CA2115650A1 - Determining brain activity including the nature of brain lesions by electroencephalography - Google Patents

Abstract

2115650 9303670 PCTABScor01 Determining brain lesions by quantified electroencephalography is effected by obtaining absolute power data in a primary frequency domain for a brain region. Power data in the primary frequency domain in relation to power in a secondary frequency domain is determined. The two sets of data are related to obtain a value representative of the electrical ouput in the brain region. The representative value is compared to as selected base value and quantified departures are mapped topographically. This map is used to identify and assess lesions associated with disorders and afflictions including dementia and demyelinating diseases. Mapping is used to determine activation during tasks such as motor and memory task, cognitive processing or other conditions, and also to assess the level of perfusion of the brain. The apparatus includes electrodes (11, 12, 13, 14, and 15) attached to the head of a patient.

Description

W093J~3670 P~T/US92/067X9 l'",'''''~

2 1 1 S ~
DETERMINING BRAIN ACTIVITY INCLUDING
THE NATURE OF BRAIN LESIONS
: BY ELECTROENCEPHALOGRAPHY ,: :

Portions~of the work leading to this ,. -,.-, application were developed:under a grant of the National ,, ',''~
Institute of Mental Health (NIMH~ under Grant No. ~ , MH 40705. The ~IMH may have rights in this application. .,' ~; 5 : ~ : :
:~ BAC~GROUND~

: Diagnoslng disorders and affli'ctions in the ,:
human~brain~with non-inva~sive procedures~is important ',::
10~ medlcally~:~and scienti,fically. Determining~activation '.
during tasks, cogn~itive processing, or in other : condit~lons as evidenced by brain activlty and through : .,.', non-lnva~sive~procedures lS also most valuable.~
Assessing~ non-lnvasi~vel;yl~when the brain ~is~,experiencing 5~ ,normal~à~ctivi:ty provides additional valuab:le data. ;,, ; This invention~relates to:determining the na~ure~of brain leslons using quantitative electro~
phys~iol~oqy.~:In particulàr, the invention~relates to ~20 ~analyzing~e;1S,ectroenc;ephalographic information~ a manner 4.'!'1 ' ' ~, t~o~pe~rmit~assessment~:of the nature of ~rain lesions.~ The nvention;~ls~further~dlrected to give a characterization :'~,',', of~::aff~lictions such~as~ dementia, being~selective for ~ : ~ .'"
mult;i-infar:ct dementia ~r:Alzheimer's;:d'isease,~ Pick:'s ;~ :
5~ ;disease~and demyelinating`diseases such~a:s~ multiple s c l er o s i s The invention is also directed;to determining : ^,~
activation tasks~by using~quantitatlve~eIectrophysiology, ,~
30~ particularly the actlvation of specific brain~regions rendered in mental:processing such as motor and memory .;
activity, cognitive processing or other conditions. ::~

; Brain-imaging used by physicians in clinical : 35 ~practice incIudes structural imaging and functional :

W O 93/03670 PCT/US92/06789 : `.. :
2 ~ :L 5 ~ 5 ` ` : `
2 ~
imaging. Structural imaging i5 effected by computed ~-axial tomography (CAT) scanning or magnetic resonance -imaging (MRI) scanning. Functional imaging is effected by positron emission tomography (PET), single photon emission computed tomography (SPECT) or electroencephalo-graphy (EEG)~ t ~ ~;

Structural imaging is performed for determining the location of a brain tumor or other kind~ of gross structural alteration of the brain. Functional imaging ests are performed~to determine functional alteration in the~brain where there may not be significant structural alteration. ~These broad categories of tests are comple-mentary. A physician evaluating a neurological or 15 psychlatric illness~could perform a test from both cate- :
;gorles to~assess and/or~diagnose a patient's~condition.
The-present invention particularly concerns~functional imag_ng.~

2~0~ PET scanning measures brain metabolism and can ~i identify areas that are hypoactive. SPECT scanniny !-measures~oerebral blood flow, which is an~indirect ~ ~
measure of metabolism~a~nd therefore-~rain function.` Both '"--of~these technologles~yield useful physlologlcal informa~
25~ tion.~ For~eXamp1e,~Alzheimer's disease presents with hypometabolism or~bypoperfusion of the parietal lobes bilaterally and multi-infarct dementi~a presents with~ ~
multiple foci of hypometabolism and hypoperfusion. ~PET ; -`
and SPECT scanning are expensive, reguiring investments ~,;
of miliions of dollars initially. A1so required are many hours of technician time per test and the produ~tion~and injection of radionuclides into a patient. .

EEG brain mapping is relatively~less expensive and can be performed without the need for radionuclides.
Technician time for performing the scan also is less ~-~
costly. A disadvantage of EEG mapping, however,~is that .:
- ~ .~.. ..

:, -W093/03670 PCT/US92/06789 ~ '~
2~65~3 it has not been possible to analyze the informa-tion '.'.
obtained by the electroencephalogram to diagnose and assess effectively different condltions of the brain, and `
thus diseases and:disorders of the brain. : ?

nformation;which:is obtainable ~rom~an EEG , includes conventiona~l EEG data representative of ,;', electrical~activity~in~different brain regions, When ..
this~data is digitlzed and~processed as in quantitative ,-, EEG;(:'iqEEG"), :it~:is~possible to obtain topographical : '.`.~.. ,.' bra~in~mapp~ing; of electrical activity in diff~erent brain .,.,.', regi`ons.~From a~qEEG;~-un:it, it is also posslble to obtai~n :.:
meas:urements~of absolute:~power and relative power, and , - ~ . .
evoked potentlals. Quantltatlve EEG techniques represent ..
15~ an advance over traditional EEG methods because they ' '~
;permit~the~detectionj~o~ trends which are dif~ficult or mposslbl:e~;to:~discern~by~d~irect visual inspection of the EEG~voltage:tracings.~ Previous efforts to generate : : :,,~' images~d~epictlng:quantitative EEG data h~ve:~had limited.
20~ cllnica~l;àpplicab:ili'ty because they ha~e~ not~been:shown Gon~v}nclngly to~ be~a~ssociated with speciflc;cllnical syndrome,s:or diagnoses~ for example, the presence of a 'qEE~ brain~map ~f~re~i;ons:with large~amounts~of power~in e~de;lta~:band~may;:~reflect~an~electrophysl~logic encepha~
`2js~ lo`pathy~from~many~dis'eases, without distlnguishing. : ~ ~ ~", ;betw~een them~

A~short~all~of~all these EEG ~nd gEEG data and information which are analyzed independently is the ~ :
i: 30 ~: lnability to provide information regar~ing brain physlo-logy that is.substantially equivalent~to~information from PET~or SPECT scans.

: 'SUMM~RY

By the present'invention, there is:provided a method and means of minimizing the~disadvantagès of EEGs W093t03670 PCT/US92/06789 ".~: ' 2 ~
and providing for enh.anced techniques of quantitative EEG . ,'-, , analysis.: The invention provides for information about !j,,,,' ~': : brain electrical:function that can be associated with specific diseases and syndromes and thus can assist in : ~.. ' 5 es:tablishing different dia~gnoses. ...

According to~the invention, the determination '~
of the~electrical output~of-~a brain:region comprises ...
obtaining::first data~representative of energy in the :' lO~ :,brain.region~in a primary~frequency domain. Second data ,.
repr~esentative of~energy:in the primary frequency domain , ~ .''.. ' :relative~to~the;ener~gy ~i~n a~secondary frequency domaln ~ . ~ ' ,.
are~determlned. ~

15~: The first~data and the secondidata are then related~ thereby~obtain:ing a~representative~.:value of the ~ ;~' electr~ical.o~utput~ln~the~:brain region.- This r~elationship is,.~és'tabllshed on the~combination of:the first data and~ i,'.''. ;th:e~second,~da~a.~

The:~repreienta;tlve value;obtalned~by thls omb1natlon~o;f flrst-data and~second~data~is;~a~concor~
''dance value~or~a~discordance value.~: S.uch~values are ~
quantlf~ied~re~lat~lve~tg the~de.~arture of~:the~:-first data ~ , ,'.. ', 25,~ and~sec:ond~data~:f:rom~a~selected:base:value:.~ The concordance~value'is~ind:lcated by:departur~o~ both the~
f,irst~data~and~the~second data:in a~:~f~irst;~direction from a~selected~base value.:.~A discordance value~:is~;indicà;ted : ~ : : ,,,',.
:by departure of the~first data and the~:~se~ond,:~data in:~ ', ! 30: opposite directions from a selected base value. In addition to the concordance and discordance states,:there is~a~state~of~ "no concordance" and "no:discordance". ; . :
Th~is~is re~ferred~to s~ "no cordance". This condition~ "`
also provides information about brain activity.

, Preferably, the concordance value:and discor dance~value are quantif~ied and mapped topographlcally W O 93/03670 PC~r/US92/06789 rj O
~,,.
- relative to the brain region. The mapplng is cffected in selected frequency domains and is employed to assess and .~
assist diagnosing disord:ers and afflictions characterize~
;: by lesions in thè brain. This mapping is referred to as - :'.'.' , . ~
cordance brain mapping.

he first data and second data are selectively ~
absolute power and relative power, respectively. : .. ~'"
Absolute power: is a determination of the intensity of :~.
lO .~electric activity in a given frequency domain in a brain .~
r~egi~on.~ Relativé~power~is a measure of the proportion of ~.
e:lectrical~activity~ in~a~given frequency domain; in a ''.-brai~n~:;regi:on.~C:ordanc~e~mapping represents an enhancement : ''.
of quantified~EEG methods that adds significant 15 ~:sensitivity for at least the detection of deep or ;:
;c~ort~ica~l brain~l~esions`.~

The invent~1on~provides for information about ''.
bra:i:n~electri~al:function that can be associated with 20~ speclf;ic~diseases~and~:thus~can distinguish~between di~fferent~;diagnoses~

: Furt~er, the: lnvention provldes~for information `~
about~:~bra'in:~fur.~tlon:associated with activation tasks, 25~ 6uch`tasks being:~selectively~a: cogniti~e, perceptual~
emb~ional,~ specific~:~memory task, a motor:task, or :: ' :' cognitive~processing.:~Preferably, ths information is ~
obta;ined~:from a concurdance or discordance value. This information is selectively the activation:,~ deactivation, ~ or absence of activation effect during:a task.

