A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss.

Age-related hearing loss (ARHL) is the most common sensory impairment mainly caused by degeneration of sensory hair cells in the cochlea with no causal medical treatment available. Auditory function and sensory hair cell survival critically depend on the Kv7.4 (KCNQ4) channel, a voltage-gated potassium channel expressed in outer hair cells (OHCs), with its impaired function or reduced activity previously associated with ARHL. Here, we investigated the effect of a potent small-molecule Kv7.4 agonist on ARHL in the senescence-accelerated mouse prone 8 (SAMP8) model. For the first time in vivo, we show that Kv7.4 activation can significantly reduce age-related threshold shifts of auditory brainstem responses as well as OHC loss in the SAMP8 model. Pharmacological activation of Kv7.4 thus holds great potential as a therapeutic approach for ARHL as well as other hearing impairments related to Kv7.4 function.

Phoenix auditory neurons as 3R cell model for high throughput screening of neurogenic compounds.

Auditory neurons connect the sensory hair cells from the inner ear to the brainstem. These bipolar neurons are relevant targets for pharmacological intervention aiming at protecting or improving the hearing function in various forms of sensorineural hearing loss. In the research laboratory, neurotrophic compounds are commonly used to improve survival and to promote regeneration of auditory neurons. One important roadblock delaying eventual clinical applications of these strategies in humans is the lack of powerful in vitro models allowing high throughput screening of otoprotective and regenerative compounds. The recently discovered auditory neuroprogenitors (ANPGs) derived from the A/J mouse with an unprecedented capacity to self-renew and to provide mature auditory neurons offer the possibility to overcome this bottleneck. In the present study, we further characterized the new phoenix ANPGs model and compared it to the current gold-standard spiral ganglion organotypic explant (SGE) model to assay neurite outgrowth, neurite length and glutamate-induced Ca2+ response in response to neurotrophin-3 (NT-3) and brain derived neurotrophic factor (BDNF) treatment. Whereas both, SGEs and phoenix ANPGs exhibited a robust and sensitive response to neurotrophins, the phoenix ANPGs offer a considerable range of advantages including high throughput suitability, lower experimental variability, single cell resolution and an important reduction of animal numbers. The phoenix ANPGs in vitro model therefore provides a robust high-throughput platform to screen for otoprotective and regenerative neurotrophic compounds in line with 3R principles and is of interest for the field of auditory neuroscience.

ExplantAnalyzer: An advanced automated neurite outgrowth analysis evaluated by means of organotypic auditory neuron explant cultures.

BACKGROUND: Neuronal outgrowth assays using organotypic explant cultures are commonly utilized to study neuroregenerative and -protective effects of drugs such as neurotrophins. While this approach offers higher organized tissue compared to single cell cultures and less experimental effort than in-vivo studies, quantitative evaluation of the neuronal network is often time consuming. Thus, we developed ExplantAnlayzer, a time-saving high-throughput evaluation method, yielding numerous metrics to objectively describe neuronal outgrowth. NEW METHOD: Spiral ganglion explants were cultured in 24-well plates, mechanically fixed in a collagen matrix and immunolabeled against beta-III-tubulin. The explants were imaged using a fluorescent tile-scan microscope and resulting images were stitched. The evaluation was developed as an open-source MATLAB routine and involves several image processing steps, including adaptive thresholding. The neurite network was eventually converted to a graph to track neurites from their terminals back to the explant body. COMPARISON WITH EXISTING METHOD(S): We compared ExplantAnlayzer quantitatively and qualitatively to common existing methods, such as Sholl analyses and manual fiber tracing, using representative explant images. ExplantAnlayzer is able to achieve similar and as detailed results as manual tracing while decreasing manual interaction and required time dramatically. RESULTS: After an initial setup phase, the explant images could be batch-processed altogether. Bright bundles as well as faint fibers were reliably detected. Several metrics describing the outgrowth morphology, including total outgrowth, neurite numbers and length estimations, as well as their growth directions, were computed. CONCLUSIONS: ExplantAnalyzer is a time-saving and objective method for an in-depth evaluation of organotypic explant outgrowth.

