The 8 pani sb JoLlín al ol Psychol (>gy Copyrigbt 20<11 ½Tbc Spanish iourna[ of Psycbology2001. Vol. 4. No. 79-lOO 1138-7416

Doeste WisconsinCard Sorting Test MeasurePrefontralFunction?

FranciscoBarcelóComplutense Univcrsity of Madrid

This revicw describes a roscarch program aimcd al evaluaíing [Licvalidity and spocificily of IheWisconsin Card Sorling Tesí (WCST). one of thc ínost widely used tesis of prefrontal fuoctionin clinical and experimental ncuropsychology. In ipito of its extensive use, voices of caution havearisen against [he use of WCST icores as direct markers of prefrontal damago or dysfunclion.Adopting a cognilive neuroscíence approach, the presení research program integrates behavioral.physiological, and anatomical informalion lo investigatc ihe cognitivo and neural mechanismahehiod WCST performance. The results show thai WCST performanco ovokes conspicuousphysiological changes over frontal as well as posterior brain regiofis. Moreover. WCST icoresconfound vory heterogeneous cognitive and neural proceises. This confounding eficcí may havelcd many aníhois Lo ovcrlook [herelativo iínportance of certain dysfunctional sutes .such as Ihosoindexed by random crrors. These findings strongly suggcsí thai WCST icores cannot be regardodas valid nor specific markers of prefronral lobo funetion. 1-lowever, lhey do provido sorne relevaníclues to updato our cunent knuwledge about profrontal funclion. lo the long run, dic integraliveapproach of cognitive neuroscíence may holp us desigo and dcvclop more valid and sensitivotools fur nouropsychological assessment.Kev nnrds: nttc,íticn, cvení-rclatccl potenticis, ne¡¡mps-vchologiccd aíscssnwnt,sct-shifting, cogiiitivor?durOscIcncc

En esta revisión se describe un programa de investigación dirigido a evaluar ¡a validez y especificidaddel Tesí de Clasificación de Cartas de Wisconsin <WCST), uno de los más empleados para evaluarla función prefrontal en neuropsicología clínica y experimental. A pesar de su amplio uso, hansurgido voces criticas en contra de ¡a interpretación de las puntuaciones del WCST como indicadoresdirectos del daño o la distunción prefrontal. Desde la perspectiva de la neurociencia cognitiva, elpresente programa de investigación integra información conductual, fisiológica y anatómica paraindagar los mecanismos cognitivos y neuronales subyacentes a la realización del WCST. [osresultados muestran que la ejecución del WCST va asociada a importantes cambios fisiológicosen áreas frontales y posteriores. Además, las puntuaciones del WCST mezclan procesos cognitivosy neuronales muy heterogéneos. Esta confusión puede haber inducido a muchos autores a pasarpor alto la importancia relativa de ciertos estados anómalos como los asociados a los erroresaleatorios. Estos hallazgos sugieren que las puntuaciones WCST no pueden ser consideradascomo marcadores válidos ni específicos de disfunción prefrontal, aunque sí proporcionan clavespara actualizar nuestro conocimiento actual sobre la función prefrontal. En un futuro, el análisisintegrador de la neurociencia cognitiva puede ayudar a diseñar y desarrollar instrumentos deevaluación neuropsicológica más válidos y sensibles.Fa/abras clave: atención, potenciales evocados, evaluación neuropsicolñgica, cambio de criterioatencional, neurociencia cognitiva

Tho research program described in Ihis reviow was partly supported by granís from Ihe Comunidad de Madrid (08.5/00 12/98), dio

Fundación Mapfre-Medicina. and [heFundación Complutense del Amo. 1 am also indebrod to Fi. Rubia for allowing me lo work al hisiaboratory.

Correspondence concerning [bis arride shuuld be addressed lo: Francisco Barceló, Facultad de Psicología. tJniVersidad do las IslasBaleares. Cría. Valídernoisa, kw 7,5. 07071 Palma de Mallorca (Spain). Fax: 34971 173! 90. E-mail: fbarcelo@uib.es

79

80 BARCEU)

Th cori es an d mclhods from mode iii cogn itiv eneoroscience ¡uve guided my inqLliry julo (lic cogfluti VCoperatiolis aud netiral niechanisnis behiud perioJJiiLIJ)Cu Qn[he Wisconsin Card Sorting Tesí (WGST; (iraní & Berg,1948), 01W of dic mosí extensive¡y usen tesIs in [he historyof clinical and experimental uicuropsychotogy (Fuster. 1997;Kimberg, DEsposito. & flaralí. 1997: KoUí & Whislíaw,1996: Lezak. 1995: Mituer. [963: Monutain & Snow. 1993:Spreen & Strauss, 1998; Sluss & l3enson, 1986). The

