J Am Acad Audiol 2 : 105-114 (1991) Reliability of Evoked Responses to High-Frequency (8-14 kHz) Tone Bursts Stephen A. Fausti,* B. Z. Rappaport,t Richard H. Frey,* James A. Henry,t David S. Phillips,* Curtin R. Mitchell,§ and Deanna J. Olson* Abstract Instrumentation to evaluate the auditory brainstem response to high-frequency ( 8-14 kHz) tone bursts has been developed in the Auditory Research Laboratory, Portland, Oregon VA Medical Center . This system is intended to monitor the audition of patients receiving ototoxic drugs who are unresponsive to behavioral test procedures . The reliability of responses obtained with the high-frequency tone-burst system was studied in 30 normal ears . Intrasubject variability of intersession data from response waves I, III, and V to tone bursts of frequencies 8, 10, 12, and 14 kHz was not significantly different from click response variability. The results of this study demonstrate the reliability of the ABR to these high-frequency tone-burst stimuli. This technique may provide early identification of hearing loss in unresponsive subjects receiving treatment with potentially ototoxic agents, thus allowing alternative treatments to minimize or prevent communicative handicap . Key Words: Auditory brainstem response, high-frequency tone-burst, response reliability, early ototoxicity identification atients administered aminoglycoside antibiotics and cisplatinum are at risk for developing hearing loss due to ototoxicity . It has been documented that such ototoxic loss is initially observed at the highest conventional frequencies tested, eventually progressing into lower frequencies (Fee, 1980). There is no generally accepted definition of what constitutes hearing loss due to ototoxicity . The following operational definition has been adopted by this laboratory : loss of 20 dB or greater at any single frequency ; loss of 10 dB or more at any two consecutively tested frequencies ; or no response at three consecutively tested frequencies where responses were previously recorded . Using behavioral high-fre- P `Director of Auditory Research, Chief of Audiology, Portland Veterans Affairs Medical Center (PVAMC) and Associate Professor, Oregon Health Sciences University, Portland, Oregon tChief, A/SP, New Mexico Regional Federal Medical Center, Albuquerque, New Mexico $PVAMC Auditory Research Lab, Portland, Oregon §Oregon Hearing Research Center, Portland, Oregon Reprint requests : Stephen A . Fausti, Portland VA Medical Center (151J), P .O . Box 1034, Portland, OR 97207 quency pure-tone audiometry (>_ 8 kHz), we have observed ototoxic loss at a rate of approximately 20 percent in a veteran subject sample being administered aminoglycosides (Fausti et al, 1984b), and 60 percent in a sample receiving cisplatinum treatment (Fausti et al, 1984c) . The reliability and validity of the behavioral monitoring technique, however, depend on the active cooperation and attention of the patient. Based on a survey of hospitalized patients at PVAMC, we estimate that 30 to 35 percent of this population are too ill to provide valid behavioral responses . These unresponsive patients are highly susceptible to significant hearing loss because they may be unaware of, or unable to report, ototoxic symptoms . A technique that does not rely on the patient's active participation would be useful in monitoring auditory effects produced by potentially ototoxic agents in unresponsive individuals. The Auditory Brainstem Response (ABR) is one such objective technique. The ABR is a neural, electrophysiologic response that reflects, in part, cochlear function . Asubject with substantially decreased hearing should reveal some differences of ABR threshold, waveform morphology, and/or latency with respect to nor- Journal of the American Academy of Audiology/Volume 2, Number 2, April 1991 mal-hearing individuals . Thus, it is logical to expect that drug-induced changes in hearing can be detected with the ABR technique. The most common stimulus used to elicit the ABR is the unfiltered click. The spectral properties of a click, although broad-band, are shaped by the resonant properties of the earphone and its coupling to the ear, with typical concentration in the 2000 to 4000 Hz region (Mitchell et al, 1989). In 