This research was funded by a Health and Labor Sciences Research Grant for Research on Rare and Intractable Diseases and Comprehensive Research on Disability Health and Welfare from the Ministry of Health, Labour and Welfare of Japan (S.U. 20FC1048, 23FC10149) and Grants-in-Aid from the Japan Agency for Medical Research and Development (AMED) (S.U. 19ek0109363h0002, 21ek0109542h003).

The described procedures were approved by the Institutional Review Board of Shinshu University School of Medicine (Approval no. 4133). The patients provided written informed consent before participating in the study. The reagents, equipment, and software used for this study are listed in the Table of Materials.
1. Preoperative evaluation
<ol>
	<li>Review the series of pure-tone audiograms in patients with residual hearing to ascertain the progression of HL in each case.</li>
	<li>Conduct genetic testing on blood samples obtained from both patients and their family members.</li>
	<li>Recommend to perform next-generation sequencing on a panel of genes associated with HL6,7.</li>
	<li>Conduct imaging tests, such as CT and/or magnetic resonance imaging (MRI). It was recommended that the CT slice thickness be 0.6 mm or less. For MRI, a strength of 1.5 Tesla was deemed sufficient.</li>
	<li>Make predictions regarding future residual acoustic hearing to the best extent possible following the collection of the audiogram series6 and the identification of etiology through imaging and/or genetic analysis.</li>
	<li>Import DICOM data from preoperative CT images into the OTOPLAN software. The software automatically measures the CDL in each case.</li>
	<li>Select the appropriate length of the CI array to cover the region where residual hearing is anticipated to deteriorate in the future. Employ only thin, straight, and flexible electrodes.</li>
	<li>Administer prednisolone orally at a dosage of 0.5-1.0 mg/kg/day beginning 2 days prior to surgery.</li>
</ol>
2. Surgical procedure
<ol>
	<li>Place the patient in the supine position.</li>
	<li>Induce anesthesia using intravenous fentanyl (1-2 &#181;g/kg), propofol (1-2 mg/kg), and rocuronium (0.6 mg/kg). Maintain anesthesia with propofol (3-8 mg/kg/h), remifentanil (0.1-0.2 &#181;g/kg/min), and fentanyl (total: 300-500 &#181;g), without vecuronium, to facilitate neuromuscular monitoring.</li>
	<li>Administer an intravenous infusion of 8 mg of dexamethasone 30 min before making the incision.</li>
	<li>Rotate the patient&#39;s head to 45 degrees during surgery.</li>
	<li>Inject local anesthesia (subcutaneous 0.5% lidocaine with 1:1,00,000 epinephrine) postauricularly.</li>
	<li>Perform a postauricular incision of 5-6 cm (lazy S-shaped) and mastoidectomy with 6.0-4.0 mm cutting bars until reaching the point where the antrum includes the lateral semicircular canal and the short process of the incus6.</li>
	<li>Perform a posterior tympanotomy between the expected facial nerve and chorda tympani using 1.5-2.0 mm diamond bars.</li>
	<li>Visualize the round window niche and remove the bony overhang of the round window using a low-speed drill with a 1.0-1.5 mm diamond bar, exposing the round window membrane.</li>
	<li>Sufficiently open the round window membrane using a pick and carefully insert the electrode slowly for over 3 min.</li>
	<li>Perform X-ray and audiograms after completing the electrode insertion.</li>
</ol>
3. Postoperative evaluation
<ol>
	<li>Administer intravenous dexamethasone at 8 mg/day, 4&#160;mg/day, and 4 mg/day for 3 days following surgery.</li>
	<li>Measure unaided auditory thresholds 6 months after the initial activation, and assess the HP rate using the classification provided by Skarzynski et al.20.</li>
	<li>Optimize map settings using a software tool based on the results of the postoperative audiogram and patient&#160;preferences.</li>
</ol>