: In a further preferred form of the invention, '''~
concordance in a:selected frequency ~omain is~associated with~normal perfusion in the brain.: Such a conrordance '~
35 :~:value correlates with both the mean perfusion of tissue : ~ ....
and~the valume of tissue with specified perfusion~
Gharacteristics.
" ~

, , W093/0367~ PCT/US92/06789 '-'`-~
~ r c 5 ~ 6 q ~'3 ~ The invention covers the method of determining the electrical output in regions of the brain, apparatus , ',' for providing the determination,-and the use of such , ;', methodology and apparatus to perform assessments and '''~
5 characterization of the human brain. ~ '-The invention is now further described with ,', ; reference to the accompanying drawings.~ ', IO~ DRAWINGS

Figure;l lncludes three views of scans of a ~ -~
patient with~multi-infarct dementia. Figure lA is a ,'"
braln map lllustrating discordance in the two frequency 15 bands in a linked ear montage; Figure lB is an MRI scan '`
lustrating the~same brain region; and Figure lC is a SPECT~scan illustrating the same brain region as the bral;n~map,~

20~ Figure 2 1ncludes three views of~ scans of the . ',~
;same patient as in Figure 1. Fi,gure 2A~is a brain map 1, illustrating concordance in the one frequency band in a linke~d~ear~montage;~ Figure 2B is^an ~RI~scan i~ilustrating the~same~brain region; and;Figure 2C is a~S~ECT scan ~ ,~
;25~ 'illustrating the same~ brain region.

Figure 3 includes three ~iews of scans~ of~a ~
patient with dementia~of unknown etiology.~ Figure 3A is ,`, a brain map illustrating discordance in the one frequency ,s,"
'30 band in'a linked~ear montage; Figure 3BIls an ~RI scan illustrating the same brain region; and~Figure 3C is an ~ :
MRI scan illustrating the same brain region. ~ '' , ; .
Figure 4 includes two views of scans of a ~ , ~'~` 35 ~ patient with Alzheimer's disease. Figure 4B~is a brain map illustrating discordance in the one frequency band in ~ a reformatted bipolar montage, herein termed bipolar -,, ~ :

W093/03670 PCT/US92/~67~9 i"`'.' '.-'-.
2 ~ 5 ~ - -. montage; Figure 4A. is a PET scan illustrating the same , brain region. , .-; Figure:5 i~ncludes two views of scans of a ,-, 5 ~ patlent with Pick's disease. Figure 5B is a brain map . ;, illustrat~ng.discordance in.the one frequency band in a . .,''-bipolar montage; Figure 5A i5 a SPECT scan illustrating the~same~brain:region.

O~ F~igure~6~are further brain scans of the patient ; ' illustrated:in Figure;5.~In Figure 6A, there is illus- ~, ratéd~ab:solute power in~ our frequency bandsi~Figure 6B : '.
lustrates~relatlve~power in four frequency bands; ;~
Figure 6C illustrates discordance maps in four frequency. :':
15 ~band~s; and Figure 6D illustrates concordance maps in four,.
equency~bands.~Fi~gures 6A and 6B are~obta~ined in a inked~:ear~montage;:~F~igures 6C and 6D are obtained in a bipQl;a~montage.`~

20~ Figure 7~ nc~1udqs two views~ of sca~ns~of a patient~-with multipl~e~sclèrosis. Figure:7B is~a~brain~
map~ lustratlng dis¢ordance in the~one fre~uency: band in:. ,"~:
a'~ ~ lar montage;~Figure~',7A is an~MRI s'can~illustrating :;~
the'same~b'rain regl~on~

Figure~8~includes~two ~iews~of scans~of a ;c~o;n,trol~subject with~white-matter disease. Figure 8B is~
a~r~aln~map illustrating~.discordance in~the one frequency~
band in a bipolar montagé; Figure 8A is a SPECT s~an 30~ illustrating the sam~:brain region.

Figure~9~:is~a schematic,of~major components illustrating:the~data~processing and~flow to obtaln:the ~~ .`.~,', cordance map from:the:electrical output:ln~a;brain ~ :,,.",i 35~ egion.~

W093/0367n PCT/US92/06789 " .-, . . . ".:

2~ 8 Figure ~0 is a blo~k schematic illustrating the relationship of a patient relative to appa,atus for obtalning cordance mapping.
: .., Figure 11 are brain scans of the patient illustrated in Figure l and 2. In Figure llA, 'here i~
1lustrated absolute power in four frequency bands;
Flgure llB illustrates relative power in four frequency bands; Figure IlC illustrates discordance maps in four ~-^
lO ~frequency;bands; and Figure llD illustrates conaordance maps in four frequency bands. Figures llA and llB are obtained in a l1nked ear montage; Figures llC and llD are obtalned in a bipolar montage.
:;
Flgure 12 are brain scans of the patient illustrated in Figure l and 2, the relationship being in ~ . - .
a linked ear montage. In Figure 12A, there is illus-trated~absolute power in four frequency bands; Figure 12B
llustrates relative power of four frequency bands; 13 ;~
20~ F~igure 12C illustrates discordance maps in four frequency~
bands~; and Figure 12D illustrates concordance maps in four~frequency bands.

Figure 13 is~an alternative preferred version '~
~of~Figur~e 1 set up~with an improved computer program and with~data obtained in the bipolar montage. Delta and theta maps of Figure l have been replaced with beta~and ~,~
theta maps as indicated.

~30 ~ Figure 14 is an alternative preferred version of Figure 2 set up with an improved computer~program and with data obtained in the bipolar montage. A delta map of Figure 2 has been replaced with a theta map as ndicated.
Figure 15 is an alternative preferred version of Figure 3 set-up with an improved computer program and -.

~ . .
,:

r ~ J I ~ I ~J U .1 M~ j ~

with data obtained in the bipolar montage. A delta map of Figure 3 has been replaced with a beta map as indicated.

;5 ; ~ ~Flgure 16 is an alternative preferred version ; of Figur~ 4 set up~ with~ an improved computer program and ,wi~th data~obtained in the bipolar montage. A delta map of~Fl~gure~4 has been replaced with a beta map as ndicated.~

Figure 17 is~an alternative preferred verslon of~Figur~e~5~ set up with an improved computer ~rogram and wlth~d~ata~ obta1ned~1n~th~e bipolar montage. A new theta ;
map is indicated.

Figure~18~is~an~`alternative preferred version of~Fl~gure~ 6~set~up with;~an improved comput~er program and~ ~-1th~;data~obta~lnéd;1n the bipolar~montage.~ New C
discordànce)~and~D~ concordance) maps are indicated.

Figure i5~is~an alterna.ive preferred version~
o~ ~igure~7 s~et~up with~an improved~computer program and w~i$h~ data~obtaLned~in the~bipolar~ monta e~.~ A delta map ; -oI~Figure~7~s~=e-1d-ed~with;a th~e-~ma=~a=~;indlcated~

;Figure~20~is~an alternative~preferred version Figure 8 set~ùp~with~an improved~computer prog~am and ; ?
with data;obtained~1n the bipolar montage.~ A~new theta map is~indicated~
Figure 21 is an alternative p~eferred version of~Figure~ll set~;~up~with an~improved~computer program and with~data obtained in~the bipolar montage.~ A new C
(discordance)~and~D;~(concordance)~are indicated.

Figures 22A, 22B and 22C are alpha concordance--and discordance~maps for the three CON;subj~ects wlth the ;~

.. ,,,, . , .,, ., . . .... ,, , .. ,, ... ,, .. .. . . . .. , ; ,, . ., .. . ; . - . -. - . - . - . .; . . , - ~

16~c'dPCT/PTO OI MA~
P~T~ U S 92 ~ O 67 89 , best performance on the reminiscence and hypermnesia paradigm (EH, LD, and LG). Subjects are identlfied on the left side, along with the ratic of correctly ~;", recalled/not recalled items on the reminiscence paradigm 5~ (the CC/NN ratio). The higher the ratio, the better the performance., ~The maps,from,the CC and NN,"co,nditi,on for ' ,~
,each subject are dlsplayed separately, with concordance ma~s in the~left column and discordance maps in the right : .
column. Each map represents the`head as viewed _rom ~ `
10~ above, with frontal regions at~the top. Concordance and ,~
discordance are mapp~d separately but on the same colorgraphic scale,~,~where~black is intense cordance ~",' (either concordànce or discordance), there are ,~
intermediate levels of~cordance, and'white is a value of '"
15 zero'(neither concordance or discordance, but a no ,; ,,, ord~nce stat Flgur~es 23A~and 23B are alpha concordance and dlscordance maps~ror the~two CON subjects with the ,',' 20~ poorest performance on the ~eminiscence~and~hypermnesia '', parà~dlgm (MG and AS);. S~ub~ects are identlfled on the left~s~ide,~along`with~the ratlo of corre~ctly recalled/not r~c,alled~ite~S on,`the~reminiscence paradigm (the CC/NN , '' ra~i;o)~ The~hlgher~the-ratio, the better the Z5~ per~ormance.~ The~maps from~the~CC and NN~condltion for e~achi~su~j~ect are~displayed~separately, with~concordance maps~in the lef~ column~and discordance maps~ in the right column~. ~ Each map~r~epresents the head as viewed from ~
above, with frontal~regions at the top. Concordance and ~ ,,,;
30~ ~dis`cordance are mapped-sPparately but,on the same ~,.
colorgraphic scale,~where black is intense cordance e1ther concordance~ or~discordance)`,~and there are intermediate levels of cordance, and~white is a value of '~
zero (neither concordance or discordance, but a no , "~

3~5~; cordance state). ; ; ~, .

~': ~ ' . ' ' ~ ' .. ''' UBSTITUTE SI~E~T ` ~ `
p~

; 11 2~1~65~ -~igures 2~A and 24B are alpha concordance and discordance maps for~two MDE subjects on the reminiscence '. - ' . and hypermnesia~paradigm (CM and AM). Subjects are - identified on the left:side, aIong with the ratio of ' correctly recalled/not recalled items on the reminiscence ~;' : -paradigm (the ~C~/NN ratio). The higher the ratio, ~;he ; ~ better the~performance~. The maps from the CC and NN
condition for-each subject~are disDlayed separately, with ~-concordance maps in the left column and dlscordance maps ~in the right column. Eac~ map represents the head as e~wé~d from above,~with frontal regions at~the ~op.
Concordance~and:discordance are mapped separately but on the~same co~lorgraphic~sca~le, where black is;l~tense '-.
cordance (either concordance or discordance), there are':' 15~ intermediate levels;:of cordance, and white is a value of ~ ."`.
zer~o'(nelther~concordance or dlscordance, but a ns : ~ Gordance state) Fi~ures 25A~and 25B are alpha concorda~ce and ~';'' 20~ di~s~corda:nce maps Cor~two MDE subjects on ~he reminlscence and:hypermnesla~paradigm~ SC and LM). Subj~ects are~
dentified on th~e~left side, alo:ng with~the~ratio of ~' correctly~recalled/not recalled items on~:ths remlni-s¢ence -~ L'~'''~'"
paradl~gm~(the~CC/~NN~ratio). The higher the~ ratio,:the 2~5~ bet`ter the~performance.~The maps f~rom~the C;C and NN
condition ;for each~sub~ject are displayed~separateIy,~:with conc~ordance:~maps ln~the~left column~and discordance maps in the:right~ column-.~ Each map represents ~he head as ~ ..
v-iewed from ab~ve, with frontal reglons at the`;~top.~
30~ Concordance and discordance are mapped separately but:on '' n ~ the same colorgraphic scale, where:~black lS lntense ~
cordance~(:either~concordance or discord:ance); there~are : in~ermediate levels of :cordance, and~white is a value of i.
zéro (neither concordance or discordance,~but a:~no 35: :'cordance state).

