Method and system for predicting deep brain stimulation parameters

Abstract

The present disclosure relates to a method for suggesting personalized and symptom-specific DBS stimulation parameters, comprising the steps of: creating a three-dimensional symptom network library comprising a data-driven three-dimensional model of symptom-specific tracts in stereotactic space created on a detailed and inclusive pathway atlas; registering patient data with the three-dimensional symptom network library for analyzing how a single patient's electrode maps to it; deriving and suggesting stimulation parameters as a function of a baseline symptom severity profile in each patient. Another object of the invention relates to a system for predicting DBS parameters, the system comprising an interface for providing DBS parameters to an electrode and receiving signals from the patient; and a computer programmable unit comprising a data storage for a three-dimensional symptom network library comprising a stored data-driven three-dimensional model of symptom-specific tracts in stereotactic space created on a detailed and inclusive pathway for predicting DBS parameters.

Description

[0001]. – e oenvenon muaoenresenarsacmoesuerrse. reaeso a meo an a ssemorrecneeran reescron oe reae ar sease.eneeraans semcuaae,o rensearcns an essaseeraorereamen oarnson’s e eecs o onsrueran newo erxsereonrcnn e a a.aram sowars sun enn an caracerzn suc neworsn smom-sec,c manneorn anox, .oersonaze. r couavee wa sease o anea ssu revaoaumocn nzueceuresamen os ane essaeases aesreea mmoesn crorcarnson’s seveomenoownenroucon oevooa.owever, wee ecaca osorc oan sm eeocmss o sunca as arnem oor aenr axraa smnesoamsasaveeene esena vasraee,n e rvanenomnczuen cnecarmreansa1, ee–cs o, eecr,can, sm. eua a.o,n. uneuerro ce.racn. crc,ums–ance,craer,. e a.euroo , e noona, we, ae .ssurer emasze a.,ron.um.eurosc., , exnrsa wor-weave unerone ea-a,. e ose no aceve sncanomarnovemroemnsarer cncaras, aroun, o smoms reeeusc,. e a.,.n..e.,n–ua, o.ee,ncee,s wee moor- aensenerom, no aoves-mos,. e a.,.euro.eurosur.sc maanr . – ar,ee–orea, a sm.onme rse oasone couseasee.oar,n csuarrnecne,n, aoc-ara,n a r ceooron was surca wneoseroaeraar oe nuceusene recman an sunaesaree suc aseeanneean,.-. e a.,.eurosur.,–r,caanmars smuaons auseosoeraveurn rorammn aneurscsn s.moe seccarameer omzaon exsn cncaraccesuc as swcnoo m- orreamen oremor, a moreorou anaarven mo rsa conacs omzaonssacn.urermore, semene e eoraen-secc smomea are curren emoe, manerorammnecrrooceesss wncre uasno sx coemen ceoxn.acser mrove cusn,care rcesseonseeonn s.mvoemnc secc neworares aearsoe a wao ase ’s, wen mecuou eor smom-secc newors sansac asar w secc s anases oeson sues reveae newors causanvove . eson c,ar.na. semuoms o asser e a.,ran,–, creor,. reur scoo o sereoaroxna, –, .ornsance,n semna wor e a. concuea oma conrse on aaon caseseween an ,asser e oaurerane, o oremornvoveesonn aooeween cereeuman nuce wc sen axon coaerasoe re nuceus ons waoeoseror .sn v cenonroroasra, csonne.oc.o.ns anromrmaaru mmooor ceo arnexerora nsuscereu es v ae.n,ran,–, a sureon oe suemenar moor areaene eo rooras.o.a. an areaa were assocae wmrovemens asserromann scoo as an r .ucaer, moern neuroma nonec smoms suc asranesa emc e a. assocaea n wor cou conrmo conces,ornsance, cereeoaamocorca cr rnsonan res an,e, aconremor w e urr.euro.eurosc.e.cu, e a.,nn.euro.,–, emc e a., newor man,s coue, conrmeurman er aam., eran,–, .sn conrmemrovemensnranesa an r a., amon oers, won aon remoor areas anrerona corex oe reaeo conneconsrom .. e a.,nn.euro.,–,ram. e a.,euromae,,-, rozer, oma onuceomes o oeseorranu caorues oronvorovme co sencreeauaeznu r eeacae s omveroam orn s cmrcuoms-, . – cusseeransooew eon corencusseaosnes: asr asn, ene neeao mra an aeccrueraaee an mouan a secc crcu. crcu moen sereoacc sanar sace.n ree-mensona smom- acemen coue reaeo suc a mo ce esase,aen-secc eecroe aen:eaenresene wreoeermne oma smuaon sensor eac maxmze mouaon oe emor-omnan smoms, sens coue auseo ua oe,e wou remor crcu.onverse, axa smomsrmar aece ecomeosseo e auseo maxmzemac one axa crcu.econ, ma swc everreameno severa sereae crcus w a sne eecroe an sn oneren conacsor comnaons o conacs – anoena usn comex anmu unaeornneussese a necesseren or aeuuoemncaees. meso wsouo s rueneesr sarmameoemr- coces smuaon sens. secc arameeurs ose a..auesne sna,o, scoses a ssem an meoor omzn a rreamen o aaen.nrecn oma acraumreeer rse,suonncsvoenao ar sawneeana ascronssu a mnuo a-rmeencsoorna ssaerm,eunconaranaa arameers.asca mercs oran r ameer sace o one or more aaor one or mores o esonse are exraceromeunconaran aass accesse, vaerer vcoxoer ss oseme,raan co vmaresesresceaosre- ssseecm,c anra an resounnsecona erverom reamen a oma arameer sensor aura oseas meas neurooca conons.ne or more oma arameers arerec s or ase one sasca mercs oran resonse ane unconaeoreaen ssem. aas vaerecor aaenu-sescec ne.u.rosauernerar,eo,caon. reea sessoem a s resceemv an meoorenn aenancuesracs an neworsneaenran, esranmanaaor a aas comrsnouaon-ase, accesses auanave connecome comrsn aa sease-secc srucura anuncona connecv mas enerom aern oracs an newors assocae w an omaare areaocao ouaon oaens, aneneseaen-secc neurosureraremannaasaeo orn ae coameanrs aonneeweaene arn oaerranc