1
Clinical Neu ophysiology 2010;121:848-858.
The a EEG sou ce localiza ion using LORETA in pa ial epilepsy pa ien s wi h and wi hou
medica ion
1
Clemens B., MD, PhD;
1
Bessenyei
M., MD;
2
Feke e I., MD, PhD;
2
Puskás S., MD;
3
Kondáko I., MD,
PhD;
4
Tó h M., MD;
5
Hollódy K., MD, PhD.
1
Kenézy Hospi al L d., Depa men o Neu ology, Deb ecen, Hunga y
2
Uni e si y o Deb ecen, Medical and Heal h Science Cen e , Depa men o Neu ology, Deb ecen,
Hunga y
3
Coun y Hospi al, Depa men o Neu ology, Kecskemé , Hunga y
4
Uni e si y o Pécs, Depa men o Neu ology, Pécs, Hunga y
5
Uni e si y o Pécs, Depa men o Pedia ics, Pécs, Hunga y
Co esponding au ho : D . Clemens Béla, Kenézy Kó ház K ., Neu ológia, Ba ók Béla ú 3., 4031,
Deb ecen, Hunga y.
TEL: ++36 52 511 777
Fax: ++36 51 511 729
E-mail: [email protected]
Key wo ds: epilepsy, EEG, LORETA, he a ac i i y
Suppo ed by g an om he Hunga ian Minis y o Heal h No. ETT 238/2006.
Abs ac
Objec i e. To in es iga e and localize he sou ces o spon aneous, scalp- eco ded he a ac i i y in
pa ien s wi h pa ial epilepsy (PE).
Me hods. 9 pa ien s wi h beginning, un ea ed PE (G oup1), 31 pa ien s wi h al eady ea ed PE
(G oup2), and 14 heal hy pe sons we e in es iga ed by means o spec al analysis and LORETA, low
esolu ion elec omagne ic omog aphy (1 Hz e y na ow band analysis, age-adjus ed, Z-sco ed
alues). The equency o main in e es was 4 o 8 Hz
Resul s. G oup analysis. G oup1 displayed bila e al he a maxima in he empo al he a a ea (TTA),
pa ie al he a a ea (PTA), and on al he a a ea (FTA). In G oup2, he a ac i i y inc eased all o e he
scalp as compa ed o he no ma i e mean (Z=0) and also o G oup1. Maximum ac i i y was ound in
he TTA, PTA, and FTA. Howe e , in he PTA and FTA he cen e s o he abno mali y shi ed owa ds
he medial co ex. Indi idual analysis: all he pa ien s showed p e e en ial ac i a ion (maximum Z-
alues) wi hin one o he h ee he a a eas.
2
Conclusion. EEG ac i i y in he he a band is inc eased in ana omically meaning ul pa e ns in PE
pa ien s, which di e s om he ana omical dis ibu ion o he a in heal hy pe sons.
Signi icance. The indings con ibu e o ou unde s anding o he sou ces o he a hy hms and he
pa hophysiology o PE.
In oduc ion
Elec oencephalog aphic he a ac i i y in humans is usually de ined as ac i i y in he 4-7 Hz equency
ange. The neu ophysiological signi icance o he a ac i i y has been highly enigma ic om he
beginning o he EEG e a. The main cause o unce ain y was i s in e media e posi ion be ween he
wo, bo de ing equency bands wi h appa en ly clea -cu signi icance: alpha, ha was conside ed as a
no mal waking EEG hy hm and del a, ha was equen ly associa ed wi h ce eb al pa hology. The old
Ge man synonym o he a ("Zwischenwelle") is pe haps he bes e lec ion o his ambigui y
(Neundö e , 1975). E en he in eg a ion o EEG and magne ic esonance imaging me hods did no
subs an ially imp o e he unde s anding and in e p e a ion o al e ed (mainly, inc eased) he a ac i i y
in pa hological s a es. The a powe o ac i i y was epo ed o be su p isingly independen o ce eb al
pa homo phology in quan i a i e s udies. Unlike del a and alpha ac i i ies, he a ac i i y is no
signi ican ly co ela ed wi h ad ancing age a e he i s wo decades (Babiloni e al, 2006a)
sugges ing ha i is no in luenced by li e ime cumula i e ce eb al pa hology. T2 elaxa ion ime, a
sensi i e indica o o b ain inju y, co ela es posi i ely wi h del a ampli ude, nega i ely wi h alpha and
be a ampli udes, bu is no signi ican ly co ela ed wi h he a ampli ude (Tha che e al, 1998).
