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Clinical application of electrically evoked compound action potentials
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ScienceDirect Journal of Otology 9 (2014) 117e121 www.journals.elsevier.com/journal-of-otology/
Clinical application of electrically evoked compound action potentials* Fei Ji, Ke Liu, Shi-ming Yang* Department of Otolaryngology, Head & Neck Surgery, Chinese PLA General Hospital, Chinese PLA Institute of Otolaryngology, 28 Fuxing Road, Beijing 100853, China Received 24 September 2014; accepted 17 November 2014
Abstract ECAPs are the summary of multiple neurons’ spikes which could be recorded by a bidirectional stimulation-recording system via the cochlear implant, with the artifact elimination paradigms of forward-masking subtraction paradigm or alternating polarity paradigm. Three kinds of FDA approved cochlear implants support ECAP testing. This article is to summarize the clinical application of ECAP test. ECAP test after insertion of electrode during implant operation has been widely used during cochlear implant surgery. In recent years, ECAP thresholds are also used to estimate the T levels and C levels helping programming. However, correlation between ECAP thresholds and psychophysical thresholds is affected by many factors. So far, ECAPs cannot yet be a good indicator of post-operative hearing and speech performance. Copyright © 2014, PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd. All rights reserved.
Keywords: Electrically Evoked Compound Action Potentials; Cochlear implant; Electrophysiology; Hearing; Intra-operative monitoring
Electrically evoked compound action potentials (ECAPs) were originally applied to research the neural response of animals to electrical stimulation. With the development of cochlear implant, it is possible to record human neural ECAPs in vivo through implanted electrodes (Abbas et al., 1999). So far, there are three kinds of FDA approved cochlear implants that support ECAP testing, which widen the clinical application of ECAPs, including: 1) evaluation of response of the VIIIth nerve to electrical stimulation, helping to validate the working status of implant; 2) assisting speech processor programming; and 3) evaluation of spatial excitation patterns and
* Funding: This work was supported by grants from the National Basic Research Program of China (973 Program) (#2012CB967900), Science and Technology Innovation Nursery Foundation of PLA General Hospital (13KMM14) and Clinical Research Supporting Foundation of PLA General Hospital (2012FC-TSYS-3056). * Corresponding author. E-mail addresses: [email protected] (J. Fei), [email protected] (S. Yang). Peer review under responsibility of PLA General Hospital Department of Otolaryngology Head and Neck Surgery.
inter-electrodes interference which may be related to postoperative speech performance. The aim of this paper is to summarize the clinical application of ECAP test. 1. ECAP test methods Similar to the compound action potentials (CAPs) in EcochG, ECAPs are the summary of multiple neurons' spikes, reflecting the neural synchronization under electrical stimulation, and can be recorded by a bidirectional stimulationrecording system via the implanted multichannel electrodes. As an objective test, ECAP does not require active participation by the patient, and the recordings are not adversely affected by attention or sleep, making this response an ideal tool for monitoring long-term changes. Being near-field recording response, both the stimulating electrode and recording electrode of ECAPs are around the spiral ganglion, which leads to relative large and robust amplitudes than those of far-field electrically evoked auditory brainstem responses (EABRs). Furthermore, in ECAPs test, relative few sweeps and thus shorter recording time, no skin preparation or any
http://dx.doi.org/10.1016/j.joto.2014.11.002 1672-2930/Copyright © 2014, PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd. All rights reserved
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F. Ji et al. / Journal of Otology 9 (2014) 117e121
skin electrode, and no additional recording equipment are needed, which makes ECAPs more suitable to be widely used in clinical practice than EABRs. A typical ECAP pattern comprises two main waveforms, including a negative wave with a latency of 0.2e0.4 ms (N1), and a positive peak or platform with a latency of 0.6e0.8 ms (P1) (Abbas et al., 1999). Because of the short latency and relatively small amplitude than stimulus, it is necessary to eliminate the stimulating artifact to avoid ECAP waveforms being swamped by them. There are two kinds of artifact elimination paradigms applied in mainstream implant systems, as following. 1) Forward-Masking Subtraction Paradigm Charlet de Sauvage et al. (1983) and Brown et al. (1990) have suggested this paradigm which subtracts the artifact from the recording to extract the relatively miniscule neural response from the accompanying stimulus artifact. This forward-masking paradigm involves three stimulation intervals. With sufficient forward-masking, the neural response can be acquired by subtraction among data obtained from different intervals (Abbas et al., 1999; Xi et al., 2009). Besides, Klop et al. have introduced a dual-masker forward masking technique based on this paradigm, to measure electrode independency in a cochlear implant and evaluate the possibility of determining the optimal locations and number of active electrodes (Klop et al., 2009). 