1978, Jerger and Mauldin reported a correlation between ABR threshold and behavioral hearing threshold at 4 kHz . Using unfiltered click stimuli, Bernard et al (1980) reported significant alteration of the ABR wave V latency in aminoglycoside-treated neonates . Also with unfiltered click stimuli, Piek et al (1985) reported latency changes in comatose adult patients receiving aminoglycosides . Frequency-specific stimuli for eliciting the ABR have been suggested by Don and Eggermont (1978), and by Gorga and Worthington (1983) . The rationale for achieving frequency specificity in the ABR evolves from the need to provide a better estimate of hearing sensitivity in difficult-to-test subjects than can be provided by click stimuli. The need for high-frequencyspecific stimuli is to identify significant shifts in high-frequency (8-20 kHz) thresholds produced by ototoxic agents before the speech frequency range is affected . Such early identification can allow the health care provider to examine treatment alternatives which may preserve, or reduce deficit in, communicative abilities. Tone-burst stimuli for frequencies above 8 kHz were not available in commercially produced ABR systems. The Auditory Research Laboratory at the Veterans Affairs Medical Center, Portland, Oregon (PVAMC) developed laboratory instrumentation to provide high-frequency tone-burst stimuli (Portland Auditory Research/Veterans Affairs-Tone Burst [PARVA-TB])(Fausti et al, 1991). Reliable ABRs to click stimuli have been documented over repeated sessions when stimulus, measurement, and subject variables are held constant (Rosenhamer et al, 1978 ; Chiappa et al, 1979 ; Edwards et al, 1982 ; Schwartz and Berry, 1985 ; Lauter and Loomis, 1986). Lower frequency-specific stimuli (<_ 8 kHz) have also been shown to produce reliable ABRs . Gorga et al (1988) reported data for wave Vlatencies using 0.5, 2, and 8 kHz tone-bursts, revealing highly reliable intrasubject wave V latencies. 106 Although it has been demonstrated that high-frequency (>- 8 kHz) tone-bursts are capable of producing measurable responses in normalhearing persons (Fausti et al, 1984a; Rappaport et al, 1985 ; Gorga et al, 1987), response reliability has not been documented for all waves of the ABR to frequency-specific stimuli above 8 kHz. Prior to using the PARVA-TB as a tool for serial monitoring of hearing, it was necessary to document the reliability of intrasubject ABRs to these high-frequency tone-burst stimuli. The purpose of this study, therefore, was to investigate the variability of ABRs to high-frequency (>_ 8 kHz) tone bursts over repeated sessions in a group of normal-hearing subjects . Waves I, III, and V, in response to tone-burst stimuli at frequencies of 8-14 kHz, were evaluated for intrasubject, intra- and intersession peak latency stability. Results were compared to stability of click responses obtained under identical testing conditions . METHOD Subjects Thirty ears from normal-hearing young adults were evaluated (21 ears from 17 females and nine ears from five males) . Subject ages ranged from 19 to 33 years with a mean of 25 .9 years. Acceptance criteria for subjects were based upon no history of ear disease, normal aural immittance results (Wiley et al, 1987 ; Shanks et al, 1988), conventional frequency (0 .25-8 kHz) hearing thresholds no greater than 15 dB HL (re: ANSI, 1989), and high-frequency thresholds no greater than one standard deviation from the mean thresholds reported by Schechter et al (1986) . Instrumentation For all testing conditions, subjects were seated in a reclining chair in an Acoustic Systems 19701A double-walled, R-F shielded, sound-treated booth. Middle-ear function screening was conducted with a Virtual 310 immittance system . Behavioral Behavioral pure-tone air conduction thresholds for conventional frequencies (octave in- High-Frequency Tone-Burst ABR Reliability/Fausti et al tervals from 0.25 to 8 kHz) were obtained with a Grason-Stadler 1701 (G-S 1701) clinical audiometer using Telephonics TDH 49 earphone transducers mounted in MX 41/AR cushions . Hearing in the high-frequency range was assessed on the Portland Auditory Research/Veterans Affairs-High Frequency (PARVA-HF) laboratory audiometer (Fausti et al, 1979 ; Fausti et