Signi ican nega i e co ela ion exis s be ween he amoun o loba whi e ma e and del a bu no
he a ac i i y ac oss he con inuum o subjec s wi h mild cogni i e impai men and Alzheime s'
demen ia (Babiloni e al, 2006b). Howe e , egional he a powe co ela es posi i ely o he olume o
ce eb al edema a ound b ain lesions (Fe nandez-Bouzas e al, 1997) and nega i ely o hippocampal
olumes in Alzheime 's disease (G unwald e al, 2001).
Se e al pieces o e idence sugges ha inc eased he a ac i i y migh equi e a mo e
unc ional in e p e a ion. Pa hologically inc eased he a oscilla ions exis in halamo-co ical ne wo ks
in pa ien s wi h gene alized and pa ial epilepsy (Llinás e al, 1999, Clemens e al, 2000; Clemens,
2004). Midpa ie al hy hmic he a ac i i y is a gene ic ma ke o inc eased seizu e liabili y in myoclonic-
as a ic epilepsy o childhood (Doose and Baie , 1988). Valp oa e and lamo igine dec eased he a
oscilla ions in success ully ea ed gene alized epilepsy pa ien s as compa ed o he un ea ed s a e
(Clemens e al, 2007a, 2008). On he o he hand, expe imen al da a a gue o he seizu e-ga ing e ec
o inc eased he a ac i i y in animal epilepsy (Mille e al, 1994; Colom e al, 2006). The abo e da a
sugges ha unde s anding he neu onal mechanism o he a hy hms in epilepsy migh be o
heo e ical and p ac ical impo ance in epilepsy.
Conce ning pa ial epilepsy (PE), a ye no emphasized con adic ion exis s be ween he p io
quan i a i e EEG s udies and he gene al concep o PE. One would expec ha PE ha is caused by
a mo e o less localized epilep ogenic p ocess in one hemisphe e (ILAE 1989) p esen s wi h he a
inc ease localized o he a ec ed pa o he co ex. In ac , isual EEG analysis o en de ec s some
ocal he a ac i i y nea by he epilep ogenic p ocess. Su p isingly, quan i a i e EEG s udies ou lined a
di e en pic u e. Inc eased he a powe was ound all o e he scalp in bo h nonlesional and lesional
PEs (D ake e al, 1998; Miyauchi e al, 1991) and in idiopa hic benign PE o childhood as well (B aga
e al, 2000). The di use he a inc ease was independen o he localiza ion o he epilep ic ocus and
was no signi ican ly al e ed by an iepilep ic medica ion (Diaz e al., 1998). Thus, he o igin and
signi icance o he a inc ease in PE emains a he enigma ic. Fo he p esen s udy we eco ded
3
es ing EEG om he scalp and analyzed he co ical gene a o s. While we ha e epo ed he esul s in
pa ien s wi h gene alized epilepsy ea lie (Clemens e al, 2007b), we now in es iga e he sou ces o
he a ac i i y om pa ien s wi h PE wi h o wi hou medica ion.
Pa ien s, heal hy con ol pe sons and me hods
The design o he s udy was app o ed by he Resea ch E hics Commi ee o Kenézy Hospi al L d. The
pa ien s we e collec ed om h ee epilepsy ou pa ien se ices in Hunga y. G oup1 was ec ui ed om
newly diagnosed, un ea ed PE pa ien s. S anda d neu ological in es iga ion, EEG and MRI (epilepsy
p o ocol, a 1.5 Tesla magne ic ield s eng h) was pe o med in hese pa ien s as pa s o he ou ine
epilepsy e alua ion p o ocol. G oup2 was ec ui ed om ch onic, al eady ea ed PE pa ien s who
a ended he ou pa ien se ice o ollow-up isi s. These pa ien s had ul illed he same e alua ion
p o ocol p e iously. Exclusion c i e ia we e he same o bo h g oups: di use s uc u al
encephalopa hy o , p io neu ological disease o su ge y dis o ing he g oss ana omy o he b ain as
assessed by c anial MRI; any como bidi y, me abolic diso de o d ug use o abuse and ha is known
o signi ican ly al e EEG spec a; a his o y o complex pa ial o seconda ily gene alized seizu es in
he 5 days be o e in es iga ion. The pa ien s we e ins uc ed no o d ink co ee o o he s imulan
p oduc s in he mo ning be o e EEG in es iga ion. PE was diagnosed and classi ied acco ding o
gene ally accep ed c i e ia (ILAE 1989). The clinical da a (including he numbe and se e i y o he
seizu es) ha e been con inuously en e ed in o he medical eco ds o he pa ien s as pa o he
ou ine ollow-up. O e all, he pa ien s we e ea ed and ollowed as usual. Heal hy pe sons we e
ec ui ed a he Depa men o Neu ology, Uni e si y o Pécs, unde he app o al o ha Local E hics
Commi ee (To h e al, 2007).
