A 40-Hz auditory potential recorded from the human scalp (hearing tests/auditory evoked potentials/40-hz brain waves/sensory processing)

Proc.Nati.Acad. Sci. USA

Vol. 78,No. 4, pp. 2643-2647,April 1981

Psychology

A 40-Hz

auditory

potential recorded from the human scalp

(hearing tests/auditory evokedpotentials/40-Hz brainwaves/sensory processing) ROBERT

GALAMBOS*t,

SCOTT

MAKE1I0,

AND PETERJ.

TALMACHOFF§$

Departmentsof*Neurosciences,tMusic, and §Applied Mechanicsand Engineering, University of CaliforniaatSanDiego, LaJolla,California92093;andtSpeech, Hearing,and Neurosensorv Center, 8001 Frost Street, San Diego, California 92123

ContributedbyRobertGalambos, December23, 1980

ABSTRACT Computer techniques readily extract from the brainwaves anorderly sequenceof brainpotentialslocked in time to sound stimuli. Thepotentialsthatappear8 to80 msec after the

stimulusresemble3 or 4cyclesofa 40-Hz sinewave;we show here that these waves combine to form asingle,stable, compositewave

when the sounds are repeated at rates around 40 per sec. This phenomenon, the 40-Hz event-relatedpotential (ERP), displays

severalproperties oftheoretical and practicalinterest. First, it

reportedly disappearswithsurgical anesthesia, and it resembles similarphenomenain the visual andolfactory system,facts which

suggestthatadequate processingofsensoryinformationmay

re-quire cyclical brain events in the 30- to 50-Hzrange. Second,

la-tencyandamplitude measurementson the 40-Hz ERPindicate it maycontain usefulinformation on the number and basilar

mem-brane location of theauditorynerve fibers agiventoneexcites. Third, the responseispresent at sound intensities veryclose to normal adult thresholds for the audiometric frequencies, afact thatcould haveapplicationin clinicalhearing testing.

When a person cannot, or will not, tell the interested observer what he hears, it has in the pastbeen difficult to obtain trust-worthy measurements of hearing. The recent advent of elec-trophysiological tests ofhearing and comprehension has radi-callychangedthissituation(1, 2).Inthesetestsonerecords the listener's brainwaves while sounds are presented via

loud-speakerorearphones; the sounds generate electric responses within the brain thatarereadilyextractedbyacomputer (Fig. 1A).Theresulting sequence ofbrainpotentials,knownas

event-related potentials (ERPs), begins within amillisecond or two

of stimulusdeliveryandcontinues thereafter forahalf second

or more. Wedeal here with theseriesofwavesthat appears 8-80

msecafter stimulus delivery, the so-called middle-latency

re-sponse (MLR). We report away to extract itfrom the brain-waves,describe several properties of the response soobtained, and, among other things, show it to predict adult auditory thresholdsin ahighly reliablemanner.

METHODS

Any groupofinstruments thatcompetently generates acoustic

signals, amplifiesbrain waves, and averagesERPs(Fig. 1A)can

be usedtodemonstrate thephenomenontobe describedhere. The response was,infact, discovered byoneofus(P.J.T.), using

a stimulator, amplifier, and computer built in the laboratory (3). Sincethenwehave used four different types ofsignal gen-erators, several types ofearphones (including a hearing aid

transducer)toproducethe monaural clicksor tonebursts

(usu-ally 6-msec duration, 2-msec rise and fall) employed in this

study, and four different commercial brands of averaging

com-puters. Thebrain waves, usuallv recorded between electrodes

atforehead and earlobe of the ear stimulated, were amplified

at againasnear to105 and withbandpassas near to 10-100 Hz as the settingsof the particular amplifierin useallowed.

