A comparison of steady-state evoked potentials to modulated tones in awake and sleeping humans.

A comparison of steady-state evoked potentials to modulated tones in awake and sleeping humans Lawrence T. Cohen, Field W. Rickards, and Graerne M. Clark Human Communication ResearchCentre,The University ofMelbourne,Departmentof Otolaryngology, Parkville 3052, •4ustralia

(Received29 September1988;revised16July 1991;accepted18July 1991) Steady-stateevokedpotentialresponses weremeasuredto binauralamplitude-modulated (AM) and combinedamplitude-and frequency-modulated (AM/FM) tones.For awake subjects,AM/FM tonesproducedlarger amplituderesponses than did AM tones.Awake and sleepingresponses to 30-dB HL AM/FM toneswere compared.Responseamplitudeswere lowerduringsleepand the extentto whichthey differedfrom awakeamplitudeswasdependent on both carrierand modulationfrequencies. BackgroundEEG noiseat the stimulus modulationfrequencywasalsoreducedduringsleepand variedwith modulationfrequency.A detectionefficiencyfunctionwasusedto indicatethe modulationfrequencieslikely to be most suitablefor electricalestimationof behavioralthreshold.In awake subjects,for all carrier frequencies tested,detectionefficiencywashighestat a modulationfrequencyof 45 Hz. In sleepingsubjects, the modulationfrequencyregionsof highestefficiencyvariedwith carder frequency.For carrier frequenciesof 250 Hz, 500 Hz, and 1 kHz, the highestefficiencies were foundin two modulationfrequencyregionscenteredon 45 and 90 Hz. For 2 and 4 kHz, the highestefficiencies wereat modulationfrequencies above70 Hz. Sleepstageaffectedboth responseamplitudeand backgroundEEG noisein a mannerthat dependedon modulation frequency.The resultsof this studysuggestthat, for sleepingsubjects,modulationfrequencies above70 Hz may be bestwhenusingsteady-state potentialsfor hearingthresholdestimation. PACS numbers:43.64.Ri, 43.64.Yp

INTRODUCTION

The accuratemeasurementof hearingin infants and youngchildrenis essentialfor their audiologicaland educational management.Auditory evokedpotentialsare important in the objectiveassessment of hearingin difficult-to-test subjects.The auditory brain-stemresponse(ABR) is particularly usefulin infantsbecauseit is unaffectedby sleep (Davis, 1976; Hall, 1983; Osterhammel et al., 1985). However,its usefulness is limited by poorauditorythresholdestimatesat frequencies below 1-2 kHz (Gorga et al., 1988). In contrast,the "40 Hz response"(Galamboset al., 1981) has beenusedto obtain goodestimationsof behavioralthresholdsin normaland hearing-impairedadultsat low and high frequencies(Stapellset al., 1983), howeverthis responseis considerablyaffectedby sleepor sedation(Galamboset al., 1981;Brown and Shallop, 1982;Shallop, 1983;Osterhammel et al., 1985) and responsethresholdsare elevatedand lessreliableduringsleep(Picton et al., 1987c).The "40 Hz response"is thoughtto be equivalentto a superposition of transientmiddlelatencyresponses (MLRs), and the detectability of transientMLRs in childrenis alsounreliablein the deeperstages(2, 3, and 4) of sleep(Kraus et al., 1989). The "40 Hz response"has beendescribedas a steadystatepotential (Stapellset al., 1984). Regan (1972, 1977) classifiedresponses assteadystatewhentransientresponses mergeinto eachotherto the extentthat they cannotbe clearly identifiedas separatetransientevents.He suggested that the higherrepetitionratesusedin producinga steady-state responsemay result in more rapid responsedetection. 2467

J. Acoust.Soc.Am.90 (5), November1991

Steady-stateresponses may be evokedby other periodically time-varyingstimuli, for example, amplitude- (AM) and frequency-modulated(FM) tones. These stimuli can be convenientlypresentedovera widerangeof modulationfrequencieswhile maintainingcontroloverthe stimulusenvelopecharacteristics. In addition,thesestimulicanhavenarrower bandwidthsthan repeatedtone burstsat comparable repetitionrates. There havebeenseveralstudieson evokedpotentialsin responseto sinusoidallyamplitude-modulated(AM) tones (Rickards and Clark, 1982;Rickards and Clark, 1984;Elliot et al., 1984;Kuwada et al., 1986;Reeset al., 1986;Picton et al., 1987b) and frequency-modulated(FM) tones (Rickards and Clark, 1972; Picton et al., 1987a, 1987b). The AM

studieshave shownthat periodicresponses, with principal spectralcomponentsat the modulation frequencyand its secondharmonic, can be found for carrier frequencies (CFs) overthe normalaudiometrictestingrangefor stimulus intensitiescloseto behavioralthreshold(e.g., Rickards and Clark, 1984; Kuwada et al., 1986; Picton et al., 1987b). Thesestudieshavealsoshownthat the responses can be obtainedfor a widerangeof modulationfrequencies: 4-450 Hz (Rickards and Clark, 1984) and 2-400 Hz (Rees et al.,

1986). While the amplituderesponsehasa broadlylow-pass characteristic(Rickards and Clark, 1984; Reeset al., 1986; Picton et al., 1987b), a peakhasbeenfound at about40 Hz and its similarity to that of the middle latency "40 Hz response"has been remarked on by Rees et al. (1986), Kuwada et al. (1986), and Picton et al. (1987b).

Most studiesof auditory steady-statepotentialshave

0001-4966/91/112467-13500.80

@ 1991Acoustical SocietyofAmerica

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usedtoneburstswith repetitionratesof 20-60 s- 1or sinusoidallyamplitude-modulated tones.To our knowledge,no studieswith tone-burststimuli have usedrepetitionratesin

excess of 60s- •, foreitherawakeor sleeping subjects. However, the awake studiesusing continuousAM tones have shown responsesto be presentat modulation frequencies much higher than 60 Hz (Rickards, 1983; Rickards and Clark, 1984; Rees et al., 1986; Kuwada et al., 1986). The studiesusingAM stimuli haveshownthat the responselatency, calculatedfrom changesof phasewith modulation frequency,is about 30 ms in the modulationfrequencyregion encompassing 40 Hz (a similar latencyto that of the "40 Hz response").The latenciesbecomelonger at lower modulation frequencies(Rickards and Clark, 1984) and shorter at higher modulation frequencies(Rickards and Clark, 1984;Kuwadaet al., 1986). For frequencies in excess of 75 Hz, the latency is about 8 ms (Kuwada et al., 1986) althoughit may dependalsoon other stimuluscharacteristics, suchas CF and soundintensity (Rickards, 1983). It is known that short latency (lessthan 10 ms) evokedpotentialsare unaffectedby sleep,and henceresponses at modulation frequenciesabove75 Hz may be usefulfor the measurement of thresholdsin sleepingsubjects.We have reported the resultsof a preliminarystudywhichsuggested that modulationratesbetween70 and2.00Hz wereappropriatefor the detectionof steady-stateresponses in sleepingsubjects(Co-

for the Tubephoneswereprovisionallevelsprovidedby the manufacturer (Etymotic Research, 1985). The additional time delay introducedby the Tubephonesrelativeto standard headphoneswas measuredand used to correct the phasemeasurements. The stimulusgenerationandresponse measurement circuitry wasspeciallydesignedandwascontrolledby a microcomputer.The stimuluslevelwasaccurateto within ñ 1 dB and both CF and modulation frequencywere accurateto within ñ 1%. Seventotally deafsubjects,testedat levelsof 120 dB HL with mumetal shieldedTDH-39 headphones, gave no detectableresponse.Two normal subjects,tested with Tubephones,gaveno detectableresponse at 100dB HL if their earswereblockedwith unperforatedEAR-plugsand the Tubephonetube openingswere obstructed.Hence, the responses reportedin this paperwere not the resultof artifact.

