Hearing Research, 51 (1991) 139-148 0 1991 Elsevier Science Publishers B.V. (Biomedical
HEARES
139 Division)
0378-5955/91/$03.50
01493
Electrically evoked auditory brainstem response: Refractory properties and strength-duration functions Paul J. Abbas and Carolyn J. Brown * Department
of Speech Pathology and Audiology, (Received
4 August
University of Iowa, Iowa City, Iowa, U.S.A.
1989; accepted
25 July 1990)
The electrically evoked auditory brainstem potential (EABR) was recorded in users of both the Nucleus cochlear implant and the Ineraid co&ear implant. The refractory properties of the EABR were evaluated by measuring the response amplitude to a two-pulse stimulus where the interpulse interval was varied. The threshold of response for a single pulse stimulus was also measured as a function of the duration of the biphasic pulse. These strength-duration functions were then used to calculate an EABR chronaxie measure. Both of these measures showed a similar range for the monopolar stimulation used with the Ineraid implant and the bipolar stimulation used with the Nucleus implant. Neither of these two measures of the temporal response properties showed any clear relationship to the ability of individual subjects to perform on a speech perception task. EABR;
Refraction;
Chronaxie
Introduction In previous work, we have measured the electrically evoked auditory brainstem response (EABR) in cochlear implant patients, investigating both the growth of response with level for different electrode configurations (Abbas and Brown, 1990) and the degree of response interaction for simultaneous stimulation of different channels of a multichannel implant (Abbas and Brown, 1988). Our rationale in the previous studies was that each of these parameters may be important in evaluating the degree to which individual cochlear implant users experience success with the device. In that work, however, we did not measure any of the temporal response properties of the EABR. The ways in which the response changes over time with stimulation, the properties of recovery from previous stimulation, and the relative sensitivity to stimuli of different durations may all provide inCorrespondence to: Paul J. Abbas, Department of Speech Pathology and Audiology, University of Iowa, Iowa City, IA, 52242, U.S.A. * Present address: Department of Speech and Hearing Sciences, Arizona State University, Tempe, Arizona, U.S.A.
formation on how the auditory system will respond to a time changing signal such as speech. Consequently, these properties may be important in determining performance with an implant. Stypulkowski and van den Honert (1984) have proposed that some measure of the refractory properties of the peripheral auditory system may serve as an index to the function of the auditory nerve and thus potentially as a means of determining clinically the utility of an implant to an individual. The rationale behind this suggestion is that because normal frequency resolution is impossible for cochlear implant users, the ability to take advantage of the temporal cues available in the signal might be especially important. Differences across implant subjects in terms of their temporal processing capabilities have been documented in psychophysical work where abnormal patterns of adaptation to a constant stimulus have been reported and where abnormally slow rates of recovery from adaptation have been reported (Shannon, 1983). Stypulkowski and van den Honert (1984) measured the refractory characteristics of the electrically evoked whole-nerve action potential (EAP) and noted differences between animals
140
with normal neurons and those in which there was likely extensive damage to the peripheral dendrites. They suggested that the nonmonotonic recovery functions that they observed in normal and neomycin deafened ears could be due in part to stimulation of the peripheral dendrite in addition to direct stimulation of the axon. We (Brown et al., 1990) have recently reported measurements of the EAP in Ineraid co&ear implant subjects. The refractory functions showed substantial variability across individual users and the time course of recovery demonstrated a good correlation to performance on speech perception tasks. The chronaxie of the strength-duration function of the neuronal response may also be an important measure characterizing the condition of the neurons and their response to temporally changing stimuli (Loeb et al., 1983). Parkins and Columbo (1987) have made measurements of the strength-duration functions in animals (threshold current level as a function of stimulus duration) for biphasic current pulses and have developed a model (Columbo and Parkins, 1987) to simulate properties of nerve stimulation. A critical parameter of the model is the length of the myelinated nerve ending, in that different chronaxie values could be obtained depending upon the length of the dendrite and the degree to which it is stimulable. Since loss of hair cells can result in degeneration of the peripheral dendrites and the myelin sheath, the measurement of strength-duration functions may be another way in which we can assess such differences in individuals who have a cochlear implant. In this study, we have measured both refractory properties and strength-duration functions using the electrically evoked auditory brainstem response (EABR). Subjects include users of both the Ineraid and Nucleus multichannel cochlear implants. Since these same subjects are included in a large protocol of tests as part of the Iowa Cochlear Implant Program Project, we were able to measure the degree to which these measures of temporal response properties correlate with performance on speech perception tasks. Our rationale in using stimulation through the implant is similar to that of the previous study (Abbas and Brown, 1990). Stimulation through the implant provides somewhat of a ‘best case’ in that the stimulating elec-