EEG eco ding
EEG was eco ded o 30 minu es while subjec s we e elaxed-waking wi h hei eyes closed. Using
he BQ 3200 EEG Sys em manu ac u ed by Mic omed, T e iso, I aly (bandpass il e om 0.1 o 33.6
Hz, sampling a e 128 1/s, 12 bi A/D con e sion), we eco ded signals om he 19 elec odes o he
10-20 sys em and bo h ea lobes agains Fpz as a e e ence. Oculog aphic and myog aphic a i ac s
we e de ec ed wi h bipola de i a ions. Elec ode impedance was < 10 kOhm. Signals we e e-
e e enced o line o digi ally a e aged ea s. EEG eco ds ha did no i he gene al quali y c i e ia o
quan i a i e EEG analysis (Nuwe e al, 1994) we e excluded om u he analysis.
Quan i a i e EEG analyses
The same EEG samples unde wen spec al and LORETA analyses. Con en ional spec al analysis
was used o assess he scalp dis ibu ion o absolu e spec al powe ac oss he 1.0 o 12.0 Hz
equency ange. Low esolu ion elec omagne ic omog aphy (LORETA) was used as a magni ying
glass ha pe mi ed a de ailed analysis o ac i i y wi hin he he a equency band including he
localiza ion o he he a gene a o s o ana omical s uc u es. Age-adjus ed, Z-sco ed da a we e used in
spec al analysis and LORETA alike. The di icul ies inhe en o he age-dependency o he EEG
a iables we e ci cum en ed in his way. Z- ans o ma ion pe mi ed he es ima ion o he s a is ical
deg ee o he abno mali y. Age-adjus ed, Z-sco ed EEG a iables a e independen o age, sex and
ace. The alida ed da abases o spec al powe and LORETA ensu ed ha he indings a e eliable
e en in he absence o a igo ously ma ched con ol popula ion (John e al, 1983, Tha che e al,
4
2003). The o e all eliabili y o he quan i a i e EEG da abases was u he con i med in a compa a i e
s udy showing ha he Tha che da abase eplica ed he esul s o he John da abase (T udeau e al,
1999).
Epoch selec ion and EEG spec al analysis
30 x 2-sec epochs o spon aneous, waking ac i i y cha ac e ized by con inuous alpha hy hm wi h
pos e io ol age maximum we e selec ed. Epochs con aining epilep i o m ansien s, a i ac s and
EEG pa e ns indica ing shi s o he le el o igilance we e excluded. Epoch selec ion was ca ied ou
blindly wi hou knowing he pa ien s' da a and was con olled by he senio au ho . Reliabili y measu es
o he sample (spli -hal eliabili y and es - e es eliabili y) we e checked and samples wi h < 95 pe
cen o hese measu es we e excluded om u he analysis. Fas Fou ie T ans o m o he selec ed
samples and spec al analysis was ca ied ou by means o he Neu oGuide so wa e o Tha che
(h p://www.appliedneu oscience.com). F equency esolu ion was 0.5 Hz. C oss-spec al absolu e
powe o he 19 de i a ions was compu ed o each equency poin . The aw da a we e a e aged
ac oss he selec ed epochs, adjus ed o age, and Z- ans o med (Tha che e al, 2003). In ou s udy
he a e aged esul s o wo, neighbou ing equency poin s we e comp essed in o a e y na ow band
(VNB, 1 Hz esolu ion). Fo example, Z-sco ed powe a 7 Hz was he a e age o he 6.5 and 7.0 Hz
alues. Spec al analysis was ocused on he he a band (de ined he e as 4.5-7.5 Hz) bu also he
neighbou ing bands: del a (1.0-4.0 Hz) and alpha (8.0-12.0 Hz) we e conside ed. The spec al esul s
we e displayed as absolu e and Z-sco ed powe spec a o indi idual analysis and we e comp essed
in o ou pu iles (. d ) o Neu oGuide. Impo ing he la e iles in o Mic oso Excel and he P ism3
s a is ical package (h p://www.g aphpad.com) allowed u he s a is ical elabo a ion o he esul s
including g oup analysis. Gi en ha no all da ase s passed he Kolmogo o -Smi no no mali y es ,
Wilcoxon signed ank one-sample es was used o e alua e he de ia ion o he spec al da a om he
heo e ical median (Z=0) o he heal hy popula ion.