SUBSTITUTE SHEET ~
IPEA/US : ~`
~: .

16 R~'d P~TIP10 ~ ~ MAt~ 5 ~ :~-Q~T/US 92/~6~89 ~-12 211 5~ 5 0 ~ ;~
Figu-es 26A and 26B are alpha concordance and discordance maps for the two DAT subjects on the reminiscence and hypermnesia paradigm (RK and DL). j Subjects are identified on the left side, along with the 5~ ratio of correctIy recalled/not recalled items on the eminiscence paradigm (the CC/~i ratio). The higher the ratio, the better the performance. The maps from the CC
and NN co~ndltion for each subject are displayed ~ i separately, with concordance maps in the left column and discordance~maps in the right column. Each map represents the head as~viewed from above, with frontal regions at~the top. Concordance and discordance are mapped~separately but on the same colorgraphic scale, where black is intense cordance (either concordance or' discordance), there are intermediate levels of cordance, and~white is~a value~of~zero (neither concordance or dlscordance, but a no cordance state).

Flgures~Z7A,~27B and 27C are a serles of maps 20 :~LOr a~subject in the resting state tA), during 20 seconàs i~
of~ co~ntinuous right-h~and~movemen~ (B), and during 20 s~econds~of~ continuous left-hand movement (C). The~
variable~ mapped~is theta concordance, with dar~er color~s -show}n~g~more intense concordance. The~rest:ing state 25~ shows~ a~slight hypof~ontal pattern, while both hand moYement conditlons;show frontal activation. Right-hand movement shows~preferential~activation~over the left ~ ;
hemisphere, whilé left hand movement shows preferential activation over the right hemisphere.~ All~ ma~s show the ~ -' 30 head as viewed from above. ~ ~~

Figure~28 shows the agreement between alpha concordance and SPE~CT in assessing~normal~regional perfusion. Twenty-seven subjects were studied with both SPECT and cordance. Each subject had a brain disease known to affect regional perfusion. The bra~in was ~-~
divided into SlX reglons (frontal, temporal, and , , ~: s~ rlTuTE ~H~E-~ .
::: IP~

~C~ S 92/06~89 i~
12/A 2 ~ l 5 ~, 5 ,~
.~
occipital, bilaterally) and the proportion of su~Jects iIl each brain region who had normal perfusion and alpha :~
:; 5 concordance were counted. In all but two regions, there . .

- .

,: , ' , ..

SUBSTITUTE SHE~T :
IPEA~US-. : : : "
,-, ~ . ~ .

,~ ~, ....

' 13 was a high level of agreement between the tw~ measures in '~defining normal perfusion.

DESCRIPTION

e~ermini~g~*he electrical o~tput of-th~ brain -~region of a subject and hence the assessment or diagnosis of a disorder or affliction of the brain as characterized by a lesion comprises obtaining first data representative O~ of the energy intensity ln the brain region in a primary frequency domain.; These data are represented by the abso~lute power ln the pr~lmary frequency domain which is ef~ined by specific frequency bands. These are the conventional four frequency bands, namely, delta, theta, 15~ alpha,' and beta frequency~bands of electrical activity.

From~these f~irst data, there are determined '~ second~data, namely, ~the relative power,~which is repre-sentat;ive of energy in~a selected primary~frequency 2~0~ domain~relative to'the~energy in a secondary frequency doma.n~

Whi:~e the pr~imary frequency domain is~any one ~-~
` ~ of~t~he frequency~bands~ delta, theta,'alpha and~beta,~ the 3~ ~ 25~ secondary~re~uency~d'omain can comprise~one or more ~han orle ~frequency band.

In some cases, the primary~frequency domain is several of the frequency bands and the secondary fre-quency domain is a~different frequency band or set ofbands which should preferably incorporate at least~part of the frequency band or bands of the primary frequency do~ain.

35~The absolute power and relative power are related to obtain a representative value of the .......
~ electrical output in the brain region. Relating is .~,.~ :: :

, ", ".

. W093/03670 PCT/US92/06789 ,~
:, ,: , .
:
14 211J~JQ
, ~ effected by determining the absolute po~er and relatl=ve .~ power compared to a selected base value. When the first .'~
.. . . .
data and the second data both increase or decrease rela- '.
?~ tlve to a selected~bas~e value, a concordance condition is '~
5~ indicated.~ Whe'n:one of the first data and the second .data-r~espectively increase.or declease relative to the ~
selected base while the other of the first data or second data r spectlvely;is oppositely directed relative to the selected~ base,:~a discordance condition is indicated.

.'~ The~relati~onship~of the absolute power and re~lative~power~is;~hen':established. When the absolute ~ :
power~ and~rel~ative p~wer~are both greater:than a selected:
base value, then a quant:ified concordance value is 15 ~ ca~lcu;lated, indicated and displayed. Similarly, when one of~the~ abso:lute:~powers:and~relative-powers are oppositely directed~re~lative~to:the~::selected base va~lue, then a quantifled~discordance~value is calculated, indicated and :
`~ .dlsplayed~

The indi~cated and displayed values provide ~he ' ~ indices~of co~cordance~and~discordance that are related '.:
' .to'~:~the presence~of~;~brain leslons. The distribution of :
oncordance~and;-dlscordance values ln the brain reglon is :
25 ";~ disp1:ayed;~topograph.~cally~through cordanc~e~ mapping.~
Theré ~ ,~`there ~is~obtaiDed~a spatial distribution and .' ' ~ information~relating~:~to~the pathophysiological nature of :
~3 `~ the~brai~n lesions~ Through this technique,:the~evalua~
f~ tion of disorders and afflictions characterizad by:: ~ :
: 30 :~ lesions~can~be a~s;sessed to assist in a~:diagnosis.
Typical of the:diseases~ and disorders that can~be deter~
mined~are~dementing:illnesses such as multi-infarct deme~ntia:, Alzheimer's disease and Pick's disease, ~ demyelinating:diseases such as multiple~ sclerosis, as :
,~q~ :35:~ well as:1esions amcng otherwise healthy control subjects.

~rf~

j W093/03670 . PCT/US92~S789 ;.

lS
~7,~A~ The de'ta frequency band is conventionally the slowest frequency, being from about Q Hz to 4 Hz; theta is from about 4 Hz to 8 Hz; alpha is from about 8 Hz to 12 Hz; and~beta is from~about 12 Hz and higher, namely, S :to about 20 Hz:or 3:0~Hz in frequency.

; In the exemplified version of the invention, th~e~primary fr~equency~domain incorporates any one of the~se~bands.~ The;~selected sec~ondary frequency domaln O~ includes~a~ll of the delt~a,~theta, alpha and beta ; fr:equency :band:s..~

The~flrst data~are the absoIute power. It is indicated in microvolts~squared and indicates the energy intens:ity in a selected single frequency band ('~primary . ~ frequenc~y~doma~in")~ The~ second data~are relative~power.
It~i~a~repre~s~entatlve;of:the energy in:a selected single ` :;~
;~ frequency:~band~relative~to all the frequenc~y bands ":secondary:::fre:quency~`domain"). The relative power .`~ 20~ répresents~;a~fr~action~;of, or the percentage~of, power in ~ the~s~élected:~single~frequency band relative to the ~ : :
,`~ abs.oluté~power:in all frequency bands. ~

In~the~determination of the~electrical output :25~ of~a:bra~in~reglon~.of~the head.of the s~ubject,~an:
obj~Qctive~:base:~alue~is first established;fo~ each :~
su~3e~t.~:This obj;ective base is conveniently;a selected base~be~ing a~midpoint~:for the absolute~power~and~a :: selected:base being a midpoint for ~he~relative power for-: 30 ~each subject. It is:a midpoint of a normaIized base ; value~of 1 which is representative of~:the respective maximum~;absolute~power:~and the maximum relatiYe power .
The maximum absolute power and maximum relative power are se~lected ~alues: of the first data and.the seCond data, 3:5~ respectively. Values other than the maximum can be selected as necessary. : ~ :

s'~l W093/03670 PCT/US92/~6789 ', ~' l6 ,~~ J a s indicated in Figure 9, the energy distribu-tion is sensed and measured by electrodes located on the head of a patient to obtain analog signals in each electrode for an EEG unit. Each pair of recording ' 5 electrodes;estab1ishes a channel. The analog signal ~P~ ;provides a~conventional~EEG wavef~orm record as indicated.
he analog signal~ 1S digitized by the A/D converter in a microcomputer to~become digital data. A Fast Fourier Transform~tFFT) process is applied to ~he digital data to 0 ~yield absolute power values for respective EEG channels.
,~ The relative power~also~is calculated. These channels represent ;each of~ ahout 20 electrodes located strate-'~ gically about the~;head of a patient. The absolute power values and the relative power values each sqrve~inde- ~ , ~pendently to provide conventional EEG brain maps as indicated.~ Such;-brain~maps would otherwise be termed as quantitative EEGs~ ~

' With reference to the objective base value 20 ;~which 1~s established~for~each.subject, the maximum ~
abs~olute power and the maximum relative~power is set up fo~r~ the~values across all channels for each frequency - , ;2~5~ The absolut~ power data and~the relative power data~are used in'~Gombination in accordance~with the nvention to esta~lish representatiVe~valUes to permit ;cordance~mapping. ~The absoIute power value-~serves as~a ,,~
basis for determining concordance and discordance calcu-lations which c~aracterize the quantity and quality of the electrical output of~the brain region. ;This is taken ~;
in the~context of energy from recording locations of all '"
electrode channels and in all the frequency bands~

35~ ; The absolute power values are processe~ by compUter means into relative power values~by dividing, for each charlnel, the amount of power present in a'gi~en 1 W 0 93/03670 PC~r/US92/06789 ~ ~J ~rjO

- frequency band by~the total power for each channel.
Relative power~thus reflects the distribution of the energy for a channel among the different frequency bands.
There can thus be an absolute power value and a relative 5~ power value for: each frequency band for each of the - ele:ctrodes loca~ed about the-head.