primary goal of the research ti nc described here lías buento asscss thc validity aud spccifici<y of [he WCST as anmdcx of prefrontal tobe paíhology. The WCST was nlctvisedby (iraní aud Berg as an index of atistraet reason ing.concepí formation and response sirategius [o clíangingcontextoal contingeucies. Sonie ycars later, Miluer (1963),a nc u ropsy eh o!ogi st froni dic M ontrea ¡ Nctirolng ¡calInstilule nl MeGuJí Llniversiíy, inlrodttced íhe WCSI’ as aíest of prefrontal tobe funclion. Evetí though ihere liavebeen several versions of the lesí (Delis, Squirc, Bi ¡irle, &Massman, 1992; Heaton, 1981; Nelson, 1976), iii jis

convciitional forrn. patieiits are adníinisícred a series ofcards and asked W sort tliern by placiug cadí julo one offour piles. Tbe cards vary according lo [bree attribuíes:[be number, color, and shape of [huir elcmeuts. A dcck ofsuch cards is handed [o [be parlicipaní wbo is [líen askedlo son (bern itt pites beneath four rcfcrencu cards ¡bat alsovary a¡ong diese saíne diíiieusions. ‘Eñe otily tbedhack givento [he partie ipant is ¡be word hg/it (ir vvrong afíer eachsorting. ltíitiatly, color is <he corred sortin« calcgory. aud

positive fecdback is given onty 1 ¡he card is placed iii [hepite witb the sarne color For exanípte, when tlíe eleníenísin ¡líe response card are red. aud [be card is placed beneatb¡be reference card thaI has red objects. However. whcnevcrthe participant sorts ¡0 consecull ve cards correctly, ¡líe“correct’ category changes. Thus, oxíly classifications thaImatch ¡líe new catcgory ¡vil> resalí in posilive fcedback.Thc category first chauges [o sbape, [hen [o number, anní[hetí repeats in ¡líe same order, sarting from color. TheparticiparÁ rnust tearn to change [he sorting categoriesaccording [o feedback. The tcst ends after two (lecks of64 cards are sorted, or afler six futí cMegories are acliicved.Sconing of [he ¡esí includes ¡wo main rueasures: ¡he numberof perseverative errors (j.c., failures ¡o change sortingstratcgy after negative fcedback) aud the number ofcategories achieved (Kimberg el al., 1997; Sprecn &S[rauss. (998). lis purporíed sensiiiviiy ¡o prefrontaldysfunction has favored jis use [o “confirm’ prefrontalinvolvernent in psyehiatric aud clinical poputatiofis. niaiulyscbizophrenic paticnts (Lcnzenwegcr & Korfine, 1994).obsessive-computsive patients (Abbruzzcse, Betlodi, Ferni.& Searone, 1995). and altentiorí dcfici¡ hypcractivi[ydisorder (Kempíon ct al., 1999). A mere Ijíeralure searchin Medline of ¡líe key words “WCST~ or “card sortiug’yietds over 500 seicutifie papersover [he pasí uve yearsalone. Ibis reflects a growing inleres[ in [he study,

[reatiiient, antí rcbahiti latiotí of defici[s iii executi ve controlsuco¡idary [o dysfunction iii prefrontal coriex.

In spiíe of [líe ex lensíve ¡tse. of [he WCSJ ¡ti bothcli nical aud experiníeníal seuings. voices of caulion haveari se u agahí st i ts use a s a dj red tííarker of piefrotí taldaniage or dysfunction (Lezak, 1995: Mountain & Snow,1993; Reitan & Wol fson, ¡994). The inflection point formosí of [hese critjcisrns was [be evideuce provided bynew 1 y aya ita ble nc u roini ag ing ícchui ques [bat o ffered ameatís to asses s ¡he local izati on aud exten si on of brai ulesions note precise y (Anderson, [)arnasio, Jones, &Tranel. 1991). Furtbermore, receul analyscs of (he coguitivesírneture nl [he tes[ 5uores suggcs¡ thai crítícisnis níightalso reflecí lack of interna! validiíy aud inconsislencies tu[he WCST scoring norms (Bowden et al., ¡998). On [heone haud. ¡bese defiejeneles wou]d nol be surprisiug forn.u insírumení [ha[ was devised frouí rallíer old—jnshionedniodels of both cognilive aiíd prefronlal func¡ion. On [heo[her bauní, i f [líesecniticisnis were lo be trusled, coníl flU(itt5

