This work was supported by the National Natural Science Foundation of China under grants (number 81670932, 81600803, 82071053). Michael Todd (MED-EL) edited a version of this manuscript.

This study was approved by the Medical Ethics Committee of Shandong Provincial ENT Hospital (approval No. XYK20211201). Informed consent was obtained from all study participants.
1. Instrumentation
<ol>
	<li>Use a standard sound booth (&#8804;30 dB [A]), including a calibrated audiometer, a computer, and two loudspeakers. &#39;A&#39; means the human hearing response to sound through a weighted filtering. The unit of measurement is dB SPL (sound pressure level). Perform all tests using the loudspeaker.</li>
	<li>Use mapping software to fit the participants. Assess the speech performance of monosyllable recognition in quiet conditions, spondee (disyllable) speech recognition in quiet conditions, sentence recognition in quiet conditions, and sentence recognition in noisy conditions. For this experiment, 20 monosyllables (i.e., cai, chu, fei, fen, feng, ge, mi, pi, qi, qiao, qing, sha, shen, shi, tao, tui, xiang, xie, xuan, and zhe), combined with four lexical tones spoken by a male native Mandarin Chinese speaker were selected.</li>
	<li>Assess tone recognition using tone test software. For this experiment, four tones in each monosyllable that retained the natural variation in durations were selected. Normalize the tokens to the same root mean square level to eliminate natural variation in amplitude.
	<ol>
		<li>Choose one correct answer from four tones in the Mandarin lexical tone task. For this experiment, 25 monosyllabic words were spoken with the four Mandarin lexical tones, 80 tone tokens were created for each test, and words were written in simplified Chinese.</li>
	</ol>
	</li>
	<li>Assess music pitch perception using music software. For the protocol here, use a test battery consisting of six objective subtests assessing several areas of music perception. The battery contains approximately 2,800 sound files.
	<ol>
		<li>For the pitch-ranking procedure, use different instruments in the range of 27-4,186 Hz. The pitch ranking test used a two-interval, two-alternative, forced-choice adaptive procedure to determine the threshold for discriminating variation of pitch.</li>
		<li>For this experiment, set the target tone to the sine note of F4 (349 Hz) and start 32 quartertones above the target tone. Set the interval size of the two tones between one and 26 quartertones. The quartertone interval was produced from the nearest semitone.</li>
	</ol>
	</li>
</ol>
2. Participant preparation
NOTE: A total of 10 participants (seven males, three females) volunteered for this study, two of whom volunteered to film the protocol. The participants were unilateral CI users with a mean age of 10.4 &#177; 1.2 years (range: 9-14 years), who were implanted at a mean age of 2.8 &#177; 1.2 years (range: 1-4 years) and had at least 5 years of experience using the CIS+ coding strategy (Table 1). All the participants were fluent in Mandarin and were willing to comply with all planned study procedures.
<ol>
	<li>To be included, ensure the potential participants have at least 5 years of experience using the CIS+ coding strategy with a TEMPO+ audio processor, speak Mandarin, and are willing to comply with the planned study procedures.</li>
	<li>Use the exclusion criteria as unwillingness or inability to cooperate with the test procedures.</li>
	<li>Screen the participants in accordance with the inclusion/exclusion criteria mentioned above. Obtain verbal and written informed consent from all participants.</li>
	<li>Position the participants 1 m from the loudspeaker, at a 45&#176; angle to the CI side in the sound booth when testing.</li>
	<li>Remove any hearing aids, if present, from the contralateral ear and make sure the masking (earplug and earmuffs) is effective for participants with residual hearing.</li>
	<li>Inform the participants that practice test sessions will be conducted until they understand the task. When the task is understood, formal testing can begin. Inform the participants that they can take breaks when needed.</li>
</ol>
3. Experimental protocol
<ol>
	<li>Complete a battery of tests at each of the following four intervals: (i) pre-upgrade (the old processor and coding strategy), (ii) immediately post-upgrade (i.e., same day as the upgrade to the new processor and coding strategy), (iii) 6 weeks post-upgrade, and (iv) 3 months post-upgrade.</li>
	<li>Immediately at the post-upgrade interval, test each participant with both coding strategies. Randomize the order in which they are tested, either CIS first or FS4. Blind the participants to which coding strategy they are being tested with.</li>
	<li>Perform mapping, as described below. 
	NOTE: Mapping refers to programming the stimulation levels of each of the 12 channels on the array. In the present study, this was done according to the responses of each CI user and resulted in each participant receiving a customized fitting map.
	<ol>
		<li>Take the participants and guardians to the mapping room (sound booth). Seat the participants in the mapping room.</li>
		<li>Click the mapping software and enter the password. Take off the speech processor and connect it to the MAX box via the programming cable.</li>
		<li>Select the participant&#39;s name on the software and choose the impedance option. Test the electrode impedance and make sure the electrode impedance is normal (2.2-12 kOhm; typical value). Abnormal electrode impedance is automatically shown with open circuits or short circuits.</li>
		<li>Ensure that the coding strategy is FS4 and a standard pulse rate of 1,224 pps/channel is used. Set single electrode stimulation to three sweeps and let the participants distinguish the loudness of each electrode by pointing to the appropriate image on a loud/comfort pictorial scale. Use up and down methods for testing and take the same results that are repeated twice as the final electrical stimulation result. Make sure the participants understand and can accomplish this task.</li>
		<li>Set the maximum comfortable level (MCL) of all the electrodes using the method mentioned above (step 3.3.4). The MCL is considered the highest (i.e., loudest) level that is not uncomfortable. In the present study, participants indicate this on a loud/comfort pictorial scale.
		<ol>
			<li>To test the real-life application of the MCL levels, activate the map by pressing the Live button. This allows the participants to hear ambient noises. Return the participants to the fitting mode. Based on their subjective feedback from listening in live mode, adjust the MCLs if needed.</li>
		</ol>
		</li>
		<li>Set other parameters with the default settings: the stimulation rate is 1,288 pps; the channel-specific sampling sequences (CSSSs) channel is four; the pulse is biphasic pulse; the phase gap (IPG) is 2.1 &#181;s; the input and output signals are logarithmic compression with the default MCL value set to 500; the compression ratio is 3:1; the sensitivity is 75%; the threshold (THR), which is the maximum sound level that the participant cannot hear, is generally 10% of the MCL. Verify the THR for each channel by retesting, as in the MCL; the frequency range is 70-8,500 Hz.</li>
	</ol>
	</li>
	<li>Perform speech tests, as described below.
	<ol>
		<li>Test speech perception in the following order: spondee (disyllable) speech recognition in quiet conditions, monosyllable recognition in quiet conditions, sentence recognition in quiet conditions, and sentence recognition in noisy conditions.</li>
		<li>Seat the participants 1 m beside the computer from the loudspeaker at a 45&#176; angle to the CI side in another sound booth.</li>
		<li>Ensure the processors are switched on and the program is correct. Click the speech software and carefully interpret the answer methods. Tell the participants to clearly repeat the content they have heard. Be careful to ensure that the practice test procedure is correct.</li>
		<li>Open the audiometry and select the hearing test options. Set the sound loudness to 30 dB HL (hearing level) above the average pure-tone threshold of 500, 1,000, 2,000, and 4,000 Hz through the audiometry.</li>
		<li>Present the practice lists at the time of the formal tests23. For each test, ask the participants to repeat the words/sentences they heard. Keep the order of contents random for each test and play the words/sentences once.</li>
		<li>Set a +10 dB signal to noise ratio (SNR) for the sentence recognition in noisy conditions test and use four-talker babble as the noise signal.</li>
	</ol>
	</li>
	<li>Perform the tone test, as described below.
	<ol>
		<li>Click the tone software and set the SPL to 65 dB in the same sound booth. Carefully interpret the answer methods.</li>
		<li>Confirm that the participants are familiar with all of the vocabulary tested. Present the practice lists at the same time as the formal test21.</li>
		<li>Direct the participants to say what they have heard once. Choose the tone in which the participants repeat the content and keep the order of contents random for each test.</li>
	</ol>
	</li>
	<li>Perform the music test, as described below.
	<ol>
		<li>Click the music software and choose the pitch selection in the same booth. Present the practice lists at the same time as the formal test24.</li>
		<li>Instruct the participant to listen to the two stimuli presented sequentially with 1 s of silence in between. Ask them to determine which of the two intervals has a falling or rising pitch contour.</li>
		<li>Input the answers of the participant and repeat. Keep the order of contents random for both practice and normal tests. Choose the answers the participants selected.</li>
	</ol>
	</li>
</ol>
4. Data analysis
<ol>
	<li>For speech and tone tests, record the percentage of correct answers provided and compare for each test. For the musical pitch test, record the quartertones and compare.</li>
	<li>Depending on the data distribution, apply repeated measures (RM) ANOVA with time as a factor, or the Friedman test to examine a change over time. Use pairwise comparisons to compare the performance after upgrading compared to pre-upgrading, with either paired samples t-testing or the Wilcoxon signed-rank test.</li>
	<li>Use the Kolmogorov-Smirnov test together with the Shapiro-Wilk test to check the data distribution. If both tests confirm that the data were normally distributed, then apply parametric statistical methods. Otherwise, apply non-parametric statistical methods. Set the statistical significance at p&#160;&#8804; 0.05.</li>
	<li>Because of multiple comparisons (three pairwise comparisons: pre-upgrade vs. immediately post-upgrade, pre-upgrade vs. 6 weeks post-upgrade, and pre-upgrade vs. 3 months post-upgrade), use the Bonferroni correction method when interpreting the obtained p values. Hence, use p&#160;&#8804; 0.017 instead of p&#160;&#8804; 0.05 as significant.</li>
</ol>