2) Alternating Polarity Paradigm This method is similar to that used in acoustic ABR test. Electrical pulses with alternating polarities are used to stimulate the spiral ganglion. Artifacts are to be canceled out from stimuli polarity reversion, while the neural response, whose polarity does not reverse with the stimuli, is not affected by stimulus polarity reversion. After repeated sweeps, most of the artifacts are eliminated and ECAP components are enhanced. ECAP thresholds obtained by this paradigm is somewhat higher than those from forward-masking paradigm (Xi et al., 2009). In three models of FDA approved cochlear implants, ECAPs can be recorded by a percutaneous technique named telemetry, via bidirectional stimulation-recording systems. ECAPs tests were first clinically introduced in Nucleus CI24M which is equipped with Neural Response Telemetry (NRT) that allows the intra-cochlear electrodes to be used both for stimulation and recording purposes (Abbas et al., 1999). The forward-masking subtraction paradigm is used in the NRT test, making it possible to measure the response of the auditory nerve to electrical stimulation without adverse effects by artifacts. NRT test was approved by FDA in 1998. The Neural Response Imaging (NRI) software was introduced by Advanced Bionics Corporation in 2002 (Frijns et al., 2002), and was approved by FDA in 2003. The ECAP test software from Med-EL was introduced as Auditory Nerve Response Telemetry (ART), with the alternating polarity
paradigm to eliminate artifacts, which obtained approval by FDA in 2007. In each product, a built-in recognition algorithm is applied to analyze the amplitude of N1eP1, and an amplitude growth function can be obtained using stimulation of different levels to demonstrate the correlation between stimuli intensity and ECAP amplitude, and the ECAP thresholds can be calculated. 2. ECAPs in intra-operative monitoring ECAP test after insertion of electrode has been widely used during cochlear implant surgery. In China, an intra-operative ECAP incidence of more than 85% has been reported (Suying et al., 2006; Hua et al., 2001). Even in patients with Mondini syndrome, the intra-operative ECAP incidence may reach 60% (Hua et al., 2001). Generally, clear differentiation of intra-operative ECAP waveforms reflects appropriate insertion position and normal activation of intra-cochlear electrodes. However, the absence of intra-operative ECAP does not necessarily imply deactivation or absent neural response. In 20% of such cases, electrodes provide a useful auditory sensation and patients show good postoperative outcomes in spite of deterioration or absence intra-operative ECAPs (Alvarez et al., 2010). 3. ECAPs in cochlear implant programming In recent years, importance has been attached to the role ECAPs play in speech processor programming. The relationship between ECAP thresholds and MAP levels has been studied to help programming in some patients who cannot cooperate in a psychophysical process to identify the audible threshold and comfort level boundaries (the T- and C-levels, respectively). ECAP thresholds are then used to estimate the T levels and C levels. Restricted to the state of arts, early studies were based on Nucleus 24M with relatively low stimulate rate in SPEAK coding strategy and straight electrode arrays. In young children, ECAP thresholds tend to be at the middle of stimulation dynamic range confined by T level and C level. In adults, ECAP thresholds are more likely at 90% of the dynamic range, close to C levels. Moreover, 1/3 of adults have ECAP thresholds higher than C levels. T levels are always lower than ECAP thresholds. In some studies, the correlation between T levels and ECAP thresholds is modest, with correlation coefficients of 0.5e0.9. The correlation between C levels and ECAP thresholds are drastically variable from 0.1 to 0.9 (Hughes et al., 2000; Polak et al., 2005), which indicates that ECAP thresholds are not a reliable predictor of psychophysical results. However, ECAP thresholds have similar profile along electrodes as indicated by MAP profile obtained from psychophysical test, which suggests it is possible to induce MAP profile from ECAPs to help programming. In the case that profiles of T levels or C levels have large differences from ECAP profiles at some electrodes, psychophysical thresholds can be adjusted according to ECAP profiles, especially for T levels (Hughes et al., 2001).
F. Ji et al. / Journal of Otology 9 (2014) 117e121
Recently, pre-curved electrodes are widely used, and the stimulate rate has been increased greatly. These two factors will influence the psychophysical thresholds, and consequently the correlation between ECAPs and psychophysical thresholds. Besides, the introduction of NRI and ART has provided additional approaches to research the new trends in correlation between ECAPs and psychophysical thresholds (Alvarez et al., 2010; Polak et al., 2005; Botros and Psarros, 2010; Eisen and Franck, 2004; Han et al., 2005; Holstad et al., 2009; Jeon et al., 2010; Potts et al., 2007). According to the results from studies with both Nucleus Freedom 24RE (Gordin et al., 2009) and Advanced Bionics CII implant (Eisen and Franck, 2004), ECAPs and behavioral thresholds (T levels, C levels/ M levels) can be significantly lowered by pre-curved arrays compared with straight arrays. The largest reductions of ECAP thresholds are observed upon apical and basal electrode stimulation. Meanwhile, in pre-curved electrode arrays, ECAP thresholds have moderate correlation with T levels and C levels (Polak et al., 2005). The standard electrode array for the MED-EL MAESTRO cochlear implant system allows a deeper insertion. This long