advantages and caveats when recording steady-state responses

J Am Acad Audiol 13 : 246-259 (2002)

Advantages and Caveats When Recording Steady-State Responses to Multiple Simultaneous Stimuli M. Sasha John* David W. Purcell* Andrew Dimitrijevic* Terence W. Picton*

Abstract

This article considers the efficiency of evoked potential audiometry using steady-state responses evoked by multiple simultaneous stimuli with carrier frequencies at 500, 1000, 2000, and 4000 Hz . The general principles of signal-to-noise enhancement through averaging provide a basis for deter-mining the time required to estimate thresholds . The advantage of the multiple-stimulus technique over a single-stimulus approach is less than the ratio of the number of stimuli presented . When testing two ears simultaneously, the advantage is typically that the multiple-stimulus technique is two to three times faster. One factor that increases the time of the multiple-response recording is the relatively small size of responses at 500 and 4000 Hz . Increasing the intensities of the 500-and 4000-Hz stimuli by 10 or 20 dB can enhance their responses without significantly changing the other responses . Using multiple simultaneous stimuli causes small changes in the responses compared with when the responses are evoked by single stimuli . The clearest of these interac-tions is the attenuation of the responses to low-frequency stimuli in the presence of higher-frequency stimuli . Although these interactions are interesting physiologically, their small size means that they do not lessen the advantages of the multiple-stimulus approach .

Key Words: Auditory evoked potentials, masking, MASTER, objective audiometry, steady-state responses

Abbreviations : MASTER = multiple auditory steady-state response ; MINT = multiple-intensity (technique)

Sumario

Este art(culo evalua la eficiencia de la audiometria de potenciales evocados utilizando respue-stas de estado-estable evocadas por estimulos multiples simultaneos, con frecuencias portadoras de 500, 1000, 2000, y 4000 Hz . Los principios generales de reforzamiento de la relacion sepal/ruido por medio de la promediacion aportan la base para determinar el tiempo requerido para estimar umbrales . La ventaja de la tecnica de estimulos multiples sobre el enfoque de estimulo 6nico es menor que la tasa del numero de estimulos presentados . Cuando se evaluan dos oidos simultanea-mente, la ventaja es tfpicamente que la tecnica de estrmulos multiples es dos o tres veces mas rapida . Un factor que incrementa el tiempo de registro de las respuestas multiples es el relativa-mente pequeno tamano de las respuestas a 500 y 4000 Hz . Incrementando en 10 6 20 dB las intensidades de los estimulos a 500 y 4000 Hz puede aumentar esas respuestas, sin modificar significativamente las otras . El use de estimulos multiples simultaneos causa pequenos cambios en las respuestas, comparado con las respuestas evocadas por estimulo 6nico . La mas clara de estas interacciones es la atenuacion de las respuestas ante estrmulos de baja frecuencia, en pre-sencia de estrmulos de alta frecuencia . Aunque estas interacciones son fisiologicamente interesantes, su pequeno tamano implica que ellas no reducen las ventajas del enfoque de estrmulos multiples .

Palabras Clave : Potenciales evocados auditivos, enmascaramiento, MASTER, audiometria objetiva, respuestas de estado-estable

Abreviaturas : MASTER = respuesta auditiva multiple de estado-estable ; MINT = tecnica de intensidad multiple

*Rotman Research Institute, Baycrest Centre for Geriatric Care, University of Toronto, Toronto, Ontario Reprint requests : M . Sasha John, Rotman Research Institute, Baycrest Centre for Geriatric Care, 3560 Bathurst Street,

Toronto, ON M6A 2E1 ; e-mail : sasha@psych .utoronto .ca

246

W hen multiple auditory stimuli are presented simultaneously at suprathreshold intensities, separate

steady-state evoked potentials can be recog-nized for each stimulus, provided that each stim-ulus is modulated at a frequency different from the others . If the recordings are evaluated in the frequency domain, each response shows up at its "signature" modulation frequency (Lins and Pic-ton, 1995) . Recording auditory steady-state responses to multiple simultaneous stimuli is an attractive approach to objective audiometry because multiple responses can be detected in the time normally required to identify a single response .

Provided that the modulation frequencies are more than 70 Hz, that the intensity is 60 dB SPL or less, and that stimuli are presented sep-arately to the two ears or separated by at least an octave in frequency within the same ear, the responses recorded with the multiple-stimulus technique are not significantly smaller than those recorded when the stimuli are presented singly (John et al, 1998) . Presenting four stim-uli with carrier frequencies of 500, 1000, 2000, and 4000 Hz to each ear (for a total of eight stimuli) should therefore bring about an eight-fold increase in the speed of a hearing test . The goal of this article is to discuss why this may not occur in actual practice and to consider several methods of decreasing the time required for objective audiometry.

Several factors must be considered when determining whether a testing session using multiple simultaneous stimuli is more efficient than multiple single-stimulus sessions . This article will discuss these various issues in rela-tion to data reported previously in the literature and will describe the results of some simple experiments conducted to address some of these issues and increase the efficiency of the multiple-stimulus technique.

BACKGROUND ELECTRICAL NOISE IN THE RECORDING

T he electrical noise in the recording derives from the brain; from the muscles of the

scalp, face, and neck ; and from the amplifier. The background electrical noise can be quantified in many ways . One can measure either its power or its amplitude, and one can make these mea-surements in the time domain or the frequency domain . Our approach is to transform averaged time domain data into the frequency domain and then measure the root mean square ampli-

Advantages and Caveats of MASTER/John et al

tude of the activity in the spectrum at frequen-cies adjacent to the frequencies at which the steady-state responses are measured. Since our typical data windows or "sweeps" last 16.384 sec-onds, the resulting amplitude spectrum has a fre-quency resolution of 0.061 Hz . We compare the amplitude of each steady-state response to the amplitudes in 120 adjacent frequencies (60 above and 60 below the modulation frequency of the stimulus, equivalent to ± 3.7 Hz) .