Hearing Preservation with Long Electrodes in Electric-Acoustic Stimulation

<ol>
	<li>Von Ilberg, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electric-acoustic+stimulation+of+the+auditory+system.+New+technology+for+severe+hearing+loss.">Electric-acoustic stimulation of the auditory system. New technology for severe hearing loss.</a> ORL J Otorhinolaryngol Relat Spec. 61 (6), 334-340 (1999).</li><li>Gstoettner, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+electrode+for+residual+hearing+preservation+in+cochlear+implantation:+First+clinical+results.">A new electrode for residual hearing preservation in cochlear implantation: First clinical results.</a> Acta Otolaryngol. 129 (4), 372-379 (2009).</li><li>Moteki, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Feasibility+of+hearing+preservation+for+residual+hearing+with+longer+cochlear+implant+electrodes.">Feasibility of hearing preservation for residual hearing with longer cochlear implant electrodes.</a> Acta Otolaryngol. 138 (12), 1080-1085 (2018).</li><li>Usami, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Achievement+of+hearing+preservation+in+the+presence+of+an+electrode+covering+the+residual+hearing+region.">Achievement of hearing preservation in the presence of an electrode covering the residual hearing region.</a> Acta Otolaryngol. 131 (4), 405-412 (2011).</li><li>Usami, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hearing+preservation+and+clinical+outcome+of+32+consecutive+electric+acoustic+stimulation+(EAS)+surgeries.">Hearing preservation and clinical outcome of 32 consecutive electric acoustic stimulation (EAS) surgeries.</a> Acta Otolaryngol. 134 (7), 717-727 (2014).</li><li>Yoshimura, H., Moteki, H., Nishio, S. Y., Usami, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electric-acoustic+stimulation+with+longer+electrodes+for+potential+deterioration+in+low-frequency+hearing.">Electric-acoustic stimulation with longer electrodes for potential deterioration in low-frequency hearing.</a> Acta Otolaryngol. 140 (8), 632-638 (2020).</li><li>Yoshimura, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetic+testing+has+the+potential+to+impact+hearing+preservation+following+cochlear+implantation.">Genetic testing has the potential to impact hearing preservation following cochlear implantation.</a> Acta Otolaryngol. 140 (6), 438-444 (2020).</li><li>Van de Heyning, P. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systematic+literature+review+of+hearing+preservation+rates+in+cochlear+implantation+associated+with+medium-+and+longer-length+flexible+lateral+wall+electrode+arrays.">Systematic literature review of hearing preservation rates in cochlear implantation associated with medium- and longer-length flexible lateral wall electrode arrays.</a> Front Surg. 9, 893839 (2022).</li><li>Buchman, C. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+cochlear+implant+insertion+depth+on+performance:+A+prospective+randomized+trial.">Influence of cochlear implant insertion depth on performance: A prospective randomized trial.</a> Otol Neurotol. 35 (10), 1773-1779 (2014).</li><li>Buchner, A., Illg, A., Majdani, O., Lenarz, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Investigation+of+the+effect+of+cochlear+implant+electrode+length+on+speech+comprehension+in+quiet+and+noise+compared+with+the+results+with+users+of+electro-acoustic-stimulation,+a+retrospective+analysis.">Investigation of the effect of cochlear implant electrode length on speech comprehension in quiet and noise compared with the results with users of electro-acoustic-stimulation, a retrospective analysis.</a> PLoS One. 12 (5), e0174900 (2017).</li><li>Canfarotta, M. W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+influence+of+electrode+array+length+on+speech+recognition+in+cochlear+implant+users.">Long-term influence of electrode array length on speech recognition in cochlear implant users.</a> Laryngoscope. 131 (4), 892-897 (2021).</li><li>Nassiri, A. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hearing+preservation+outcomes+using+a+precurved+electrode+array+inserted+with+an+external+sheath.">Hearing preservation outcomes using a precurved electrode array inserted with an external sheath.</a> Otol Neurotol. 41 (1), 33-38 (2020).</li><li>O'Connell, B. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrode+location+and+angular+insertion+depth+are+predictors+of+audiologic+outcomes+in+cochlear+implantation.">Electrode location and angular insertion depth are predictors of audiologic outcomes in cochlear implantation.</a> Otol Neurotol. 37 (8), 1016-1023 (2016).</li><li>Moteki, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+results+of+hearing+preservation+cochlear+implant+surgery+in+patients+with+residual+low+frequency+hearing.">Long-term results of hearing preservation cochlear implant surgery in patients with residual low frequency hearing.</a> Acta Otolaryngol. 137 (5), 516-521 (2017).</li><li>Von Ilberg, C. A., Baumann, U., Kiefer, J., Tillein, J., Adunka, O. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electric-acoustic+stimulation+of+the+auditory+system:+A+review+of+the+first+decade.">Electric-acoustic stimulation of the auditory system: A review of the first decade.</a> Audiol Neurootol. 16, 1-30 (2011).</li><li>Ariyasu, L., Galey, F. R., Hilsinger, R., Byl, F. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Computer-generated+three-dimensional+reconstruction+of+the+cochlea.">Computer-generated three-dimensional reconstruction of the cochlea.</a> Otolaryngol Head Neck Surg. 100 (2), 87-91 (1989).</li><li>Danielian, A., Ishiyama, G., Lopez, I. A., Ishiyama, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Morphometric+linear+and+angular+measurements+of+the+human+cochlea+in+implant+patients+using+3-dimensional+reconstruction.">Morphometric linear and angular measurements of the human cochlea in implant patients using 3-dimensional reconstruction.</a> Hear Res. 386, 107874 (2020).</li><li>Kawano, A., Seldon, H. L., Clark, G. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Computer-aided+three-dimensional+reconstruction+in+human+cochlear+maps:+Measurement+of+the+lengths+of+organ+of+Corti,+outer+wall,+inner+wall,+and+Rosenthal's+canal.">Computer-aided three-dimensional reconstruction in human cochlear maps: Measurement of the lengths of organ of Corti, outer wall, inner wall, and Rosenthal's canal.</a> Ann Otol Rhinol Laryngol. 105 (9), 701-709 (1996).</li><li>Rask-Andersen, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+cochlea:+Anatomical+characteristics+and+their+relevance+for+cochlear+implantation.">Human cochlea: Anatomical characteristics and their relevance for cochlear implantation.</a> Anat Rec (Hoboken). 295 (11), 1791-1811 (2012).</li><li>Skarzynski, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Towards+a+consensus+on+a+hearing+preservation+classification+system.">Towards a consensus on a hearing preservation classification system.</a> Acta Otolaryngol Suppl. 564, 3-13 (2013).</li><li>Yoshimura, H., Watanabe, K., Nishio, S. Y., Takumi, Y., Usami, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determining+optimal+cochlear+implant+electrode+array+with+OTOPLAN.">Determining optimal cochlear implant electrode array with OTOPLAN.</a> Acta Otolaryngol. 143 (9), 748-752 (2023).</li><li>Skarzynska, M. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preservation+of+hearing+following+cochlear+implantation+using+different+steroid+therapy+regimens:+a+prospective+clinical+study.">Preservation of hearing following cochlear implantation using different steroid therapy regimens: a prospective clinical study.</a> Med Sci Monit. 24, 2437-2445 (2018).</li><li>Geerardyn, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+histology+after+structure+preservation+cochlear+implantation+via+round+window+insertion.">Human histology after structure preservation cochlear implantation via round window insertion.</a> Laryngoscope. 134 (2), 945-953 (2023).</li><li>Campbell, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intraoperative+real-time+cochlear+response+telemetry+predicts+hearing+preservation+in+cochlear+implantation.">Intraoperative real-time cochlear response telemetry predicts hearing preservation in cochlear implantation.</a> Otol Neurotol. 37 (4), 332-338 (2016).</li></ol>

The authors declare no conflicts of interest.