LORETA analysis
LORETA is a ecen ly de eloped me hod o localize mul iple dis ibu ed co ical sou ces o EEG
ac i i y in he h ee-dimensional space (Pascual-Ma qui e al, 1994; Pascual-Ma qui e al, 2002).
LORETA compu es squa e oo ans o m o he squa ed sou ce cu en ec o s (A / m
2
) o each
oxel. Fo he sake o b e i y, his is called "ac i i y" in his pape . Each indi idual LORETA analysis
was pe o med a he equency o he maximum posi i e Z-sco ed he a alue wi hin he 4.5-8.0 Hz
equency ange as es ablished in he indi idual EEG spec um (Fig-1). Raw LORETA alues
unde wen age-adjus men and Z- ans o ma ion as desc ibed in he LORETA No ma i e EEG
Da abase (Tha che e al, 2005). The use o s a is ical mapping was epo ed o be supe io o he aw
LORETA esul s in de ec ing EEG abno mali ies (Zums eg e al, 2005). The ou pu o LORETA
analysis was a omog aphically a anged se ies o pic u es displaying he colo -coded Z-sco ed ac i i y
in he selec ed 1 Hz VNB o each oxel. The maximum posi i e Z-sco e o he le and igh
hemisphe e we e ound by means o he LORETA Viewe . The indi idual esul s (maximum Z- alues)
we e abula ed acco ding o la e ali y and localiza ion, speci ying he name o he gy us and he
B odmann a ea (BA). Desc ip i e LORETA g oup analysis was ca ied ou by a e aging o he
indi idual LORETA analysis (.lia) iles o LORETA g oup analysis (.lga) ile o ma . A e aged LORETA
pic u es we e analyzed in he same way han he indi idual LORETA pic u es. In o de o es ima e he
opog aphic dis ibu ion o he a ac i i y in heal hy pe sons, he 6.5 o 8 Hz a e aged absolu e ( aw)
5
LORETA esul s o 14 heal hy pe sons we e gi en. These da a came om a p io s udy whe e hey
had no been explici ly published (To h e al, 2007).
Resul s
Se ial numbe o he pa ien s, demog aphics, MRI indings and ea men we e summa ized in Table-1.
G oup1 pa ien s wi h newly diagnosed, un ea ed epilepsy (N= 9, age limi s: 13-43 yea s, a e age
age: 22.6) di e ed om G oup2 pa ien s (N= 31, age limi s: 13-56 yea s, a e age age: 27.0 yea s).
The membe s o he la e g oup had di icul - o- ea epilepsy albei he e was conside able dispe sion
ega ding he du a ion o he disease (in e al: 2-17 yea s, a e age: 12.3 yea s) and he equency o
he seizu es (1 o 30) in he las 6 mon hs. Two pa ien s (No 27. and 28.) had e y equen bu mild
senso y o ocal mo o seizu es. Fou pa ien s did no egula ly en e he numbe o seizu es in o he
dia y. In his g oup 24 pa ien s we e ea ed wi h ca bamazepine mono he apy, 7 pa ien s wi h o he
d ugs o bi he apy. None o he pa ien s p esen ed wi h complain s o neu ological signs indica i e o
d ug- ela ed neu o oxici y. The a e age age o he heal hy pe sons was 23,6 yea s.
Spec al indings
Spli -hal eliabili y and es - e es eliabili y we e g ea e han 95 pe cen in e e y EEG sample. The
he a peak was sepa able om he del a and alpha peak alues in he indi idual spec a. The he a
spec um showed simul aneous inc ease, peak, and dec ease o powe in mos o all de i a ions in he
majo i y o he pa ien s, sugges ing a opog aphically di use p ocess ( Fig-1.)
VNB spec al da a o he wo g oups a e summa ized in Table-2. All he G oup1 pa ien s
showed Z-sco ed powe wi hin he ± 1 Z ange. Rema kably, he scalp-a e ages in he he a ange
and a he bo de equencies we e sca e ed a ound ze o
On he con a y, all Z-sco ed he a alues in G oup2 we e posi i e, and he medians di e ed
conside ably om Z=0. The e was a s epwise inc ease o he Z-sco es om 1 Hz o 7 Hz as
demons a ed by he scalp-a e ages and he inc easing numbe o he Z>1 alues in he indi idual
de i a ions in Table-2. All bu one alues e u ned below he Z=1 le el a 9 Hz and he u he
equencies in he alpha ange. Compa ison o he wo g oups showed ha spec al powe in he 3 o 9
Hz ange was highe in G oup2 han in G oup1.