In relation to the steady-state responses, this background activity (quantified in the 120-bin noise estimate) can be considered as random noise. If several sweeps are averaged together, the amplitude of the background noise attenuates with averaging according to the square root of the number of sweeps averaged . The time taken to reach a required signal-to-noise ratio is

T = S(BR/A)2 (Equation 1)

where S is the sweep duration, A is the ampli-tude of the response, B is the amplitude of the background activity in a single sweep, and R is the signal-to-noise ratio (in terms of amplitude) required to conclude that a response is signifi-cantly different from the background noise . This equation assumes that, during the averaging procedure, the amplitude of the response and the amplitude distribution of the noise both remain constant . We have provided empirical evidence that this is generally true (John and Picton, 2000a) . The equation demonstrates that doubling the amplitude of the background noise (B) will increase the required averaging time by 4 ; dou-bling the amplitude of the response (A) will decrease the time by 4 .

The amplitude of the background electrical activity decreases with increasing frequency. Since most multiple-stimulus paradigms use modulation frequencies that are close together, the background noise levels for these paradigms can be considered as relatively uniform across the range of modulation frequencies . Figure 1 illustrates some noise measurements from the frequency domain . These data are taken from experiments reported in John and Picton (2000a) . The left graph of the figure shows a small decrease in noise amplitude with increasing fre-quency. The right graph shows that the noise amplitudes decrease over time (as sweeps are averaged together) according to a square root rule .

The noise should be the same regardless if one stimulus or more than one stimulus is being

247

Journal of the American Academy of Audiology/Volume 13, Number 5, May 2002

m N=1 A N=4 v N=12 O actual data - " 1/-~_N_ Model

Figure 1 Residual background noise. This figure presents a re-evaluation of some data already published (John and

Picton, 2000a) . On the left, the root mean square noise levels are plotted as a function of frequency over the range at

which the steady-state responses were recorded . Each data point combines noise data over ± 3.7 Hz from the plotted

frequency (the modulation frequency of the stimulus) . There is a small decrease in the amplitude of the noise with increas-

ing frequency. In addition, the noise decreases as the number (N) of sweeps averaged increases. This is further evalu-

ated in the right graph, which combines data across all of the frequencies measured in the left graph and then follows

the averaged noise level as N increases. The large circles represent the actual data (averaged over 10 subjects) and the

small dots represent the theoretical decrease according to a VVYrule.

tested during an experiment. In a recent exper-iment, we evaluated the evoked potentials to multiple tone pairs. The amplitude spectra of these stimuli contain only two frequencies rather than having a carrier with two side-bands, as in the case of a sinusoidally ampli-tude-modulated carrier. However, the evoked responses to tone pairs are similar to those pro-duced by amplitude-modulated tones (Dolphin et al, 1994), and, for the issues addressed here, these two types of stimuli can be considered identical. Each tone pair produced a beating stimulus with a repetition rate that was equal to the difference between the tones. We exam-ined responses to these beating stimuli at dif-ferent beat frequencies (82, 84, and 88 Hz or 178, 180, and 183 Hz), at different response ranges (near 85 Hz or near 180 Hz), and under single-stimulus or multiple-stimulus conditions . We shall discuss the responses data from this exper-iment in a subsequent section of this article and only consider the noise levels here . The noise lev-els were significantly greater in the 85-Hz range compared with the 180-Hz range (F = 410.3, df = 1, 9, p < .001). Within these ranges, there

50

40

30

20

10 -

80 85 90 95 100 0 2 4 6 8 10 12

Modulation Frequency (Hz) Sweep Number (N)

75 0

was a small effect of the beat frequency with smaller noise levels at higher beat frequencies (F = 6.1, df = 2, 18, p < .05) . There were no sig-nificant differences in the noise levels between the single and multiple conditions (F = .2, df = 1, 9, p = .63) .

The results reviewed in this section indicate several characteristics of the background elec-trical noise in which the auditory steady-state responses are recorded . The noise decreases reg-ularly according to the square root of the num-ber of trials averaged, decreases slightly with increasing frequency, and does not change sig-nificantly when the number of simultaneous stimuli is increased.

AMPLITUDE OF THE RESPONSE

A nother factor that affects the testing time for multiple-stimulus technique concerns any changes in the amplitude of the responses when using multiple rather than single stimuli. When there is no change in the background noise, the multiple-stimulus technique remains more efficient if the decrease in the size of the

248


response in the multiple-stimulus condition is less than where M is the number of stim-uli (John et al, 1998). As a specific example, when presenting four stimuli together in a sin-gle ear, the multiple-stimulus technique is more efficient as long as the amplitudes of the responses do not decrease to less than half of their amplitude when the stimuli are presented singly. John and colleagues (1998) used this principle to evaluate the use of multiple simul-taneous stimuli at different modulation fre-quencies, at different intensities, and at different separations between the carrier frequencies of the stimuli. In no case was it less efficient to record responses to multiple stimuli simulta-neously. The amplitudes could be sufficiently reduced so that there was no significant differ-ence between the multiple- and single-stimulus techniques at modulation rates of 30 to 50 Hz, at an intensity of 75 dB SPL or when the car-rier frequencies were separated by less than an octave . For example (John et al, 1998, Table 3), at 75 dB SPL, the amplitudes recorded when four stimuli were presented were reduced to 56 percent and 49 percent of what they were in the single-stimulus condition. This approximately equals the 50 percent obtained from 1/when M = 4.