Auditory Threshold Variability in the SAMP8 Mouse Model of Age-Related Hearing Loss: Functional Loss and Phenotypic Change Precede Outer Hair Cell Loss.

Age-related hearing loss (ARHL) is the most common sensory deficit in aging society, which is accompanied by increased speech discrimination difficulties in noisy environments, social isolation, and cognitive decline. The audiometric degree of ARHL is largely correlated with sensory hair cell loss in addition to age-related factors not captured by histopathological analysis of the human cochlea. Previous studies have identified the senescence-accelerated mouse prone strain 8 (SAMP8) as a model for studying ARHL and age-related modifications of the cochlear redox environment. However, the SAMP8 population exhibits a large variability in auditory function decline over age, whose underlying cause remains unknown. In this study, we analyzed auditory function of SAMP8 mice by measuring auditory brainstem response (ABR) thresholds at the age of 6 weeks (juvenile), 12 weeks (young adult), and 24 weeks (adult). Consistent with previous studies, SAMP8 mice exhibit an early progressive, age-related decline of hearing acuity. However, a spatiotemporal cytohistological analysis showed that the significant increase in threshold variability was not concurrently reflected in outer hair cell (OHC) loss observed in the lower and upper quartiles of the ABR threshold distributions over age. This functional loss was found to precede OHC loss suggesting that age-related phenotypic changes may be contributing factors not represented in cytohistological analysis. The expression of potassium channels KCNQ4 (KV7.4), which mediates the current IK,n crucial for the maintenance of OHC membrane potential, and KCNQ1 (KV7.1), which is an essential component in potassium circulation and secretion into the endolymph generating the endocochlear potential, showed differences between these quartiles and age groups. This suggests that phenotypic changes in OHCs or the stria vascularis due to variable oxidative deficiencies in individual mice may be predictors of the observed threshold variability in SAMP8 mice and their progressive ARHL. In future studies, further phenotypic predictors affected by accumulated metabolic challenges over age need to be investigated as potentially underlying causes of ARHL preceding irreversible OHC loss in the SAMP8 mouse model.

Age-related hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway.

Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly and constitutes the third highest risk factor for dementia. Lifetime noise exposure, genetic predispositions for degeneration, and metabolic stress are assumed to be the major causes of ARHL. Both noise-induced and hereditary progressive hearing have been linked to decreased cell surface expression and impaired conductance of the potassium ion channel KV7.4 (KCNQ4) in outer hair cells, inspiring future therapies to maintain or prevent the decline of potassium ion channel surface expression to reduce ARHL. In concert with KV7.4 in outer hair cells, KV7.1 (KCNQ1) in the stria vascularis, calcium-activated potassium channels BK (KCNMA1) and SK2 (KCNN2) in hair cells and efferent fiber synapses, and KV3.1 (KCNC1) in the spiral ganglia and ascending auditory circuits share an upregulated expression or subcellular targeting during final differentiation at hearing onset. They also share a distinctive fragility for noise exposure and age-dependent shortfalls in energy supply required for sustained surface expression. Here, we review and discuss the possible contribution of select potassium ion channels in the cochlea and auditory pathway to ARHL. We postulate genes, proteins, or modulators that contribute to sustained ion currents or proper surface expressions of potassium channels under challenging conditions as key for future therapies of ARHL.

Band-Limited Chirp-Evoked Compound Action Potential in Guinea Pig: Comprehensive Neural Measure for Cochlear Implantation Monitoring.