electrode array is capable of stimulating the most apical region of the cochlea, and significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes can be observed in the apical region (Brill et al., 2009). Increasingly higher stimulation rates have been used in cochlear implant speech coding strategies, in order to improve temporal resolution. The initial stimulation rate in SPEAK coding strategy of Nucleus was 250 PPS, while in ACE strategy it has been improved up to 900e1800 PPS. In the HiRes strategy of Advance Bionics about 3000 PPS stimulation rate per channel is used. Patient temporal resolution can be improved with the improvement of stimulation rate, while T levels and C levels drop accordingly. However, considering the refractory period and adaptation of nerve fibers to the stimulation rate, ECAP test cannot use extremely stimulation rates (Lai and Dillier, 2009). In the case of fast stimulation, ECAP thresholds may be close to or over the C levels or M levels, sometimes even twofold of the M level, which may affect correlation between ECAP threshold and behavioral thresholds (Eisen and Franck, 2004; Han et al., 2005; Holstad et al., 2009; Jeon et al., 2010; Potts et al., 2007). Thresholds for all electrodes decrease between surgery and initial stimulation and remain relatively stable at 3 months poststimulation. ECAP thresholds are consistently lower for children compared with adults. ECAP thresholds and amplitude growth functions will change very little over a 5e6 year observation interval (Brown et al., 2010; Wesarg et al., 2010). Significant differences have been found in ECAP thresholds of different electrode positions. Basal electrodes had higher ECAP thresholds than apical electrodes and that relationship was consistent for each time period (Su-ying et al., 2006; Hua et al., 2001; Brill et al., 2009; Spivak et al., 2010). Mid-array ECAP thresholds showed the least amount of change over time, suggesting ECAP thresholds obtained intraoperatively at these electrodes may be helpful in creating a first MAP when no other
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behavioral or electrophysiological data are available (Spivak et al., 2010). Statistically, the correlation between ECAP threshold and behavior threshold (T level) would not increase with the stimulation rate, and even goes to opposite direction (Botros and Psarros, 2010; Wesarg et al., 2010). Further research revealed stronger correlation between ECAP threshold and C level than that between ECAP threshold and T level (Botros and Psarros, 2010; Holstad et al., 2009; Potts et al., 2007). ECAP thresholds recorded from Advanced Bionics cochlear implant users always indicated T levels. However, the correlation between ECAP thresholds and M-levels (the primary metric used to program the speech processor of the Advanced Bionics CI) was modest (correlation coefficient ¼ 0.56e0.74). If programming levels are to be determined on the basis of ECAP thresholds, the stimulation may be uncomfortably loud, particularly on the basal electrodes (Eisen and Franck, 2004; Han et al., 2005; Jeon et al., 2010). In Med-El Tempoþ Cochlear Implant Speech Processor, estimation of T levels has less effect on hearing quality than that of C levels, and the correlation between ECAP thresholds and C levels is also mild (correlation coefficient ¼ 0.53) (Alvarez et al., 2010). The correlation between ECAP thresholds and psychophysical thresholds is affected by many factors. 1) Electrode locations. ECAP thresholds are significantly higher for recordings from the basal side of the probe versus apical (Hughes and Stille, 2009). 2) Psychophysical test signals. It has been reported that correlation between ECAP thresholds and M levels obtained by tone burst is higher than that obtained by speech burst in AB cochlear implant (Jeon et al., 2010). 3) ECAP thresholds calculation. It has been reported that thresholds manually calculated from ECAP amplitude growth function are higher than those from an automatic linear regression in NRI test (Han et al., 2005; Potts et al., 2007). Similarly, because stimulation rates cast different influences on the forward-masking subtraction paradigm and the alternating polarity paradigm in artifact elimination, ECAPs from these two paradigms may demonstrate different thresholds, which consequently result in different correlations (Eisen and Franck, 2004). To sum up, in devices applying coding a strategy with high stimulation rate, the correlation between ECAP thresholds and T/C levels varies depending on electrode positions and individual patients. Reasonable methods should be used in predicting T/C levels from ECAPs. Botros and Psarros (2010) has suggested a profile scaling model constructed from the data prescribing a flattening of the ECAP threshold profile by a simple linear regression. The scaled ECAP threshold profile method provides a clinically significant enhancement to ECAP-based fitting methods, confirming the value of the ECAP threshold profile to cochlear implant fitting. Alvarez et al. (2010) provided a normalization procedure, by which ECAP measurements allow the C-level profile to be predicted with a mean relative error of 6%. On the other hand, even limited behavioral responses (e.g. T/C levels obtained in a few separate electrodes) can help improve the correlation greatly when they are combined with ECAP
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thresholds in predicting T/C profiles (Hughes et al., 2000; Eisen and Franck, 2004).
a good indicator of post-operative hearing and speech performance in these patients (Fei et al., 2014).