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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=Changes+in+tinnitus+prevalence+and+distress+after+cochlear+implantation.">Changes in tinnitus prevalence and distress after cochlear implantation.</a> Trends in Hearing. 26, 23312165221128431 (2022).</li><li>Lassaletta, 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=Using+generic+and+disease-specific+measures+to+assess+quality+of+life+before+and+after+12+months+of+hearing+implant+use:+a+prospective,+longitudinal,+multicenter,+observational+clinical+study.">Using generic and disease-specific measures to assess quality of life before and after 12 months of hearing implant use: a prospective, longitudinal, multicenter, observational clinical study.</a> International Journal Environmental Research and Public Health. 19 (5), 2503 (2022).</li><li>Seligman, P., McDermott, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Architecture+of+the+Spectra+22+speech+processor.">Architecture of the Spectra 22 speech processor.</a> The Annals of Otology, Rhinology &amp; Laryngology. 166, 139-141 (1995).</li><li>van Hoesel, R. 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P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Perception+of+Cantonese+lexical+tones+by+pediatric+cochlear+implant+users.">Perception of Cantonese lexical tones by pediatric cochlear implant users.</a> Journal of Speech, Language, and Hearing Research. 61 (1), 174-185 (2018).</li><li>Gu, X., 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+follow-up+study+on+music+and+lexical+tone+perception+in+adult+Mandarin-speaking+cochlear+implant+users.">A follow-up study on music and lexical tone perception in adult Mandarin-speaking cochlear implant users.</a> Otology &amp; Neurotology. 38 (10), 421-428 (2017).</li><li>Mao, Y., Xu, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lexical+tone+recognition+in+noise+in+normal-hearing+children+and+prelingually+deafened+children+with+cochlear+implants.">Lexical tone recognition in noise in normal-hearing children and prelingually deafened children with cochlear implants.</a> International Journal of Audiology. 56, 23-30 (2017).</li><li>Tan, J., Dowell, R., Vogel, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mandarin+lexical+tone+acquisition+in+cochlear+implant+users+with+prelingual+deafness:+A+review.">Mandarin lexical tone acquisition in cochlear implant users with prelingual deafness: A review.</a> American Journal of Audiology. 25 (3), 246-256 (2016).</li><li>Tang, P., Yuen, I., Rattanasone, N. 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None of the authors have any financial disclosures or conflicts of interest.