These findings indicate that, under certain circumstances, the amplitude of the responses

500 1000 2000 4000

Carrier Frequency (Hz)

may decrease when the number of simultaneous stimuli is increased. However, even when this occurs, this decrease does not overcome the increased efficiency of the multiple-stimulus technique. As long as certain caveats are respected, in many conditions there is little change in the response amplitude in the multiple-stimulus condition compared with the single-stimulus condition.

EFFECTS OF CARRIER FREQUENCY

0 ur discussion so far has assumed that all of the multiple simultaneous stimuli evoke

responses of similar size . However, in practice, this is not true . Responses to carrier frequencies between 1000 and 3000 Hz are generally larger than those outside this range (John et al, 2001, 2002). Figure 2 illustrates results from several studies.

This difference in amplitude across carrier frequency causes some responses to become sig-nificant before others . This increases the time needed when using the multiple-stimulus tech-nique to assess thresholds . Although it is always certain that more data will be collected using the multiple- rather than the single-stimulus tech-nique, the testing time will be prolonged if the recording period has to be extended so that the

" MM, 30 dB HL, BC (Dimitrijevic et at, 2002)

O AM, 60 dB SPL, D (Herdman and Stapells, 2001)

m MM, 20 dB SL (Dimitrijevic et al, 2002)

13 MM, 40 dB SPL (John et al, 2001)

A AM, 40 dB SPL (John et a1, 2001)

A AM 2, 30 dB pSPL (John et al, 2002)

Figure 2 Carrier frequency. This figure plots the amplitudes of responses recorded using the multiple-stimulus tech-nique at each of the audiometric frequencies 500, 1000, 2000, and 4000 Hz in several studies. All responses are for air-conducted sounds except the Dimitrijevic and colleagues bone-conduction (BC) responses. The B responses are relatively large because both cochleae are activated by each stimulus . The Herdman and Stapells data are from their dichotic (D) condition (four stimuli in each ear) . The mixed-modulation (MM) stimuli from the Dimitrijevic and colleagues' and John and colleagues' studies combined 100 percent amplitude modulation (AM) with 25 percent frequency modulation . The AM2 stimuli used in the John and colleagues (2002) study were modulated using an exponential envelope .

249


smallest of the multiple responses becomes sig-nificantly larger than noise. For example, when stimuli with carrier frequencies of 500, 1000, 2000, and 4000 Hz are presented singly at 20 dB SL, the time required to detect each response will vary. To obtain typical times, we can sub-stitute values in equation 1 from our studies of subjects with sensorineural hearing loss (Dim-itrijevic et al, 2002). The amplitudes (A) of the responses at 20 dB SL are, on average, 29, 46, 45, and 37 nV (plotted in Fig. 2) . The back-ground noise level of a single unaveraged sweep (B) in these studies is approximately 80 nV (data not shown). This is almost twice as high as that obtained in the sleeping normal sub-jects studied in the experiments that provide the data for Figure 1. Many of the hearing-impaired subjects were older volunteers who tended to be less able to sleep for the entire recording period, and, accordingly, their muscle activity was higher. The minimum signal-to-noise ratio (S) that allows us to state that the response is sta-tistically different from noise is 1.7, which is the square root of F at p = .05 with degrees of free-dom 2 and 240. For the purposes of this illus-tration, we shall make S equal to 2. Given a sweep of 0.27 minutes (16.384 seconds), the times required to detect the responses are 8.4, 3 .4, 3 .5, and 5.1 minutes. The testing time for the single-stimulus technique is the sum of these times - 20.4 minutes. The testing time for the multiple-stimulus technique is the maximum of these times - 8.4 minutes. Rather than being 4 times as fast as the single-stimulus technique, the multiple-stimulus technique is only 2 .43 times as fast . If one stimulus evokes a response that is much smaller than all of the others, the recording time for the multiple-stimulus tech-nique will approach (but never reach) that for the single-stimulus technique

These results demonstrate that the effi-ciency of the multiple-stimulus technique can be decreased if the amplitudes of the different responses are not equal. This attenuation can-not render the multiple-stimulus technique less efficient than the single-stimulus technique.

SLOPING AUDIOGRAMS

A n issue that arises when performing thresh-old evaluations is that it takes longer to

determine that a response is absent than it does to recognize that a response is present (signifi-cantly different than the background noise lev-

els) . The decision that a response is not present

usually requires that the response is not recog-nizably different from the background noise after this noise has been reduced to a criterion level. The time (T) required to reach this crite-rion noise level is

T = S(B/N)z (Equation 2)

where S is the sweep time, B is the single-sweep noise level, and N is the noise level at criterion. Using the values from the Dimitrijevic and col-leagues' (2002) study (B = 80 nV and S = 0.27 minutes) and a criterion (N) of 10-nV noise would predict a total test time of 17.5 minutes. Using a testing period of 17.5 minutes would allow the detection of a 17-nV response using the F test at the p = .05 level of significance .