OBJECTIVES: Patients with severely impaired high-frequency hearing and sufficient residual low-frequency hearing can be provided with a cochlear implant (CI), thereby facilitating ipsilateral electric and acoustic stimulation with established advantages over electric stimulation alone. However, partial or complete hearing loss often occurred after implantation due to, inter alia, acute mechanical trauma to cochlear structures during electrode insertion. Possibilities of intraoperative monitoring using electrocochleography (ECochG) have recently been studied in CI patients, primarily using the ongoing response to low-frequency tone bursts consisting of the cochlear microphonic (CM) and the auditory nerve neurophonic. By contrast, the transient neural response to tone bursts, that is, compound action potential (CAP), was generally less detectable or less sensitive as a monitoring measure, thus falling short of providing useful contribution to electrocochleography analysis. In this study, we investigate using chirps to evoke more robust CAP responses in a limited frequency band by synchronizing neural firing, and thereby improving CAP sensitivity to mechanical trauma in a guinea pig model of cochlear implantation. DESIGN: Stimuli were band-limited between 100 Hz and 10 kHz to investigate their frequency range selectivity as a preliminary model for low-frequency hearing. They were constructed by adding a harmonic series either with zero phase delay (click) or by adjusting the phase delay at a rate that is inversely related to a traveling wave delay model (chirp), with three different parameters to examine level-dependent delay compression. The amplitude spectrum was thus identical between stimuli with differences only in phase. In Experiment 1, we compared input-output functions recorded at the round window in normal-hearing guinea pigs and implemented a high-pass noise masking paradigm to infer neural contribution to the CAP. In Experiment 2, guinea pigs were implanted with a custom-built CI electrode using a motorized micromanipulator. Acute mechanical trauma was simulated during the electrode insertion. At each insertion step, CAP and CM responses were measured at the round window for the following stimuli: broad-band click, band-limited click, and band-limited chirps (3 parameters), and tone bursts at frequencies 1, 2, 4, and 8 kHz. RESULTS: Chirps compared with the equal-band click showed significantly lower thresholds and steeper slopes of sigmoid-fitted input-output functions. The shorter chirp evoked significantly larger amplitudes than click when compared at equal sensation level. However, the click evoked larger amplitudes than chirps at higher levels and correspondingly achieved larger saturation amplitudes. The results of the high-pass noise masking paradigm suggest that chirps could efficiently synchronize neural firing in their targeted frequency band, while the click recruited more basal fibers outside its limited band. Finally, monitoring sensitivity during electrode insertion, defined as relative amplitude change per unit distance, was higher for chirp-evoked CAP and tone burst-evoked CM, but smaller for CAP responses evoked by clicks or tone bursts. CONCLUSION: The chirp was shown to be an efficient stimulus in synchronizing neural firing for a limited frequency band in the guinea pig model. This study provides a proof of principle for using chirp-evoked CAP as a comprehensive neural measure in CI patients with residual hearing.

Evaluation of a bone groove geometry for fixation of a cochlear implant electrode.

PURPOSE: Electrode migration is a rare, but relevant complication in cochlear implant (CI) surgery. An effective countermeasure is to create a bone groove in the facial recess to secure the electrode lead. We use this method routinely since 2013, but still experienced sporadic electrode migration events most likely due to an improper surgical execution. The aim of this study was to determine the optimum groove geometry. METHODS: Grooves of defined geometry were created in specimens of fresh porcine femur compacta by use of a CNC milling machine. Electrode dummies were fixed in the groove and then exposed to tensile stress. Force measurements were carried out to examine the effect of groove diameter and opening width on the holding force. The mechanical impact on the electrode cable during insertion into the groove was recorded and the electrode lead was examined under microscopic magnification to assess potential structural damage. RESULTS: Optimum groove geometry (diameter 1.10 mm, opening width 0.90 mm) ensured an average holding force of 830 mN which is equivalent to the established fixation by use of a titanium clip. None of the microscopic inspections revealed any morphological deterioration of the electrode lead. CONCLUSION: The fixation of a CI electrode in a bone groove in the facial recess appears to be effective and safe. Furthermore, this method does not require additional costs or foreign material. The optimum geometry defined in this study helped us to refine our surgical standard produce and to generate more consistent results.

Pitch Matching in Cochlear Implant Users With Single-Sided Deafness: Effects of Electrode Position and Acoustic Stimulus Type.