LORETA g oup analyses
Heal hy pe sons. G oup analysis showed he dis ibu ion o aw (absolu e) LORETA ac i i y in he 6.5
o 8 Hz na ow band. (Fig-2). Maximum alues we e ound bila e ally in medial pa s o he co ex:
p ecuneus (BA 7) and pos e io cingula e (BA 31) in he pa ie al lobes, an e io cingula e (BA 32) and
medial on al gy us (BA 11) in he on al lobes. In e media e alues we e ound in he empo al lobes
and a he empo o-pa ie al junc ion. The emaining pa s o he co ex showed lesse amoun o
ac i i y, wi h minimum alues a he on al con exi y. Indi idual LORETA analysis disclosed indi idual
a iabili y in he localiza ion o he maximum abno mali y. Six pa ien s showed pa ie al maxima, i e
pa ien s on al maxima, and 3 pa ien s on al and pa ie al maxima. Rema kably, no maximum he a
alues we e ound ou side he speci ied, medially loca ed a eas.

6
Unmedica ed pa ien s (G oup1). Con iguous a eas consis ing oxels o inc eased (Z>0) o dec eased
(Z<0) ac i i y in he 4-9 Hz ange we e ound in bo h hemisphe es. A eas o inc eased he a ac i i y
we e oughly symme ical and we e sepa a ed by a eas o lesse ac i i y. The o me a eas we e
labelled as he on al he a a ea (FTA), empo al he a a ea (TTA), and pa ie al he a a ea (PTA) as
depic ed in Fig-3. Ana omical localiza ion and he deg ee o he maximum abno mali y (g ea es Z-
sco e) om 4 o 8 Hz wi hin hese a eas we e gi en nume ically in Table-3. Ac i i y in he le and igh
PTA ose om 4 o 7 Hz and dec eased wi h u he inc ease o equency. Maximum ac i i y ac oss
his equency ange was consis en ly ound in he supe io pa ie al lobule. The deg ee o abno mali y
g adually dec eased owa ds he p ecuneus, pos cen al gy us, and in e io pa ie al lobule. The PTA
showed some asymme y in ha he lowe pa o he in e io pa ie al lobule and he empo o-pa ie al
junc ion showed mode a ely highe Z-sco es on he le han on he igh side. Ac i i y in he le and
igh FTA inc eased om 4 o 8 Hz and dec eased wi h u he inc ease o equency. Maximum
ac i i y was con ined o he supe io and medial on al gy i (BA 8) and a limi ed pa o he cingula e
gy us below he medial on al gy us. Maximum abno mali y in he TTA was loca ed in he usi o m gy i
bila e ally and dec eased owa ds he pa ahippocampal and in e io empo al gy i. Howe e , he le
and igh maxima eme ged a di e en equencies.
Pa ien s unde medica ion (G oup2). The amoun o he a ac i i y showed an o e all inc ease ac oss
he en i e co ex wi h espec o he s a is ical baseline (Z= 0) and also when compa ed o G oup1. No
oxel showed nega i e alues a 7 Hz (Fig-4). The TTA, PTA, and FTA we e iden i iable also in
G oup2 as gi en in de ails in Table-3. The deg ee o abno mali y inc eased as a unc ion o equency
om 4 o 7 Hz in he PTA and TTA and ended o dec ease a 8 Hz. The deg ee o he maximum he a
abno mali ies a 7 Hz was abou wo o ou imes g ea e in G oup2 han in G oup1. In addi ion, in he
PTA and FTA he cen e o he abno mali y shi ed owa d he midline co ex (p ecuneus and cingula e
gy us) as compa ed o he loci o he maximum abno mali ies in G oup1.
LORETA indi idual analysis
LORETA indi idual analysis was ca ied ou in all he pa ien s. Table-4. shows he e ogenei y
conce ning he localiza ion and he equency o he maximum abno mali y. The mos in e es ing
inding was ha one o he h ee he a a eas was p e e en ially ac i a ed ( ha is, showed g ea e Z-
alues han he emaining he a a eas) in all bu h ee pa ien s. Pa ien s showing p e e en ial ac i a ion
o he TTA, PTA, and FTA we e ound in bo h G oup1 and G oup2. Rega ding equency, maximum
he a alues we e ound a 6 o 7 Hz in mos pa ien s. Howe e , hese pa ien s displayed lesse alues
o ac i i y in he same ana omical dis ibu ion a 5 Hz and e en a 4 Hz o , a ely, 3 Hz. A he o he
end o he he a ange, he pa e n o ac i i y a 6-7 Hz equen ly ex ended in o he VNB a 8 Hz bu
no a 9 Hz.
