. Posttreatment with a MMP-3 inhibitor also protected the hair cells and reduced the permanent threshold shift. These findings suggest that acoustic injury up-regulated CysLT signaling in the cochlea and cochlear injury could be attenuated by LTRA through regulation of MMP-3 expression. This study provides mechanistic insights into the role of CysLTs signaling in noise-induced hearing loss and the therapeutic benefit of LTRA.

Presynaptic activity regulates Na(+) channel distribution at the axon initial segment.

Deprivation of afferent inputs in neural circuits leads to diverse plastic changes in both pre- and postsynaptic elements that restore neural activity. The axon initial segment (AIS) is the site at which neural signals arise, and should be the most efficient site to regulate neural activity. However, none of the plasticity currently known involves the AIS. We report here that deprivation of auditory input in an avian brainstem auditory neuron leads to an increase in AIS length, thus augmenting the excitability of the neuron. The length of the AIS, defined by the distribution of voltage-gated Na(+) channels and the AIS anchoring protein, increased by 1.7 times in seven days after auditory input deprivation. This was accompanied by an increase in the whole-cell Na(+) current, membrane excitability and spontaneous firing. Our work demonstrates homeostatic regulation of the AIS, which may contribute to the maintenance of the auditory pathway after hearing loss. Furthermore, plasticity at the spike initiation site suggests a powerful pathway for refining neuronal computation in the face of strong sensory deprivation.

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.

Noise-induced cochlear F-actin depolymerization is mediated via ROCK2/p-ERM signaling.

Our previous work has suggested that traumatic noise activates Rho-GTPase pathways in cochlear outer hair cells (OHCs), resulting in cell death and noise-induced hearing loss (NIHL). In this study, we investigated Rho effectors, Rho-associated kinases (ROCKs), and the targets of ROCKs, the ezrin-radixin-moesin (ERM) proteins, in the regulation of the cochlear actin cytoskeleton using adult CBA/J mice under conditions of noise-induced temporary threshold shift (TTS) and permanent threshold shift (PTS) hearing loss, which result in changes to the F/G-actin ratio. The levels of cochlear ROCK2 and p-ERM decreased 1 h after either TTS- or PTS-noise exposure. In contrast, ROCK2 and p-ERM in OHCs decreased only after PTS-, not after TTS-noise exposure. Treatment with lysophosphatidic acid, an activator of the Rho pathway, resulted in significant reversal of the F/G-actin ratio changes caused by noise exposure and attenuated OHC death and NIHL. Conversely, the down-regulation of ROCK2 by pretreatment with ROCK2 siRNA reduced the expression of ROCK2 and p-ERM in OHCs, exacerbated TTS to PTS, and worsened OHC loss. Additionally, pretreatment with siRNA against radixin, an ERM protein, aggravated TTS to PTS. Our results indicate that a ROCK2-mediated ERM-phosphorylation signaling cascade modulates noise-induced hair cell loss and NIHL by targeting the cytoskeleton. We propose the following cascade following noise trauma leading to alteration of the F-actin arrangement in the outer hair cell cytoskeleton: Noise exposure reduces the levels of GTP-RhoA and subsequently diminishes levels of RhoA effector ROCK2 (Rho-associated kinase 2). Phosphorylation of ezrin-radixin-moesin (ERM) by ROCK2 normally allows ERM to cross-link actin filaments with the plasma membrane. Noise-decreased levels of ROCK results in reduction of phosphorylation of ERM that leads to depolymerization of actin filaments. Lysophosphatidic acid (LPA), an agonist of RhoA, binds to the G-protein-coupled receptor (GPCR) leading to activation of RhoA through Gα12/13 and RhoGEF. Administration of LPA rescues the noise-diminished F/G-actin ratio.

Green Tea Polyphenols Protects Cochlear Hair Cells from Ototoxicity by Inhibiting Notch Signalling.