Subjectswere 20adults, includingtwoof the authors(R.G.

andS.M.) all of whom (exceptR.G.)wereaudiometrically

nor-mal.Three subjects,repeatedlystudiedover a3-monthperiod,

provided most ofthe data reported here. Recordingsweremade with subjects seated or lying comfortably, usually awake but

sometimesdozingor inlight sleep. Ambient sound ranged from thatin asound-proofed chambertothatofan ordinary labora-tory room. R.G. mademostof his ownrecordings by himself, wearing earphones while seated facing the apparatus he was operating. We wishto emphasize that successful recording of thephenomenonwereportcanbecomeroutinewherever avail-ableinstruments and expertise make therecordingof human evokedpotentialspossible.

RESULTS The40-Hz ERPphenomenon

Ourmethod fordisplayingtheMLRcanbe describedasfollows,

with the help of Fig. 1. Fig. 1B shows typical click-evoked MLRs extracted from the electroencephalogram recorded

throughelectrodes locatedatforehead andontheear.The

re-sponseconsistsofa seriesofforehead-negative(N) and positive (P)wavestowhichsubscripts a, b, c, and d have been assigned. The timeinterval between thesuccessive waves in theseries isabout25msec,andsothe sequenceresemblesa trainof three

orfoursinewavesapproximately40 Hz infrequency.

Thelowersection of Fig. 1B shows what might happen if: (i) everyauditorystimuluswere toevoke sucha trainof40-Hz sinusoids, (ii) these stimuliwere toberepeatedat a rateof40

persec, and (iii)acomputertriggered byeveryother stimulus

in thetrain were to extract anaveragefrom the ongoing elec-troencephalogram measurements. The computed average, rep-resentedatthebottom of the figure, would show single waves

ineach 25-msecepoch, all of which would be identicalinform because each representsthe composite, or algebraic sum, of the waveslabeled a, b, and c in the MLR sequence.

That this diagrammatic formulation must be approximately

correct issuggestedbythe severalrecordings of Figs. 1, 2, and 3, whichshow actual computer-extracted responses to sounds repeatedat rates near 40persec. Wewishto namethis com-positeof the MLRtheauditory40-Hzevent-relatedpotential

orthe40-HzERP.

Therateseries

Fig. ICillustrates the synthesis of the 40-Hz ERP by using

ac-tualrecordings. Each recordis displayed ona 100-msec time

Abbreviations: ERP, event-related potential; MLR, middle-latency re-sponse;dB, decibel;dBSL, decibels above threshold.

¶Presentaddress: Allegheny General Hospital, 320E. North Avenue, Pittsburgh,PA 15212.

2643 Thepublicationcostsof this articleweredefrayedinpartby pagecharge payment. This article must therefore beherebv marked "advertise-nent"inaccordance with18 U. S. C. §1734

solely

toindicatethis fact.

BI 40dBSL,500Hz, X2000 25 msec msec N,. Averaged AI response i f I V ', 50msec

FIG. 1. (A) Blockdiagram ofequipmentforextracting auditory ERPs.Electrodespastedtothesubject'sscalp(left)conduct brainwaves

toamplifierandcomputer.Astimulatorsimultaneously energizesthe

earphoneandinitiatesthecomputeraveragingprocess.After the sub-jectreceivesseveral hundred stimuli thecomputermemorycontains

onlythose brainpotentialstimelockedtothestimuli,the othershaving algebraicallysummed towardzero. (B)Upper,time-lockedbrain

po-tentials evokedduringthe first100msecafter click stimuli(arrow;10 persec)consistof the brainstemwaveV(latencyabout6msec) and the MLR,asequenceofnegative (N) andpositive(P)wavessubscripted

a,b,c,and d(subjectS.M.).Lower,diagramtoshow howthecomputer couldsumtheseveral MLRwavesshown aboveintoasinglewaveif

the stimuliwerepresentedatarateof40 persec.(C)Recordingsfrom

asubject(R.G.) receiving 500-Hztoneburstsatdifferentrates (in-cludingthe40 persecrateofB)toillustrate actualsynthesisof the singlewaveat40Hzfrom themultiplewavesatlower stimulus fre-quencies. dB, Decibel; dBSL,decibels abovethreshold;Y.indicates the number ofresponsesaveraged.