Identifying the etiology of HL in the preoperative evaluation is crucial for predicting the future audiogram in each case. In our earlier study, pathogenic variants in the CDH23, ACTG1, Mit1555A&#62;G, MYO7A, MYO15A, SLC26A4, and TMPRSS3 genes were frequently identified in patients with high-frequency HL7. In most of these patients, the residual hearing gradually deteriorated (see CDH23-related HL case in Figure 2). In these cases, the natural course of HL was considered when selecting the CI electrode for broader cochlear coverage.
Determining the length of the CI array required measuring the cochlear duct length (CDL). To facilitate this process, the OTOPLAN software proved to be clinically feasible21. In earlier versions, such as OTOPLAN 3.0, the CDL was manually measured to plot each cochlea&#39;s diameter, width, and height. However, with OTOPLAN 4.0, automatic measurement of the CDL became possible, offering increased convenience for surgeons and minimizing measurement variation. Notably, CT images with a slice thickness of 0.6 mm or less were suitable for the automatic analysis provided by OTOPLAN. Subsequently, the length of the CI array should be selected to achieve the optimal angle of insertion depth (AID) in each case.
To perform a less invasive EAS surgery, pre-, intra-, and post-steroid administration was required to minimize the acute inflammation that could elevate the hearing threshold22. In the near future, to minimize not only acute but also chronic reactions following CI and EAS surgery, the use of dexamethasone-eluting electrodes will be desirable. In addition to steroid administration, flexible lateral-wall electrodes were essential for minimizing trauma to the cochlea. Inserting such electrodes into the cochlea carefully and slowly using the round window approach resulted in minimal invasiveness. To aid in this, performing surgery using exoscopes and endoscopes was useful for generating a clearer field of view and confirming the tiny components of the middle ear. To prevent inducing extensive fibro-osseous tissue formation in the cochlea, the extended round window approach and cochleostomy must be avoided23.
EAS with longer electrodes was useful not only to prepare for the future deterioration of HL but also to offer three types of map strategies. If the inserted electrodes overlap with the residual hearing region, patients with EAS can use ES with or without AS: &#34;EAS (Overlap/ON) map&#34; or &#34;ES-only map.&#34; Alternatively, they can turn off some of the apical contacts and activate the AS: &#34;EAS (Overlap/OFF) map.&#34; If hearing deteriorates, all the contacts can be later switched on to provide better pitch matching (Figure 3). All these findings show that EAS with longer electrodes allows users to optimize maps for more natural hearing.
Herein, it is shown that preoperative preparation and advanced surgical techniques are essential to minimize surgical trauma. Performing the above-named series of pre-and intra-operative procedures allowed patients to benefit from EAS with longer electrodes.




Limitations 
Despite advances in the aforementioned less-invasive surgical procedures, residual hearing still deteriorates in a certain number of patients after CI. Intra-operative monitoring, such as cochlear microphonics (CM), would be clinically feasible to measure cochlear damage during the electrode insertion24. However, how to evaluate EAS with longer electrodes and what to do in the case of certain CM responses, such as a decrease in amplitude, remains unclear to date. Further studies in this area are required.

Conventional cochlear implantation (CI) is a standard treatment for improving hearing ability in patients with severe-to-profound hearing loss (HL). Subsequently, electric-acoustic stimulation (EAS) is used to treat patients with severe high-frequency hearing loss and residual low-frequency hearing1. In such patients, preserving the residual acoustic hearing is important to achieve better speech perception in noise, sound localization, and improved sound quality when listening to music2. To address this,&#160;the use of&#160;shorter electrodes in EAS patients has been preferred to avoid interfering with the residual function in the acoustic region of the cochlea. However, our earlier studies3,4,5,6&#160;documented that even in EAS cases, less invasive CI surgery combined with thin, straight, and flexible &#34;longer&#34; electrodes enabled the preservation of residual hearing. Additionally, we reported that hearing preservation was unrelated to the length of the inserted cochlear implant electrode7, consistent with the systematic review8.
In patients who underwent conventional CI, longer electrodes led to better speech perception9,10,11&#160;as longer electrodes provide broader cochlear coverage and better place-pitch matching. Similarly, a&#160;correlation between a deeper angle of insertion (AID) and better hearing was reported12,13. In most EAS patients, the residual hearing gradually deteriorates over time14. Identifying the responsible gene for HL allows&#160;one to predict future hearing. When it is anticipated that their hearing would be lost across all frequencies in the future, EAS with longer electrodes, not shorter electrodes, is&#160;ideal in providing&#160;a higher percentage of cochlear coverage15. The optimal AID was thought to range from 630&#176; to 720&#176;16,17,18, corresponding to the distribution of spiral ganglion neurons in the human cochlea. However, as each cochlear duct length (CDL) has a wide range of variation19, measuring the CDL in each case was required to achieve the appropriate AID, even in EAS patients. Recently, commercially available software (see Table of Materials) allowed the measurment&#160;of each CDL easily based on computed tomography (CT) data, which was clinically feasible.
This protocol describes the following: (1) a preoperative evaluation that included genetic analysis to identify the etiology of HL and cochlear duct length measurement to determine the optimal electrode length, (2) a less invasive surgical procedure via exoscopy and endoscopy, and (3) the postoperative hearing outcome and mapping strategy in patients with high-frequency HL who underwent EAS with a longer electrode.