The~absolute~power and relative power values :
,~ are~normalized by~d~ivision by the maximum absolute and lO~ maximum~relatlve;~power.~:valUes,:respectively, across all ;;2~0~channels~and each~;of the:four frequency~bands. The ,maximum~absolute~power;value and the maximum relative power value~s~are determlned by examining the absolute and relative~power values for each channel, and selecting the 15:~ greatest absolute power value and greatest relative power value,;~The~s~e normal~ized~ ratios or~values are called ;resp:ectively~the "aratio":and "rratio" and~are compared . ~ wlth~;~the~maximum values~normalized to l.O ("normalized , ~ base")~.~ This, compari~son:~yields the concordance and .20~ disco~rdance~quantlfication. These procedures are e~ffected~:by~appropriate~computing and~microprocessing means,programmed to~ef~fect the requisite dat~a calcula~
tio~,s~and~prcc~es~,~ing.~

;25~ A~channel~:~exhibits a disccrdant:~pattern and~is ~ :
quant:ified~w:ith:a~dis:cordance value when thei absolute:
,power~is~diminished relative to its selected base value : .
while~the:rPl:ati~e power-is increas:ed in~relation~to its selected base value.: A sel~cted~base value is specifi-30 ~cally defined as~a percentage, fraction, or proportion of ,the~normalized value~l ("normallzed basei'). In a~dis-cordant condition,:the aratio is less than "1/2 of the maximum absolute power" ("selected base") and the rratio is:-greater than "l/2 of~the maximum relatlve: power" :
35: ~("selected base"). ~ ~

' W093/03670 PCT/US92/06789 ~
.
18 2~ J o :; :
}~ In this sense, the normalize~ value is a "normalized" base, and the midpoint or half point of the base is a "selected base" or proportionate value repre-sentative of that~normalized base value. The quantified discordance value or score is determined by the sum of the~devia~lon of the absolute power from "1/2 of its base value" ("selected base") and the deviation of the relative value from-"1/2 of its base value" ("selected base"), as can be expressed by the form:
10~ discordance score = (rratio - 0.5) + (0.5 - aratio) ; A large discordance-score de.scribes the condition of a channel with a~ low power signal that is confined mostly to~;a given frequency band.

J~
~ Should the absolute power and relative power both b~ increased, the aratio and rratio are both greater than ~1/2 ma~ximum, namely, "1/2 of ltS base value"
("selected~base").~ Such a channel is considered to show a~concordant pattern.~ The concordance quantification 20~ score~is then equ~al to the cumulatlve~elevation above the 1/2 power level for the two normalized values, as can be expressed by the~form: ;
concordance~score = (rra~i~o - 0.5j + (a~atio - 0.5).
A~large~concordance score describes the condition~of a 25~ ;~;channel~wlth a high~power signaI that is confined mostly to~a~given frequency band.

The concordance and discordance values can be expressed in terms of a mathematical erivation. This ,, ~ : , 30~ derivation is ~et out as follows:

Let ahf = -absolute power iD channel ch at frequency c, band f. Typically, ch is in ~he range 1 -j~ to 20 in 20 channels of EEG data, and f represents the frequency bands delta, theta, alpha, beta , ~

~ ~ ' ,.... ,,.. , .-:
.`j ~
W093/03670 PCT/US92/06789 ~-.

c~ 19 Then rchf relative power in channel ch at frequency : ~band f h, f '' ~all bands ch,i 10 Define a~x f = maximum absolute power in frequency band f, of all channels r~xf - maximum relative power in frequency : band f, of all channels.

lS ~ Normalized values of "aratio" and "rratio" are formulatPd: ~

aratloch,~ f rratioch f =
25:~ ' rmax f These~normalized values are then~compared with a ::threshold level,:~g~, half-maximal values, i.e., the ~ :
seleated base valuP
30~. : If (aratlo~h f < 0.5) and (rratloch~ ~ 0.5) then :: : channel ch is termed "discordant" in frequency : : band f; ~ ~
If (aratioch f >:0.5) and (rratioch f ~ 0.5) then ~:;:;: channel ch is termed "concorqant" in frequency 3;5~ ~ band f.

"~

.,~

i`

W093/0367~PCTIUS92~067~9 -r n ~1 L ~ r~ 3 U

For concordance or discQrdanse, the magnitude : o~ the quantification score can be calculated by the formula:
score = I rratio~-: 0.5 1 + I aratio - 0.5 1 5 whére~ denotes the:absolute value, and 0.5 represents --he normali:zed l~:2;maximum value.

A typical~ ca~lculation of quantified values is ;set out~

Dlscordan~::Site~
arat~io =~0:.3 rratio~ =;0.7:
aratio <~ 0.5 and rratio ~ 0.5 ~: . -15:~ so:discordance value =:0~2 + 0.2 = 0.4 Concordant~Site aratio =~0:.~7 . ~ rratio =~0:~.8 ~ : :
i ,~0 ~ arati~o~> 0.~5:and rratio > 0.5 :, ~ so~ oncordance value~=~0.2 + 0.3 =~0.5:

3~ In some~situationsl it i-s productive t~o :~
c~onsider~a~"selected~base" level other ~han 1/:2 the `~ 25~ maximum~power~va~lues.~: ~0r example, if a recording~is notable~ or~a singl:e~channel with much higher~power~than the~others,:~this~atypically high value:sk ws~ the basis of :: :
a~comparison sca:l~e.~ Such a value would be discarded~as:~
~ an:atypical value~or outlier.
,,, .~ 30~
A ~hreshold of 40% or 30% of the normalized maximum of 1 could y:ield more useful sets of~discordance :~
:and~concordance comparisons in:differ~nt situations.
SimlIarly, situations could arise where the threshold `~ 35 ; level~ is set at 60% or 70~ of the normallzed~maximum.
Su~ch 40%, 30~, ~60%:or 70~ values would be the;l'selected base."
',`' ~

`'~
,,~

~W093/03670 PCT/US9~/06789 ,~ 6 j~ 21 ~7ith the quantitati-~e EEG rPsults, the cordance - -mapping is topographically illustrated in a primary frequency domain in Figures lA, 2A, 3A, 4B, 5B, 6C, 6D, 7B and 8B, respectively, and also Figures 13A, 14A, 15A, 16B, 17B, 18C, 18D, l9B and 20B. Each respective domain is illustrated as the de~ta, thetaj alpha Gr beta ran~e~ --in each ol the respective Figures lA, 2A, 3A, 4B, 5B, 6C, 6D, 7B and 8B~ and Figures 13A, 14A, 15A, 16B, 17B, 18C, 18D, l9B an~ 20B,~ respectively, as indicated.

The most informative cordance map or detecting lesions is usually in the theta or beta frequency bands.
' Such mapping'is illustrated in Figures 13A, 14A, 15A, ~. -: .
16B, 17B, 18C, 18D, ~9B and 20B. The data are obtained from ~he 20 elèctrodes connected to the EEG unit which measure~;the electrical activity in the~;head.

Information~is obtained that may indicate the disconnection of cerebral cortex from the fibers that connect brain~regions one to another. This may be the common denomlnator in Alzheimer's disease, Pick's dis~ease~,~multi-infarct dementia and multiple sclerosis.~ ' In~these diseases, gr~adual-severing of~the connections~
'~ that~ nk~different brain areas eventually may cause the 25~ symptoms of mental~nd neurological disability. The representative values~as given by the dis ordance and concordance representative values in the cordance maps of ;~ Figures l~to 8 and Figures 13 to 20 as a determination of the electrical output of these region5 of the brain 3'0 ; prcvides useful~interpretive data to enable the evaluation of the diseases.

The results for the brain rPgion depicted in Figures 1 through 8 and Figures 13 to 20 were obtained 35 from measuring EEG data on subjects in a supine position with eyes closedO Electrodes were applied in the standard 20 locations on the head. At least 30 seconds ~ W~93/Q3670 P~T/US92/0~789 i-2 1 i .~ O
i~ 22 ;~ of relatively artifact free EEG measurements of distribution were effected. The electrodes were applied usin~ standard clinical procedures and the data obtained ~jJ'` were stored on an EEG unit.
~` 5 In this exa~ple as-illustratedj the EEG uni~
employed was a system known as QSI 900O produced by Quantified Signal Imaging, Inc. of Toronto, Ontario, Canada. This system provides data relating to conven-tional qEEG information, topographical mapping of fourfrequency~bands in the central, frontal, temporal, parietal, and occipital brain regions. Absolute power P~ and relative power data for the different frequency domains are obtained from the EEG measurements.
~ ~
The avoidance of inaccurate data readings from electrodes~about the~head can be avoided by using ~ diff~erent~relationships between any number of selected ;~ electrode channels.~ ~Computing vector relationships ZO;~ bet~een selected electrodes avoids the effect of referentia1 monopolar values relative to reference elèctrodes set up in adjacency with the ears of a `~ subject. ~As such, it has been common in EEG~determi-nations;to use~monopolar referencing by having a 1inked 25~ ears reference electrode: this means~by having elec-;~ trodes;in adjacency to each ear relatlvely linked. Use of~re~erential monopolar data for the purpose~of cal-`~ culating concordance and discordance creates inaccuracies ;~ ~ ;; in cordance calculations having to~do with intere1ectrode distances. While rèlative power calculations are un-;~ affected by the mon~ages selected, absolute power changes ~ ;~
are in proportion to the square of the interelectrode distance. Thus, the fronta1 and occipital power estimates are inflated, since these are the furthest points from the reference electrodes. Temporal power isunderestimated since this region is closes~ to the reference electrodes.

W093/03670 PCT/US~2/06789 --, - . .

A c~nfiguration is de~cribed with refPrence to-Figure 9 to eliminate this problem. Absolute power data --collected from the linked ears reference montages are~
~ first reformatted. This is effected using vector `~; 5 ~calculations set up in~ a grid of bipolar electrode data, comprising equally-spa~ed pa-irs of longitudina~l and ~- --t~ansverse electrode chains. Power for each individual ,'!: ::
electrode is then~recalculated by averaging power for all Yl ~ : respectlve pairs of electrodes in the chain longitu-dinally and transversely. Each pair of electrodes in the hain is regarded as a bipolar pair. The concordance and discordance for each lhdividual electrode may be calculated from the data from the bipolar pairs either before averaging, or from the individual electrodes after : . i ~ :
averaging. Thè data are thén employed to establish the maximum, mldpoint and other values as necessary.

As an example with reference to Figure 9, the electrodes lI,~12,~13, 14 and 15 are set out in the first 2~0~ 1ine, 1~6-, 17, 18, 19 and 20 in a second linej and 21, 22, `~ 23~,~Z4 and 25 in a~third line. The ears 26 and 27 are indicated~relative to nose 28. In a linked ear montage, ea~h~of the electrodes~ll to 25 is referenced to the ears 26~and~ 27 which ~re "electrically" linked as a reference.
25~ The~grid of blpolar~electrodes is establlshed along the ne~defined~by~electrodes 11 to 15, 16 to 20, and 21 to 2~5. ~The vertical grid~is 11, 16 and 21; 12, 17 and 22, ~i~t ~
for example.~ The bipolar data are set up by measuring the data from each electrode in relation to the adjacent electrodes. As such, for example, the power is measured for~electrode 18 relative to electrodes 17, 13, 19 and 23. This is repeated for each electrode~relative to its adjacent vertical and transverse electrodes. By computer calculation, the calculations are effe ted to obtain a .
measure of electrical activity at each electrode and have a power estimate in-the region of the brain. This -,~ .