base with the moments of stimulus applications indicated by

arrows. At the lowest rate shown the N.7Pa deflection is fol-lowedby alarge negativewave atabout70 mnsecwhose

rela-tionship to the N1 wave seenbythose who stimulate ateven

lowerrates(1)isunclear.Atthe10stimulipersecrate(actually

slightlyless than this soas topermit every response to enter

thecomputerforaveraging) theNb-Pbdeflectionappearsand thewave sequencenowresembles that shown for the subject

ofFig. 1B, despitesomedifferencesindetail. Atthe20 persec rate every 50-misec interstimulus interval contains a pair of

waves notunlike the twothat occupythe first50 msecof the

10 persecresponse.When the stimulusraterises to40per sec,

each25-msecinterstimulus intervalcontainsasinglewave, the approximatealgebraicsumof thetwowaves seenat

correspond-ingplacesinthe20 persecresponse. Fig. iCthussuggests that the40-Hz ERPdoes indeed result from theconsolidation, or

superimposition,ofthesuccessiveN-Pdeflectionsseenin

rec-ordingsmade atlowerrates.

Still anotherwaytovisualize how the40-Hz ERPevolvesout

of themoreorlessindependent40-Hzsinusoids that makeup the MLR is to plotwave amplitudesagainst stimulus rate, as in Fig. 2A. The maximalresponse amplitude isattained with

a40-Hzstimulus rate, aswould bepredictedifalgebraic

sum-mationofseparate40-Hzsinusoidswere

taking place. Similarly,

the minimal

amplitudes

seen at stimulus rates around25and

55 Hzarealso

predicted by

the

theory

becauseneartheserates

thesuccessive40-Hzwavesshouldappearoutof

phase

and thus cancelinthecomputermemory

during

theaveragingprocess.

Theserate studies,

though

so far

performed

on

only

a few normaladults, permitseveralconclusions. First, theMLR, in

the

frequency

domain,resemblesone or more

cycles

ofa40-Hz

sinusoid. Next,

though

individuals varyinthe number of such

cycles

they produce

atlow stimulusrates,atthe40-Hzratetheir

responsesaresimilar. Third, the40-Hz ERPiseasytorecord from normal

subjects;

we havenotfailedinover20attempts.

Finally,

the40-Hz ERPhas withoneexception

always

peaked

in the35to 45-Hzregionatarate near40Hz, but the actual

optimal

rate

probably

variesfromoneperson tothenext. Val-idation of these

conclusions

awaitstheoutcomeof theextensive parametricstudiesthat need tobe

performed.

Theintensityseries

A

plot

ofresponse

amplitude

againstintensityfor250-Hztone

burstsappearsinFig.2B,

along

with severalof the records used

in its construction.The40-Hz ERPvarieswithintensityinthe

following

twointerestingways.

First, response

amplitude

riseswithintensityincrease, and this

amplitude

rise is so

rapid

nearthreshold thatat 10or 15

dBSL it reaches

nearly

half the size itwill

display

at40 or50

dBSL. This

relationship

undoubtedly

reflects a similar steep

amplitude

riseknowntocharacterizecertainof theMLRwaves

(4,

5).

This remarkable property canbe

applied

to threshold esti-mationsas in Fig. 2C, where 40-Hz ERPsto clicksand tones

are shown to approximate, within a few dB, the behavioral threshold

(0

dBSL)

oftwo

subjects.

Theseestimatesweremade withno

difficulty

and withinashort

period

oftime

(each

tracing

shown there took about2minto

obtain).

The

reliability

of the

40-Hz ERPas anestimatorofthresholdwasfurther tested with sevenyoungadults,who received monaural500-Hztones at5, 10,and15dBSL. All

developed

40-HzERPstothe 15-and

10-dB

signals,-

and all but two did so to the 5-dB

signals.

These resultsindicateitshould be

possible

to

apply

thetest

routinely

toclinicalpatient

populations,

and toexpect

reasonably

accu-ratethreshold estimationsfrom them.

The40-Hz ERPalsovaries in

latency

with stimulusintensity.