Notch signalling pathway plays an essential role in the development of cochlea, which inhibits the proliferation of hair cells. Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea, which presents strong antioxidant activation and has been applied for anti-cancer and anti-inflammatory. In this study, we treated the cochlear explant cultures with EGCG and found that EGCG can protect cochlear hair cells from ototoxic drug gentamicin. We demonstrated that EGCG could down-regulate the expression of Notch signalling pathway target genes, such as Hes1, Hes5, Hey1 and Hey5. However, the Notch pathway ligands such as Delta1, Jag1 and Jag2 were not affected by EGCG. To further illustrate the mechanism of recover cochlear hair cells, we demonstrated that EGCG inhibited the activity of γ-secrectase to suppress Notch signalling pathway and promoted the proliferation and regeneration of hair cells in the damaged cochlea. Our results suggest for the first time the role of EGCG as an inhibitor of the Notch signalling pathway, and support its potential value in hearing-impaired recovery in clinical therapy.

Modified areal cartography in auditory cortex following early- and late-onset deafness.

Cross-modal plasticity following peripheral sensory loss enables deprived cortex to provide enhanced abilities in remaining sensory systems. These functional adaptations have been demonstrated in cat auditory cortex following early-onset deafness in electrophysiological and psychophysical studies. However, little information is available concerning any accompanying structural compensations. To examine the influence of sound experience on areal cartography, auditory cytoarchitecture was examined in hearing cats, early-deaf cats, and cats with late-onset deafness. Cats were deafened shortly after hearing onset or in adulthood. Cerebral cytoarchitecture was revealed immunohistochemically using SMI-32, a monoclonal antibody used to distinguish auditory areas in many species. Auditory areas were delineated in coronal sections and their volumes measured. Staining profiles observed in hearing cats were conserved in early- and late-deaf cats. In all deaf cats, dorsal auditory areas were the most mutable. Early-deaf cats showed further modifications, with significant expansions in second auditory cortex and ventral auditory field. Borders between dorsal auditory areas and adjacent visual and somatosensory areas were shifted ventrally, suggesting expanded visual and somatosensory cortical representation. Overall, this study shows the influence of acoustic experience in cortical development, and suggests that the age of auditory deprivation may significantly affect auditory areal cartography.

Micro-CT scan, electron microscopy and optical microscopy study of insertional traumas of cochlear implants.

PURPOSE: Knowledge of cochlear trauma resulting from the implantation of electrodes is important for the development of atraumatic surgical techniques. The purpose of this study was to demonstrate the advantages of micro-CT scanning, back-scattered electron microscopy (BSEM) and optical microscopy (OM) in understanding the mechanisms of cochlear trauma due to cochlear implantation. METHOD: Our study involved six petrous bones removed from fresh human cadavers: one control specimen plus five other specimens that were surgically implanted with Neurelec Digisonic SP EVO electrode arrays. All six specimens underwent glycol methyl methacrylate embedding, were examined via micro-CT scan and were then sectioned for histological analysis of undecalcified samples via BSEM and OM. RESULTS: The 2D micro-CT scan reconstructions did not display cochlear microtrauma due to a limited resolution and the loss of information caused by the metallic artifacts of the intracochlear electrodes. The 3D reconstructions displayed the quality of the electrode array positioning in the cochlea and enabled determining the axes on which to section the specimens for histological examination. BSEM afforded a clear view of the damage to the osseous structures of the cochlea, but did not display the soft tissue injuries. OM enabled viewing and grading the histological lesions resulting from insertion. CONCLUSION: In our opinion, the combination of 3D micro-CT scan reconstructions and histological analysis using OM appears to be the best method to analyze this type of trauma.

Intraoperative Measured Electrocochleography and Fluoroscopy Video to Detect Cochlea Trauma.

