Processing of novel sounds and frequency changes in the ...

Processing of novel sounds and frequencychanges in the human auditory cortex:Magnetoencephalographic recordings

KIMMO ALHO, a,b ISTVÁN WINKLER,a,c CARLES ESCERA,b MINNA HUOTILAINEN, a,d

JUHA VIRTANEN,a,d,e IIRO P. JÄÄSKELÄINEN,a,d EERO PEKKONENa,d,f

and RISTO J. ILMONIEMIdaCognitive Brain Research Unit, Department of Psychology, University of Helsinki, FinlandbNeurodynamics Laboratory, Department of Psychiatry and Clinical Psychobiology, University of Barcelona, SpaincInstitute for Psychology, Hungarian Academy of Sciences, Budapest, HungarydBioMag Laboratory, Medical Engineering Centre, Helsinki University Central Hospital, FinlandeDepartment of Radiology, Helsinki University Central Hospital, FinlandfDepartment of Neurology, University of Helsinki, Finland

Abstract

Whole-head magnetoencephalographic~MEG! responses to repeating standard tones and to infrequent slightly higherdeviant tones and complex novel sounds were recorded together with event-related brain potentials~ERPs!. Devianttones and novel sounds elicited the mismatch negativity~MMN ! component of the ERP and its MEG counterpart~MMNm! both when the auditory stimuli were attended to and when they were ignored. MMNm generators werelocated bilateral to the superior planes of the temporal lobes where preattentive auditory discrimination appears to occur.A subsequent positive P3a component was elicited by deviant tones and with a larger amplitude by novel sounds evenwhen the sounds were to be ignored. Source localization for the MEG counterpart of P3a~P3am! suggested that theauditory cortex in the superior temporal plane is involved in the neural network of involuntary attention switching tochanges in the acoustic environment.

Descriptors: Auditory cortex, Attention, MEG, Novel sounds, Mismatch negativity, P3a

Event-related potentials~ERPs! elicited in the scalp-recorded elec-troencephalogram~EEG! by auditory stimuli enable noninvasiveexamination of auditory information processing in the human brainwith millisecond accuracy~for reviews, see Hillyard & Picton,1987; Näätänen, 1992; Woods, 1990!. For example, the mismatchnegativity~MMN ! component elicited in the ERP to deviant soundsthat occur in a sequence of repeating standard sounds provides atool to study cerebral processing of unattended auditory stimuli~e.g., Näätänen & Alho, 1995!. The MMN overlaps with the neg-ative N1~peak latency about 100 ms from stimulus onset! and thesubsequent positive P2 components, which are elicited by bothstandard and deviant stimuli. Therefore, the MMN is best seenfrom the difference wave calculated by subtracting the standard-

stimulus ERP from the deviant-stimulus ERP. It is assumed that theMMN is elicited by a mismatch between the neuronal activitycaused by the deviant stimulus and an automatically formed sensory-memory trace representing physical and temporal features of therepeated standard stimulus~e.g., Cowan, Winkler, Teder, &Näätänen, 1993; Näätänen, 1992; Ritter, Deacon, Gomes, Javitt, &Vaughan, 1995; Winkler, Karmos, & Näätänen, 1996!. This as-sumption is supported, for example, by results showing that noMMN is elicited by infrequent sounds presented without interven-ing standard sounds~Lounasmaa, Hari, Joutsiniemi, & Hämäläinen,1989; Näätänen, Paavilainen, Alho, Reinikainen, & Sams, 1989;Sams et al., 1985a!.

Scalp current density mapping~Giard, Perrin, Pernier, & Bouchet,1990! and the modeling of ERP sources~Giard et al., 1995; Scherg,Vajsar, & Picton, 1989! suggest that the main MMN generators arelocated in the left and right auditory cortices in the superior tem-poral gyri, where the mismatch process activated by the deviantauditory input presumably occurs. Because of the orientation ofthese bilateral auditory cortex sources, the MMN is usually largestover the frontocentral scalp areas. Generation of the MMN in theauditory cortex has been also indicated by intracranial recordingsin animals~Csépe, Karmos, & Molnár, 1987; Javitt, Steinschneider,

This research was supported by The Academy of Finland, the FinnishFoundation for Alcohol Studies, The National Scientific Research Fund ofHungary ~OTKA T022681!, and the Spanish Ministry of Education andCulture ~DGES UE96-0038!.

We thank Ms. Suvi Heikkilä for her assistance in the measurements.Address reprint requests to Dr. Kimmo Alho, Cognitive Brain Research

Unit, Department of Psychology, P.O. Box 13, FIN-00014 University ofHelsinki, Helsinki, Finland. E-mail: [email protected].

Psychophysiology, 35~1998!, 211–224. Cambridge University Press. Printed in the USA.Copyright © 1998 Society for Psychophysiological Research

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Schroeder, & Arezzo, 1996; Kraus et al., 1994! and humans~Hal-gren et al., 1995a; Kropotov et al., 1995!.

In accordance with the electrical data, the generator sourceof the magnetoencephalographic~MEG! counterpart of MMN~MMNm! has been found to be located in the auditory cortex onthe superior temporal plane~e.g., Hari et al., 1984; Lounasmaaet al., 1989; Sams et al., 1985a!. The magnetic fields recordedoutside the head are produced by the tangential~with respect to theskull! components of primary currents, mainly because of currentflow in cortical pyramidal cells~for a review, see Hämäläinen,Hari, Ilmoniemi, Knuutila, & Lounasmaa, 1993!. These sourcesare usually modeled as equivalent current dipoles~ECDs!, whichoptimally, in the least-square sense, explain the recorded magneticfields. Because the pyramidal cells of the auditory cortex on thesuperior temporal plane are oriented approximately tangentially tothe skull, MEG can be used to locate activity in these brain areaswith high spatial and temporal neural resolution~e.g., Mäkeläet al., 1993; Nakasato et al., 1995; Pantev et al., 1990, 1995; Reiteet al., 1994; Rogers, Papanicolaou, Baumann, Eisenberg, & Saydjari,1990!. A number of studies have shown that the ECD for theMMNm to a frequency change is located on the superior plane ofthe temporal lobe about 1 cm anterior to the source of the magneticcounterpart of N1, the N1m~Alho et al., 1996; Csépe, Pantev,Hoke, Hampson, & Ross, 1992; Hari, Rif, Tiihonen, & Sams,1992; Huotilainen et al., 1993; Levänen, Ahonen, Hari, McEvoy,& Sams, 1996; Levänen, Hari, McEvoy, & Sams, 1993; Levänen& Sams, 1997; Sams, Kaukoranta, Hämäläinen, & Näätänen, 1991;Tiitinen et al., 1993!. A similar spatial separation was also sug-gested by source modeling of electrically recorded MMN and N1~Scherg et al., 1989!.