a1,1990) using matched Koss HV/lA earphone transducers . Pure-tone conventional frequency stimuli from the G-S 1701, presented at a 50 percent duty cycle, were of 200 msec duration with rise-fall times of 50 msec . Pulsed pure-tone high-frequency stimuli, of 300 msec duration and rise-fall times of 25 msec, were also presented at a 50 percent duty cycle with the PARVA-HF . Five-dB steps were utilized in obtaining all threshold results with the clinically accepted, modified Hughson-Westlake ascending-descending audiometric test technique (Carhart and Jerger, 1959). Click stimuli were presented by a Nicolet 1170 evoked-potential signal averager using Telephonics TDH 49 earphone transducers with MX 41/AR cushions mounted in Amplivox circumaural Audiocups. High-frequency toneburst stimuli were generated by the PARVA-TB (Fausti et al, 1991). Tone bursts centered at frequencies of 8, 10, 12, and 14 kHz were gated at zero-crossing with rise times of 0.1 msec (linear between the 10% and 90% on-condition). Duration between zero voltage points was 2.0 msec . Stimulus artifact was reduced by alternating stimulus polarity . Tone-burst stimuli were delivered through Koss HV/lA earphone transducers. An active amplifier/filter network* (Fausti et al, 1979) was utilized to match earphone transducer input impedance, improve the signal-to-noise ratio, lower the sidebands and narrow the bandwidth in order to provide a signal with exceptionally sharp cutoff slopes and low background noise (as described below) . The PARVA-TB was connected to the external From stimulus triggering (electrical onset) to stimulus arrival at the earphone transducer (acoustic onset), a constant time delay will occur from passing the stimulus through a filter . In this network, the delay constant equals 0.27 msec across frequency. Data can be corrected for this time delay. trigger input of the Nicolet 1170 for synchronization with signal averaging. Calibration The acoustic spectra of the tone-burst stimuli (shown in Fausti et al, 1991) were measured with a Hewlett-Packard 3561A Dynamic Signal Analyzer, using a rectangular window (0 - 20 kHz) and peak hold mode . Signal output was measured through the high-frequency transducer (Koss HV/1A) centered on a flat-plate coupler with a Bruel & Kjaer (B&K) 1/2" pressure condenser microphone as reported by Fausti et al (1979) . Although stimuli were not generated by digital methods, the acoustic spectra are comparable to those reported by others (Dolan and Klein, 1987 ; Gorga et al, 1988). The roll-off, the bandwidths measured at 20, 40, and 60 dB down, and the noise floor were all comparable to, or more sharply defined than, reported digitally generated signals. The acoustic output for each click and tone burst was displayed on a Tektronix 7633 digital oscilloscope to determine the peak equivalent SPL. For clicks, a continuous pure tone of 3500 Hz (maximum peak of spectrum) was matched to the maximum scope displacement value (peak-peak) of the waveform . For tonebursts, a continuous pure tone at the frequency of the tone burst was matched in the same manner . A Hewlett-Packard 3400A True RMS Voltmeter, calibrated at 94 dB sound pressure level (SPL) via a B&K 4930 1 kHz microphone calibrator, was then used to determine dB SPL of the continuous pure tone . This value was then assigned as the peak equivalent sound pressure level (peSPL) of the click or tone burst . ABR Testing Procedures Responses were obtained from each subject in two sessions of approximately 60 minutes each . During each session, behavioral thresholds to pulsed pure tones and tone bursts were obtained . Two ABR averages were obtained per session for each of the five stimuli. To prevent an order effect, the stimuli were presented in a counter-balanced, pseudorandom order. Each ABR average was the sum of 1024 stimulus presentations within a response window of 10 .24 msec . Each of the five stimulus conditions 107 Journal of the American Academy of Audiology/Volume 2, Number 2, April 1991 (four high-frequency tone-burst stimuli and clicks) was presented in two separate sessions. Thus, a total of four ABRs was obtained for each stimulus condition. This test format allowed reliability to be determined within a session as well as across sessions. A