Supplememicroelecrecordedfelectrodeselectrodesmicroelect

entaryFiguctrodearrafromasinglonthearraonthearratrodearray

ure1.Prograythatwasemicroelecayduringthayduringthchannelsdu

ressionofsnotrecruitctrodedurinheseizureinheseizureinuringthese

seizureactitedintothngaseizurena.(b)Averna.(d)Multeizureina.

ivityrecordeictalcore.(b)Averagragedmultitiunitraster

dedfromae.(a)RawLgedhigh‐gamunitfiringrrplotover

aLFPtracesmmaoverrateover

SeinacrrhKasa(Tdc

Supplemenelectrophysntervals(IDadjacentECocorrespondiightoftheIecordedonhistogramsaKullback‐LieandECoGareizure.TheaccordinglydifferentcoThedottedldivisionbetwcoefficiento

taryFiguresiologicalsDI)foraseizoGelectrodengcolorsfoIDIplotsthrtheMEA(dareagainshebler(K‐L)dreshownabseizureinwhasahigheolors)duringinesforeacweenpost‐rfvariationo

e2.Inter‐dscalesandazurerecordee(orangecioreachrecoroughtime.dottedlines)howntothedivergencesbovethesehwhichtheMrK‐LdiverggasinglesechcorresponrecruitmentoftheIDIs.

dischargeinarerelatededfrompatircles).Ictalordingmoda(b)IDIsfor)andnearerightasdotsbetweendhistogramsuMEArecordigence.(c)IDeizure,withndinglycolotandpre‐te

ntervalsaredtoseizuretient5withlhighgammality.AnIDIrallictalcorestECoGeletted(MEA)distributionsusingthecongwascurtDIsdetermihIDIhistogroredECoGerminatione

econsistenestage.(a)ItheMEA(b

matracesarhistogramreseizuresectrodes(soandsolidlisofIDIsrecorrespondintailedisshonedfromearamsagainselectrodeinepochsoccu

ntacrossInter‐dischablackcircleseshowninisshownto(differentcolidlines).IDnes(ECoG)cordedonthngcolorforowninpinkachECoGelshowntothndicatewherurred,based

arges),andan

otheolors)DI.TheheMEAeachkandlectrodeheright.rethedonthe

SupplementaryFigure3.Alternativemeasuresoftravelingwavespeedacrosstheelectrodearray.(a)Meanmagnitudeofthevelocityvectorquantifiedoversixrecruitedseizuresinthreeepochs(color‐codedasinFigure1).(b)Meantravelingwavespeedquantifiedoversixrecruitedseizuresinthreeepochs(color‐codedasinFigure1).Asterisksindicatesignificantcomparisons.Barsindicatestandarderror.

SupsynshopairofEand(c)seizprinthedetforandmic(gra

pplementarnchrony.(aowninblue.rsofmicroeECoGandmdCwererecThreechanzureasinAncipalcomppre‐terminerminethetheexampldmeanamocroelectrodeay).

ryFigure4)TheendoMedianmuelectrodesisicroelectrodcorded.ColonnelsofLFPandarepreponent,acronationepochslopeoftheeseizure.(duntofvariaesimplante

4.Large‐scafaseizurerutualinformsshownbeldelocationsoredelectrorecordedfresentativeinossallECoGh.Theblackevarianceed)Scatterpanceexplaindintheicta

alepre‐termrecordedonmationformlowforthesforthepatodescorrespromECoGencreaseinvGelectrodeskdottedlinexplaineddulotofpre‐tenedforeachalcore(blac

minationinnthemicroemultiunitevesameseizurtientfromwpondtovoltlectrodesdvarianceexponthegrideshowslineuringtheprerminationhseizureinck)andout

ncreasesinelectrodearenttimingare.(b)Recowhomseizurtagetracesiuringthesaplainedbytdshowninbearregressire‐terminatiincreasesinpatientswioftheictalc

nLFPrrayisamongonstructionresinAinaandc.amethefirstb,duringontoionepochnvariance,ithcore

SupplementaryFigure5.IllusoryhypersynchronyinlowfrequencyLFP.(a)LowfrequencyLFPrecordedfromgridECoGelectrodesduringadischargethatoccurredearlyinthepre‐terminationphaseoftheseizure.Eachcoloredtracerepresentsadifferentelectrode.(b)LowfrequencyLFPrecordedfromgridECoGelectrodesduringthefinaldischargeintheseizure.Eachcoloredtracerepresentsadifferentelectrode.