trodes are within the cochlea and they have been stable in their position for some time. If correlations with performance are observed with implant stimuIation, then more extensive tests with preimplant stimulation may be warranted. Methods Stimulus delivery and recording procedures were the same as those described in the companion paper (Abbas and Brown, 1990). Subjects were drawn from the same pool of implant patients; 13 subjects used the Ineraid implant and 16 subjects used the Nucleus implant. For Nucleus implant users, the stimuli were delivered in a bipolar stimulation mode to electrode pair 10-15. For the Ineraid implant users, the stimuli were delivered to electrode pair 1-8, where electrode 1 is the most apical intracochlear electrode and electrode 8 is an extracochlear electrode that is implanted in the temporalis muscle. Not all subjects participated in both experiments (measurement of refractory properties and measurement of strength-duration functions). In particular, we were selective in choosing subjects for inclusion in experiments in which measures of refractoriness were made. This experiment required that relative response amplitudes be measured in several different stimulus conditions. Subjects whose responses were particularly variable or noisy were not used. In the experiments measuring threshold of EABR response for different pulse durations, single pulses were presented and the recorded potential was averaged to extract the EABR. Stimuli were biphasic square pulses from 50 to 400 ps per phase. For the Ineraid subjects, the initial phase of the biphasic current pulse was alternated in the average in order to reduce the stimulus artifact. At least two averages of IO00 sweeps were measured in each stimulus condition. To make data collection more efficient, the response to individual stimuli were monitored on line. Current levels were chosen to elicit a clear EABR response and then several levels below that were used. Each response trace was subsequently analyzed off-line. The stimulus artifact was removed and the waveform digitally filtered (FIR bandpass filter, 57th order). Response threshold was defined as the lowest current level at which a repeatable response
141
was observed. EABR thresholds were determined for each stimulus duration. In experiments where the refractory properties of the EABR were measured, a stimulus was used that consisted of two biphasic pulses separated in time. We refer to the first pulse as the masker pulse and the second as the probe pulse. The masker and probe pulses are typically presented at the same current level. We measured the response to the probe pulse as a function of the time between probe and masker pulses (or interpulse interval). The stimulus presentation alternates between the condition where both pulses are presented and the condition where a single masker pulse is presented. The averaged response to each stimulus condition is recorded separately. In this way, the response to the masker pulse alone is determined and the response to the probe pulse in the presence of the masker pulse is also measured. Particularly for small interpulse intervals, the EABR to the masker may overlap the response to the probe stimulus. Consequently, we can subtract the averaged waveform recorded in the maskeralone condition from the averaged waveform recorded in the masker-plus-probe condition in order to extract the response to the probe that is recorded in the masker plus probe condition. The subtracted traces were truncated to eliminate the stimulus artifact and then digitally filtered using a 57th order FIR bandpass filter with cutoff values of 150 Hz and 3 kHz. After filtering, the amplitude of the EABR was measured on the subtracted trace. Results and Discussion Experiment
I : Refractory
measures
Fig. 1 illustrates the response to the probe pulse in a series of stimulus presentations designed to assess the time course of recovery from the refractory state. Each trace represents the subtracted (response to the masker-plus-probe subtracted from the response to the masker alone) and filtered response as described above. The masker pulse is always delivered at time zero. The arrow on each trace indicates the time at which the probe pulse is presented. All of the traces shown in Fig. 1 were recorded with both masker and probe pulse cur-
11
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rent levels set to 0.462 mA. For short interpulse intervals (lower traces), the response is depressed. As the interpulse interval is lengthened, the response amplitude recovers. The amplitude of wave V of the EABR was used in subsequent analyses as an indicator of the degree of recovery. Figs. 2A and 2B show the effect of varying the length of the interpulse interval on the amplitude of the EABR for both Nucleus and Ineraid cochlear implant users. For each subject, the amplitude of the EABR is smallest at short interpulse intervals and increases to an asymptotic level as the interpulse interval becomes progressively longer. This asymptotic value approximates the EABR amplitude recorded when the probe stimulus is presented alone. Stimulus levels in the upper part of each subject’s dynamic range were used, so that the actual current level and response amplitude that is measured across subjects is quite
142
variable. This variability is reflected in the differences in asymptotes at long interpulse intervals. The similarities among the recovery functions for different subjects are better illustrated in Figs. 2C and 2D where the amplitude of response is normalized by dividing each response by the amplitude in response recorded when the probe pulse is presented alone. The normalized recovery functions of the 8 subjects with the Nucleus implant are all quite similar. The 12 Ineraid users show slightly more variability in the time course of recovery. If we simply average the normalized amplitude for each interpulse interval across subNucleus 1.0
jects, we can calculate an average recovery curve for subjects with each implant type. These average data are illustrated in Fig. 3. The recovery functions for the two implant types are quite similar. The differences in the recovery functions recorded across subjects may be due to a number of factors. One of these may be related to differences in the level of the stimuli used to record the response. In three subjects, we measured recovery functions for two different current levels (both probe and masker pulse were always the same). An example is illustrated in Fig. 4. When plotted on a normalized scale the time course of recovery
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Fig. 2. Amplitude of the EABR in response to the second pulse in a two-pulse sequence is plotted as a function of interpulse interval or the time between the two pulses. (A) shows recovery functions from 8 Nucleus implant users. (B) shows recovery functions from 12 Ineraid implant users. The current level of the two pulses was always the same and was chosen to be in the upper part of the subject’s dynamic range. (C) shows the same data as part A with amplitude normalized by dividing each point by the response amplitude measured to a single pulse, i.e., the unadapted state. (D) shows the normalized data for the Ineraid users.