The stimuli used were sinusoidally modulated AM tonesand sinusoidallysweptFM tonesthat were alsosinusoidallyamplitudemodulated(AM/FM). The modulation frequenciesfor amplitude and frequencymodulationwere identical.AM/FM stimuliwere usedbecausethey had been found to evokeresponses of a very similar form to those evokedby AM stimuli,but of greateramplitude. As responseamplitude has been found to increase monotonicallywith amplitudemodulationdepth (Rees et hen and Rickards, 1987). al., 1986), an amplitudemodulationdepth of 100% was The first aim of this studywasto compareresponses to usedto obtainthe largestresponse amplitude.The frequency combinedamplitude-and frequency-modulated(AM/FM) modulationdepth was 20%, where depth was definedas tonesand AM tones.This comparison(experiment 1) was 100(gmax -- Frein)/Fcarrie r . This waschosento keepthe specto confirm that larger responseamplitudespreviouslyobtrum of an FM stimulusroughlywithin a criticalband.The servedfor AM/FM responses at a modulationfrequencyof phasesof the amplitude and frequencymodulation enve40 Hz (Cohen, 1990) were obtained at other modulation lopeswere adjustedso that maxima of amplitudeand frefrequencies.Stimuli that evoke responses of larger ampliquencyoccurredsimultaneously. This resultedin an upward tudemay well bemoreeffectivein evaluatinghearingthreshshiftof the stimulusspectrum.To compensate for thiseffect, olds,as hasbeensuggested by Cohen (1990). the CF wasreducedby 5% when amplitudeand frequency The second,but principal,aim of the presentstudywas modulationwerecombined.Differentrelativephasesof amto determinethe characteristicsof steady-stateresponses plitudeandfrequencymodulationenvelopeswerenot investigated. from awakeandsleepingsubjectsat low soundintensities,as functionsof carrier and modulationfrequency.The stimuli When amplitudeand frequencymodulationwere comusedin this part of the studywere combinedamplitude-and bined, the spectrawere broaderthan for amplitudeor frefrequency-modulated(AM/FM) tones.The resultsof this quencymodulationalone. In Fig. 1, spectraare shownat study (experiment2) were usedto estimatethe modulation CFs of 500 Hz and 2 kHz and a modulationfrequencyof 90 Hz, for AM and AM/FM stimuli. Theseare line spectrain frequencyrangeslikely to be suitablefor usein evokedpotential thresholdmeasurementin sleepingsubjects. whichthe linesarejoined to makethe diagramsclearer.The bandwidthof a stimulusis approximatelyproportionalto its modulationfrequency. I. METHODS A puretonewasusedto calibratethe stimuluslevel.The A. Stimuli introductionof frequencymodulationdid not changethe Soundwas deliveredin experiment1 by TDH-39 headpeak-to-peakamplitude of the stimuluswaveform.When phoneswith MX-41/AR ear cushionsand in experiment2 amplitudemodulationwas introduced,the waveformwas by Etymotic ResearchER-3a Tubephones,usedwith foam multipliedby [ 1 -{-cos(2•rF,•t)], whereF,• isthemodulaEAR-plugs.Both transducers werecalibratedusinga BrQel tion frequency,thusincreasingthe energyby 1.76dB. Behavioral measurements were consistent with these observa& Kjaer (B & K) 4144condenser microphone,a B & K 2613 microphoneamplifieranda B & K 2120frequencyanalyzer. tions.The meanbehavioralthresholds,for a separategroup A B & K 4152 artificial ear (6 cc) was used with the headof ten normal hearingsubjects,were found to reduceby no phones,while a PhonicEar HA-1 (2 cc) couplerwasused morethan 2 dB when eitheramplitudeor combinedampliwith the Tubephones.The headphoneswere calibratedin tude and frequencymodulation was introduced.Further, accordance with ISO 389, while the calibration levels used 2468

J. Acoust.Soc. Am.,Vol. 90, No. 5, November1991

the mean differences between the thresholds

for AM

Cohenotal.' Evokedpotentials,awake and asleep

and

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trodesand the EEG wasrecordedfrom Cz -- .4•. The sleep stageswereclassifiedaccordingto Rechtschaffenand Kales (1968) and three categorieswere chosenfor consideration: stage2, stage3/4, and stageREM (rapid eye movement sleep). Stages2 and REM are consideredto be shallow stages,while stages3 and 4 are deep.Stage1 wasnot consideredto betrue sleepandwastoo fleetingfor satisfactorydata

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FIG. 1. Spectraof AM andAM/FM stimuliwith carrierfrequencies of 500 Hz and 2 kHz and modulationfrequencyof 90 Hz, logarithmicfrequency axis.Energyof eachstimulusis equalto that of a puretoneof level0 dB.

AM/FM

stimuli did not exceed 1 dB. The modulation fre-

quencywas40 Hz in thesemeasurements. Responses were measuredat CFs of 250 and 500 Hz, 1, 2, and 4 kHz. The modulationfrequencywas varied from 30-185 Hz in experiment1 and from 30-190 Hz in experiment 2. At 250-Hz CF, the modulation frequencydid not exceed125 Hz. In all experiments,modulationfrequencies were tested at intervals of 5 Hz or less for modulation

fre-

quenciesbelow 100 Hz, and 10-20 Hz for modulationfrequenciesabove 100 Hz. B. Recording

Fourier analysiswasperformedat the fundamentaland secondharmonicof the modulationfrequency,usinganalog multiplicationfollowedby low-passfiltering (Regan, 1966). For eachharmonic,two multipliersand two low-passfilters wereusedto extractboth amplitudeand phaseinformation. Each low-passfilter producedan effectivetime windowapproximatinga Hanning window of 64 modulationperiods duration.The stimulusgenerationsystemproducedpulses at intervalsof 32 modulationperiods,instructingthe computer to samplethe outputsof the four low-passfilters. In measuringthe responseof a subjectto a particular stimulus,a "run" comprisedbetween120 and 256 samples for experiment1 or between128and 540 samplesfor experiment 2 dependingin each caseon the amplitude of the response.A larger maximum numberwas allowedin experiment 2 than in experiment1 becauseresponseamplitudes were smaller. For pure-tone calibration signals of 0.2 • Vp -- p, response amplitudeandphaseat the completionof a run wereaccurateto within + 2% and + 3ø,respectively. The meanresidualamplitudewith preamplifierinputsshorted was lessthan 0.01 •Vp--p, althoughamplitudeswere recordedto only two decimalplaces.A muscleartifact rejection systemrejectedan individual sampleif its amplitude exceededan appropriatemultiple of the steadybackground EEG. This multiplewaschosensothat onesamplein a thousandwould be rejectedif the human subjectwasreplacedby a Gaussiannoisesourcegivingan equalnoiselevelmeasurement.

C. Analysis

The taking of numeroussamplesduring a run allowed severalstatisticalquantitiesto be calculated,for both fundamentaland secondharmonicresponses, includingmeansfor the amplitudeandphaseof the responses. The standarddeviation of the samplephaseanglesand a measureof the EEG noise level were calculated.

These allowed estimation of the

EEG activity wasrecordedusingsilver-silverchloride diskelectrodesgluedto the vertexand mastoidswith collodion.Activeelectrodeswereplacedonthevertex( Cz, + re) and the fight mastoid(•42), while the groundelectrodewas placedon theleft mastoid(•41). The signalwasamplifiedby a speciallydesignedpreamplifierwith a bandwidth of 0.2 Hz-10.0 kHz. Interelectrodeimpedancewaslessthan 10kCt

noisefloorand standarderrorsfor the amplitudeand phase. The noisefloor wasdefinedasthe meanamplituderesponse measurement that wouldbeexpectedwith a givennoiselevel and with no true responsepresent.An estimatewas also made of the probability that the distribution of samples couldhavearisenfrom a randomnoisebackground. Mean backgroundEEG narrow band noiselevelsare at 260 Hz. plottedin Fig. 2 for awakeand sleepingsubjects,as a funcIn orderto assess sleepstagesin experiment2, the EEG, tion of frequency(from experiment2). The noiselevel was electro-oculogram(EOG), and electromyogram(EMG) calculatedin sucha way that it was essentially.thesamein wererecordedon a polygraphduringthe sleepingsessions. the presenceor absenceof a response.It was calculatedby The EOG was recorded from two electrodes,situated above subtractingthe mean vector amplitude derived from the the outer canthusof oneeye and belowthe outer canthusof sampleswithin a run from the vectoramplitudeof eachsamthe other. The EMG was recorded from submental elecple, and then calculatingthe rms of the correctedsamples. 2469

J. Acoust. Soc. Am., Vol. 90, No. 5, November 1991

Cohen et aL' Evoked potentials, awake and asleep

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the amplitudeiscloseto the noisefloor.The efficiencies plotted in this study have beencorrectedfor the presenceof a noisecomponentequalto the meannoisefloor,by usingthe approximationthat the squareof the mean measuredresponseamplitudeequalsthe sumof the squaresof the true responseamplitudeand the meannoisefloor. While the detectionefficiencyfunctionprovidesa quantitative measureof the relativedetectabilityof differentstimuli, someassumptionsare involvedin its useto predictthe optimummodulationfrequencyfor electricalestimationof behavioralthreshold.As stimuluslevel varies,responseamplitudesat differentmodulationfrequenciesare assumedto maintainthe samemagnitudesrelativeto eachother.There are additionalassumptionsconcerningthe distributionsof possibleamplitudeandnoisemeasurements for onestimulus conditionrelativeto another,within a givenstate(awake or asleep).Similar assumptionsare alsoimplicit, however,in the selectionof optimum modulationfrequencybasedsolely on the variationof responseamplitudewith modulationfre-