SuppcorreacrosoccurrateothesabetwactiviHistodetertermiof0.0

plementaryespondingsstheMEA,r.ColorsranoneachchaameMEAcheenMEAchitypeaksacogramofp‐vrminedfrominationdisc05.Allofthe

yFigure6.Tmultiunitacoloredbyngefromconnelina.Mhannels.(c)hannelrankcrossallprevaluesforWmtravelingwchargesfromep‐valuesw

Travelingwactivitydelwhentheirpper(earlie

MatchingcolHistogramsdetermine‐terminatio

Wilcoxonsigwaveslopesmallseizureweregreater

wavesacrolays.(a)Exapointsofmer)toblackorsindicateofz‐valuesedfromtravondischargegned‐ranktesandmultiues.Thedottrthan0.05.

ossMEAmicampleLFPd

maximumde(later).(b)ethesignalsforWilcoxovelingwaveesfromallsestsbetweeunitactivityted‐lineindi

croelectroddischargesrescent(greeNormalizedswererecoonsigned‐reslopesandseizures.(d)enMEAchanypeaksacroicatesacriti

desandrecordedencrosses)dfiringrdedonanktestsdmultiunit)nnelranksossallpre‐icalvalue

SupplementaryTable1.Computationalmodelparameters

Parameter Notation ValueInputresistance 1/ 125MΩRestingmembranepotential ‐68mVMeanmaximalintra‐networksynapticconductance

60nS

Meanintra‐networksynapticconductancereversalpotential

‐30mV

Extra‐networkfeedforwardinput 0~3nSReversalpotentialofextra‐networkfeedforwardinput

0mV

Synapticdepressionconstant 200msSynapticdepressionratio 0.6Meanmaximalfiringrate 100HzSpikingthreshold ‐42mVSpikingthresholdstandarddeviation 4.5mVSynaptictimeconstant 25ms

SupplementaryTable2.ClinicaldetailsfromstudypatientsPatient(Age/Gender)

1(30/F) 2(30/M) 3(32/F) 4(19/F) 5(24/M)

ArrayRecruitedintoictalCore?

No(penumbral)

No(penumbral)

Yes Yes Yes

MEAlocation Leftsupplementarymotorarea,3cmsuperiortoBroca’sarea

Leftlateralfrontal,2cmsuperiortoBroca’sarea

Leftinferiortemporalgyrus,2.5centimetersfromtemporalpole

Rightposteriortemporal,1cminferiortoangulargyrus

Leftmiddletemporalgyrus3cmfromtemporalpole

Clinically–DefinedSeizureOnsetZone

Leftsupplementarymotorarea(includingMEAsite)

Leftfrontaloperculum(includingMEAsite)

Leftbasal/anteriortemporal(includingMEAsite)

Rightposteriorlateraltemporal(includingMEAsite)

Leftmesialtemporallobespreadtolateraltemporallobe(includingMEAsite)

NumberofSeizuresexamined

7 3 3 1(MEArecordingcurtailedduringpost‐recruitmentepoch)

2

SeizureTypes

Complexpartial

Complexpartial

Complexpartial

Complexpartialwithsecondarygeneralization

Complexpartial

Pathology N/A(multiplesubpialtransectionsperformed)

Nonspecific MildCA1Neuronalloss;lateraltemporalnonspecific

Nonspecific Nonspecific(nohippocampalsclerosis)

