Study of focal epilepsy by multichannel neuromagnetic measurements

358

Electroencephalography and chmcal Neurophyslologv, 1987, 66, 358-368

Elsevier Scientific Pubhshers Ireland, Ltd EEG01808

Study of

focal epilepsy by muitichannel neuromagnetic measurements 1

G.B. Ricci, G.L. Roman_i, C. Salustri, V. Pizzella, G. Torrioli 2, S. Buonomo, M. Peresson and I. Modena lstrtuto dl Elettromca dello Stato Sohdo, C N R , 00156 Rome (Italy)

(Accepted for pubhcatlon 28 August, 1986) A systematic investigation of several cases of focal epilepsy has been performed in an unshlelded environment using a 4-channel neuromagnetac sensor The loCallzatlons provided by the magnetic measurements have been compared with chmcal ewdence and confirmed by X-ray findings, and an one case also by lntracramal surgery The results show the importance of simultaneous detection of magnetic fields at different sates of the scalp in order to get a dynamic view of the epileptic activity and to detect multffocal activity unsuspected on the basis of the EEG investigation Summary

Key words. Neuromagnetlsm, Focal epilepsy, Forward and reverse problem, Brain activity mapping

O n e of the most p r o l m s i n g clinical a p p h c a t i o n s of the b i o m a g n e t i c m e t h o d is its capability of 3 - d i m e n s i o n a l localization of focal activities in patients affected b y partial epilepsy (Barth et al. 1982, 1984; C h a p m a n et al 1983). Since 1980 we have been investigating this k i n d of clinical material (Ricci et al. 1981; M o d e n a et al. 1982), strongly basing our approach o n previous experience in chnical E E G a n d addressing it to reveal b y m e a n s of the m a g n e t o e n c e p h a l o g r a m ( M E G ) what was n o t evident i n the c o r r e s p o n d i n g EEG. I n agreement with the predictions of a simple theoretical analysis ( W l l l i a m s o n a n d K a u f m a n 1981), those first findings supported the idea that the investigation of cerebral magnetic fields was a new, powerful tool to investigate intracellular current activity directly, with only a i m n o r c o n t r i b u tion from extracellular, i.e., volume, currents. These volume currents, b y contrast, do influence the spatial d i s t r i b u t i o n of electrical potentials, 1 Work partially supported by Progetto Flnahzzato 'Tecnologae Blomedache e Samtane,' C N R 2 Supported by grant by Elettromca S p A Correspondence to Prof G L Romam, Istatuto da Elettromca dello Stato Sohdo, C N R, Via Cmeto Romano 42, 00156 Rome, Italy

typically spreading their a p p e a r a n c e rather widely over the scalp. O n e of the most significant examples reported at that time was that, in the study of r o l a n d i c epilepsies, the M E G systematically revealed pathological signals whale the simultan e o u s l y recorded E E G was silent, even d u r i n g seizures ( M o d e n a et al. 1982; Raccl 1983). The reason for this effect is still unclear, b u t could be because in rolandic epilepsies the sources are m a i n l y in the wall of the central fissure a n d thus optimally seen b y M E G (Williamson and K a u f m a n 1981) It is worth r e m a r k i n g that n o a t t e m p t was made either i n those m e a s u r e m e n t s or i n the ones performed later b y our group, i n c l u d i n g the electrical m e a s u r e m e n t s reported in this paper, to record the E E G with high spatial resolution. O n the other hand, it is n o t yet clear from the literature whether the high spatial resolution E E G would be as successful as the M E G i n localizing epileptic focl. T h e use of single-channel magnetic detectors has forced experimentalists to measure magnetic signals sequentially at different sites of the head surface a n d it has n o t been possible to o b t a i n a s i m u l t a n e o u s d i s t r i b u t i o n of the magnetic field over the scalp This p r o b l e m was partially worked out b y correlating the magnetic signals with the