HYPOTHESIS: Gross electrode movements detected with intraoperative, real-time X-ray fluoroscopy will correlate with fluctuations in cochlear output, as measured with intraoperative electrocochleography (ECochG). BACKGROUND: Indications for cochlear implantation (CI) are expanding to include patients with residual hearing; however, implant recipients often lose residual hearing after CI. The objective of this study was to identify probable traumatic events during implantation by combining electrophysiological monitoring of cochlear function with simultaneous X-ray monitoring. The surgical timing of these apparently traumatic events was then investigated. METHODS: For 19 adult patients (21 surgeries, 2 bilateral), the ECochG responses were measured during implantation of a cochlear nucleus slim modiolar electrode (CI532/CI632, Cochlear Ltd Australia Nucleus slim modiolar). Simultaneous fluoroscopy was performed, as well as a postoperative cone-beam computed tomography (CT) scan. For all patients, pre- and postoperative audiograms were recorded up to 1 year after surgery to record the loss of residual hearing. RESULTS: Electrode insertions for 21 surgeries were successfully monitored. A drop in ECochG response was significantly correlated with reduced hearing preservation compared with patients with preserved responses throughout. Drops in the ECochG response were measured to occur during insertion, because of movement of the array after insertion was complete, including while sealing of the electrode array at the round window or coiling of the array lead within the mastoid cavity. In some patients, a reduction in cochlear output, resulting in poor ECochG response, was inferred to occur before the beginning of implantation. CONCLUSION: The combination of perioperative ECochG measurements, microscope video, fluoroscopy, and postoperative CT scan may inform on what causes the loss of residual hearing after implantation. These findings will be used to improve the surgical procedure in future.

Exploring Trauma Patterns and Contributing Factors With Slim Straight Electrode Array After Cochlear Implantation.

OBJECTIVE: To assess trauma patterns associated with the insertion of lateral wall electrode arrays. The study focused on 3 categories-scala tympani (ST), intermediate, and scala vestibuli (SV)-to identify traumatic patterns and contributing factors. STUDY DESIGN: Retrospective study. SETTING: Data from 106 cochlear implant recipients at a tertiary otologic center. METHODS: Demographic and surgical data were collected from recipients who underwent cochlear implantation manually and with RobOtol®. Measurements included cochlear dimensions, angular depth of insertion, and position of the first electrode. Three-dimensional reconstructions were used to analyze the electrode array location relative to the basilar membrane, categorized into ST, intermediate, and SV electrodes. Nontraumatic insertion was defined as all electrodes in the ST, while traumatic insertions had 1 or more electrodes in intermediate or SV locations. RESULTS: Out of 106 cases, 44% had nontraumatic and 56% had traumatic insertions. Demographic and surgical characteristics showed no association with traumatic insertions. A deeper position of the first electrode, relative to the round window, was associated with traumatic insertions (P = .03). Three trauma patterns were observed: distal (facing the apical electrodes), proximal (facing the middle electrodes around 180°), and distal/proximal. CONCLUSION: This study considers the intermediate position which could be associated with basilar membrane lesions. Risk zones for intracochlear trauma with lateral wall arrays were identified distally and proximally. Traumatic insertions were independently linked to deeper array placement. Future studies should explore whether gentler insertion, without insisting on further electrode array insertion depth, could reduce the trauma during cochlear implantation.

Intracochlear Trauma and Local Ossification Patterns Differ Between Straight and Precurved Cochlear Implant Electrodes.

HYPOTHESIS: Trauma to the osseous spiral lamina (OSL) or spiral ligament (SL) during cochlear implant (CI) insertion segregates with electrode type and induces localized intracochlear ossification and fibrosis. BACKGROUND: The goal of atraumatic CI insertion is to preserve intracochlear structures, limit reactive intracochlear tissue formation, and preserve residual hearing. Previous qualitative studies hypothesized a localized effect of trauma on intracochlear tissue formation; however, quantitative studies failed to confirm this. METHODS: Insertional trauma beyond the immediate insertion site was histologically assessed in 21 human temporal bones with a CI. Three-dimensional reconstructions were generated and virtually resectioned perpendicular to the cochlear spiral at high resolution. The cochlear volume occupied by ossification or fibrosis was determined at the midpoint of the trauma and compared with regions proximal and distal to this point. RESULTS: Seven cases, all implanted with precurved electrodes, showed an OSL fracture beyond the immediate insertion site. Significantly more intracochlear ossification was observed at the midpoint of the OSL fracture, compared with the -26 to -18 degrees proximal and 28 to 56 degrees distal to the center. No such pattern was observed for fibrosis. In the 12 cases with a perforation of the SL (9 straight and 3 precurved electrodes), no localized pattern of ossification or fibrosis was observed around these perforations. CONCLUSION: OSL fractures were observed exclusively with precurved electrodes in this study and may serve as a nidus for localized intracochlear ossification. Perforation of the SL, in contrast, predominantly occurred with straight electrodes and was not associated with localized ossification.