Previous studies in patients with single-sided deafness (SSD) have reported results of pitch comparisons between electric stimulation of their cochlear implant (CI) and acoustic stimulation presented to their near-normal hearing contralateral ear. These comparisons typically used sinusoids, although the percept elicited by electric stimulation may be closer to a wideband stimulus. Furthermore, it has been shown that pitch comparisons between sounds with different timbres is a difficult task and subjected to various types of range biases. The present study aims to introduce a method to minimize non-sensory biases, and to investigate the effect of different acoustic stimulus types on the frequency and variability of the electric-acoustic pitch matches. Pitch matches were collected from 13 CI users with SSD using the binary search procedure. Electric stimulation was presented at either an apical or a middle electrode position, at a rate of 800 pps. Acoustic stimulus types were sinusoids (SINE), 1/3-octave wide narrow bands of Gaussian noises (NBN), or 1/3-octave wide pulse spreading harmonic complexes (PSHC). On the one hand, NBN and PSHC are presumed to better mimic the spread of excitation produced by a single-electrode stimulation than SINE. On the other hand, SINE and PSHC contain less inherent fluctuations than NBN and may therefore provide a temporal pattern closer to that produced by a constant-amplitude electric pulse train. Analysis of mean pitch match variance showed no differences between stimulus types. However, mean pitch matches showed effects of electrode position and stimulus type, with the middle electrode always matched to a higher frequency than the apical one (p < 0.001), and significantly higher across-subject pitch matches for PSHC compared with SINE (p = 0.017). Mean pitch matches for all stimulus types were better predicted by place-dependent characteristic frequencies (CFs) based on an organ of Corti map compared with a spiral ganglion map. CF predictions were closest to pitch matches with SINE for the apical electrode position, and conversely with NBN or PSHC for the middle electrode position. These results provide evidence that the choice of acoustic stimulus type can have a significant effect on electric-acoustic pitch matching.

The Effect of a Bone Groove Against Cochlear Implant Electrode Migration.

HYPOTHESIS: The risk of electrode migration in cochlear implant (CI) surgery can be reduced by securing the electrode lead in a bone groove in the chorda-facial angle. BACKGROUND: Electrode migration is an important complication in CI surgery, which affects hearing performance, may induce pain and facial nerve stimulation, and requires surgical revision. A potential method to secure the electrode is to use a bone groove created in the facial recess to fixate the electrode lead. This surgical measure is a standard procedure for lateral wall electrodes (LWE) in our clinic since 2013. METHODS: Retrospective analysis of consecutive CI cases of a tertiary referral center from 2006 to 2016 and comparison of incidence rates between group A (without bone groove, years 2006-2012) and group B (with bone groove fixation, years 2013-2016). Clinical cases were reviewed with respect to electrode type, migration length, time interval to migration, and findings during revision surgery. RESULTS: Seventeen cases of electrode migration were found in a total of 1,603 cochlear implantations. Only LWE designs were affected by migration. The cumulative incidence for LWE in group B (0.5%) was significantly lower than in group A (3.7%, p < 0.01). The two migration cases in group B revealed insufficient geometric design of the bone grooves. Only one patient experienced a remigration after revision surgery. CONCLUSION: The fixation in a bone groove in the chorda-facial angle is an effective measure against migration of LWE. Proper surgical execution is mandatory to ensure a tight and enduring fit.

Hearing Preservation Outcomes After Cochlear Implantation Depending on the Angle of Insertion: Indication for Electric or Electric-Acoustic Stimulation.