0013-4649/87/$03 50 © 1987 Elsewer Scientific Publishers Ireland, Ltd

NEUROMAGNETISM IN THE STUDY OF FOCAL EPILEPSY s t m u l t a n e o u s l y r e c o r d e d electrical ones. This corr e l a t i o n was p e r f o r m e d either b y selecting s p o r a d i c spikes ( B a r t h et al. 1982) or b y e x t e n d i n g the i n v e s t i g a t i o n to r h y t h m i c c o m p o n e n t s of the pathologacal activity ( C h a p m a n et al. 1983). A d i p o l a r - l i k e d i s t n b u t i o n was often observed, and this s u p p o r t e d the i d e a that a simple c u r r e n t dip o l e can be used, at least in a first approxamation, to i d e n t i f y the l o c a t i o n of the active source in the p a t i e n t ' s brain. This a p p r o a c h p r o v e d to be successful with a single-channel system in a first set of 13 cases studied d u r i n g 1984 ( R i c o et al. 1985a), in the m a j o r i t y of which a l o c a h z e d p a t h o l o g y was a l r e a d y k n o w n f r o m X - r a y a n d / o r prexaous surgical findings. A n i m p o r t a n t d r a w b a c k o f m a p p i n g sequentially is that the m e a s u r e d fields are g e n e r a t e d in successive time intervals. F o r this reason the m e a s u r e m e n t s are affected b y the t e m p o r a l v a n a t l o n s of the p s y c h o l o g i c a l and chnlcal c o n d i t i o n s of the subject, a n d m o r e o v e r require o v e r l e n g t h y m e a s u r ing sessions - - 6 - 8 h. F r o m the above, it is clear that the single-channel a p p r o a c h p r o v i d e d a h r m t e d t e m p o r o - s p a t l a l view. T h e need for a m u l t i p l e - s e n s o r m a g n e t i c d e t e c t o r b e c a m e therefore i m p e r a t w e . T h e final goal is i n d e e d a system with a n u m b e r of a d j a c e n t m a g n e t i c channels suitable to m e a s u r e fully at the s a m e time the entire m a g n e t i c field d i s t r i b u u o n p r o d u c e d b y the c e r e b r a l event u n d e r investigation. H a r d technical p r o b l e m s are involved in this p r o j e c t a n d at the m o m e n t only a few 4-, 5- a n d 7-sensor units are b e i n g used m the world. D u r i n g 1984 we d e v e l o p e d in our l a b o r a t o r y a 4 - c h a n n e l s y s t e m that has been used since the b e g i n n i n g of 1985 in the s t u d y of b r a i n activity. T h e p r e s e n t p a p e r r e p o r t s on the m a g n e t i c results o b t a i n e d m the s t u d y of focal epilepsies using this 4-sensor instrument. P r e l i m i n a r y findlngs were p r e s e n t e d at the I C M B c o n f e r e n c e m Helsmka (Racci et al. 1985b), a n d at the l l t h I C E C N in L o n d o n ( R a c o et al. 1985c)

Methods T h i r t e e n cases of p a r t i a l (focal) e p i l e p s y were extensively studied. T a b l e I s u m m a r i z e s the seizure

359

Fig 1 a close-up view of the 4 gra&ometers of the muluchannel system operating at the tstltuto dl Elettromca dello Stato Sohdo, CNR, m Rome The 4 second-order gradlometers are permanently balanced (Romam et al 1985) b the system dunng a recording session on an epdeptlc patient s y m p t o m a t o l o g i e s a n d the findings o b t a i n e d b y m e a n s of X - r a y a n d E E G studies A suggestion of the cortical areas revolved was p r o v i d e d b y the seizure p a t t e r n s for all p a t i e n t s and, in 10 cases o u t of the 13, this suggestion was s u p p o r t e d b y C T scan or other X - r a y findings T h e r e were 4 cases of cortical a t r o p h y , two of p o r e n c e p h a l y , two of m e n l n g i o m a (left sylvian fissure a n d right uncus region respectively), one of left p a r i e t a l scar (bullet w o u n d ) a n d one of left p a r i e t a l n o n - t u m o u r a l calcification T h r e e cases d i d n o t exhibit any p a thology. T h e drug t r e a t m e n t was i n t e r r u p t e d or r e d u c e d to a half dose a b o u t 12 h before the m a g n e t i c m e a s u r e m e n t session T h e e x p e r i m e n t a l a p p a r a t u s a n d the p r o c e d u r e for a n a l y s i n g d a t a have been described elsewhere ( R o m a m 1984; R o m a n i a n d Leoni 1985, R o m a n i et al 1985) F o r clarity the m a i n features are reviewed here. M a g n e t i c m e a s u r e m e n t s were p e r f o r m e d using 4 s e c o n d - o r d e r gradiometers, p e r m a n e n t l y balanced ( R o m a n l et al. 1985), each c o u p l e d to its own r f S Q U I D ( S u p e r c o n d u c t i n g Q u a n t u m Interference Device) ( R o m a n l et al. 1982) T h e system, shown in F i g 1, allowed s i m u l t a n e o u s measurem e n t s of the m a g n e t i c field at 4 sites of the head l o c a t e d at the vertices of a square with 2 cm side E a c h p i c k - u p cod d i a m e t e r was 1 5 c m a n d the