<table><tbody><tr><td>DEXART 3.3 mg</td><td>Fuji Pharma</td><td>22100AMX01404</td><td>equal to dexamethasone sodium phosphate (4 mg)</td></tr><tr><td>DEXART 6.6 mg</td><td>Fuji Pharma</td><td>22100AMX01402</td><td>equal to dexamethasone sodium phosphate (8 mg)</td></tr><tr><td>Fentanyl injection 0.1 mg</td><td>TERUMO</td><td>22100AMX00009</td><td></td></tr><tr><td>MAESTRO 7.0</td><td>MED-EL</td><td>4582290238456</td><td>fitting software for map settings</td></tr><tr><td>Midas Rex MR8&amp;nbsp;</td><td>Medtronic</td><td>301ADBZX00046000</td><td>high speed drill</td></tr><tr><td>OTOPLAN software</td><td>Cascination / MED-EL</td><td>REF 20125</td><td>for measuring cochlear duct length (CDL)&amp;nbsp;</td></tr><tr><td>Predonine tablets</td><td>Shionogi</td><td>16000AMZ01740000</td><td></td></tr><tr><td>Propofol 1% 50 mL</td><td>Maruishi Pharmaceutical Co.,Ltd</td><td>30100AMX00158</td><td></td></tr><tr><td>Remifentanil 2 mg</td><td>Daiichi-Sankyo</td><td>22800AMX00090</td><td></td></tr><tr><td>Rocuronium bromide 50 mg/50 mL</td><td>Maruishi Pharmaceutical Co.,Ltd</td><td>22800AMX00534</td><td></td></tr><tr><td>SONNET2 EAS</td><td>MED-EL</td><td>4582290241807</td><td>processor</td></tr><tr><td>Synchrony2 FLEX28</td><td>MED-EL</td><td>4571573943026</td><td>cochlear implant (electrode)</td></tr><tr><td>Xylocaine 0.5% with epinephrine</td><td>Sandoz Pharma</td><td>4KUZ13127</td><td></td></tr></tbody></table>

enhanced cochlear coverage and hearing preservation in high-frequency hearing loss via electric acoustic stimulation with longer electrode

Electric-acoustic stimulation (EAS) is a promising treatment to improve hearing ability in patients with high-frequency hearing loss (HL). In EAS surgeries, shorter electrodes have been preferred to avoid the presence of an electrode covering the residual hearing region. However, our earlier studies showed that EAS with longer electrodes (28 mm) could preserve acoustic hearing. Additionally, we reported that the hearing preservation (HP) scores were independent of the length of the inserted electrodes, consistent with the systematic review. As most EAS patients gradually lose residual hearing over time due to the natural course of HL, in these cases, providing broader cochlear coverage using longer electrodes was beneficial toward better place-pitch matching. In addition to preparing for the deterioration in&#160;hearing in&#160;the future, EAS with longer electrodes could offer various types of map strategies. Herein, we show the pre-, intra-, and post-procedures for EAS surgery. Appropriate preoperative evaluation, less invasive surgery, flexible lateral-wall electrodes, and steroid administration resulted in good HP following EAS with longer electrodes.