In the present study, the hearing performance of adolescent Mandarin-speaking CI users were systematically evaluated. The results showed significant improvements in speech recognition in quiet conditions, tone recognition, and musical pitch recognition after upgrading from the CIS+ to the FS4 coding strategy. This approach can help establish guidance for exploring clinical evaluation tools to evaluate the comprehensive effects with the new fine structure coding strategy in young Mandarin-speaking CI users.
Within the current study, the primary outcome measure was speech performance, especially speech performance in noisy conditions. Due to the difficulty of the test materials for young participants, the tests were presented in the order of easiest to hardest: spondee speech recognition in quiet conditions, monosyllable recognition in quiet conditions, sentence recognition in quiet conditions, and sentence recognition in noisy conditions. Throughout the sentence recognition in noisy conditions test, participants were asked to focus on the speech rather than the babble noise. All participants performed adequately on the sentence recognition in noisy conditions. Recognition of monosyllables in quiet conditions significantly improved at each of the three sessions compared to pre-upgrade. Similarly, the spondee and the sentence recognition in quiet conditions significantly improved between pre-upgrade and 3 months post-upgrade. These results are consistent with the previous findings in adult Mandarin-speaking CI users21,22. Although the results in the present study were not statistically significant for the sentence recognition in noisy conditions test, mean scores did increase from 59.8% at pre-upgrade to 85.8% after 3 months of use. This was in accordance with the previous report21. This test procedure and the results shown here verify the effective use of a newer speech processor for adolescent Mandarin-speaking CI users and demonstrated the usefulness of the proposed testing method.
After the speech performance tests, the tone test was conducted. In contrast to speech recognition in noisy conditions, the tone test appeared to be more interesting than speech tests for participants, with shorter test times. All participants understood the testing method after one practice session and performed well. As previously stated, recognition of tone is a crucial aspect of hearing and communication for Mandarin speakers. Normal hearing children can discriminate lexical tones in a domain-general fashion as early as 12 months17; however, this is certainly not the case in children with pre-lingual bilateral deafness. Previous studies have shown that pediatric CI users with pre-lingual deafness have marked deficits in tone recognition compared to their normal-hearing counterparts14,17. Studies on adult Mandarin-speaking CI users have shown that tone perception significantly improves over time with the FS4 coding strategy22. Similarly, the present study demonstrated that tone recognition significantly improves after both 6weeks and 3 months of using FS4. 
The music software was chosen because it takes less time and thus helps keep the overall test time short. As indicated earlier, pitch perception, especially musical pitch perception, alongside tone recognition, is important for CI users. However, this is the most difficult and tedious portion of the battery of tests. Due to the difficult nature of the testing, four participants needed more than one practice session, six needed one practice round, three needed two practice rounds, and one needed multiple rounds. Due to the practice sessions, all the participants had a clear understanding of the test protocols and were able to perform the tests. The results showed significant improvements in pitch perception after 3 months of using FS4. These results were in accordance with previous literature in adult Mandarin-speaking CI users9. This validates the importance of fine structure information for music recognition in pediatric, Mandarin-speaking CI users, and the suitability of this method for evaluating young, non-Mandarin-speaking CI users of any language.
In the present study, assessing the utility of upgrading to the new coding strategy in the short term can be fully validated and tested by this battery of tests. Mandarin-speaking CI users demonstrated significantly better scores in all tests except the sentence recognition in noisy conditions test. In addition to the test methods being applicable to participants, all the tests were convenient and intuitive for the evaluation of the effect. Other than the results of musical pitch perception, all results are presented as percentages. The higher the percentage score, the better the result. For musical pitch, the lower the result, the better the effect. Researchers should ensure that all the test software have strict pre-experimental and formal test tables and the content is not repeated.
Therefore, the present study, for the first time, explored a battery of tests that could be used for clinically evaluating hearing performance in young Mandarin-speaking CI users after upgrading to the FS4 coding strategy. The approach presents valid test material, appropriate preparation, a strict test sequence, and a rigorous test procedure. However, the current study was not without limitations. Firstly, the sample size makes it difficult to extrapolate these findings to larger populations. Future studies must benefit from having a greater number of participants. Secondly, future studies must test timings, to determine how long completing each part of the test battery takes, thus being more useful for younger populations, especially those with a limited attention span. An easier methodology that shortens the overall testing time can be of clinical benefit.
Overall, the present study demonstrates that fine structure information plays a crucial role in the discrimination of speech in quiet conditions, pitch contours, and lexical tone recognition amongst adolescent Mandarin-speaking unilateral CI users. This battery of tests provides guidance for both CI users and candidates and doctors to choose different technologies, as well as to steer their clinical rehabilitation.