360 basehne of the gradiometers was 5.3 cm. The overall noise level of the instrument was typically 40-55 ffF (Hz) -x/2 (1 femtoTesla= 10 is Tesla, the value of the earth's magnetic held is 5 x 1010 fT) during actual measunng conditions. The magnetic field perpendicular to the scalp was measured, simply orienting the dewar tall, containing the pick-up coals parallel to the bottom, perpendicularly to the patient's head. The flatness of our dewar tail introduced a small systematic error m the orientation of the 4 gradlometers; this error was estimated to be about 6 °. Particular care was devoted to sensor positioning, as it dramatically affects the rehabihty of source localization (Roman1 and Leoni 1985). To get the best positioning accuracy, each subject was required to wear a plastic cap, onto which an appropriate reference system was drawn on the basis of anatormcal features (naslon-mlon hne, ear-to-ear through the vertex, etc.). A pre-deterrmned grid with 4 cm spacing was then drawn on the cap and the dewar tail was positioned with great accuracy with respect to each grid crossing, using a simple but effective optic fibre system. Each patient was required to lie and relax on a specml wooden bed moveable m a horizontal plane to make positioning easier - - and his head was supported by a VAC-PAC pillow (Olympic Medical Co.) to help keep the head steady d u n n g the time needed to record signals from each posiUon. The total duration of a complete recording session was typically 2 h, corresponding to about 100 recorded sites. N o magnetic shielding was required in our wooden hut and the residual signal at the power hne frequency and harmomcs was elirmnated by means of standard comb filters. Simultaneously the EEG was recorded from AgC1 electrodes according to the standard 10-20 system, with contralateral ear reference Both magnetic and electrical signals were bandpass filtered in the frequency bandwidth of 0.5-32 Hz with 48 d B / o c t a v e rolloff and flat delay characteristics After analog to d~g~tal conversion of 128 samples/sec, digital data were stored on a magnetic disc for off-hne processing. To get on-line momtormg of the measurements, 4 EEG traces (typically those which showed the most interesting pathological activity) and the simultaneous 4 M E G ones were chart recorded -

G B RICCI ET AL using a standard E E G machine. The analysis of experimental data was performed using the Relative Covariance Method (RCM). Tlus procedure was proposed for the first time by Chapman et al. (1984) for the study of magnetic alpha rhythm, and successfully used also in the analysis of data from patients affected by focal epilepsy (Chapman et al. 1983). In short, the RCM consists of the following steps. First, the MEGs and the EEGs are analysed in the frequency domain by means of a standard F F T procedure and the components corresponding to a pathological activity, ff any, are identified. Second, the signals are digitally filtered to cancel out those spectral components which are outside a 2 Hz bandwidth around the frequencies identified during the previous step. Third, the covanance between the magnetic signal detected at one site on the scalp and the simultaneously measured EEG is calculated Each covarmnce value is then divided by the variance of the corresponding EEG to compensate for possible variation in source intensity. The new values are defined as Relative Covanance figures This can be expressed m mathematical terms by the simple formula: Y~ B(tl)E(tl)

-

RC=

1

Y' E2(t~) 1

where B(tl) and E(t~) are respectively the values of the magnetic field perpendicular to the head and of the electrical potential at a particular t~me t~. This quantity can be shown to be proportional to the value of the magnetic field perpendicular to the head at a certain location. Both the covanance and the variance should be calculated on the deviations of B and E from the corresponding average values B0 and E 0 which, however, are assumed to be zero as the operation is performed after AC fdtenng. The same procedure repeated for all the positions provided, within the constant factor, the spatial distribution of the magnetic field perpendicular to the scalp. The map of this field on the surface of the head was then made by plotting the RC values for each of the scalp posit~ons as a topologtcal display This could be repeated for each EEG lead and for each selected frequency

