182 Electroencephah)graphy and clinical Neurophysioh>gy, g2 ( I g92) 182- I t)6 ~' 1992 Elsevier Scientific Publishers Irchmd, Ltd. 0013-464t)/92/$05.00

EEG 9163(I

Generator sites of spontaneous MEG activity during sleep

Sing-Teh Lu, Matti Kajola, Sirkka-Liisa Joutsiniemi *, Jukka Knuutila and Riitta Hari Low Temperature Laboratory,, th, lsinki University of Technolog,9', 02150 Espoo (Finland)

(Accepted for publication: 18 October 1991)

Summary We have recorded spontaneous magnetoencephalographic (MEG) activity during overnight natural sleep in 4 healthy adults with a 24-channel SQUID gradiometer, mainly over the sides of the head. All sleep stages were obtained. The MEG wave lk)rms resembled the EEG phenomena recorded simultaneously from the scalp midline, but the electric and magnetic signals did not always coincide. The source locations of different signals were studied by using a current dipole model. The equivalent sources of magnetic transients, resembling and often coinciding with the electric vertex waves and K-complexes, as well as the transients during REM sleep, were concentrated within a volume of 4 × 4 × 3 cm 3 in the inferior parietal lobe. For spindles and slow waves, no such focal generators were found.

Key words: Magnetoencephalography; Sleep; K-complex; Vertex wave; Slow-wave sleep; Spindle; Current dipole: Source h~calization: (Man)

Noc tu rna l E E G record ings are convent iona l ly ana- lyzed by classifying s leep s tages on the basis of occur- rence and a b u n d a n c e of d i f fe ren t wave forms. Since the gene ra t i on sites and mechan i sms of the E E G sig- nals a re not known, the record ings canno t be used to m on i to r funct ions of d i f fe ren t b ra in a reas dur ing sleep. Recent ly , with the d e v e l o p m e n t of mu l t i channe l mag- ne tome te r s , m a g n e t o e n c e p h a l o g r a p h i c ( M E G ) s tudies of gene ra to r s of s p o n t a n e o u s bra in rhy thms have be- come feasible . In ea r l i e r s ing le -channe l M E G studies of s leep (Hughes et al. 1976; N a k a s a t o et al. 1990; U e n o and l r a m i n a 1990), it was diff icult to draw con- clusions about the re la t ionsh ips be tween the e lec t r ic and magne t i c activity or abou t the source locat ions.

He re we r epo r t the first mu l t i channe l M E G record- ings dur ing sleep; with the large sensor a r ray it was poss ible to d e t e r m i n e the source locat ions f rom a r eco rd ing at one site, wi thout moving the ins t rument . Since evoked responses of the aud i to ry cor tex were m o n i t o r e d s imul taneous ly (Lu et al. in prep. ) , most of the record ings were o b t a i n e d from the la te ra l aspects of the head.

Correspondence to: Dr. R. HarL Low Temperature Laboratory, Helsinki University of Technology, 02150 Espoo (Finland).

* Present address: Tammiharju Hospital, 106(10 Tammisaari, Fin- land.

Methods

Subjects and experimental setup Four hea l thy adul t s (3 females , 1 male; ages 2 0 - 5 0

years) v o l u n t e e r e d for the exper iments . Subjects 1 and 4 were au thors of this pape r , and subjects 2 and 3 (a m o t h e r and her daugh te r ) were pa id volunteers . None of the subjects had his tor ies of medica l abnormal i t i e s or s leep d isorders .

The record ings were m a d e in the magnet ica l ly sh ie lded room of our labora tory . The room was dark dur ing the s leep me a su re me n t s ; the awake s tage record ings were made with l ights on but o therwise u n d e r ident ica l condi t ions . The subject was lying on a bed with h e r / h i s head fixed by a vacuum cast to p reven t head movemen t s and was ins t ruc ted to relax and to fall as leep wheneve r s h e / h e was ready. No s leep depr iva t ion nor med ica t ion was used. In spi te of the r a the r unusual s leep ing condi t ions , the subjects fell as leep within 5 - 3 0 min af ter the lights were switched off. All s leep s tages were r eached , except for subject 3 in whom R E M s leep was not r ecorded . M e a s u r e m e n t s on subjects 2 and 4 were made dur ing 1 night for 7 - 8 h. Subject 1 was s tud ied dur ing 3 nights ( 7 - 8 h / n i g h t ) and subject 3 dur ing 2 nights (for 3 and 8 h, respec- tively).