Technically, latency

isthetimeinterval between stimulusonset

and theresponse it initiates. In the presentcontext this

"re-sponse"

mustbe defined

arbitrarily

assomefeature of the 40-Hz ERPthat

regularly

follows thestimulus,and forconvenience

this feature will be takentobe the

peak

of the

forehead-positive

wavethat follows the stimulus. InFig. 3Athispointismarked

by

arrows.

The

latency

of the40-Hz ERPasdefinedinthisway

ranged

between 100and200Asec (mean 156)for each dB ofintensity

change

in 11determinations on twoofour

subjects

(R.G. and

P.G.).The

signals

used includedclicks andtones(250,350, and

500Hz)

presented

atintensitiesbetween5and50dBSL.

(The

variability

inthe datais

probably

measurement error, nota sys-tematic

relationship

to stimulus type or

intensity.)

The

corre-sponding change

in

latency

foradifferentERPthreshold

mea-sure, the

auditory

brainstem response, is

precisely

known: 40

,usec/dB

(2). Asfor theMLR, the valuesaresaid tovaryfrom

0for the Nawave

through

75forNbto 175

pLsec/dB

for

Pc

(1, 5).Ourestimateofabout150

usec/dB

for the40-Hz ERP agrees

reasonably only

with the

P,

estimate, and so,

tentatively,

we

may supposethat thephysiologicalprocessesthat determine the

way

P,

latency changes

with stimulusintensityalsooperate for the40-Hz ERP.

A~

Proc.Natl.Acad. Sci. USA78(1981) 2645 0.8 a 0.6 S 0.4 al 0.2

A

10 20 30 40 50

Stimuliper sec

100 B 250Hz Ed 80 X0 -6a 20 40 co 10 20 30 40 50 dBSL

FIG. 2. (A) Response amplitudesatdifferentstimulus rates foronesubject (P.G.), showingapeakat about40 stimuliper secand minimaat about 25 and 55 stimulipersec.(B) Response amplitudesat differentintensitiesofa250-Hzstimulus. Insetshowssomeofthe data and thestimulus

sequenceemployed,on a50-msec time base(subject P.G.). Responseisgivenin terms ofpeak heights at constantx-yplotter settings. (C) Threshold estimates obtained with click stimulifromamale adult(S.M.;upperleftrecordings)and withclick and tone stimulifromafemaleadult(P.G.; other threesetsofrecordings).Ineachcase0dBSL refers to the monaural thresholdintensityestablishedimmediately priortoobtainingthe recordsshown.

Recordingsatlowerright illustrateinadditionthe masked thresholdapproximation;the 40-Hzresponsetothe 7-dBSL tonedisappeared when wide-band noisejust sufficienttoabolishthesensationwasadded,butreemerged when,after the toneintensitywasraised to17dBSL, the tonewasheard

once more.

Thefrequency series

Justasstimulus rateandintensitycontrol the40-HzERP

am-plitudesandlatencies, sotoodoesstimulusfrequency. An

ex-ample is illustratedfor asingle subjectin Fig. 3A, where re-sponses to four different tones have been redrawn and superimposed on thesame 25-msectime base. Twoeffects of

stimulusfrequencyonthe 40-Hz ERPstandout:response

am-plitude dropsasfrequency rises, and theresponse latency (as

definedintheprevioussection) shortens. Thesetwoeffects have

been observedinallsubjectssofartested, andtoapproximately

thesame degreein each of them. Specifically, theratioof the response amplitudes yielded by 250-Hz tones and 5000-Hz tones, whichin Fig. 3A approximates3,has been foundtobe

3and2,respectively,intwoother subjects. Similarly, when the latencyof the5000-Hzresponseissubtracted fromthat of the 250-Hzresponse, whichin Fig. 3A yields about 12msec, this

latency difference was found to be 10.5 and 6 msec,

respec-tively,inthetwoother subjects. The subject yielding the

small-estnumbersineachcase(R. G.)istheonlyonewitha high-fre-quencyhearingloss.