Furthermore, scalp current density maps~Giard et al., 1990!and chaos analysis~Molnár, Skinner, Csépe, Winkler, & Karmos,1995! of the electrically recorded MMN suggest that frontal ac-tivity also contributes to the MMN~see also Levänen et al., 1996!.This activity might be generated in the frontal mechanisms initiat-ing an attention switch toward stimulus changes occurring outsidethe current focus of attention~Näätänen, 1992!. The functionalrole of the frontal cortex in the neural circuitry generating theMMN is also indicated by the attenuation of MMN in patients withlesions of the dorsolateral prefrontal cortex~Alho, Woods, Algazi,Knight, & Näätänen, 1994!. The initiative role of MMN generatorsin involuntary attention switching has been suggested by increasedreaction times and decreased performance accuracy in auditoryand visual discrimination tasks caused by task-irrelevant MMN-eliciting changes in the auditory stimulus preceding the auditory orvisual target stimulus~Schröger, 1996; Escera, Alho, Winkler, &Näätänen, 1997a!. Moreover, occasional involuntary switching ofattention to MMN-eliciting deviant sounds is indicated by re-sponses of the autonomic nervous system sometimes accompany-ing the MMN ~Lyytinen, Blomberg, & Näätänen, 1992!.

The positive P3a response, which is maximal over the centraland frontal scalp, sometimes follows the MMN to a change in anunattended auditory stimulus sequence. Such a P3a response mightindicate that attention was involuntarily oriented to an MMN-eliciting stimulus change occurring outside the current focus ofattention~Escera et al., 1997a; Näätänen, Simpson, & Loveless,1982; Sams, Paavilainen, Alho, & Näätänen, 1985b; Snyder &Hillyard, 1976; Squires, Squires, & Hillyard, 1975!. In ERPs todeviant auditory stimuli in an attended stimulus sequence, MMNand P3a are overlapped by other ERP components, for example, bycentrally maximal negative N2b and parietally maximal positiveP3b~P300! components, if the deviant sounds are target stimuli to

be discriminated by the listener~Näätänen et al., 1982; Novak,Ritter, Vaughan, & Wiznitzer, 1990; Picton, 1992; Pritchard, 1981;Sams et al., 1985b; Sutton, Braren, Zubin, & John, 1965!.

The association of P3a with involuntary orienting of attention issuggested by results showing that the P3a is elicited with a largeamplitude by distracting novel sounds, for example, by naturalenvironmental sounds, both when these occur as nontarget soundsamong standard and target tones and when they appear in an un-attended stimulus sequence~Woods, 1990!. The role of P3a gen-erators in involuntary attention switching is also suggested bystudies showing prolonged reaction times to target stimuli follow-ing irrelevant P3a-eliciting novel sounds~Escera et al., 1997a;Grillon, Courchesne, Ameli, Geyer, & Braff, 1990; Woods, 1992!.Brain areas involved in eliciting the P3a to novel sounds include,at least, the dorsolateral prefrontal cortex, the temporoparietal junc-tion, and the posterior hippocampal region; focal lesions in any ofthese areas attenuate the P3a~Knight, 1984, 1996; Knight, Scabini,Woods, & Clayworth, 1989!. Intracranial recordings also suggestthe existence of P3a generators in multiple brain areas, includingthe dorsolateral prefrontal, temporal, and parietal cortices and thecingulate and parahippocampal gyri~Alain, Richer, Achim, & Saint-Hilaire, 1989; Baudena, Halgren, Heit, & Clarke, 1995; Halgrenet al., 1995a, 1995b; Kropotov et al., 1995; Smith et al., 1990!.

Several MEG studies have aimed at identifying the generatorsources of the magnetic counterpart of P3b~hereinafter the P3bm!elicited by target sounds. According to these studies, the P3bm toauditory targets has sources at least in the temporal cortex, hippo-campal region, and thalamus~Lewine et al., 1990; Rogers et al.,1991; Tesche, Karhu, & Tissari, 1996!. In line with these results,source modeling of the electrical P3b to target sounds has sug-gested contributions from sources in the temporal cortex and in themedial temporal lobe, either in the hippocampus or in the para-hippocampal gyrus~Tarkka, Stokic, Basile, & Papanicolaou, 1995!.According to another recent source modeling study, the electricalP3b to auditory targets would get a major contribution from themedial temporal lobe, whereas the P3a to distracting novel soundspresented in the same condition would have main sources in themedial temporal lobe and in the frontal lobe~Mecklinger &Ullsperger, 1995!. Large P3b-like responses have been also re-corded intracranially directly from many brain structures, includ-ing the temporal cortex, hippocampus, and thalamus~e.g., Alainet al., 1989; Halgren et al., 1980, 1995a; McCarthy, Wood, Will-iamson, & Spencer, 1989; Smith et al., 1990; Velasco, Velasco,Velasco, Almanza, & Olvera, 1986!. However, contribution of suchdeep sources to the scalp recorded ERPs might be rather weakbecause of the distance between the source and the scalp electrodes~Lutzenberger, Elbert, & Rockstroh, 1987!. Moreover, the contri-bution of hippocampal activity to the P3b recorded from the scalphas been questioned because hippocampal lesions have no or verylittle effect on the scalp-recorded P3b~e.g., Johnson, 1988; Knight,1996; Paller, Zola-Morgan, Squire, & Hillyard, 1988; Polich &Squire, 1993; Stapleton, Halgren, & Moreno, 1987!.

The primary aim of the present study was to examine whetheror not it is possible to record a magnetic counterpart of P3a~herein-after the P3am! to novel sounds and perhaps also to slightly de-viant tones occurring among standard tones and to locate the P3amsources. Because the P3a has been suggested to be associated withinvoluntary switching of attention, responses to these sounds wererecorded in two experimental conditions. In the first condition, theparticipants were instructed to ignore the auditory stimuli and toconcentrate on watching a silent film, and in the second one theparticipants attended to the auditory stimuli to detect the deviant

212 K. Alho et al.

tones. This design enabled us also to examine whether attentionaffects the MMNm responses elicited by deviant tones and bynovel sounds.

Methods

ParticipantsEight healthy adults~ages 22–38 years,M 5 30 years; 2 women,6 men! volunteered to participate in the study. All were right-handed, and none had any hearing disorders.

Stimuli and ProcedureParticipants were presented with auditory stimulus sequences con-sisting of 600 Hz standard tones~probability of occurrence,p 5.85!, 660 Hz deviant tones~ p 5 .075!, and complex novel sounds~ p 5 .075! delivered in a random order, except that each devianttone and novel sound was preceded by at least one standard tone.In each auditory sequence, there were 400 stimuli occurring at aconstant rate of 1 stimulus in 800 ms. The stimuli were generatedby a Macintosh II computer and delivered binaurally to the earsthrough plastic tubes and earpieces using a correction filter tocompensate for the differential attenuation of different frequenciesin the tubes. Standard and deviant tones had sinusoidal waveforms,an intensity of about 75 dB SPL at each ear, and a duration of200 ms, including 10-ms rise and fall times. The novel soundswere drawn from a pool of 60 different digitized complex sounds~telephone ringing, electric drill, rain, etc.! with a duration of200 ms, including 10-ms rise and fall times, and a maximumintensity of 70–80 dB SPL at each ear. None of the novel soundsappeared twice within the same stimulus sequence.

In the first experimental condition~ignore!, the participantswere instructed to ignore the tones and to watch a silent filmpresented on a television monitor at a distance of about 2 m. In thesecond condition~attend!, the participants were asked to fixate atthe center of a black television screen and to count silently thenumber of deviant tones occurring in the auditory stimulus se-quence. The count was reported after each sequence. In each con-dition, four or five stimulus sequences were presented so that atleast 100 acceptable trials were collected for both deviant tonesand novel sounds after online rejection of trials with large extra-cerebral artifacts in MEG or EEG.