4. ECAPs and post-operative speech recognition
References
Another research focus is the relationship between ECAP characteristics and patient speech recognition. In multichannel cochlear implants (CIs), spectral representation of the signal is achieved by stimulation of various electrodes located along the longitudinal axis of the cochlea. Current from each electrode creates an electric field that stimulates surrounding neural tissue. Current fields tend to overlap with one another to some extent, which may affect speech perception with the implant. For CI users, the ability to discriminate electrodes on the basis of pitch is likely influenced by the spatial overlap of stimulated neural populations. Spread of excitation patterns (SOE function) for CI electrodes can be measured with the ECAPs, SOE function may help predict patient speech recognition outcomes objectively (Xi et al., 2009; Hughes and Stille, 2008). Two different methods can be used to measure SOE. One test method is to fix stimulation electrode and shift recording electrode along the electrode array while recording the ECAP amplitude as a function of the recording electrode position, known as exciting spatial spread function. Another method is used in the forward-masking subtraction paradigm in which the probe pulse is presented on one electrode and the masker is shifted along electrode array. The response to the masked probe is dependent on the extent of SOE. The waveform as a function of masker electrode then reflects the degree of overlap between the population of neurons responding to the masker and those stimulated by the probe, which is known as spatial masking function (Hughes and Stille, 2010). However, the correlation between ECAP test and psychophysical test is still not definite. Some studies have found that the more excited space overlapping, the worse the pitch recognition in patients. While some other studies found no significant relationships between pitch recognition and the SOE functions (Busby et al., 2008). In view of this situation, ECPAs cannot be used to predict speech recognition separately until they are combined with psychophysical tests (Hughes and Stille, 2008). In addition to SOE, other characteristics of ECAPs may also help predict speech performance. Kim et al. (2010) suggested that slope of the ECAP growth can show significant correlation to performance with a cochlear implant, especially in patients using Hybrid RE CI. Cohen (2009) provided a model which was fitted to ECAP recovery data in a case where the masker current was highly correlated to that of the probe and masking assumed to be almost complete. The model should provide the means to improve speech processing algorithms for cochlear implants, by allowing the systematic incorporation of additional information concerning the neural response to electrical stimulation. Besides, JI Fei et al. studied amplitudes of ECPAs in cochlear implantees with auditory neuropathy, reporting low incidence, low differentiation and large variation as the characteristics. However, ECAPs cannot yet be
Abbas, P.J., Brown, C.J., Shallop, J.K., et al., 1999. Summary of results using the nucleus CI24M implant to record the electrically evoked compound action potential. Ear Hear. 20 (1), 45e59. Alvarez, I., de la Torre, A., Sainz, M., et al., 2010. Using evoked compound action potentials to assess activation of electrodes and predict C-levels in the Tempoþ cochlear implant speech processor. Ear Hear. 31 (1), 134e145. Botros, A., Psarros, C., 2010. Neural response telemetry reconsidered: I. The relevance of ECAP threshold profiles and scaled profiles to cochlear implant fitting. Ear Hear. 31 (3), 367e379. Brill, S., Mu¨ller, J., Hagen, R., et al., 2009. Site of cochlear stimulation and its effect on electrically evoked compound action potentials using the MEDEL standard electrode array. Biomed. Eng. Online 16 (8), 40. Brown, C.J., Abbas, P.J., Gantz, B., 1990. Electrically evoked whole-nerve action potentials: data from human cochlear implant users. J. Acoust. Soc. Am. 88, 1385e1391. Brown, C.J., Abbas, P.J., Etlert, C.P., et al., 2010. Effects of long-term use of a cochlear implant on the electrically evoked compound action potential. J. Am. Acad. Audiol. 21 (1), 5e15. Busby, P.A., Battmer, R.D., Pesch, J., 2008. Electrophysiological spread of excitation and pitch perception for dual and single electrodes using the nucleus freedom cochlear implant. Ear Hear. 29 (6), 853e864. Charlet de Sauvage, R., Cazals, Y., Erre, J.P., et al., 1983. Acoustically derived auditory nerve action potential evoked by electrical stimulation: an estimation of the waveform of single unit contribution. J. Acoust. Soc. Am. 73, 616e627. Cohen, L.T., 2009. Practical model description of peripheral neural excitation in cochlear implant recipients: 5. refractory recovery and facilitation. Hear. Res. 248 (1e2), 1e14. Eisen, M.D., Franck, K.H., 2004. Electrically evoked compound action potential amplitude growth functions and HiResolution programming levels in pediatric CII implant subjects. Ear Hear. 25 (6), 528e538. Fei, J., Jia-nan, L., Ke, L., et al., 2014. NRT test in auditory neuropathy patients with cochlear implants. Acta otolaryngologica 134 (9), 930e942. Frijns, J.H., Briaire, J.J., de Laat, J.A., et al., 2002. Initial evaluation of the Clarion CII cochlear implant: speech perception and neural response imaging. Ear Hear. 23 (3), 184e197. Gordin, A., Papsin, B., James, A., et al., 2009. Evolution of cochlear implant arrays result in changes in behavioral and physiological responses in children. Otol. Neurotol. 30 (7), 908e915. Han, D.M., Chen, X.Q., Zhao, X.T., et al., 2005. Comparisons between neural response imaging thresholds, electrically evoked auditory reflex thresholds and most comfortable loudness levels in CII bionic ear users with HiResolution sound processing strategies. Acta Otolaryngol. 125 (7), 732e735. Holstad, B.A., Sonneveldt, V.G., Fears, B.T., et al., 2009. Relation of electrically evoked compound action potential thresholds to behavioral T- and C-levels in children with cochlear implants. Ear Hear. 30 (1), 115e127. Hua, Y., Ke-li, C., Xiao-li, Z., et al., 2001. The intraoperative application of neural response telemetry with the nucleus CI24M cochlear implant. Chin. J. Otorhinolaryngol. 36 (5), 352e356. Hughes, M.L., Stille, L.J., 2008. Psychophysical versus physiological spatial forward masking and the relation to speech perception in cochlear implants. Ear Hear. 29 (3), 435e452. Hughes, M.L., Stille, L.J., 2009. Psychophysical and physiological measures of electrical-field interaction in cochlear implants. J. Acoust. Soc. Am. 125 (1), 247e260. Hughes, M.L., Stille, L.J., 2010. Effect of stimulus and recording parameters on spatial spread of excitation and masking patterns obtained with the electrically evoked compound action potential in cochlear implants. Ear Hear. 31 (5), 679e692.