os ane nreacwsor ans a nsesowcoares wromeeran . – coennneceomreo amase comouraseso an oseaasee-nsseneuanave connecome aas.euanave aroveenmeneso arn cc,ouaon-aseuanave connecome aasm ea ocmaseasaerneoecaoounaoorn oreamaeenns a.ssocae w a maxma cnca orerauseevere..a meen ,, reaesoecnuesor moeneraes se oeraarameers anc reareesvencess w areereescerrae. wacroearaaeerom moeeesraase on a evernera accornoe se oeraarameers.er ssem useunune mocaon oeraarameers.s oae moes mae comares an aormc moe o ae ne exame, arocessoreas oneeraarame raeo a reerenceerae an auss a aeas oneeraarameerearseon ocnreaese co anm oarersaonn. es anoer exame, arocessor auss susana mananne moeeerae. cenc oeera ssem wememeunes meeo..aancen acaon scoses a comuer- aserverom anass ou aesu sraorn o a vaoeunmse. oaesnsuea aacsv raecoenveor aavae srucure eaenaa reresenn an assessmen o aaen co naen, evauae reaveoeaenaaoeerm non.e aa srucures eraeuc eecorevenaen. ne aare or acevn aesre ummar oescosure smom-sresc ascec o semuascoonsurear raemaeeso a meoor suesnersonaze an mensona smom n ers, comrsne ses o: crean aree- smom-seccracsenw soerreoacrarc s coamce crrseane a ona aa-eraveen anree-mensona moe o resernaenaa weree-mensona sm ncusveawa aas a sneaen’s eecroe maso om neworraror anaznow uncon o aasene smom severreorvenn a enac suaeesn.n smuaonarameers as a ssem conmorers one acn onereacneveonrorno rveaneso a ssareammeoerrsreo acnn eecroea arnam reeceersv,ne . – srenea-smroemnsoneaa smeno an a comuerrorammae un comrsn aaa soraeor a moe o smom-secmc nerawcosrn srearreo coacmcrsn a soreaa-rvenree-mensona awaorrecn arameers. sace creae on aeae anncusve romeo oowern aseecas,eeauersecsr, ano an,v samnaes oeusrreasennnrveeneraone ar eem reaome anarenmemenaons.eresennvenons aso ca s an s severaeas c ae o oer aneren emomens an sr an scoe oaneere mseonnevenno vna.roucsco orvnous resecs, a wouearnrome reare asusraven naure, an no as resrcve,.erawonnas o anecess acnrons areoe envenon we seorscrnoanr onr meaesecrearnoen avanaes o romeescron, ore wcracocoew os anennveanr won.e ovous reescron oeures emomeensn avnen aosnec ws oeeenscrease onures. we unersooae no venonescreneures are on exames ano anmer eeuvroaeecnsv.e sc woe oe une cerasmoosn aane waa.envenonsene e camsnvenon cane comne w aeaure o aerenure ass oec on oer a asseeccs o or e omeomen oe oenvenon,n wc: r emomens sea.rae sowos er a c en eanc exe re om o vear ar e aeeec o cnerno coeerosr oacem aeen, weren acve conacs are vsuaze coor, on nscoeverros coecovre, cwooo cren.res o vaaon e.. sows smom seccracsn a saa vew an mane aeeve o rac.sre seow osueor s smaaom co-smecarsconr.acs searae ae eve we oer . – ew.een sow asnea seurme,aoonow on s am smomars r wosron caunarecosearowraona conrnaecenon.s . sowse corca orns o errecroecons. as w.e a ssowes corremcaorrraocescnocnsureomroercmoarns mroomor ceor ceerxeeoar nuc.eoaamus e.eun scouwosornacnse a nsusocceause re won. axa smomsncue aransem connecono a.s c sononwesc soenresarnven axaa smanom nosno oaer axemas s vsm. aom ose.rems reveas so.oca sow asas a comuasrseono eroecon se w a macn scerom a euroanaom. ouome an coeaues ronersn sec.c sracows.s a smuaone o e sameaens sownoeer w smom-rac.s ass socowase an w examoeaaen’s s-mumaroonve vmoeunmse.s sown aonsee oma o.arn ssoonw’ssseea ssemnome sseccovecrra ccoso arss.ocae w mrovemensn smoms o.arn ssoonw’ssseea ssemnome s vaecaconra ccos aosrsocae = w mrzruorve,me =nsn semno.ms coo.r an sowesree ccoerremaornovemoensewaseenre emcercameroscvoevmeerns conor va.aon corr.eaon cuoseracesen a raenwceoeun esoma weer aen ea ecmaaon reresens a earman’s sensn one o e eecroes. one-se-recsas sn-canm,ruosvermaennsoar . – e.arm.an's re ro ecssoessv uese across mosaens =., =.e-,verae =.mrovemenn avenaeno r,e wreseene ceo snmacu caoosn conac a renerse es aue ecse, corresonn smuaones are sowennoree m exoamese m eaercero wes. was. ree saoew,sue smsomm seecc max omae mo wee:ne anarassneecen orreaons across sensne sa smoms. wa eecroes were amos a osve wene moe ros uese woen es usmnaemororevemcenmsrnora nesamrovemens,u sncaneseweenewo moess sncanve.men =s.n r, =m.rove.mens. are- was. ree saeowse smom secc o e moe:e anassecen a ,u sme maxma we n r smoms.orreaonsocr eosssm seaenmsnroveeme eecroes were amos a osve wene moe was use usn orecmronvesmenn rsnramrnoevseamemnsr,oveume snnscan roe wen ewo moess sncan., =. , =.. . are-eseween san.ar s oow csare see conmsa arnsonee swmeeunaoen samraumaeeornseanraemraeeersroenerae rom accornoeresen scosure. me meo a sn.e s smowusa a wone v-ouamcee, saan eaura om converrsec ao snamoem-rsonecccrac ese.croe w . sows a oecauure conce w a moern eecroe. . sows an exame re-racromeawa aasase ne. o cr.eaeee scmsaom neewroocresssra rre.eae across a reracsneawa aas . – cros.s-va saowese s esnmerac moeconoroa moormrovemens wcs acvaon oerac.an moormrovemensne-ouaensase oner our.mes soowrs ea ac mo srem eaomoraraec s amnom-seccrac moe reeassroceure smom. we esmaesasenenenses o eac me.o o sowesrnes aenn examscoesu are n.ove oecaaen wosreaease one sr.uo sno ows co sraresacosn o vvaeruesorer-aoons cro oss-v-a caroosnss vanaeoons.eane: conrase wesruon o correaon vauesor-o cross-vaur-araocns mnoe snerac moe.e meane secese corr e mrovemen anre eaonoeween emrca secese