, s~:~
., ~

WO9}/03670 PCT/US92/06789 24 ~ ' r 6 ~ ~
bipolar electrode montage avoids artifacts caused by the linked ear montage. ~ ',-;' i, ~,. .
This reformatting method effectively stan-~dardizes electrode~distances and may yield information ' about'-l-ongitudinally-oriènted and transverse1-~-oriented ~ - -; recording;~vectors. It lS sometimes helpful to map concordance,and discordance for differently oriented generators~(or flber tracts) on separate maps~. In other ;lO~ clr~cumsta~nces, it~is;helpful to calculate concordancç and discordance after the bipolar~data have aIready been ,,'~ r~ecalcu;lated back~to~the monopolar format.

; The electrode head box which is-positloned near~
the subject contains 20 channels of opticalIy isolated , ~ amplif~iers~ When~the~patient is prepared, a;keyboard -command records~data f~rom~all 20 analog channels. EEG
'informa~tion~is then~seleoted for Fast Fourier Transform càlculation. Power;~and spectral amplitudes are calcu-20~ lated~ fo~r~absolute~power and relative power and the~
,;results of~the~Fast~Fourier Transform~are set out in a ta~ular~ value of~absolute~power and relative power. ~-"

'~ After~analyzing the EEG using the Fast Fourier 25~, Trans~orm,~the;~operator~generates a topographic~map of ;~ ~, a~so}ute p~wer,~ relative~power and ~a~cordance map~for~
ea~h~of~the four~conventional EEG frequency bands, ,'~ name~ly,,~the~selected~primary frequency domain. The~data can be stored or displayed on scre ns or hard copy in a -' ''~ 30 'conventional manner.' As illustrated in the flow dlagram of Figure 9, ;~ the conventional~qEEG maps are obtained from the absolute power~and relative~power values. The absolute power is 35~ optionally subjected to the process for standardizing the electrode distances by the bipolar montage. Thereafter, the absolute power is normalized to establish~the maximum ~s;~. :

l'i,' W~93/U3670 PCT/US92/067~9 '~
j6`j . 25 ~:
absolute power value, namely, the aratio. The midpoint value is established and thereafter, calculations of : departures upwardly or downwardly from the midpoint value are determined. The relative power value is normalized ,.
5:: by establishing the maximum relative power value, nam ly, the rratio. The m~idpoint value is established-and ~h~re- :-after;, relative power values upwardly or downwardly depart~ing from~the midpoint value are established. From this~data~, respect~ive discordance maps can be obtained in~
10~ selected frequency bands~or concordance maps~obtained in ~r~ s,'elected'~frequency~:bands. The discordance~map and con-cordance~map can:~:~be~merged into a cordance'map as indi- :

~ 15~ In Figure'lO, there is illustrated a sample EEG
.~ unit.~ The~electrod~e head box is shown connected~with the héa~d~of~ the~patient~whereby,~power measurements can be~
',~ taken ~rom~the'bra:i:n~-of;the patient. :~These are fed to the.'preampl1fier and from such an amplifier:, conventional " 20','~:EEG data~wou1d~be~recorded.,This would constitute a d.~ -conventi~ona:l EEG.unit. Specialized within that construc- :
;'~ s"~ tion~are~the elements~for a qEEG unit. Data from the : preampllfier;would~be;~directed to the analog to digital ''' ;'~ con~erter:and~ in~turn,, to a microprocessor. The proces-~ 25~ sor~ s~operated~by~a~keyboard console~and the output can .~ :
s,.'.~ be~ directed~to a~ video:display, storage or printer unit.
; `The~microprocessor~would operate in terms of the 1nven-~ ion::to~generate~the~appropriate standardized ~alues, ',~
'"~ : normalization, selected base values, departures from the ~selected base values, discordance and concordance calcu-lat1ons as indicated~in Figure 9.

Figures ll and 12 are illustrativ of the ~:
diff:erent cordance maps obtained for the same patient in :~respectively the bipolar montage and the linked ear montage. Illustrated in Figures llA,:llB, 12A and 12B, , :respectively, are the absolute power and relative power ~ , ....
. s : ~ , , ~ .
i~;
;'.~ ' ~., W093/~3670 ~ PCT/US92/06789 26 ~ 65 a in each of the four frequency bands, theta, delta, alpha and beta. In Figures llC and 12C, there are discordance maps in four frequency bands and in Figures llD and 12D, thPre are concordance maps in four frequency bands.
An ex mplary data Ta~le I for patient JL is set out below. ~Table I includes the data for the frequency bands~delta,~ theta, alpha and beta in a bipolar montage. !' In~each~such~band, there is set out the absolute power, " ~
O~ ~relatlve~power and~respective discordance or concordance value, ~Readings from~electrodes of an EEG unlt have been taken.~ These discordance and concordance values are t~opographically~depicted~as cordance maps illustrated in Figure~

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SUBSTITUTE SHEET

~:~ W093/~3670 PCT/US~2J067~9 ~ 28 211~650 In a revlsed form of the computer program implementing the cordance mapping, the data would be ,.
represented in Table II for patient JL as set out below.
The data from Table II corresponds to the cordance mapping of Figure 21.

Table II gives relatively better informative data about the sub~oct JT, ,~

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~,~ WO 93/03670 - 29 - PCI/US92/06789 - -`
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SUBSTITUTESHEET

~ W 0 93/03670 PCT/US92/06789 !~
,~ 5 ~
' ~n interpretation of the electric output in the brain region and diagnosis is set out for Figures l through 8. ~ -' In Figure 1, the brain imaging studies are for '~ subjec~'JL, a 67 ye'ar-old ma'lè'with'muIt'i-i'n~arct ' ' dementia. The cordance brain maps (Figure lA) show discordance in the delta and theta bands. In the ~ preferr-d forms in Figure 13A, discordance is in the beta i ~ 10~ and theta~bands. The MRI scan (Figure lB) is a T2-weighted image showing three discrete white-matter lesions separated from the ventricles, that correspond with the areas of discordance (highlighted wlth arrowsj.
~ ;The SPECT scan (Flgure lC) shows three prominent areas of q~ 15 hypoperfusion that also correspond with the areas of d~i.scordance ~(highlighted with arrows). Absolute power mapping and relative power mapping, which are shown in Figures 12A and 12B respectively do not provide this nformation. Brain~maps represent the head as viewed 20 ~ from above, whi~le MRI and SPECT scans represent the head as viewed from below. ~ ~

'~ The~discordance as illustrate'd`'in Figure~lA~"is closely~associated~;with the presence~of deep white-matter -25~ ischemic lesions~detected by MRI. The decreased absolute 'slow~wave power and~'increased relative slow wave power seen~in the elec~.rodes overlying deep white-matter~ ~
lesions is demonstrated graphically in Figure lA. The discordance map of Figure lA shows an in~ense area of discordance in' the delta band in the right ~rontal region. In the preferred form in Figure 13Aj discordance '~
~ is in the beta band in the right frontal region. Three `~',t`: ~ i areas of discordance also are seen in the the~a band with the largest and most intense focus present in the right frontal region. These areas of discordance coincide closely with three deep white-matter ischemic lesions seen on a T2-welghted MRI scan. In the MRI~images, right ~I ~
.,~ .

1 W O 93/03670 P ~ /US92/06789 ~......... ., .-;, s -~ 31 .~
and left are reversed compared to brain maps. The single -~ largést deep white-matter lesion seen on MRI (right 3~ frontal region) corresponds to the largest and most ~ intense area of discordance, seen in both the delta and ,t ,~ ~ : ~t~ ` 5 theta bands (Figure lA) br beta and theta bands igure 13~A). The ischemi~ nature of these ~esions is'`'~"''~''" ''''''`
confirmed by the sub~ect's SPECT scan, which shows areas of diminished perfusion in the right and left frontal and right posterior head regions over the deep white-matter 0~ le~ions~(Figure lC; samé right-left orientation as MRI).
More associations may be~determined from the brain c~ordance map~

~:t: ~ In Figure`2, there are additional brain imaging J~ 5~ ~ studies for subject JL. The cordance brain map (Figure 2A)~shows an~intense area of concordance in the delta band~in~the right posterior head region. In the preferred~f~orms in Figure 14A, there is shown ~ concordance in the theta band in the right posterior head ,t,~ 20~ region.... The MRI scan (Figure.2B) is a T1-weighted image showlng'~focal atrophy and ex vacuo ven~trlcular enlargement in the right posterior head region,~
~'r`.~ sùggestlng~an~infarction invol~ing the cerebral cortex ''~
'f~ and~corresponding wlth the area of concordance 25~ highlighted with arrow). The SPECT~scan (Figure 2'C) shows~a~prominent~ar~ea~of hypoperfusion that~also c~orr~esponds wi~h the~area of concordance (high-lighted with~arrow). ~Absolute power mapping and relative power mapping, which are shown in Figures 12A and ~2B
30~ -respectively do not`provide this information. Brain maps represent the head as viewed from above, while MRI and SPECT scans represent the head as viewed from below.

Concordance is associated with se~eral condi- -35~ tions including infarctions with cortiral involvement.
Interestingly, SPECT scanning may have difficulty distinguishing between ischemia that is due to deep W093/~3670 PCT/US92~06789 . . . ~:`
32 ~ 0 ~ white-mat~er ischemic lPsions or to infarction with ;~ : cortical involvement. Cordance mapping yields additional ~ : valuable diagnostic~information about the na~ure of these ;~ lesions.
: 5 ~ Accordingly, di:scorda~c~ is associated wit~' ' '"''"'''''''''' "~ deep white-matter lesions and concordance is associated:
,~ with:~lnfarction wlth cortical involvement.

10 ~ ~ In;Figure~3, there are the brain imaging studies~for sub~ec~t~RC, a 67 year-old female with demen-: .tia of unknown'etiology. The cordance brain~map (Figure~3'A)~ shows ~ a broad area of intense dlscordance in the delta band in the left posterior head:region. In the ~ lS ~preferred form in Figure 15A, there is intense ;~ discordance in:the~ beta~band. The first MRI image Figure~3B? :is a:T2-weighted axial view~showing a large patch:~of presumed,deep white-matter ischemic disease in ~Y.~ the;~.left~po~sterlor~head region adjacent:to the ~-r;~. .20 ,~;~.ventrlcular~hor~n~,~:that corresponds with the intens:e :
dlscordance~ hlghlighted with arrow). A~second MRI~ image Figure~::3C~) shows:~muitiple punctate areas of presumed ~ :
ischem;ic~;disease~that~also correspond w:ith''areas of: ~' .`,~ discordance:~(high~lighted:~with arrows). Absolute power 25~ mapplng~and r~elatlve.power mapping do~not provide this: ., inf~ormatlon.~ Bra~in maps~represent the head as viewed ~ .
;from~above, whi~le~MRI scans repr sent the head as viewed ,from~below.