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is quite similar. It should be noted, however, that we have observed similar data on only two other subjects and in each case the current levels that we
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O.Oti for Ineraid users and 4.63 ms (SD = 1.59 ms) for Nucleus users. We were interested in the extent to which the differences in the recovery time constant are related to performance with the implant. We used the same measures of speech perception as reported in the previous paper, the Iowa Sentence Test (sound-only) and the Iowa NU-6 word list (Tyler et al., 1983; Tyler
0 Pulse Duration
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Fig. 6. Threshold of EABR response as a function of pulse duration is plotted for 15 Nucleus implant users and 8 lneraid implant users. Pulses are biphasic with equal positive and negative phases.
tract two numbers at long pulse durations that would characterize the EABR strength-duration function obtained for a particular cochlear implant user. For each function, we calculated a best-fit exponential function of the form y = a/(1 - eebr) where a is the asymptote at long durations and b characterizes the time course of change (van den Honert and Stypulkowski, 1984). The calculated values of EABR chronaxie based on the fitted functions were variable across subjects with a mean of 427 p.s (SD = 235 ps) for the Ineraid users and a mean of 309 ps (SD = 211 ps) for the Nucleus users. Since we have used a limited range of pulse durations, the calculation of chronaxie is particularly sensitive to the variability in threshold measures. Although our estimates of threshold when repeated in the same recording session show relatively little variability (mean difference is 128, based on 24 repeated measures in 13 subjects), the large variability in chronaxie measures are likely due in part to variation in threshold estimate. The measures of strength-duration functions and chronaxie also show some similarity to measures of single neuron responses in animals. There are significant differences in the methodology used to calculate the EABR chronaxie and the true chronaxie measures of single neuron response. The stimulus we have used is biphasic, in some cases bipolar, and the response measure is a far-field potential. Nevertheless, while the values of chronaxie are slightly less than those calculated based on auditory nerve or cochlear nucleus measures (Loeb et al., 1984; Parkins and Columbo, 1987), the EABR strength-duration functions show a similar functional form. To demonstrate the similarities, we have averaged the data from both the Nucleus and Ineraid users and plotted threshold (in dB relative to 0.707 mA) in order to better compare our data with those of Parkins and Columbo (1987). They used biphasic pulse stimulation similar to that used here and made measures with both bipolar and monopolar stimulation. Fig. 7 illustrates the range of values ( + 1 SD) from the single neuron data for both monopolar (solid lines) and bipolar (dashed lines) stimulation. The data from Ineraid users fall within or close to the range for monopolar stimulation. The data from Nucleus users fall well within the range for bipolar stimulation. For both the single unit and the EABR data,
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Fig. 7. Threshold of the FABR response is plotted in dB relative to 0.707 mA as a function of pulse duration. Average data for the 15 Nucleus implant users and for the 8 Ineraid implant users are plotted. Standard deviations are indicated by the error bars. For comparison, the range ( f 1 SD) of single neuron data from Parkins and Columbo (1987) are plotted on the same axis. The dashed lines indicated the range for bipolar stimulation. The solid lines indicate the range for monopolar stimulation.