E ec o he lesion on he a ac i i y
In o de o in es iga e he po en ial e ec o he MRI-de ined lesion on he a ac i i y he nonlesional
g oup (n= 20) , he le hemisphe e lesion g oup (n= 10) and he igh hemisphe e lesion g oup (n= 8)
we e compa ed. Pa ien s No. 39. and 40. wi h mul iple ce eb al lesions escaped his analysis.
A e aged maximal indi idual Z-sco es in he nonlesional g oup we e 2.04 in he le hemisphe e and
1.87 in he igh one. The g oup wi h le hemisphe e lesions showed 1.35 and 1.39 sco es ipsi- and
7
con ala e ally, espec i ely. The g oup wi h igh hemisphe e lesions showed 1.82 and 2.13 sco es
ipsi- and con ala e ally, espec i ely. No s a is ically signi ican di e ences eme ged be ween he
h ee g oups (p=0.38) sugges ing ha he p esence and la e ali y o he lesion did no signi ican ly
in luence he eme gence and deg ee o he he a abno mali y.
The pa ien s wi h p e e en ial ac i a ion o he TTA had no mal MRI (n=9), o a single lesion in
he empo o-pa ie o-occipi al a ea (n=5), o mul i ocal abno mali ies (n=2). No single on al lesion was
ound in his g oup. The PTA pa ien s had no mal MRI (n=7) o a single lesion in he empo o-pa ie al
a ea (n=2). The FTA pa ien s had no mal MRI (n=4), o a single lesion in he on al lobes (n=4),
empo al lobes (n=2), o mul i ocal lesions (n=1). These indings aise he possibili y ha p e e en ial
ac i a ion eme ges in he he a cen e nea by o he epilep ogenic p ocess. Howe e , he numbe o
he lesional cases is oo small o pe o m s a is ical analysis o p o e o e u e his possibili y.
Discussion
The ad an age and he esul s o VNB spec al analysis
The au ho s who in es iga ed b oad-band powe in PE (D ake e al, 1998; Miyauchi e al, 1991; B aga
e al, 2000; Diaz e al., 1998) did no add ess he p oblem ha he he a band comp ises an unce ain
numbe o hy hmic oscilla ions. As a co olla y hei esul s e lec compound ac i i y implying
signi ican blu ing ega ding he exac equencies o he la ge scale he a oscilla ions. Na ow band
analysis was ecommended o imp o e he esolu ion o equency analysis (Sza a e al, 1994). In
ac , in his s udy VNB analysis esul ed in no el indings. We ound ha ac i i y ( ha is, he in ensi y o
synch onous oscilla ions) inc eased as a unc ion o equency om 4 o 7 o 8 Hz and apidly ell a 8
o 9 Hz. Howe e , his phenomenon e lec ed a g oup e ec composed o a leas wo cons i uen s.
Fi s , he equency-dependence o ac i i y was obse ed in mos indi idual spec a and LORETA
analyses sugges ing ha , de ining sha p bo de s be ween neighbou ing equency bands poo ly
e lec s physiological eali y. Second, he indi idual dispe sion o he VNBs wi h maximum ac i i y
indica es biological a iabili y conce ning he wo king equency o ha he a ne wo k. The indi idual
peak equencies should be emphasized in planning a ge ed s udies and in he e alua ion o
indi idual pe sons (Klimesch, 1999).
Unmedica ed pa ien s (G oup1)
This was he i s quan i a i e EEG s udy ca ied ou in a g oup o PE pa ien s wi h beginning,
un ea ed epilepsy. Albei his g oup was small, analysis o he spec al esul s disclosed ha he
o e all inc ease o he a ac i i y is no cha ac e is ic o beginning, un ea ed PE. Howe e , his inding
was g ea ly e ined by sou ce analysis. LORETA demons a ed ha some pa s o he co ex showed
inc eased while o he s showed dec eased ac i i y (as de ined in he Resul s sec ion). In his s udy we
ocussed on a eas o inc eased ac i i y because hey e lec inc eased neu onal synch oniza ion, he
basis o epilep ic mal unc ioning. Disc e e maxima o inc eased he a ac i i y we e ound in h ee,
ana omically sepa a ed co ical a eas in bo h hemisphe es. The alling g adien s o ac i i y om hese
a eas in any di ec ion sugges ha he TTA, PTA, and FTA a e " he a cen e s" playing an impo an
ole in gene a ing spon aneous co ical he a ac i i y. In ana omical e ms, he usi o m gy us, supe io
pa ie al lobule, and he supe io and medial on al gy i we e he si es o he main he a gene a o s.