: 30~ The sensitivity of the cordance technique to the presence of small~er lesions is demonstrated by the '`~ case'of subject RC, whose cordance maps are shown in~
Flgure~:3A. The less intense area of dlscordance over the ;~
right temporal region coincides with a~few scattered 35~ punctate ischemic lesions seen deep below the temporal cortex (Figure 3C). :~

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' W093/03670 PCT/US92/067~9 -~
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~,~ Figure 4 are the scans of GK, an 87 year old ~ male who presented with prominent memory loss and word-3~ finding difficulties. He was given provisional diagnosis of Alzheimer's~disease. A PET scan, Figure 4A, shows prominent~biparietal hypometabolism, as well as right frontotem~oral hypometabolism ~arrows~. The discorda~ce -map for~ the same sub~ect (Figure 4B) shows biparietal delta ~iscordance, more prominent on the right, corr~esponding to~the PET pattern. In the preferred form in Figure~ 16B, there is biparietal beta discordance. In addi~tion~, there~is a right frontotemporal focus of discor:dance corre'lating with the PET scan (arrows). The PET~scan~shows the;bra~in as viewed from~below, while the discordance map shows the brain as viewed from above.
, ~ ~ . i .
}5 Figure~5~ depicts scans of LB, a 51 year old female with~ a diagnosis of Pick's disease.~ A SPECT scan (Figure~5A)~highly~suggests this diagnosis, with promi-`nènt~and~severe frontal hypoperfusion (arrows). The dis-ao ~cordance map (Figure~5B) shows intense bilateral frontal dis~ordance (arrow)~ In the preferred form in Figure }7B~ there is intense~bilateral frontal theta discordance as well.~ The SPE~T~scan is viewed from below, and the~
discordance scan Is~viewed from abo-e.~

~ Flgure~6~ls additional brain lmaging studies '~ for~sub~ject LB.~ In~Figure 6A, the brain maps o~ absolute ~ power are~shown in the;~delta, theta,~a1pha, and beta ~ ~, bands (from top). Figure 6B shows the maps of'relative 30~ power in the same frequency bands. Both of these~columns show a diffuse excess~of slow-wave activity that does not ~ ;
h~ave~any clear regional predominance. The map in Figure '' 6C'is a discordance map of the same~subject, showing clear and prominent frontal discordance in th~ theta~band most prominently, and most significantIy affecting the - right hemisphere. In the map in Figure 6D, there is a diffuse concordance that is usually bilaterally ~ ~ .

W093/03670 PCT/US92/~6789 ,,' ~ , 34 21l 565 0 '''' J
symmetrie, and is of no significance in this case. In the preferred form, discordance is shown in Figure 18C
"4~ and concordance is shown in,Figure 18D.

Figure 7 illustrates a scan of SE, a 26 year "old w~ite''male~'with multiple sc~erosis.' The MRI'sc'an ''' '`
(Figure 7A) shows a single large demyelinating lesion ~ underlying the left frontotemporal cortex (arrow). The ,~ ' discordance~map (Figure 7B) shows a prominent area of lO~ discordance in the~left frontotemporal region. In the pre~erred~form in~Figure~19B, the theta discordance map ~ shows~discordance;in the left frontal temporal region.
'~ The ~RI~shows the brain~as viewed from below~,~ while the ~ discordance map~shows the brain as viewed from above.
'. ~15 Figures 8 an~d 20 show scans for~PH, a 76 year '~ old~male~control~subject with deep white-matter ischemic ,`~ e~slons in the~frontal lobes. A HMPAO SPECT scan for the `~ subject, (Figure~8A) shows globally diminished cerebral 2~0~ p~er~usio~n, with the most striking decreases seen in the rontal lobe (arrows). ~Figures 8B and 20B (the preferred orm)~show a theta~discordance map for~this same subject/
wlth~a~'~least mild~discordance in most~brain~regions, and ,'~ pr~omi~nent~frontal~discordance correspondin~to the areas 25~ bf; greatly~diminished~perfusiQn (arrows). The SPECT scan;
is~iewed~from~belo`w~ while the discordance map lS viewed from~above.

The cordance mapping is used to ass'ess the 30 presence and nature of brain lesions. 'The data obtained by~the cordance~mapping conforms substantially~and~
equi~alently to the data obtained by the MRI scan, PET or SPECT scan as illustrated in the figures. The values ~, representative of;the combination of the~absolute power 35 - data and reIative power data provide for cordance brain mapping. Such mapping thus provides a valuable ad~ance.
Absolute power and relative power mapping considered i ~

`

W093/03670 PCT/~S92/06789 .

?~3;J separately does not provide these data. It is thus --possible with the cordance brain mapping technique using ...
the quantitative EEG data to obtain effective information . to facilitate evaluation of electrical output of the ~b : 5 brain, and hence the presence and nature of disease conditio~s.~

It may be unnecessary to resort to the relatively expensive SPECT and PET techniques. The 10: ~diseases represented~by the information obta~ined by cordance brain mapping are the result of deep lesions in the:braln that produce excessive delta and theta slow wave~activity in an~EEG. Detection of these lesions by conventional EEGs or currently available methods of qEEGs 15~ ~is~not possible. Thus, a conventional qEEG would provide only~data:~about absolute power and about relative power independently~ From such unrelated data, it~is not.
p~os~sible~to~obtain~the same information as cordance mapping to assl~st in characterizing the human brain.

The:quantified~methods increase the sensitivity of-~the EEG~and the cordance~mapping extends this sensi- -~
;.~ :t~ivi~ty~t~o provlde~:use~fu1 information.:: The~ examination of ~;
`~ the~;cordanc:e map~distribution:of the absolute power~and 25~ relativè;power in~the~delta and theta bands particularly over~the~sur~ace~of the brain provides useful informa-t~ion~ The discor;dance and concordance values are~:
determined~by a ca1culation of the comparison Df ~he : : individual electrode absolute and relative power with the maximal absolute and maximal relative~power values over the~whole brain. ~ A brain region shows a discordant pattern~in a given:frequency band if the relative power from the corresponding electrode is increased above half the;maxImum relative power value for the subject while :
the absolute power is decreased below half the maximum absolute power value of the subject. Conversely, the brain region shows a concordance pattern where both the ,. . ~

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i~ W093/03670 PCT/US92/~789 ,. . ..
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absolute power and relative power value from the site are increased about the half maximal values of that subject.

The sensitivity and specificity of both 5~; dlscordan:ce and concordance may be adjusted by changi:ng the-thresh:olds~at which 't~e two measures àre"define~'. '-By'"''""'~ '' '"'' equlrlng:that concordant lncreases in absolute and relativé~power:be 5%, 10~, or 20% above the half-maximal 'value (~"selected~base"): for that subject, the specificity '~ 10~: of the::~easure:may~:b~increased. Similarly, by requiring . ' ~ that;discordant~absolute and relative power~be separated by~:~large differences',~the specificity of the~discordance measur~e~:may be:increased~. ;There are other parameters that may be ad]usted as well. For example, the half- :
~;maximal~value may~be calculated in several d~fferent .~ ways~ :It~may~be~based'on half-maximal value~from all regi~ons~for~that indi~fiidual subject, the mean or median:
-~ value:~for~that subj;ect~ or a half-maximal value after the~ :
or~ highest valu~es~(which may be outlier~s)~ have been ~ :~
2~0 ~ e1imlnated.~ These~f:urther.adjustments may change the ~ .
s~ensltivity,~spec~ifi~ity, or~usefulness~in~different ;~ cl'inical~situations:.-~

Cord~ance~mapping has been developed:on the ''~ ''25~ p'o ~ ation.of~:mostly~elderly subjects with~possib~le ~ : ~
~ '~ organic`mental~syndromes~ as well as young adults with ~ ~ :
5 ~ mult~iple~sclerosis~ There~are a number of other possible :~
àpplications:for~:this;technique among young and:older : :~
: :adult populations as well. Possible other applications ~.
:`: :3b~ include populations at risk for deep brain tumors, such as~patients with~a::;history of brain tumor:who~are being ;mon-itored for possible~recurrence, patients with~AIDS who are at risk for central nervous system lymphoma, multiple sclerosis, patients with epilepsy, and other brain ~:
35~: ~ diseases. ~

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. W~93/03670 PCT/US92/06789 :.''' Appllcatiol~_ Oe the invention relate to :: different fields:of neurophysiology. The cordance mapping can be continually monltored during medical procedures such as surgery or in treatment in intensive:5`,,~ 5~ care units. ~Similarly, during treatment of patients :ch~ange~s in the mapping would indicate data relating to~
hhe~effectiveness~of treatment, or improvement or deter1oration~:of sub~jects. The cordance mapping tech- :
i~t~ n'ique:s~;can be used~to~determine or assess the brain in lO~ accident~situations:~or`'~'diseases such as cerebral vascular diseas~es~or~:strokes~wh1~ch may be the result of genetic or eve~lopment:al-~congenital~problems, traumat1c head injury, exposure.:to~toxic:-a~ge;nts~or the product of other patho-~
gen~ic~physiological processes such as ele~ated blood :.
15~ pressures, stress~responses, and arterial blockages.

It~should~be~possible with: cordance~methods to '.~ f:aci~l~itate~diagnosls of~;epilepsy, substance abuse,.
~'! ' ~ y~eneti:c~disorder~s:~dlseases of the kidney or liver~
20~ af~ect~ing~brain~:f~unctlon,~ sensitivities r~elating to:foodand:~odo'r~wh1ch;correlate~with behavioral';~changas,- ill-.`'~ nesses a'ccompanièd;~by~h~igh fevers,:viral';or bacterial in;fection,~sensory~or motor handicaps~which would~ nclude ~'~ 'visua:l~handicaps~ auditory~and motor handicaps, learning '~
~25~ dlsabi11t1es~, psychiatric~disorders, headaches, cyclicalormo~ reactlons,~and other dysfunctions.~

;Th1s~ nVent1on~has application to~any disease ~ :
::: state that affec~s the gray- or white- mat~er of the~::: :' 3~o~ brain, either at the' cortical, subcortical white-matter, or subcortical grey;~matter level. There~ore, patients w~ith:~epi;lepsy who~have cortical or subcortical:~
dys~unction, patients~-with inheritable diseases that :affect brain function at the cortical or subcortical 35 ~level~, as well:as tumors, trauma~ or infectious pro~cesses ; tha~ might-affect brain function all may be~usefully evaluated using cordance mapping. ~ :
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W0~3/03670 PCT/US92/06789 ,', ' ' 38 2 By this invention, there is provided a method, ~' ~ apparatus, and system for obtaining useful assessment and '~
diagnosis of the brain based upon electrical activity.

Assessment Of Activation Tasks Cordance has applications beyond detection of lesions~ caus~ing corti~cal deafferèntation. Cordance is sensitive to the presence o~ brain tissue with high or ,,'~ lO~ low~perfusion~in subjets with brain disease. Since cordance is~ standardized to a midpoint of electrical en~rgy production~for~an individual, it is~possible to detect states~of~h~lgh or low perfusion even within the normal range. Such states of high and low perfusion likely~accompany the augmented flow in some brain areas 3~ during~actlvation~tasks. Concordance and~discordance, uri-g~a~tivation task~s are set out.