F. Ji et al. / Journal of Otology 9 (2014) 117e121 Hughes, M.L., Brown, C.J., Abbas, P.J., et al., 2000. Comparison of EAP thresholds with MAP levels in the nucleus 24 cochlear implant: data from children. Ear Hear. 21 (2), 164e174. Hughes, M.L., Vander Werff, K.R., Brown, C.J., et al., 2001. A longitudinal study of electrode impedance, the electrically evoked compound action potential, and behavioral measures in nucleus 24 cochlear implant users. Ear Hear. 22 (6), 471e486. Jeon, E.K., Brown, C.J., Etler, C.P., et al., 2010. Comparison of electrically evoked compound action potential thresholds and loudness estimates for the stimuli used to program the advanced bionics cochlear implant. J. Am. Acad. Audiol. 21 (1), 16e27. Kim, J.R., Abbas, P.J., Brown, C.J., et al., 2010. The relationship between electrically evoked compound action potential and speech perception: a study in cochlear implant users with short electrode array. Otol. Neurotol. 31 (7), 1041e1048. Klop, W.M., Frijns, J.H., Soede, W., et al., 2009. An objective method to measure electrode independence in cochlear implant patients with a dualmasker forward masking technique. Hear. Res. 253 (1e2), 3e14. Lai, W., Dillier, N., 2009. Neural adaptation and the ECAP response threshold: a pilot study. Cochlear Implants Int. 1 (10 Suppl. l), 63e67.
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Polak, M., Hodges, A., Balkany, T.E.C.A.P., 2005. ESR and subjective levels for two different nucleus 24 electrode arrays. Otol. Neurotol. 26 (4), 639e645. Potts, L.G., Skinner, M.W., Gotter, B.D., et al., 2007. Relation between neural response telemetry thresholds, T- and C-levels, and loudness judgments in 12 adult nucleus 24 cochlear implant recipients. Ear Hear. 28 (4), 495e511. Spivak, L., Auerbach, C., Vambutas, A., et al., 2010. Electrical compound action potentials recorded with automated neural response telemetry: threshold changes as a function of time and electrode position. Ear Hear. 4. Su-ying, G., Yue-hui, L., Ke-liang, X., 2006. The application of neural response telemetry in the mapping after cochlear implant surgery. Chin. J. Otol. 4 (3), 220e222. Wesarg, T., Battmer, R.D., Garrido, L.C., et al., 2010. Effect of changing pulse rate on profile parameters of perceptual thresholds and loudness comfort levels and relation to ECAP thresholds in recipients of the nucleus CI24RE device. Int. J. Audiol. 49 (10), 775e787. Xin, X., FeiJ, Dong-yi, H., et al., 2009. Electrode interaction in cochlear implant recipients: comparison of straight and contour electrode arrays. ORL J. Otorhinolaryngol. Relat. Spec. 71 (4), 228e237.
Available online at www.sciencedirect.com
ScienceDirect Journal of Otology 9 (2014) 117e121 www.journals.elsevier.com/journal-of-otology/
Clinical application of electrically evoked compound action potentials* Fei Ji, Ke Liu, Shi-ming Yang* Department of Otolaryngology, Head & Neck Surgery, Chinese PLA General Hospital, Chinese PLA Institute of Otolaryngology, 28 Fuxing Road, Beijing 100853, China Received 24 September 2014; accepted 17 November 2014
Abstract ECAPs are the summary of multiple neurons’ spikes which could be recorded by a bidirectional stimulation-recording system via the cochlear implant, with the artifact elimination paradigms of forward-masking subtraction paradigm or alternating polarity paradigm. Three kinds of FDA approved cochlear implants support ECAP testing. This article is to summarize the clinical application of ECAP test. ECAP test after insertion of electrode during implant operation has been widely used during cochlear implant surgery. In recent years, ECAP thresholds are also used to estimate the T levels and C levels helping programming. However, correlation between ECAP thresholds and psychophysical thresholds is affected by many factors. So far, ECAPs cannot yet be a good indicator of post-operative hearing and speech performance. Copyright © 2014, PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd. All rights reserved.