bipolar stimulation results in consistently higher thresholds but the shape of the functions are quite similar. Shannon (1983) has made measurements of psychophysical threshold with changes in pulsewidth of a biphasic pulse. Two of his subjects showed a decreasing slope of approximately 6 dB/doubling of pulse duration which represents equal charge for each threshold pulse. He also reported data from a subject whose threshold function asymptoted at high pulse durations which would be indicative of an increasing charge at threshold with increasing pulse duration. To better assess this observation in our data, the measurements shown in Fig. 6 are replotted in Fig. 8 as the charge/phase at threshold as a function of pulse duration. The functions are generally flat only at very low pulse durations and for most subjects increase as pulse duration increases. For several subjects, there is little or no change observed over the range of pulse durations used. We should note, however, that the range of pulse
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durations used here (50-400 ps) was much smaller than the range used in the psychophysical measures (up to 8 ms). Columbo and Parkins (1987) plotted their model and single neuron data in a similar way and also report an increasing function with pulse duration. Their measurements were also over a much greater range of pulse duration, and consequently they showed relatively large changes in charge at threshold. In fact, a substantial limitation of the present data is the range of durations used. We were, however, limited in the choice of duration by the software controlling the Nucleus device. Also, in the Ineraid implant, if longer pulse durations were used, the duration of the stimulus artifact also would become longer and could interfere with the measured potential. Finally, since there was variability across subjects with these measures, we were interested in the extent to which these differences were indicative of differences in performance. To do this, we used the calculated values of chronaxie to correlate with the word r~ognition scores. No clear relationship for either group was evident (r = 0.08 for Iowa sentence test; r = 0.12 for NU6). General Discussion Both the refractory measures and the strengthduration were similar to measures in animal subjects and each showed variability across individual subjects. However, neither measure showed any consistent relation to the performance on word
recognition tests. We have observed relatively poor correlation of all measures of the EABR with performance with the implant (Abbas and Brown, 1989), the best correlation being the relationship to EABR threshold. The reason for this lack of correlation may of course be that there is no relation between these neural properties and performance on speech tests. However, we expect that one reason for the relatively poor correlations may be the small amplitude of the potential and the inherently noisy measure of auditory neural activity that is obtained using far-field electrodes. Growth of response and refractory measures which require the measurement of the amplitude of the EABR are particularly susceptible to noise in the estimation of the response amp~tude. In other work (Brown et al., 1989), we have used intracochlear electrodes to overcome this difficulty and record the whole-nerve action potential in response to electrical stimuli (EAP). Measures of dynamic range and recovery from refraction made using the EAP both showed better correlations to performance than do the corresponding EABR measures. Acknowledgements We would like to acknowledge the help of Mary Lowder, Holly Fryauf-Bertschy, Nancy Tye-Murray and Richard Tyler who were responsible for the word recognition data collection. This work was supported by NIH Program Project Grant N520466 and NIH Grant RR59 from the General Clinical Research Centers Program, Division of Research Resources. References Abbas, P.J. and Brown, C.J. (1988) Electrically evoked brainstern potentials in cochlear implant patients with multi-electrode stimulation. Hear. Res., 36, 153-162. Abbas, P.J. and Brown, C.J. (1991) Electrically evoked auditory brainstem response: Growth of response with current level. Hear. Res. 51, 123-138. Brown, C.J., Abbas, P.J. and Gantz, B.J. (1990) Electrically evoked whole-nerve action potentials: I. Data from Ineraid co&ear implant users. J. Acoust. Sot. Am. (ii press). Columbo, 3. and Parkins. C.W. (1987) A model of electrica excitation of the mammalian auditory nerve neuron. Hear. Res., 287-312.
147 Loeb, G.E., White, M.W. and Jenkins, W.M. (1983) Biophysical considerations in the electrical stimulation of the nervous system. Ann. N.Y. Acad. Sci. 405, 123-136. Parkins, C.W. and Columbo, J. (1987) Auditory-nerve singleneuron thresholds to electrical stimulation from Scala tympani electrodes. Hear. Res., 31, 267-286. Shannon, R.V. (1983) Multichannel electrical stimulation of the auditory nerve in man. I. Basic psychophysics. Hear. Res., 11, 157-189. Stypulkowski, P.H. and van den Honert, C. (1984) Physiological properties of the electrically stimulated auditory nerve: 1. Compound action potential recordings. Hear. Res., 14, 205-223.
Tyler, R.S., Preece, J.P. and Lowder, M. (1983) The Iowa Cochlear Implant Test Battery, University of Iowa, Department of Otolaryngology-Head and Neck Surgery, Iowa City. Tyler, RX, Preece, J.P. and Tye-Murray, N. (1986) Iowa Videodisc Tests of Speech Perception and Speechreading, University of Iowa, Department of Otolaryngology-Head and Neck Surgery, Iowa City. van den Honert, C. and Stypulkowski, P.H. (1984) Physiological properties of the electrically stimulated auditory nerve II. Single fiber recordings. Hear. Res. 14, 225-243.