Data Collection and AnalysisMEG was recorded in a magnetically shielded room~EuroshieldLtd., Finland! with a 122-channel magnetometer~Neuromag Ltd.,Finland; Knuutila et al., 1993!. This whole-head magnetometerconsists of 61 dual-sensor units each with two orthogonal planargradiometers recording maximal signal directly above the source.Planar gradiometers differ from axial gradiometers, which recordmaximal signals over locations of maximal magnetic flux goinginto or coming out of the head, such maxima being located, forexample, on opposite sides of a dipolar source oriented tangen-tially to the skull ~Hämäläinen et al., 1993!.

The participant sat still in a chair under continuous closed-circuit television surveillance with his0her head inside the helmet-shaped magnetometer. The magnetometer position with respect tothe head was determined in the beginning of each condition byrecording the magnetic fields produced by currents fed into threeindicator coils at known scalp locations. The locations of thesecoils in relation to the preauricular points and nasion were, in turn,determined with an Isotrak 3D-digitizer~PolhemusTM, USA! be-fore the start of the experiment. Concurrently with MEG, EEG was

recorded with gold-plated electrodes placed at 25 scalp sites of anextended version of the International 10-20 system and referred tothe electrode attached to the tip of the nose. To monitor eye move-ments and blinks, bipolar electro-oculograms~EOGs! were mea-sured between electrodes above and below the left eye and betweenelectrodes at the outer canthi of the left and right eye.

MEG, EEG, and EOG epochs~recording passband 0.03–100 Hz, sampling rate 397 Hz!, starting 100 ms before and ending800 ms after each stimulus onset, were averaged separately forstandard and deviant tones and for novel sounds. Epochs contam-inated by eye movements or blinks~EOG variation.150 mVduring the epoch! or by other obvious extracerebral artifacts~MEGvariation.1,500 f T0cm or EEG variation.500mV in any chan-nel! were automatically omitted from online averaging, as were theepochs for the first five stimuli of each stimulus sequence~to alloweach participant to get used to the auditory stimulation! and theepochs for each standard stimulus following a deviant or novelsound~these standards may elicit responses that differ from thoseto other standards; Sams, Alho, & Näätänen, 1984!. Averaged re-sponses were digitally filtered with a passband of 1–30 Hz.

In each condition and for each participant, the amplitudes ofP1m, N1m, and P2m responses to standard tones were measured atdifferent MEG channels in relation to the mean amplitude duringthe 100-ms prestimulus period. Then, ECDs were determined, usinga spherical head model, at the peak of the ECD moment separatelyfor the two hemispheres by using magnetic responses in sets of 44MEG channels over the left and right hemispheres centered at theapproximate locations of the left and right auditory cortices, re-spectively. The location and orientation of each ECD was deter-mined by a computer algorithm of the Neuromag software, whichiteratively adjusted the dipole parameters separately for each timepoint until a maximal fit between the magnetic field pattern cal-culated from the ECD and the measured field was obtained. Thus,the ECD location was determined purely by the computer algo-rithm on the basis of measured MEG data. For example, no initialguess for the source location by the program user was needed. Thetime ranges used to determine the P1m, N1m, and P2m ECDs were30–80 ms, 80–140 ms, and 140–240 ms from stimulus onset,respectively. If no local maximum of an ECD moment was ob-served in the time range of the brain response under study, an ECDwas determined within this time range at the latency of the max-imal goodness of fit between the measured magnetic field and thefield calculated from the ECD.

ECDs for the MMNm and P3am responses elicited by devianttones and novel sounds were modeled in the same way as theECDs for the P1m, N1m, and P2m, except that these ECDs weredetermined from the difference curves obtained by subtracting ateach channel the response to standard tones from the responseselicited in the same experimental condition by deviant tones andnovel sounds. The time windows used to determine the devianttone MMNm and the novel sound MMNm were 100–200 ms and80–200 ms, respectively, and the time window for the P3am ECDwas 200–400 ms both for the deviant tones and novel sounds.

For all the responses studied, only individual ECDs explaining$60% of the magnetic field measured with the 44 channels overone hemisphere are reported here. All accepted ECDs had suchorientations that they would produce the respective ERP compo-nent with an appropriate polarity~positive for the P1m, P2m, andP3am; negative for the N1m and MMNm! at the frontal and centralscalp areas. A goodness-of-fit percentage of 60% could be consid-ered too low to accept an ECD. However, for.70% of the ECDsreported in the current study, the goodness of fit was$75%. Fur-

MEG responses to novel sounds and deviant tones 213

thermore, as in a previous MMNm study~Alho et al., 1996!, whereECDs with $60% goodness of fit values were accepted for theanalyses, a large array of 44 channels over each hemisphere wereused to determine the ECDs. Had smaller channel arrays beenapplied, higher goodness-of-fit percentages could have been ob-tained because an array of 44 channels necessarily includes manychannels with no or only a small signal generated by the ECDunder study. However, usage of small arrays of selected channelswould have biased the ECD locations by tending to place the ECDinto the area of brain covered by the applied channel array.

To correlate the locations of the ECDs with macroanatomicalbrain structures, magnetic resonance images of the brain of oneparticipant~Participant 5! were acquired with a Siemens Vision1.5-T system~Siemens, Germany! using a set of 1-mm-thick sag-ittal images. Then ECD locations of this participant were placedwith his brain images.

The peak latencies and amplitudes~in relation to the 100-msprestimulus baseline! of the electrical P1, N1, and P2 waves tostandard tones were determined for each participant from the ERPsrecorded at the central midline site~Cz electrode! because theseresponses were largest over the central scalp. The peak values ofelectrical MMN and P3a responses to deviant tones and novelsounds were determined from the deviant–standard and novel–standard ERP difference waves. The P3a peak amplitudes andlatencies were measured at the central midline electrode~Cz!, butthe MMN peaks were measured at the frontal midline site~Fz!because the MMN was larger over the frontal than over centralscalp sites, as usually is the case with the MMN to a frequencychange~see Alho, 1995!. The time windows used to determine theP1, N1, P2, MMN, and P3a peaks were the same as the timewindows used to determine ECDs for the magnetic counterparts ofthese responses. For the attend condition, where deviant toneswere targets to be counted by the participants, the N2b peak~thenegative peak following the MMN peak at Cz! and P3b peak~thepositive peak following the P3a peak at the parietal midline site,Pz! were also measured from the deviant–standard difference waves.Here, the ERP peak latencies and amplitudes will be used only asreference data for the analysis of the corresponding magnetic fields.A more detailed analysis of the ERP data will be reported else-where~Escera et al., 1997b!.

Grand-average ERPs were calculated for descriptive purposesby averaging ERPs across the 8 participants. In contrast, grandaverages of magnetic responses were not calculated because thedistributions of magnetic fields are usually much more local and,therefore, show higher interindividual variance than do the scalpdistributions of the respective ERP waves. Furthermore, unlike theERP distributions over the applied array of electrodes, the distri-butions of magnetic fields over the sensor array vary slightly be-tween participants also because of differences between the individualhead positions in relation to the helmet-shaped magnetometer. How-ever, this variation in head position with respect to the magnetom-eter does not affect source localization in individuals because thehead position inside the magnetometer is measured before eachrecording and then taken into account in the source analysis.