Keywords: Electrically Evoked Compound Action Potentials; Cochlear implant; Electrophysiology; Hearing; Intra-operative monitoring
Electrically evoked compound action potentials (ECAPs) were originally applied to research the neural response of animals to electrical stimulation. With the development of cochlear implant, it is possible to record human neural ECAPs in vivo through implanted electrodes (Abbas et al., 1999). So far, there are three kinds of FDA approved cochlear implants that support ECAP testing, which widen the clinical application of ECAPs, including: 1) evaluation of response of the VIIIth nerve to electrical stimulation, helping to validate the working status of implant; 2) assisting speech processor programming; and 3) evaluation of spatial excitation patterns and
* Funding: This work was supported by grants from the National Basic Research Program of China (973 Program) (#2012CB967900), Science and Technology Innovation Nursery Foundation of PLA General Hospital (13KMM14) and Clinical Research Supporting Foundation of PLA General Hospital (2012FC-TSYS-3056). * Corresponding author. E-mail addresses: [email protected] (J. Fei), [email protected] (S. Yang). Peer review under responsibility of PLA General Hospital Department of Otolaryngology Head and Neck Surgery.
inter-electrodes interference which may be related to postoperative speech performance. The aim of this paper is to summarize the clinical application of ECAP test. 1. ECAP test methods Similar to the compound action potentials (CAPs) in EcochG, ECAPs are the summary of multiple neurons' spikes, reflecting the neural synchronization under electrical stimulation, and can be recorded by a bidirectional stimulationrecording system via the implanted multichannel electrodes. As an objective test, ECAP does not require active participation by the patient, and the recordings are not adversely affected by attention or sleep, making this response an ideal tool for monitoring long-term changes. Being near-field recording response, both the stimulating electrode and recording electrode of ECAPs are around the spiral ganglion, which leads to relative large and robust amplitudes than those of far-field electrically evoked auditory brainstem responses (EABRs). Furthermore, in ECAPs test, relative few sweeps and thus shorter recording time, no skin preparation or any
http://dx.doi.org/10.1016/j.joto.2014.11.002 1672-2930/Copyright © 2014, PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd. All rights reserved
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F. Ji et al. / Journal of Otology 9 (2014) 117e121
skin electrode, and no additional recording equipment are needed, which makes ECAPs more suitable to be widely used in clinical practice than EABRs. A typical ECAP pattern comprises two main waveforms, including a negative wave with a latency of 0.2e0.4 ms (N1), and a positive peak or platform with a latency of 0.6e0.8 ms (P1) (Abbas et al., 1999). Because of the short latency and relatively small amplitude than stimulus, it is necessary to eliminate the stimulating artifact to avoid ECAP waveforms being swamped by them. There are two kinds of artifact elimination paradigms applied in mainstream implant systems, as following. 1) Forward-Masking Subtraction Paradigm Charlet de Sauvage et al. (1983) and Brown et al. (1990) have suggested this paradigm which subtracts the artifact from the recording to extract the relatively miniscule neural response from the accompanying stimulus artifact. This forward-masking paradigm involves three stimulation intervals. With sufficient forward-masking, the neural response can be acquired by subtraction among data obtained from different intervals (Abbas et al., 1999; Xi et al., 2009). Besides, Klop et al. have introduced a dual-masker forward masking technique based on this paradigm, to measure electrode independency in a cochlear implant and evaluate the possibility of determining the optimal locations and number of active electrodes (Klop et al., 2009). 2) Alternating Polarity Paradigm This method is similar to that used in acoustic ABR test. Electrical pulses with alternating polarities are used to stimulate the spiral ganglion. Artifacts are to be canceled out from stimuli polarity reversion, while the neural response, whose polarity does not reverse with the stimuli, is not affected by stimulus polarity reversion. After repeated sweeps, most of the artifacts are eliminated and ECAP components are enhanced. ECAP thresholds obtained by this paradigm is somewhat higher than those from forward-masking paradigm (Xi et al., 2009). In three models of FDA approved cochlear implants, ECAPs can be recorded by a percutaneous technique named telemetry, via bidirectional stimulation-recording systems. ECAPs tests were first clinically introduced in Nucleus CI24M which is equipped with Neural Response Telemetry (NRT) that allows the intra-cochlear electrodes to be used both for stimulation and recording purposes (Abbas et al., 1999). The forward-masking subtraction paradigm is used in the NRT test, making it possible to measure the response of the auditory nerve to electrical stimulation without adverse effects by artifacts. NRT test was approved by FDA in 1998. The Neural Response Imaging (NRI) software was introduced by Advanced Bionics Corporation in 2002 (Frijns et al., 2002), and was approved by FDA in 2003. The ECAP test software from Med-EL was introduced as Auditory Nerve Response Telemetry (ART), with the alternating polarity