If the subject has a sloping audiogram, there are several intensities at which an inves-tigator must decide that at least one response is absent . Recordings at these intensities need to be continued until the criterion noise level is reached (rather than until the other responses are recognized). Let us work through an exam-ple in which a subject has hearing thresholds of 30, 40, 50, and 60 dB HL at frequencies of 500, 1000, 2000, and 4000 Hz, respectively. We shall begin the recording at 70 dB HL and work down in 10-dB steps for both multiple- and single-stimulus recordings . We shall arbitrarily set the threshold levels for the steady-state responses at 10 dB above the hearing thresh-olds . Table 1 shows the times that would be required to measure the thresholds for the steady-state responses. These were predicted on the basis of typical response amplitudes and background noise levels from the study of Dim-itrijevic and colleagues (2002) . The total time to measure thresholds using the single-stimulus technique was 137.6 minutes compared with 83.5 minutes for the multiple-stimulus tech-nique. The multiple-stimulus technique is only 1.65 times as fast . If both ears were evaluated simultaneously and if the thresholds in the two ears were similar, then the multiple-stimulus technique would be 3.3 times as fast . If there were an asymmetry in the ranges of the thresh-olds between the two ears, the improvement in speed would be less than 3.3 .

Deciding that a response is absent requires a longer time than deciding that a response is present. This may attenuate but not completely remove the advantage of the multiple-stimulus technique, particularly when the subject has a sloping audiogram.


Table l T

Sin

hreshold Testi

gle-Stimulus Tech

ng in a

nique

Subject with a Sloping Audiogr

Multiple-

am

Stimuli Technique

Intensity 50 0 Hz 100 0 Hz 200 0 Hz 4000 Hz Simult aneous Stimuli

(dB HL) R T R T R T R T R R R R T 70 + 4 .8 + 3.2 + 3 .5 + 13 .6 + + + + 13 .6 60 + 6.3 + 3.4 + 5 .7 - 17 .5 + + + - 17 .5 50 + 8.44 + 6 .0 - 17 .5 0 + + - - 17.5 40 + 12.9 - 17 .5 0 0 + - - - 17 .5 30 - 17 .5 0 0 0 - - - - 17 .5

R = whether a response was recognized (+), not recognized (-), or not recorded (0) ; T = time taken in minutes to detect response or decide that it was absent

The time taken for the multiple-stimuli recording (rightmost column) is equal to the longest time for any individual stimulus .

MULTIPLE-INTENSITY (MINT) TECHNIQUE

0 ne way to compensate for problems incurred when multiple stimuli evoke responses of

different sizes is to present stimuli with differ-ent intensities at different carrier frequencies. The intensities of the stimuli evoking the smaller responses can be increased so that the magni-tudes of all of the individual responses being recorded are more or less the same. For sim-plicity, we shall refer to this approach as the MINT or multiple-intensity technique.

An obvious concern about this technique is that the tones presented at higher intensities might mask those presented at lower intensities . We therefore examined the advantages of adjust-ing individual stimuli, within the multiple stim-uli, to different intensities and investigated if any masking effects occurred for the stimuli pre-sented at lower intensities . We used four stim-uli in one ear (at carrier frequencies of 500, 1000, 2000, and 4000 Hz) in conditions wherein all stimuli were of equal intensity or wherein the 500-Hz and the 4000-Hz stimuli were either 10 or 20 dB more intense than the other stimuli

(Table 2) . The stimuli were sinusoidally amplitude-modulated tones with the depth of modulation at 100 percent and modulation fre-quencies as described in Table 2. The conditions of this study contained two experiments: one examined a 10-dB enhancement at several inten-sities (conditions 1-6) and another investigated a 20-dB enhancement at the highest intensity (conditions 1 and 7-9).

Steady-state responses were recorded in 10 subjects with normal hearing using the multi-ple auditory steady-state response (MASTER) data collection system (John and Picton, 2000a; www.hearing.cjb .net) . The system performed digital-to-analog conversion of the stimulus wave-forms at 32 kHz and routed them to a Grason Stadler Model 16 audiometer, where they were amplified to a calibration intensity, attenuated to achieve the desired intensity levels, and pre-sented using Etymotic-2A insert earphones .

Mixing stimuli of different intensities is more easily performed using analog circuity than within the digital-to-analog converter since the resolution of the converter can cause the representation of the stimuli of lower intensity to be less accurate . Stimuli of different intensi-

Table 2 Experimental Conditions to Evaluate MINT Protocols

ondition

Recording Duration (min)

f = 500 f = 80 Hz

Stimulus

f = 1000 f = 85 Hz

Intensity (dB SPL)

f = 2000 f = 90 Hz

f = 4000 f = 95 Hz

1 5 .4 50 50 50 50 2 5 .4 60 50 50 60 3 12 .6 40 40 40 40 4 12 .6 50 40 40 50 5 19 .6 30 30 30 30 6 19 .6 40 30 30 40 7 5 .4 70 50 50 70 8 5.4 70 50 50 50 9 5 .4 50 50 50 70


ties were therefore created in separate digital-to-analog channels. For example, in condition 2, the 500- and 4000-Hz stimuli were created and routed to the tape A input of the audiometer, where they were amplified to 60 dB SPL, and the 1000- and 2000-Hz stimuli were sent to the tape B input, where they were amplified to 50 dB SPL. Both tape A and tape B were then routed to the left ear insert, which caused an analog addi-tion of the signals prior to acoustic transduction .