HEARES
139 Division)
0378-5955/91/$03.50
01493
Electrically evoked auditory brainstem response: Refractory properties and strength-duration functions Paul J. Abbas and Carolyn J. Brown * Department
of Speech Pathology and Audiology, (Received
4 August
University of Iowa, Iowa City, Iowa, U.S.A.
1989; accepted
25 July 1990)
The electrically evoked auditory brainstem potential (EABR) was recorded in users of both the Nucleus cochlear implant and the Ineraid co&ear implant. The refractory properties of the EABR were evaluated by measuring the response amplitude to a two-pulse stimulus where the interpulse interval was varied. The threshold of response for a single pulse stimulus was also measured as a function of the duration of the biphasic pulse. These strength-duration functions were then used to calculate an EABR chronaxie measure. Both of these measures showed a similar range for the monopolar stimulation used with the Ineraid implant and the bipolar stimulation used with the Nucleus implant. Neither of these two measures of the temporal response properties showed any clear relationship to the ability of individual subjects to perform on a speech perception task. EABR;
Refraction;
Chronaxie
Introduction In previous work, we have measured the electrically evoked auditory brainstem response (EABR) in cochlear implant patients, investigating both the growth of response with level for different electrode configurations (Abbas and Brown, 1990) and the degree of response interaction for simultaneous stimulation of different channels of a multichannel implant (Abbas and Brown, 1988). Our rationale in the previous studies was that each of these parameters may be important in evaluating the degree to which individual cochlear implant users experience success with the device. In that work, however, we did not measure any of the temporal response properties of the EABR. The ways in which the response changes over time with stimulation, the properties of recovery from previous stimulation, and the relative sensitivity to stimuli of different durations may all provide inCorrespondence to: Paul J. Abbas, Department of Speech Pathology and Audiology, University of Iowa, Iowa City, IA, 52242, U.S.A. * Present address: Department of Speech and Hearing Sciences, Arizona State University, Tempe, Arizona, U.S.A.
formation on how the auditory system will respond to a time changing signal such as speech. Consequently, these properties may be important in determining performance with an implant. Stypulkowski and van den Honert (1984) have proposed that some measure of the refractory properties of the peripheral auditory system may serve as an index to the function of the auditory nerve and thus potentially as a means of determining clinically the utility of an implant to an individual. The rationale behind this suggestion is that because normal frequency resolution is impossible for cochlear implant users, the ability to take advantage of the temporal cues available in the signal might be especially important. Differences across implant subjects in terms of their temporal processing capabilities have been documented in psychophysical work where abnormal patterns of adaptation to a constant stimulus have been reported and where abnormally slow rates of recovery from adaptation have been reported (Shannon, 1983). Stypulkowski and van den Honert (1984) measured the refractory characteristics of the electrically evoked whole-nerve action potential (EAP) and noted differences between animals
140
with normal neurons and those in which there was likely extensive damage to the peripheral dendrites. They suggested that the nonmonotonic recovery functions that they observed in normal and neomycin deafened ears could be due in part to stimulation of the peripheral dendrite in addition to direct stimulation of the axon. We (Brown et al., 1990) have recently reported measurements of the EAP in Ineraid co&ear implant subjects. The refractory functions showed substantial variability across individual users and the time course of recovery demonstrated a good correlation to performance on speech perception tasks. The chronaxie of the strength-duration function of the neuronal response may also be an important measure characterizing the condition of the neurons and their response to temporally changing stimuli (Loeb et al., 1983). Parkins and Columbo (1987) have made measurements of the strength-duration functions in animals (threshold current level as a function of stimulus duration) for biphasic current pulses and have developed a model (Columbo and Parkins, 1987) to simulate properties of nerve stimulation. A critical parameter of the model is the length of the myelinated nerve ending, in that different chronaxie values could be obtained depending upon the length of the dendrite and the degree to which it is stimulable. Since loss of hair cells can result in degeneration of the peripheral dendrites and the myelin sheath, the measurement of strength-duration functions may be another way in which we can assess such differences in individuals who have a cochlear implant. In this study, we have measured both refractory properties and strength-duration functions using the electrically evoked auditory brainstem response (EABR). Subjects include users of both the Ineraid and Nucleus multichannel cochlear implants. Since these same subjects are included in a large protocol of tests as part of the Iowa Cochlear Implant Program Project, we were able to measure the degree to which these measures of temporal response properties correlate with performance on speech perception tasks. Our rationale in using stimulation through the implant is similar to that of the previous study (Abbas and Brown, 1990). Stimulation through the implant provides somewhat of a ‘best case’ in that the stimulating elec-