EAS was conducted on 10 patients (11 ears) who fulfilled the audiological criteria for EAS (refer to Table 1). The inclusion criteria comprised the following: bilateral pure-tone hearing levels &#8804;65 dBHL for 125 Hz, 250 Hz, and 500 Hz; &#8805;80 dBHL at 2000 Hz; and &#8805;85 dBHL at 4000 Hz and 8000 Hz. Additionally, minimal benefit from conventional hearing aids was required, defined as monosyllable scores in quiet below 60% even in the optimal aided condition. All participants underwent EAS using longer electrodes (see Table of Materials). Figure 1 shows the preoperative and 6-month postoperative audiograms following EAS surgery, suggesting that residual low-frequency hearing was well-preserved in all cases. According to the hearing preservation (HP) classification system reported by Skarzynski et al.20, 36.4% (4 of 11 cases) showed complete HP, and 63.6% (7 of 11 cases) showed partial HP. There were no cases of significant hearing deterioration.
Case presentation (Case #8) 
At the age of 5, during a routine elementary school wellness check-up, a 14-year-old girl who had not undergone newborn hearing screening was flagged for suspected hearing loss (HL). Subsequently diagnosed with high-frequency HL, she began using hearing aids. Given the observed deterioration in her hearing, she sought evaluation at our department at the age of 13.
Pathogenic variants of the CDH23 gene were identified via genetic testing6. Since the residual hearing was likely to deteriorate&#160;due to CDH23-related HL, a longer electrode was selected to cover the acoustic region. She underwent EAS surgery on the left ear at the age of 14. The residual hearing was completely preserved 6 months after surgery. She preferred &#34;electric-stimulation (ES)-only mapping&#34; with activated apical electrodes traversing the region of residual hearing at that time (Figure 2). The patient was satisfied with the acoustic amplification obtained using ES at low frequencies.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/66565/66565fig01.jpg" /> 
Figure 1: Average air-conduction hearing thresholds. The dashed and solid lines indicate preoperative and 6-month postoperative measurements, respectively. Gray and black lines show the individual data and the mean, respectively. This figure has been adapted from Yoshimura et al.6. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66565/66565fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/66565/66565fig02.jpg" /> 
Figure 2: Clinical findings of Case #8. (A) Pedigree of the patient. (B) Preoperative and 6-month postoperative audiograms. Electrode array illustrations represent insertion depth. (C) Postoperative X-ray findings, with numbers corresponding to individual channels. (D) Imaging for each electrode location and the reference tonotopic map. This figure has been adapted from Yoshimura et al.6. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66565/66565fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/66565/66565fig03.jpg" /> 
Figure 3: Three types of mapping strategy in patients with EAS using longer electrodes. (A) EAS (Overlap/OFF) map. Some of the apical contacts were deactivated, while the acoustic stimulation (AS) was activated. (B) EAS (Overlap/ON) map. Both electrical stimulation (ES) in the cochlear implantation (CI) default setting and AS were utilized. (C) ES-only map. In the ES setting, the frequency range was set from 70-8,500 Hz. AS was deactivated. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66565/66565fig03large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Patient&#160;</td>
			<td></td>
			<td>Implanted&#160;</td>
			<td>Implanted&#160;</td>
			<td>Responsible</td>
			<td>Pre-op</td>
			<td>6M post-op</td>
			<td>HP numerical</td>
			<td>HP</td>
		</tr>
		<tr>
			<td>No.</td>
			<td>Gender</td>
			<td>age (years)</td>
			<td>side</td>
			<td>Gene</td>
			<td>LFA (dB)</td>
			<td>LFA (dB)</td>
			<td>scale (%)</td>
			<td>classification</td>
		</tr>
		<tr>
			<td>1</td>
			<td>F</td>
			<td>12</td>
			<td>L</td>
			<td>SLC26A4</td>
			<td>63.3</td>
			<td>70</td>
			<td>70.8</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td>2</td>
			<td>F</td>
			<td>9</td>
			<td>L</td>
			<td>SLC26A4</td>
			<td>50</td>
			<td>65</td>
			<td>62.5</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td>3</td>
			<td>M</td>
			<td>50</td>
			<td>L</td>
			<td>CDH23</td>
			<td>50</td>
			<td>56.7</td>
			<td>78.6</td>
			<td>Complete</td>
		</tr>
		<tr>
			<td>4</td>
			<td>F</td>
			<td>31</td>
			<td>L</td>
			<td>Unknown</td>
			<td>45</td>
			<td>61.7</td>
			<td>67.7</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td>31</td>
			<td>R</td>
			<td></td>
			<td>46.7</td>
			<td>56.7</td>
			<td>75.9</td>
			<td>Complete</td>
		</tr>
		<tr>
			<td>5</td>
			<td>F</td>
			<td>57</td>
			<td>R</td>
			<td>Unknown</td>
			<td>38.3</td>
			<td>65</td>
			<td>59</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td>6</td>
			<td>F</td>
			<td>55</td>
			<td>R</td>
			<td>Unknown</td>
			<td>26.7</td>
			<td>55</td>
			<td>68.4</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td>7</td>
			<td>M</td>
			<td>21</td>
			<td>R</td>
			<td>LOXHD1</td>
			<td>33.3</td>
			<td>66.7</td>
			<td>37.2</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td>8</td>
			<td>F</td>
			<td>14</td>
			<td>R</td>
			<td>CDH23</td>
			<td>56.7</td>
			<td>48.3</td>
			<td>100</td>
			<td>Complete</td>
		</tr>
		<tr>
			<td>9</td>
			<td>M</td>
			<td>20</td>
			<td>L</td>
			<td>Unknown</td>
			<td>51.7</td>
			<td>73.3</td>
			<td>48.1</td>
			<td>Partial</td>
		</tr>
		<tr>
			<td>10</td>
			<td>M</td>
			<td>64</td>
			<td>R</td>
			<td>Unknown</td>
			<td>51.7</td>
			<td>58.3</td>
			<td>82.1</td>
			<td>Complete</td>
		</tr>
	</tbody>
</table>
Table 1: Summary of subject characteristics and hearing preservation outcomes. This table has been adapted from Yoshimura et al.6.

Author Spotlight: Optimizing EAS with Long Electrodes for Enhanced Cochlear Coverage and Hearing Preservation

Electric acoustic stimulation (EAS) with longer electrodes can offer broader cochlear coverage and various types of maps in cases of high-frequency hearing loss. Combining less invasive surgery, flexible lateral-wall electrodes, and steroid administration permits deeper insertion with little or no surgical trauma, resulting in good preservation of hearing.

Enhanced Cochlear Coverage and Hearing Preservation in High-Frequency Hearing Loss via Electric Acoustic Stimulation with Longer Electrode

Electric-acoustic stimulation (EAS) is a promising treatment to improve hearing ability in patients with high-frequency hearing loss (HL). In EAS ...

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Nanyang Technological University

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Research

JoVE Journal

Medicine

722 Views.  Shinshu University School of Medicine. Elektrische akoestische stimulatie met langere elektroden kan een bredere cochleaire dekking en verschillende soorten kaarten bieden in geval van hoogfrequent gehoorverlies. We werken aan een veiligere benadering van EAS-chirurgie met behulp van minder invasieve technieken, flexibele elektroden en toediening van steroïden. Dit maakt een diepere insertie mogelijk met minimaal chirurgisch trauma, waardoor het gehoor goed behouden blijft.Onze eerdere stu...