Thesenoiselevelscan be related to the EEG noisespectral

quency.

density bytheexpression N = 3.55X 10- 4 VsF •/2,whereN

The mean phasefor groupsof severalsubjectswas derived from the vector mean of the response.However, the mean amplitudeis the scalar,rather than vector,mean becausethe latter canbe smallwhenindividualamplitudesare large, due to substantiallydifferingindividual phases.Responsedetectabilitydependsnot on phasebut on amplitude. Variability of phaseresponses can be assessed from phase standarderrorsor by comparingindividualphaseresponses. For amplitudeandphasemeansovergroupsof subjects,

is the noiselevelin/• Vp - p, Vsis the noisespectraldensity

in n[/'rms / (Hz) 1/2andF isequalto themodulation frequency. The effectivebandwidth was 1.57%. A responsewasrejectedif its noiselevelexceededa certain value,which wasselectedaccordingto modulationfrequencyand to whetherthe subjectwasawakeor asleep.For awake subjects,the maximum allowed noiselevel at 40 Hz was 1.3/• Vp -- p, while at otherfrequencies it variedin proportionto the meanawakenoiselevelof Fig. 2. For sleeping subjects,the maximum allowednoiselevelat 90 Hz was0.5 /• Vp - p, whileat otherfrequencies it variedin proportionto the meansleepingnoiselevelof Fig. 2. To estimatethe probabilitythat the setof samplescould have arisen from a random noise source, the distribution of

samplephaseanglesrelativeto the modulationenvelopewas considered. This response detectioncriterionwasequivalent to that of the "phasecoherence"techniqueusedby Galambos et al. (1984), Jergeret al. (1986), and Stapellset al. (1987) in the measurementof steady-stateevokedpotentials.This testwasusedto determinewhethera responsewas

standard errors were derived from the sets of individual

sub-

ject means.The estimationof the phasestandarderror was complicatedby the cyclicnature of phaseangles.Standard error should reduce, for small standard deviation, to the

standarddeviationdividedby the squareroot of the number of subjects.However, for random phaseanglesconstrained to within 180ø of the mean, in which case the theoretical

standarddeviationis 103.9ø,the standarderror shouldequal 103.9øif it, also,is constrainedto be within a rangeof 360ø. The estimateof standard error used,basedon the theoretical

relationshipbetweenstandarddeviationsof sampleangles and standarderrors of mean anglesin individual subjects, satisfiedthe requirementsdescribedabove.This approximapresent. In order to assess the relativedetectabilityof responses tion to the estimationof standarderror, wasusedin plotting error bars. for various stimulusconditions,a detectionefficiencyfuncLatenciesmay be estimatedfrom the slopeof the linear tion was defined. Its value was calculated from the means of regression of phaseon modulationfrequency,subjectto the amplitudeand noiselevel over severalsubjects.It was apvalidity of certain assumptions(Regan, 1972, 1977). The proximatelyinverselyproportionalto the time requiredto latenciesgivenin this studyare the meansof individualsubdetecta responseand, in its simplestform, wasgivenby ject latencies. Eft = (modulation frequency) Analysesof variance(ANOVAs) were performed,followed where appropriateby Scheft6post hoc testing.The X (signalamplitude/EEGnoiselevel)2. ( 1) The efficiencyis proportionalto the squareof the signal-to- ANOVA useda weightedanalysisfor unequalnumbersof In addition,t-testsfor pairedsamplesand innoise ratio becausethe noise componentof an averaged observations. dependent samples were used and the probabilitiesgiven quantity is inverselyproportionalto the squareroot of the weretwo tailed. A significance level ofp < 0.05 wasused. time overwhichit is averaged.It is proportionalto the modulationfrequencybecausethe rate of processing of informaD. Subjects tion is proportionalto the modulationfrequency. A limitation of the above form for the detection effiAll subjectshad pure-tonethresholdsbetween - 10 ciencyfunctionis that it givesan unduly large value when and + 10dB HL at 250 and500Hz, 1, 2, and4 kHz. Experi2470


Cohen eta/.: Evoked potentials,awake and asleep

2470


ments were performed in a standardaudiometricsound-

In experiment2, when a subjectarrivedat the laboratory at about7 pm, behavioralthresholdswere measured,all electrodeswereattached,the Tubephoneswereinsertedand awaketestingcommenced. At about10.30pm awaketesting ceased,the subjectwentto bedin the sameroomwithoutany changeto the electrodesor the Tubephoneearplugplacement, and went to sleepwithout sedation.The entire sequenceof sleepingtestswascompletedduringonenightand

that do not extendbeyondthe radiusof the symbol (circle) do not appear in this figure or subsequentfigures.Large uncertaintiesin the phasecorrespondto responseamplitudes very closeto the noisefloor (indicated by a dashed line). The figure illustratesthe nature of the data obtained for individualsubjects. This subjecthada lowerthan average noiselevel (and hencenoisefloor) and consequentlythe standarderrorsin his responses werelower than average. The meanresponses overfivesubjectsare shownin Fig. 4, for the five CFs and two stimulustypes.Error bars are plottedfor the AM responses only. The standarderrorsfor AM/FM responses were equal to or smallerthan thosefor AM responses. For clarity, in the region 30-52.5 Hz, error bars are shownon alternatingpoints of the amplitude responses.The omitted error bars are comparableto those

the session concluded at 6-8 am. The remainder of the awake

shown. The mean noise floors are indicated as dashed lines.

treated

room. Behavioral

thresholds

were obtained

with

TDH-39 headphones usinga descending procedurewith 2dB intervals.For awakeevokedpotentialtests,subjectssat in a comfortablechairreadingandwereencouraged to relax. For sleepingteststhey lay on a stretcherbed in the same room.

testingwasdoneat a later date, with all conditionsthe same exceptfor the absenceof EOG and EMG electrodes. The subjectsof experiment1 were 4 malesand 12 femalesrangingin agefrom 15-42 years(mean 24.9 years). In ,h ..... part •,r experiment9 •,,bj•-*• •,•,-o a ,•• •,a • femalesrangingin agefrom 20-27 years(mean 22.1 years). The subjectin Section5 of experiment2 wasa 20-year-old

At each CF, the mean amplitude responsesto AM tones showeda primary peaknear 45 Hz, and tendencyto a minimum at 70-80 Hz. A secondarypeakappearedto be present in the region85-110 Hz. The minimum and secondarypeak are clearlysignificantin the amplituderesponseof the individual subjectof Fig. 3. Exceptfor the responseat 500 Hz wherethe response waslargest,the amplitudeof the primary male. peakshowedan orderly declinewith increasingCF. Although the responses to AM/FM resembled,in genII. RESULTS eral, thoseto AM, the amplitudesin the regionof the primary peak were significantlylarger than for AM. In the reA. Experiment 1- AM and AM/FM responses in awake gion 30-60 Hz, AM/FM amplitudes were significantly subjects largerfor eachCF except4 kHz (p < 0.001). Here, t-testsfor 1. Cornpar/son of AM and AM/FM responses pairedsampleswereusedon the data for all individualsubResponseswere recorded to AM and AM/FM tones jects.Amplitudeswerealsolargerfor AM/FM than for AM presentedbinaurallyat 55 dB HL, a levelat whichresponses with CFs of 2 and 4 kHz at modulationfrequenciesof 80 Hz could be obtainedreliably in all normal subjects(Cohen, and above (p < 0.001 ). 1990). Eachsubjectwastestedat all modulationfrequencies In order to confirmthat the larger responseamplitude and at up to three of the five CFs. Five subjectswere meafor AM/FM stimuli was consistentacrosssubjects,the sured at each CF.