S p o n t a n e o u s M E G and E E G activi t ies were moni- t o r ed cont inuous ly dur ing the night on a rea l - t ime display and se lec ted par t s were r e c o r d e d on a digi tal

MEG DURING SLEEP 183

tape for later off-line analysis. The total recording times were 2-4 h /n igh t (in 2.5-10 min periods). Audi- tory stimuli (tone pips once every 1.1 sec) were pre- sented during 50-80% of the time for subjects 1, 3 and 4, and continuously for subject 2 through a head phone in the pillow. On visual inspection of the recordings, no transients (K-complexes or vertex waves) were time- locked to the sounds; this is most probably because the stimuli were repeated relatively fast.

Recording and data analysis" The magnetic signals outside the head were mea-

sured with a 24-channel SQUID gradiometer (Ahonen et al. 1991). This device uses a planar flux transformer configuration: its two orthogonal figure-of-eight loops per sensor unit measure the tangential derivatives OB./Ox and OB,/Oy of B,., the field component normal to the head, simultaneously at 12 locations 30 mm apart. While a conventional axial gradiometer detects field extrema on both sides of a current dipole, a planar gradiometer detects the largest signal just above the dipole. The sensors cover an area of 12.5 cm in diameter and the source location can often be deter- mined during a single experiment without moving the instrument; this is especially important for studies of spontaneous brain activity.

Signals were measured over the side of the right hemisphere in all subjects, with the magnetometer center approximately above the crossing of the sylvian and rolandic fissures. In addition, recordings were ob- tained over the upper part of the right hemisphere near the midline in subject 1, and over the left hemi- sphere in subject 4. The locations and orientations of the 24 sensors with respect to external landmarks on the scalp were determined before each measurement, by recording the magnetic field produced by 3 small coils fixed on the scalp at known positions (Knuutila et al. 1987).

The passband of the MEG recordings was 0.05-100 Hz (3 dB points, roll-off for the high-pass filter 35 dB/decade and over 80 dB/decade for the low-pass filter). The data were digitized at 297 Hz. We also recorded the electro-oculogram (FOG; vertical in all subjects, also horizontal in subjects 2 and 4), EEG from electrodes Fz, Cz, and Oz referred to the mastoid contralateral to the MEG recording, the electrocardio- gram (ECG) between the two wrists (subjects 2 and 4), and the surface electromyogram (EMG) from submen- tal muscles. Passbands were 0.1-100 Hz (6 dB points) for EEG, FOG, and ECG and 30-10,000 Hz for EMG. The wide passband for EMG recordings, in spite of the low sampling rate, was adequate since only the mean EMG amplitude was of interest. One or two MEG channels were occasionally noisy but, to avoid any disturbance to the sleeping subject, no attempt was made to adjust them during the recordings.

To determine the equivalent source locations of the magnetic signals, representative epochs of 200-2000 msec were chosen from the continuous record for further analysis. The baseline for amplitude measure- ments was defined as the mean of the visually deter- mined no-signal region for the magnetic counterparts of vertex waves and K-complexes and as the mean amplitude of the whole analysis period for spindles and slow waves.

Our classification of sleep stages was based on elec- tric signals, according to guidelincs of Rechtschaffen and Kales (1968):

Waking: rhythmic alpha activity in the occipital lead. Stage la: alpha rhythm is waxing and waning, dis-

continuous, and "spreads" towards anterior scalp re- gions.

Stage lb: mixed theta activity and occasional sharp vertex waves appear.

Stage 2: sleep spindles and K-complexes appear. Stage 3: slow-wave sleep, 20-5(/% of the epoch

consists of 0.5-2.5 Hz activity, at least 75 /,V peak-to- peak.

Stage 4: slow-wave sleep at least 50% of the epoch. REM sleep: rapid eye movements in the FOG chan-

nel, low-voltage EEG background, decreased tone in the submental muscles.