Technological improvements in cochlear implants (CIs) have given users increasingly greater benefits, particularly in speech understanding in quiet and noisy environments, but also through tinnitus reduction and increased quality of life1,2,3,4. It is common and necessary to evaluate how technological upgrades potentially alter postoperative outcomes. Therefore, establishing a strict battery of tests is of benefit, as it can better enable the direct comparison of results of different types of hearing implant users from different clinics. This can enable the pooling of data and provide more robust results that can better inform patients and health care providers in the decision-making process. The sound coding strategy of a CI audio processor is one of the core technologies that affects a CI user&#39;s hearing performance5,6,7. Coding strategies have progressed from the previous envelope-based continuous interleaved sampling (CIS) strategy to the newer FS4, a temporal fine structure strategy8,9,10,11,12.
Sound coding strategies are responsible for processing sound signals into electrical pulses that are sent to the implant&#39;s electrode channels. In CIS, all electrode contacts on the array are stimulated with envelope-modulated strains of pulses at a constant rate (i.e., there is no temporal coding). In fine structure coding, the apical region (low frequencies) is stimulated at a variable rate so as to mimic the phase-locking of the inner hair cells in normal (acoustic) hearing, and thereby mimic the perception of normal hearing as closely as possible. Channels in the basal and middle regions are stimulated at a constant rate, as in CIS8,9,10,11,12,13.
In this study, a strict battery of tests was used to evaluate performance with the FS4 coding strategy. Tonal languages, such as Mandarin and Cantonese, use pitch cues to provide lexical meaning14. Apart from the frequently used speech tests, the battery of tests can carefully consider the pitch cues used in most tonal languages. Mandarin contains four lexical tones, characterized by variations in the fundamental frequency (F0 or pitch) in speech. Therefore, it is of key importance when evaluating Mandarinspeaking CI users to be able to identify these variations in frequency and speech15,16,17,18,19.
Throughout the years, there has been a considerable lack of tests which evaluate music perception in young Mandarinspeaking CI users. However, fine structure coding strategies must help tonal-speaking CI users discriminate pitch contours and lexical tones20. So far, only two studies have investigated coding strategies on speech and tone perception in adult CI users who are Mandarin speakers21,22. To the best of our knowledge, no investigation has assessed the hearing performance of adolescent Mandarin-speaking CI users when upgraded to the FS4 coding strategy. Therefore, the current study aimed to establish a battery of tests to evaluate the performance of adolescent Mandarin-speaking CI users, following an upgrade from an audio processor using the CIS+ coding strategy to one using the FS4 coding strategy.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>&#160;INVENTIS PIANO audiometer&#160;</td>
			<td>Russia</td>
			<td></td>
			<td>This audiometer is mainly used for the behavioural audiometry in this study.</td>
		</tr>
		<tr>
			<td>HOPE software</td>
			<td>Chinese PLA General Hospital</td>
			<td></td>
			<td>This software is used for testing the speech performance including adequate test lists for testing the monosyllable recognition in quiet, spondee (disyllable) speech recognition in quiet, sentence recognition in quiet, and sentence recognition in noise</td>
		</tr>
		<tr>
			<td>JAMO Loudspeaker</td>
			<td>China</td>
			<td></td>
			<td>these loudspeakerw are used for all the tests in the sound booth.</td>
		</tr>
		<tr>
			<td>Lenovo computers</td>
			<td>China</td>
			<td></td>
			<td>They are used for mapping and manipulating all the test softwares.</td>
		</tr>
		<tr>
			<td>MAESTRO mapping device</td>
			<td>MED-EL</td>
			<td></td>
			<td>These devices include the MAX box and programming cable used for connecting the processor to the mapping software.&#160;</td>
		</tr>
		<tr>
			<td>MAESTRO software</td>
			<td>MED-EL</td>
			<td></td>
			<td>This software is used for mapping</td>
		</tr>
		<tr>
			<td>Mandarin Tone Identification in Noise Test (MTINT)&#160;</td>
			<td>Beijing Tongren Hospital</td>
			<td></td>
			<td>This software is used to measure tone recognition. A 4-alternative forced-choice (4AFC) Mandarin lexical tone task is used. The test material consists of 25 monosyllabic words spoken with the four Mandarin lexical tones to create 100 different words for each talker.</td>
		</tr>
		<tr>
			<td>Musical Sounds in Cochlear Implants (MuSIC)</td>
			<td>MED-EL</td>
			<td></td>
			<td>The MuSIC test battery consists of six objective subtests assessing several areas of music perception. This software is chosen as it takes less time and thus helps keep the overall test time rather short. The battery contains approximately 2800 sound files recorded at the Royal Scottish Academy of Music and Drama by prefessional musicians playing natural instruments.&#160;</td>
		</tr>
	</tbody>
</table>

systematic hearing performance evaluation process for adolescents with cochlear implantation at early ages

Cochlear implant (CI) provision is the most effective clinical treatment to restore hearing performance in individuals with profound sensorineural hearing loss (SNHL). It has been successful in providing improved speech perception outcomes, especially in quiet environments. However, speech perception performance within complex environments, lexical tone recognition, and music perception have been shown to only improve with newer fine structure coding strategies or related techniques. Therefore, the methods used to assess hearing performance in noisy environments, lexical tone recognition, and music perception are of vital importance. These assessments must reflect the postoperative outcomes and also provide guidance for the programming, rehabilitation, and application of new coding strategies. In this study, hearing performance in simple and complex situations was evaluated before and after upgrading to a fine structure strategy. The participants were a cohort of Mandarin-speaking adolescents, who were experienced CI users. The comprehensive clinical workflow involved assessments of speech in quiet conditions, speech in noisy conditions, lexical tone recognition, and music perception. This battery of tests is explained in detail, from the coding strategy to the test methods, including the test process, environment, device, material, and order. The details that require special attention are discussed, such as the position of the participants, the angle of the loudspeaker, the intensity of the sound, the noise type, the practice test, and the way of answering questions. Each test step, method, and material for speech, lexical tone, and music perception is presented in detail. Finally, the clinical results are discussed.