In statistical analyses of the data, locations of the P1m, P2m,and MMNm ECDs were compared with the location of the N1mECD, which in numerous previous studies has been found in ornear the primary auditory cortex on the superior temporal plane~e.g., Hari, 1990; Mäkelä et al., 1993; Nakasato et al., 1995; Pantevet al., 1990, 1995; Reite et al., 1994; Rogers et al., 1990!, theMMNm ECD for a frequency change being usually about 1 cmanterior to the N1m ECD~Alho et al., 1996; Csépe et al., 1992;

Hari et al., 1992; Huotilainen et al., 1993; Levänen et al., 1993,1996; Levänen & Sams, 1997; Sams et al., 1991; Tiitinen et al.,1993!. Moreover, locations of MMNm and P3am ECDs were sta-tistically compared to determine whether the same or differentneuronal populations generate these two responses elicited by stim-ulus change. Statistical tests were also applied to examine thesignificance of hemispheric differences in the latencies and mo-ments of the ECDs for the different brain responses and effects ofattention on moments, latencies, and locations of these ECDs andon amplitudes and latencies of the corresponding ERPs. Further-more, separability of P20P2m and P3a0P3am was investigated bystatistically comparing their latencies and by comparing the loca-tions of the P2m and P3am ECDs. In all statistical comparisons,analyses of variance~ANOVAs! for repeated measures were used,applying the Greenhouse-Geisser correction when appropriate.

Results

PerformanceIn the attend condition, the number of deviant tones in the se-quences reported by participants differed on the average only by2.0% ~SE 5 0.5%! from the actual number of target stimuli de-livered.

Brain Responses to Standard TonesStandard tones elicited ERPs with P1, N1, and P2 waves that wereusually largest over the central scalp~Figures 1a and c!. The meanpeak amplitudes and latencies of these waves are given in Table 1.ANOVAs showed no significant differences in any of these peakamplitude and latency values between the ignore and attendconditions.

P1m, N1m, and P2m responses were observed in magneticfields to standard tones~Figure 2b!. ECDs could be determined forthese responses in 6–8 participants, depending on response, hemi-sphere, and condition~Table 2!. The mean latencies of the left andright hemisphere ECDs optimally explaining these magnetic re-sponses coincided quite closely with the mean peak latencies of thecorresponding ERP peaks~Table 1!, except perhaps for the P10P1m: the optimal ECDs for the P1m responses to standard tonesoccurred on the average 10 ms after the P1 peaks in the ERPs.

As seen in Figures 3a and 4a and Table 3, the coordinates forthe P1m, N1m, and P2m ECDs all suggest generators in the au-ditory cortex on the superior plane of the temporal lobe. Single-variable ANOVAs for the spatial coordinates of the P1m and N1mECDs activated by the ignored standard tones indicated no signif-icant differences in any spatial dimension between the locations ofthese ECDs in either hemisphere. In the right hemisphere, thiscould be studied in all 8 participants because in all of them righthemisphere ECDs could be determined reliably for the P1m andN1m to the ignored standard tones. However, in the left hemi-sphere, locations of the corresponding N1m and P1m ECDs couldbe compared only in those 5 participants who had determinable lefthemisphere ECDs for both of these responses. For similar reasons,the number of participants~n! in the ANOVAs reported in thefollowing ranges from 5 to 8~no ANOVAs were performed forn , 5!.

In the right hemisphere, the P2m ECD for the ignored standardtones was significantly anterior~along they axis! to the ECD forthe corresponding N1m~n 5 6; for these participants, the meandifference on they-axis was 20 mm!, F~1,5! 5 15.44,p , .012,whereas an ANOVA~n 5 5! for the left hemisphere P2m ECDsfailed to show such difference.

214 K. Alho et al.

Significant hemispheric differences in the strength of the P1mand N1m ECDs were found. Single-variance ANOVAs indicatedhigher dipole moments in the left than in the right hemisphere bothfor the P1m~n 5 6; mean difference 3 nAm!, F~1,5! 5 7.68,p ,.04, and N1m~n 5 8; mean difference 2 nAm!, F~1,7! 5 17.85,p , .006. No such hemispheric difference was observed for theP2m. In accordance with the respective ERP peak amplitudes andlatencies~Table 1!, there were no significant effects of attention onthe moment or latency of the P1m, N1m, or P2m ECDs~Table 2!.

Neither were significant effects of attention on the locations ofthese ECDs found.

Brain Responses to Deviant TonesIn the ignore condition, MMN and P3a responses were elicited bythe deviant tones~Figures 1a and b!. Deviant–standard ERP dif-ference waves revealed that this MMN was usually maximal overthe frontal scalp, whereas the P3a to deviant tones was maximal atcentral scalp sites~Figure 1b!. In the attend condition, deviant

Figure 1. Grand-average ERPs recorded at the frontal~Fz!, central~Cz!,and parietal~Pz! midline scalp sites and averaged across the 8 participantsto standard tones~thin solid lines!, deviant tones~thick solid line!, andnovel sounds~dashed lines! in the ignore condition~a! and the attendcondition ~c! and the respective difference waves~b,d! obtained for eachcondition by subtracting the standard tone ERPs from those to devianttones~thick solid difference waves! and novel sounds~dashed differencewaves!. Stimulus onset at 0 ms.

Table 1. Mean (6SE) Peak Amplitudes and Latencies of ERPsto Standard Tones Measured at the Central Midline Site (Cz)From 8 Participants

Wave ConditionLatency

~ms!Amplitude

~mV !

P1 ignore 626 6 0.76 0.1attend 596 6 0.76 0.1

N1 ignore 1046 4 21.1 6 0.2attend 1056 3 21.0 6 0.2

P2 ignore 1676 7 1.46 0.3attend 1746 10 1.66 0.3

Figure 2. Data from an individual participant~Participant 1!. ~a! ERPs atthe central midline site~Cz! to standard tones~thin solid lines!, devianttones~thick solid line!, and novel sounds~dashed lines! in the ignore andattend conditions.~b! The corresponding magnetic responses at recordingsites showing maximal responses over the approximate locations of theauditory cortices in the left and right hemispheres.~c! Magnetic differencewaves for the respective recording sites obtained by subtracting for eachcondition the standard-tone response from the responses to deviant tones~thick solid difference waves! and novel sounds~dashed difference waves!.~d! Magnetic field gradients~difference between the adjacent lines 5 f T0cm! over each hemisphere superimposed on the helmet-shaped magnetom-eter for the MMNm and P3am responses to deviant tones and for theMMNm0N1m and P3am responses to novel sounds in the ignore and attendconditions. The arrows indicate the locations and orientations of the ECDsexplaining the magnetic field over the shown hemisphere~for this partici-pant, ECDs could not be reliably determined for the P3am responses todeviant tones in the attend condition or for the P3am fields measured overthe right hemisphere in the ignore condition!.


tones, which were now the target stimuli, also elicited the MMN~Figures 1c and d!. The mean peak amplitude and latency of thisMMN ~measured at Fz! were equal to those in the ignore condition~Table 4!. In the attend condition, a subsequent centrally maximalN2b negativity was observed~Figures 1c and d, Table 4!. This N2bwas followed by a centrally maximal positivity, which was pre-sumably mainly caused by the P3a, and another later and parietallymaximal positivity, the P3b~Figures 1c and d, Table 4!. Althoughno effects of attention on the MMN peak values were observed,single-variable ANOVAs showed that the P3a peak amplitude atCz was significantly larger,F~1,7! 5 9.26, p , .02, and thatthe P3a peak latency was significantly longer,F~1,7! 5 10.15,p , .02, in the attend condition than in the ignore condition~seeTable 4!.