OBJECTIVE: This study reviewed outcomes of hearing preservation (HP) surgery depending on the angle of insertion (AOI) in a cochlear implant (CI) patient population who used electric stimulation (ES) or combined electric-acoustic stimulation (EAS). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral university hospital. PATIENTS: Ninety-one patients with different degrees of preoperative low-frequency residual hearing who underwent HP surgery with a free-fitting lateral-wall electrode array (MED-EL Flex) with lengths ranging from 20.0 to 31.5 mm. INTERVENTION: Cochlear implantation using HP surgery technique and subsequent fitting with CI speech processor for ES, or combined CI and hearing aid speech processor for EAS. MAIN OUTCOME MEASURES: Individual AOI were estimated using modified Stenvers' projection. Freiburg monosyllable test in quiet (free-field presentation at 65 dB SPL) and pure-tone averages for low frequencies (125, 250, and 500 Hz; PTAlow) were evaluated during a follow-up period of 12 months after implantation. RESULTS: Estimated AOIs showed bimodal distribution: shallow insertion (SI) with mean AOI of 377 degrees and deep insertion (DI) with mean AOI of 608 degrees. Speech test scores after 12 months were comparable between AOI groups, however, they were significantly different between stimulation types with better scores for EAS. Only ES showed a positive correlation (r = 0.293) between speech test score and AOI. When HP was possible, both SI and DI showed significant postoperative PTAlow shifts with mean of 17.8 and 21.6 dB, respectively. These were comparable between AOI groups and no significant shifts were observed in follow-up intervals. Audiometric indication for HP and subsequent EAS is proposed up to 65 dB HL at 500 Hz, and up to 87 dB HL for HP. CONCLUSIONS: CI candidates can benefit from HP surgery with deep insertion when only using ES due to insufficient residual hearing. Conversely, candidates with preoperative threshold up to 65 dB HL at 500 Hz could perform significantly better with EAS which requires shallow insertion.

A method for determining precise electrical hearing thresholds in cochlear implant users.

OBJECTIVE: A psychoacoustic procedure designed for the precise assessment of perceptional threshold (T-level) in cochlear implant (CI) users is presented. The impact of this procedure on speech perception was investigated. DESIGN: Individual T-level measurements were obtained with the proposed procedure and three different speech processor fitting conditions were applied: (1) fitting familiar to the subject, T-levels unchanged, (2) T-level set to thresholds determined with the new procedure, (3) T-level set to thresholds determined with the new procedure, but T-level is decreased by 10 clinical units (CU). The impact of the different fitting conditions was measured by means of categorical loudness scaling (CLS) and speech perception tests in quiet and noise. STUDY SAMPLE: A prospective study at a tertiary referral university hospital. 18 experienced postlingually deafened cochlear implanted adult subjects. RESULTS: Average sound-field thresholds obtained by CLS were lowest in condition using the new procedure yielding a larger dynamic range with significantly higher speech scores in quiet compared to those with a subject's commonly used programme, and significantly improved in noise even after reducing T-levels by 10 CU. CONCLUSION: The precise determination of T-levels by means of the proposed procedure improved performance in several speech recognition tasks. Compared to the default behavioural setting, T-level increased on median by 9 CU. Average speech reception threshold in noise for soft speech levels (50 dB sound pressure level) decreased by 1 dB.

Preventing Facial Nerve Stimulation by Triphasic Pulse Stimulation in Cochlear Implant Users: Intraoperative Recordings.

HYPOTHESIS: Triphasic pulse stimulation of the auditory nerve can prevent unintended facial nerve stimulation (FNS) due to a different electromyographic (EMG) input-output function compared with biphasic pulses. BACKGROUND: FNS is sometimes observed in cochlear implant (CI) users as an unpleasant side effect of electrical stimulation using biphasic pulse patterns (BPP). Clinical remedies to alleviate FNS are 1) to extend stimulus phase duration or 2) to completely deactivate the electrode. In some cases, these options do not provide sufficient FNS reduction or are detrimental to subject performance. Stimulation using triphasic pulse patterns (TPP) has been shown to prevent FNS more effectively, yet the underlying mechanism remains unclear. METHODS: EMG potentials of muscles innervated by the facial nerve (orbicularis oculi and oris muscles) were recorded to quantitatively compare the effect of BPP and TPP stimulation on FNS. Recordings were conducted in five subjects during CI surgery. In two exemplary cases, different leading phase polarities in alternating and non-alternating order were tested. RESULTS: Compared with our previous study in awake patients using surface electrodes (Bahmer and Baumann, 2016), intraoperative recordings using subdermal electrodes showed lower noise content and allowed higher sampling resolution. While inter-subject variation remained high, intra-subject results for different electrode positions were comparable: FNS was strongly reduced for cathodic-first TPP stimulation. In contrast, exemplary cases showed little reduction for anodic-first TPP as well as for alternating stimulation. CONCLUSION: FNS in CI users can be reduced using TPP stimulation, but the ameliorative effect appears to be dependent on the leading stimulus polarity.