Video: Auteur in de schijnwerpers: EAS optimaliseren met lange elektroden voor verbeterde cochleaire dekking en gehoorbehoud

Making Sense of Listening: The IMAP Test Battery

The ability to hear is only the first step towards making sense of the range of information contained in an auditory signal. Of equal importance are the abilities to extract and use the information encoded in the auditory signal. We refer to these as listening skills (or auditory processing AP). Deficits in these skills are associated with delayed language and literacy development, though the nature of the relevant deficits and their causal connection with these delays is hotly debated.
When a child is referred to a health professional with normal hearing and unexplained difficulties in listening, or associated delays in language or literacy development, they should ideally be assessed with a combination of psychoacoustic (AP) tests, suitable for children and for use in a clinic, together with cognitive tests to measure attention, working memory, IQ, and language skills. Such a detailed examination needs to be relatively short and within the technical capability of any suitably qualified professional. Current tests for the presence of AP deficits tend to be poorly constructed and inadequately validated within the normal population. They have little or no reference to the presenting symptoms of the child, and typically include a linguistic component. Poor performance may thus reflect problems with language rather than with AP. To assist in the assessment of children with listening difficulties, pediatric audiologists need a single, standardized child-appropriate test battery based on the use of language-free stimuli.
We present the IMAP test battery which was developed at the MRC Institute of Hearing Research to supplement tests currently used to investigate cases of suspected AP deficits. IMAP assesses a range of relevant auditory and cognitive skills and takes about one hour to complete. It has been standardized in 1500 normally-hearing children from across the UK, aged 6-11 years. Since its development, it has been successfully used in a number of large scale studies both in the UK and the USA. IMAP provides measures for separating out sensory from cognitive contributions to hearing. It further limits confounds due to procedural effects by presenting tests in a child-friendly game-format. Stimulus-generation, management of test protocols and control of test presentation is mediated by the IHR-STAR software platform. This provides a standardized methodology for a range of applications and ensures replicable procedures across testers. IHR-STAR provides a flexible, user-programmable environment that currently has additional applications for hearing screening, mapping cochlear implant electrodes, and academic research or teaching.

A test battery (IMAP) for performing an in-depth assessment of auditory and cognitive abilities contributing to listening skills is described. It is quick to administer, child-friendly and free from linguistic confounds. Stimulus generation and protocol management are controlled via a software platform (IHR-STAR) to ensure replicable procedures.

The ability to hear is only the first step towards making sense of the range of information contained in an auditory signal. Of equal importance are the ...

Permanent Cerebral Vessel Occlusion via Double Ligature and Transection

Stroke is a leading cause of death, disability, and socioeconomic loss worldwide. The majority of all strokes result from an interruption in blood flow (ischemia) 1. Middle cerebral artery (MCA) delivers a great majority of blood to the lateral surface of the cortex 2, is the most common site of human stroke 3, and ischemia within its territory can result in extensive dysfunction or death 1,4,5. Survivors of ischemic stroke often suffer loss or disruption of motor capabilities, sensory deficits, and infarct. In an effort to capture these key characteristics of stroke, and thereby develop effective treatment, a great deal of emphasis is placed upon animal models of ischemia in MCA.
Here we present a method of permanently occluding a cortical surface blood vessel. We will present this method using an example of a relevant vessel occlusion that models the most common type, location, and outcome of human stroke, permanent middle cerebral artery occlusion (pMCAO). In this model, we surgically expose MCA in the adult rat and subsequently occlude via double ligature and transection of the vessel. This pMCAO blocks the proximal cortical branch of MCA, causing ischemia in all of MCA cortical territory, a large portion of the cortex. This method of occlusion can also be used to occlude more distal portions of cortical vessels in order to achieve more focal ischemia targeting a smaller region of cortex. The primary disadvantages of pMCAO are that the surgical procedure is somewhat invasive as a small craniotomy is required to access MCA, though this results in minimal tissue damage. The primary advantages of this model, however, are: the site of occlusion is well defined, the degree of blood flow reduction is consistent, functional and neurological impairment occurs rapidly, infarct size is consistent, and the high rate of survival allows for long-term chronic assessment.

Permanent Cerebral Vessel Occlusion via Double Ligature and Transection

We describe a highly reproducible method for the permanent occlusion of a rodent major cerebral blood vessel. This technique can be accomplished with very little peripheral damage, minimal blood loss, a high rate of long-term survival, and consistent infarct volume commensurate with the human clinical population.

Stroke is a leading cause of death, disability, and socioeconomic loss worldwide. The majority of all strokes result from an interruption in blood flow ...

Optogenetic Stimulation of the Auditory Nerve

Direct electrical stimulation of spiral ganglion neurons (SGNs) by cochlear implants (CIs) enables open speech comprehension in the majority of implanted deaf subjects1-6. Nonetheless, sound coding with current CIs has poor frequency and intensity resolution due to broad current spread from each electrode contact activating a large number of SGNs along the tonotopic axis of the cochlea7-9. Optical stimulation is proposed as an alternative to electrical stimulation that promises spatially more confined activation of SGNs and, hence, higher frequency resolution of coding. In recent years, direct infrared illumination of&#160;the cochlea has been used to evoke responses in the auditory nerve10. Nevertheless it requires higher energies than electrical stimulation10,11 and uncertainty remains as to the underlying mechanism12. Here we describe a method based on optogenetics to stimulate SGNs with low intensity blue light, using transgenic mice with neuronal expression of channelrhodopsin 2 (ChR2)13 or virus-mediated expression of the ChR2-variant CatCh14. We used micro-light emitting diodes (&#181;LEDs) and fiber-coupled lasers to stimulate ChR2-expressing SGNs through a small artificial opening (cochleostomy) or the round window. We assayed the responses by scalp recordings of light-evoked potentials (optogenetic auditory brainstem response: oABR) or by microelectrode recordings from the auditory pathway and compared them with acoustic and electrical stimulation.