NEUROMAGNETISM

IN THE STUDY OF FOCAL EPILEPSY

T h e m a p s o b t a i n e d were visually i n s p e c t e d to i d e n t i f y a d i p o l a r distribution, if any, and, in the a f f i r m a t i v e case were used for source localization T h e criterion to select the m a p s to be further p r o c e s s e d was p u r e l y qualitative However, the l o c a l i z a t i o n p r o c e d u r e used for source identification p r o v i d e d an a p o s t e r t o r t c o n f i r m a t i o n of the a p p r o p r i a t e n e s s of the initial choice (see below) T h e p r o c e d u r e for source localization, which has been extensively described elsewhere ( R o m a n i 1984, R o m a m a n d Leoni 1985; Rlcci et al. 1985a) consists of a s t a n d a r d 5 - p a r a m e t e r , least squares fit using the c u r r e n t - d i p o l e - i n - a - s p h e r e m o d e l (see, for instance, W d h a m s o n a n d K a u f m a n 1981). T h e localization in the 3 - d i m e n s i o n a l space is given b y 3 p a r a m e t e r s that are the c o o r d i n a t e s of the equivalent source, the 4th is the strength a n d the 5th is the direction O n l y the c o m p o n e n t of the current d i p o l e tangential to the sphere c o n t r i b u t e s to the e x t e r n a l field, thus e l i m i n a t i n g the sixth p a r a m e t e r ( W l l l i a m s o n a n d K a u f m a n 1981) The fit was perf o r m e d using a spherical m o d e l with h o m o g e n e o u s c o n d u c t i v i t y as a m e d i u m W e chose a ' l o c a l ' sphere, which fits the 3 actual profiles of the p a t i e n t ' s h e a d (saglttal, vertical through the vertex a n d the ear canals, a n d horizontal, 2 c m a b o v e the n a s i o n - l n i o n h o r i z o n t a l p l a n e ) a n d satisfactorily r e p r o d u c e s the d i s t r i b u t i o n of the e x p e r i m e n t a l p o s i t i o n s over the scalp. These profiles were derived from direct c r a m o m e t r l c m e a s u r e m e n t s a n d f r o m X - r a y and C T scan pictures N o a t t e m p t was m a d e d u r i n g the analysis of the d a t a r e p o r t e d in the p r e s e n t article to account for variations of the d i s t a n c e of each e x p e r i m e n t a l p o i n t from the center of the fitting sphere with respect to the value of the sphere radius (Barth et al. 1986) Similarly, n o c o n t r i b u t i o n of tangential fields to the m e a s u r e d m a p was considered. A s t a n d a r d X 2 test p r o v i d e d a level of significance which can be r e g a r d e d as a figure of merit for the a d e q u a c y of the model. A d d i t i o n a l l y the 95% c o n f i d e n c e interval on the values of the 5 p a r a m e t e r s is o b t a i n e d using traditional statistical a l g o r i t h m s (see, for instance, Darcey, thesis 1979). T o get an estimate of the noise to be used in these tests we r e p e a t e d several times the field m e a s u r e m e n t at a few scalp sites. T h e resulting R C values were a v e r a g e d a n d the s t a n d a r d d e v i a t i o n was calculated for each site

361

T h e average value of all these s t a n d a r d deviations was considered as the noise characterizing the R C distribution.

Results A d i p o l a r - l i k e d i s t r i b u t i o n was often observed, as in the e x a m p l e shown in Fig 2 The figure shows, in the f o r m of an lSO-field c o n t o u r m a p , the d i s t r i b u t i o n over the right t e m p o r a l scalp of the c o m p o n e n t of the m a g n e t i c field p e r p e n d i c u l a r to the scalp itself, as m e a s u r e d b y the m u l t i c h a n nel system d e s c r i b e d above. T h e crosses identify the l o c a t i o n s of r e c o r d i n g sites. The origin of the c o o r d i n a t e system is at the crossing between the n a s i o n - l n l o n h o r i z o n t a l p l a n e a n d the line connecting the ear canal to the vertex The d l p o l a r l t y of the d i s t r i b u t i o n in the u p p e r p a r t of the m a p is evident from o b t a i n i n g a positive a n d negative p a i r of m a x i m a

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Fig 2 Spatial dtstnbutlon of the magnetic field perpendicular to the scalp as measured over the temporal region of the scalp of subject MC, at the sites Identified by the crosses using the 4-channel system operating at the Istltuto dt Elettromca dello Stato Sohdo in Rome Shaded and unshaded areas represent regions of opposite field polarity The true value of the magnetic field is unknown since it is denved by the calculation of the RC (see text) Vertical and horizontal units are expressed in centlmetres, and the oragm of the coordinate system lies on the right hemisphere, at the crossing of the ear canal-vertex line with the naslon-mlon horizontal line Modified from Rlccl et al (1985a)