reí lance on WCSI’ seores may be iii sin forrningneo rop syc ho log. ical assess nicnt, as w el 1 as h amlíen tigprogress in ¡be nn¡lers¡auding of prefrontal bbc funclion.tu [bese circunistances, aud before we coitíd takc WCSTseores as direct 1 udexes of prefrontal futíction, it \vasdecuied ¡íecessary ¡o address Ihese fundamental qitestiotís.Ibis was done by integraíi ti g líehavioral informa¡i on froti~WCSÑti1w tasks wi¡h brain physio iogy (i.e., even í—relaiedpotení ia Is- ERPs), ami lesion siodies (le., prefrontalpatlen t s). 1 u orden to derive fruitfo 1 concíosious abotit (bereta[ionsbip bctwcen dognitíve aud brain processes, it isfirsí necessarv Lo estabí ish a solid corresporidence betweeutask desigu (j.c., coguitive processes) and brain physiotogy.In doiug so, currení cogxíitive modeis of working mernoryand a¡tention lírovide a slrong conceptual framcwork inorder ¡o isotate [he cognitive proccsses behiud WCSTperformance (Delíncíie & Clinngeox, 1991; Robbiuís, 1998b:Rober[s. Robbins, & Eveni[, 1988). Likewise. ERI’s wercchosen as fasí and re[a[ively itíexpensive mensures of brainfunetion. lii [he next section, 1 explain how ERPs can beused lo extradl meaningful infortijation aboul [he cognitiveand brain processes involved ti WCST performance. Asknowledge about [he fonetion of prefronlal cortex is s¡iIltíconípícte aud patchy, it is impor¡an[ ¡o keep an openníind lo integrate kuowledge from related cognitive,neoroirnagiug, and lesion studies lo irnerpret ERP data.[lic bird aud fourdi secrions describe our main fiudiugstu normal participanís aud [heir iulerprdtation in retationI.o convcrgítig evtdence from neuroimaging studics. in ¡hefif¡h section, clinical dala frorn neurological palien[s withprefrontal lesiofis are presetíted. The así two scctíonsdescribe ¡he main ncuropsychological implications for ¡heassessmen( of prefronlal tobe funetion, as wctt as sorneconcluding remarks abou¡ [he new honizons opened op bycoguíilive neuroselence for [líe objecdve assessment ofhiglíer brain functions.

TRE WCST AND PREFRONTI4ALFUNCTION 81

Wlíal can ERPs ¡dl us about the WCST?

Thc principIes of measurement, physiologicaltulerpíelalion, aid Iimi[ations of ERPs bave been adequaíetyreviewed elsewhere (Koighí, 1997b; Rugg, 1992) aud willnot be addrcsscd any furlber bere. Two main reasous josíjiledottr choice of ERPs as indexes of brain adlivalion. First[y,Iheir excelleul lemporal reso[ulion makes ¡bern a good mdcxbr exptoriug ¡he associa[iou betweeti fast changes in brainadlivalion and cognitive processes (j.c.. a norma! personneeds lcss ¡han 1 second lo sor¡ a WCST card). Secondly,Iheir spa¡iat resolution is enough lo resolve gross anatomicalqoeslious (j.c., a frontal versos noufron¡al loctts of WCSTeffec[s). From a scientiftc poin¡ of view, Ihere was the exírabeneft[ thaI ouly one prcviotts s[ody had used ERPs lo assessWCST performance (Maites, Cohen, Berg, Canavan, &Hoprnanu, 1991). boL Ihese au¡hors did nol fiud auysignif¡can¡ difíeretíces jo <be pallern of ERPs evoked duriugWCST performatíce (see Barceté, Sanz, Molina, & Rubia,1997, br a diseussion).

Measurcrnent of brain pbysiology relalive [o coguitionrequires a compoterized sysletn so as ¡o ¡ime precisety [heonse¡ of íask s¡imu[i atíd responses for laler averaging. Ibiswas nol aB issue siuce a compoter version of [he WCSTwas already comniercial Iy available (Harris, 1990). Moreimpor[aully, one role of lbumb in cognitive ERP researchts <bat brain adlivi[y from cogni[ivcty similar ¡rials shouldbe averaged togeiher Tuis requiremeu¡ motivated a detailedanalysis of Ibe cognitive operalions (Iuring eaeb WCST ¡rial.It soon became appareu¡ Ibal, itt coguitive terrns, the WCSTwas a poorly desigtíed <asIc Ihe lirsí faulí was ¡haí atmos[oiíe (bird of alí responses coold uot be inlerpretedonatnbigttously. For instauce, a card wi¡h fon red circíescan be sorted in ihe foorth pite, attcnding either [o ihenumber or ¡he shapc of i¡s eletuenís (see Figure 1). In sucha case, Ibere is no way ¡o know ¡he actual rule from [heparticipau[’s behavior alone. lb ¡he response is incorrecí, itwilt nol be dlear whethcr a perseverative or anonperseveralivu error should be seored. Atnbigoousresponses are a source of noise and a íbrea[ lo construcívalidi¡y, and have lcd lo an ar[ificially complex scoringsys[em (Healon, Chelune, Tatlcy, Kay. & Corlis, 1993) thaIhas only made [be problem worse (Greeve, 1993). re otítypossibte way lo [ag cognitivety similar processes foraveraging ERPs was lo eliminate ¡he arnbiguous cards frotíioor compoler verston, an option already adopted by o¡heratt¡hors (Nelson, 1976).