The speech test results indicate speech recognition ability both in quiet and in noisy conditions. The tone test results indicate the lexical tone discrimination for Mandarin lexical tones. The pitch results indicate musical discrimination ability. For speech and tone test results, all results are presented as percentages. A higher percentage score indicates a better test result. For speech tests, the results for words and sentences are presented separately. This enables the results to be analyzed and compared separately. The result for the pitch test is displayed as a visualized resolution threshold. Lower limens indicate better results. These data are easy to analyze and compare.
Spondee recognition in quiet conditions 
Spondee recognition in quiet conditions significantly improved from pre-upgrade to 3 months post-upgrade (on average 16.1% better; z = 2.497; p = 0.013). The improvement was not significant from pre-upgrade to 6 weeks post-upgrade (on average 9.4% better; z = 1.735; p = 0.083) or from pre-upgrade to immediately post-upgrade (on average 5.8% better; z = 1.429; p = 0.153; Table 2 and Figure 1).
Monosyllable recognitionin quiet conditions 
Monosyllable recognition in quiet conditions significantly improved from pre-upgrade to immediately post-upgrade (on average 8.2% better; z = 2.494; p = 0.013), from pre-upgrade to 6 weeks post-upgrade (on average 11.8% better; z = 2.570; p = 0.010), and from pre-upgrade to 3 months post-upgrade (on average 22.5% better; z = 2.810; p = 0.005; Table 2 and Figure 2).
Sentence recognition in quietconditions 
Sentence recognition rate in quiet conditions significantly improved from pre-upgrade to 3 months post-upgrade (on average 17.8% better; z = 2.670; p = 0.008). No significant improvement was observed from pre-upgrade to 6 weeks post-upgrade (on average 13.0% better; z = 2.314; p = 0.021) or from pre-upgrade to immediate post-upgrade (on average 0.8% better; z = 0.255; p = 0.798; Table 2 and Figure 3).
Sentence recognition in noisy conditions 
The pairwise comparisons from pre-upgrade to each of the post-upgrade sessions confirmed the non-significant differences in sentence recognition in noisy conditions (Wilcoxon signed-rank test: z = 1.355; p = 0.176 to z = 0.674; p = 0.500). However, sentence recognition in noisy conditions did increase on average 26% from pre-upgrade to 3 months post-upgrade (Table 2).
Tone recognition 
Tone recognition significantly improved from pre-upgrade to 6 weeks post-upgrade (on average 5.0% better; t = 11.180; p &#60; 0.001) and from pre-upgrade to 3 months post-upgrade (on average 9% better; t = 4.803; p = 0.001). No significant improvement was found from pre-upgrade to immediately post-upgrade (on average 1.6% better; t = 1.652; p = 0.133; Table 2 and Figure 4).
Musical pitch perception 
Musical pitch perception significantly improved from pre-upgrade to 4 months post-upgrade (on average, 12.7 limen better; z = 2.371; p = 0.018). A non-significant improvement was observed from pre-upgrade to 6 weeks post-upgrade (on average 5.5 limen better; z = 0.840; p = 0.401), and a non-significant deterioration was observed from pre-upgrade to immediately post-upgrade (on average 7.2 limen worse; z = 0.491; p = 0.623; Table 2).
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>ID</td>
			<td>Gender</td>
			<td>Ear implanted</td>
			<td>Age at time of surgery (years)</td>
			<td>Age at time of evaluation (years)</td>
			<td>Implant type</td>
		</tr>
		<tr>
			<td>S01</td>
			<td>M</td>
			<td>R</td>
			<td>2.0</td>
			<td>14.2</td>
			<td>COMBI 40+</td>
		</tr>
		<tr>
			<td>S02</td>
			<td>F</td>
			<td>L</td>
			<td>1.5</td>
			<td>10.3</td>
			<td>COMBI 40+</td>
		</tr>
		<tr>
			<td>S03</td>
			<td>M</td>
			<td>L</td>
			<td>4.4</td>
			<td>12.2</td>
			<td>COMBI 40+</td>
		</tr>
		<tr>
			<td>S04</td>
			<td>F</td>
			<td>R</td>
			<td>1.6</td>
			<td>9.4</td>
			<td>COMBI 40+</td>
		</tr>
		<tr>
			<td>S05</td>
			<td>M</td>
			<td>R</td>
			<td>3.8</td>
			<td>10.6</td>
			<td>COMBI 40+</td>
		</tr>
		<tr>
			<td>S06</td>
			<td>M</td>
			<td>R</td>
			<td>4.2</td>
			<td>11.1</td>
			<td>COMBI 40+</td>
		</tr>
		<tr>
			<td>S07</td>
			<td>F</td>
			<td>R</td>
			<td>4.2</td>
			<td>11.7</td>
			<td>COMBI 40+</td>
		</tr>
		<tr>
			<td>S08</td>
			<td>M</td>
			<td>R</td>
			<td>2.3</td>