362

G B RICCI ET AL

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Fig 3 Simultaneous EEG (upper 4 traces) and MEG (lower 4 traces) as recorded from subject GC at a site approximately corresponding to the location of C3 m the standard 10/20 EEG system For detaals see text

In Fig. 3 the 4 upper traces are the most slgmficant EEGs, and the 4 lower ones are the simultaneous M E G s as recorded from the left temporal region (at a site approximately corresponding to the position C3 of patient G C The characteristic we beheve worth noting ts the ' b o r d e r ' between the proper epileptic activity (spikes) and the surrounding, generally slow, act]vlty. In part]cular, the first 2 M E G traces reveal only slow waves whereas the last 2 show spike-hke actlv]ty Note that this trans~tlon occurred between recording positions that were only 2 cm apart. The neuromagnetic locahzatlon (see F]g 4) showed the equivalent generator to be m close proxirmty (about 2 cm) to the pathological area revealed by the X-ray analysis Data on the neuro-

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Fig 4 Three-&menslonal locahzat~on of the equivalent generator fitting the magnetic field distribution measured over the left temporal lobe of subject GC Crosses represent the expenmental positions as projected onto the sphere best fitting the appropraate portions of the 3 actual profiles of the patient's head, obtained from X-ray pictures and &rect cramometnc measurements (Raccl et al 1985a) The CT scan is shown at the bottom left The boxes represent the 95% confidence interval on the localization

NEUROMAGNETISM

IN THE STUDY OF FOCAL EPILEPSY

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magnetic locahzation are reported in Table I, where they can be compared with the anatomical evidence. The case of patient FA is even more interesting. FA showed a focal activaty related to a non-tumoural calcified lesion m the left parietal lobe. The lesion had been identified by X-ray and CT scan analyses, which clearly showed a quite shallow location of the calcified area (Fig. 5, bottom left). Because of the shallowness of the firing area the on-line MEGs clearly showed dunng the same measurement a reversal of field polarity in a region approximately above the focus. Thas is illustrated in Fig. 6, the polarity reversal being observable between traces 2 and 3 (see arrows in the figure). Multlfocal activity, unsuspected on the basis of the typical clinical EEG analysis, was observed in 2 cases (see Table I). The bifocal neuromagnetic

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Fig 6 Simultaneous E E G (upper 4 traces) and M E G (lower 4 traces) as recorded from subject FA at the midpoint between T3 and T5 Note the polarity reversal of the pathological complexes identified by the arrows between traces 2, and 3 and 4

364

G B RICCI ET AL

TABLE I Summary of the symptomatologles, pathologies and locahzatlons obtaaned by means of X-ray and EEG studies on 13 subjects affected by partaal epalepsy, as compared with the results of the neuromagnetac mvestagataon Name

Sex

Age

Cllmcal htstory

MEG locahzauon

Seizures

X-ray CT scan

EEG "

Scalp sate ~'

Depth (cm) ~

L advers~ve R motor speech arrest L adversave

Normal Normal

R frontal L frontal alphold rhyt R temporal

F3-F7 C3-T3

31 33 42 22

L temporal

C4 P4 (2 foo) Fpl-F3 Fp2-F4 (2 focl) C3

31

L parietal

T3-T5

20

R frontotemporal R frontal

F4-C4

28

Fp2-F4

41

L temporal L frontal

T3 F3-T3

42 32

L postrolandlc

P3-O1

31

R temporal

T4-T6

43

R temporal

C4-T4

35

SL OD

M F

20 31

MA

F

19

VS

M

33

Psychomotor speech arrest

GC

F

56

Psychomotor

FA

F

15

MC

M

14

AS

M

25

Postural speech arrest R motor Psychomotor and postural R adversave

SD AC

F F

22 42

Psychomotor Generahzed

CF

M

51

CL

M

16

R jacksoman motor and psychomotor Psychomotor

EC

F

31

Psychomotor

R panet temporal atrophy L frontal parasag atrophy L temporal atrophy L parietal CalClflC R OCClp porenceph R front porenceph Normal L sylvlan menagloma L fr atrophy L parietal scar (bullet wound) R temporal scar R temporal (uncus memngloma)