Ihere was a secotid issue thai liad ¡o be tackled beforebrain adliv¡ty coold be meaningfully retaled ¡o any spccificcognitive process. Ihe WCST is administered wilhoulunstrodling about [be íask’s rules, so lba¡ parlicipan¡s need[o work ou[ (he rotes by Iheníselves wi¡h [he help offeedback añer each card sorling. Ihe olficial <cM instruclinusread: ‘‘This lesí is a titIle unosoal hecause 1 aní nol atlowed¡o ¡dl you very uíuch aboo¡ how lo do it’ (Heaton, 1981).

‘Phis aspecí of Ihe lesí is meau¡ [o draw on problem-solvingaud concepí-formalion abiliíy, which are indexed by [heseore “Nomber of Irjats lo achieve Ihe first calegory’(Healon, 1981; Lezak, 1995). Howeve~ soch processcs areclearly distincí from ¡he alíenlional set-shif[ing aspcct ofIhe lesí (Miltier, 1963) aud are probabty far loo complex tube tinked lo simple phasic ERP responses. In coutrast, currení[heories of selective allenlion offer a solid framcwnrk loiu[erprel Ihe atíentional seí-shifíing aspecí of Ihe tesí(Desimone & Duncan, 1995; Duncan, H¡tmphreys, & Ward.1997). Specifically, previotts animal rescarch whb ananatogoe of ihe WCST had revealed behavioral audphysiological changes associatcd wiíh early aud late ¡rialswi[bin eacb sedes (Roberls el ¿tI., 1994; Roberts el a]., 1988).tu ¡be early trials of a new WCST series, Ihe sobjec[ shouldshif[ from an oíd calegory lo a new one. Ibis coguitiveprocess has beetí defined as extrad¡n¡enswnal set-shi/ting.Late [r¡als in a WCST series demaud setection of cardswiíbin <be same slimutus dimension reinforced in thepreviotts ¡rijIs, a process referred lo as intradimensionalset-sIúfiing (Roberís el al., 1988). Many s¡udies have reponedprefrontal activalion mosúy doring <he early triats in eachWCST series, white <he par¡icipan[ is in [he process ofshifling between differenl slirnulus seis or dimensions(Gauntíet¡-Gilber[, Roberís, & Brown, 1999; Keete & Rafal,2001); Konishi et al., 1999; Kouishi el al., [998). Inconsequence, for both praclical aud Iheoretical reasotis, wedecided to focus un attentional sel-shifting railíer ¡han ono[her cognilive processes also tapped a[ by Ihe original tesí.The computerized WCST adaptation designed [o measureERPsduring atíentional scí-sbifling has been called theMadrid Card Sorting Tesí (MCST: Barceid & Santotné,2000).

The Madrid C’ard Sorting Test(MCST)

A seheniatie itlus¡ration of one series of ibe MCST isshowu itt Figure 1. Participaots are instrueled [o match theresponse card wilh one of Ihe four reference cards fotlowingone of Ibree possibte rules: number, color, or shape.Parlicipanís can practice ¡he lask for 5 min¡tíes before [heexperimental run. The new soríing principie is lo bedetermined wilh [be hetp of audi[ory feedback detiveredafler cacb respotíse. 1-IeaI¡hy individuals uormally [md ¡henew rule afler ei[her Ihe firsí or ¡he second disconftrmiugfeedback (j.c.. ití Ihe second or [hird Irials of a sedes). Triatsare ordered semi-randomty with [he cons[rain¡ thaI alt cardscan be sorted unambignously. Series vary randomly betweensix aud nine ¡rials, so thaI <he star[ of a new sertes can no¡be anticipated. A session consis¡s of 36 series, wilh anaverage duration of 25 minutes for normal youngparticipanís. Ihe electroencephalogram (EEG) is concunentlyrecorded from a sufficieuí number of electrodes ¡o mapprefronlal, fronlo-lemporal, central, parietal, temporal,temporo-parielal, and occipital arcas of boíh hemisplíeres

82 BARCELO

Late trials

Early trials

3rcl

TIMiNO:

EVENTS:

2nd

ERP14 1700 ms

it it1600 ms

time

H

IastIast -1

— RED

m OREEN

7 YELLOWBLUE

2 - 3 sec

Card onset Response Feedback Next trial(Card onset)

Figure 1. Seheníatie it [osíration of one series of [he Madrid CatéSorOng Tesí. Ladi trial begi os wilh the onset of foitr WCST key-cardson top of one response eard. al! ceotered on Ihe eooi[iot.er scíeen. Participants ose a 4-bolton response panel Ibr sotting, are informedabout llie ¡ask’s rotes, aud reecive 5-mm practice. Aoditorv feedbaek is detivered [600 tns ¿tiler tbe response (a 21.100 Hz tone for corred.a 500 Hz tone for incorreet). ERPs are recorded for 1700 iv Locked lo ¡he caré s onsel.. i nel oding a

200—ns presti 010 los period. Aconíplete ¡mt consisís of two ntos of 18 series each. As part jcipatíts canno¿ autic¡ pate tite Mart of a new series, they oecd to níake a‘‘Iirst—trial error, atíd osctatty finé <he new rote ejíber i u ¡he seeood or jo the Ihíté ni cts of the new series.