"Equivalent current dipoles" (ECDs), i.e., current dipoles that best explain the measured field pattern, were determined by using a spherically symmetric con- ductor model. The origin and radius (95-115 ram) of the sphere were chosen to fit best the local curvature of the head in the measurement area. The fitting algorithm, which was used to compute the locations and strengths of the ECDs, took into account the measured sensor locations and orientations so that the effects of primary and w)lume currents were properly dealt with (Sarvas 1987).

Results

Figs. 1-7 show examples of magnetic and electric recordings in subjects 1 and 2 during the different stages of sleep. During wakefulness (Fig. 1), the occipi- tal EEG displays rhythmic 10-11 Hz alpha activity in subject 1 and 8-9 Hz activity in subject 2. The simulta- neous MEG over the lateral aspect of the head is of rather low amplitude but displays rhythmic activity of the same frequency within (}.5 Hz. During light drowsi- ness (stage la; Fig. 2), the occipital electric alpha becomes discontinuous, "spreads" more anteriorly and its frequency slows down by about 1 Hz. Simultane- ously rhythmic activity of the same frequency appears in MEG, more clearly in subject 1 and especially in the middle lower channels.

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Fig. 1. Spontaneous activity in subjects 1 and 2 during the awake stage with the eyes closed. The recording locations are indicated on the schematic heads; the x gradients at 12 locations are plotted above and the y gradients below. In the electric channels EOGv and EOGh refer to vertical and horizontal oculograms, respectively. The whole recording period shown is 12 sec. The electric amplitude scale refers to all other

electric recordings except the EMG for which only relative amplitudes are of importance.

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drowsiness. Note the increase of rhythmic MEG activity compared with the awake stage. Other details as in Fig. 1. Channel y12 was noisy during the recordings on subject 2.

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Fig. 4. Stage 2, light sleep. K-complexes occur both in MEG and EEG. Other details as in Figs. 1 and 2.

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Fig. 5. Stage 3, deep sleep. Other details as in Figs. 1 anti 2.

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Fig. 7. R E M sleep. O t h e r detai ls as in Fig. 1.

MEG DURING SLEEP 191

During deep drowsiness and light sleep (stages lb and 2; Figs. 3 and 4) vertex waves of 150-250 msec duration appear in the frontocentral EEG leads. Simi- lar wave forms are seen in MEG; we will designate them "V waves." The magnetic and electric V waves do not always coincide.

Magnetic spindles of 11-15 Hz in frequency and 0.3-2 sec in duration appear during stage 2 (Fig. 4). Sometimes they are superimposed on high-amplitude transients, thereby resembling the typical electric "K- complexes," and we shall call them K-complexes as well. Thc magnetic V waves and K-complexes were often repeatedly seen in similar wave form and distri- bution but clear differences were also evident between successive transients. A typical K-complex lasted 0.8- 1.2 sec.

During slow-wave sleep (stages 3 and 4; Figs. 5 and 6), the 0.5-2 Hz polymorphic MEG activity is widely spread and there arc no consistent differences between the signals detected by the two orthogonal loops, indi- cating that the orientation of the source currents changes frequently. In subject 1, where recordings were available from 2 locations, the magnetic recordings showed much less slow-wave activity in the uppermost than the lower part of the right hemisphere, in the presence of the same amount of electric slow-wave activity.

Three subjects reached REM sleep, defined on the basis of rapid eye movements, decreased muscular tone, and absence of spindles and K-complexes in the EEG. REM appeared around 1-2 a.m. for 15-20 min and between 4:30 and 6 a.m. for 35-60 min. During the REM stage the M E G activity was lower in amplitude and faster in frequency than during other sleep stages (Fig. 7). Sharp magnetic transients resembling the V waves were frequently seen.

Fig. 8 shows examples of different magnetic signals, chosen to illustrate the variability in wave form and distribution from one signal to another in the same subject. Fig. 8a compares the distribution of the audi- tory evoked magnetic fields (AEFs), recorded during wakefulness, and V waves. The main AEF deflection, Nl00m, peaks about 100 msec after the tone onset. The amplitude maximum is more posterior for the V wave than for N l00m, suggesting different source loca- tions. Furthermore, the different amplitude ratios of signals on x- and y-gradients during AEF and V wave suggest different orientations for the source currents. During REM sleep, magnetic transients do not coin- cide with electric signals on the midline scalp (Fig. 8b). In Fig. 8c, the two electric K-complexes resemble each other whereas the magnetic distributions are different. The same is true for the spindles (Fig. 8d). The typical maximum amplitudes of different wave forms were 400 l T / c m for V waves, 600 f T / c m for K-complexes, 800

t T / c m for slow waves, 300 f F / c m for spindles and 400 f T / c m for transients during REM sleep.