L frontal

31 36

a The electrodes were placed according to the 10/20 system b The scalp site designation refers to the projectaon of the source on to the surface of the scalp usang the 10/20 system position Centnmetres from the scalp

l o c a h z a t l o n f o r p a t i e n t M A ~s s h o w n i n Fig. 7 T h e C T s c a n s h o w s a w~de c o r t i c a l a t r o p h y o f t h e right posterior temporal and parietal regions The bl-focality in this subject was suggested by the application of the RCM in two different bandwidths (one in the delta range and one in the theta one) and with respect to two different leads (C4 a n d P4, r e s p e c t i v e l y ) . There was general agreement on the cerebral lobe Indicated by X-ray, CT scan, EEG and MEt3 d a t a , at l e a s t t o t h e c o a r s e level o f l o c a l i z a t i o n

indicated by general cortical area Magnetic and X - r a y d a t a p o i n t e d t o t h e s a m e c e r e b r a l l o b e s an 9 o f t h e 10 c a s e s t h a t s h o w e d X - r a y a b n o r m a h t i e s The remaining 3 cases did not show X-ray abnormalities, but did show MEG data mdxcatmg m a g n e t i c loci. T h e M E G a n d E E G d a t a i n d i c a t e d t h e s a m e c e r e b r a l l o b e s i n 10 o f t h e 13 cases. H o w e v e r , ~t is i m p o r t a n t t o n o t e t h a t t h e M E G data yielded more specific localization, including the depth of the equivalent dipole source (Table I).

NEUROMAGNETISM IN THE STUDY OF FOCAL EPILEPSY

365

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Fag 7 Bifocal neuromagnetlc localization in the case of subject MA For details see text A wide cortical atrophy is shown by the CT scan image (bottom left) The equivalent generator under C4 was identified applying the RCM with respect to lead F4 m the frequency bandwidth 0 5-3 Hz The other source (P4) was identified using lead T4 as a reference and m the frequency bandwidth 4-7 Hz

O n e of the best examples of n e u r o m a g n e t i c localization of epileptic focl, in our opinion, is the case of EC. This p a t i e n t had been suffering for 8 years from complex partial seizures (psychomotor), i n t r o d u c e d b y a gustatory aura sometimes triggered by olfactory stimuli I n the last 2 years the seizures b e c a m e worse a n d worse ( m a n y per day, p o o r response to anti-epileptic drugs). The X-ray findings revealed a r o u n d i s h calcified lesion in the right u n c u s region (Fig. 8). This lesion was eventually identified d u r i n g surgery as a m e n i n g l o m a h a v i n g approxamately a spherical shape, a b o u t 2 c m diameter. Pre-operative E E G s showed delta

a n d theta activities a n d sporadic sharp waves over the right anterior temporal region. The M E G investigation provided a 3 - d i m e n s i o n a l localization of the equivalent source as shown in Fig. 8. This location was near the outer b o r d e r of the m e n i n gioma. The parameters o b t a i n e d d u r i n g surgery a n d the E C o G c o n f i r m e d the M E G source identification. Fig 9 (top a n d b o t t o m ) shows m an a p p r o x i m a t e l y equal scale and in a sagittal vtew the location of the equivalent generator o b t a i n e d from the M E G study a n d the position of the lesion as derived from the X-ray picture, respectively

366

G B RICCI ET AL

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Fig 8 Neuromagnetlc locahzatlon of the equivalent generator accounting for the magnetic field d i s t n b u h o n as measured from subject EC A clear-cut calclficat,on m the right uncus region xs shown by the CT (bottom left)

2

V

cm

Discussion

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As we have already pointed out (Romam 1984), a 4-channel magnetic sensor represents a first step toward a proper detection of cerebral magnetic fields, the final target being a multi-probe system with a large number of channels spread over a wide portion of the scalp. This will allow appropriate investigation of cerebral phenomena which, as in the case of epilepsy, often arise suddenly and sometxmes show a complex evolution, both in space and m time. Nevertheless, the present possxbility of explonng at the same txme with 4 sensors an area about 8 times larger than that investigated with a single one, ~s indeed a signifiFig 9 Comparison m a sagmal view of the location of the eqmvalent generator obtained from the M E G analysis (top) and the posltaon of the lesion as derived by the X-ray analysis (bottom)