Cochlear implants (CIs) enable hearing by direct electrical stimulation of the auditory nerve. However, poor frequency and intensity resolution limits the quality of hearing with CIs. Here we describe optogenetic stimulation of the auditory nerve in mice as an alternative strategy for auditory research and developing future CIs.

Direct electrical stimulation of spiral ganglion neurons (SGNs) by cochlear implants (CIs) enables open speech comprehension in the majority of implanted ...

Neuroscience

High-frequency Ultrasound Imaging of Mouse Cervical Lymph Nodes

High-frequency ultrasound (HFUS) is widely employed as a non-invasive method for imaging internal anatomic structures in experimental small animal systems. HFUS has the ability to detect structures as small as 30 &#181;m, a property that has been utilized for visualizing superficial lymph nodes in rodents in brightness (B)-mode. Combining power Doppler with B-mode imaging allows for measuring circulatory blood flow within lymph nodes and other organs. While HFUS has been utilized for lymph node imaging in a number of mouse&#160; model systems, a detailed protocol describing HFUS imaging and characterization of the cervical lymph nodes in mice has not been reported. Here, we show that HFUS can be adapted to detect and characterize cervical lymph nodes in mice. Combined B-mode and power Doppler imaging can be used to detect increases in blood flow in immunologically-enlarged cervical nodes. We also describe the use of B-mode imaging to conduct fine needle biopsies of cervical lymph nodes to retrieve lymph tissue for histological&#160; analysis. Finally, software-aided steps are described to calculate changes in lymph node volume and to visualize changes in lymph node morphology following image reconstruction. The ability to visually monitor changes in cervical lymph node biology over time provides a simple and powerful technique for the non-invasive monitoring of cervical lymph node alterations in preclinical mouse models of oral cavity disease.

This protocol describes the application of high-frequency ultrasound (HFUS) for imaging mouse cervical lymph nodes. This technique optimizes visualization and quantification of cervical lymph node morphology, volume and blood flow. Image-guided biopsy of cervical lymph nodes and processing of lymph tissue for histological evaluation is also demonstrated.

High-frequency ultrasound (HFUS) is widely employed as a non-invasive method for imaging internal anatomic structures in experimental small animal ...

Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice

Cochlear implants (CIs) are neuroprosthetic devices that can provide a sense of hearing to deaf people. However, a CI cannot restore all aspects of hearing. Improvement of the implant technology is needed if CI users are to perceive music and perform in more natural environments, such as hearing out a voice with competing talkers, reflections, and other sounds. Such improvement requires experimental animals to better understand the mechanisms of electric stimulation in the cochlea and its responses in the whole auditory system. The mouse is an increasingly attractive model due to the many genetic models available. However, the limited use of this species as a CI model is mainly due to the difficulty of implanting small electrode arrays. More details about the surgical procedure are therefore of great interest to expand the use of mice in CI research.
In this report, we describe in detail the protocol for acute deafening and cochlear implantation of an electrode array in the C57BL/6 mouse strain. We demonstrate the functional efficacy of this procedure with electrically-evoked auditory brainstem response (eABR) and show examples of facial nerve stimulation. Finally, we also discuss the importance of including a deafening procedure when using a normally hearing animal. This mouse model provides a powerful opportunity to study genetic and neurobiological mechanisms that would be of relevance for CI users.

Animal models of cochlear implants can advance knowledge of the technological bases of treating permanent sensorineural hearing loss with electrical stimulation. This study presents a surgical protocol for acute deafening and cochlear implantation of an electrode array in mice as well as the functional assessment with auditory brainstem response.

Cochlear implants (CIs) are neuroprosthetic devices that can provide a sense of hearing to deaf people. However, a CI cannot restore all aspects of ...

Performing Intracochlear Electrocochleography During Cochlear Implantation

Electrocochleography (ECochG) measures inner ear potentials generated in response to acoustic stimulation of the ear. These potentials reflect the residual function of the cochlea. In cochlear implant candidates with residual hearing, the implant electrode can directly measure ECochG responses during the implantation process. Various authors have described the ability to monitor the inner ear function by continuous ECochG measurements during the surgery. The measurement of ECochG signals during surgery is not trivial. There are no interpretable signals in up to 20% of cases. For a successful recording, a standardized procedure is recommended to achieve the highest measurement reliability and avoid possible pitfalls. Therefore, seamless collaboration between the CI surgeon and CI technician is key. This video consists of an overview of the system setup and a stepwise procedure of performing intracochlear ECochG measurements during CI surgery. It shows the surgeon's and the CI technician's roles in the process, and how a smooth collaboration between the two is made possible.

Electrocochleography (ECochG) measures inner ear potentials generated in response to acoustic stimulation. In cochlear implant (CI) candidates, such inner ear potentials can be measured directly with the implant electrodes. In this video, we systematically explain how to perform ECochG recordings during CI surgery.

Electrocochleography (ECochG) measures inner ear potentials generated in response to acoustic stimulation of the ear. These potentials reflect the ...