(Figure 2). lo assess ¡he effccls of a¡[entional se[-shiftingon vtsual evoked potentiats, mean amplicude values areob[aiued frorn bo¡h sborl-latency (Pl, 100-130 ms: Nt, 155-175 ms; P2, 185-215 nís), aud loug-la¡ency (N2, 305-335ms; P3b, 450-600 ms) ERP comportenís (see inser[ i Figure2). Fas¡ exírastriate ERPs are also modolated by alteutionalsetshiftíng (Barceló, Muñoz-Céspedes, Pozo, & Rubia.2000), but <he presení review wit[ focos un findingsperlainuííg lo 23b aclivily on]y.

A s[rict control over behavioral perforníanee ts ofparamoun¡ imporlatíce if we are ¡o make vatid infereocesaboot brain physiology aud ondertying cognitive processes.Accordingly, ERP avera”es are comp¡¡[ed separately dom[bose írials whose associated behavior maiched one of [líe

two conslrud¡5 of interesi: either att extradiníensiouat sbif[or an iníradiníensional shif¡ in atíention. lo be consideredití [bu avetage~, WCST series oeed lo mecí al! <he tbttowiugconstrainís: (a) ¡here is no anticipation of <be new soriingrute, (b) ¡he new role is fouud itt cilber ¡he seconé or ¡birdtrials o [he series, aoci (e) ¡he calegory i s no¡ níissedthereaf¡er. As series are ordered raudoííty. par[icipant.s bavelo guess af[er Ihe firsí negative feedback of a new series(Figitre 1). Hence.iii idea] participaul has a 50% chaoce ofehoosing ¡he wroug calegory u Ihe secoud trial of a newWCST series. flíese secoud—¡rial errors have been ¡lelinedas ‘efficieol enons,’ as they ¡ivolve a sbi ft in ealegory audare fotIo\ved by eorrect sorlings iii alt remaining [rials of<bat series (Barcetó. 1999; Barceló, Muñoz-Céspedes. e¡ al.,

4,

IHE WCST ANI) PREFRONTRALF(JNCTION 83

2000).Therefore,uníy une firsí-tria! elTor and one efficie,íterror are allowed in any valid WCST series. In previousslítdies. ¡be

2nd aud 3rd irjais frum alí valid WCST serieswere used lo compute earty WCST ERPs, and [he tasI [wotrials served [o compule [ate WCST ERPs. The formermeasored exíradjmensional seí-shiftiug, atid Ihe tatermeasured intradimeusional sel-shifíing (Bareeló, Muñoz-Céspedes, el al., 2000; Owen eta!., [993; Robbins. 1998b;Roberís el al., 1988).

h’~lf a Secondbeyondtite Frontal Lobes

Ihe ERPdifferences belween eauly and tale WCST Irjalsare illustrated in Figure 2. Ihe mosí conspicuous ehangeswere ¡he larger P3b amplitudes on late as compared withearly triats (Batceld, Muñoz-Céspedes, e[ al., 2000; Barceló& Rubia, (998; Barce[ó el al., 1997). lnlerestingty, earlyand late ¡riats prodoced targely similar ERPs over fronlalregions. Given thai iníracraneal recordings and lesion studiessttggest Ihal [he ue¡tra[ genetatos for Ihe P3b lic al [emporo-parielal and mesial temporal associaíion cortices (1-lalgren,Baudena, Ctarke, Heit, Liégeois, el al., 1995; Halgren,Baudena, Ctarke, Heil, Marinkovic. e¡ al., 1995; Heil, Smith,& Halgren, 1990; Kuigh[, [997a; Rugg, 1995), our resutís

F3 F4

ir7 e

e e a-”44~ ..

pQ’p~~

1~•’ ‘1

appareutly defy [he validity of a test dial had beenhistoricat[y used as an indicator of prefrunlal funetion(Kimberg e¡ al., 1997; Lezak, 1995; Milner, 1963; Stuss &Benson, 1986).

Mos¡ of our kuowledge aboní [he ¡argel P3b derivesfrom simple Iarget de[ec[ion “oddbalt” lasks. lí isconcetvable ¡bat P3b-like aclivaliun recorded duriug acompara¡ivety more complex task such as <he WCST rnightreceive some direcí contribution from prefrontal generators.This hypothesis was investigaled ttsing Brain EtecíricalSuorce Ana[ysis (BESA; Scherg & Bcrg. 1990). The resu[tssbown in Figure 3 suggested ¡bat nonfroníal dipote modelsof <he P3b response derived from auditory audsomalosensory oddbatl ¡asks accounted for np lo 93.7% ofoor WCST-retaled P3b dala (Tarkka, Stokic, Basile, &Papauicotaou, 1995). In [orn, alí altemp[s [o fi[ frontaldipoles lo oor WCST P3b model were unsuccessfu! (Barcetó& Rubia, 1998). Finalty, a nonfrontal [bree-dipole modelmanaged ¡o acconní br up ¡o 94.6% of variance from ¡heobserved WCST P3b changes in amplitude (Figure 3b).Ibis dipole so[u[ion was in une wi¡h evidence frotn tesionstudies (Knigh¡, Grabowecky. & Scabini, 1995), audintracranial recordiugs in humans (Hatgren, Baudena,Clarke, Heit, Liégeois, el al., 1995; I4atgren, Baudena,Clarke, Hei¡, Marinkovic, el al., 1995; Heil el al., 199(1;