NEUROMAGNETISM IN THE STUDY OF FOCAL EPILEPSY cant improvement, even though a correlation analysis across all magnetic channels is still not possible, the basic procedure for data analysis being essentially the same as that followed in singlechannel measurements. The reduction of the time needed to record a complete map to less than 2 h (instead of more than 5 h) is one of the most evident advantages It reduces the stress of the patient, providing at the same time a better homogeneity in his basic condition during the run. Although the surface covered by our instrument was in general too small to allow monitonng of a field reversal d u n n g a single measurement, this was sometimes observed. For example, in the case of GC (Fig. 3) It was possible to observe within one measurement the border between different morphological activities and in the case of FA even a polarity reversal (Fig. 6). Seeing polarity reversals between detectors spaced only 2 cm apart is favoured by shallow sources, since they produce closer spatml magnetic field maxima at the scalp than do deeper sources. However, very shallow sources are not often observable. More often single or even multiple loci are located in deeper cortical areas. Additionally, several sources could be independently active and could show different spatial and temporal evolutions. This lmphes the need for a recording area as large as possible. The possibilities offered by simultaneous signal detection at different sites of the scalp are of primary importance A current dipole is used as a model source. This choice might seem to oversimplify the problem, as more adequate model sources are certain to be studied and used in future studies Nevertheless, at least in a first approximation, the current dipole represents a sufficiently realistic means from a physiological point of view and yet mathematically tractable The relative covariance method (RCM) we have used for acl'neving localization perhaps requires additional critical discussion. We remark that the R C M purposely limits the view of the phenomenon under investigation, as xt takes into account only those electrical and magnetic signals which are correlated with each other, and does not follow the time evolution of the event This proce-

367 dure is particularly suitable for investigation of 'focal' rhythms In this case an F F T analysis identifies the abnormal components in the frequency spectrum of the recorded signals and the covarlance is calculated after filtenng within specific bandwldths More complex pathological morphologies, like spikes, have several components in the frequency domain and, consequently, more difficult will be the task of proper analysis. As we have demonstrated on several occasions (Chapman et al. 1983; R i c o et al. 1985a, b, c) the R C M provides results in the analysis of spike complexes which agree well with those obtained by an alternative method of signal processing, originally proposed by Barth et al (1982), consisting in averaging the intenctal M E G spike activity Nevertheless, this averaging method, although giving a satisfactory morphological resolution, works only when the EEG spikes, acting as triggers, are high enough in voltage and many in number. Moreover spike trlggenng does not work satisfactorily in cases of abnormal rhythmic activity, particularly for polymorphic delta activity where, on the contrary, the RCM proves to be a very powerful tool. Both methods can be used at present only for limited kinds of pathology The RCM is somewhat more powerful, in that it permits studying rhythmic activities, but this advantage is balanced by the loss of information on the temporal evolution of the activity. The investigation of infrequent and non-repetitive spikes or sharp waves, particularly if having a small amplitude, is still based on visual inspection of tracings by the neurologist We have mentioned that the bottom of our dewar tail is flat. This imphes that the orientation of the gradlometer axis is not rigorously perpendicular to the scalp, thus making the system partially sensitive to the tangential component of the field. Consequently a slight contribution from volume currents is present in the measured field. An estimation of this contribution is possible in the simplified case of a current dipole in a homogeneously conducting sphere (Cuffin and Cohen 1977). the contribution corresponding to a deviation of 6 ° from perpendicularity is negligible ( - 10%), at least at the present stage of approximation. In conclusion, we want to emphasize that, de-

368

G B RICCI ET AL

s p i t e the ~ m p r e s s l v e p r o g r e s s a c h x e v e d in t o m o grapluc imaging (CT scan, M R I , PET), only the s t u d y of the e l e c t r o m a g n e t i c signals can provide information on cerebral events lasting a fraction of a s e c o n d hke t h o s e relatwe to i n f o r m a t i o n p r o c e s s i n g as well as to s p e c i f i c p a t h o l o g i c a l b r a i n abnormahtles the

quahty

This should encourage improving of

our

measurements

and

p r o c e s s i n g m o r d e r t o get t h e m a x i m u m

data profit

from a combined magnetic and electrical app r o a c h m the i n v e s t i g a t i o n o f b r a i n p h y s i o l o g y and pathology

R6sum6 Etude de l'Jptlepste focale par des mesures neuromagn~ttques ~ multtcanaux U n e Investigation syst6matique de plusleurs cas d ' 6 p i l e p s l e f o c a l e a 6t6 e f f e c t u & e n e n v i r o n n e m e n t sans ~solement en utllisant une sonde neuromagn6tlque h 4 canaux. Les locahsatlons fournles par les m e s u r e s m a g n & i q u e s o n t 6t6 c o m p a r & s a u x d o n n 6 e s c l i n l q u e s e t c o n f l r m & s p a r l ' e x a m e n ra& o l o g i q u e et, d a n s u n cas, p a r la n e u r o c h i r u r g x e Les