The electroencephalographic (EEG) data were obtained from an electrode placed at Cz, using a posterior midline neck electrode as ref-erence and an electrode on the clavicle as ground . The EEG was obtained using a Grass P55 pre-amplifier with a gain of 10,000, a low-pass set-ting of 300 Hz, and a high-pass filter setting of 0.3 Hz. The recorded EEG data were again ampli-fied with a gain of 5 by the analog/digital board and then analog-digital converted at 1000 Hz. During data collection, the data were submitted to an online weighted averaging procedure to reduce the effects of spurious bursts of unwanted noise, which occurred in our data (John et al, 2001).

Because the signal-to-noise ratio is better at higher stimulus intensities, less time is needed for responses to reach significance . At 50 dB SPL or higher, several of the eight stimuli will reach significance within the first minute of testing, whereas, in most subjects, about 6 min-utes may be required for all eight stimuli to reach significance . At near-threshold intensi-ties, up to 20 minutes may be required to obtain significant responses for all eight stimuli. Accord-ingly, we used increased durations for condi-tions for which stimuli were presented at lower intensities (see Table 2) . The order in which the conditions were recorded was randomized across subjects . For the responses collected when the stimuli had equal intensity at 50, 40, or 30 dB SPL (conditions 1, 3, and 5), the number of sig-nificant responses was 38, 37, and 33 out of 40, indicating that the test durations were adequate .

Figure 3 shows representative data from a single subject and Figure 4 shows the average amplitudes of the responses across all 10 subjects . We decided to evaluate the 500- and 4000-Hz responses separately from the 1000- and 2000-Hz responses since the experimental manipula-tion affected them differently (a change in intensity of the stimulus or the effect of that on other stimuli) . For the 500- and 4000-Hz responses, a repeated measures analysis of vari-ance (ANOVA) (3 intensities x 2 stimulus types x

2 carrier frequencies) indicated significant main

effects for intensity (F = 44.5, df = 2, 18, p < .001) since amplitude increased as intensity increased from 30 to 50 dB SPL, for stimulus type (F = 34.4, df = 1, 9, p < .001) since the MINT stimuli pro-duced larger responses than equal intensity stim-uli, and for carrier frequency (F = 10.6, df = 1, 9, p < .01) since the 500-Hz response was signifi-cantly bigger than the 4000-Hz response . There was a significant interaction between intensity level and carrier frequency (F = 10.4, df = 2, 18, p < .01) because the 500-Hz responses grew more rapidly with increasing intensity than the responses at other frequencies.

A second ANOVA performed using the ampli-tudes of the 1000- and 2000-Hz stimuli showed a main effect of intensity (F = 49.5, df = 2, 18, p < .001) but no effect of stimulus type (F = 0.6, df = 1, 9, p = .45) . There was also a significant interaction between stimulus type and carrier frequency, to which we shall return later.

The main findings clearly indicated that the responses to the 500- and 4000-Hz stimuli can be increased in amplitude by raising the inten-sity of these stimuli. This increase in amplitude occurs without any general effect on the responses to the other stimuli. The second experiment using stimuli that were 20 dB rather than 10 dB more intense showed similar results, with the more intense stimuli evoking larger responses, also without significantly affecting the responses to the other stimuli (Fig . 5).

In general, the use of the MASTER tech-nique provides a rapid method for collecting auditory steady-state response data because multiple stimuli are tested in the time normally required to test a single stimulus . The tech-nique becomes less efficient if one of the responses being evaluated is considerably smaller than the other stimuli and is charac-terized by an amplitude that is near noise lev-els. In the results presented here, the 4000-Hz response shows a smaller response at all three intensity levels in the equal-intensity condi-tions. In actual practice, this unequal ampli-tude would cause the MASTER technique to become considerably less efficient . The MINT condition more than compensated for this pos-sibility by using +10-dB relative intensity, sug-gesting that as little as +5 dB could be used to make the size of the 4000-Hz response equiva-lent to the others .

The 500-Hz responses in the equal-inten-sity 50 dB SPL and 40 dB SPL conditions were generally larger, rather than smaller, than the responses to the 1000- and 2000-Hz carriers (see Fig. 4) . This is unlike previously reported data

252


f~ fm

500 80

1000 85

2000 90

4000 95

40 dB SPL

Equal Intensity

30 dB SPL

MINT with 500 and 4000 Hz 10 dB more intense

V V

20 nV

0

70 80 90 100 110 70 80 90 100 110

Modulation Frequency (Hz)

Figure 3 Multiple-intensity stimuli: single subject. This figure plots in the frequency domain responses recorded from a single subject for the multiple-intensity technique. The carrier frequencies (f) and modulation frequencies (f) for the stimuli are shown in the upper left of the figure . The responses show up at the stimulus modulation frequencies as lines that are higher than the background noise levels at adjacent frequencies . Filled triangles indicate responses that are significantly different from the noise at p < .05 and open triangles indicate responses that cannot be distinguished from the background noise. The graphs on the left show response amplitudes in the equal-intensity condition. The responses are smaller for the 500- and 4000-Hz responses than for the 2000-Hz responses. The graphs on the right show how the response amplitudes increase when the 500- and 4000-Hz stimuli are increased in amplitude by 10 dB (MINT condi-tion). The noise levels at 30 dB SPL are lower than at 40 dB SPL since more trials were averaged (see Table 2) .

from the literature (Fig . 2) and might be related to interindividual variability in the response amplitudes . The single-subject data shown in Figure 3 contain amplitudes that more closely follow the expected distribution of response amplitudes for the four frequencies examined .