<~ The. measure of concordance appears to be '2Q~ associated;with the~activation of speci~fic brain reglons involved~in men~al processing. This is demonstrated uslng~: a hand open~lng;and closing task in a~normal control ;es~bject.~ The~conco~dance in the alpha;~band~for t'his subject~is shown in~Figure 27A, in which~ther is~minimal 2~5'~ concordance~seen in~the frontocentral region. ~With~
opening and clos~ing~of the right hand, there is a prominent increase in concordance in the~frontocentral region on the left, roughly corresponding to the area of the motor strip (Figure 27B). This finding ;is consistent with'previous blood flow studies showing increases in low to this area during motor tasks. With opening and t ~
,,~ cIosing of the left hand, a slightly different pattern is seen, with an increase in concordance in'the frontocentral region but more prominently on the ri~ht 35~ (Flgure 27C3. The change in laterality corresponds with the physiology of motor control; the less-specific ,., ~ , .
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' W~93~03670 ' PCT/US9~106789 ''~
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~i r~ ~ pattern on opening and closing of the left hand could reflect the fact that the subject was right handed.

While concordance appears to be associated with ;5 ~-the activation, discordance appears to be associated with deactivation~. This~association is shown b~ cor'dance' ``''' ~apping of the alpha frequency band (8-12 Hz) during the encoding phase of the visual memory reminiscence and hypermnesia paradi~gm.~ Eleven subjects were studied:
lO~ ~ive were~normal elder~ly controls (COM), four had ma3Or depressive~episodes ~(MDE), and two suffered from early demen~tla,~probably of~the AIzheimer's type (DAT).

Thé reminiscence paradigm is discussed below.
15~ Subjects were;shown slides of pen-and-ink drawings of eas~ily~identified objects, each for a peri~od~of five seconds~ Quantitative~EEG (qEEG) data were collected in synchrony~with~the~pres~entations, for later ~ identlfication~of the~ data recorded durlng each slide `~ 20 ~ presentatlon. The sub~ects were asked;to reaall as many ~ tems as~possible three~iminutes after~presentation of the`--~ stimuli,~ and then~again~after a four-minute rec~ll test and~two~lnter-test~interva'ls. All the'stimuli~presented were~then scored~as~to whether they were recalled ~ ' '25~ correctly~in both recall~periods (a CC rating),~only~on one~-~occasion (~CN~or~NC rating), or neither (NN rating).
Thé~C~C~and NN data~were~analyz~ed, slnce these conditions represent the extremes~of~succèssful~(CC)~and ` unsuccessful (NN) memory encoding.
After both~recall periods,~a post-hoc analysis ~ ~-was~performed and~data from all CC and NN recording ~' epochs were pooled t~ create average cordance maps for ; the su~jects in the CC and NN memory encoding states.
Performance of subjects was rated according to a ratio of the number of items recalled correctly on both recall ,: ,,.~
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40 , 21 15~'~'o '' ~;"Il attempts divided by the number o,r items not recalled on either recall attempt (the CC/NN ratio).

There was;a broad range of performance among subjects in the CON;and MDE categories. Three of the flve~CON s~bj~ec-ts~had CC/NN ratios betwèen l'and 3; wi'th '~ ,the other two subjects~having ratios between 0.5 and 1.
Two of th~e MDE sub~jects had CC/NN ratios of approximately l,, a thi~rd~subject had a ratio between 0.5 and 1, and the 10~ fourth a ratio~of 0.18~. ~inally, the two demented , ~subject~ had~CC/N~ratios between 0.3 and o.~.

Two patterns of neurophysiologic activation were seen in all subjects, that were strongly associated ~ ' ,~l5~with the;degree~of success in performance of the memory task.~ The flrst pattern involved the~temporal regions bil~aterally~(spec~lf~lcally, the T3 and T5 recording electrod~es on the~left, and the T4 and T6 recording èl~ectrodes on the~~lght)~. A high CC/NN ratio ~as 0 '~assoclated with~p~eferential lef~ temporal~concordance in the~CC state; for-~hes~e "good pe~~ormers," the NN state~
was réadily distinguished by a shift to right temporal 'concord~ance ~n~the~ condition. This patter~: ~s'evident ~'"' f:or:thè top thre~e~performers on the~test~(subjects EH, 2~5~ LD,~ and;~LG,~Figures 22A, 22B and 22C).~ ~lso~evident for the~two~highest~performers (EH and LD) is a~pattern of c~entral~discordance, or deactivation (speclfically in~olving the Cz~eléctrode). Thus, optimal~performance w~s characterized~by both a pr ferential left-temporal activation and'a oentral deactiva~ion~ in the CC
condltion The :two CON subjects who performed more poorly had a different pattern (Figures 23A and 23B~. While one :35 ~ ~ - of them (subject MG,) showed the pattern of left temporal concordance in the CC condition, shifting to ri~ht temporal concordance in the NN condition, the subject gU~ l iTUTE SH~T

l6 R~ctd PC~ Q a i~ l99 ~T/lJS ~06~89 i~
41 2il~6~3 also had prominent central concordance in the ~C-state.
The C~ON subject who performed most poorly (subject AS) lacked any features of the successful performance pattern;~ the~sub~ect had no left temporal c~oncordance, 5~ but had prominent~central concordancè in the CC
condi~tion.~

The four depressed subjects, who performed more poorly than the best CON subjects on the reminiscence ~ 10~ ta'sk,~lacked the neurophysiologic characteristlcs of qood .~ test~performance,~and'~had features consistent with poor performance (~Flgures~24~A and 24B; and Figures 25A and 25~B~ Sub~ects CM~and AM lacked left temporal concordance seen in optimal CC performance. They did,~
l5~' however,~show~central discordance, and were able to ma~lnta~in~a~CC/NN~rati-o~slightly greater than 1 Subject SC~showed~left~temporal concordance in the CC condition, wh;lch~was~exagger'ated~compared to that seen among the control~subjects~ The subject lacked~the pat~ern of 20"~central~discordance,~ however, and had a~CC/NN _atlo of less~than one~ FLnally, subject LM lac~ed~left temporal concordance in the CC condition,~but had~prominent~
oen~ral concordance;~the subject reglstered the~worst ' ~ r;fo~mance~of~any~of~the depressed~sub~ects. ~

Flnally;,~both sub~ects wlth dementia~, who had unif~o~mly~poor~ performance, showed a~;prominent pattern of central~concordanc~e~(~Figures 26A~and~26B).~ This~pattern ~s similar to that~ of subject LM in th=e~depressed~group, ';30~ who had the most profound cognitive impairment on clinical neuropsychological testing of any~of the depressed subj~ects. Int~erestingly, subject LM also had prominent deep~white-matter ischemlc disease, ''' sl~nificantly~more~than any of the;other subjects in ~his ~ '-~ 35 ~ sample. ~ Afte~r two months of antidepressant treatment~
7 ~ the subject's mood improved significantly. ~-~~

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~ W093/03670 PCT/US9~/06789 `~

The ~onsistency of the rPsults shows that there are neurophysiologic;differences between successful and unsuccessful memory encoding~detected by cordance mapping. There is an association between certain patterns of neurophysiologic activation (concordance~ and -dea~tiva-tion ~dLscordance)--and good'or poor'memory'ta'sk ''-' ' 5'` " ' performance. ~ ~ ~

These~data are consistent with the nature of ~"~ 10 ,the memory task and~with the previous results on the neurophysiology of memory. Optimal encoding appears to depend on~hoth the~le~ft~and~right temporal regions in ; these~subjects;, but primarily the left temporal region.
This is consistent with the structure of the paradigm, 15 ~ which involvès both encoding of visual stimuli and later verbal~written rèporting of the stimulus. The data could ~ be interpreted as showing that left temporal activation K ':}~ 'is~more imp9rtant~than~right temporal activation for K .'~ successful~completion of the task, possibly~because of a 20~ verbal~naming~and~encoding process that occurs contemporaneous~ly with'visual memory~encoding.

This findi'n~'g coincides with results that a~ '''' ' J
le~t/~rlght ratio~of~alpha power incrèased during tasks 25,~ that~require~greater left hemispheric proce~ssing. Three of~four~depress~ed~subjects lacked the pattern of left temporal~activation~in thé CC condition, and the fourth had~an~exaggerated response. This observation is~
consistent with that dysregulation of left and right hemispheric activation ~specifically including the temporal regions) seen in depression.

,~
,~ The pattern of central activation associated ; with unsuccessful~ task completion also is consistent with 35~ observations in neurophysiology.~ In the res~ing state there is a'prominent "alpha rhythm'i present over the posterior ~head regions, and with cognitive tasks thi~ ~

~ . -~`~
~ W093/~3670 PCT/US92/06789 .:
t~ jO 43 rhythm atten--ates. ~esult~ show that there is prominent alpha concordance over these regions at rest. Successful engagement in the task may suppress this concordance, just as it does the alpha rhythm. Central alpha concordance may be a marker for failure to engage in a ta-sk, ~and-d-isc~rdance a mar~er--fo~ s~cceSsful-engag~ment.` - - -~

Cordance reliably characterizes the perfus1onof brain tissue. While in certain frequency bands, ;concordance~is associated with an infarction, in other bands. Concordance is a signal indicating that normally-perfused bra1n tissue underlies a record1ng electrode.
Discorda~nce is a signal indicating that hypoperfused brain tissue underlies a recording electrode. Cordance is both a qualitative and quantitative indicator of the nature of brain perfusion. Cordance indicates whether normal1y-perfused~or~hypoperfused tissue is present (the qual~1tative ind1c~ator), and also provides information about the mean tissue perfusion and the volume of 2~0~ normally-perfused or hypoperfused tissue~(the quan~itative indicator).

In~part1cular, there is a strong~relationship between mean perfu~sion and concordance in the alpha 2~$~ frequency range thereby providing a quantitative indicator~of pèrfusion. As illustrated in Figure 28 results of comparative data between~SPECT scans and concordance mapping for six different brain r gions in 27 subjects show a high level of agreement in four of the brain regions~examined.

While alpha concordance is an ind1cator of normal perfusion, and beta and theta discordance are indicators of hypoperfusion, the no cordance condition in `~ 35~ certain frequency bands is an indicator of even lower perfusion.

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WO93/0367Q PCT/US92/0~789 ~: 2 1 '~ r3 $j rj U
any other examples of the invention exist each difering from another in matters of detail only. For instance, although the data have been set out as power, ; it is possible that other representations of energy can be used. This could~be voltage, amplitude, or coherence.
'Al-thoug~each of th2~first data~and~sècond d~ta are defined relative to their own base value, it may be ' possible to have a common base value.

10~ Also, whereas the primary frequency domain ~s described as~essentially~a single frequency band of the total relevant spectrum of the four conventional bands from~zero to greater than about 12 Hz, the primary freque`ncy domain could be differently defined. It could be more than any one of the four frequency bands. Also, the~ sacondary frequency domain may be greater or less than any one of the~four conventional frequency bands.