Severalexplanationsfor thesedramaticinfluences of stimulus

frequencyuponthe40-Hz ERParepossible. First,the stimulus

envelopeispartly responsible, becauseit risestomaximal

am-plitudeover a2-msecinterval during which12completecycles

ofa6-kHztone,eachprogressivelygreaterinamplitude,move

theeardrum,whereasforthe 500-Hztoneonlyonesuchcycle appears.Itcanbecomputed from this that,except atthreshold,

the 6-kHz tone will almost always activate a given auditory nervefiber somewhat earlier than the500-Hztonethatcanalso

activate it. Asecond possible factoris relatedtotheintensity effectsdiscussedintheprevious section. Themeasurementsof

Fig. 3A were nominally made at 40 dB above threshold (40

dBSL), butan errorof1dBin this estimatewould introduce alatencyerrorof about150/lsec. If thiserrorweretobe10dB,

whichishighly unlikely, the latencyerrorwould,however, be

only1.5msec.

Thereappears,finally,tobeonlyoneviable explanationfor

thecoupled facts that amplituderisesand latencyincreaseswith

adropin stimulusfrequency. With such adropthe lengthof

basilarmembraneputintomotion increases,thepositionofthe peakofthe basilarmembrane excursionmovesawayfromthe

stapes, and more time is needed for the mechanical wave to

reach thispeakregion. Inother words, asBekesy showed, the

mechanical wave activates increasingly larger amountsof the

basilarmembraneand takesalongertimetodothisasstimulus

frequency drops. Correspondingly, increasingly larger

num-bers ofneurons become excited, and moretime is needed to

initiateandcomplete theirexcitation.Theextent towhich these changes taking placeatthecochlear levelareactuallyreflected inthe40-Hz ERPamplitude and latency changes showninFig.

Click C dBSL dBSL 20 12 10 k6 5 3 0 / 1

t

t

I

t

t

0

25

50

I0.2

AV

msec 500-Hz 7 7 5

Masking7

noise 2 added -2 17 25msec

D Forehead ear Forehead-neck Ear-neck 50 msec

FIG. 3. (A) The 40-Hz ERPs evokedatthesamesensation level

(40 dB) but bytonesofdifferentfrequency. Thesamestimulusenvelope

wasused for all stimuli; the bottomtraceshows the 2500-Hztoneburst. Arrowslocate thepoints where forehead-positive deflections peak for thedifferentfrequencies. Note thatasfrequency drops the peaksmove

to the right and the response amplitude increases. (B) Recordings taken within minutes of eachother, showingthata500-Hz toneburst thatproducesthe40-Hz ERPfromanormaleardoes not dosowhen

presentedtoadeafeardespitea12-dB increase inintensity. (C) The 40-HzERPproduced byanear-threshold 500-Hzsignal (top trace)

dis-appeared whenanearplugwasinsertedinto theear(second trace);a

5-dB increase insignal intensity didnotmakethe toneaudiblenordid

itproducea40-Hz ERP(third trace) until the earplugwasremoved

(bottom). Subject: P.G. (D) The 40-HzERPrecorded between electrodes

atforehead and earlobe(top trace) closelyresembles that recorded be-tweenforeheadandneck,which shows that 40-Hz ERPgeneratorsare

locatedneartheforehead, theearand neckregions,orboth. Thenearly flatrecordingwith theear-neckcombination demonstrates that the

40-Hz ERPatboth sitesisnearlythesame,presumably nearlyzero

because it isimplausible that potentialsofeither muscleorbrainorigin

would be bothlarge and equalatthesetwosites. Neck electrode ison

spinousprocessof the seventh cervical vertebra. Stimuli:clicks,about 40 dBSL.Subject:R.G.

3A isofcourseanopenquestion. Onecan,however, estimate

thatperhaps5msecof thelatencyincreasecould beexplained inthis manner, and virtuallyallof theamplitude change.

Ar-gumentssupportingtheseassertionswillbepresented elsewhere.