Forward Masking in Cochlear Implant Users: Electrophysiological and Psychophysical Data Using Pulse Train Maskers.

Electrical stimulation of auditory nerve fibers using cochlear implants (CI) shows psychophysical forward masking (pFM) up to several hundreds of milliseconds. By contrast, recovery of electrically evoked compound action potentials (eCAPs) from forward masking (eFM) was shown to be more rapid, with time constants no greater than a few milliseconds. These discrepancies suggested two main contributors to pFM: a rapid-recovery process due to refractory properties of the auditory nerve and a slow-recovery process arising from more central structures. In the present study, we investigate whether the use of different maskers between eCAP and psychophysical measures, specifically single-pulse versus pulse train maskers, may have been a source of confound.In experiment 1, we measured eFM using the following: a single-pulse masker, a 300-ms low-rate pulse train masker (LTM, 250 pps), and a 300-ms high-rate pulse train masker (HTM, 5000 pps). The maskers were presented either at same physical current (Φ) or at same perceptual (Ψ) level corresponding to comfortable loudness. Responses to a single-pulse probe were measured for masker-probe intervals ranging from 1 to 512 ms. Recovery from masking was much slower for pulse trains than for the single-pulse masker. When presented at Φ level, HTM produced more and longer-lasting masking than LTM. However, results were inconsistent when LTM and HTM were compared at Ψ level. In experiment 2, masked detection thresholds of single-pulse probes were measured using the same pulse train masker conditions. In line with our eFM findings, masked thresholds for HTM were higher than those for LTM at Φ level. However, the opposite result was found when the pulse trains were presented at Ψ level.Our results confirm the presence of slow-recovery phenomena at the level of the auditory nerve in CI users, as previously shown in animal studies. Inconsistencies between eFM and pFM results, despite using the same masking conditions, further underline the importance of comparing electrophysiological and psychophysical measures with identical stimulation paradigms.

Management of Cochlear Implant Electrode Migration.

OBJECTIVE: The present study reviewed a cochlear implant (CI) patient population after surgery, which received a free-fitting electrode carrier designed for hearing preservation. The aim was to determine the rate of electrode migration of the CI electrodes and present clinical and surgical implications. STUDY DESIGN: Retrospective patient review. SETTING: Tertiary referral university hospital. PATIENTS: Two hundred seventy-eight patients implanted uni- or bilaterally with lateral wall electrodes designed for hearing preservation (358 implants). The control group was 323 patients implanted uni- or bilaterally with preformed perimodiolar electrodes (468 implants). INTERVENTIONS: Determination of CI electrode migration was conducted according to a clinical test protocol. Revision surgery was offered in confirmed patients of electrode migration. A bone groove was considered to improve the fixation of the electrode. MAIN OUTCOME MEASURES: Audiological testing including speech audiometry, subjective sound quality rating, and bilateral pitch comparison in bilateral patients, as well as radiological examinations, were conducted. RESULTS: Electrode migration was observed solely in patients implanted with lateral wall electrodes; 10 of 358 patients with free-fitting electrodes (2.8%) had electrode migration, which was successfully confirmed by the proposed clinical test protocol. Nine of the 10 confirmed patients underwent reinsertion surgery. Mean perception score decreased from 75.0% to 62.1% after electrode migration and recovered completely after reinsertion surgery. A flowchart to detect electrode migration was designed for clinical practice. CONCLUSION: Although electrode migration is a rare complication in CI surgery, long-term follow-up diagnostics should include a test protocol to detect electrode shifts of lateral wall electrode arrays. A reinsertion surgery should be conducted in confirmed patients to recover speech perception.

Long-term Hearing Preservation Outcomes After Cochlear Implantation for Electric-Acoustic Stimulation.