paradigm to eliminate artifacts, which obtained approval by FDA in 2007. In each product, a built-in recognition algorithm is applied to analyze the amplitude of N1eP1, and an amplitude growth function can be obtained using stimulation of different levels to demonstrate the correlation between stimuli intensity and ECAP amplitude, and the ECAP thresholds can be calculated. 2. ECAPs in intra-operative monitoring ECAP test after insertion of electrode has been widely used during cochlear implant surgery. In China, an intra-operative ECAP incidence of more than 85% has been reported (Suying et al., 2006; Hua et al., 2001). Even in patients with Mondini syndrome, the intra-operative ECAP incidence may reach 60% (Hua et al., 2001). Generally, clear differentiation of intra-operative ECAP waveforms reflects appropriate insertion position and normal activation of intra-cochlear electrodes. However, the absence of intra-operative ECAP does not necessarily imply deactivation or absent neural response. In 20% of such cases, electrodes provide a useful auditory sensation and patients show good postoperative outcomes in spite of deterioration or absence intra-operative ECAPs (Alvarez et al., 2010). 3. ECAPs in cochlear implant programming In recent years, importance has been attached to the role ECAPs play in speech processor programming. The relationship between ECAP thresholds and MAP levels has been studied to help programming in some patients who cannot cooperate in a psychophysical process to identify the audible threshold and comfort level boundaries (the T- and C-levels, respectively). ECAP thresholds are then used to estimate the T levels and C levels. Restricted to the state of arts, early studies were based on Nucleus 24M with relatively low stimulate rate in SPEAK coding strategy and straight electrode arrays. In young children, ECAP thresholds tend to be at the middle of stimulation dynamic range confined by T level and C level. In adults, ECAP thresholds are more likely at 90% of the dynamic range, close to C levels. Moreover, 1/3 of adults have ECAP thresholds higher than C levels. T levels are always lower than ECAP thresholds. In some studies, the correlation between T levels and ECAP thresholds is modest, with correlation coefficients of 0.5e0.9. The correlation between C levels and ECAP thresholds are drastically variable from 0.1 to 0.9 (Hughes et al., 2000; Polak et al., 2005), which indicates that ECAP thresholds are not a reliable predictor of psychophysical results. However, ECAP thresholds have similar profile along electrodes as indicated by MAP profile obtained from psychophysical test, which suggests it is possible to induce MAP profile from ECAPs to help programming. In the case that profiles of T levels or C levels have large differences from ECAP profiles at some electrodes, psychophysical thresholds can be adjusted according to ECAP profiles, especially for T levels (Hughes et al., 2001).
F. Ji et al. / Journal of Otology 9 (2014) 117e121
Recently, pre-curved electrodes are widely used, and the stimulate rate has been increased greatly. These two factors will influence the psychophysical thresholds, and consequently the correlation between ECAPs and psychophysical thresholds. Besides, the introduction of NRI and ART has provided additional approaches to research the new trends in correlation between ECAPs and psychophysical thresholds (Alvarez et al., 2010; Polak et al., 2005; Botros and Psarros, 2010; Eisen and Franck, 2004; Han et al., 2005; Holstad et al., 2009; Jeon et al., 2010; Potts et al., 2007). According to the results from studies with both Nucleus Freedom 24RE (Gordin et al., 2009) and Advanced Bionics CII implant (Eisen and Franck, 2004), ECAPs and behavioral thresholds (T levels, C levels/ M levels) can be significantly lowered by pre-curved arrays compared with straight arrays. The largest reductions of ECAP thresholds are observed upon apical and basal electrode stimulation. Meanwhile, in pre-curved electrode arrays, ECAP thresholds have moderate correlation with T levels and C levels (Polak et al., 2005). The standard electrode array for the MED-EL MAESTRO cochlear implant system allows a deeper insertion. This long electrode array is capable of stimulating the most apical region of the cochlea, and significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes can be observed in the apical region (Brill et al., 2009). Increasingly higher stimulation rates have been used in cochlear implant speech coding strategies, in order to improve temporal resolution. The initial stimulation rate in SPEAK coding strategy of Nucleus was 250 PPS, while in ACE strategy it has been improved up to 900e1800 PPS. In the HiRes strategy of Advance Bionics about 3000 PPS stimulation rate per channel is used. Patient temporal resolution can be improved with the improvement of stimulation rate, while T levels and C levels drop accordingly. However, considering the refractory period and adaptation of nerve fibers to the stimulation rate, ECAP test cannot use extremely stimulation rates (Lai and Dillier, 2009). In the case of fast stimulation, ECAP thresholds may be close to or over the C levels or M levels, sometimes even twofold of the M level, which may affect correlation between ECAP threshold and behavioral thresholds (Eisen and Franck, 2004; Han et al., 2005; Holstad et al., 2009; Jeon et al., 2010; Potts et al., 2007). Thresholds for all electrodes decrease between surgery and initial stimulation and remain relatively stable at 3 months poststimulation. ECAP thresholds are consistently lower for children compared with adults. ECAP thresholds and amplitude growth functions will change very little over a 5e6 year observation interval (Brown et al., 2010; Wesarg et al., 2010). Significant differences have been found in ECAP thresholds of different electrode positions. Basal electrodes had higher ECAP thresholds than apical electrodes and that relationship was consistent for each time period (Su-ying et al., 2006; Hua et al., 2001; Brill et al., 2009; Spivak et al., 2010). Mid-array ECAP thresholds showed the least amount of change over time, suggesting ECAP thresholds obtained intraoperatively at these electrodes may be helpful in creating a first MAP when no other