The amplitudeand phaseresponses of a singlenormal subjectto an AM stimulusat 1 kHz are givenin Fig. 3. The error bars representone standard error in the mean responsesderivedfrom many responsesamples.Error bars

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Hodulefion F•equency FIG. 3. Phaseandamplituderesponses of a singlesubjectto binaural1-kHz AM stimulusat 55 dB HL, as a functionof modulationfrequency.Error barsare plusand minusonestandarderror in the meanof many response samples(seeSec.I). Noisefloor is shownby dashedline. 2471

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J. Acoust.Soc. Am., Vol. 90, No. 5, November 1991

FIG. 4. Mean responses of awakesubjectsto binauralstimulationat 55 dB HL with AM andAM/FM stimuli.Mean phaseand amplituderesponses (upper and lower curves,respectively)versusmodulationfrequencyfor carrier frequenciesof 250 and 500 Hz, 1, 2, and 4 kHz. Noise floor is a dashedline. Error barsof plusand minusonestandarderror are shownfor AM responses only. In region30-52.5 Hz, error barsare omittedon every secondpoint of the amplituderesponses. In eachframe,the linearregression line of best fit for 4 kHz between 90 and 185 Hz is shown as a solid line

(see text).

Cohen et al.: Evoked potentials,awake and asleep

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mean ratio of AM/FM amplitudeto AM amplitudewas calculatedfor individualsubjectsat eachCF. In the region

wherethe phaseincreased.Further, above125 Hz, for CFs of 1kHz and especially500 Hz, the phasebecameverysimi-

30-60 Hz, for CFs of lessthan 4 kHz, the mean ratios were

lar to that for 4 kHz.

all greaterthan 1.0,rangingfrom 1.10-1.80. At modulation frequencies of 80 Hz and above,for 2 and 4 kHz, the mean ratiosrangedfrom 1.28-2.17. The phaseresponses to AM/FM and AM stimuli were similar.The phasedifferences, CAM-- ½AM/FM, werefound not to varysignificantly with modulationfrequency.For the five CFs, the mean phase differenceswere 6.8, 3.1, 0.8, -- 2.6, and -- 13.6ø,calculatedoverall subjectsand modulation frequencies.The phasedifferenceswere significant only for CFs of 250 Hz (p < 0.05) and 4 kHz (p < 0.0001). The meandifferences weresubtractedfrom the AM phases at all modulationfrequenciesand the AM and AM/FM phaseswere then lumped togetherfor subsequent latency

Becauseof theseobservations, it did not seemjustifiable in calculatinglatenciesto considerthe modulationfrequency regionabove90 Hz asonehomogeneous regionfor CFs of

calculations. 2. Latencies

for comb/ned

AM and AM/FM

data

The basicform of the phaseresponses, from Fig. 4, was of a slopebelow70-Hz modulationfrequency,corresponding to a latencyof about30 ms,and a smallerslopeabove70 Hz, corresponding to a latencyof about 10 ms.The individual phaseresponses in Fig. 5 confirmthispattern.Latencies were calculatedfor eachsubjectin two regionsof modulation frequency,30-60 Hz and 90 Hz and above.Thesetwo regionswerechosento avoidthe transitionbetweenlatencies

1 kHz and below. Therefore, latencieswere calculated be-

tween90 Hz and the highestfrequencyat which the mean phasedid not showan upward deflection.The modulation frequencyregionsand meanlatenciesare listedin Table I. The latenciesin thehigh-frequency regionweresignificantly shorter, for each CF, than for the region 30-60 Hz (p < 0.0001, usingt-testsfor pairedsamples). B. Experiment 2: AM/FM responses in awake and sleeping subjects

Sincewe had foundthat AM/FM tonesevokedlarger responses than AM tonesin awake subjects,the AM/FM tonesusedin experiment1werealsousedin thisexperiment. Binauraltoneswerepresentedat 30 dB HL. In orderto con-

trol for the effectsof stimulus order, four different stimulus sequences were used.Each subjectwastestedat all CFs and almostall modulationfrequencies.Each subjectwastested asleepand awakewith one of the four stimulussequences. During sleepa stimulussequence wasinterruptedonlywhen the subjectawoke,wasvery restlessor had a veryhighnoise level. Sleepstagevaried during the sequenceand, as each that occurred at around 70 Hz. stimuluswas presentedonly once,a subject'sresponseto a With reductionof CF, onewouldexpecta smallincrease stimuluswasmeasuredduring only onesleepstage. The amplitudeandphaseresponses of a singlesubjectto in latencyand slope,due to increasedtravellingwavedelay an AM/FM stimulus at 1 kHz are given in Fig. 6. The awake on the basilarmembrane.As a consequence, at any given results are of similar form to those described in experiment1 modulationfrequency,there would be a decreaseof phase and the onset of sleep caused a reduction in response ampli(increasingnegativity) with reducing CF. The responses tude and noise floor. Clear responses, as judged by small werefoundto deviatefrom thispattern,especiallyat CFs of standarderror in phase,were recordedfor modulationfre1 kHz and below. To illustrate this effect, a solid line is quenciesup to at least 170 Hz. shownoneachphaseplot in Fig. 4, whichisthelineof bestfit to the mean4-kHz phaseresponsefor modulationfrequenI. A wake ciesof 90-185 Hz. For modulationfrequencies of 90-125 The meanresponses overten awakesubjects(representHz, the mean phasereducedas the CF variedfrom 4 to 1

kHz. However, this trend did not continue for lower CFs,

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ß

1.75

ed by opencircles),are shownin Fig. 7 for the five CFs. Sincethe amplituderesponses to 30-dB HL stimuli were smallerthan thoseto 55-dB HL, the responses in Fig. 7 and

TABLE I. Mean latenciesfor responses to 55 dB HL binaural stimuli, awake.

Carrier freq. (Hz)

Modn. freq. range(Hz)

Latency (ms)

Latency s.d.

...

250

30-60

31.6

-720

500

30-60

33.0

1.6

-900

1000

30-60

24.8

4.0

2000

30-60

28.9

3.1

4000

30-60

28.6

2.1

250

90-125

11.6

2.6

500

90-115

12.7

7.2

1000

90-125

13.0

3.9

2000

90-185

9.4

1.2

4000

90-185

8.9

0.8

-540

•.50

0.75 ,,•.

-1080 -1260

0.50

-1440

02•

2.0

,

•

40 80 120 160 0

40 80 1•0 160

ModulationFrequency (Hz)

FIG. 5. Individualphaseandamplituderesponses (upperandlowercurves, respectively)of awakesubjectsto binauralstimulationat 55 dB HL. These responses gaveriseto the meanAM/FM responses of Fig. 4.

2472

J. Acoust.Sac.Am.,Vol.90, No.5, November1991

Coheneta/.: Evokedpotentials, awakeandasleep

2472


o•[ , [ [ [ ,30, dB]HL ] [z.o -a6o•-% • 1.6k

-360

-540

..

-720

I i i l

] '•L

0 Awoke -

-900 -1080

-1260 ,"- -1440

• -1620

.

-360

o.,.

o.,

0.8

• -s4o

0.7

cx. -720

0.6

20

40

60

80

l•

120 I•

160 I•

0.2 0.0

-o,o k

o.,.

o.s•

-1440•

0.4• 60

•0

1•

---

120 140 160 180

80

120

160

0

40

80

I•0

160

0.2

0.0

FIG. 6. Phaseand amplituderesponses (upper and lower curves,respectively) of a singlesubject,awakeand asleep,to binaural 1-kHz AM/FM stimulusat 30 dB HL, asa functionof modulationfrequency.Error barsare plusand minusonestandarderror in the meanof many responsesamples (see Sec.I). Noise floor is shownby dashedline.

subsequent figuresare plotted on a smallerscalethan was usedin previousfigures.The noisefloorsfor awakesubjects are indicatedby dashedlines. Relative to the results for 55-dB HL AM/FM

FIG. 7. Mean responses of awakeand sleepingsubjects(openand filled circles,respectively)to binauralstimulationat 30 dB HL with AM/FM stimuli.Mean phaseandamplituderesponses (upperandlowercurves,respectively)versusmodulation frequency for carrierfrequencies of 250and 500 Hz, 1, 2, and4 kHz. Noisefloorsfor awakeand sleepingare dashedand dottedlines,respectively. Error barsof plusandminusonestandarderror are shownfor awakeand sleepingcases.