These cen e s o ac i i y clea ly di e ed om he he a cen e s ound in he 14 heal hy pe sons. Ou
indings: he medial on al and pa ie al he a maxima in heal hy pe sons con i med p io esul s as
8
ollows. A single-dipol magne oencephalog aphic analysis localized he main he a sou ce in he
pos e io co ex nea he mid-saggi al plane (Puligheddu e al, 2005). A op iew LORETA igu e
published in ano he pape demons a ed he p esence o he a ac i i y all o e he co ex wi h pa ie al
midline maxima in heal hy young and heal hy old pe sons. Un o una ely, de ailed quan i a i e esul s
and he medial iew o he hemisphe es we e no p esen ed in ha pape (Babiloni e al, 2006a). We
concluded ha he PTA and FTA a e ana omically no iden ical o he cen e s o he a ac i i y in
heal hy pe sons. The a maxima ou side he no mal he a cen e s (in pa icula , hose loca ed a he
co ical con exi y) seem o be clea ly abno mal indings. The same holds ue o he TTA because
heal hy pe sons ne e showed he a maxima in he empo al lobe. The unc ional signi icance o hese
indings is no sel -e iden and going in o de ails is beyond he scope o his s udy. Thus we only
b ie ly men ion ha he h ee he a a eas co espond o unimodal and he e omodal associa ion
co ices (Mesulam, 1985; Zilles, 2004). All bu wo pa ien s in G oup 1 showed bila e al, a he
symme ical he a inc ease, independen o he p esence and la e aliza ion o he epilep ogenic lesion.
This ac indica es a unc ional o igin o he a inc ease a he han a lesional in e p e a ion o i . Ou
indings weakly sugges ha he localiza ion o he epilep ogenic p ocess migh in luence p e e en ial
ac i a ion, a ou ing ac i a ion o he ana omically nea by he a sys em. In pa icula , on al lobe
lesions we e associa ed wi h ac i a ion o he FTA bu no he TTA and PTA. A ecen s udy seems o
suppo his suspicion. Mo e o less hy hmic in e ic al he a ac i i y in he on al de i a ions was
equen ly ound in pa ien s wi h on al epilepsy bu a ely in empo al lobe epilepsy pa ien s (Beleza
e al, 2009). In any case, he ela ionship be ween he epilep ogenic p ocess and he ac i a ed he a
ne wo k migh con ibu e o unde s and he unc ional meaning o he a inc ease in PE.
Pa ien s unde medica ion (G oup2)
Ou spec al esul s con i med he p esence o di use he a inc ease in pa ien s wi h ch onic, ea ed
PE as desc ibed in p io s udies (D ake e al, 1998; Miyauchi e al, 1991; B aga e al, 2000a; Diaz e
al., 1998). Again, he VNB spec al indings we e g ea ly e ined by LORETA analysis. G ea es ac i i y
was ound a 7 Hz in he TTA ( usi o m and pa ahippocampal gy i), PTA (p ecuneus and supe io
pa ie al lobule), and he FTA (an e io cingula e). The eason o his he a inc ease is no clea
because se e al causes migh exis and in e e e wi h one ano he . Fi s , one componen o i is he
"baseline" he a abno mali y discussed in he p e ious pa ag aphs. Howe e , he a maxima in he TTA
and PTA in G oup2 we e somewha shi ed owa ds he midline co ex as compa ed o he he a
maxima o G oup1, u he indica ing he complexi y o he causes.
The di e ence be ween he unmedica ed and medica ed pa ien s is demons able wi h he
di e ence be ween he ex ension and deg ee o he abno mali y in Fig-2. e sus Fig-3. This e ec is
due o medica ion, pa icula ly ca bamazepine. This d ug is known o inc ease he a powe (Clemens
e al, 2006), as con i med in his s udy. Bo h spec al indings and LORETA showed ha d ug- ela ed
inc ease was p esen ac oss he en i e he a ange in all oxels. Howe e , maximum di e ence
be ween he wo g oups was de ec ed a 7 Hz in he pos e io and medial pa s o he co ex as
opposed o lesse he a inc ease in he on al and an e io empo al co ex. The ana omically une en
dis ibu ion o he co ical e ec o ca bamazepine is a new inding ha seems o be wo hy o
in es iga e in p ospec i e s udies.