Slmilar1y, the time interval evaluation of 20 ~;4~-second periods for~measuring.data in each ~of the channels~may be dif~erent. In different situations, data from~;a~different~number of selected electrode channels may~be'us~ed to gener~te-the appropriate ~first~data an~`~'" i"~' second data in;t-- dlfferent frequency domains.

Also,~although the concordance;has been~
described~with~re~erence to increases in a p~r~entage pro'portional or f~ractional~value of a~base value,~ it is possible that a concordance value where both first and 30 ~ second data are lower than this base value can be used.
Also, although the system has been described with ~-ref~rence to 20 channels, more or less channels may be '-' used. It is possible, for instance, to increase the' number of channels to at least about 128. Indeed, it is 35 ~possible that the greater th2 number of channels, the greater th'e amount of data will be obtained. This should provide for more effective analysis.

W093/03670 PCT/US92/~6789 ~, 45 j Q DifLer~nt techniques can ~e-used to overcome thé artifacts caused by linked ear reference montage.
For instance, compensation factors can be ascertained and applied for different power intensities and/or electrode distances ln each braln region. This application can be c~mputed into--the absoluté-power ~eterminator-to permit;~
establishlng the appropriate referential value.

The lnventlon~is defined in the following lO ~ clal~s.~

,'~
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Claims (52)

1. A method of determining the electrical output of a brain region in the head of a subject comprising obtaining first data representative of energy in the brain region in a primary frequency domain, determining second data representative of energy in the primary frequency domain relative to the energy in a secondary frequency domain, and relating the first data with the second data thereby obtaining a value repre-sentative of electrical output in the brain region.

2. A method as claimed in claim 1 wherein relating is effected by determining the first data and second data relative to a selected base value and wherein when the first data and the second data both increase or decrease relative to the selected base value, a concor-dance condition is indicated, and wherein when one of the first data and the second data respectively increase or decrease relative to the selected base while the other of the first data or second data, respectively, is oppo-sitely directed relative to the selected base, a dis-cordance condition is indicated.

3. A method as claimed in claim 2 including providing a selected base for the first data and a selected base for the second data.

4. A method as claimed in claim 2 wherein the first data are compared to a selected base value of the first data and the second data are compared to a selected base value of the second data thereby to obtain respectively either the concordance of discordance indication, and wherein the discordance and concordance is established in the primary frequency domain.

5. A method as claimed in claim 1 wherein the first data are divided by a selected first data value, and the second data are divided by a selected second data value thereby to obtain a normalized base value for normalizing the first data, and a normalized base for normalizing the second data, respectively, and wherein the first data relative to the normalized base value of the first data and the second data relative to the normalized base value of the second data yields concor-dance and discordance indications.

6. A method as claimed in claim 5 including employing a selected percentage of the normalized base value of the first data as a first selected base value, and employing a selected percentage of the normalized base value of the second data as a second selected base value and wherein when the first data are relatively less than the first selected base value and the second data are relatively greater than the second selected base value, respectively, a discordance is indicated, and wherein when the first selected data is increased relative to the first selected base value and the second data is relatively increased relative to the second selected base value, a concordance is indicated.

7. A method as claimed in claim 2 including obtaining a quantified value of the amount of departure of the discordance indication and the concordance indication by determining the amount of departure from the selected base.

8. A method as claimed in claim 7 including mapping topographically the quantified value over the brain region.

9. A method as claimed in claim 7 including having multiple primary frequency domains and including mapping the quantified value for multiple primary frequency domains.

10. A method as claimed in claim 7 including displaying a topographical map of the quantified value in a primary frequency domain.

11. A method as claimed in claim 7 wherein the primary frequency domain includes at least one of a beta region and a theta region.

12. A method as claimed in claim 1 wherein the first data are obtained from energy measured by selected electrode channels, and locating the selected electrode channels strategically about the brain.

13. A method as claimed in claim 1 wherein the first data are an absolute power, and the second data are a relative power, the absolute power being power measured by selected electrode channels over the primary frequency domain and the relative power being the distribution of power in the primary frequency domain relative to the power in the secondary frequency domain in the selected electrode channels.

14. A method as claimed in claim 13 wherein relating the absolute power and the relative power is defined by the combination of the absolute power is relative power such that the relative power at a selected primary frequency domain is equal to the absolute power at the selected primary frequency domain divided by the power for the secondary frequency domain.

15. A method as claimed in claim 1 including comparing the representative value with a selected base representative of the brain region and assessing from the comparison the physiology in the brain region.

16. A method as claimed in claim 1 including diagnosing from the representative value the existence or non-existence of a brain lesion characterized by at least one of the disorders indicated by dementia, such dis-orders being selectively multi- infarct dementia, Alzheimer's disease, Pick's disease or a demyelinating disease, selectively, multiple sclerosis.

17. A method as claimed in claim 12 wherein multiple channels are obtained by locating multiple electrodes over the head of the subject in strategic locations about the head, obtaining data in an analog form from the electrodes, digitizing the analog data from the electrodes, and subjecting the digitized data to Fourier Transformation to obtain absolute power for each channel in the primary frequency domain.

18. A method as claimed in claim 17 including obtaining a relative power for each channel, such relative power being obtained by dividing the absolute power in the primary frequency domain by the absolute power in the secondary frequency domain.

19. A method as claimed in claim 12 wherein the energy is measured by the electrode for each channel, the energy measurement being obtained with reference to at least one other electrode located on the subject.

20. A method as claimed in claim 19 wherein the energy measured by the electrodes for each channel is obtained with reference to multiple electrodes about the head.

21. A method as claimed in claim 1 including normalizing the effect of a selected energy distribution in the brain region, such region being selectively adjacent to at least one of the ears of the subject, the normalizing being effected by determining an energy measurement of different electrodes relative to data of at least one other electrode.

22. A method of determining the electrical output of a brain region in the head of a subject comprising obtaining first data representative of energy in the brain region in a primary frequency domain, determining second data representative of energy in the primary frequency domain relative to the energy in a secondary frequency domain, relating the first data with the second data thereby obtaining a value, representative of electrical output in the brain region, and obtaining a brain map of the representative value.

23. A method as claimed in claim 22 including obtaining a normalized base value for the first data and a normalized base for the second data respectively, obtaining a selected base values from the normalized base values and obtaining the representative value based on departures from the selected base values.

24. A method as claimed in claim 22 including comparing the representative value with a selected base representative of the brain region and assessing from the comparison the physiology in the brain region.

25. A method of determining the electrical output of a brain region in the head of a subject comprising obtaining first data representative of energy in the brain region in a primary frequency domain, determining second data representative of energy in the primary frequency domain relative to the energy in a secondary frequency domain, normalizing the first data, normalizing the second data, selecting a base value relative to the respective normalizations, determining departures of the first data and the second data from the respective selected base values, and relating the departures thereby to obtain a brain map representative of electrical output in the brain region.

26. A method as claimed in claim 25 including having multiple primary frequency domains and including effecting mapping for the multiple primary frequency domains.

27. A method as claimed in claim 26 including displaying a topographical map of the representative values in a primary frequency domain.

28. A method of determining the electrical output of a brain region in the head of a subject comprising measuring an absolute power in the brain region in a primary frequency domain, determining a relative power in the primary frequency domain relative to the absolute power in a secondary frequency domain, normalizing the absolute power, normalizing the relative power, selecting a base value relative to the respective normalizations, determining departures of the absolute power and the relative power from the respective selected base values, and relating the departures thereby to obtain a cordance brain map representative of electrical output in the brain region.

29. A method as claimed in claim 28 including obtaining a topographical map of the representative values in a primary frequency domain.

30. A method as claimed in claim 29 wherein the primary frequency domain includes one of a beta region and a theta region, and the secondary frequency domain is selectively at least both of the delta and theta regions.

31. A method as claimed in claim 30 wherein the absolute power is obtained from selected electrode channels, and locating the selected electrode channels strategically about the brain.

32. Apparatus for determining the electrical output of a brain region in the head of a subject comprising means for obtaining first data representative of an energy in the brain region in a primary frequency domain, means for determining second data representative of energy in the primary frequency domain relative to the energy in a secondary frequency domain, and means for relating the first data with the second data thereby obtaining a value representative of electrical output in the brain region.

33. Apparatus as claimed in claim 32 including means for determining a selected base value, the value being selectively normalized, means for relating the first data and second data relative to the selected base value, and means for determining selectively concordance and discordance conditions of the first data and second data relative to the selected base value.

34. Apparatus as claimed in claim 33 including means for determining a selected base value for the first data and a selected base value for the second data.

35. Apparatus as claimed in claim 32 including means for comparing the first data to a selected base value of the first data and means for comparing the second data to a selected base value of the second data.

36. Apparatus as claimed in claim 35 including means for quantifying an amount of a departure of the first data from a selected base value and the amount of departure of the second data from a selected base value.

37. Apparatus as claimed in claim 36 including means for mapping the quantified value over the brain region.

38. Apparatus for the method as claimed in claim 36 including means for selecting multiple primary frequency domains and including means for mapping quantified value for multiple primary frequency domains.

39. Apparatus for the method as claimed in claim 36 including means for displaying a topographical map of the quantified value in a primary frequency domain.

40. Apparatus as claimed in claim 32 including electrode channels for location about the head and wherein the first data are absolute power, and the second data are relative power, the absolute power being power from a selected electrode channel over the primary frequency domain and the relative power being the distri-bution of power in the primary frequency relative to a secondary frequency domain the selected electrode channel.

41. Apparatus as claimed in claim 40 including means for measuring the energy by the electrode for each channel, and means for obtaining the energy measurement with reference to at least one other electrode about the subject.

42. A method as claimed in claim 1 including applying the representative value and assessing an activation task from activity in the brain region.

43. A method as claimed in claim 1 including determining from the representative value selectively the activation, deactivation or absence of activation effect during an activation task, such task being selectively at least one of a motor or memory task, or cognitive processing.

44. A method as claimed in claim 22 including applying the representative value and assessing an activation task selectively from activity in the brain region.

45. A method as claimed in claim 2 including applying a cordance value to assess an activation task in the brain region.

46. A method as claimed in claim 2 including applying a cordance value to assess selectively a motor or memory task.

47. A method as claimed in claim 46 wherein selectively the cordance values in an alpha frequency range are selected for a memory task, and the concordance value in a theta frequency range is selected for a motor task

48. A method as claimed in claim 22 including applying the representative value for assessing an activation in the brain region, such activation being selectively a motor cognitive, perceptual, emotional task or cognitive processing.

49. A method as claimed in claim 48 wherein the representative value in an alpha frequency band is representative of a cognitive memory task, and a representative value in a theta band is representative of motor task.

50. A method as claimed in Claim 1 including applying the representative value for assessing perfusion.

51. A method as claimed in Claim 2 including applying a concordance value for assessing normal perfusion.

52. A method as claimed in Claim 51 including applying a concordance in an alpha frequency band for assessing normal perfusion.