correaocnemoroveewmeeenno ermercour-rac moe.e r ane mrovemenn - vauesore sneraca momerovemen anrece . sowsranesa an r racs vsuazeoeer. rom. r sow caevems .roeveemaeens a anna vssce a veerrsa reressn ouranesamrovemens anaom oes no sowuaave canes on an eaeescron oescosure urer seececc enmcaormoenems os soevenvenoen.neenen cams.eeenen cams cover reuenc,euersme w smu,auornsarreamueenecrs, r aemaeuoe,e a numer ouseserurs,use ura o eecroes anacemenocaonor aeas one enec croome.neusesrou a . – scorn seseemrmo ‘rs asmsesosmn scosreea’s ree saeveso a suse oemsrom a vaae, rerouce measure sever,reuenc ec. oremeror w ann reseon mseooorearra o.oer unnsaence,aremnssa sease ran scae - wou consue aremor ‘smom on’s emseore an aer sureror une score’.anesnese s acorecameroove smmenso.mse ocecrumrr ‘nsmn mormov secmoerne’s v s ws. oren co rs.en meaonnns w ooue rereaseeno sscmosoumre creane arerseeen-msecnossounrea crorvcues m ao meeoor ansea as se sseemc acn ams a manroress e moen a meoo sues oma smuaonar smoms an everan asene smom severroen eacaen. ameers comrsn auncon oe ranens eax,e rnson o,ae m aone remaunrner a sxereaonnoour smom caeoresremor, com...oreover,e c a smomsaseen exemareveoe osessve-comusve-sorer, wonecree s camnoem rseaave aeeen seor oeaereseoase os, suc as comusons, anxe,eresson, conveex , anoaunconn. sessons, romree moaeen wa csoeovreso oe aeccornoeresenscosure an cross-vaae onaa =,ern com.ae scover coor=,rzur,=mseram an coor o vaa ewoaen coors oe vaaon coor, oneaen coo on coor aneverosecveaens. aensnescover omnrr uenceornwaen eecraoeersaer-oncore waa srmnusoan’osn acseavsaee usnour conac ecroes wereocaze an acve conacs noemseres. aens..nca scores resene suaamc reon across a anca across aaensa an averaenearnsonsease ..neerz-uasene score o.. an meanmrovemen o. wasnvesaern coeorm,seeram a-nern w caos aonras,s rees,e wcevreeascoem co.nvaeneona. . – Aim DNB / fSem caelentre Aygeears D Diusreaatsioen U IBIIaPsDelRinSe- L reesvpoodnospea U ImMPpeDrdoRvSe-m OIIeIFnt L reEdDucDtion P imosatgoipng OMPFoeFid % nts D%BS ONF% D CNois=hc1oo2rvt9ery E omstablishment mfuoldteislymptom W44ü / r1z2burg 680.2.4 ± 142.5.6 ± 4192..8345 ± 6118..84± 49.3± 24.861.4 ± 25.1 CT B5e1r / l1in875670.9.0 ± 130.9.4 ± 3182..69 ± 5137..52± 45.3± 23.052.8 ± 41.6 M 4 C5RIN = Amsterdam 50.53 ± 12.7 ± 47.03 ± 68.8± 46 41.82 ±TN = 6 34 / 8 9.8 6.1 15 .9± 15.7 CT V 93alidation V .5 26.1 38.17 cohort IN = R m seaplildicaatitoionn o &f W52ü / r1z9burg 539.9.22 ± 10.84± 42.46 ± 62.39 ± 46.37 ±50.94 ± CT myuomldtpeitlom B4e1i / 2in0g 675.1.9388 ± 48. 3.1 .88 757 ± 156 138..2065 ± 157 12. 5.4 .64 351 ± 252 12. 5.2 .63 153 ± 32 ± 23 M 8 CRIN = 33TN = V c =oa 1hl0iodratti IoInN M R Vonopolar Cologne 61.54 ± 9.72± 44.2 ± 22.7 ± 27.99 ± 34. Syeamvliidpeawtotimo Dnat oaf: s s1ti0m / 4u;latio 1n869.15 3.03 17.5 14.5 648 ± 11 CT S mpecificity ofettings P f crospective Proodseplective Würzburg 60.6 ±14 ± 449.8 ± 62.8 ± 65.4 ± 12.0557 5eoahsoibrtilitNy = A Clpepalrictuantieon of5 / 1 4.98 22.1 15.87 7C3l.1ea ±rt 1u1n.e8: ± 24.43 CT ae.emoracnormaon verson oor creean a sramcoorma new aoarsrare accrooorsn,oeresenscosure, an exene –, was useoene anaomca conn.ec. e a.,m..eurorao., meos wc was vaae exensveeraure conronsrom anoe see nersseconserormen coaoraon maon an weneverosse, erern meoaermann,.. e a., w exer neuroanaomss.snenvesae wcracsncueneawao. asasc coarrrea,–, , was ranesa, r ,remor, an axa smomssmom nee wmrovemensn neworrar ma conser oerracs wc are rea worrar.e smom smom neworrar caneesnencaon secec.o oer smoms soae . – suc as,neerreseernn casse a, masesa-rumnavna’rsa raen a cororraeca wceaso sasca coecens conneceoerou o smuaon vou on coecensor eacraca mue comars mes.orreaon coecens were correceoreve o., ano onns us snnecanenraamcsn-aoc surverveec wnereu reeaanese.scosv sern race a an ^^- ers reveae asnc rosrocauaraen o smommrov an se oeve ..moran,e sameraen was reecemens ae suaamc suesn a “smomaoc” arranem e acrosse enre newor, aosuaamcroecons.e rosrocaeno wn errecawas ano was conssen we ore ua orer onrecroeconsromaum aove.. rn oerreccorcosuaamcnns menone oserorr-macoss as resocoane o we mroemororm.rovsem exenecsero,ercemeorrormacsrmar moor corexoe ecussan cereeoaamcawa.racs assoca aonancuee romre-uemenaroorrea an sme w r mrovemensroece anerorar oe suaamcremo arronaremoor reonsoe a assocae w or reon.neweeneremor an r racs,racs anerooseror axs.mowreovveerm, wense oraranesneasraac ans en axerae srommome mse overae one , axaracsermnae asaera asecseenses a surace oe anaera aacen corca reons.xaracsn. –o ornanrom ransem conneoeeuncuoonne nuceus u rreeorn.ncue a conneconoe sows sm.om so swesc a scmracosmn-n ae swaora vraerw a acncornoeresenscosure.. smom seccracsoow a rosrocauaos mane aeeve oe.e occaoseror,oowe ranes eroronaraen wremor mos sncan aer correc a, axa smoms, an r . sownracs are arenroxmo onnor mue comarsons ..soe noeaeracs sne we-ac e anoer, manosseo mouae a – or mos oem w a es oen caea eee ocr aoeevwanc m aanreesa w mo corn scma exomesreonc soe,m weeerer aee s.ne smuaon . – veavea weerr on resen u oo se arnrac. ors, earceee s sm omuo oom mr- ss saec ecac c cor rmac acas .r asroen v ..sunasez sse o re se wsresaera ene a ser-eoe cross smoms wnnrecawa conneconseween anaum,oown aaon o rosrocauaoseroronaraen.. sowse corca orns o smar roecons.racs assocae wremormrovemens orna errec oe corex, wereaseracs assocaeer wsersem enermar moor reon ornaeromremoor reonsn a moren arosveomne.nsnonec smoms comarsosn ms.enoonuesn,e ass oracss s moowne wnase.se areur sencan aer correconor mueracs were sueceo aermuaon an r.oo so,rs, smom-secc sncan exane more v ass.ere, aueremorrac ane axarac ermunmro arancen oucomesan re-cacuaerac moes aer were s vemen vaues acrossaens, mes ..econ,rac moes amounus oec vearaonce-o we cnro ssus-veaceaoons.