In general, the 500-Hz response is often dif-ficult to detect at lower intensity levels (Aoyagi et al, 1994 ; Rance et al, 1995 ; Lins et al, 1996 ; Perez-Abalo et al, 2001 ; Dimitrijevic et al, 2002). Several factors might contribute to the small size of this response . The activation pattern of the 500-Hz stimulus on the basilar membrane spans a broader area than the activation patterns of stimuli with higher frequency, and this area is in a region where the traveling wave is slowing down . Latency jitter between responses gener-ated through different parts of the activated basilar membrane may therefore decrease the size of the compound response . Lins and col-leagues (1996) also suggested that recording

the 500-Hz response could be difficult owing to the masking effect of ambient background noise at the lower frequencies . Alternatively, higher frequen-cies within the set of simultaneous stimulus might mask the response to the 500-Hz carrier. However, as pointed out by Perez-Abalo and coleagues (2001), similar difficulties in the estimation of low-frequency thresholds have been reported for single-stimulus techniques (e.g ., Aoyagi et al, 1994), suggesting that masking is unlikely.

The 4000-Hz response was the smallest at all three intensity levels in the equal-intensity condition. The relatively small size of these responses is likely not owing to masking since both this study and previous studies (Dolphin, 1997) have shown that lower frequencies tend to enhance, rather than suppress, responses to higher-frequency stimuli. Part of the decreased amplitude is owing to the higher hearing level threshold at this frequency compared with 1000 Hz, but the small size persists when the

253


50 dB SPL 40 dB SPL 30 dB SPL 80 ,

60

40

20

0

500 1000 2000 4000 500 1000 2000 4000 500 1000 2000 4000


O 500- and 4000-Hz stimuli 10 dB more intense

0 All carriers at same intensity

Figure 4 Multiple-intensity stimuli: mean data . The figure shows averaged mean response amplitudes computed across

10 subjects for both the MINT (+10 dB) and equal-intensity stimuli presented at 30, 40, and 50 dB SPL. In the MINT conditions, there is a clear enhancement of the responses to the more intense stimuli. There is also a small enhance-ment of the 1000-Hz response and a small attenuation of the 2000-Hz response . Although this interaction was signif-

icant, only the 1000-Hz enhancement reached significance with post hoc testing. The response to the 500-Hz stimulus

at 40 dB SPL is larger when the stimulus is presented with other stimuli at 40 dB (filled circle in the middle graph) than when it is presented with other stimuli at 30 dB SPL (open circle in the right graph) . This is likely due to the greater

noise levels in the recordings at 40 dB (owing to less averaging) .

stimuli are calibrated in hearing level or sound level (e.g., the Dimitrijevic et al, 2002, data plotted in Fig. 2) . The range of activation on the basilar membrane is smaller, and fewer neu-rons respond at 4000 Hz than at lower carrier frequencies.

The use of MINT stimuli with the 500- and 4000-Hz stimuli being presented at levels 5 to 10 dB higher than the other stimuli may help to compensate for the decreased response ampli-tudes and lead to increased recording efficiency when using multiple simultaneous stimuli. The small changes in the responses to the other stimuli following these manipulations are too small to affect the recording efficiency.

INTERACTIONS BETWEEN STIMULI

n evaluating the multiple-stimulus effect, we have so far assumed that if the responses

are decreased in the multiple-stimulus condition, this reduction occurs uniformly across the dif-ferent responses. The evidence presented in the literature on the human steady-state responses has generally found no significant effects of using multiple stimuli compared with using sin-

gle stimuli (Lins and Picton, 1995 ; John et al, 1998; Herdman and Stapells, 2001) provided that the stimuli are 60 dB SPL or less, are sep-arated by ear or by an octave in carrier fre-quency, and are modulated at rates above 70 Hz . However, the literature also reports evidence for small interactions, and these are shown in some of our recent data .

If we look closely at the amplitudes of the responses to the 1000- and 2000-Hz stimuli in the MINT experiment (see Fig. 4), we note a sig-nificant interaction between stimulus type (MINT versus equal intensity) and carrier fre-quency (F = 13.9, df = 1, 9, p < .01) . This inter-action was owing to the 1000-Hz responses having enhanced amplitudes in the MINT con-dition (F = 6.7, df =1, 9, p < .05) and the 2000-Hz responses showing a small but not significantly decreased amplitude (F = 0.7, df = 1, 9, p > .42) . These data clearly indicate that the presence of a low-frequency stimulus at a higher intensity than the other stimuli can enhance the amplitude of the response to a stimulus with a carrier fre-quency one octave higher. A similar effect was noted in an experiment reported by John and col-leagues (1998) . The response to a 1000-Hz stim-ulus (the "probe") was increased from 59 to 80 nV

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80 ,

60

40 -

L 0

0

u

20 -

0

500 1000 2000 4000 500 1000 2000 4000


O 500 and 4000-Hz stimuli 20 dB more intense 0 500 stimulus 20 dB more intense

0 All carriers at same intensity A 4000 stimulus 20 dB more intense

Figure 5 Multiple-intensity stimuli: +20 dB . The left graph shows averaged mean response amplitudes computed across 10 subjects for both the MINT (+20 dB) and equal-intensity stimuli presented at 50 dB SPL. The right graph shows the amplitudes when the MINT stimuli have either a 500- or a 4000-Hz carrier at the greater intensity level.

when the stimulus was presented in the pres-ence of a 500-Hz stimulus (the "masker") .

Our experiment using tone pairs indicated that high-frequency sounds may attenuate responses to low-frequency sounds . The multi-ple tone-pair recordings employed three tone pairs with the higher stimulus frequencies of each pair (f2) separated from one another by an octave (approximately 900, 1800, and 3600 Hz), as shown in Table 3 . We employed two groups of beat frequencies (near 85 Hz and near 180 Hz) to determine the frequency of the lower tone in each pair (f1) . Tone pairs were presented at 50 dB SPL, one pair at a time (single condition), and three pairs together (multiple condition) using either the 85-Hz or 180-Hz separation between each f2 and fl .