Fig. 9 shows the locations of ECDs for all subjects during the V waves, K-complexes, slow waves, and REM transients. Only dipoles with goodness-of-fit val- ues of at least 90% were included, and ECDs with source depths exceeding 50 mm and with strengths exceeding 500 h a m were excluded. This was because the source depth and strength arc strongly correlated (cf., Hari et al. 1988); in the worst case dipole depths (between 10 and 50 mm) explained almost 80% of the dipole strength. The dep th / s t r eng th criterium resulted in rejection of less than 1(1~5~ of all ECDs. Typical strengths were 100-300 nAm for dipoles located 30-40 mm beneath the scalp; the 95~4 confidence limits for the depth estimates were 6-12 mm.

The equivalent sources of vertex waves and K-com- plexes are clustered in an area of 4 x 4 cm e in the xy-planc, a few centimeters toward the parietal lobc from the sources of N100m, which is generated at the auditory cortex on the superior surface of the temporal lobe (Hari 1990). Since the MEG signals primarily originate from currents in the fissural cortex, Fig. 9 also shows the estimated courses of two fissures from which the different wave forms might come: these estimates were obtained by drawing lines orthogonal to the main orientation of the ECDs. The main source orientations were similar for V waves, K-complexes, and REM transients, the "fissures" forming an angle of 30-45 ° with the sylvian fissure, whose course is derived from the orientation of lhe ECD for N100m. For subject 4, recordings were available from both hemispheres with rather symmetric source locations and "fissure" orientations.

Sources of REM transients (shown for 3 subjects in Fig. 9) also clustered to the same area as the sources of V waves and K-complexes. During slow-wave sleep the ECDs were more widely distributed but concentrated in the lower parts of the lateral recording sites.

A single dipole model could not explain the ob- served spindle distributions satisfactorily; even during one spindle, multiple ECDs operated successively or simultaneously, sometimes several centimeters apart. Principal component analysis showed that to explain at least 90% of the field variance, 4 -6 components were needed for about 1 sec. Neither was it possible to explain the spindle distribution with a 2-dipole time- varying model. These results emphasize the complexity of the sources underlying spindles.

Discussion

This is the first report of multichannel MEG record- ings during sleep. In spite of different sensitivities of

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-4 -2 0 2 4 cm -4 -2 0 2 4 cm -4 -2 0 2 4 cm -4 -2 0 2 4 cm Fig. 9. Locations of ECDs for V waves, K-complexes, and slow waves m all 4 subjects and lk)r REM transients m 3 subjects. For subiect 4 data are shown from both hemispheres. The coordinate system is shown on the schematic heads: the x-axis forms a 45 '~ angle with the line connecting the

ear canal and the cyc corner, and the origin is 7 cm posterior to the eye corner. The thick lines in the V wave "boxes" illustrate the estimated course of the syKian fissure and the thin lines the "fissures" of the ECDs (see text for more details). The orientation of E( 'Ds of N10IIm arc

shown by arrows, and their locations by open circles.

4 ~

Fig. 8. Examples of distributions of different magnetic phenomena. The signals are from subjects 1 3, recorded within 1(/ min over the same location in each subject. In the magnetic signals, the upper traces of each pair indicate the vertical gradient and the lower trace the horizontal gradient of the magnetic field: the recording locations are shown on the insert head. Simultaneous electric signals from the midline are shown in the inserts. Note that the scales are different in frames a-d . The time calibration is 100 msec, and the amplitude calibration 300 fT /cm for the

magnetic and 1()0/*V for the electric signals.

194 S.-T. LU ET AL.

the E E G and M E G methods to currents of different orientations and locations, the primary currents are the same for both signals (Williamson and Kaufman 1981; Hari and Lounasmaa 1989). The observed similarities between the M E G and E E G wave forms were thus to be expected, and it was possible to classify sleep stages on the basis of both recordings. Both methods have their advantages in sleep studies. The subject is able to move more freely during E E G recordings, whereas MEG studies can be focused easily on activity of local areas in the fissural cortex.