In both the ignore and the attend conditions, magnetic deviant–standard difference waves showed MMNm and P3am responses todeviant tones corresponding to the electrical MMN and P3a re-sponses~Figures 2a–c and 5!. However, as seen in Figures 2b, 2c,and 5, magnetic responses to deviant target tones in the attendcondition revealed no sign of a magnetic counterpart of the N2bobserved in the ERPs to the same tones.

ECDs with coordinates suggesting location on the superior tem-poral plane could be determined for the MMNm in all participantsin both hemispheres and conditions~Figures 2c, 3b, and 4b,Table 3!. The latencies of these ECDs were quite similar to theMMN peak latencies in the ERPs to deviant tones~Tables 4 and 5!.In accordance with the lack of attention effects on electrical MMNs,two-variable~Condition3 Hemisphere! ANOVAs ~n 5 8! showedno significant effects of attentional condition on the deviant toneMMNm latencies or ECD moments. Moreover, attention had nosignificant effects on the coordinates of the MMNm ECDs~seeTable 3!.

Similar to the P1m and N1m to standard tones, the deviant toneMMNm ECDs were significantly stronger in the left than the righthemisphere,F~1,7! 5 32.45,p , .001 ~see also Table 5!. How-ever, the N1m and MMNm were not generated by the same neu-ronal population of the superior temporal cortex. Comparison ofECD locations for the deviant tone MMNm and standard toneN1m in the ignore condition indicated that in the right hemisphere

the ECD for the MMNm was significantly anterior~on they-axis!to that for the N1m~n 5 8; mean difference 17 mm!, F~1,7! 59.76,p , .02, as also seen in Figures 3b and 4b and Table 3. In theleft hemisphere, the corresponding difference was much smallerand did not quite reach significance~n 5 7; mean difference 6 mm!F~1,6! 5 3.57, p , .11. However, in this hemisphere, ANOVAsshowed that the MMNm ECD for the ignored deviant tones wasslightly medial~n 5 7; average difference on thex-axis 6 mm!,F~1,6! 5 6.02,p , .05, and inferior~n 5 7; average difference onthez-axis 7 mm!, F~1,6! 5 7.15,p , .04, to the N1m ECD for theignored standard tones.

In the ignore condition, a left hemisphere ECD could be mod-eled for the deviant tone P3am in 7 participants and a correspond-ing right hemisphere ECD could be modeled in 3 participants~Table 5!. The coordinates of the P3am ECDs suggested sourcelocations in the superior temporal cortex~Table 3, Figures 2d, 3b,and 4b!. In the attend condition, a left hemisphere ECD for thedeviant tone P3am could be modeled only in 3 participants, whereasno corresponding right hemisphere ECD could be modeled in anyparticipant. Presumably, in the attend condition overlapping con-tributions from P3am and P3bm sources activated by the devianttarget tones made modeling of the temporal cortex P3am sourceimpossible with the present simplified approach assuming only asingle dipole in each hemisphere. Thus, the location of the P3amECD could be reliably compared with the location of the MMNmECD only in the ignore condition and only in the left hemisphere.These ANOVAs showed no significant differences along any spa-tial dimension between the MMNm and P3am source locations,although the P3am ECDs tended to be slightly anterior to theMMNm ECDs ~see also Figures 3b and 4b and Table 3!. Thus, itappears that the MMN and P3a responses to a frequency devianceare generated by overlapping or adjacent neuronal populations inthe superior temporal cortex.

It might be argued that the response to deviant tones called herethe P3a or P3am was actually caused by an enhancement of the P2to deviant tones. However, an ANOVA for the Cz peak latencies ofP2 to standard tones and P3a to deviant tones including attentionand stimulus as variables showed that the P3a to deviant tonespeaked significantly later than did the P2 to standard tones,F~1,7! 5 199.98,p , .0001~see also Tables 1 and 4!. A statisticalcomparison of the magnetic P2m to standard tones and the P3amto deviant tones could be performed only for the left hemispheredata in the ignore condition where left hemisphere ECDs could bedetermined for both responses in 5 participants~for the left hemi-sphere data of the attend condition and for the right hemispheredata of the ignore and attend conditions, there were, in each case,0–2 participants with a determinable ECD both for the P2m tostandard tones and the P3am to deviant tones!. These left hemi-sphere data for the ignore condition indicated that the latency ofthe P3am dipole was significantly longer than the latency of theP2m dipole,F~1,4! 5 65.69,p , .002 ~see also Tables 2 and 5!.Moreover, the P3am ECD was almost significantly anterior to theP2m ECD ~n 5 5; average difference on they-axis 11 mm!,F~1,4! 5 6.90,p , .06, and tended to be located medially to theP2m ECD ~n 5 5; average difference on thex-axis 11 mm!,F~1,4! 5 2.61,p , .20.

Brain Responses to Novel SoundsIn both the ignore and attend conditions, MMN and P3a responsesalso were observed in ERPs to novel sounds~Figure 1!. Theseresponses were larger and earlier than the corresponding responsesto deviant tones~Table 4!. However, the negativity seen in the

Table 2. Mean (6SE) Latencies, Moments, and Goodnessof Fit for ECDs for the Magnetic P1m, N1m, and P2mResponses to Standard Tones

Wave Hemisphere Condition naLatency

~ms!Moment~nAm!

Fitb

~%!

P1m left ignore 6 726 3 7.76 0.7 916 2attend 6 746 2 6.76 0.9 866 3

right ignore 8 666 4 4.76 0.7 836 3attend 7 676 5 4.06 0.9 826 3

N1m left ignore 7 1096 5 6.26 0.7 886 3attend 6 1106 4 5.36 0.9 876 4


P2m left ignore 6 1666 6 5.86 1.1 826 3attend 6 1746 5 6.76 1.3 816 3


aNumber of participants for whom this ECD could be reliably deter-mined. bPercentage of the field measured over a given hemisphere ex-plained by the ECD determined in this hemisphere.