Figure 6 presents the mean response ampli-tudes (for 10 subjects) measured under single-and multiple-stimulus conditions . The data were analyzed using a three-factor (single versus multiple, f2 frequency, beat-frequency range) ANOVA. The responses to beats in the 180-Hz range were smaller than the responses to beats in the 80-Hz range (F = 10.3, df = 1, 9, p < .01) . There was no significant effect of the f 2 fre-

quency or single versus multiple for the three-factor ANOVA. However, there was an interac-tion between single versus multiple and the f 2 frequency (F = 7.1, df = 2, 18, p < .01) . Post hoc testing showed a small but statistically signifi-cant decrease in the magnitude of the response for the multiple tone-pair condition only when f 2 was 900 Hz and the beats were in the 180-Hz range (F = 8.4, df = 1, 9, p < .05) . There was also a small decrease when f 2 was 900 Hz and the beats were in the 80-Hz range; however, it was not statistically significant (F = 2 .0, df = 1, 9,

Table 3 Tone-Pair Parameters

Response Range (Hz)

Stimulus Pair f2 (Hz) f, (Hz)

Beat Frequency

(Hz)

85 1 904 822 82 2 1800 1716 84 3 3593 3505 88

180 4 904 727 178 5 1798 1618 180 6 3589 3406 183

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85-Hz Range 180-Hz Range

50

40

30

20

10

0

" Single 900 1800 3600 900 1800 3600

O Multiple Frequency of f2 (Hz)

Figure 6 Multiple stimuli versus single stimulus . This graph compares the responses to tone pairs (beats) presented singly (one tone pair) or multiply (three tone pairs) . The amplitudes were vector averaged across 10 subjects . The responses were recorded using beating frequencies that were near 85 Hz (left) or near 180 Hz (right) . The stimulus frequency is plotted as the second frequency of the pair (f2) . For both ranges of beat frequency, the response amplitude for the low-est frequency is slightly decreased in the multiple-stimulus condition (open circles) .

p =19) . The amount of attenuation was -15 per-cent at 85 Hz and -35 percent at 180 Hz .

These results indicate that when using mul-tiple stimuli, higher-frequency stimuli can atten-uate the responses to the lower-frequency stimuli. Other studies have found similar decreases in the low-frequency responses, although these have not been significant on sta-tistical testing. Lins and Picton (1995, Table 4) found a multiple-stimulus effect of -18 percent for the 500-Hz stimulus for four stimuli in one ear and -9 percent for four stimuli in each ear. Herdman and Stapells (2001, Fig. 2A) found effects of -9 percent for four stimuli in one ear and -24 percent for the dichotic condition (four stimuli in each ear) . Dolphin (1997) found that the gerbil responses to tone pairs were attenu-ated when tone pairs of higher frequency were simultaneously presented. The attenuation was larger for the tone pairs of lower frequency (both in terms of the tones and in terms of the beat fre-quencies). The greatest attenuation occurred for the 299- to 337-Hz pair, which had a 38-Hz beat frequency. This attenuation was sufficient to make the efficiency of the multiple-stimulus technique equal to that of the single-stimulus technique. A modulation rate of 38 Hz is lower

than normally used for audiometry with the auditory steady-state responses, and the response may be generated as much in the cor-tex as in the brain stem . All other interactions were smaller; thus, the multiple-stimulus tech-nique was generally more efficient. Indeed, the presence of the lower-frequency tone pair could enhance the amplitude of the responses to higher-frequency tone pairs.

If the tone pairs are very close together, such that tones are all within the same critical band, Dolphin (1996) found that the responses in dolphins were attenuated to a level (-3 dB) where it was not advantageous in terms of effi-ciency to record responses to simultaneous stim-uli. This is similar to data reported by John and colleagues (1998, Fig. 4), which found that pre-senting two sinusoidally amplitude-modulated tones with carrier frequencies of 1000 and 1050 Hz reduced the responses to one half of what they were when the stimuli were presented alone.

Dolphin and his colleagues (Dolphin and Mountain, 1993 ; Dolphin et al, 1994) looked at the interaction between an "interfering" pure tone on the gerbil response to a probe stimulus that was either a sinusoidally amplitude-modulated tone or a tone pair. The probe

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response was attenuated when the frequency of the interfering tone was higher than the probe stimulus . This is the opposite of what is found for tone-on-tone masking, for which low-fre-quency tones attenuate the response to (or raise the threshold for) higher-frequency tones. Very similar findings were found for the human steady-state response (John et al, 1998) . The mechanism of the effect is not known. Dolphin and Mountain (1993) suggested either some desynchronization of envelope-following neu-rons or some effects of suppression . Bernstein (1994) suggested that there may be some acoustic disruption of the envelopes when the interfer-ing tone is too close to the probe tone .

Other possible interactions between stimuli may occur, but these are smaller than those already described. Lins and Picton (1995) found that the responses to dichotic stimuli (two stim-uli in each ear - 500 and 2000 Hz) were sig-nificantly larger than those to single stimuli, but this effect was not replicated when four stimuli were presented to each ear.