A State-of-the-Art Method for Preserving Residual Hearing During Cochlear Implant Surgery

The developments in surgical techniques and cochlear implant (CI) electrode design have expanded the indications for CI treatment. Currently, patients with high-frequency hearing loss may benefit from CIs when low-frequency residual hearing can be preserved, as this enables combined electric-acoustic stimulation (EAS). The possible benefits of EAS include, for example, improved sound quality, music perception, and speech intelligibility in noise.
The risks of inner ear trauma and a deterioration or even complete loss of residual hearing vary according to the surgical technique and the type of electrode array used. Short, lateral-wall electrodes with shallower angular insertion depths have demonstrated higher rates of hearing preservation than longer electrodes. The very slow insertion of the electrode array through the round window of the cochlea contributes to insertion atraumaticity and, thus, may lead to favorable hearing preservation results. However, residual hearing can be lost even after an atraumatic insertion. 
Electrocochleography (ECochG) can be used to monitor inner ear hair cell function during the insertion of the electrode. Several investigators have demonstrated that the ECochG responses during surgery may predict postoperative hearing preservation results. 
In a recent study, we correlated the patients' subjective hearing perception with simultaneously recorded intracochlear ECochG responses during the insertion. This is the first report evaluating the association between intraoperative ECochG responses and hearing perception in a subject undergoing cochlear implantation under local anesthesia without sedation. The combination of intraoperative ECochG responses with the patient's real-time feedback to sound stimuli has excellent sensitivity for the intraoperative monitoring of cochlear function. This paper presents a state-of-the-art method for the preservation of residual hearing during CI surgery. We describe this treatment procedure with the special consideration of performing the surgery under local anesthesia, which makes it feasible for monitoring the patient's hearing during the insertion of the electrode array.

The preservation of cochlear structures and possible residual hearing is one important factor to consider during cochlear implant surgery. Here, we present a state-of-the-art method for preserving residual hearing during cochlear implant surgery under local anesthesia.

The developments in surgical techniques and cochlear implant (CI) electrode design have expanded the indications for CI treatment. Currently, patients ...

Enhancing Electrode Location Assessment in Cochlear Implantation via Computed Tomography Image Fusion

This study aimed to determine whether fusing pre-&#160;and post-operative computed tomography (CT) images could help in assessing electrode placement and center frequency (CF) in cochlear implant (CI) recipients. A secondary objective was to compare automatic fusion with manual methods for measuring cochlear parameters. The study included twenty ears with CIs that underwent both pre-&#160;and post-operative CT scans. Manual measurements of cochlear parameters were initially taken from the post-operative CT images, followed by automatic detection using fused pre-&#160;and post-operative CT images with otological software (OTOPLAN). Angular insertion depth (AID) and CF of each electrode contact were calculated using both methods, and error differences were assessed. The analysis showed significant differences between the two methods for cochlear width (B-value) and cochlear duct length (CDL); however, these differences were not clinically significant. Furthermore, there was no statistically significant difference in cochlear diameter (A-value). The mean differences were 0.04 mm for the A-value, 0.21 mm for the B-value, and 0.73 mm for the CDL. The comparison of AID and CF revealed non-significant differences between manual and automatic fusion methods across all electrode contacts, except for electrode number five. According to this study, fusing pre-&#160;and post-operative CT images can be used to determine electrode positions in CI recipients. Automatic fused images can potentially measure cochlear parameters, AID, and CF with reduced human interference. Therefore, this method may serve as another basis for creating anatomy-based fitting.

This protocol demonstrates a method for fusing pre-operative and post-operative computed tomography images for cochlear implant recipients. The approach may enhance the measurement accuracy of insertion depth and the center frequency of electrode array contacts. Additionally, this method has potential applications in anatomy-based fitting, an emerging area within the cochlear implant field.

This study aimed to determine whether fusing pre-&#160;and post-operative computed tomography (CT) images could help in assessing electrode placement and ...

Measuring Electrically Evoked Stapedius Reflex for Cochlear Implant Fitting

Electrically Evoked Stapedius Reflex Measurements in Cochlear Implantation and Its Application in the Postoperative Fitting Process

Measuring the electrically evoked stapedius reflex during the fitting of cochlear implants (CIs) provides a reliable estimation of maximum comfort levels, resulting in the programming of the CI with high hearing comfort and good speech understanding. Detection of the stapedius reflex and the required stimulation level on each implant channel is already being performed during surgery, whereby intraoperative stapedius reflexes are observed through the surgical microscope. Intraoperative stapedius reflex detection is both an indicator that the auditory nerve is responding to electrical stimulation up to the brainstem and a test for the ability to perform postoperative stapedius reflex measurements. Postoperative stapedius reflex thresholds can be used to estimate upper stimulation levels in the CI fitting process. In particular, in children or patients unable to provide feedback on loudness perception, this method avoids inadequate stimulation with the CI, which can result in poor hearing performance. In addition, overstimulation can be avoided, which could even lead to refusal to use the device.

The present protocol describes the measurement of the electrically evoked stapedius reflex (eSR) via cochlear implant (CI). Two applications are discussed: intraoperative detection of eSR for verification of the coupling between the cochlear implant and the auditory nerve and postoperative measurement of eSR thresholds (eSRT) for CI fitting.

Measuring the electrically evoked stapedius reflex during the fitting of cochlear implants (CIs) provides a reliable estimation of maximum comfort levels, ...

Recording Electrically-Evoked Auditory Brainstem Responses in a Deafened Mouse

Source: Navntoft, C. A., et al. <a href="https://app-jove-com.remotexs.ntu.edu.sg/v/58073">Cochlear Implant Surgery and Electrically-evoked Auditory Brainstem Response Recordings in C57BL/6 Mice.</a> J. Vis. Exp. (2019)
This video demonstrates the procedure to implant a cochlear device in a deafened mouse and apply electrical stimuli to record auditory brainstem responses. This procedure enables to understand the basic mechanisms of electrical hearing and can contribute to advancements in cochlear implant technology and auditory neuroscience.

All procedures involving animal models have been reviewed by the local institutional animal care committee and the JoVE veterinary review board.
1. ...

Enhanced Cochlear Coverage and Hearing Preservation in High-Frequency Hearing Loss via Electric Acoustic Stimulation with Longer Electrode

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