-oan c,ro ass-vuaaeorenmsorrarac enxesaane sncan . r o =ms. ex,ce =r.emo arx caou sme coamcsua = : =., = we a sm e. on,e =u. co, aosro, seee ana.s.s orrceamor,nmcue on oe aens,ven aensa aaseneremor scoreeow or rourove wc exans wremor moes, aeen sncan, were no as anass assae ooerera recssr wceen snu aec meannoerermau sancoen oar creonsss-v waoauon suesn.eremor asene cou o course nomrove muc even smua sanaremor a amrove couaveoenamroveurere mo oremream, ane ones eenresen, aasene.e samessueoes no a oe o ors wouave acora srucure oe aneseaseaso see meos.er smomsvene , sream.ne ss aoswsoscaee an waommcar voavemaenons o o are smmoronmcu neew coerreeraor-.asam sownn. oeer w corcaroeconsrecse ornanromrmar moo cawas. ese exac conneconsaveeen wemcae wremor a r corex., eraureasser e a.,ran,–, ram,. e a.,ceross aareo oe oenen,.. e a.caeurocr.en,–,uromeamec e, a.,–nn,. . – raecurso a.ssoc,a–, emc e a.,ran.euro.,– .mar, nuc e w axamrovemensncue aransem connecon conneoe aeurs reon..e as serve ase mosromsn smuaonareorea azoems – wc arear oe axa smomrou – aou w varae success venzones e c an.c,eurosurer,, rnzo,. e a.,ran, –, .m a reevance, wasese weerese connecons coue seccoa axaro svemmenomosrn wcouuee a a csosnonceaceon wew aee anxae smoomse.eraucnscu asosoconaene w na an sereanea secc smomsrome axa smom soweaaueceus, an res - connecon. .nce msrove a axa smoms an esecaaroems ..aroe mosroemac smomsorea w awans,..,ov.sor. secc vavu.esnor.socn.n, wa–, onne e a.,euroo , –, , assocaonseween anaom ans o moseorvreu.ncuornserm.eo.r,e a, seesce rces ausssoc aaaonn maecwenownmrovemens ane reon, wc mauaave vaaeeresen resuseunrear.oremorrornn,n.s.n ee a a. sxa.ree neura susraesorranesa an r n conras e uro.,–, , wcoes norec mac exoeree o searaon wc waseneeween r anranesaracs.o an vrcee-vesrsuar aner, r reeaemer aonvaemsens,s w wecre reereossee o saumero smereraaen reessuasmroveme.ns mue-come aars roenssu,s w saoswnurner ex.ore wer we seaesrcae en sren mocan aer correconor smomrac woue aeo rous esmaeoa moormroveno eacnvuao cross-vaaons.. sowss anass.oo so emens wen sueceo one o os.en,eour-rac moe wa ,aens were ranom assne ou one-o oaens.muaon s serave recacuae, eacmeeavn es oe ouaens were o esexresse eecrce vecor manues,- omaracseac exresseverae wearerac moe an mue we weeeanoer scoresor man’s ran correaon assneo eacrac, weease o eac smuaone an eac smom.en,ese esmaes were severeremor anaseener,eoeraveer s scmoreosm or sconrae enacromaeneraemor.e.r,acor w aerea ween we . – morerec seron.ro-mms,ro av semnenes c uosmnn aenearer m socoere c eamceurae, wc was maeo o os.rca,e moe no see anaarome onerann se.e., esmaen eaceraonsee meosoreas.eee-ouo wc was sncan correae w reave-oue e-rror:mr.o serecemrovemens aens =., =., mean as vemens. em.rca. o.serve across oa-e same- anamssro wvaesm reenesa.es c aanere c saecuan a sneracarec coeor o wener scores ornan enn.,s moe was smer.nsea cacuaeerae rom eac smom-rac, a sneer score was monrneec rea n,rec conor- -mrovemens.s snerac moe co mmcsrevous wor, wc ame aeermnne oma srucura rveu,.r eo a.eoeurroomaae moo,rmrov,emen.nornre,c. co em aa.rsnonn.oeueroo.u,–, moe,e snerac moeerorme worse =., =., me r-smom . ....enesn across mueeraons wan asoue error: correaonsase one mu-rac moe were snca sueos, snerac moe =., = e-. n erane onesase one n anoa-voen aa s cron, w ss vcaaansa amen onac ca w oreno c ae ru raees o nuuse.a eer see mo creo a,ce r re o es aunan ssors- wo oas r cero eessa v mea u waon --o ., a =n. =. an, = =..,. =., res rac = . ecve an snerac moe =., = o samne a saecaosen o vaa reonro sseec, wvee usaee onur moeo esmae cnca oucomesn an ou cenersurzur =,e s warnson’sseaseromwoeren coor was aeo s n =.e smom secc moerane onescover ..uaave,necanarec oucomesne vaaon coor =., = coor was smaroeswas wc correae w smomsne vaaon we as cereearracs assoccoaveer w coorre.moarmmer,o cvoenmneencso.nsxeaw seemnom ane as correae w sreamnes aacen aneroroow mrovemens r mrovemens anrerona reons.e e onesa assocae w . – accornooaeerees venerscrsosu sree wsasoweavreo ane a caacaeo on mna cxmnczan sracmucea,one meo smomracn noveaens.s meo accornoeresenscos o eer surroae omzer an suess smuaon sensa areen ure emos a anaoousoe mu-racrecon anasses useorece oucomes aen’sasene moor scores,e m cre aove.onsern annvua smuaon voume overas eo seeso omze conacoson maxmzn exac same we reevan smom-seccracs.n conseuence,ereem usoer seove ur eec a vsro e.e sue aa sxceame onsmn oa w rromu aeenn.ea seur mo neoer e ae scncao s nre onns eon re a seraea sseee ,nn w assceors eu.re., cou roeeveos overeears. smom aens wo vaaeerse o mue oo sa amccoer vnaoaone croesoernscosure, wasrs aeo a omaarameers,ase oneasene s e rerosecve cooro sues wereen comareorounru momroes o eacaen.roose