Vertex waves, K-complexes and REM transients The ECDs of magnetic V waves, K-complexes, and

REM transients were in a rather localized area which agrees with the inferior parietal lobe. This brain region seems to be involved in the regulation of attention since its lesions can lead to neglect syndromes. Inter- estingly, Doricchi et al. (1991) recently observed that in patients with left visual hemi-inattention, rapid eye movements (REMs) towards the left were virtually absent during sleep. We may thus hypothesize that the inferior parietal lobule is phasically activated during some sleep stages, The functional role of this is ob- scure at present but seems to agree with the early hypothesis that K-complexes are linked to arousal and orientation (Roth et al. 1956).

The main ECD orientation for V waves and K-com- plexes, pointing towards the Fz location, agrees with the electric scalp distribution, with larger amplitudes at Fz than at Cz (cf., Fig. 8a and c). The sources are bilateral and may evidently function independently since the midline E E G did not always coincide with the magnetic signals of the lateral aspect of the head.

In a recent MEG study with a single-channel mag- netometer combined with EEG mapping (Ueno and Iramina 1990), it was suggested that the K-complexes have bilateral deep (possibly thalamic) sources pointing towards frontal areas. ECDs show similar orientations in the present study. However, dipole moments of the observed strength can hardly be generated in the thala- mus. This is because the number of structures in which current flow can be modelled with dipoles - - such as the pyramidal cells - - is considerably smaller in the thalamus than in the cortex. Assuming a cortical source, a dipole moment of 200 nAm would necessitate activa- tion of 40-100 cm 2 of the cortex (cf., Hari 1990), corresponding to an area of 7-11 cm in diameter. If the source was deeper, e.g., thalamic, it would have to be stronger to produce the observed signals, and be thus still more extended. Consequently, we consider the sources of K-complexes to be cortical, although probably driven by subcortical input.

In the early E E G studies, similarities were empha- sized between the electric K-complexes and the "non- specific" auditory evoked "ver tex" potentials (Roth et

al. 1956). M E G studies have later indicated that an important part of the auditory vertex potential arises from the supratemporal auditory cortex (see Hari 1990 for a review). The present data, showing different locations and orientations of the ECDs for N 100m and for V waves and K-complexes, indicate that the genera- tors of these phenomena are distinct.

Our data differ from early suggestions about the generation of vertex waves at cytoarchitectonic areas 6 and 9 (Brazier 1949). However, we did not record activity from the whole head, and differences can also arisc from MEG's selectivity to tangential currents. Some of the discrepancies concerning multiple sources cannot be resolved without combined EEG and MEG recordings, both covering the whole head.

Slow-wace sleep In scalp EEG recordings the delta activity below 2

Hz is widely distributed all over the head. Delta is not a truc rhythmic phenomenon, nor is it considered to have any local sources. The latter s tatement is sup- ported by the present MEG data although there was a trend for larger slow-wave activity over the lower than the upper measurement locations. One possible mech- anism for the generation of polymorphic delta activity during sleep is partial functional deafferentation of the cortex, as suggested by animal experiments (Steriade et al. 1990). Slow-wave sleep can be considered "synchro- nized" activity where a large number of neurons have to fire simultaneously; consequently the dipole mo- ments are the strongest among all sleep phenomena that we recorded.

Spindles Signal distributions indicate that spindles probably

involve smaller areas for each generator than the slow-wave activity. At present, the role of the reticulate thalamic nucleus is emphasized as the t r igger /modula- tor of the cortical spindling activity (Steriade et al. 1990). Combining this idea with our findings of diverse source areas would mean that thalamocortical fibers drive spindles at various neocortical areas. Complexity of spindle generation, with a multitude of sources and different frequencies, has been assumed from animal experiments (Buser 1987), and from depth electrode and scalp topography studies in humans (Niedermeyer 1982; Scheuler et al. 1990). It is evident that sophisti- cated source models ought to be applied to the inter- pretation of spindle distributions. The diversity of the sources also implies that results obtained by single- channel MEG recordings, with an EEG signal as a trigger, can be misleading since activities of various source areas are intermixed.