— Early WCST trialsLate WCST trials

Figore 2 Ear!y-tale WGST P3b effeels. Mai,i pone!: Graud ERP averages tor early and tale WCS’f trinís a[ two frotíla! aud lwo posterior

etecítodes. Verlical has indicare <he ouseí of <he WCST key-ca¡-ds ptits response caíd compoond. Waveforrns represení tinked-niastoid-efet-encud averages foro [6 nornial parlieipants. I,,serr: Delai lcd iIt ttsltalion of Ihe -nain PR 1’ componenís nícasored al <he right parido—occipital etecírode (P02).

PSb4

P2~, ~

P02

1000 14003 pV miLliseconds

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Rugg, 1995), and suggesled an involvemen¡ of temporal-parietal aud mesial temporal associaíion corlices wiíbin afraclion of a second afíer eacb WCST eard soríing. Theseresulís indicated Ibal ¡he WCST cotíd nol be regarcted asa spec¡fw marker of prefroníal funclion. bol <bey did noliuform tts aboot <he nalure of Ihe cognilive processes bebiudIhose P3b changes, nor did <bey lo[a[ly discard acontribution from prefrontal cortez [o WCST perfortííance.Indeed, Ihe P3b component has buen titíked lo a variely ofmental processes (Donchin & Coles, 1988) but i[simplication in basic cognitive operatiofis such as memory¡w allenlion is sU II a matter of conlroversy (Knight &Scabiui, 1998). Moreover, failure ¡o obtaití ERP changesover prefrontal regions could be simp[y due lo a closedficíd configoration of Ihe neural genera¡ors involved inatíentional sel-shitIing. However, as witt be sbown betow,a shrewd combinalion of ERPs wilh lask seí-sbiftingparadigms may help os etucidale sorne of [he cognitiveoperalions underlying P3b changes during WCSTperformance. Hence, ¡he nexí step was tu delineale thecognitive meaniug of <he earty-laIe WCST [rial ehanges ittP3b amplitude.

Earty-la[e WCST P3b changes were originalty alíributed[o [he gradual bui[d-up of a memory template br <hestimutus category along each series (Barceló el al., 1997).AI[ernativety, it was also feasible [bat P3b changes werelinked <o an “on-off’ swilch mechanism [riggered by <heactual slíif[ in ca¡egory (j.c., a shifl u atíenlional set). ‘1’wocontrol tasks were designed lo examine whc[her earty-tateP3b chauges reflected category selection (atten¡ion) orcalcgory slorage (memory) operalions. One coíí[rol lasl<at,nottnced [be new correc¡ calegoty a[ <he starl of each newseries, aud hence, it contained onty intra-dimeusiona] shiftssimilar [o <hose present during [ate WCST trials (<be WIDtask). In a second control ¡ask, participanís were requesíedlo sorí itt ibe pite thaI shared none of [be response cardsfeatores (Figure 1). Ihis demanded consíant extra-dimensional sortings, and so prectuded Ibe s[orage of anysingle stimulus diníension (¡he WED [ask). Neitber ¡he WIDnor WED lasks can be regarded as comptelcty nettlralconditions, as ¡bey botb consist of retevaní s[iínoti ¡bat areexpected ¡o elicit a P3b response. Howevet, a gradual bujíd-op of a meníory templare for [be síimtttus eategory couldbe assumed ouly u Ihe WID lask, bol nol u <he WED Iask.Figure 4 shows ¡he group averages for earty aud tale Irjatsin ¡he WCST and ¡he two control tasks. Surprisingly, neilberof <he two conírol ¡asks showed any sigus of a P3bmodutalion as a funclion of <rial order. This ou¡coníesuggesíed ¡he existence of a unique cognitive mechanism¡u [he WCST <bat was not shared by any of [líe lwo conírol[asks. Perbaps <he mosí distinetive feature of ¡he WCSt’ is¡he uced ¡o cndogcnoosly shifí ¡be soríing rule and guess[he nexí new one (Miltier, 1963). None of [he lwo conírolrasks involved suclí a lype of shif[. Shifís werc cxtcrna!lypromp¡ed by <he fl.st card in each WID series. wbereas llie

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<he WCST P3h dalaset (b) A 3-dipote model offered <he besípossib[e fil anO explained op [o 946% of variance in <be WCST