ModulationFnequency

stimuli in

Fig. 4, the overallform at 30 dB HL was similar,although theamplitudeswerereducedandphases weremorenegative. There wasa peak at about40 Hz and a tendencyto a minimum at about70 Hz and a correspondingsecondarypeak at 80-100 Hz. However, the apparentirregularitiesin phase behaviorobservedat 55 dB HL did not seemto be presentat 30 dB HL. For 1 kHz, the phaseappearsto deviatefrom a regulardescentbut, for this CF, standarderrorswere large at modulationfrequencies above120 Hz. The latenciesfor awakesubjectsat 30 dB HL (Table II) tendedto be longer than thoseat 55 dB HL (Table I ), for modulationfrequency rangesof 30-60 Hz and 90 Hz and above. In subsequent statisticalcalculationsinvolvinglatencies in the highermodulationfrequencyrange,the 250-Hz case has not been included because values for this CF have been

calculatedovera smallrangeof modulationfrequencies. 2. Sleeping

Responseamplitudeswere reducedduring sleep.The meanresponses overten sleepingsubjectsare shownasfilled circlesin Fig. 7 for the fiveCFs. The individualresponses of 2473

40

Nodulation Frequency (Hz)

-•so

40

0.1

0

I ikHz •'"• O•i • i i i i i30 i i - 2.0 dBHL- •.s[

20

0.2

-1620

-iso

-1620 • •

'

-1440

-•so• •

- 18• •

0.4 o.•

-1260

Modulation FPequency (Hz)

,...

0.5

-900 -10•0

-1620• 18•-•

_

;o ';•'..... ,•o ,•0


the sleepingsubjectsarealsogivenin Fig. 8. While therewas a peakin the sleepingamplituderesponses at approximately 40 Hz, it wasreducedin magnitudeby a factorof between2.5 and 4.0 relativeto the awakeresponses. There tendedto be a minimum at about 70 Hz and a correspondingsecondary peakat 80-100 Hz. The individualresponses of Fig. 8 show the presenceof a minimumandsecondarypeakin mostsubjectsfor CFs of 1 and 2 kHz, but not 250 and 500 Hz. For 4 kHz, responseamplitudeswere stronglymaintainedover a wide rangeof modulationfrequencies above70 Hz. For this CF, sleepingamplitudeswerereducedby a meanfactorof only 1.3 relativeto awake amplitudesin the region90-190 Hz.

In the 30- to 60-Hz range,latencydid not vary significantly betweensubjectsawakeand asleep,or with CF (see Table II). A two-way ANOVA was used,with state (awake or asleep) and CF as independentvariables.In the 90- to 190-Hz range,latencywas significantlylongerfor subjects awakethan asleep(p < 0.05), with a meandifferenceof 1.3 msand standarderror of 0.5 ms.The latencyalsovariedwith CF (p < 0.001), reducingwith increasingCF. TABLE II. Mean latencies(in ms) for responses to binauralAM/FM stimuli at 30 dB HL, awakeand asleep.Frequenciesare in Hz.

Carrier Modn. freq. Awake freq. range latency s.d.

Asleep latency s.d.

250

30-60

31.8

7.6

34.1

10.8

500

30-60

34.1

4.9

34.6

9.0

1000

30-60

34.1

4.1

26.5

5.7

2000

30-60

31.3

4.1

30.7

14.2

4000

30-60

28.4

3.6

33.8

13.9

250

90-110

28.9

11.5

17.8

9.3

500

90-190

14.8

3.1

14.1

3.7

1000

90-190

13.9

2.8

11.2

3.1

2000

90-190

11.8

2.0

10.3

1.1

4000

90-190

9.9

1.1

9.4

1.2

Cohen ot a/.' Evoked potentials,awake and asleep

2473


-18o / , -38o[-540•-720 •-

,

, , 250 Hz

,

,

,

,

,

,

,

,

FIG. 8. Individualphaseandamplituderesponses (upperandlowercurves, respectively)for sleepingsubjectstobinauralAM/FM stimulationat 30 dB

only 2-5 observations for eachsleepstageat eachmodulation frequency.Therefore,for statisticalanalysis,we increasedthe numberof observations by groupingthe responsesinto low, intermediate,and high ranges of modulationfrequency(30-60 Hz, 80-110 Hz, and 120-190 Hz). Variationwith modulationfrequencyof the meanresponse phaseandamplitudeisshownin Fig. 10,for thethree sleepstages. The variationof EEG noise,responseamplitude,and detectionefficiencyhave been consideredwith three independentvariables: CF, sleepstage,andmodulationfrequency range ("range"). Three-way ANOVAs performedon amplitudeandthe squarerootof efficiency revealedsignificant interactionsbetweenrange and both CF and stage (p < 0.0001). Hence,statisticalanalysiswasperformedseparatelyfor eachrange.The squarerootof efficiency wasused

HL. Theseresponses gaveriseto themeansleeping responses of Fig. 7.

in statistical calculations because its distribution was more

0.80

z

0.70

0.60 0.50

-900 t

-1080

0.40

0.$0 0.20

-1620[

0.10

, 40

80

120

0.00

160

_

- 182o

.'.',•, • .•,Z;;,;•:*•_.

•

.............

0

40

80

120

160

';;;,• :-_-' =_?.*• 0

40

80

120

O. lO

160

Nodulafion Frequency (Hz)

Meannoiselevelsfor thisexperimenthavebeenplotted in Fig. 2. Thesenoiselevelsweremeasured overa frequency interval proportionalto the modulationfrequency,and hence the noise spectraldensitydecreasedat a further 3 dB/oct. For awakesubjects therewasa gradualreductionof noise level between 30 and 190 Hz. The mean noise levels in

sleepingsubjectswere not only much lower than in awake subjects,but experienceda greaterproportionalreduction overthe samerange. The detectionefficiencyis plotted in Fig. 9 for awake and sleepingsubjects,calculatedfrom the meanamplitudes of Fig. 7 and the mean noiselevelsof Fig. 2. For subjects asleepcomparedto awake,therewas a reductionof detection efficiencybelow a modulation frequencyof 70 Hz. There was, however, an increasein efficiencyabove 70 Hz for 1, 2 and 4 kHz but not for 250 or 500 Hz.

3. Further analysis of 30-dB HL data

a. Variationwithsleepstage.Of the total sleepingtime for the ten subjectsof experiment2 (Section2), 53% was judgedto be in stage2, 26% in stage3/4 and 21% in stage REM. Segregating the responseat eachstimuluscondition into threesleepstages(stage2, 3/4, and REM) resultedin

nearly normal than that of the efficiency. Two findingsalloweda simplificationof the analysis. First, asonewouldexpect,EEG noisedid not vary with CF for any range (p > 0.7). EEG noiseis independentof responseamplitudeand henceshouldnot dependon stimulus parametersother than modulationfrequency.Second,in

eachrange,neitheramplitudenor efficiencyvariedsignificantlybetweenstages2 and 3/4. The samewastrue for noise exceptfor the intermediaterangeof modulationfrequency, for which noisewas greaterin stage2 than in stage3/4 (p < 0.001). Althoughthisonedifference wasfound,stages 2 and3/4 havebeengroupedtogetheranddesignated stage NREM. The abovefindingsfor EEG noise,amplitude,and efficiency werefrom two-wayANOVAs with CF and sleep stageas variables. EEG noisewassignificantlysmallerin stageREM than NREM in theintermediaterange(p < 0.0001) andthe high range (p 0.45). This resultsuggests that the variationof amplitude with sleepstagefor modulationfrequenciesin the high range,in the main part of experiment2, wascausedby data for the sleepstagesbeingdrawn from differentsetsof subjects,with quitesmallsamplenumbersfor stageREM.

Latenciesof approximately30 and 10 ms were found, for AM and AM/FM stimuli,at modulationfrequencies of 30-60 Hz and90-195 Hz, respectively.Latenciesof about30 ms have alsobeenfound for AM responses at modulation frequencies in the vicinityof 40 Hz by Rickardsand Clark (1984), Kuwada et al. (1986), and Picton et al. (1987b). Latencies of about 10 ms have been found for modulation

frequenciesabove about 90 Hz by Rickards and Clark (1984) and Kuwada et al. (1986). It has been found in animal studies that the modulation

frequenciesto which the auditory systemis mostsensitive decreaseas one ascendsthe auditory pathway (Rees and M•ller, 1983, 1987; Batra et al., 1989). This has beenseen for animalsin locallyrecordedevokedpotentials(Rickards

I •....I I I I I I I '•.

c = Sfoge

- 13,,,•, o---a Stoge 2314-

0.4

_I

0.3

REM_

2 kHz .... ::'::'::t m 0.1

4 kHz o

> 0.0 o

-,-• -.•

0.0 100

III. DISCUSSION A. General

1.A wake responses to AM tones

The resultsobtainedin the initial part of the study,for AM tones,weregenerallyconsistentwith thosereportedby our group (Rickards and Clark, 1984) and by others (Rees et al., 1986;Kuwada et al., 1986;Picton et al., 1987b). The response amplitudepeakfoundat about40 Hz hasbeennoted in, or can be seenin the resultsof, all the cited studies.The

existenceof an amplituderesponse minimumandmaximum at about70 and 90 Hz, respectively,hasnot beenshownin the literature.That they havenot beenobservedmay be attributedprimarily to inadequatetestingin this modulation 2476


o,m,

1

I

!