Rhythmic activity during drowsiness The rhythmic activity during drowsiness is of special

interest when evaluating the generators of alpha-like

MEG DURING SLEEP 195

phenomena . The " s p r e a d " of a lpha towards more an-

ter ior regions, with slightly lower f requency, has been

cons idered a sign of dec reased vigi lance (Bente 1964;

San tamar ia and Chiappa 1987). This type of spread

would be in c lear contras t to ideas emphas iz ing local

genera to rs for the alpha activity (Lopes da Silva and

Storm van Leeuwen 1977, C h a p m a n et al. 1984). Ti iho-

hen et al. (1991) recent ly r epor t ed a magne toen -

cepha lograph ic 11) Hz rhythm, with E C D s si tuated at

the supra tempora l audi tory cortex. Since currents in

this area would p roduce the maximum E E G ampli-

tudes in the f ron tocent ra l midl ine, we can assume the

spread of the electr ic alpha activity dur ing drowsiness

to reflect changed relative contr ibut ions from the oc-

cipital alpha and from the t empora l lobe 10 Hz genera-

tors (cf., Hari 1991). Such a hypothesis is suppor ted by

the present results showing more abundant magne t ic

10 Hz activity over the lateral aspects of the head

during stage l a than during wakefulness , in contras t to

the behavior of the occipital e lectr ic alpha activity. In

addit ion, the recent depth e lec t rode recordings of Nie-

de rmeye r (1990, 1991) indicate that t empora l 6-11 Hz

activity, evidently arising from the convexial t empora l

cortex, is more resistant to vigilance decrease than the

occipital alpha.

Conclusions

Spon taneous M E G and E E G activities dur ing sleep

have complex spatial distr ibutions. In o rder to be confi-

dent that the E C D s really are physiologically meaning-

ful, and to compa re electr ic and magnet ic wave forms,

s imul taneous E E G and M E G recordings cover ing the

whole head are necessary, especial ly because the

sources in both hemispheres seem to funct ion sepa-

rately. A l though our present 24-channel ins t rument

has a coverage large enough for accura te de te rmina-

tions of various sources of evoked responses, it is not

ex tended enough to give precise informat ion about the

depths of deep sources. The present results, however ,

are promis ing in that they show phasic act ivation of

localized brain areas dur ing sleep. Moni to r ing these

areas might give new insights into the poorly under-

stood organiza t ion of cortical funct ions dur ing sleep.

This study was financially supported by the Academy of Finland, by the KSrber Foundation (Hamburg, Germany), and by the Sigrid Jusdlius Foundation.

We thank Mr. J. Karhu, Dr. Jyrki Mfikelfi, Dr. L. Leinonen. Prof. O.V. Lounasmaa, and Ms. Ritva Paetau for comments on the manuscript.

R e f e r e n c e s

Ahonen, A., HS.mS.lfiinen, M., Kajola, M., Knuutila, J., Lounasmaa, O., Simola, J., Tesche, C. and Vilkman, V. Multichannel SQUID systems for brain research. IEEE Trans. Magn., 1991, 27:2786 2792.

Bente, D., Die Insuffizienz der Vigilit~tstonus. Habilitationschrift. University of Erlangen-Niirnberg, 1964.

Brazier, M. The electrical fields at the surface of the head during sleep. Electroenceph. clin. Neurophysiol., 1949, 1: 195-2(14.

Buser, P. Thalamocortical mechanisms underlying synchronized EEG activity. In: A. Halliday, S. Butler and R. Paul (Eds.), A Textbook of Clinical Neurophysiology. Wiley, Chichester, 1987:595 621.

Chapman, R.M., llmoniemi, R.J., Barbancra. S. and Romani, G.L. Selective localization of alpha brain activity with neuromagnetic measurements. Electroenceph. clin. Neurophysiol., 1984, 58: 569-572.

Doricchi, F., Guariglia, C., Paolucci, S. and Pizzamiglio, L. Disap- pearance of leftward rapid eye movements during sleep in left visual hemi-inattention. NeuroReport, 1991, 2: 285-288.