OBJECTIVE: This study reviewed outcomes of hearing preservation (HP) surgery in a cochlear implant patient population, with clinical follow-up results up to 11 years after implantation. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral university hospital. PATIENTS: Ninety six patients (103 ears) with partial deafness who underwent HP surgery at the University Hospital Frankfurt since 1999 were included. Electrode carriers were Cochlear Slim Straight, MED-EL Standard, Medium, Flex, and Flex. INTERVENTION: Cochlear implantation using the HP surgery technique with either the cochleostomy or round window approach. MAIN OUTCOME MEASURES: Pure-tone averages for low frequencies (125 Hz, 250 Hz, 500 Hz, PTAlow) and speech perception scores of the Freiburg monosyllable and number tests in quiet. PTAlow shifts were used to evaluate HP as complete for ≤10 dB, partial between 10 and 30 dB, and minimal for ≥30 dB. Time intervals were: preoperative, postoperative, after 12 months, and long-term (>24 months, mean 51.4 months, range 2-11 years). Impacts of electrode design and surgical approach were analyzed. RESULTS: Postoperatively (n = 103), HP was complete in 32 (31.1%), partial in 49 (47.6%), minimal in 14 (13.6%), and loss of hearing occurred in 8 cases (7.8%). After 12 months (n = 81), HP was complete in 22 (27.2%), partial in 33 (40.7%), minimal in 11 (13.6%), and loss of hearing occurred in 7 additional cases. For long-term outcomes (n = 62) HP was complete in 7 (11.3%), partial in 24 (38.7%), minimal in 9 (14.5%), and loss of hearing occurred in 7 additional cases (total 22/103, 21.4%). Cases with residual hearing who could utilize acoustic amplification (i.e., PTAlow < 80 dB HL) were 82/95 (85.3%) postoperatively, 58/66 (87.9%) after 12 months, and 38/40 (95.0%) for long-term outcomes. CONCLUSIONS: Long-term HP is feasible in a subset of patients. Patients with sufficient long-term residual hearing had the prerequisite to benefit from additional acoustic stimulation. No correlation of total hearing loss with etiology, electrode design, or surgical approach was evident. Apart from individual effects of structural damage or inflammation, genetic factors are suggested to influence HP. Cases with total hearing loss still demonstrated successful speech perception in long-term monosyllable recognition scores.

Place dependent stimulation rates improve pitch perception in cochlear implantees with single-sided deafness.

In normal hearing, the pitch of an acoustic tone can theoretically be encoded by either the place of stimulation in the cochlea or the corresponding rate of vibration. Thus spectral attributes and temporal fine structure of an acoustic signal are naturally correlated. Cochlear implants (CIs), neural prosthetic devices that restore hearing in the profoundly hearing impaired, currently disregard this mechanism; electrical stimulation is provided at fixed electrode positions with default place independent stimulation rate assignments. This does not account for individual cochlear encoding depending on electrode array placement, variations in insertion depth, and the proximity to nerve fibers. Encoding pitch in such manner delivers limited tonal information. Consequently, music appraisal in CI users is often rated cacophonic while speech perception in quiet is close to normal in top performers. We hypothesize that this limitation in electric stimulation is at least partially due to the mismatch between frequency and place encoding in CIs. In the present study, we determined individual electrode locations by analysis of cochlear radiographic images obtained after surgery and calculated place dependent stimulation rates according to models of the normal tonotopic function. Pitch matching in CI users with single-sided deafness shows that place dependent stimulation rates allow thus far unparalleled restoration of tonotopic pitch perception. Collapsed data of matched pitch frequencies as a function of calculated electrical stimulation rate were well fitted by linear regression (R(2) = 0.878). Sound processing strategies incorporating place dependent stimulation rates are expected to improve pitch perception in CI users.

Speech Perception With Combined Electric-Acoustic Stimulation: A Simulation and Model Comparison.