216 K. Alho et al.

Figure 3. Locations of the ECDs for an individual participant~Participant 5! in the ignore and attend conditions~a! for the P1m~whitecircles!, N1m~dotted circles!, and P2m~black circles! responses to standard tones,~b! for the MMNm ~dotted circles! and P3am~blackcircles! responses to deviant tones, and~c! for the MMNm0N1m ~dotted circles! and P3am~black circle! responses to novel sounds.~For this participant, no left hemisphere ECD for the N1m could be reliably modeled in either condition, no P3am sources could bedetermined either for deviant tones or novel sounds in the attend condition, and only a left hemisphere P3am source could be modeledfor novel sounds in the ignore condition!. The ECD locations are projected on a tilted horizontal magnetic resonance imaging slice ofthis participant’s brain at the level of the Sylvian fissure. The level and orientation of this slice are shown at the top in left sagittal viewsof the left and right hemispheres.


novel-standard difference wave was presumably partly caused byan enhanced N1 component, because this negativity was, unlikethe frontally maximal MMN, largest over the central scalp~Fig-ures 1b and d!. The N1 was presumably enhanced by the novelsounds that had wide frequency spectra and therefore activated inthe auditory cortex large populations of nonrefractory frequency-specific neurons not responsive to repeating standard tones withonly one frequency component~cf. Scherg et al., 1989!. There-fore, the negativity to novel sounds will be called hereinafter theMMN0N1.

No significant effects of attention on the novel sound MMN0N1peak amplitude or latency was observed. In contrast, as also seenin Table 4, the P3a had a significantly longer peak latency,F~1,7! 5 10.15,p , .02, and nearly significantly larger amplitude,F~1,7! 5 4.42,p , .075, in the attend condition than in the ignorecondition.

Novel sounds elicited also the magnetic MMNm0N1m re-sponse corresponding to the electrical MMN0N1 ~Figures 2a and b

and 5!. The ECDs for the MMNm0N1m could be modeled in all 8participants in both hemispheres and conditions. The coordinatesof these ECDs suggested bilateral sources in the superior temporalcortex ~Figures 2d, 3c, and 4c, Table 3!. Attention had no signif-icant effect on the strength, latency, or location of these ECDs~Tables 3 and 5!.

Consistent with the corresponding ERP peak latencies, the ECDsfor the MMNm0N1m responses to novel sounds were earlier thanthe MMNm ECDs for deviant tones~Table 5!. Moreover, in linewith the ERP peak amplitudes, the right hemisphere ECD for theMMNm0N1m to novel sounds had a stronger dipole moment thandid the MMNm to deviant tones. In the left hemisphere, no suchmarked dipole moment differences were observed. Three-way~Stim-ulus 3 Condition3 Hemisphere! ANOVAs for the ECD coordi-nates indicated that the MMNm0N1m ECDs for novel sounds weresignificantly posterior to the MMNm ECDs for deviant tones~n 5 8; mean difference on they-axis 8 mm!, F~1,7! 5 9.14,p , .02 ~see also Table 3, Figures 4b and c!. Because the N1m tostandard tones was also generated posteriorly to the MMNm todeviant tones, at least in the right hemisphere~Table 3, Figures 4aand b!, this result might suggest that the MMNm0N1m to novelsounds was caused merely by an enhanced N1m, with no contri-bution from the MMNm generator. However, this seems not to bethe case. Although in the left hemisphere there were no distinctdifferences in the coordinates between the MMNm0N1m to novelsounds and the N1m to standard tones~Figure 4a and c, Table 3!,a two-way~Stimulus3 Condition! ANOVA indicated that in theright hemisphere, the ECDs for the MMNm0N1m to novel soundswere nearly significantly anterior to the N1m ECDs for standardtones~n 5 8; mean difference on they-axis 9 mm!, F~1,7! 5 3.63,p , .10.

Magnetic responses to novel sounds showed also a prominentP3am response corresponding to the electrical P3a~Figures 2a–cand 5!. In the ignore condition, left hemisphere ECDs for themagnetic P3am could be modeled in all participants and thecorresponding right hemisphere ECDs could be modeled in 6participants. These P3am responses appeared to have a generatorin the superior temporal cortex~Figures 2d, 3c, and 4c,Table 3!. ANOVAs for moments and latencies of ECDs for theseP3am responses in the 6 participants with a determinable ECDfor both hemispheres indicated no significant hemispheric differ-ences although in these participants the average ECD momentwas somewhat higher~15 nAm vs. 11 nAm! and latency wasshorter~221 ms vs. 237 ms! for the left than for the right hemi-sphere. In the ignore condition, no significant differences werefound in either hemisphere between the locations of the MMNm0N1m and P3am ECDs activated by novel sounds, although theP3am ECDs tended to be anterior to the MMNm0N1m ECDs~Figure 4c, Table 3!. These data, just as the ECDs for devianttones, suggest that MMN and P3a get contributions from adja-cent or overlapping neuronal populations of the superior tempo-ral cortex.

In the attend condition, it was possible to model a left hemi-sphere ECD for the P3am to novel sounds in 6 participants, buta right hemisphere P3am ECD could be modeled reliably onlyin 3 participants~see Table 3!. The fact that P3am ECDs couldbe determined in a smaller group of participants in the attendcondition than in the ignore condition suggests that in the attendcondition multiple sources contributed simultaneously to the P3amto novel sounds. ANOVAs~n 5 6! showed no significant dif-ferences between the ignore and attend conditions in the loca-tion, strength, or latency of the left hemisphere ECD for the

Figure 4. Average locations of the ECDs~a horizontal view of the brainfrom above! in the ignore and attend conditions~a! for the P1m~whitecircle!, N1m~dotted circles!, and P2m~black circles! responses to standardtones,~b! for the MMNm ~dotted circles! and P3am~P3am0P3bm in theattend condition! responses~black circles! to deviant tones, and~c! for theMMNm0N1m ~dotted circles! and P3am responses~black circles! to novelsounds. The number of participants for each mean coordinate values andthe standard errors of these mean values are shown in Table 3, where thecoordinate system is also explained.

218 K. Alho et al.

P3am to novel sounds, although the ECD latency tended to belonger in the attend condition,F~1,5! 5 4.72,p , .09 ~Table 5!,similar to the peak latency of the electrical P3a to novel sounds~Table 4!.

As for the P3a deviant tones, the separability of the P2 tostandard tones and the P3a to novel sounds was indicated by anANOVA showing that the P3a to novel sounds peaked at Czsignificantly later than the P2 to standard tones,F~1,7! 5 124.68,p , .0001 ~see also Tables 1 and 4!. A statistical comparison ofthe magnetic P2m to standard tones and P3am to novel soundscould be performed only for the left hemisphere data for theignore condition where ECDs could be determined for both re-sponses in 6 participants~for the left hemisphere data of theattend condition and for the right hemisphere data of the ignoreand attend conditions there were, in each case, only 3 or 4participants with a determinable ECD both for the P2m to stan-dard tones and for the P3am to novel sounds!. These left hemi-sphere data for the ignore condition indicated that the latency ofthe P3am dipole was significantly longer than the latency of theP2m dipole,F~1,5! 5 54.69, p , .001 ~see also Tables 2 and5!. Moreover, the P3am ECD was almost significantly medial tothe P2m ECD~n 5 6; average difference on thex-axis 13 mm!,F~1,5! 5 6.28, p , .055.