trodes are within the cochlea and they have been stable in their position for some time. If correlations with performance are observed with implant stimuIation, then more extensive tests with preimplant stimulation may be warranted. Methods Stimulus delivery and recording procedures were the same as those described in the companion paper (Abbas and Brown, 1990). Subjects were drawn from the same pool of implant patients; 13 subjects used the Ineraid implant and 16 subjects used the Nucleus implant. For Nucleus implant users, the stimuli were delivered in a bipolar stimulation mode to electrode pair 10-15. For the Ineraid implant users, the stimuli were delivered to electrode pair 1-8, where electrode 1 is the most apical intracochlear electrode and electrode 8 is an extracochlear electrode that is implanted in the temporalis muscle. Not all subjects participated in both experiments (measurement of refractory properties and measurement of strength-duration functions). In particular, we were selective in choosing subjects for inclusion in experiments in which measures of refractoriness were made. This experiment required that relative response amplitudes be measured in several different stimulus conditions. Subjects whose responses were particularly variable or noisy were not used. In the experiments measuring threshold of EABR response for different pulse durations, single pulses were presented and the recorded potential was averaged to extract the EABR. Stimuli were biphasic square pulses from 50 to 400 ps per phase. For the Ineraid subjects, the initial phase of the biphasic current pulse was alternated in the average in order to reduce the stimulus artifact. At least two averages of IO00 sweeps were measured in each stimulus condition. To make data collection more efficient, the response to individual stimuli were monitored on line. Current levels were chosen to elicit a clear EABR response and then several levels below that were used. Each response trace was subsequently analyzed off-line. The stimulus artifact was removed and the waveform digitally filtered (FIR bandpass filter, 57th order). Response threshold was defined as the lowest current level at which a repeatable response
141
was observed. EABR thresholds were determined for each stimulus duration. In experiments where the refractory properties of the EABR were measured, a stimulus was used that consisted of two biphasic pulses separated in time. We refer to the first pulse as the masker pulse and the second as the probe pulse. The masker and probe pulses are typically presented at the same current level. We measured the response to the probe pulse as a function of the time between probe and masker pulses (or interpulse interval). The stimulus presentation alternates between the condition where both pulses are presented and the condition where a single masker pulse is presented. The averaged response to each stimulus condition is recorded separately. In this way, the response to the masker pulse alone is determined and the response to the probe pulse in the presence of the masker pulse is also measured. Particularly for small interpulse intervals, the EABR to the masker may overlap the response to the probe stimulus. Consequently, we can subtract the averaged waveform recorded in the maskeralone condition from the averaged waveform recorded in the masker-plus-probe condition in order to extract the response to the probe that is recorded in the masker plus probe condition. The subtracted traces were truncated to eliminate the stimulus artifact and then digitally filtered using a 57th order FIR bandpass filter with cutoff values of 150 Hz and 3 kHz. After filtering, the amplitude of the EABR was measured on the subtracted trace. Results and Discussion Experiment
I : Refractory
measures
Fig. 1 illustrates the response to the probe pulse in a series of stimulus presentations designed to assess the time course of recovery from the refractory state. Each trace represents the subtracted (response to the masker-plus-probe subtracted from the response to the masker alone) and filtered response as described above. The masker pulse is always delivered at time zero. The arrow on each trace indicates the time at which the probe pulse is presented. All of the traces shown in Fig. 1 were recorded with both masker and probe pulse cur-
11
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I
I
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;
:
I,
8
9
10
MS Fig. 1. EABR waveforms in response to the second pulse in a two-pulse sequence. The first pulse in all traces is presented at time = 0 ms. The time of presentation of the second pulse is indicated by the triangle below each trace. The initial portion of each trace (past the presentation of the second pulse) is zeroed and then the trace is subjected to digital filtering before being plotted here.