			<td>9.8</td>
			<td>COMBI 40+</td>
		</tr>
		<tr>
			<td>S09</td>
			<td>M</td>
			<td>R</td>
			<td>4.3</td>
			<td>9.4</td>
			<td>COMBI 40+</td>
		</tr>
		<tr>
			<td>S10</td>
			<td>M</td>
			<td>R</td>
			<td>3.7</td>
			<td>9.3</td>
			<td>COMBI 40+</td>
		</tr>
	</tbody>
</table>
Table 1: Demographic data of all participants. Abbreviations: M = male; F = female; R = right; L = left.
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Tests</td>
			<td>Pre-upgrade</td>
			<td>Immediately post</td>
			<td>6-weeks post</td>
			<td>3-months post</td>
		</tr>
		<tr>
			<td>Monosyllables (quiet; %)</td>
			<td>59.6 (&#177;14.3)</td>
			<td>67.8 (&#177;17.6)</td>
			<td>71.4 (&#177;13.3)</td>
			<td>82.1 (&#177;12.2)</td>
		</tr>
		<tr>
			<td>Spondees (quiet; %)</td>
			<td>69.2 (&#177;16.1)</td>
			<td>75.0 (&#177;14.5)</td>
			<td>78.6 (&#177;14.1)</td>
			<td>85.3 (&#177;10.0)</td>
		</tr>
		<tr>
			<td>Sentence (quiet; %)</td>
			<td>78.0 (&#177;19.4)</td>
			<td>78.8 (&#177;19.2)</td>
			<td>91.0 (&#177;7.8)</td>
			<td>95.8 (&#177;7.9)</td>
		</tr>
		<tr>
			<td>Sentence (noise; %)</td>
			<td>59.8 (&#177;33.78)</td>
			<td>70.2 (&#177;13.5)</td>
			<td>80.0 (&#177;12.9)</td>
			<td>85.8 (&#177;10.7)</td>
		</tr>
		<tr>
			<td>Tone recognition (%)</td>
			<td>75.4 (&#177;13.3)</td>
			<td>77.0 (&#177;14.8)</td>
			<td>80.4 (&#177;13.1)</td>
			<td>84.4 (&#177;12.3)</td>
		</tr>
		<tr>
			<td>Musical pitch (quartertone)</td>
			<td>16.5 (&#177;11.5)</td>
			<td>23.7 (&#177;20.4)</td>
			<td>11.0 (&#177;13.2)</td>
			<td>3.8 (&#177;3.4)</td>
		</tr>
	</tbody>
</table>
Table 2: Hearing performance on each test at each interval. All data are presented as mean values (&#177; standard deviation). There are significant differences in spondee, monosyllable, and sentence recognition in quiet conditions in favor of the FS4 coding strategy (p&#160;&#8804; 0.017). However, no significant differences can be found in the sentence recognitions in noisy conditions test (p &#62; 0.05).
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/64552/64552fig01.jpg" /> 
Figure 1: Spondee recognition results for each interval. Spondee recognition in quiet conditions significantly improved from pre-upgrade to 3 months post-upgrade (p = 0.013). Data are presented as mean values (&#177; standard deviation). *p &#60; 0.05. Circles, squares, and triangles indicate individual participant&#39;s results. <a href="https://www.jove.com/files/ftp_upload/64552/64552fig01large.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/64552/64552fig02.jpg" /> 
Figure 2: Monosyllable recognition results for each interval. Monosyllable recognition in quiet conditions significantly improved from pre-upgrade to immediately post-upgrade (p = 0.013), from pre-upgrade to 6 weeks post-upgrade (p = 0.010), and from pre-upgrade to 3 months post-upgrade (p = 0.005). Data are presented as mean values (&#177; standard deviation). *p &#60; 0.05. Circles, squares, and triangles indicate individual participant&#39;s results. <a href="https://www.jove.com/files/ftp_upload/64552/64552fig02large.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/64552/64552fig03.jpg" /> 
Figure 3:&#160;Sentence recognition in quiet conditions results for each interval. Sentence recognition rate in quiet conditions significantly improved from pre-upgrade to 3 months post-upgrade (p = 0.008). Data are presented as mean values (&#177; standard deviation). *p &#60; 0.05. Circles, squares, and triangles indicate individual participant&#39;s results. <a href="https://www.jove.com/files/ftp_upload/64552/64552fig03large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/64552/64552fig04.jpg" /> 
Figure 4: Tone recognition results for each interval. Tone recognition significantly improved from pre-upgrade to 6 weeks post-upgrade (p &#60; 0.001) and from pre-upgrade to 3 months post-upgrade (p = 0.001). Data are presented as mean values (&#177; standard deviation). *p &#60; 0.05. Circles, squares, and triangles indicate individual participant&#39;s results. <a href="https://www.jove.com/files/ftp_upload/64552/64552fig04large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Read this Scientific Article Protocol about Systematic Hearing Performance Evaluation Process for Adolescents with Cochlear Implantation at Early Ages at JoVE.com