Discussion

As a new finding, the present data demonstrate the magnetic coun-terpart of P3a, the P3am, which is elicited with a large amplitudeby novel sounds and with a smaller amplitude by slightly devianttones occurring among standard tones. According to the presentresults, P3am has generators in the auditory cortex on the superiorplane of the temporal lobe adjacent to and perhaps slightly anteriorto the MMNm sources. The activation of these P3am sources co-incided with the electrical P3a in both conditions. However, asshown by previous lesion studies~Knight, 1984, 1996; Knightet al., 1989! and intracranial recordings~Alain et al., 1989; Baudenaet al., 1995; Halgren et al., 1995a, 1995b; Kropotov et al., 1995;Smith et al., 1990!, the electrical P3a has multiple sources. Con-sistent with these findings, the activity of the P3am sources local-ized to the superior temporal cortex in the present study appears toexplain only a part of the electrical P3a recorded over the frontaland central scalp areas, as indicated for example by the fact that theelectrical P3a to novel sounds was about two times as large inamplitude as the MMN0N1 to these sounds~see Table 4!, whereasthe P3am ECDs for novel sounds located in the superior temporalcortex were somewhat weaker than the adjacent ECDs for theMMNm0N1m responses to these sounds~see Table 5!.

Table 3. Mean (6SE) x, y, and z Coordinates for the Locations of ECDs Determined for the MagneticP1m, N1m, and P2m Responses to Standard Tones, the MMNm and P3am Responses to Deviant Tones,and for the MMNm0N1m and P3am Responses to Novel Sounds

Stimulus Wave Hemisphere Condition nax

~mm!y

~mm!z

~mm!

Standard P1m left ignore 6 2466 1 46 3 546 4attend 6 2466 2 56 5 546 4

right ignore 8 566 3 176 4 516 4attend 7 596 3 146 3 596 4

N1m left ignore 7 2486 3 66 3 586 4attend 6 2506 3 66 4 656 4


P2m left ignore 6 2506 2 116 4 436 7attend 6 2456 3 176 6 586 7


Deviant MMNm left ignore 8 2406 2 106 3 506 4attend 8 2406 2 106 3 536 3


P3am left ignore 7 2406 4 216 6 506 5P3am0P3bm attend 3 2386 2 22 6 10 726 3P3am right ignore 3 466 7 256 15 476 7P3am0P3bm attend 0 — — —

Novel MMNm0N1m left ignore 8 2466 3 16 3 566 6attend 8 2466 3 46 5 496 3


P3am left ignore 8 2406 5 96 7 506 8attend 6 2436 4 246 7 576 7


Note: In the attend condition, deviant tones were target stimuli and therefore presumably elicited overlapping P3a andP3b responses, the origin of the coordinate system is at the point of orthogonal projection of the nasion on the lineconnecting the left and right preauricular points. The positivex-axis points to the right preauricular point, they-axis tothe nasion, and thez-axis toward the top of the head orthogonal to the other two axes.aNumber of participants for whom this ECD could be reliably determined.


Furthermore, a difference between the P3a and P3am distribu-tions over the two hemispheres also indicates that the activity ofthe P3am ECDs in the superior temporal cortex could explain onlypart of the electrically recorded P3a. A P3am ECD was more oftendeterminable in the left than in the right hemisphere, whereas theelectrical P3a is usually quite symmetrically distributed over thetwo hemispheres~see Friedman & Simpson, 1994; Friedman,Simpson, & Hamberger, 1993; Knight, 1996; Knight et al., 1989!,as was also the case with the present ERPs~Escera et al., 1997b!.Bilateral P3a generators are also indicated by studies showing thatboth left hemisphere and right hemisphere lesions of the temporalor frontal cortex markedly attenuate the P3a to novel sounds~Knight,1984; Knight et al., 1989!.

Moreover, although the P3am was largely explained by activitygenerated in the superior temporal cortex, the measured P3amfields probably got some contributions from other P3a sources,too. This might explain why the P3am sources located in the su-perior temporal cortex could not be modeled in all subjects for

Table 4. Mean (6SE) Peak Amplitudes and Latencies Measuredfrom the 8 Participants for the MMN (or MMN0N1), for P3aResponses to Deviant Tones and Novel Sounds, and for theN2b and P3b Responses to Deviant (Target) Tones

Stimulus Wave ConditionLatency

~ms!Amplitude

~mV !

Deviant MMN ignore 1536 6 22.46 0.3attend 1536 7 22.46 0.3

P3a ignore 2776 9 1.46 0.1P3a0P3b attend 3486 10 3.76 0.7N2b attend 2306 15 22.36 0.6P3b attend 4166 15 2.76 0.5

Novel MMN0N1 ignore 1116 6 23.46 0.6attend 1146 8 23.06 0.6

P3a ignore 2296 4 6.56 0.8attend 2636 9 7.66 1.0

Note: In the attend condition, deviant tones were target stimuli andtherefore elicited overlapping P3a and P3b responses. The MMN~orMMN0N1! peaks were measured from deviant–standard or novel–standard ERP difference waves at the frontal midline site~Fz!, the N2band P3a~or P3a0P3b! peaks at the central midline site~Cz!, and the P3bpeaks at the parietal midline site~Pz!.

Table 5. Mean (6SE) Latencies, Moments, and Goodness of Fit for the ECDs for the Magnetic MMNm(or MMNm0N1m) and P3am (or P3am0P3bm in the Attend Condition to Deviant Target Tones)Responses to Deviant Tones and Novel Sounds

Stimulus Wave Hemisphere Condition naLatency

~ms!Moment~nAm!

Fit~%!

Deviant MMNm left ignore 8 1536 6 22.96 2.3 876 1attend 8 1586 8 26.66 2.9 866 3


P3am left ignore 7 2526 7 12.56 1.8 776 2P3am0P3bm attend 3 2956 33 15.36 2.3 716 4P3am right ignore 3 2396 18 10.06 2.0 756 5P3am0P3bm attend 0 — — —

Novel MMNm0N1m left ignore 8 1306 9 23.26 6.0 836 4attend 8 1156 4 22.16 3.5 776 4


P3am left ignore 8 2166 7 18.36 4.9 746 3attend 6 2556 15 17.96 5.9 716 3


aNumber of participants for whom this ECD could be reliably determined.

Participant

Figure 5. Magnetic difference waves for individual participants in theignore~thick lines! and attend~thin lines! conditions obtained by subtract-ing for each condition the magnetic responses to standard tones from theresponses to deviant tones and from those to novel sounds. Differencewaves are shown for individually chosen recording sites showing maximalresponses over the auditory cortices in each hemisphere.

220 K. Alho et al.

each condition, stimulus~a deviant tone or a novel sound!, orhemisphere and why even in the cases where P3am ECDs could bemodeled they explained on the average,80% of the P3am fieldmeasured with 44 channels over one hemisphere~see Table 5!.However, the residual magnetic fields not explained by the mod-eled P3am ECDs did not show systematic distributions, and there-fore, possible additional contributions to the P3am from P3agenerators outside the superior temporal cortex indicated by pre-vious lesion studies and intracranial recordings could not be mod-eled. The same was true for the MMNm discussed below.

Another reason for the lack of a determinable P3am source insome cases, and for the relatively low percentages of the P3amfields explained by the determined ECDs, might be that the ori-entation of the superior temporal ECD contributing to the P3amfield was not always optimal~tangential to the skull! for the MEGsource localization, for example, if the superior temporal P3a sourcewere formed by pyramidal neurons in the convexity of the superiortemporal gyrus rather than in the superior temporal plane.