P3lí dala, tu both instances, neo-al generators for seatp-reeordedWCST P31, ae<ivi<y were eslimaled ar mesial temporal aud lenipoto-pariera! regiofis Posilive voltage values ate plotíed rtpwards.

same extradimensional rule was cunsistenlty used u altWLD tria[s. In conseqoence, it seetued tikely Ihal [beendogenoos sbift ti set in earty WCST [riats was responsiblefor <he observed P3b modulaliotis. [bis bypo¡besis wasconststenl wilb a targe number of s¡odies bo¡h of norníalatíd clinical satfhítes (Debaene & Changeox. 1991; Lezak,1995: Milper, 1963; Rogers el al., 1998; Sbatljce. 1994),aud xvas pors¡ted f¡írther with a fuer [riat-by-tria! analysisof shi fi aud nouslíjfl <riaL.

TIllE WCST AND PREFRONTRALFUNCTION 85

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[ti ¿II previous studies, [he 2r0 aud 3rO trials of alt validWCSTsedes baO been co!lapsed logelber julo an ear¡y ERPwaveforní. However, parlicipanís normally learn the newcorrect category u Ihe 200 Irial on 50% of alt vahO series,wbose 3rO Irjals tben do nol involve any sUfí in set.Iherefore, corred 3rO Irlais were split op mb 3(0 ~fi~f¡anO3r0 nonshift trials for a more precise analysis of Ihe inflttenceof scl-shifting on the P3b response. Figure 5 shows ¡hecrilical comparison beíween 3r0 sbifl anO 3r0 nonshift Irjaisfrom valid WCST series. Itere was a significaní mercasein P3b amp!itude between ¿3rO shift aud 3r0 nonshifí trials.Ihis comparisonalso reveals a P3b asymmeíry acrosstemporal etectrodes. a resu]¡ already noliced líefore (Barceló& Rubia, 1998; Barceló et a]., 1997). Uowcver, [he mercasetu P3b amplilude frum 3r0 shif[ ¡o 3rd nonshif[ Irjats Oid nolaccoun¡ br the ful! size of [he P3b waves elicited in late¡riáIs (see Figures 2 ¿md 5). Even if [he parlicipau¡ fiadleamed ¡he new corred category afler ¡he 200 tria! feedbaek,il took hiín or her sorne exíra Irjats lo achieve ¡he full-b]ownP3b amp!iludes observed in tale WCST ¡daIs. In other words,[he ear[y-Iate change in P3b amplilude was not indexing amere “on-off’ swiích mcchanism ¡clated lo the shif¡ isí set,buí also involved a gradual buitd-op in P3b amplitudeexlending over several nonsbifl tria]s. Ibis oulcome isiltusírated in Figure 6 wilb a íriat-by-írial ploL of P3bamplitudes across shiñ aud nonsbifí periods. [lis worlhnotiug that ¡líe P3b asynímetry was apparenl only doringearly shif[ triats, bit nol duiríg early nonshift or [¡ter Iríais(Barcetó, Muñoz-Céspedes, el a!., 2000).

Al! in aH, [hese resulís suggest [fiat early-Ia¡e WCSTP3b effecls seem ¡o be indexing Ibree difleretfl processes:(a) a sharp redoction in lib amplilude, anO (b) a slight P3basymme¡ryduring shif[ ¡rials, plus (e) a gradual post-shiftP3b buitd-up extending over sevetal uoushifl trials (Figure6). According to task-se¡-shifting evidence, endogenous sluiftsin sel níay be responsible br Ibe sharp attenuation and ¡heslight asymmelry in P3b activity during early WCST Irjats(Dehaene & Changeur, 1991; Rohbins, 1998b; Rogers &Monsetí, 1995; Sballice, 1994). On Ibe oíher haud, thegradual pos[-shift P3b bui[d-up may líe a pbysiotogicalconcomitan[ of ¡be recont’iguration of [he atten[ionat set Oversevera> post-sbift [rials (Atíporí, Sly!es, & Hsieh, 1994;Rogers el al., 1998).This account is consistení with curreníiníerpretaíions of [líe P3b response in lerms of altenhionalset-shifíing aud ¡he upda[ing of working meníory templatesfor perceptualcategories (Barceid el al., 1997; Donchin &Coles, 1988). Ti) OUr know!edge, Ibis was Ihe firsí lime thaIsuch a P3b modulation was reported using a íask-set-shiflingparadigm. Further research is c¡trren[ly onder way lo conftrmatid erleud [bis novel finding.