In heo y, he ole o mild bu dis ibu ed p og essi e co ical damage cumula ing in he cou se
o he illness canno be excluded. All he G oup2 pa ien s had di icul - o- ea epilepsy gi ing ise o
his possibili y. Howe e , he epo ed mo phological al e a ions: he ana omical pa e ns o educed
neoco ical hickness (Lin e al, 2007) and neoco ical olume loss in T1 weigh ed MRI images (Liu e
al, 2003) did no esemble he ana omical dis ibu ion o he TTA, PTA, and FTA. An in e media e
9
possibili y be ween he di ec lesional and he ne wo k- ela ed he a inc ease is ha slowly e ol ing
neu onal loss in c i ical s uc u es like he halamus and hippocampus migh a ec ne wo k
synch oniza ion. In ac , p og essi e neoco ical and hippocampal a ophy we e desc ibed in PE
pa ien s (Ma he n e al, 2002; Cendes, 2005) bu hippocampal quan i a i e MRI da a and he he a
measu es ha e ne e been co ela ed in PE. This was done in Alzheime 's disease whe e nega i e
linea co ela ion was ound be ween hippocampal body olume and he a powe o e he on al
egions (G unwald e al, 2001).
Localizing accu acy
The ela i ely small numbe o elec odes is a equen ly c i icized poin in LORETA s udies. In ac ,
localizing accu acy conside ably inc eases om 19 o abou 64 elec odes. Howe e , inaccu acy
dec eases when he elec odes a e e enly dis ibu ed o e he scalp (Michel e al, 2004), as in his
s udy. Fu he mo e, he LORETA li e a u e sugges s ha 19 o 23 scalp elec odes pe mi co ec sub-
loba localiza ion o e i ied sou ces o ac i i y. Using his numbe o elec odes LORETA solu ions
we e some imes blu ed o unin e p e able bu ne e clea ly inco ec (Zums eg e al, 2005, 2006).
Fu he mo e, he accu acy o he me hod should be discussed in e ms o he spa ial scale o he ask
and he signal- o-noise a io as well. We in es iga ed he a, a pe asi e and obus hy hm
(Puligheddu e al, 2005) ha was inc eased in la ge co ical a eas. The he a cen e s we e desc ibed
in e ms o ela i ely la ge ana omical uni s (gy us, BA) ha ole a e some mislocaliza ion wi hou
signi ican blu ing o he indings
Conclusions
In e ic ally eco ded EEG he a hy hms ha e p ac ical signi icance in ela ion o clinically e y
impo an issues: seizu e p opensi y, seizu e con ol, and d ug- ela ed neu o oxici y. In his pape we
e i ied ha LORETA may be a use ul in es iga ion ool o add ess he abo e men ioned p oblems.
The impo ance o his ac is suppo ed by he inabili y o o he neu oimaging me hods (magne ic
esonance imaging me hods, posi on emission omog aphy) o add ess hese p oblems. Ou indings
comple ed he exis ing knowledge ega ding he a oscilla ions wi h ana omical aspec s. The
in es iga ion o newly diagnosed, un ea ed PE pa ien s esul ed in indings ha a e no con ounded
by an iepilep ic d ug e ec s and o he ac o s ela ed o long-las ing epilepsy. Ou indings migh be
u ilized in planning o hcoming, a ge ed s udies add essing he ela ionship be ween clinical a iables
and co esponding he a oscilla ions in selec ed pa s o he co ical man le.
Re e ences
Babiloni C, Bine i G, Cassa ino A, Dal Fo no G, Del Pe cio C, Fe e i F, Fe i R, F isoni G, Galde isi
S, Hi a a K, Lanuzza B, Miniussi C, Mucci A, Nobili F, Rod iguez G, Luca Romani G, Rossini PM.
Sou ces o co ical hy hms in adul s du ing physiological aging: A mul icen ic EEG s udy. Hum B ain
Mapp 2006a; 27:162-172.
Babiloni C, F isoni G, S e iade M, B esciani L, Bine i G, Del Pe cio C, Ge oldi C, Miniussi C, Nobili F,
Rod iguez G, Zappasodi F, Ca agna T, Rossini PM. F on al whi e ma e olume and del a EEG