single-channel differential electrode recording montage was utilized . The electrode to the noninverting amplifier input was placed on the vertex, with electrodes to the inverting and common amplifier inputs at the ipsilateral and contralateral mastoids, respectively . Absolute impedance did not exceed 2 k.Q and the interelectrode impedance differences were at or below 1 kQ . Bioamplifier filter settings were 150 and 1500 Hz . Stimuli were presented at a 60 dB sensation level (SL) with respect to behavioral click and tone-burst threshold, at a rate of 11 .1 per second. A moderate suprathreshold intensity level (60 dB SL) was chosen to increase the likelihood of obtaining all response waves (1,111, and V) . Additionally, as clicks, and 8, 10, 12, and 14 kHz tone bursts, were to be tested on a repeated basis, a single presentation level was selected in the interest of reducing overall testing time . The Koss HV/lA earphone utilized to deliver high-frequency tone-burst stimuli has an interaural attenuation of about 35 dB (Rappaport et al, 1982). Therefore, band-pass masking (7 .5 -25 kHz) was presented contralaterally at an intensity level 30 dB less than the toneburst signal SPL to prevent potential transcranial interference . The reclining chair remained upright for all behavioral measures, and was lowered to full reclining position (45 degrees from horizontal) for all evoked potential measures . Wave identification techniques used with ABR click stimuli (Chiappa et al, 1979 ; Beattie et al, 1986 ; Picton et al, 1988) were employed as a guideline for peak picking with high-frequency tone-burst stimuli. For all stimulus conditions, reliability of high-frequency tone-burst responses for each ABR wave was evaluated using analysis of variance (ANOVA) procedures (Collyer and Enns, 1986). RESULTS igure 1 shows the latencies of each subject's Fresponses for each wave and stimulus condition . Thus, all individual raw data points are displayed, although many points are obscured due to overlapping of symbols. This graphic 108 provides an overall picture of the results of this study in terms of the consistency of intra- and intersubject responses . In each subject, four ABR averages (runs), two in the first session and two in the second, were obtained for each stimulus . The intersubject means of the four runs were compared using a repeated measures ANOVA (Table 1) . No sigTable 1 Mean Intersubject, Intra-run Latencies (in msec)' Stimulus Run 1 Run 2 Run 3 Run 4 8 kHz 10 kHz 1 .96 1 .86 1 .95 1 .89 1 .96 1 .85 1 .98 1 .86 8 kHz Wave III 10 kHz 12 kHz 4 .15 4 .15 4 .09 4.14 4 .19 4.08 4.17 4.10 4.14 4.18 4.12 4.09 6 .04 6 .10 6 .10 6 .10 6 .07 6 .10 6 .09 6 .16 6 .10 6 .08 6 .10 6 .11 6 .07 6 .07 6 .11 6 .13 Wave l 12 kHz 14 kHz 14 kHz Wave V 8 10 12 14 kHz kHz kHz kHz 1 .81 1 .72 4 .02 1 .76 1 .72 4 .04 1 .78 1 .70 4 .07 1 .78 1 .72 4 .06 `Runs 1 and 2 represent ABR trials 1 and 2 within session 1, while runs 3 and 4 represent trials 1 and 2 within session 2; for each stimulus and wave condition, no significant differences were found between means of runs (p > 0 .05) . nificant difference was detected either intra- or intersession for any of the three waves at any of the four tone-burst conditions (p > 0.05) . Reliability of intrasession high-frequency tone-burst responses was demonstrated by calculating intrasubject latency differences between runs with each session. For each subject, the first run within each session was subtracted from the second run resulting in intrasubject, intrasession latency differences . These differences were then summed across subjects to determine mean intrasession differences . Absolute values of the differences reflect magnitude of the mean latency differences, and, as shown in Table 2, are minimal. Actual values of the differences reflect magnitude and direction of the mean latency differences, and are shown in Table 3 . A positive value indicates that, on average, the latencies of the second runs within a session were longer than those of the first runs . Examination of Table 3 indicates no preponderance for the second runs within a session being either longer or shorter than the first runs . High-Frequency Tone-Burst ABR Reliability/Fausti et al Table 2 Mean