I

Fr'equency (Hz)

FIG. 13.Mean backgroundEEG noise,amplituderesponse, andefficiency for a singlesleepingsubjectwith carder frequency/modulation frequency combinationsof 1 kHz/40 Hz, 2 kHz/90 Hz, and 4 kHz/160 Hz. Stimula-

tionwasbinauralAM/FM at 30 dB HL. Sleepstages2, 3/4, andREM are shownassolid,dashed,anddottedlines.Error barson amplitudeandnoise are plusand minusone standarderror.

Coheneta/.' Evokedpotentials,awakeandasleep

2476


and Clark, 1972) and in single-unitmeasurements(e.g., compare M•ller, 1974b and Rees and M•ller, 1983). As modulation frequencyis reduced,the main site of evoked potentialgenerationis likely to moveup the auditorypathway and the responselatencyis likely to increase. The neural originsof transientevokedpotentialpeaks may provideinsightinto the possiblesitesof generationfor steady-stateresponses, if one assumesthat responses with similar latencieshave commonorigins.A correspondence existsbetweenlatenciesdeducedfrom steady-stateand transientevokedpotentials(Rickards and Clark, 1984). In the region30-60 Hz the mean latencyfor 2- and 4-kHz CFs at

(Nelsonetal., 1966;M•ller, 1974a)andbya neuromagnetic study(M/ikel/i et al., 1987). The introductionof FM may produceadditionalresponsecomponentsdue to suchsystems,and thesecomponents may add algebraicallywithin the volume conductorof the head to give larger total responses.

$. Differences between awake responses to AM/FM tones

at $$ dB HL and $0 dB HL

petitionrate is thoughtto be producedprimarily by a cortical generator(M/ikel/i and Hari, 1987). The MLR peakPa, probablyimportantin the productionof the steady-state responseat about40 Hz, appearsto be generatedmainly in the areaof the Sylvianfissure(Zimmerman et al., 1981;Cohen, 1982; Schergand Von Cramer, 1984). Hashimoto et al.

We believethat irregularitiesfoundin phaseresponses at 55 dB HL indicatethat responses to low CFs werein part the resultof excitationby low-frequencystimuliof basalregionsof thecochlea.Somebasalexcitationcouldbeexpected at 55 dB HL. At 30 dB HL, where no phaseirregularities were seen,excitationwould be localizedto the appropriate cochlearsite.Further, the detectionof responses at levelsof 30 dB HL stronglysuggests that the steady-state responses originatefroma regionin thecochleathat corresponds to the stimuluscarrier frequency. For the mostpart, the formsof the amplituderesponse functionsat 55 and 30 dB HL were similar,althoughthere wasan overallreductionat 30 dB HL. This findingsupports the assumptionthat the relativeresponse amplitudesat variousmodulationfrequencies will remainsimilarasthe stimuluslevelsapproachbehavioralthreshold.This assumption is implicit in the useof the detectionefficiencyfunction to determinethe parametersto be usedfor thresholdmeasure-

(1984) and M•ller and Jannetta (1985) have concluded

ment.

55 dB HL, 28.8 ms, is similar to that of the click-evoked

MLR peakPa, 26.5 msaccordingto Kavanaghet al. (1984)

fora levelof 75dBnHL, witha repetition rateof9.7s- • and a filter setting of 15-3000 Hz (24 dB/oct Butterworth filters). Similarly, in the region above90 Hz the mean latency for 2- and 4-kHz CFs, 9.1 ms, is similar to that of the peakSN-10 (or 2Vo), 9.7 msaccordingto Kavanaghetal. for the sameclick stimuliand filter settings.

The response to transientstimuliwith about40 s- • re-

from intracranialrecordingsin humansthat the inferiorcolliculusistheprimarysourceof thetransientpeak2Vo(or SN10). Hence, it is possiblethat the 10-msresponseto AM or AM/FM tonesis generatedprimarily in the midbrain. Differences between awake responses to AM and AM/FM

tones

The larger responseamplitudesfor AM/FM than for AM tonesmay be due to peripheralor centralfactorsor to both. Responses to AM/FM tonesmay be larger because thesestimuli excitelarger regionsof the basilarmembrane, asindicatedby the spectraof Fig. 1. In additionit shouldbe observed that frequencyresponse anomaliesof earphoneand subjectwould causesomeamplitudemodulationto be producedby the frequencyvariation in the AM/FM stimulus, andthat thisadditionalAM mightcombinewith the original AM to producea stimuluswith increasedenergy.However, onewouldexpectthat for somestimulusconditionsthe energy would be unaffectedor evenreduced.As an almostuniform increasein responseamplitudewasobservedwith the introductionof FM, it is unlikely that the productionof additionalAM can explainthe increasedamplitudes. A possiblecentralmechanismto accountfor the larger responseamplitudesfor AM/FM stimuli may be that they activateadditionalprocessing channelsassociated with frequencymodulation.The existenceof systemsin the auditory neural pathwaysselectivelysensitiveto frequencychange, rather than amplitudemodulation,has been indicatedby psychophysical studies(Kay and Matthews, 1972; Regan andTansley,1979;Tansleyet al., 1982;Tansleyand Suffield, 1983;Reesand Kay, 1985), by singlecell studiesin animals 2477

J. Acoust.Soc.Am.,Vol. 90, No.5, November1991

4. Differences between sleep/rig and awake responses to AM/FM

tones at 30 dB HL

The fact that responseamplitude reductionsduring sleepwere greaterfor modulationfrequenciesat around40 Hz than for thosein excessof 70 Hz suggests that the generator primarily responsible for awakeresponses at around40 Hz, with latencyof about 30 ms, is more affectedby sleep than the generator primarily responsiblefor awake responsesabove70 Hz, with a latencyof about 10 ms. It hasbeenshownthat the amplitudedifferencebetween the MLR peaksP• and 2Vb,thoughtto be primarily cortical in origin,is reducedby almost50% duringsleep(Osterhammeletal., 1985). As it islikelythatthesepeaksareimportant in the productionof steady-state responses with latenciesof about 30 ms, it is not surprisingthat the amplitudesof the steady-stateresponsesare also reducedduring sleep.The transientpeak SN- 10 (2Vo) and the steady-state10-msresponsehave similar latenciesand both possiblyoriginate mainlyin themidbrain.SN- 10appearsto belittle affectedby sleep(Osterhammelet al., 1985) and,indeed,is usedin conjunction with wave V of the ABR in frequencyspecific thresholdestimationin sleepingor sedatedinfants (Davis, 1979and e.g.,Hyde et al., 1987). The only publishedstudiescomparingawakeand sleeping steady-stateresponseshave been for repeated tone

bursts.For repetitionratesof around40 s- •, theresponses to suchstimuliappearto be very similarto thoseevokedby AM (or AM/FM ) tones.The two responses may yetbe seen to differ in importantrespectsbut a cautiouscomparisonof Coheneta/.' Evokedpotentials,awakeand asleep

2477


the findingsmay be made. In tone-burststudies,response

amplitudes atabout40s- i havebeenfoundtoreduce during sleep(Linden et al., 1985;Jergeret al., 1986;Pictonet al., 1987c).Backgroundnoise,a quantityindependent of stimulus,alsofell (Linden etal., 1985;Jergeretal., 1986) asin our study.Two studieshave found that the detectabilityof responses,and henceresponseamplitudeto noiseratio, remainedmuch the same (Linden et al., 1985;Jergeret al., 1986). However, a more recent paper by Picton et al. (1987c) reportedthat detectabilityreducedduringsleep,in agreementwith our findings. 5. Response variation with sleep stage