Systematic Hearing Performance Evaluation Process for Adolescents with Cochlear Implantation at Early Ages

This paper describes a battery of tests used to clinically assess the hearing performance of adolescent, Mandarin-speaking, experienced cochlear implant users upgraded to a new fine structure coding strategy. The battery of tests include speech in quiet conditions, speech in noisy conditions, lexical tone, and music perception.

Cochlear implant (CI) provision is the most effective clinical treatment to restore hearing performance in individuals with profound sensorineural hearing ...

systematic-hearing-performance-evaluation-process-for-adolescents

Research

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Medicine

282 Views.  Shandong University,. This paper describes a battery of tests used to clinically assess the hearing performance of adolescent, Mandarin-speaking, experienced cochlear implant users upgraded to a new fine structure coding strategy. The battery of tests include speech in quiet conditions, speech in noisy conditions, lexical tone, and music perception. 

Video: Systematic Hearing Performance Evaluation Process for Adolescents with Cochlear Implantation at Early Ages

Cerenkov Luminescence Imaging (CLI) for Cancer Therapy Monitoring

In molecular imaging, positron emission tomography (PET) and optical imaging (OI) are two of the most important and thus most widely used modalities1-3. PET is characterized by its excellent sensitivity and quantification ability while OI is notable for non-radiation, relative low cost, short scanning time, high throughput, and wide availability to basic researchers. However, both modalities have their shortcomings as well. PET suffers from poor spatial resolution and high cost, while OI is mostly limited to preclinical applications because of its limited tissue penetration along with prominent scattering optical signals through the thickness of living tissues.
 Recently a bridge between PET and OI has emerged with the discovery of Cerenkov Luminescence Imaging (CLI)4-6. CLI is a new imaging modality that harnesses Cerenkov Radiation (CR) to image radionuclides with OI instruments. Russian Nobel laureate Alekseyevich Cerenkov and his colleagues originally discovered CR in 1934. It is a form of electromagnetic radiation emitted when a charged particle travels at a superluminal speed in a dielectric medium7,8. The charged particle, whether positron or electron, perturbs the electromagnetic field of the medium by displacing the electrons in its atoms. After passing of the disruption photons are emitted as the displaced electrons return to the ground state. For instance, one 18F decay was estimated to produce an average of 3 photons in water5. 
 Since its emergence, CLI has been investigated for its use in a variety of preclinical applications including in vivo tumor imaging, reporter gene imaging, radiotracer development, multimodality imaging, among others4,5,9,10,11. The most important reason why CLI has enjoyed much success so far is that this new technology takes advantage of the low cost and wide availability of OI to image radionuclides, which used to be imaged only by more expensive and less available nuclear imaging modalities such as PET.
 Here, we present the method of using CLI to monitor cancer drug therapy. Our group has recently investigated this new application and validated its feasibility by a proof-of-concept study12. We demonstrated that CLI and PET exhibited excellent correlations across different tumor xenografts and imaging probes. This is consistent with the overarching principle of CR that CLI essentially visualizes the same radionuclides as PET. We selected Bevacizumab (Avastin; Genentech/Roche) as our therapeutic agent because it is a well-known angiogenesis inhibitor13,14. Maturation of this technology in the near future can be envisioned to have a significant impact on preclinical drug development, screening, as well as therapy monitoring of patients receiving treatments.

Cerenkov Luminescence Imaging CLI for Cancer Therapy Monitoring

Use of Cerenkov Luminescence Imaging (CLI) for monitoring preclinical cancer treatment is described here. This method takes advantage of Cerenkov Radiation (CR) and optical imaging (OI) to visualize radiolabeled probes and thus provides an alternative to PET in preclinical therapeutic monitoring and drug screening.

In  molecular imaging, positron emission tomography (PET) and optical imaging (OI)  are two of the most important and thus most widely used modalities1-3. ...

Techniques for Processing Eyes Implanted with a Retinal Prosthesis for Localized Histopathological Analysis: Part 2 Epiretinal Implants with Retinal Tacks

Retinal prostheses for the treatment of certain forms of blindness are gaining traction in clinical trials around the world with commercial devices currently entering the market. In order to evaluate the safety of these devices, in preclinical studies, reliable techniques are needed. However, the hard metal components utilised in some retinal implants are not compatible with traditional histological processes, particularly in consideration for the delicate nature of the surrounding tissue. Here we describe techniques for assessing the health of the eye directly adjacent to a retinal implant secured epiretinally with a metal tack.
Retinal prostheses feature electrode arrays in contact with eye tissue. The most commonly used location for implantation is the epiretinal location (posterior chamber of the eye), where the implant is secured to the retina with a metal tack that penetrates all the layers of the eye. Previous methods have not been able to assess the proximal ocular tissue with the tack in situ, due to the inability of traditional histological techniques to cut metal objects. Consequently, it has been difficult to assess localized damage, if present, caused by tack insertion.
Therefore, we developed a technique for visualizing the tissue around a retinal tack and implant. We have modified an established technique, used for processing and visualizing hard bony tissue around a cochlear implant, for the soft delicate tissues of the eye. We orientated and embedded the fixed eye tissue, including the implant and retinal tack, in epoxy resin, to stabilise and protect the structure of the sample. Embedded samples were then ground, polished, stained, and imaged under various magnifications at incremental depths through the sample. This technique allowed the reliable assessment of eye tissue integrity and cytoarchitecture adjacent to the metal tack.

Here we describe histological techniques for visualising ocular tissue directly adjacent to a metal epiretinal tack and retinal prosthesis.

Retinal prostheses for the treatment of certain forms of blindness are gaining traction in clinical trials around the world with commercial devices ...

Neonatal Murine Cochlear Explant Technique as an In Vitro Screening Tool in Hearing Research

While there have been remarkable advances in hearing research over the past few decades, there is still no cure for Sensorineural Hearing Loss (SNHL), a condition that typically involves damage to or loss of the delicate mechanosensory structures of the inner ear. Sophisticated in vitro and ex vivo assays have emerged in recent years, enabling the screening of an increasing number of potentially therapeutic compounds while minimizing resources and accelerating efforts to develop cures for SNHL. Though homogenous cultures of certain cell types continue to play an important role in current research, many scientists now rely on more complex organotypic cultures of murine inner ears, also known as cochlear explants. The preservation of organized cellular structures within the inner ear facilitates the in situ evaluation of various components of the cochlear infrastructure, including inner and outer hair cells, spiral ganglion neurons, neurites, and supporting cells. Here we present the preparation, culture, treatment, and immunostaining of neonatal murine cochlear explants. The careful preparation of these explants facilitates the identification of mechanisms that contribute to SNHL and constitutes a valuable tool for the hearing research community.

Neonatal Murine Cochlear Explant Technique as an In Vitro Screening Tool in Hearing Research

The goal of this protocol is to demonstrate the preparation, culture, treatment, and immunostaining of neonatal murine cochlear explants. The technique can be utilized as an in vitro screening tool in hearing research.

While there have been remarkable advances in hearing research over the past few decades, there is still no cure for Sensorineural Hearing Loss (SNHL), a ...

