Assessing auditory nerve recovery function with a modified subtraction method: results and mathematical modeling
Introduction
One of the main difficulties in the clinical management of cochlear implant users is to correctly fit the implant's speech processor. This fitting procedure requires an estimation of two psychophysical measures: the detection threshold (T) and the comfort threshold (C) levels. The current method for setting T- and C-levels in young children requires a conditioning phase which might be difficult and time consuming. During the last decade, an attempt was made to correlate the results of various electrophysiological measurements such as electrically evoked auditory brainstem responses (Brown et al., 1994, Gallégo et al., 1998) or sympathetic skin responses (Péréon et al., 2001) with the cochlear implant user's behavioral responses. The aim of these objective measurements was to facilitate the cochlear implant fitting process by saving time in speech processor parameters adjustment. The neural response telemetry (NRT) software has been developed by Dillier et al., 1995 at Zurich University, in collaboration with Cochlear company, to provide a simplified tool for electrophysiological measurements in cochlear implantees. The NRT system has been validated in 1997 for in situ recordings of neural activity within human cochlea in response to electrical stimulation (Lai et al., 1997). Among the potential applications of the neurophysiological signal obtained, some are of great interest for the follow-up of the cochlear implant recipient: confirmation of device integrity and physiological responsiveness, psychophysics estimation based on amplitude growth function measurement, and assessment of the auditory nerve's refractory properties. The results of several studies suggest that NRT response threshold (T-NRT) may be of use for predicting the T- and C-levels (Brown et al., 1996, Brown et al., 1998, Abbas et al., 1999). Correlation between electrical compound action potential (ECAP) threshold and T-level was found to range between 0.6 and 0.7. The possible influence of auditory nerve's refractory properties on this correlation remains to be elucidated. We believe that the relationship between T-NRT and psychophysical measurements may be linked to the refractory properties of the auditory nerve. In order to test this hypothesis, the present paper will focus on the measurement of refractory properties and examine two different measurement methods.
The fact that neural response amplitude is very small compared to the electrical stimulation (with an amplitude ratio of 1/1000) explains that neural response is difficult to extract from stimulus artifact. An original algorithm based on the refractory properties of auditory nerve has been developed and implemented in the NRT software. The NRT software allows the auditory neural response to be extracted from the stimulus artifact using a forward-masking algorithm described in detail elsewhere (see Brown et al., 1990, Dillier et al., 2002). Fig. 1A illustrates this algorithm.
In the A1 sequence, only probe stimulus is delivered, exciting the auditory nerve. In the B1 sequence, a masker stimulus is first delivered. The probe is delivered after a short delay called ‘Masker Probe Interval’ (MPI). If MPI is too short, the auditory nerve will be in a refracted, or partially refracted, state as explained by Bear et al. (1997). The A1−B1 subtraction sequence is the difference between auditory nerve responses in a non-refracted vs. a refracted state; however, this subtracted response remains contaminated by the masker artifact. In order to eliminate the masker artifact, the C1 sequence sends only the masker, and this C1 sequence is then added to A1−B1. A final sequence, D1, consists simply of the recording of the response with no applied stimulus. The final step involves the calculation of the auditory nerve response using the (standard) equation A1−B1+C1−D1. This subtraction method utilizes the refractory properties of the electrically excited nerve fibers and has been successfully used in ECAP waveform recordings (Brown et al., 1995, Brown et al., 1998). An extension subtraction method has been proposed in order to obtain recovery functions of the auditory nerve system. Recovery properties demonstrate the rate at which the auditory nerve returns to its initial state. For different MPI values, the response amplitude as a function of MPI values represents the refractory recovery function. Miller et al. (2000) suggested that this method was not completely effective for measuring refractory properties. The reason cited by Miller et al. (2000) relies on the assumption that ECAP waveform in the masked probe stimulus sequence is simply an amplitude-scaled version of the ECAP response obtained in unmasked status. It is then assumed that the subtracted response waveform morphology is identical to the response in both conditions. But according to them, and with regard to other studies in humans (Finley et al., 1997) or animals (Kandel and Schwartz, 1985), this assumption is incorrect, due to the possible delay of the response in the refracted state which could result in a distortion of the actual ECAP responses. For this reason, a modified subtraction method was suggested in order to take this difference into account. Fig. 1B illustrates the modified method algorithm proposed by Miller et al. (2000). The subtraction paradigm for the modified method is as follows: the first sequence A2 differs from the standard A1 sequence (A1 consists of delivering a probe stimulus; A2 is a masker followed by a probe stimulation). Note that in this A2 situation, the auditory nerve is now in a masked state. The second modified sequence, B2, is also a masker+probe stimulus, but with a shorter MPI. The auditory nerve response is then determined by the subtraction of two equivalent refracted states (A2−B2); nevertheless, this response is contaminated with the maskers of both sequences. Extraction of the masker artifacts is accomplished with C2 and D2 sequences. Neural response is then calculated using the modified equation A2−B2−C2+D2. The purpose of this paper was to establish an experiment to test the validity of the modified technique in adult patients. Miller et al. (2000) tested the modified method on a limited number of electrodes in 12 patients; our group decided to test fewer patients and to assess the influence of electrode location among the 20 active electrodes. A mathematical model was used to simulate the obtained results. Experimentation and model results were then analyzed and commentated. The purpose of the paper is to demonstrate the influence on recovery function measurement of the modified subtraction method as compared to the standard method and to assess the influence of the electrode position on the recovery function.
Section snippets
Methods
ECAP responses were recorded in 4 adult patients (age ranging between 30 and 60 years) implanted with the Nucleus 24 device at Edouard Herriot Hospital, Lyon, France. Table 1 summarizes patients' characteristics.
ECAP responses were recorded for each patient along the 20 active electrodes. The recording electrode was two away from the stimulated electrode (i.e. if electrode 12 was stimulated, electrode 10 was used for recording). The following measurement protocol was used for each electrode:
Results
The simplest way to compare the two methods was to compare the number of valid responses obtained with each. Jagged traces were not taken into account. Traces were considered as valid when both P1 and N1 peaks could be clearly identified and the amplitude of the response was measurable between P1 and N1 peaks. To eliminate possible errors due to the subjectivity of this decision, two experienced audiologists analyzed the traces. The decision of valid or invalid response was obtained after
Discussion
The purpose of this study was to assess two different methods of recording the recovery functions in NRT measurements. Valid responses were observed with both methods. (An NRT response was considered as valid if a clearly definable amplitude and type of response could be observed.) Preliminary results show that the number of valid responses is greater using the modified method. Two possible reasons why the standard method yields fewer valid responses: (1) using the standard method, when a
Conclusion
Auditory nerve responses have been studied using standard and modified subtraction methods. Comparison showed a higher number of valid ECAP responses obtained using the modified method. Using this modified method, P1 peak was sometimes attenuated when MPI was increased. With the standard method, response quality decreased quickly when MPI was increased. Moreover, in many cases, when using the standard method, the N1 peak often disappeared with increasing MPI values; consequently, many responses
Acknowledgements
The authors would like to thank Miss Christelle Coudert and Rachelle Miano for reading this paper. Mr Ernst Von Wallenberg, Matthijs Killian, and Jochen Nicolai for their collaboration.
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