We have also found significantvariationsof response amplitude,backgroundEEG noise,andresponse detectability betweensleepstages,specifically betweenstageRœM and a groupof stagescomprisingstages2, 3, and4. No significant variationshave been found between stagesin tone-burst -1 studies,althoughrepetitionrateshavenot exceeded60 s anddatafor stageRœM in particularweresparsein Jergeret al. (1986). Our findingthat backgroundœœGnoisedid not differwith stagein the range30-60 Hz isconsistentwith that of Lindenet al. (1985) for repetitionratesbetween30 and 50 s-•. However,the significant variationof response amplitudewith stagein a similarmodulationfrequencyrangehas not beenpreviouslyreported.While Pictonet al. (1987c) revisedtheir earlier finding that thresholdmeasurements were similar for subjectsawakeand asleep(Linden et al., 1985), in the light of improvedexperimentaltechniques, they did not reconsiderthe questionof variationwith sleep stage.Our measurements performedon a singlesubjectin experiment2 tendto confirmthat stagedifferences exist,at least for AM?FM stimuli. Kraus et al. (1989) have observed

stagedifferences in detectabilityof transientmiddlelatency responses to clicksin children. The greater detection efficiencyfound during stage REM than during stages2, 3, and 4 in the 80- to 110-Hz range, was attributableto a combinationof lower backgroundœœGnoiselevel and larger responseamplitudein REM sleep."EEG noise"is in fact a combinationof true EEG noiseand myogenicactivity.Low noisein REM sleep may resultfrom low myogenicactivity,reflectedin the minimum EMG observedin stageREM. However, although myogenicactivityisleastin stageRœM, it isconsideredto be a shallowstageof sleep.Largerevokedpotentialamplitudes, intermediatebetweenawakeand non-REM sleepingamplitudes,may reflectthat aspectof REM sleep. B. Clinical application

Althoughthe MLR andthe "40 Hz response"havebeen usedin the assessment of hearingin infantsand youngchildren, the detectionof the responses has been found to be inconsistent (ShallopandOsterhammel,1983;Krauset al., 1985;Stapellset al., 1988). Kraus et al. (1985) haveshown that the detectabilityof the Pa wave ( 30 ms) of the MLR is dependenton the subject'smaturationanddecreases to less than 50% in very young children. Kraus et al. (1989) further found that the detectability of the MLR in 4- to 92478

J. Acoust.Soc. Am., Vol. 90, No. 5, November 1991

year old childrendependson sleepstage,whichcouldaccountin part for inconsistent detectabilityin previousstudies.

In contrast, the SN-10 transient responsehas been foundto be consistentlyrecordedin normallyhearingnewborns(HawesandGreenberg,1981;ShallopandOsterhammel, 1983), which suggests that the 10-msresponse is less affectedby maturationand sleepstage.The useof steadystateevokedresponses in the assessment of hearingin sleeping infantsand youngchildrenmay be mosteffectivewhen usingresponses with latenciesof about10ms.Our resultsin adultssuggest that modulationratesin excess of 70 Hz will berequiredin orderto producetheselatencies.Thesehigher modulationratesmay givemore consistentand reliableresponses than ratesaround40 Hz, whichproduce30-msresponses.

ACKNOWLEDGMENTS

This researchwassupportedin part by grantsfrom the National

Health and Medical Research Council of Austra-

lia, the DeafnessFoundation of Victoria, and the Australian

Bionic Ear and Heating ResearchInstitute, Australia.We wishto thankespeciallythe two anonymous reviewerswho, by their constructivecommentsand patience,helped to shapethepaper.Our thanksareduealsoto Dr. JohnTrinder for hisexpertassistance with sleepstaging,to Dr. PeterBlamey and Dr. Peter Busbyfor valuablecommentson the manuscript,and to OrioleWilsonand LouisFanchettefor assistance with sleepsessions.

Batra, R., Kuwada, S., and Stanford,T. R. (1989). "Temporalcodingof envelopes andtheir interauraldelaysin the inferiorcolliculusof the unanesthetized rabbit," J. Neurophysiol.61, 257-268. Brown,D., andShallop,J. (1982). "A clinicallyuseful500Hz evokedresponse,"Nicolet Potentials1, 9-12. Cohen, L. T. (1990). "Automated detection of auditory steady-state evokedpotentialsin wakingand sleepingsubjects,"unpublished Ph.D. thesis.

Cohen,L. T., and Rickards,F. W. (1987). "Steady-stateevokedpotentials in sleepinghumansto continuousmodulatedtones,"J. Acoust.Soc.Am. Suppl. 1 82, S118. Cohen,M. M. (1982). "Coronaltopographyof the middlelatencyauditory evokedpotentials(MLAEPs) in man,"Electroencephalogr. Clin. Neurophysiol.53, 231-236. Davis,H. (1976). "Principlesof electricresponse audiometry,"Ann. Otol. Rhinol. Laryngol.Suppl.28, 4-96. Davis, H. (1979). "A slowbrainstemresponsefor low-frequency audiometry," Audiology18, 445-461. Elliot, C., Green,G. G. R., andLindsey,L. A. (1984). "A rapidmethodfor the objectiveestimateof pure toneand intensitydiscrimination thresholds," Br. J. Audiol. (London) 18, 248-249.

EtymoticResearch(1985). "EtymoticResearchER-3a TubephoneInsert Earphone Calibration Instructions,"Etymotic Research,61 Martin Lane, Elk Grove Village, IL 60007. Galambos,R., Makeig,S.,andStapells,D. R. (1984). "The phaseaggregation of steadystate(40 Hz) eventrelatedpotentials:its usein estimating hearingthresholds,"Paperpresented at theXVII InternationalCongress of Audiology,SantaBarbara,CA, 26-30 August. Galambos,R., Makeig,S.,andTalmachoff,P. J. (1981). "A 40 Hz auditory potentialrecordedfrom the human scalp," Proc. Nat. Acad. Sci. 78, 2643-2647.

Gorga,M.P., Kaminski,J. R., Beauchaine, K. A., andJesteadt, W. (1988). "Auditory brainstemresponses to toneburstsin normallyhearingsubjects," J. Sp. Hear. Res.31, 87-97. Hall, J. W., III (1983). "Auditory brainstemresponseaudiometry,"in Cohen et al.: Evoked potentials,awake and asleep

2478


HearingDisorders in Adults,editedbyJ. Jerger(College-Hill,SanDiego, CA), pp. 1-55. Hashimoto,I., Ishiyama, Y., Nemoto, S., Kuroiwa, A., Yasuda, K., and Sekine,Y. (1984). "Intracranialorigin and scalpdistributionof slow brainstemauditoryevokedpotentials,"in EvokedPotentials II, editedby R. H. Nodar and C. Barber (Butterworth, Boston,MA), pp. 145-156. Hawes,M.D., and Greenberg,H. J. (1981). "Slow brainstemresponses (SN 10) to tonepipsin normallyhearingnewbornsandadults,"Audiol. 20, 113-122.

Hyde, M. L., Matsumoto,N., andAlberti, P. W. (1987). "The normative basisfor click and frequencyspecificBERA in high-riskinfants,"Acta Otolaryngol.103, 602-611. Jerger,J., Chmiel,R., Frost,J. D., Jr., and Coker,N. (1986). "Effectof sleepon the auditorysteadystateevokedpotential,"Ear Hear. 7, 240245.

Kay, R. H., andMatthews,D. R. (1972). "On theexistence in humanauditorypathways of channels selectively tunedto themodulationpresentin frequency-modulated tones,"J. Physiol.225, 657-677. Kavanagh,K. T., Harker,L. A., andTyler,R. S. (1984). "Auditorybrainstemand middle latencyresponses. I. Effectsof responsefilteringand waveformidentification;II. Thresholdresponses to a 500-Hz tonepip," Ann. Otol. Rhinol. Laryngol. (Suppl. 108) 93, 1-12. Kraus, N., Smith, D. I., Reed, N. L., Stein, L. K., and Cartee, C. (1985).

"Auditorymiddlelatencyresponses in children:effectsof ageanddiagnosticcategory,"Electroencephalogr. Clin. Neurophysiol.62, 343-351. Kraus, N., McGee, T., and Comperatore,C. (1989). "MLRs in children are consistently presentduringwakefulness, Stage1, and REM sleep," Ear Hear. 10, 339-345.

Kuwada, S., Batra, R., and Maher, V. L. (1986). "Scalppotentialsof nor-

malandhearing-impaired subjects in response to sinusoidally amplitudemodulated tones," Hear. Res. 21, 179-192.

Linden, R. D., Campbell,K. B., Hamel, G., and Picton,T. W. (1985). "Human auditory steadystate evoked potentialsduring sleep," Ear Hear. 6, 167-173.

M•ikel•i,J.P., andHari, R. (1987). "Evidencefor corticaloriginof the 40 Hz auditoryevokedresponse in man," Electroencephalogr. Clin. Neurophysiol.66, 539-546. M•ikel•i, J.P., Hari, R., and Linnankivi, A. (1987). "Different analysisof frequency andamplitudemodulations of a continuous tonein thehuman auditorycortex:A neuromagnetic study,"Hear. Res.27, 257-264. M•Jller,A. R. (1974a). "Codingof sounds withrapidlyvaryingspectrumin the cochlear nucleus," J. Acoust. Soc. Am. 55, 631-640.