Hari, R. The ncuromagnctic method in the stndy of the human auditory cortex. In: F. Grandori, M. Itoke and G. Romani (Eds.), Auditory Ew~ked Magnetic Fields and Potentials. Advances in Audiology, Vol. 6. Karger, Basel, 199(h 222 282.

ttari, R. Idling 10-Hz rhythm in the human auditory cortex? Soc. Neurosci. Abst., 1991, 17: 1484.

Ilari, R. and Lounasmaa, O.V. Recording and interpretation of cerebral magnetic fields. Science, 1989, 244:432 43(7.

Hari, R., Joutsiniemi. S.-L. and Sarvas, J. Spatial resolution of neuromagnetic records: theoretical calculations Jn a spherical modeh Electroenceph. clin. Neurophysiol., 1988, 71:64 72.

Hughes, J.R., Hcndrix, D.E., Cohen, J., Duffy, F.H., Mayman, C.I., Scholl, M.L. and Cuffin, B.N. Relationship of the magnctoem cephalogram to the electroencephalogram. Normal wake and sleep activity. Electrocnceph. clin. Ncnrophysiol., 1976, 40:261 278.

Knuutila, J., Ahlfors, S., Ahoncn, A., H~.illstr~'~m, J., Kajola, M., Kiviranta, M., Lounasmaa, O.V., Vilkman. V. and Tesche, C. Large-area low-noise seven-channel dc SQUID magnetometer for brain research. Rev. Sci. lnstrum., 1987, 58: 2145-2156.

Lopes da Silva, F. and Storm van Leeuwen, W. The cortical source of alpha rhythm. Neurosci. Left., 1977, 6:237-241.

Lu, S.-T., Kajola, M., Joutsiniemi, S. L. and Knuutila, J. In prepara- tion.

Nakasato, N., Kado, tE, Nakanishi. M., Koyanagi, M., Kasai, N., Niizuma, H. and Yoshimoto. T. Magnetic detection of sleep spindles in normal subjects. Electrocnccph. olin. Neurophysiol., 1990, 76:123 130.

Niedermeyer, E. Depth electroencephak)graphy. In: E. Niedermeyer and F. Lopes da Silva (Eds.), Electroencephalography. Basic Principles, Clinical Applications and Related Fields. Urban and Schwarzenberg, Baltimore, MD, 1982: 519-536.

Niedermeyer, E. Alpha-like rhythmical activity of the temporal lobe. Clin. Electroenceph., 199{), 21:21(1 224.

Niedermeyer, E. The "third" rhythm: furthcr observations. Clin. Electroenceph., 1991, 22: 83-%.

Rechtschaffen, A. and Kales, A. (Eds.). A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages in Human Subjects. U.S. Government Printing Office, Washington, DC, 1968.

Roth, M., Shaw, J. and Green, J. The form, w)ltage distribution and physiological significance of the K-complex. Elcctroencepb. clin. Ncurophysiol., 1956, 8: 385-4(t2.

Santamaria, J. and Chiappa, K. The EEG of drowsiness in normal adults. J. Clin. Neurophysiol., 1987, 4:327 382.

Sarvas, J. Basic mathematical and electromagnetic concepts of the biomagnetic inverse problem. Phys. Med. Biol., 1987, 32:11 22.

Scheuler, W., Kubicki, S., Scholz, G. and Marquardt, J. Two differ- cnt activities in the sleep spindle frequency band discrimination based on the topographical distribution of spectral power and coherence. In: J. Home (Ed.), Sleep '9(/. Pontenagel Press, Bochum, 1990: 13-16.

196 S.-T, LU ET AL.

Steriade, M., Gloor, P., Llinfis, R.R., Lopes da Silva, F.H. and Mesulam, M.-M. Basic mechanisms of cerebral rhythmic activi- ties. Electrocnceph. clin. Neurophysiol., 1990, 76: 481-508.

Tiihonen, J., Itari, R., Kajola, M., Karhu, J., Ahlfors, S. and Tissari, S. Magnetoencephalographic 10-Hz rhythm from the human au- ditory cortex. Neurosci. Lett.. 1991, 129: 303-305.

Ueno, S. and Iramina, K. Modeling and source localization of MEG activities. Brain Topogr., 19911, 3:151 165.

Witliamson, S.J. and Kaufman, L. Biomagnctism. J. Magn. Magn. Mat., 1981, 22: 129-202.