rent levels set to 0.462 mA. For short interpulse intervals (lower traces), the response is depressed. As the interpulse interval is lengthened, the response amplitude recovers. The amplitude of wave V of the EABR was used in subsequent analyses as an indicator of the degree of recovery. Figs. 2A and 2B show the effect of varying the length of the interpulse interval on the amplitude of the EABR for both Nucleus and Ineraid cochlear implant users. For each subject, the amplitude of the EABR is smallest at short interpulse intervals and increases to an asymptotic level as the interpulse interval becomes progressively longer. This asymptotic value approximates the EABR amplitude recorded when the probe stimulus is presented alone. Stimulus levels in the upper part of each subject’s dynamic range were used, so that the actual current level and response amplitude that is measured across subjects is quite
142
variable. This variability is reflected in the differences in asymptotes at long interpulse intervals. The similarities among the recovery functions for different subjects are better illustrated in Figs. 2C and 2D where the amplitude of response is normalized by dividing each response by the amplitude in response recorded when the probe pulse is presented alone. The normalized recovery functions of the 8 subjects with the Nucleus implant are all quite similar. The 12 Ineraid users show slightly more variability in the time course of recovery. If we simply average the normalized amplitude for each interpulse interval across subNucleus 1.0
jects, we can calculate an average recovery curve for subjects with each implant type. These average data are illustrated in Fig. 3. The recovery functions for the two implant types are quite similar. The differences in the recovery functions recorded across subjects may be due to a number of factors. One of these may be related to differences in the level of the stimuli used to record the response. In three subjects, we measured recovery functions for two different current levels (both probe and masker pulse were always the same). An example is illustrated in Fig. 4. When plotted on a normalized scale the time course of recovery
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Fig. 2. Amplitude of the EABR in response to the second pulse in a two-pulse sequence is plotted as a function of interpulse interval or the time between the two pulses. (A) shows recovery functions from 8 Nucleus implant users. (B) shows recovery functions from 12 Ineraid implant users. The current level of the two pulses was always the same and was chosen to be in the upper part of the subject’s dynamic range. (C) shows the same data as part A with amplitude normalized by dividing each point by the response amplitude measured to a single pulse, i.e., the unadapted state. (D) shows the normalized data for the Ineraid users.
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is quite similar. It should be noted, however, that we have observed similar data on only two other subjects and in each case the current levels that we
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O.Oti for Ineraid users and 4.63 ms (SD = 1.59 ms) for Nucleus users. We were interested in the extent to which the differences in the recovery time constant are related to performance with the implant. We used the same measures of speech perception as reported in the previous paper, the Iowa Sentence Test (sound-only) and the Iowa NU-6 word list (Tyler et al., 1983; Tyler
0 Pulse Duration
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Fig. 6. Threshold of EABR response as a function of pulse duration is plotted for 15 Nucleus implant users and 8 lneraid implant users. Pulses are biphasic with equal positive and negative phases.
tract two numbers at long pulse durations that would characterize the EABR strength-duration function obtained for a particular cochlear implant user. For each function, we calculated a best-fit exponential function of the form y = a/(1 - eebr) where a is the asymptote at long durations and b characterizes the time course of change (van den Honert and Stypulkowski, 1984). The calculated values of EABR chronaxie based on the fitted functions were variable across subjects with a mean of 427 p.s (SD = 235 ps) for the Ineraid users and a mean of 309 ps (SD = 211 ps) for the Nucleus users. Since we have used a limited range of pulse durations, the calculation of chronaxie is particularly sensitive to the variability in threshold measures. Although our estimates of threshold when repeated in the same recording session show relatively little variability (mean difference is 128, based on 24 repeated measures in 13 subjects), the large variability in chronaxie measures are likely due in part to variation in threshold estimate. The measures of strength-duration functions and chronaxie also show some similarity to measures of single neuron responses in animals. There are significant differences in the methodology used to calculate the EABR chronaxie and the true chronaxie measures of single neuron response. The stimulus we have used is biphasic, in some cases bipolar, and the response measure is a far-field potential. Nevertheless, while the values of chronaxie are slightly less than those calculated based on auditory nerve or cochlear nucleus measures (Loeb et al., 1984; Parkins and Columbo, 1987), the EABR strength-duration functions show a similar functional form. To demonstrate the similarities, we have averaged the data from both the Nucleus and Ineraid users and plotted threshold (in dB relative to 0.707 mA) in order to better compare our data with those of Parkins and Columbo (1987). They used biphasic pulse stimulation similar to that used here and made measures with both bipolar and monopolar stimulation. Fig. 7 illustrates the range of values ( + 1 SD) from the single neuron data for both monopolar (solid lines) and bipolar (dashed lines) stimulation. The data from Ineraid users fall within or close to the range for monopolar stimulation. The data from Nucleus users fall well within the range for bipolar stimulation. For both the single unit and the EABR data,
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Fig. 7. Threshold of the FABR response is plotted in dB relative to 0.707 mA as a function of pulse duration. Average data for the 15 Nucleus implant users and for the 8 Ineraid implant users are plotted. Standard deviations are indicated by the error bars. For comparison, the range ( f 1 SD) of single neuron data from Parkins and Columbo (1987) are plotted on the same axis. The dashed lines indicated the range for bipolar stimulation. The solid lines indicate the range for monopolar stimulation.