sensmrovemensna cncaarameers.os-ocess reveaea cnca recommenee sensor wce meo accornoeresenscosure aensn ame conacs were sncan errom cncamrovemensor con wce meo accornoeresenscosure recommene eren suaecs =., =..rca, acua cncamrovemensorearameer vensoen rse mroaseecve nea muree oo aec ccoororn,oenceerses aennasssconsueres o coue nroecev oane en va.n oer wors,recons o oucomesorarameers s e moe accornoeresenscosure were comareorecouese e meo arameers. ns o oucomesor cnca scoverv ceonore suocceressuc r semrosoecve vaaon oe meo, we aemeo a our revewaaonoor,oom seccnenaens wo unerwen monooar w oucomes assocae w sne.ecca,eseaensa reeaeaaons m – mor un se eemuaon o eac conacor a rane o amues,rom oucomes w cs arose.ereore, acrosseaens, aoa o cncaoreceenreer maae avaame.rovresm,ene mneeo va accaoronn cooore,r wesenc wsacsosousrev weaso urs ae . – wuas oosvee eec =ro.es.,er =eo.ree,- a on.e soarm eace s-emsu oaoen se-vanue,s aracrossne eecroesmrovemens were avaae searae.oesor smom-se esa an r anasswo moremes, eacme maxma wen eerracc, we reeaee mu-rac moe.e moe weeore correc smomenoes san or r ne correaonseween esmaes an emrcamrovemens ac can er ore correc vs. resecve oer smom .oro arnoasss seesnsn ea acn ee.croe acaoonse,s w weeeseer meo sm acucoaronnaorameeerresse sunesscosure coueeasen cnca resenscosurenveaens. sows eecroee e meo accornoe roocosresenscosure vs.ana ocazaons anewo smuaon e mu-rac moe.nre,rom ar oareooeer werrac overasrom meo accornoeresenscosuraese sene o.. -ons, unere ..ner sanar o care sens, sconres, scoresmrove ..ons ..nour oeveaens, senseos amreorvemrovem.e .ons. e aen,mrovemens were comarae vs.onsmnroano sens.n oeveaensreerree meo accornoresenscovemen. ereewoaens,ese senseo se-eecssnesa sure overo sens,n .s emaszesae curren moe wasurernaen anzznessnaen se-eecs, wcs a cearmaonor cnca acvenmrovemensan no or se-eecs soue aeoe moenuurea.racs o avoancea coe eweene smuaonarameersenera aems.. sowse comarson arameerseneraerome meo accoernromo sanearrese on caresc seosunre.s ane smuaon o smoem-sreseecncsrcacossurneresensorersmee use o aree-mensona moe anncusv sereoacc sace creaen aaa-rvenason on aeaeo cross-vaeaaonws.a as aans. exaemsec,o asuoress soew usseaasse senm soowmn-n oenw aor snerarrs rous cacuae onoa -mrovemens.ase oneenerae moe,a ac moe caae o suesnersonaze an smom-secc smuaonaramee meo creae on aens anremnar vaae wnescover coor anrs was eren ou o sameaasesvaaon coor, = an vaaon coor, on =wo . – rroemsenvescoesruerne w ceenreerrso.snecave,e ae se onnvse suaeensse.sme mroeveo m acocornoe wen comareoe cnca sennour ou oveaens. or smoms corr e resusrove eresenscosure suore noonaeren newors seeasaee. wamem,ro wvaesmeonsss oe caor senare sameoema csaaeaonresanaaem eox-acmoeorarnson’s smoms arrane aon a rosro-cauaraen wne se rca mooroo zone oe. enerserse on a cor nsormoor-remooruncona reomnan ornaeromere caeve, eac oe smom-seccracs connecon n corca reons.urer,remor conneconsncueneranssermom. cereear nuce we axa smomsncue conneconso reon oman casnme moroaunaoe canree anenson a saecec resraucs.oe nreo w seure ceosnsaer one smom eween connecons, mos eseca on a corcaeve a ae overas aosuaamcroecons.ne oeran,roecon zonen aonenrecnuoe seemeue sereae – ae ver coseo onse oerreccorca s coue seen as oose cnca exerence:n anoer. rsance, mouae man smoms a once, seemn w smaree,e same sen can no conc weresene resus:aso nens.owever,s noonoes coseo eac oer, sannn acros e emaszeaeneracs are ver zone oe eve.s s a reon o mmeres wne sensormooruncona smuaon voumea m . sows, a sne we-ace eecroe marouce a owever,. ouaes aeneracsanence smoms, smuaneous. eecro sowsoena use oerac moe w a moern-conac semene onroeecsunco aos,esosnocn scmenuaco mno voeumaerse csanae. acsnvaeu aonenee saemneen eecurrren eac w eren amues anreuencesmmermann,. e a.,anc oe, –, .neoeca exame sownn., one cou seer oene veouro., reuenc zoeremorrac an a secon oowreuenc zouem aex o aracoreaewo smoms as oma, asosse. a rs, seemnecne,ee e reescuros oes aeowreseonr anscnocsreuares cnou reoneenarecsecoonm oen c wnceare ex reacevano: . – moecuso ssm wuaoenc voomuemnes.senssaeaeso aone exero,so.n e o a.a,ramoeve.r sace weremanueooceazaer,on.s ee ac.omannce ever m.oreearecs,e e,–eere,sen.scosurmasnor m.e,os a–n e,ecroe smom-neworrares suc aseresen eroves a meoor usn one smomeman o eacaen oneone-une smuaon senseenn resusoeer,. e a.an .s wacaerosecve vaaons oresen scar, .econ, wece a sne. smeauao, e–e, ao,. e a.,o. e maor oeneracs, m s n se o a we-ace eecroe can cover an no aeas areace oma. maer wereeea oe smuaon reses suesoons oeve somoms-suercerc, arooa-roam-ceoenrcse.erocreoscsess wa asownsroouc see, wo oan smomsa areorevaen anurensomeor aaen an wc au es o maxmze smuaon o smom-secc newors.orn sarameerso w a smomroe o acaremor-o sance, one cou runerocessowernens oranec-r smomms,nanaen w nens oremor anareeremor conneconsromrmar moor w corcex w aonu ceraevoeuru sme.nsa maxma smom-esecresecnracssc oonsureroosesors use normave connecvaaoene resun smom-rac- aroueve.ex,aenaas saa resere we e acuaersonazaon orare ao arnoaaczeaeosw aac sen oneeaeevne’ os e secmrooem ms,a ussno a c.oncen, wc caneerme neworenn,n e e easouner,. e a.roressn anuroeuoo , ouner e a.,oocascar:onveeuroscence smomro nemwaornso,e–, .e concesoen – or we –eenen