A contribution of temporal cortex activity to the P3a has beenpreviously observed in intracranial ERP recordings using novelsounds~Alain et al., 1989; Baudena et al., 1995; Halgren et al.,1995a, 1995b!. Moreover, unilateral lesions of the posterior supe-rior temporal cortex attenuated the P3a to novel sounds~Knightet al., 1989!. However, because these lesions were too posterior toaffect the MMN generator in the auditory cortex~Woods, Knight,& Scabini, 1993!, they probably could not have affected the adja-cent P3am source, which in the present study tended to be slightlyanterior to the MMNm source. Thus, there might be separate P3asources in the anterior and posterior temporal cortices, the afore-mentioned lesions affecting the posterior one whereas the presentdata demonstrates the anterior one.

In the attend condition, P3am ECDs for deviant tones could bemodeled in the left hemisphere for only 3 of the 8 participants andin the right hemisphere for none of them. Presumably additionalcontributions from P3bm sources~cf. Lewine et al., 1990; Rogerset al., 1991; Tesche et al., 1996! activated by deviant tones servingas targets overlapped with the P3am fields and prevented modelingof the P3am0P3bm fields measured over one hemisphere with asingle dipole. Attempts were also made to model ECDs for P3bmto target tones at latencies longer than 400 ms where the electricalP3b reached its maximum. However, no P3bm ECDs could bedetermined at these latencies, perhaps because in the present studythe P3b, and thus also the P3bm, was much smaller than the P3b~P300! elicited by target stimuli in previous studies. One reason forthe small amplitude of the present P3b might be the small physicaldifference between the standard and target tones~see Picton, 1992!.

The number of participants in whom ECDs could model theP3am to novel sounds also decreased from the ignore condition tothe attend condition. In the attend condition, activity may havebeen generated by some other P3a source, for example by a pre-frontal, cingulate, or hippocampal source~Baudena et al., 1995;Halgren et al., 1995a, 1995b; Knight, 1984, 1996; Knight et al.,1989!, was enhanced by attention and prevented the single-dipolemodeling of the P3am field elicited by novel sounds. Attentionalenhancement of P3a activity generated outside the superior tem-poral cortex is suggested by a nearly significant enhancement ofthe electrical novel-sound P3a in the attend condition in relation tothe ignore condition, which was not accompanied by an enhance-ment in the strength of the P3am ECD located in the superiortemporal cortex. This attentional enhancement of activity gener-ated by nonsupratemporal P3a sources, presumably participating inthe control of attention, might be related to the fact that although

novel sounds occurring in the attended part of the auditory spaceeasily engage one’s attention, novel sounds occurring outside thecurrent focus of attention do not always do so. However, althoughactivation of P3a sources outside the superior temporal gyrus maydepend on attention, in the auditory cortex of the superior temporalgurus novel sounds are, according to the present P3am and MMNm0N1m responses, processed similarly whether they occur in an un-attended or attended part of auditory space.

In conclusion, the P3am source found in the present study in theanterior superior temporal gyrus appears to contribute substantiallyto the electrical P3a response. However, activity of this source byno means explains all of the P3a, which has generators in severalother brain areas~Baudena et al., 1995; Halgren et al., 1995a,1995b; Knight, 1984, 1996; Knight et al., 1989!. The present re-sults suggest that the anterior areas of superior temporal cortexmay have an important role in the neural circuitry involved ininvoluntary switching of attention to auditory stimulus changesreflected by the P3a. The process in the superior temporal cortexreflected by the P3am is presumably triggered by the adjacentMMN generator activated in the auditory cortex by changes in theacoustic environment and perhaps also by the enhanced N1 activ-ity, for example, for widely deviant auditory stimuli such as thenovel sounds of the present study. The superior temporal P3a gen-erator might in turn trigger generators of the other P3a subcom-ponents, which probably reflect activity of brain mechanismscontrolling the switching of attention to acoustic changes.

The present ECDs for the standard tone responses support theresults of previous studies indicating a major contribution of su-perior temporal activity to the P10P1m, N10N1m, and P20P2mresponses~for a review, see Hari, 1990; for recent studies, seeMäkelä et al., 1993; Mäkelä, Hämäläinen, Hari, & McEvoy, 1994;Nakasato et al., 1995; Pantev et al., 1990, 1995; Reite et al., 1994;Rogers et al., 1990!. Moreover, in accordance with previous results~Rif, Hari, Hämäläinen, & Sams, 1991!, the P2m was generatedanteriorly to the N1m source in the right superior temporal cortex.

As in previous studies, deviant tones differing in frequencyfrom standard tones elicited an MMNm with a superior temporalsource anterior to the N1m source, at least in the right hemisphere~Alho et al., 1996; Csépe et al., 1992; Hari et al., 1992; Huotilainenet al., 1993; Levänen et al., 1993, 1996; Levänen & Sams, 1997;Sams et al., 1991; Tiitinen et al., 1993!. No significant differencesin the MMNm ~cf. Lounasmaa et al., 1989! or MMN ~cf. Näätänen,Gaillard, & Mäntysalo, 1978; Näätänen et al., 1982; Sams et al.,1985b! responses or in the locations of the MMNm ECDs in thesuperior temporal cortex were found between the ignore and attendconditions. The same was true for the MMN0N1 and MMNm0N1m responses to novel sounds. Of course, the instruction of theignore condition to ignore the sounds and to concentrate on watch-ing a film does not guarantee that the participants did so all thetime. Actually, in some studies applying much more demandingattentional tasks than the present ones, amplitude differences be-tween MMN0MMNm responses to deviant sounds occurring inattended and ignored sound sequences have been observed~e.g.,Alho, Woods, Algazi, & Näätänen, 1992; Näätänen, Paavilainen,Tiitinen, Jiang, & Alho, 1993; Trejo, Ryan-Jones, & Kramer, 1995;Woldorff, Hackley, & Hillyard, 1991; Woldorff, Hillyard, Gallen,Hampson, & Bloom, in press!.

The MMN0N1 negativity and its magnetic counterpart elicitedby the novel sounds presumably received a prominent contributionfrom the superior temporal N10N1m source because the novelsounds had wide frequency spectra and therefore activated in theauditory cortex large populations of frequency-specific neurons


that did not respond to standard tones of 600 Hz and were thereforein a nonrefractory state at the moment of the occurrence of a novelsound~cf. Scherg et al., 1989!. However, the MMN0N1 responseto novel sounds was presumably partly caused by the MMN elic-ited by these sounds. This conclusion was suggested by the loca-tion of the right hemisphere generator of this MMNm0N1m response,which was found between the N1m and MMNm generators~seeFigure 3!.

In the attend condition, deviant target tones elicited ERPs withan N2b component peaking at the central scalp around 230 ms

from stimulus onset~cf. Näätänen et al., 1982; Sams et al., 1984,1985b!. No magnetic equivalent of the N2b was observed. Perhapsthe N2b is generated by a source formed by pyramidal cells in thesecondary auditory areas on the lateral convexity of the temporallobe, as suggested by Sams, Aulanko, Aaltonen, and Näätänen~1990!. A dipolar source located in these areas would not be ob-servable by MEG because its orientation would be approximatelyradial to the skull. Another possibility is that the N2b originatesfrom a deep source~Halgren et al., 1995b! that would have only aweak contribution to the extracranially recorded magnetic fields.

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~Received April 18, 1997;Accepted August 21, 1997!

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