Controls

Themeasurementssummarizedin Fig. 3B, C,andDseemto

exclude thepossibilitythat the 40-Hz ERPisanuninteresting

artifact ofeither electricalorphysiologicalorigin.Theyallargue

againstthe idea that the electrical signal energizing the

ear-phone enters the recording apparatus through the recording

electrodes andcreatesa"response" through ampliferoverload.

Fig. 3 Band C make the furtherpointthat the 40-HzERPhas beeninvariablyrelatedtowhetherasensation isexperienced,

not towhetherorhow much electrical energyhas been

deliv-ered to theearphone. Fig. 3C is an especiallyconvincing

ex-ample

of this rule:the

earplug

abolished both

auditory

sensation and the 40-Hz ERP atsignal intensities (5 and 10 dBSL) that,

in the absenceoftheplug, produced them both. Themasking

example of Fig. 2Csimilarlystressesthat without thesensation ofa soundrepeated40timespersecond there is no 40-HzERP. Reflex muscle contractions initiated by the sound stimulus represent physiological artifacts that potentially contaminate all

MLRs. Themusclesofprincipal concern here lie near the ear-lobe electrode, where they vary in size, responsivity, and

thresholdsensitivity from onesubject to the next. It is

improb-able that ourrecordings represent or even contain muscle ar-tifact because the weak stimulus levels used generally fail to

produce reflex responses. Fig. 3D specifically argues thatthe

forehead electrodeis the major source of the 40-Hz ERP re-sponseintheforehead-earcombination of this study. The

ear-lobeelectrode, thoughclose to the periauricular muscles ofcon-cern, isevidentlynotnear animportant 40-Hz ERPgenerator

because little deflection appears in the earlobe-to-neck

elec-trodecombination. Allrecords employing an electrode on the

forehead, bycontrast, showlarge40-Hzwaves ofapproximately

the sameamplitudeand phase. The data of Fig. 3D,

inciden-tally,arepart ofamappingstudywedo not report here except

to state that theforehead electrode site usually yields larger responsesthan does Pz(as defined in the 10-20 international systemforelectrodeplacementonthescalp) and slightly smaller

onesthanCzand Fz.

DISCUSSION

The auditory brainstem response, currently the most widely used method of estimatinghearing threshold by electric re-sponseaudiometry (seeref. 1 forareview), has revolutionized

thehearingassessmentof infantsandchildren. Itprovides se-cureestimatesofhearing threshold,even inthe premature in-fant,butunfortunatelynot atthosetonefrequenciesuponwhich

perception ofspeechsoundscritically depends. Tofill this gap both Suzukietal.(6)andDavisand Hirsh(7)offeran ERPthat appears about10msecafterpresentation oftones inthespeech

range(500-2000Hz)as analternativeoradjunct.

Historically, MLRshave beenrepeatedlyadvocated forthis

purpose(seeref.8forareview) becausetheyoffer"perhapsthe bestmeansofevaluatingthresholdsat avariety offrequencies" (1).The40-Hz ERPdescribedhere, acomposite of the several

waves makingup this MLR, may provetobe apracticalway

toestablish the reliablefrequency-specificthreshold estimates so badlv needed in electric response audiometry. No other

known

method,

inany event, revealssopromptlythe sensitivity

tostimulus

frequency

and intensityshownintherecordingsof

Figs. 1-3. Itremains tobe seen, however, whethersimilarly reliable datacanbeobtained from those patients whomostneed this evaluation-the infants and difficult-to-test children who arecandidates for

hearing

aids.

ThedramaticchangesinamplitudeandlatencyshowninFig.

3A to accompany stimulus frequency change are properties sharedbythe40-Hz ERPwithitsprogenitor, the MLR(4). If

these

changes accurately

reflect mechanicaleventsgoingonat

the basilarmembrane

level,

aswesuggesthere,both responses

containuseful andperhapsevendetailed information aboutthe

population

ofauditory neurons

being

excited within the

coch-lea. Iffurther researchsupports this

hypothesis,

the40-HzERP

could offera

practical

waytoexamine,

through

largeelectrodes

placed

onthe human

scalp,

thedistant basilar membraneevents

now visualized mainly through microelectrodes inserted into animalbrains.