annvuaarve a an oma smuaonareore smomroerevaenmmeaeeeacoen.ran sensn comne w macneearnn m rove neworaresas e ssema cou auomacanormerocesso swcremor uner se onenvua nee oeaen aeme a smom – suc as cou oen newress – emereser,. e a.x.euro., , .nea,s connecomcs,owoarrzosn asnon anvnuearzaeonr oec asoan mveecne aecrnooacoo an smn reoam- smeec.c . – mensonna con ccrcuuson m,oeeroersenseassec soseucrecro svmesom as m aenos w usecos suasees o snm auareoe- ararmeoeveerr,s coemrerssenn ascuonscuroenn oroue n o cesa ase mneeo sm caoame se overeveraronens a moaeeno. smureosve s cmncoam o-suceocmecs s anmuaaoenn saarasmaecerosn.or rorammn, wc ma umae wo unoerr sweonwne- eecso or aa mrensoon’ asccorsenaseoer wesenscosure, aens scover coor. ese, werereaenern,nrezreu rerosecve sue aen caracerscs anemoracaa arerovenaer. an nmseram mom - ems aesan an sanarevaon o ranesa nera a ene cnca scores oea an asene: an moven an m.. e a an rovemen: an –oean an. .. rre n aenc, r. arm an,asene: m.rov. .emen: remor remor r . an es arm an,remor reseasene: neaccornremoran an m.rove.menresoe: reemoran an . . conmsoarncaw xa o resremor. orssuer cear asene: a m.ro. osura s vemen: oeezraa . . -rn onesaao ae:ascs o cnca scores an su scores across coors. . – eraens wereaeramane wwouaroar eecroesmoe ec onc,nneaos, .e su was carre oun accorance w e nvaerrasonsm oezens.nur aenrm woraes, ae mroeveoroseecnsveu aona revew seonars oase oanr– rerosecveaaaseoveaens w wo unerwen surer ae e osa rzur.s acaon was arove ensuona revewnovers nvers rzur. ar o seaseercaennaecmaerovemens- meas wureere cacuea meoorasear oenearnson’s reoerave anosoerave scoresv oneerenceeweenreamen oucome e reoerave scores as a measure ooa u mse.mrovemen.s oorer-zurem cos woerr,e sem revarse cacua veersoan r oereeseneou-r m waaosr moovoerm senm, roams anern:arna anneseaems,,, wc measureneran,an r e a emsoean were avaae, e ms wcrem moeasure r oe nec, arme,remorems an o resaw an con rems: osuraremor, necremor, remor , sanc o resremor were avaae, an axa smomsems,, were a wc measureosure,osura sa, ana emsreezn a were a cvoamanea.ona o s acor aexsae smmso amns w wouereeusreear snemes-.ounne a su-anass, as suscore aeasenea a sanarevaon.. anass,remor e oer su score vauesae.aens wre ons, wen comareo anoseaens womrov mor scoreseowwoons aasene, anases. eo reavemrovemen, were excueromremor aen-secucs aneacoramcraeoaerraesv.eos-o scearansv weere, aaceunres eurn cnca rouneoene scannn =oocaze eecroes. er unerwen = or –, eecrooes wereocaze usnea- sowareorn e a.,euromae, revserooco o vrner,s. n,..,euromae,–, oownencuenear co-reoneuorer e a.,euromae, , .nre,s oos svanss era ao.,n oeo.sm-a anerneao.era,ve–ma,es us.no-revansceereomrmaaesza weorne . – een normsaze anrooace weecovne:neoawrsarmanmceerc su“cor”cae rmenaemee snacero usn asmemenenea- wer,. e a.,euromae,–, .e reoco o eacre-rocessn se were vsuansece an rene n sus errorsnarcuar were revse ecessar.ormazaon euorer,. e a.euroma usnearrve moue avaaenea- eecroes wereocaze usnee, , .oownre-rocessn, euromaen.,–, oranosomo-vaaea aroacusc e a., manuaocazaon meoorosoeraveerave ore meo or ,–, . aaorn,. n,..euromae eecroeo es-mease weere s cmuaon voume, eecrce vecor manues aroune snusn acuae.s wasonease on aour-comarmen mes reons wereerane an wee maer a, easecroe conacs, annsuaears.ra maer n wer,. e a.euromae,–, . , aa cre,e verson oeer-moeneorwer e a.,ome.n.nne szeom waans reernes uesneeo soeveeraee saracoourrm-cuomaoarnm oen meesa.ace euaon on a neworr meaann an a anarooamcceasavnec uusseveaaa-wrave ana csononree sucorca reon:ue weemanaseracora aermann comeserveromuson- orn e a.,nn.euro.,–, -a e e a a.,.,or.scar,–, a.,a.ommun., , .owever, esecanane su,aa–m, e aases oenac accurac eseca rearnnro c reon,ese aoaamcroeconsansa anasccu econunes, suc ase cereeoaamcawa usencuares,ner’s comers ore eersen e a.,eurons eroos e a.,m..eurorao., –, euromouaonoc , -.e, oecer e a.,euromouaon.n. a.,euroo , e.–,e–,,.o ovo e a.ov.sor.,–, orn e e conce o manua cu ercomesmaon, aeeveomen was aman e a. raeawa aasesene usnror anaomcanowee , v, ,.raesneaa,se–s co,mrse mearacnuo eus a., curave.naa.wamsr ano. areeencoe.reer,om– . – aaasese-sossvae croancnsecaonsavera ncoseaenoe none exsneran.owever, oneownse oese as c e anaomcaeam can aso noeene concruscaonsorn success os-oc use oe aas.s coueaoase-neave aaseneo seeeenrracsa exsneran.ornsance, cerane mos accurae euron, -sen.e e, a.,ac,sunes suc ase ansa suaamcaeersen e a., connecons, amon oers, sme ccoanunseec aonseween an or sraonraracs an canno exausvencue aran anaomcaeam musocus on a numer o receves corca errecnuromecs enare exrosnaneran.urermore,e , saacs e a.,ron.euroana., , w ccoresx noe re,rease.nommun., awa aases.o overcomesmao enca e n,ere, exsn aases eroos e a.m.. comurorea coo.mr,sn c–orca, an seersen e a.,euron, -.e, were mssn conneconsase on anaoumccoarcaaaaaweas.raversne suaamus an ae en ctoceaton omet neam aneatomca ename ene ase on - nsaentcuars a44nexureoratn see44entoantomst’s o 4unato , 457o,4r6e atans: - eanstcccuuaurss en44nexureoratnatomst’ see44enton s ounato , 45o,4re atans: 476- ranteartoorn taamc atr48– . – - reancttatorurotaamcrtt-48–– – - reancttatorurotaamcrtt- resent stu –– – - oenn-ecussatn nrtt48– – racttatorurotaamc –- uenaeoreran m48–c–- toutoauasmac