bipolar stimulation results in consistently higher thresholds but the shape of the functions are quite similar. Shannon (1983) has made measurements of psychophysical threshold with changes in pulsewidth of a biphasic pulse. Two of his subjects showed a decreasing slope of approximately 6 dB/doubling of pulse duration which represents equal charge for each threshold pulse. He also reported data from a subject whose threshold function asymptoted at high pulse durations which would be indicative of an increasing charge at threshold with increasing pulse duration. To better assess this observation in our data, the measurements shown in Fig. 6 are replotted in Fig. 8 as the charge/phase at threshold as a function of pulse duration. The functions are generally flat only at very low pulse durations and for most subjects increase as pulse duration increases. For several subjects, there is little or no change observed over the range of pulse durations used. We should note, however, that the range of pulse
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durations used here (50-400 ps) was much smaller than the range used in the psychophysical measures (up to 8 ms). Columbo and Parkins (1987) plotted their model and single neuron data in a similar way and also report an increasing function with pulse duration. Their measurements were also over a much greater range of pulse duration, and consequently they showed relatively large changes in charge at threshold. In fact, a substantial limitation of the present data is the range of durations used. We were, however, limited in the choice of duration by the software controlling the Nucleus device. Also, in the Ineraid implant, if longer pulse durations were used, the duration of the stimulus artifact also would become longer and could interfere with the measured potential. Finally, since there was variability across subjects with these measures, we were interested in the extent to which these differences were indicative of differences in performance. To do this, we used the calculated values of chronaxie to correlate with the word r~ognition scores. No clear relationship for either group was evident (r = 0.08 for Iowa sentence test; r = 0.12 for NU6). General Discussion Both the refractory measures and the strengthduration were similar to measures in animal subjects and each showed variability across individual subjects. However, neither measure showed any consistent relation to the performance on word
recognition tests. We have observed relatively poor correlation of all measures of the EABR with performance with the implant (Abbas and Brown, 1989), the best correlation being the relationship to EABR threshold. The reason for this lack of correlation may of course be that there is no relation between these neural properties and performance on speech tests. However, we expect that one reason for the relatively poor correlations may be the small amplitude of the potential and the inherently noisy measure of auditory neural activity that is obtained using far-field electrodes. Growth of response and refractory measures which require the measurement of the amplitude of the EABR are particularly susceptible to noise in the estimation of the response amp~tude. In other work (Brown et al., 1989), we have used intracochlear electrodes to overcome this difficulty and record the whole-nerve action potential in response to electrical stimuli (EAP). Measures of dynamic range and recovery from refraction made using the EAP both showed better correlations to performance than do the corresponding EABR measures. Acknowledgements We would like to acknowledge the help of Mary Lowder, Holly Fryauf-Bertschy, Nancy Tye-Murray and Richard Tyler who were responsible for the word recognition data collection. This work was supported by NIH Program Project Grant N520466 and NIH Grant RR59 from the General Clinical Research Centers Program, Division of Research Resources. References Abbas, P.J. and Brown, C.J. (1988) Electrically evoked brainstern potentials in cochlear implant patients with multi-electrode stimulation. Hear. Res., 36, 153-162. Abbas, P.J. and Brown, C.J. (1991) Electrically evoked auditory brainstem response: Growth of response with current level. Hear. Res. 51, 123-138. Brown, C.J., Abbas, P.J. and Gantz, B.J. (1990) Electrically evoked whole-nerve action potentials: I. Data from Ineraid co&ear implant users. J. Acoust. Sot. Am. (ii press). Columbo, 3. and Parkins. C.W. (1987) A model of electrica excitation of the mammalian auditory nerve neuron. Hear. Res., 287-312.
147 Loeb, G.E., White, M.W. and Jenkins, W.M. (1983) Biophysical considerations in the electrical stimulation of the nervous system. Ann. N.Y. Acad. Sci. 405, 123-136. Parkins, C.W. and Columbo, J. (1987) Auditory-nerve singleneuron thresholds to electrical stimulation from Scala tympani electrodes. Hear. Res., 31, 267-286. Shannon, R.V. (1983) Multichannel electrical stimulation of the auditory nerve in man. I. Basic psychophysics. Hear. Res., 11, 157-189. Stypulkowski, P.H. and van den Honert, C. (1984) Physiological properties of the electrically stimulated auditory nerve: 1. Compound action potential recordings. Hear. Res., 14, 205-223.
Tyler, R.S., Preece, J.P. and Lowder, M. (1983) The Iowa Cochlear Implant Test Battery, University of Iowa, Department of Otolaryngology-Head and Neck Surgery, Iowa City. Tyler, RX, Preece, J.P. and Tye-Murray, N. (1986) Iowa Videodisc Tests of Speech Perception and Speechreading, University of Iowa, Department of Otolaryngology-Head and Neck Surgery, Iowa City. van den Honert, C. and Stypulkowski, P.H. (1984) Physiological properties of the electrically stimulated auditory nerve II. Single fiber recordings. Hear. Res. 14, 225-243.