Cochlear Implantation in the Guinea Pig

Cochlear implants are highly efficient devices that can restore hearing in subjects with profound hearing loss. Due to improved speech perception outcomes, candidacy criteria have been expanded over the last few decades. This includes patients with substantial residual hearing that benefit from electrical and acoustical stimulation of the same ear, which makes hearing preservation during cochlear implantation an important issue. Electrode impedances and the related issue of energy consumption is another major research field, as progress in this area could pave the way for fully implantable auditory prostheses. To address these issues in a systematic way, adequate animal models are essential. Therefore, the goal of this protocol is to provide an animal model of cochlear implantation, which can be used to address various research questions. Due to its large tympanic bulla, which allows easy surgical access to the inner ear, as well as its hearing range which is relatively similar to the hearing range of humans, the guinea pig is a commonly used species in auditory research. Cochlear implantation in the guinea pig is performed via a retroauricular approach. Through the bullostomy a cochleostomy is drilled and the cochlear implant electrode is inserted into the scala tympani. This electrode can then be used for electrical stimulation, determination of electrode impedances and the measurement of compound action potentials of the auditory nerve. In addition to these applications, cochlear implant electrodes can also be used as drug delivery devices, if a topical delivery of pharmaceutical agents to the cells or fluids of the inner ear is intended.

The goal of this protocol is to provide an animal model of cochlear implantation, which can be used to address a multitude of research questions. Potential applications include the evaluation of pharmaceutical interventions or electrical stimulation for beneficial effects on hearing thresholds or electrode impedances.

Cochlear implants are highly efficient devices that can restore hearing in subjects with profound hearing loss. Due to improved speech perception ...

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 ...

Robotic Cochlear Implantation for Direct Cochlear Access

Robot-assisted systems offer great potential for gentler and more precise cochlear implantation. In this article, we provide a comprehensive overview of the clinical workflow for robotic cochlear implantation using a robotic system specifically developed for a minimally invasive, direct cochlear access. The clinical workflow involves experts from various disciplines and requires training to ensure a smooth and safe procedure. The protocol briefly summarizes the history of robotic cochlear implantation. The clinical sequence is explained in detail, beginning with the assessment of patient eligibility and covering surgical preparation, preoperative planning with the special planning software, drilling of the middle ear access, intraoperative imaging to confirm the trajectory, milling of the inner ear access, insertion of the electrode array, and implant management. The steps that require special attention are discussed. As an example, the postoperative outcome of robotic cochlear implantation in a patient with advanced otosclerosis is presented. Finally, the procedure is discussed in the context of the authors' experience.

Robotic cochlear implantation is a procedure for minimally invasive inner ear access. Compared to conventional surgery, robotic cochlear implantation involves additional steps that need to be carried out in the operating room. In this article we give a description of the procedure and highlight the important aspects of robotic cochlear implantation.

Robot-assisted systems offer great potential for gentler and more precise cochlear implantation. In this article, we provide a comprehensive overview of ...

The Miniature Pig: A Large Animal Model for Cochlear Implant Research

Cochlear implants (CI) are the most effective method to treat people with severe-to-profound sensorineural hearing loss. Although CIs are used worldwide, no standard model exists for investigating the electrophysiology and histopathology in patients or animal models with a CI or for evaluating new models of electrode arrays. A large animal model with cochlea characteristics similar to those of humans may provide a research and evaluation platform for advanced and modified arrays before their use in humans. 
To this end, we established standard CI methods with Bama mini-pigs, whose inner ear anatomy is highly similar to that of humans. Arrays designed for human use were implanted into the mini pig cochlea through a round window membrane, and a surgical approach followed that was similar to that used for human CI recipients. Array insertion was followed by evoked compound action potential (ECAP) measurements to evaluate the function of the auditory nerve. This study describes the preparation of the animal, surgical steps, array insertion, and intraoperative electrophysiological measurements. 
The results indicated that the same CI used for humans could be easily implanted in mini-pigs via a standardized surgical approach and yielded similar electrophysiological outcomes as measured in human CI recipients. Mini-pigs could be a valuable animal model to provide initial evidence of the safety and potential performance of novel electrode arrays and surgical approaches before applying them to human beings.

Miniature pigs (mini-pigs) are an ideal large animal model for research into cochlear implants. Cochlear implantation surgery in mini-pigs can be utilized to provide initial evidence of the safety and potential performance of novel electrode arrays and surgical approaches in a living system similar to human beings.

Cochlear implants (CI) are the most effective method to treat people with severe-to-profound sensorineural hearing loss. Although CIs are used worldwide, ...

Real-Time Telemetric Impedance Measurements During Cochlear Implantation

Performing Repeated Intraoperative Impedance Telemetry Measurements during Cochlear Implantation

Impedance measurements are routinely performed during cochlear implantation (CI) after finalized electrode insertion. They may allow conclusions on the electrode's and implant's function. In the postoperative setting, the analysis of impedance changes enables the identification of scarring or inflammation processes around the electrode. Recent studies report associations between impedance telemetry and the site of stimulation. Consequently, repeated impedance measurements during cochlear implant electrode insertion may enable objective feedback on whether the electrode is positioned inside the perilymph or outside the inner ear. With the presented novel method, impedances can be measured in real-time during cochlear implantation. This protocol systematically explains how to perform repeated impedance recordings during CI surgery. These repeated measurements are challenging since they depend on multiple intraoperative methodological factors starting with the draping of the patient. Thus, for successful recordings, a standardized procedure is mandatory. In this article, we comprehensively illustrate the system setup and procedure of performing intraoperative measurements during CI surgery.

Author Spotlight: Advancements in Impedance Monitoring for Cochlear Implant Surgery

Here we present a protocol to conduct repeated impedance telemetry measurements during cochlear implantation (CI). They may allow conclusions on the electrode's and implant's function. Repeated impedance measurements enable objective feedback on whether the electrode is positioned inside the perilymph or outside the inner ear.

Impedance measurements are routinely performed during cochlear implantation (CI) after finalized electrode insertion. They may allow conclusions on the ...

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, ...