OBJECTIVE: The aim of this study is to simulate speech perception with combined electric-acoustic stimulation (EAS), verify the advantage of combined stimulation in normal-hearing (NH) subjects, and then compare it with cochlear implant (CI) and EAS user results from the authors' previous study. Furthermore, an automatic speech recognition (ASR) system was built to examine the impact of low-frequency information and is proposed as an applied model to study different hypotheses of the combined-stimulation advantage. Signal-detection-theory (SDT) models were applied to assess predictions of subject performance without the need to assume any synergistic effects. DESIGN: Speech perception was tested using a closed-set matrix test (Oldenburg sentence test), and its speech material was processed to simulate CI and EAS hearing. A total of 43 NH subjects and a customized ASR system were tested. CI hearing was simulated by an aurally adequate signal spectrum analysis and representation, the part-tone-time-pattern, which was vocoded at 12 center frequencies according to the MED-EL DUET speech processor. Residual acoustic hearing was simulated by low-pass (LP)-filtered speech with cutoff frequencies 200 and 500 Hz for NH subjects and in the range from 100 to 500 Hz for the ASR system. Speech reception thresholds were determined in amplitude-modulated noise and in pseudocontinuous noise. Previously proposed SDT models were lastly applied to predict NH subject performance with EAS simulations. RESULTS: NH subjects tested with EAS simulations demonstrated the combined-stimulation advantage. Increasing the LP cutoff frequency from 200 to 500 Hz significantly improved speech reception thresholds in both noise conditions. In continuous noise, CI and EAS users showed generally better performance than NH subjects tested with simulations. In modulated noise, performance was comparable except for the EAS at cutoff frequency 500 Hz where NH subject performance was superior. The ASR system showed similar behavior to NH subjects despite a positive signal-to-noise ratio shift for both noise conditions, while demonstrating the synergistic effect for cutoff frequencies ≥300 Hz. One SDT model largely predicted the combined-stimulation results in continuous noise, while falling short of predicting performance observed in modulated noise. CONCLUSIONS: The presented simulation was able to demonstrate the combined-stimulation advantage for NH subjects as observed in EAS users. Only NH subjects tested with EAS simulations were able to take advantage of the gap listening effect, while CI and EAS user performance was consistently degraded in modulated noise compared with performance in continuous noise. The application of ASR systems seems feasible to assess the impact of different signal processing strategies on speech perception with CI and EAS simulations. In continuous noise, SDT models were largely able to predict the performance gain without assuming any synergistic effects, but model amendments are required to explain the gap listening effect in modulated noise.

Yield Responses of Direct-Seeded Wheat to Rhizobacteria and Fungicide Seed Treatments.

Field trials were conducted with winter and spring wheat in eastern Washington and northern Idaho over several years to determine the benefit, as measured by grain yield, of seed treatments with rhizobacteria and formulated fungicides in cropping systems favorable to root diseases. The trials were conducted with wheat direct-seeded (no-till) in fields with a history of intensive cereals and one or more of the root diseases: take-all caused by Gaeumannomyces graminis var. tritici, Rhizoctonia root rot caused by Rhizoctonia solani AG8 and R. oryzae, and Pythium root rot caused mainly by Pythium irregulare and P. ultimum. The seed treatments included Bacillus sp. L324-92, Pseudomonas fluorescens Q69c-80, Pseudomonas fluorescens Q8r1-96, difenoconazole + metalaxyl (Dividend + Apron), difenoconazole + mefenoxam (Dividend + Apron XL = Dividend XL), tebuconazole + metalaxyl (Raxil XT), and tebuconazole + thiram (Raxil-thiram). Controls were nontreated seed planted into both nontreated (natural) soil and soil fumigated with methyl bromide just prior to planting. Although the data indicate a trend in higher wheat yields with two rhizobacteria treatments over the nontreated control (171 and 264 kg/ha, respectively), these higher yields were not significantly different from the nontreated control (P = 0.06). Fungicide seed treatments alone similarly resulted in yields that were 100 to 300 kg/ha higher than the nontreated control, but only the yield responses to Dividend on winter wheat (289 kg/ha) and Dividend + Apron on spring wheat (263 kg/ha) were significant (P ≤ 0.05). The greatest yield increases over the nontreated control occurred with certain rhizobacteria-fungicide combinations, with three treatments in the range of 312 to 486 kg/ha (6.1 to 17.7%; P ≤ 0.05). Some rhizobacteria-fungicide combinations brought average yields to within 85 to 90% of those obtained with soil fumigation. Only soil fumigation produced a measurable reduction in the incidence of take-all and Rhizoctonia root rot, as assessed on washed roots. No reliable method exists for visual quantification of Pythium root rot on wheat.