M•Jller,A. R. (1974b). "Responses of unitsin thecochlearnucleusto sinusoidallyamplitude-modulated tones,"Exp. Neurol. 45, 104-117. M•Jller,A. R., andJannetta,P. J. (1985). "Neural generators of the auditorybrainstemresponse," in TheAuditoryBrainstemResponse, editedby J. T. Jacobsen(Taylor Francis,London), pp. 13-31. Nelson,P. G., Erulkar, S. D., andBryan,J. S. (1966). "Responses of units of theinferiorcolliculusto time-varyingacousticstimuli,"J. Neurophysiol. 29, 834-860.

Osterhammel,P. A., Shallop,J. K., andTerkildsen,K. (1985). "The effect of sleepon the auditorybrainstemresponse(ABR) and the middlelatencyresponse(MLR)," Stand. Audiol. 14, 47-50. Picton,T. W., Dauman,R., andAran, J.-M. (1987a). "R6sponses 6voqu6es en 'r6gimepermanent'chezl'hommepar la modulationsinuso'idale de fr6quence,"J. Otolaryngol.16, 140-145. Picton,T. W., Skinner,C. R., Champagne, S.C., Kellett, J. C., andMaiste, A. C. (1987b). "Potentialsevokedby the sinusoidalmodulationof the amplitudeor frequencyof a tone,"J. Acoust.Soc.Am. 82, 165-178. Picton,T. W., Vajsar,J.,Rodriguez,R., andCampbell,K. B. (1987c). "Reliability estimatesfor steady-state evokedpotentials,"Electroencephalogr. Clin. Neurophysiol.68, 119-131. Rechtschaffen,A., and Kales, A. (1968). "A manual of standardizedterminology,techniques andscoringsystemfor sleepstagesof humansubjects,"Instituteof Health PublicationNo. 204 (U.S. GovernmentPrinting Office,Washington,DC).

2479


Rees,A., Green, G. G. R., and Kay, R. H. (1986). "Steady-stateevoked responsesto sinusoidallyamplitude-modulatedsoundsrecorded in man," Hear. Res. 23, 123-133.

Rees,A., and Kay, R. H. (1985). "Delineationof FM ratechannelsin man by detectabilityof a three-component modulationwaveform,"Hear. Res. 18, 211-221.

Rees,A., and M•Jller,A. R. (1983). "Responses of neuronsin the inferior colliculusof the rat to AM and FM tones," Hear. Res. 10, 301-330. Rees,A., and M•Jller,A. R. (1987). "Stimuluspropertiesinfluencingthe responsesof inferior colliculus neurons to amplitude-modulated sounds," Hear. Res. 27, 129-143.

Regan,D. (1966). "Somecharacteristics of averagesteady-stateand transientresponses evokedby modulatedlight," Electroencephalogr. Clin. Neurophysiol.20, 238-248. Regan,D. (1972). EvokedPotentials in Psychology, Sensory Physiology, and ClinicalMedicine(ChapmanHall, London). Regan,D. (1977). "Fourier analysisof evokedpotentials;Somemethods basedon Fourieranalysis,"in VisualEvokedPotentialsin Man: New Developments, editedby J. E. Desmedt(Oxford U. P., Oxford), pp. 110117.

Regan,D., andTansley,B. W. (1979). "Selectiveadaptationto frequencymodulatedtones:Evidencefor an information-processing channelsensitive to frequencychanges,"J. Acoust.Soc.Am. 65, 1249-1257. Rickards,F. W. (1983). "Auditory steady-state evokedpotentialsin humansto amplitude-modulated tones,"unpublishedPh.D. thesis. Rickards,F. W, and Clark, G. M. (1972). "Field potentialsin cat auditory nucleiin response to frequencyand amplitudemodulatedsound,"Proc. Aust. Physiol.Pharmacol.Soc.3, 201. Rickards,F. W., and Clark, G. M. (1982). "Steady-stateevokedpotentials in humansto continuousamplitudemodulatedtones,"J. Acoust. Soc. Am. Suppl. 1 72, S54. Rickards,F. W., and Clark, G. M. (1984). "Steady-stateevokedpotentials to amplitude-modulated tones,"in EvokedPotentialsII, editedby R. H. Nodar and C. Barber (Butterworth, Boston,MA), pp. 163-168. Scherg,M., and Von Cramer,D. (1984). "Topographicalanalysisof auditory evokedpotentials:Derivationof components," in EvokedPotentials II, editedby R. H. Nodar andC. Barber(Butterworth,Boston,MA), pp. 73-81.

Shallop,J. K. (1983). "Electricresponse audiometry:the morphologyof normalresponses," Adv. Oto-Rhino-Laryng.29, 124-139. Shallop,J. K., and Osterhammel,P. A. (1983). "A comparativestudyof measurements of SN-10 andthe 40/seemiddlelatencyresponses in newborns," Scand. Audiol. 12, 91-95.

Stapells,D. R., Galambos,R., Costello,J. A., and Makeig, S. (1988). "Inconsistency of auditorymiddlelatencyand steady-state responses in infants,"Electroencephalogr. Clin. Neurophysiol.71, 289-295. Stapells,D. R., Linden, D., Suffield,J. B., Hamel, G., and Picton, T. W. (1984). "Human auditory steadystatepotentials,"Ear Hear. 5, 105113.

Stapells,D. R., Makeig, S., and Galambos,R. (1987). "Auditory steadystateresponses: thresholdpredictionusingphasecoherence," Electroencephalogr.Clin. Neurophysiol.67, 260-270. Stapells,D. R., Picton, T. W., and Smith, A.D. (1983). "Predictionof audiometricthresholdsin normaland hearing-impaired subjectsusing the40 Hz eventrelatedpotential,"CanadianSpeechandHearingAssociation annualconvention,13 May 1983,Montreal, Canada. Tansley,B. W., Regan,D., and Suffield,J. B. (1982). "Measurementof the sensitivitiesof information-processing channelsfor frequencychange andfor amplitudechangeby a titrationmethod,"Can. J. Psychol.36(4), 723-730.

Tansley,B. W., and Suffield,J. B. (1983). "Time courseof adaptationand recoverychannelsselectively sensitive to frequencyandamplitudemodulation," J. Acoust. Soc. Am. 74, 765-775.

Zimmerman, J. T., Reite, M., and Zimmerman, J. E. (1981). "Magnetic auditory evokedfields:Dipole orientation,"Electroencephalogr. Clin. Neurophysiol.52, 151-156.

Cohen eta/.: Evoked potentials,awake and asleep

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The effect of intrathecal morphine on somatosensory evoked potentials in awake humans.

Selective attention and evoked potentials in humans--a critical review.

Frontal negativity of pattern-reversal visual evoked potentials in humans.

Audiometric comparison of the middle and late components of the adult auditory evoked potentials awake and asleep.

Visual evoked potentials during etomidate administration in humans.

Short latency mechanically evoked somatosensory potentials in humans.

Stimulus-specific adaptation in field potentials and neuronal responses to frequency-modulated tones in the primary auditory cortex.

Measurement of Electroretinograms and Visually Evoked Potentials in Awake Moving Mice.

Principal pitch of frequency-modulated tones with asymmetrical modulation waveform: a comparison of models.

Evoked spinal cord and nerve root potentials in humans using a non-invasive recording technique.

Frequency discrimination for pulsed versus modulated tones.

An automated and reliable method for breath detection during variable mask pressures in awake and sleeping humans.

Frequency-modulated steady-state visual evoked potentials: a new stimulation method for brain-computer interfaces.

Motor-Evoked Potentials in the Lower Back Are Modulated by Visual Perception of Lifted Weight.

Origin and distribution of brain-stem somatosensory evoked potentials in humans.

Tradeoff between User Experience and BCI Classification Accuracy with Frequency Modulated Steady-State Visual Evoked Potentials.

Effects of timing of inspiratory occlusion on cerebral evoked potentials in humans.

An objective indicant of binocular vision in humans: size-specific interocular suppression of visual evoked potentials.

Prandial States Modify the Reactivity of the Gustatory Cortex Using Gustatory Evoked Potentials in Humans.

Electrophysiologic studies of cervical vagus nerve stimulation in humans: II. Evoked potentials.

Interaction of Musicianship and Aging: A Comparison of Cortical Auditory Evoked Potentials.

Monitoring electrophysiologic function during carotid endarterectomy: a comparison of somatosensory evoked potentials and conventional electroencephalogram.

Flash evoked potentials in migraine.

[Evoked potentials in HIV infection].