Outcome EngelIII Engel1a Engel1a Engel1a Engel1a

SupplementaryNote1

LFPsynchronyincreasestowardtheendofseizures

WeobserveddecreasedMUAdesynchronizationovertheMEA

(SupplementaryFigure4A),andcorrespondingdecreasesinhighgammaoverictal

coreECoGsitesinallfivepatientsleadinguptoseizuretermination.Weinterpreted

thesesignalstobeindicativeofaprogressivedesynchronizationleadingupto

seizuretermination,whichisincontrasttotheincreasedsynchronyobservedin

previousECoGstudies1‐4.Inordertoconfirmlarge‐scale(centimetersofbrain

area)pre‐terminationsynchronyinthecurrentdataset,andcontrolforthe

possibilitythattheseizuresexaminedherehavedifferentdynamicsthanthose

reportedintheliterature,weexaminedsynchronyinthebroadbandLFPrecorded

acrosstheECoGgridsoverlyingeachMEAchannel.Synchronywasmeasuredina

similarmannertopreviousstudies1,5,byexaminingtheamountofvariancethatcan

beexplainedbythesinglelargestcovariancedimensionusingprincipalcomponents

analysis.WefoundthatsynchronyincreasedacrosstheECoGgridspriortoseizure

termination,consistentwithpreviousobservations.However,thisincreasein

synchronywasapparentonECoGelectrodesinpatientswiththeMEAineitherthe

ictalcoreorthepenumbra(SupplementaryFigure4Band4C).Therewasalsono

significantdifferenceamongpatientsinthepre‐terminationincreaseinsynchrony

(Mann‐WhitneyU,p=0.12,SupplementaryFigure4D).Theseresultssuggestthat

previouslyobservedincreasesinsynchronyaredominatedbythelowfrequency

LFP,whichaccountsforanexponentiallylargeportionoftheECoGsignalvariance,

comparedtohighgamma.

SupplementaryNote2

ComputationalModel

Wemodeledmacrocolumnsofcellsintheictalcoreusingameanfield

approach,wherethefiringrateofatypicalcellwasusedtoapproximatetheentire

macrocolumn.Cellsreceivedintra‐networkrecurrentsynapticinputandextra‐

networkcurrentinput.Thetypicalcellmembranepotential,V,wasmodeledwith

thefollowingsetofequations:

∞

∞

∗ ∗ D ∗ f V ∗ ∗∗ D ∗ f V

∗ D ∗ f V

Where istheeffectivetimeconstantforchangeinthemembranepotentialover

timeand isthesteadystatemembranepotential.Inputtothenetworkofcells

wasrepresentedwiththe termandrecurrentconnectionsamongcellswere

treatedasintra‐networksynapticinput,whichwasmodeledwiththe ∗ D ∗

f V ∗ term.Inthisterm, andf V standformaximalintra‐network

recurrentsynapticconductanceandfiringprobabilityasafunctionofmembrane

potential,respectively.Firingprobabilityfollowedthefollowingerrorfunction

1

√2/

∞

Synapticdepressionevokedbyrepeatedactivationswasincludedinthe

model.Becauserepetitivesynaptictransmissionsinthecerebralcortexhasbeen

foundtoinduceshort‐termsynapticdepression(STD)6,theeffectivesynaptic

strengthDwasmodeledwiththefollowingsetofequations:

∞

∞

11 1 ∗ ∗ ∗

Where representsthesynapticdepressionratio(i.ehowmuchapostsynaptic

potentialisdepressedfollowingaprecedingpotential)and representsatypical

cell’smaximalfiringrate. ∞wasobtainedbyassumingapre‐synapticPoisson

spikingproperty7.Notethatverysophisticated,biologicallyinspiredmodelsexhibit

similarproperties8.

TableS1showsparametersusedforcomputationalsimulation.The

parameterswerechosenbasedonexperimentaldatafromlayer5pyramidal

neurons9,10.Twoexceptionswerethemeanmaximalrecurrentconductanceand

averagereversalpotential, and respectively.Thevalueof waschosen

byaveragingthereversalpotentialsofGABAandglutamatereceptorsinorderto

modelbothinhibitoryandexcitatoryintra‐networkconnections.Thevalueof

waschosentomakethetypicalcellsdemonstratetonicfiringwhilereceiving

maximalrecurrentinput.NumericalresultswerecalculatedbyXPPwitha0.1ms

timestepusingtheRunge–Kuttafourthordermethod11.

Thecomputationalmodelwasthusestablished,anddecreasinginputwas

appliedinordertosimulatetheeffectsofaprogressivelyweakeningormovingictal

wavefront.Thevalueof wasthereforedecreasedlinearlyfrom3to0nS,with

seizuredynamicsbeingreproducedbetweenapproximately2.7and2.2nS.

CorticalreconstructionandECoGalignment

Corticalreconstructionandvolumetricsegmentationwasperformedwith

theFreesurferimageanalysissuite,whichisdocumentedandfreelyavailablefor

downloadonline(http://surfer.nmr.mgh.harvard.edu/).

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