Intrasubject, Intrasession Latency Differences (in msec) (Absolute Values)' Wave I Clicks 8 kHz 10 kHz 12 kHz 14 kHz Session 1 08 Combined 11 09 08 10 09 08 09 08 09 09 09 06 10 08 Session 2 Wave III Session 1 Session 2 Combined 03 03 03 10 10 10 13 07 10 11 09 10 Wave V Session 1 Session 2 Combined 05 05 05 10 07 08 12 11 11 10 09 09 10 12 10 12 12 12 Differences calculated by subtracting run 1 from run 2 for each subject . Table 3 Mean Intrasubject, Intrasession Latency Differences (in msec) (Actual Values)' Clicks Session 1 Wave I 00 01 01 00 01 00 03 00 Combined Wave V 10 kHz - .02 Session 2 Wave III 8 kHz Session 1 Session 2 Combined 00 00 00 - .01 06 00 04 Session 1 00 Combined 01 02 -.02 Session 2 00 -.08 00 - .04 00 14 kHz 00 02 01 05 01 -.01 - .02 - .01 - .01 07 - .01 00 04 00 03 12 kHz -.02 00 01 00 02 `Differences calculated by subtracting run 1 from run 2 for each subject . Intrasubject intersession reliability was evaluated. For each subject's two identical runs within a session, the mean latency was computed. For the same stimulus and wave, the mean of the first session was subtracted from the mean of the second session. These latency differences were then summed across subjects and analyzed for intersession reliability of latencies. Means of the absolute values of these differences are shown in Table 4. A repeated Table 4 Mean Intrasubject, Intersession Latency Differences (in msec) (Absolute Values)" Wave I Wave 111 Wave V Clicks 8 kHz 10 kHz 12 kHz 14 kHz 13 08 10 12 13 13 12 13 10 11 13 10 11 17 13 `Differences calculated by subtracting session 1 from session 2 for each subject; no significant differences were found between clicks and any tone-burst frequency (p > 0 .05), except for wave III between clicks and 14 kHz (p < 0.05) . measures ANOVA was performed to determine if there were significant differences between clicks and high-frequency tone-bursts when intersession latency differences were compared . No significant differences were found for waves I and V (p < 0.05) . Additionally, no significant differences were found for wave III (p < 0.05) except between clicks and 14 kHz (p < 0.05) . Intersession latency differences were also analyzed to determine if there was a tendency for the second session latencies to be either consistently shorter or longer than those collected during the first sessions . Table 5 shows the actual values of mean intersession differences . Range values of intersession differences are also included in Table 5, which show the extreme individual values of actual differences between sessions . Examination of this table shows no directional preponderance between sessions . Table 6 shows means and standard deviations (± 1) of high-frequency tone-burst latencies across subjects . Mean values for each stimulus condition and wave were calculated by determining intrasession means for each subject, averaging the means of the two ses109 Journal of the American Academy of Audiology/Volume 2, Number 2, April 1991 Table 5 Mean Intrasubject, Intersession Latency Differences (in msec) (Actual Values)' Stimulus Clicks 8 kHz 10 kHz 12 kHz 14 kHz - .04 03 - .02 00 00 (- .38/.28) (- .28/.26) (- .34/.30) (- .26/:28) (- .26/.34) - .03 04 - .05 04 04 (- .22/ .10) (- .22/ .38) (- .36/ .34) (- .26/ .36) (- .36/ .42) 03 04 - .03 02 01 (- .23/ .60) (- .42/ .30) (- .36/ .36) (- .18/ .30) (- .26/ .44) 'Differences calculated by subtracting session 1 from session 2 for each subject . sions, and then collapsing across subjects to determine the means shown in Table 6. Significant differences were found between frequencies (p < 0 .01) for wave I, so StudentNewman-Keuls paired comparisons tests (Collyer and Enns, 1986) were done . Between any two frequencies for wave I, mean latencies were significantly shorter for the higher frequencies (p < 0.01 for each comparison except 12 versus 14 kHz significant at p < 0 . 