nuucseus senso-rmo-tor44nexureoratnat see44ntenrsnoursm co omst’s se ontonrectoenrs oenton , 45uo,nrea attoans: 4746- toutoauasmac nuucseus- assoc-atv-e44nexureoratnatom see44nterncuast cvoenn st’s asso ecetrosn oenton , 4unaton 457o,4r6e atas: - toutoauasmac nuucseus senso-rmeo-tor44nexureoratnatomst’ see44externusm cootnonrec s sensor teorns oenton , 4unaton 457o,4r6e atas: . – - toutoauamc nuceus- -e-44xert see44externsaus assocatve neuroanatomst’s assocuast cvoennecetrson oeunntaton , 4457o,4r6e atoans: - extoerunsusa tous senes-ormo-tor44nexureoratnat see44sutaamc nuce omst’s connecton us enton , sensormotorers o 45uo,4nr6ea attoans: 47- extoerunsusa tous ase--44xert see44sutaamc nuceu socatve neuroanatomst’s connecton s rs oenton , assocatvee4unaton: -457o,4r6e atas tutaamc nuceus -49– coon sunecsttaonnta nra - atwaroecton48–– atera––- ntoernuussaus - resent stu – neucuenucsu t coo ononnetctnoe s n aeccmorenntat toon50- nuecuenucsu toooontunse - resent stu anua aus connecton entons . – - nuecuenucsuoontne - resent stu – connect toon - nuecuencuoontne - resent stu – conneucst toon - t nou uceta euusna ccm ouc no n neou ctncte onnues - resent stu s aeccm- orenntat toon50- ortcosna tract cst resent stu roetor remootor 5n 1sene a mtasra –n m sancuea- eaemnscus m resent stu eannuatons- urocortca tract rcot resent stu eannuatons- urosna tract rst resent stu eannuatons- urocereear tract rcet resent stu eannuatons- uroovar tract rot resent stu eannuatons- a croena toroman - resent stu necton52ortcatas oomra –tosensor °tex° ,°,- area to conrnoecmtaonn - resent stu ortcatas – . – - area to conrnoecmtaonn - resent stu52ortcatas – - area to conrnoecmtaonn - resent stu52ortcatas ee –ersonta - area to cornonemcatnon - resent stu52ortcatas aret –a croorntteox- - area to cornonemcatnon - resent stu52ortcatas cortex –nsuar - area to cornonemcatnon - resent stu52ortcatas anuteru –nea cnuoarte cortex- ar toroman - resent stu52ortcatas –orsa coenanecton anteror onrteuxate rneunea nteruor ortexate- a toroman - resent stu croenanect aonn52ortcatas ront –anerruosr aeracsenene revse verson oe racora aas. . – meooossn us ceonnoec corenase noe rerressen veersonn a on aeas a waesr,e ceascuaeoowne same eroos,.. e a., meurorao,,cr.eren, uea esewereemaee,.-. e a.,euromae,–, comeromsnar acuson eumanonnecomeroecanssen,.. e a.,euroma ans o seesenerom varous aasesae were useo maere, –, , e asene e aas,wer,. e a.,eurom conneconso anrom s a resu,s revse verson oe racora aasaeero,o–, . m..eurorao., –, consss o a more exausv s,.. e a., rom anoe. e se o connecons eru-erranc cmonceemennaroonuc oenaerermaenrnn:eresen meosu uone , an exenen,. e a.,a.omm,u.n.. e, a.,,o.scar,– assocae w canes across mue moor smomo osoaeracs meo was useou exemar a “smom newmans..ners se,smrovemens o cnca suscores orrar” assocanracs w cvaon oeseourr orremor,ranesa, r , an axa smoms.nc ac ses correae wmrovemensn resecve smoms.oe nuuenoerar, eacracaoassrouow numer o-es. ooa snmceer w oas-neense ao a ex racuereracseaa wneernes no o sron. mmomu.aes co annsra snme was se u a awcneor cou s oan correaon vaues su-resouaone correae w cncamrovemens.anne arrar cos nenses an.mm e..,o an mm nouaave aener v raesuuess. -es earman’s ran correaons wereen cacu .or eacrac, correane resecve su-s aeor eac smomrou searae, sreamneassero core weea amue o eacaen’s-e aven correaon coecens,u w.c wser measrse-sunovaera ae a a-vroaauceea.s aoe ar correc nuomner o ran comarsons usnease-scover rae . or mue ersrosmmaen res cuncamrovemensase one smom neworrar:o cross-vaaonesnnra ocve sreas wnere- useeso o esem-aoeu canceansm wrov reemseencsven s am-oom . – reaacrns.neree,.eneurmener n oumoerss we.as., se =o a sncess a sanar cocene macne sncan resus. n wereroe an ee smar, wcearna,c eacaaasrs oracs an-es wasuane eeanensrou sron assocae wem, mrouvemene o a seec-vca suem assomn.eoor eacera-ceu,voesne vracs were averae resunn a meaner scoreer sm aues wee easene scores o smo om an-e.cores wereen oeremorracn eacaen woumesr aevareeanernm eacacane an.aesn a r wesu, mreooumanaonnremor. mrovemesnse.oe ar c scoomresn weereeurr sceorr mea coenoor aaen-seccen o smom usn anear moe aeoe res emrovemensn eac smom eac smom wa ecverann coor.erecemrovemenor averae meo, wseeren eraacns woremeosee nroermcaezeasene smcorreovoermena sm a woee excueeoss o a ranom assnmen oaensnoera m.on a sncan resu cance,eroce n- anes-se resun weren eaceraon resuen a ranomss as wsasnmeerane o oa-ens crnosos vaeoaso.n mes, rar: meeroeseno susceossureroroosersam am mneoara cmaeaerse oase su onesne smo smm newor arameersase one smom neworrar ..e meo uaon omzero conser aosse monooar s uses a surroae eecroe an esmaesmr muaoneswn a raneor aven escr ovemensor eac oeca smuaonee same wa as sescer aeov eea.rer,ernac rasn msareec weonseo, eenere s mmoso emc sacous smuaon sen. aenreerence.ornsance, a ever,aenuren or aensurene ma sron we maeu onremormrovemen erexma remor, or a sens souor secc suaonsn wc^mor soue suresse.eaeeowescrese aormnea. . – ^^ =. suc^a^−^m c ^^^or^c =^^m^o^c =^conacsearuneorm . nuem oerm oz rearnaormam saemers,e es.o. cree maxmum numer o sames,e mnmum .en ae a surroae moe,e oecvem, ec. .naee cuinrrenounssee. . woveneite currenroouemnsoro cirneita.e necessar, sovee aona