r6sultats

dlustrent

l ' l n t 6 r & d e la d & e c t l o n

slmultan6e des c h a m p s m a g n & i q u e s aux d i f f & e n t s sites du scalp afin d ' a v o l r une vue d y n a m l q u e de l ' a c t i v i t 6 e p i l e p t ~ q u e et d e d & e c t e r u n e act~vit6 multffocale que l'lnvestlgatlon EEG ne lalssmt pas suspecter. The authors are indebted to P Carelh, R Leom, S Barbanera, V Foghett~ and L Na.ncl for helpful discussions and suggestions Thanks are due to S D'Angelo for his skilled techmcal assistance The authors want to express their gratitude to Prof A Paoletti for h~s continuous encouragement Special thanks are due to Prof A Fortuna for his kind collaboration in checking the neuromagnetlc localization during surgery, and to Prof R Chapman for his crttical revision of the manuscript

References Barth, D S, Sutherhng, W , Engel, J and Beatty, J, Neuromagnetic localization of eplleptlform spike activity in the human brain Science, 1982, 218 891-894 Barth, D S, Sutherhng, W , Engel, Jr, J and Beatty, J Neuromagnetic evidence of spatially distributed sources underly-

mg epdeptfform spikes m the human brain Science, 1984, 223 293-296 Barth, D S, Sutherling, W, Broffman, J and Beatty, J Magnetic locahzatmn of a dipolar current source implanted in a sphere and a human cranium Electroenceph chn Neurophyslol, 1986, 63 260-273 Chapman, R M , Romam, G L, Barbanera, S, Leom, R , Modena, I, Raccl, G B and Campitelh, F SQUID instrumentation and the relative covanance method for magnetic 3D localization of pathological cerebral sources Nuovo Camento, 1983, 38 549-554 Chapman, R M , Ilmomema, R, Barbanera, S and Romana, G L Selective locahzatlon of alpha brain activity with neuromagnetic measurements Electroenceph clan Neurophyslol, 1984, 58 569-572 Cuffin, B N and Cohen, D Magnetic fields of a dipole in special volume conductor shapes IEEE Trans biomed Engng, 1977, BME-24 372-381 Modena, I, Racci, G B, Barbanera, S, Leom, R , Romam, G L and Carelh, P Blomagnetlc measurements of spontaneous brain activity m epileptic patients Electroenceph clan Neurophyslol, 1982, 54 622-628 RlCCl, G B Chnlcal magnetoencephalography Nuovo Clmento, 1983,2D 517-537 Rlccl, G B, Romanl, G L, Modena, I, Barbanera, S, Leom, R and Carelh, P Magnetic recording (MEG) in epilepsy Electroenceph chn Neurophyslol, 1981, 52 $95 Ricca, G B, Leom, R, Romam, G L, Campitelh, F , Buonomo, S and Modena, I 3-D neuromagnetlc localization of sources of antenctal activity an cases of focal ep,lepsy In H Wemberg, G Strolnk and T Katfla (Eds), Blomagnetasm Applications and Theory Pergamon Press, New York, 1985a 304-310 R~cc~, G B, Buonomo, S, Peresson, M, Roman1, G L, Salustn, C and Modena, I Muhachannel neuromagnetac investigation of focal epilepsy Med blol Engng Comput, 1985b, 23 (Suppl Part 1) 42-43 Raccl, G B, Romanl, G L, Modena, I, Buonomo, S, Leom, R and Peresson, M Mult~channel neuromagnetlc measurements an focal epilepsy Electroenceph clan Neurophystol, 1985c, 61 $34 Romanl, G L Baomagnetlsm an application of SQUID sensor,, to me&tree and physiology Physaca, 1984, 126B 70-81 Roman~, G L and Leom, R Locahzat~on of cerebral sources by neuromagnet~c measurements In H Wemberg, G Stromk and T Katila (Eds), B~omagnehsm Applications and Theory_ Pergamon Press, New York, 1985, 304-310 Romani, G L, Wllllamson, S J and Kaufman, L Blomagnetac instrumentation Rev Sci Instrum, 1982, 53 1815-1845 Romani, G L, Leonl, R and Salustn, C Mult,channel Instrumentation for Baomagnetism In H D Hahlbohm and H Lubblg (Eds), SQUID 85 Walter de Gruyter, Berhn, 1985 919-932 Walhamson, S J and Kaufman, L Magnetic fields of the cerebral cortex In- SN Ern6, H D Hahlbohm and H Lubblg (Eds), Blomagnet~sm Walter de Gruyter, Berhn, 1981 353-402