Tonotopic reorganization and spontaneous firing in inferior colliculus during both short and long recovery periods after noise overexposure.

BACKGROUND: Noise induced injury of the cochlea causes shifts in activation thresholds and changes of frequency response in the inferior colliculus (IC). Noise overexposure also induces pathological changes in the cochlea, and is highly correlated to hearing loss. However, the underlying mechanism has not been fully elucidated. In this study, we hypothesized that overexposure to noise induces substantial electrophysiological changes in the IC of guinea pigs. RESULTS: During the noise exposure experiment, the animals were undergoing a bilateral exposure to noise. Additionally, various techniques were employed including confocal microscopy for the detection of cochlea hair cells and single neuron recording for spontaneous firing activity measurement. There were alterations among three types of frequency response area (FRA) from sound pressure levels, including V-, M-, and N-types. Our results indicate that overexposure to noise generates different patterns in the FRAs. Following a short recovery (one day after the noise treatment), the percentage of V-type FRAs considerably decreased, whereas the percentage of M-types increased. This was often caused by a notch in the frequency response that occurred at 4 kHz (noise frequency). Following a long recovery from noise exposure (11-21 days), the percentage of V-types resumed to a normal level, but the portion of M-types remained high. Interestingly, the spontaneous firing in the IC was enhanced in both short and long recovery groups. CONCLUSION: Our data suggest that noise overexposure changes the pattern of the FRAs and stimulates spontaneous firing in the IC in a unique way, which may likely relate to the mechanism of tinnitus.

Otoacoustic emission sensitivity to exposure to styrene and noise.

The ototoxic effect of the exposure to styrene is evaluated, also in the presence of simultaneous exposure to noise, using otoacoustic emissions as biomarkers of mild cochlear damage. Transient-evoked and distortion product otoacoustic emissions were recorded and analyzed in a sample of workers (15 subjects) exposed to styrene and noise in a fiberglass manufacturing facility and in a control group of 13 non-exposed subjects. Individual exposure monitoring of the airborne styrene concentrations was performed, as well as biological monitoring, based on the urinary concentration of two styrene metabolites, the Mandelic and Phenylglyoxylic acids. Noise exposure was evaluated using wearable phonometers, and hearing loss with pure tone audiometry. Due to their different job tasks, one group of workers was exposed to high noise and low styrene levels, another group to higher styrene levels, close to the limit of 20 ppm, and to low noise levels. A significant negative correlation was found between the otoacoustic emission levels and the concentration of the styrene urinary metabolites. Otoacoustic emissions, and particularly distortion products, were able to discriminate the exposed workers from the controls, providing also a rough estimate of the slope of the dose-response relation between otoacoustic levels and styrene exposure.

Mild therapeutic hypothermia protects against inflammatory and proapoptotic processes in the rat model of cochlear implant trauma.

OBJECTIVE: Mild therapeutic hypothermia (MTH) has been demonstrated to prevent residual hearing loss from surgical trauma associated with cochlear implant (CI) insertion. Here, we aimed to characterize the mechanisms of MTH-induced hearing preservation in CI in a well-established preclinical rodent model. APPROACH: Rats were divided into four experimental conditions: MTH-treated and implanted cochleae, cochleae implanted under normothermic conditions, MTH only cochleae and un-operated cochleae (controls). Auditory brainstem responses (ABRs) were recorded at different time points (up to 84 days) to confirm long-term protection and safety of MTH locally applied to the cochlea for 20 min before and after implantation. Transcriptome sequencing profiling was performed on cochleae harvested 24 h post CI and MTH treatment to investigate the potential beneficial effects and underlying active gene expression pathways targeted by the temperature management. RESULTS: MTH treatment preserved residual hearing up to 3 months following CI when compared to the normothermic CI group. In addition, MTH applied locally to the cochleae using our surgical approach was safe and did not affect hearing in the long-term. Results of RNA sequencing analysis highlight positive modulation of signaling pathways and gene expression associated with an activation of cellular inflammatory and immune responses against the mechanical damage caused by electrode insertion. SIGNIFICANCE: These data suggest that multiple and possibly independent molecular pathways play a role in the protection of residual hearing provided by MTH against the trauma of cochlear implantation.