05) . The same analysis was performed for wave III, revealing significantly longer mean latencies only for 8 and 10 kHz compared to 14 kHz (p < 0.05) . Table 6 Mean Intersubject Latencies (in msec) and Standard Deviations (±1) for High-Frequency Tone Bursts' Stimulus 8 kHz 10 kHz 12 kHz 14 kHz Wave l 1 .95± .16 1 .87 ± .13 1 .78 ± .12 1 .71 ± .12 Wave /// Wave V 4 .16± .21 4 .14 ± .21 6 .07 ± .28 4.09 ± .26 4 .03 ± .24 6 .09± .27 6.10+ .29 6.13 ± .25 `Data for 30 ears collapsed within and between sessions . Figure 1 Raw latency values from 30 ears used in this study. Each point represents a single ABR average from a specific stimulus condition (clicks, 8, 10, 12, and 14 kHz) and wave (waves I, III, and V) . Reliability of responses can be observed in the patterns seen within and between subjects . .out g o ose Wave / S - Session / R = Run W ' O W1 S1 R1 OW1S1R2 AW1S2R1 + W1 S2 R2 O W3 S1 R1 =W3S1R2 ~tr ~r IV "" " l ow E U C Q) ca J o W3 S2 R1 " W3S2R2 wW5S1R1 " W5 S1 R2 o W5 S2 R1 vW5S2R2 'Psome 11 1 1110111411 .1 . me ollonsilin loom .i' ~ = " , " 'xi """" :ot~i~~"e~""."t, "" rrr, " jf P m" I . . r.!. 91 111 Volvo NJ To $3811121 Von // " =I=*, 10 110 15 20 25 30 10 """ 5 Subjects a ls,t 10 15 20 25 30 High-Frequency Tone-Burst ABR Reliability/Fausti et al Figure 2 Cumulated percentage distributions ofabsolute values of latency differences between sessions for each of 30 ears . For each wave and stimulus condition, differences were calculated by finding the intrasession means, and subtracting the mean of session 1 from the mean of session 2. Any given intersession latency difference can be indexed against these normal ears, providing an estimate of the percentage of the population having larger or smaller differences . o Wave I o Wave III e Wave V 14 kHz .6 .4 .2 0 0 mro~ 20 40 60 80 100 0 Percentile 20 There were no significant latency differences between frequencies for wave V. Figure 2 shows cumulated percentage distributions for absolute values of intersession latency differences for each wave and stimulus condition. These graphs provide a method to determine, for any given stimulus condition (click or tone-burst) and any given wave (1, 111, or V), where the magnitudes of an individual's intersession latency differences fall in relation to the group of 30 normal ears . Thus, each intersession difference value can be indexed relative to the normal group in terms of the percentage of subjects having smaller differences, and the percentage having larger differences . Figure 3 is analogous to Figure 2 except that actual values of differences are displayed, allowing further comparison of latency differences when direction of change is taken into account. 40 60 8o 100 DISCUSSION A BR variability has been described primarily in groups of subjects as betweensubject variability (Thornton, 1975 ; Kendall and Lawes, 1978 ; Rosenhamer et al, 1978 ; Sohmer et al, 1978 ; Chiappa et al, 1979 ; Kjaer, 1979 ; Stockard et al, 1979 ; Spreng, 1979 ; Bergholtz, 1981 ; Rosenhamer and Holmkvist, 1982 ; Lauter and Loomis, 1986 ; Gorga et al, 1987 ; Picton et al, 1988). By comparison, only a few studies have reported within-subject variability (Chiappa et al, 1979 ; Edwards et al, 1982 ; Lauter and Loomis, 1986 ; Gorga et al, 1988). The within-subject measures are of two types: within a single session and across sessions. Most studies have used clicks with only a few using tone bursts as stimuli. Journal of the American Academy of Audiology/Volume 2, Number 2, April 1991 Figure 3 Cumulated percentage distributions of actual values of latency differences between sessions for each of 30 ears . Difference values were calculated in the same way as in Figure 2, except that the actual differences were used, resulting in positive and negative values . A negative value indicates that the second session's latency was shorter than the first. Positive values indicate longer latencies during the second session and, depending on degree, may reflect hearing loss . o o W-. Wave III , v Wave V B kHz U C J 60 100 100 Percentile In these studies different measures of variability have been used . The standard deviation is commonly reported while the difference, difference squared, and coefficient of variation are occasionally reported . The clinical use of variability has only occasionally been discussed (Jerger et al, 1985 ; Oken, 1990 ; Sklare, 1990). Since there is no accepted standard of ABR reliability, standard deviations and differences were chosen in this study to best describe reliability . In this investigation, the intrasubject reliability of auditory brainstem responses to high-frequency tone bursts was