ranom sames .nvesaeearameer s a surroae moe. a.anom same aace usne surroae moe unconaaancreosu enxoreanocnum oeneareameeser se oserve usn a mer e surroae.e same w ace an mnmzaon o .ovee roe e smaes vauese aave same. c. aencumen am neworoe aaa mnvme suamm.ee. a,n mn remnueme surroae. v error or maxmum . aanaeaeu seams onservsee.rsoneenn one rae o success o aave sames . ev consvernceunmceesn rse.aceeoree maxmum numer o oanusa.e vaues sowerane oecve vaue, reseeraoscnasr aren ru an, auaeve eseeaes meo o w aasrsn exaem mneeo anoe same rerosecve coor,uoese.owever,s meo was no aonw ae crencoae sse nn,veaens wererosecve meo over an exsn meos. on-neror or sueror os rovnnoeerre ocece o smeuareosennarasmceoseurrseos e ae scsroemes.orere sscn arameers an rorammae un w aaa sorae comrsn areeem- cmomensrosensa a c sommuoemr . – nne sweoreroacracr s caocme crresane aaa-rvenree-mensona moe o smom-seccracso reseraenaa w on aee careeae annreceu-svmeenasownaa. smeom nseuwrorer conrarure anaznow a sneaen’s eecroe masoorervn a or oreaen’s smomroe. n oma smuaon voume e aee vna annearraamcee oerseav seseemenor eeeccreoeos m oe aeaeena wen’s reuremen,e can surcamane.s ovousor a see caveeenrevousmanen aeas one rsona aeas one eecroe waveoe eecroeseenmane r.eoen e oecreoersa mna as wee se asmeneree m eaecroavees ween aura o smuae morean onerac. c are aeo us e ssem maurer comrse auseeneraor wcs reureoreneran reveosuosr so.as aeso ernevscaeearaameeeruss oeeneer sasore maaveeen surcamaneneraceoeuseeneraor wcransmseusesmo we aeeasra onnsee erreecroreo.u e wcs a senesoor s sensseem an marac asoe sarna os wec s asreemra ancscmorenoee srseesmenscosure ssem ma asoe useoeecncomn s unsaesor .e sensor soaaenaas aan wc cane romreec enec oromesz aenrovaerameoerse. reseneeororueronescron oereerre emomen oenvenonaseen menvenonoosese o exaucsroarmon asncoseesc,r ano mno.sca noonnseneoe exausve oro oe aoveeacns or mae ac an varaons areossen aseen cose ureromracce oenvenon.e emomen acaon, sona anoseesc sreeon exea anr mear unseceesn oveneonnvnen vaornou ansracca suaeorearcuar acaon.sneneae s s emomens e aene cams aner euvaens. coe oenvenoneene

Claims

. – . ara mmeeeo or suesn ersonaze an smom-secc smuaon -rsr, re c eaom e-nr m asn ensreoen-e am se mens os o eon:a o s smmomom ne-sweocrcrararc csomnr ssn aaa-rven creae on aeae ereoacc sace - esern aen anncusveawa aas or anazn ow a sana weaene’ree-mensona smom newor rar - semrvnom a sneve sruersone sn emaucas aon eec ena.rraomee merass aso auncon o aasene. come mreseo o cam, weren crean eree-mensona smom newor rar -s - een sne ss om coenenremcns snm cuoo armre-s oae n voc onu cc moeerac s wcsen asno cra enaces snm a somm-somec scocrrac wc - eeermcnenns. sncan smom-secc e co racs correcn e correaon. roem m aneoo oe s cuamaa,m wce nruecneuse.nn smom-seccracs reaesoawas. mero mveemeons on craamnes oar, r, w,erreemnor,e an s amxuaa somn voomusm.es correae w. we m meuoe o c aonm oanreso ons c uasmnseo,en wamerenn-oec corerreaeocnn coeue.cens are correce. – . rea mre coom ors aen one o cams o, wereneree-mensona smom newor smom reonss c aomourr-ssnmreommor n,erwaornesraar, r rean ano axeao sumr caormns.a moor. rea mreso va oa ane onreo oro c raemsseron, weeareenneaar wee-m.ensona smom newor. sme moem-ose oc ccarmacs,. werene smuaonarameers are sueseor eac o e. scoere mse areo co ons anere on aes oar ca omseaoen wearae.nnvuaaen’sasene smom . come mreseo max om anzn on se om cams o, werene suese smuaonarameers racs. uaon voume overas w e resecve smom secc . aream meeerso co ons aenrs s oeneme one ca smmsuaoon e,ec wroerees.n e sueson o smuaon . n se mmeoom oro anes onne oe caamensaoaor, s wuereesnn we smus oao snmaroammes aerres. consere . een meeeo s om anom o-snee oc ccarmas o , weren normave connecv aas useo w cs on aroueve an saa resern aenaa aen’es e reescurone marese-om.ensona smom-rac-rar o anaseow a sne . sue mese aooca oo anno orn ae oac cemaemns o eoecr,o weserernoroe s surmeura.onarameers reaeo . ss -em anornereraccenorrovanrameers,araem seseersmo co amrsn romeaen an n eecroe an recevn snas. – - am coenmsounear srmoroammm naeweor unr caomrsn aaa soraeor aree- mensona moe o smom-secrc coramcsrsnn ser aeo soacrec saaac-ervenree- eae anncusveawaorrecn arameers. creae on a.aee snseama o w came,r wee-eremnenseo cnoam sumerormo nreamwaore unrars coonr anuarezno reser sneaen’s eecroe maso. ow a. ane s suseems o e s c n.maumaon, warearmeenerse a csomuerrorammae uns conureoerve n eaca auncon o aasene smom severroe.uese sss wemc o ar aenro ovnee o caromus a coonne,c coomnor asna aenu’ss aeeeansera onoer eoercreoneer.an.race snsem o s anna osn aen oo craomrs recevon s, conmasrrsomn a a saenesnor. ssemor sensn an. me -ooonrnecenrea am sense om moorvemreencnsorers, caormamresernsoe a sees o mane eecroen aeas one r as one surca - n arameersoe aeeoans o o aaen’sran rom a movemens ne eecroe o aaen suern e orer, werene arameers wererevous comermrsnne aaa c-reravenn aree-remee-nsmoennasona smom newor rar n sereoacc sace moe o smom-seccracs reser creae on aeae anncusveawa aas anaznnoawene aaaea ws onee eecrereo-em meanssoona s amom neworraror e arameersoe ae as aun nervn an suesn roen eacaen. con o aasene smom sever

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