Few data exist concerning the anatomical structures and Volt Deaf child 500-Hz

across stimulus earphone

/artifact

0.4 Normallistener 0.1 50msec c dBSL 5 5 6 arlug /inear

10

Earplug 7/removed 10 50msec

Proc.Natl. Acad. Sci. USA 78 (1981) 2647

physiological processes that give rise to either the MLR or the 40-HzERP. Furthermore, the literature is largely silent on the extent to which sleep, drugs, anesthesia, post-traumtic coma, and stillother altered statesofconsciousnessinfluence theMLR

except to state that sleep and lightsedation have little effect, whereas surgical anesthesia abolishes them (8, 9). It is com-monly held that the MLR reflects activity in the classical

au-ditory pathway (8), although its sensitivity to anesthetics (9) makes the additional involvement ofanextralemniscal, or

re-ticular formation, path seem atleast probable. An exclusively "cortical" origin for either the MLR orthe40-Hz ERP seems

doubtful for still another reason; Fig. 2Ademonstrates its

am-plitudes to be largest at rates around40 Hz, whereas inboth animals (10) andman (1)cortical responses diminishin ampli-tude when sounds arerepeatedasslowly as once eachsecond, andthey approach zero at rates of20per sec. Further experi-ments aimed at identifying the brain structures and processes that generate both the40-Hz ERPand theMLR areclearlyin

order.

Theexistenceof the auditory 40-Hz ERPhas led ustolook for comparable phenomena in vision and the other sensory

modalities.Inhis classicaldescription ofthe human ERP to light flash (11),Ciganek showedapair ofdeflectionsinthe 30- to

90-msecpoststimulus interval (his "primary response") that could be consideredanalogues of the auditoryMLR.Indescribing the

ERPsassociated with modulations of light intensity, Regan (12) said thev "reacha maximum amplitude inthe high frequency range between 45and 55c/sec." Regan's optimal rate is ap-proximately double the frequency ofCiganek's primary re-sponse, and so his ERPs are notreadily related to Ciganek's components in the way the auditory40-Hz ERP is related to the MLR. However, Regan's discovery that flickering lights

produce largeERPswhen the flickerrate isaround50 Hzclearlv definesavisual "50-Hz"ERPthatis atleastconceptually like the auditory40-Hz ERPdescribed here. Whether,foragiven subject, the visual and auditory rate series(asin Fig. 2A) are

similarwould be interestingtoknow.

Namerow etal. (13) studied somesthetic ERPs elicited bv shockstothe median nerve at the wrist. Their graph of response amplitudevs. increasingstimulus rate (comparable to our Fig. 2A) drops nearly linearly except for a small peak at 60 Hz. It

should,however, bepointed out that if a somesthetic response comparable to the auditory 40-Hz ERP did exist Namerow et al.might have missed it because they used large (20-Hz) jumps

in stimulus rate and presented their data as the average over

17subjects.

Inthe olfactory bulb theappearanceofaburst of40-Hzbrain

waves when animals sniff, an act that presumably stimulates smell receptors in the nose, has been known for many years (14). A similar 40-Hz rhythm regularly appearsin other

mam-malian(man,monkev,dog, andcat)andavianbrainregions(see

ref. 15 for asummary), whereit canbe significantly increased

in amount if the animals(cats)aregiven milkreward whenthey produce thewaves (16) and if the people performarithmeticand other cognitive tasks (17). Whether these widespread, labile, ongoing 40-Hz rhythms, which have been interpreted as

in-dexing "a focusedstateof cortical arousal" (17)arerelatedinany

way to the auditory 40-Hz ERP reported hereis a matter for

futureexperiments to settle.

Wethank PhyllisJohnson-Galambos for importantcontributionsas subject andcomputer operator.This workwassupported bygrantsfrom

the National Institutes of Health (NS11707 and11154)and theNational

ScienceFoundation(BNS77-14923).

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