evaluated using clicks as the standard . Results indicated clinically acceptable reliability of intra- and intersession ABRs to high-frequency tone bursts when compared to clicks (see Tables 2-5) . Intrasubject, intersession variability of high-frequency tone bursts was not significantly different from variability of click stimuli. Reliability was demonstrated for waves I, III, and V using 8, 10, 12, and 14 kHz tone bursts . There are two (progressive) effects that may be seen in Table 6. First, variability (stand112 and deviation) increases from wave I to wave V for all stimuli used . This progressive increase in the standard deviation from waves I through V was also found by Lauter and Loomis (1986) and Fausti et al (1991) . Second, latencies changed as a function of frequency for some waves. That is, latency decreased as frequency increased for wave I. The same effect occurred for wave III, but to a lesser degree, while no effect was seen for wave V. These results replicate and extend similar findings in a previous study of rise time (Fausti et al, 1991). The measures of variability shown in Tables 4 and 6 might, at first, appear to be contradictory . Waves I and V show similar variability in Table 4, as demonstrated by intersession mean latency differences . Wave I shows less variability than wave V in Table 6, as demonstrated by standard deviations. Table 4 reflects the variability within subjects while Table 6 describes the variability between subjects. Because the standard deviations in Table 6 are calculated across subjects, the progressive increase in the standard deviation is probably due to an increase in the intersubject variability High-Frequency Tone-Burst ABR Reliability/Fausti et al of higher auditory pathways . However, in contrast to these individual differences, Table 4 demonstrates no increase in variability within subjects as the evoked activity progresses from the cochlea through the brainstem. In serial monitoring of patients receiving ototoxic agents, intersession change, or evidence of hearing loss, is based upon each subject's own response variability . That is, each subject serves as his/her own control. Occasionally, however, subjects cannot produce stable baselines. Subjects demonstrating elevated intrasubject variability may not be good candidates for this method of testing. The majority of subjects, however, produce a tight pattern of responses, and, with these subjects, this method can be expected to perform as an effective monitoring tool . Figures 2 and 3 present cumulated percentages of subjects versus absolute values of differences and actual differences, respectively, in latency between sessions . For a given wave and stimulus, one can determine what percentage of the difference scores were greater than or less than a given value. The intrasubject, intersession latency differences are similar for waves I, 111, and V (Tables 4 and 5 and Figs . 2 and 3), and similar criteria could be used to detect a change in latency for each wave . On the basis of the cumulative percent data in Figures 2 and 3 it is possible to determine the false-positive rate for a chosen criterion. Figure 2 could be used for any change, i.e ., latency delay or advance between sessions . Figure 3 would be more useful for detecting ototoxic change, where the relevant change would be a delayed latency relative to the initial (or baseline) session, resulting in a positive difference value. For example, if, during a later testing session, a subject's latency is 0.2 msec longer than the baseline session, the intersession difference of 0.2 msec would be compared to the normal group (see Fig. 3) . If a delay of 0.2 msec for wave I, for the 8 kHz tone burst, is chosen as the criterion, the expected falsepositive rate would be about 15 percent. Any difference of 0.2 msec or greater would indicate change had taken place at the 85 percent confidence level. If a delay of 0.3 msec is chosen, the expected false-positive rate would be about 9 percent, resulting in a 91 percent confidence level. Our results, thus far, demonstrate that high-frequency-specific tone bursts can be used to evoke ABRs in order to assess high-frequency auditory function objectively . 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