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behavioral or electrophysiological data are available (Spivak et al., 2010). Statistically, the correlation between ECAP threshold and behavior threshold (T level) would not increase with the stimulation rate, and even goes to opposite direction (Botros and Psarros, 2010; Wesarg et al., 2010). Further research revealed stronger correlation between ECAP threshold and C level than that between ECAP threshold and T level (Botros and Psarros, 2010; Holstad et al., 2009; Potts et al., 2007). ECAP thresholds recorded from Advanced Bionics cochlear implant users always indicated T levels. However, the correlation between ECAP thresholds and M-levels (the primary metric used to program the speech processor of the Advanced Bionics CI) was modest (correlation coefficient ¼ 0.56e0.74). If programming levels are to be determined on the basis of ECAP thresholds, the stimulation may be uncomfortably loud, particularly on the basal electrodes (Eisen and Franck, 2004; Han et al., 2005; Jeon et al., 2010). In Med-El Tempoþ Cochlear Implant Speech Processor, estimation of T levels has less effect on hearing quality than that of C levels, and the correlation between ECAP thresholds and C levels is also mild (correlation coefficient ¼ 0.53) (Alvarez et al., 2010). The correlation between ECAP thresholds and psychophysical thresholds is affected by many factors. 1) Electrode locations. ECAP thresholds are significantly higher for recordings from the basal side of the probe versus apical (Hughes and Stille, 2009). 2) Psychophysical test signals. It has been reported that correlation between ECAP thresholds and M levels obtained by tone burst is higher than that obtained by speech burst in AB cochlear implant (Jeon et al., 2010). 3) ECAP thresholds calculation. It has been reported that thresholds manually calculated from ECAP amplitude growth function are higher than those from an automatic linear regression in NRI test (Han et al., 2005; Potts et al., 2007). Similarly, because stimulation rates cast different influences on the forward-masking subtraction paradigm and the alternating polarity paradigm in artifact elimination, ECAPs from these two paradigms may demonstrate different thresholds, which consequently result in different correlations (Eisen and Franck, 2004). To sum up, in devices applying coding a strategy with high stimulation rate, the correlation between ECAP thresholds and T/C levels varies depending on electrode positions and individual patients. Reasonable methods should be used in predicting T/C levels from ECAPs. Botros and Psarros (2010) has suggested a profile scaling model constructed from the data prescribing a flattening of the ECAP threshold profile by a simple linear regression. The scaled ECAP threshold profile method provides a clinically significant enhancement to ECAP-based fitting methods, confirming the value of the ECAP threshold profile to cochlear implant fitting. Alvarez et al. (2010) provided a normalization procedure, by which ECAP measurements allow the C-level profile to be predicted with a mean relative error of 6%. On the other hand, even limited behavioral responses (e.g. T/C levels obtained in a few separate electrodes) can help improve the correlation greatly when they are combined with ECAP
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thresholds in predicting T/C profiles (Hughes et al., 2000; Eisen and Franck, 2004).
a good indicator of post-operative hearing and speech performance in these patients (Fei et al., 2014).
4. ECAPs and post-operative speech recognition
References
Another research focus is the relationship between ECAP characteristics and patient speech recognition. In multichannel cochlear implants (CIs), spectral representation of the signal is achieved by stimulation of various electrodes located along the longitudinal axis of the cochlea. Current from each electrode creates an electric field that stimulates surrounding neural tissue. Current fields tend to overlap with one another to some extent, which may affect speech perception with the implant. For CI users, the ability to discriminate electrodes on the basis of pitch is likely influenced by the spatial overlap of stimulated neural populations. Spread of excitation patterns (SOE function) for CI electrodes can be measured with the ECAPs, SOE function may help predict patient speech recognition outcomes objectively (Xi et al., 2009; Hughes and Stille, 2008). Two different methods can be used to measure SOE. One test method is to fix stimulation electrode and shift recording electrode along the electrode array while recording the ECAP amplitude as a function of the recording electrode position, known as exciting spatial spread function. Another method is used in the forward-masking subtraction paradigm in which the probe pulse is presented on one electrode and the masker is shifted along electrode array. The response to the masked probe is dependent on the extent of SOE. The waveform as a function of masker electrode then reflects the degree of overlap between the population of neurons responding to the masker and those stimulated by the probe, which is known as spatial masking function (Hughes and Stille, 2010). However, the correlation between ECAP test and psychophysical test is still not definite. Some studies have found that the more excited space overlapping, the worse the pitch recognition in patients. While some other studies found no significant relationships between pitch recognition and the SOE functions (Busby et al., 2008). In view of this situation, ECPAs cannot be used to predict speech recognition separately until they are combined with psychophysical tests (Hughes and Stille, 2008). In addition to SOE, other characteristics of ECAPs may also help predict speech performance. Kim et al. (2010) suggested that slope of the ECAP growth can show significant correlation to performance with a cochlear implant, especially in patients using Hybrid RE CI. Cohen (2009) provided a model which was fitted to ECAP recovery data in a case where the masker current was highly correlated to that of the probe and masking assumed to be almost complete. The model should provide the means to improve speech processing algorithms for cochlear implants, by allowing the systematic incorporation of additional information concerning the neural response to electrical stimulation. Besides, JI Fei et al. studied amplitudes of ECPAs in cochlear implantees with auditory neuropathy, reporting low incidence, low differentiation and large variation as the characteristics. However, ECAPs cannot yet be
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