Interactions occur when stimuli are pre-sented simultaneously. The most reliable of these are an attenuation of the responses to lower-frequency stimuli when presented with stimuli of higher frequency and an enhance-ment of the responses to higher-frequency stim-uli when presented with lower-frequency stimuli. These interactions are worth studying in their own right since they indicate physiologic inter-actions in the cochlea or auditory nervous sys-tem . However, these interactions are generally small and do not substantially affect the effi-ciency of the multiple-stimulus technique .

AUTOMATICALLY TRACKING THRESHOLDS

T here are two main indications for using stimuli with different intensities at differ-

ent carrier frequencies . The first reason is to enhance small responses by making the stimuli that evoke these responses more intense . By making responses roughly the same size, the recording is not delayed by the requirement that smaller responses have to have more time to reach significance . A second reason why dif-ferent intensities might be used is to evaluate patients with hearing losses that differ signifi-cantly across frequency. Individual stimuli could be independently increased or decreased in intensity to determine thresholds independently at the different frequencies as long as using stimuli of different intensity did not substantially

attenuate the responses to other stimuli. Even with differences of 20 dB between the simulta-neously presented stimuli, this appears true.

At present, the MASTER system records responses to a set of modulated tones that are all presented at the same intensity. The duration of the recording period at that intensity is deter-mined by how long it takes to recognize the response with the smallest amplitude or how long it takes to determine that one or more of the responses is not present. A more dynamic version of the MASTER technique could adjust the inten-sity of the stimulus on the basis of whether a response has been recognized . For example, the system could begin with all of the stimuli at 50 dB HL. As the larger responses to some stimuli become significant, the system could present these stimuli at 40 dB HL, while maintaining at 50 dB HL the stimuli that have not yet evoked significant responses . If one of the responses does not become significant after some criterion averaging time has passed or some criterion noise level has been reached, the intensity of that stimulus can be increased . The program will assess the responses in the frequency domain after each sweep . Rather than using one averaged sweep, the responses (and the appropriate noise values) will be allocated to separate averages on the basis of the modulation frequency and intensity of the stimulus . The computer will thus store a set of responses at different intensities, with each response averaged sufficiently either to recognize it as different from noise or to deter-mine that it is not significantly larger than some criterion. The software will have to include algo-rithms to assess responses, decide on the next intensity, allocate responses to appropriate mem-ory locations, and keep track of these different responses . The hardware will also have to be more sophisticated than that used presently. Producing stimuli at different intensities will require a high-precision digital-to-analog con-verter. Alternatively, a digital-to-analog system with eight channels of audio output would allow the intensity of the individual carrier frequencies to be independently adjusted prior to being mixed and sent to the left or right ear.

A dynamic MASTER system could thus con-tinually adjust the intensities of the stimuli on the basis of the significance of the recorded response until the intensities begin to hover around the thresholds for the response . The present system automatically determines when a response is present. In the envisioned sys-tem, even the decision about which intensity or intensities to use would be automatic.

257


CONCLUSION

T his article has considered the efficiency of evoked potential audiometry using steady-

state responses evoked by multiple simultane-ous stimuli. The general principles of signal-to-noise enhancement through averaging have allowed us to evaluate empirical results and estimate times using simple mathematical equa-tions. Having obtained normative values for both signal and noise levels, we can estimate how long recordings must last for stimuli of different intensities . These calculations can also be used to assess the required testing time for an indi-vidual subject using the signal and noise values from the data collected early in the recording procedure.

In the clinical setting, the advantage of the multiple-stimulus technique over a single-stimulus approach is generally less than the ratio of the number of stimuli presented. This occurs when the responses are of different sizes or when the thresholds are not equal for the different stimuli. Response amplitudes evoked by multiple stimuli can be made similar by increasing the intensities of those stimuli that are producing smaller or no responses. Within the limits that we have evaluated so far (20 dB), this can be done without producing significant changes in the responses to the other stimuli.

The issues raised here are important when using the MASTER technique in clinical audiom-etry, for which one needs to determine as quickly as possible if a response is present or absent . Within the laboratory setting, the concern may be more related to response parameters (ampli-tude and phase) rather than to response detect-ability. When investigating how an experimental manipulation affects responses evoked by stim-uli of different frequencies, the MASTER tech-nique generally decreases the time required by a factor of the number of stimuli. In addition, nonexperimental factors such as the arousal level of the subject or the placement of the stim-ulus transducer will be the same for the responses to all frequencies. In John and Picton (2000b), we examined the phase of responses evoked by carriers modulated at several differ-ent modulation rates and then converted the phase data into latency. The standard devia-tions of the latency data were very small because long recording durations were used to decrease background noise to very low levels and obtain stable estimates of phase. Rather than 2 hours, it would have taken closer to 16 hours to obtain

these data with equivalent noise levels using the single-stimulus technique.

Our general experience is that using mul-tiple stimuli rather a than single stimulus increases the speed of measuring response para-meters such as amplitude or latency by the number of stimuli presented simultaneously. Certain caveats concerning the stimulus inten-sity and the differences in carrier frequency between stimuli need to be followed for this to be true . In the context of evoked potential audiometry, for which decisions are based on the presence or absence of a response, the advan-tage of using multiple stimuli rather than a sin-gle stimulus is reduced. When using eight stimuli, we would estimate the multiple-stimulus technique as two to three times faster than the single-stimulus technique.

Acknowledgment. This research was funded by the Canadian Institutes of Health Research . The authors would also like to thank James Knowles, the Catherall Foundation, and the Baycrest Foundation for their sup-port . Patricia van Roon assisted with the data collection and preparation of this manuscript .

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advantages and caveats when recording steady-state responses

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