Imaging prefrontal funclion

Ihe boregoing findings did not discard a plausibleimplication of prefrontal cortex in WCSI performance. evenif ¡hcy did quesdon its speciticity as a marker of prefrontalfoncíjun. Bo¡h ¡esion studies and ueutoimaging sludies with

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with ]0 <ri.íts tu eneh sob-average.. wilh <he sanie noníber of lefr- anO riglil-haud soriings pu> sob-average Waveforms fioní níjd-Jitie Czano Pz. anO tateral T7/TS anO Pl/PS elecirodes are plolíed frorsí -21)1) <o <400 rns relative <o <he onsel of <he key-eards píos responsecarO compooud. 3ré shif¡ ¡rials evokedrelialuíy smaller P3b amplitudes <lían 3r<> uonshifl Irjals al midOte anO letí tateral elceirodes Ip <

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healtlíy individnals converge in ¡bat an mIad dorsolateralprefrontal eortex (dPFCx) is required for corred WCSTperfunnance. 1-iowever, few imaging stodies have investigaledwhieb cognitive proeesscs behisíd WCST performance depeudon <he OPFCx atid which ones depend on nonfronlal stnJetures.Metabo]ic imaging <ecliniqítes offer bou advaniages anOlirnitatioxís for linking specif¡e cognitive processes fo brainstruclure atid funetion. Table 1 presents a sunírnary of sorneWCST studies <bat have coucurren[ly imaged brain fttnctionin normal individuals. Almosí wittíout exception, [besesíndiesreport an increase in [he me[abo]ism of prefrontal regiotis

during WCSI execulion. Active arcas niostty conespond wi¡hdic dPFCx, bu¡ activation is also reponed in thc ventro-medialprefronla! cortes (vPFCx) (Hernian el a]., >995; Konishi elal., 1998; Mentid e¡ al., 1998; Nagahama e¡ al., 1996, 1997,1998; lien, Schlaepfer, Orr, & Pearíson, >998), and <heorbilofronlal cortes (oPFCx) (Bemían el al., >995). 1< is 00<yet elear whe¡her the predominant pattem of activation affec¡s¡líe tef (Kawasaki el al., 1993; Mattay el al., 1996; Nagabamae¡ al., 1996. 1998; Ragland et al., 1998) or <be rigb¡beníisphere (Mareneo, Coppola, Daniel, Zigun, & Weinberger,1993; Mentid el al., 1998; VoIz et al., 1997).

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Cx, Pz, 15. 16, P7. PS, P07, anO POS electrodes are showu Vertical tines indicate standard error of <he mean. A uou!inear b-splinefouction was used lo connedí trial-by-tria¡ changes u tnean P36 amplitode. Cosed aves: (Uppcrpanel): GranO mean readtion times fromcomplele WCST series are plotíed as a fonetion of <rial order. (Lower panel): Mean pereent of errors froro failed WCST series are plottcdas a fotiction of Irial order. Vertical Ijues indicate síandard error of <líe mean.Asterisks indicate siguificaní differences with Ihe previoos¡rial in [he series; * ji <05; ** ji <QL Trianglesindicatesignificantdifferenceswiffi <he <ast trial in the series: Ap <.05; AA ji <.0<.

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overlooked. WCST pertormance increases Ibe metabolismin a wide neural network comprising [he inferior parietalcortes (Berman e¡ a]., 1995; Konishi et al., 1998; Nagalianiael al., >996, 1997, 1998; Parellada el a!., 1998), [empuro-parietal associaíion corles (Marenco et a]., 1993; Nagahamael a]., 1996; Raglaud el al., 1998; Tien el a]., 1998), lemporooccipital corles aud temporal pole (Herman e[ al., 1995;Raglaud el a]., 1998), atid primary and assoeiation visualcorlices (Berman et al., 1995; Marenco eL al., 1993;Nagabamaet al., 1996; Raglaud et a]., 1998). Ihere issomewbat less consensos as lo whether Ibere is an increaseor a decrease in adlivalion in o¡her neural toci .such as ¡heIhatamus anO basal ganglia (Menízel el al., ¡998),parahippocampal gyrtts (Nagahama el al., 1996), andhippocampus proper (Herman el a]., 1995; Mattay eL a>,

1996; lien el a!., 1998). Whether [bese incremenís anOdecremenís in bluod tlow correspond witb neural activationor inhibilion is nol known. In any evení, these results arecompalible wi¡h currení accounís of higher brain functionsjo temis of distriboted neural networks (Dehaene &Changeus, 1991; Posner & Dehaene, ¡994), aud wi[hevidence of interconnecting patlíways be¡ween prefronlal audposterior associa[ion cotices (Goldnian-Rakic, 1958), as wellas wiíb sttbcorlical síruclures such as [he basa! gang>ia(Rayes, Davidson, Keele, & Rafal, 1998).

Neuroimagiug stttdies, Iberefore, eonfirm thaI WCSIperfttmance cannot be directty taken as an immediale markerof prefroníal fttnction, an idea consistení with Ihe ERPfindings reporteO jo [he previous sedlion. Buí ¡his condlusionis noncommitta] anO has little applica[ion in clinien] practice.Tbe key question is: Are WCSI seores indesing prefronta!

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fonetion or are <bey not? Ihe solotion lo Ibis dilemniarequires thaI Ibe cogtíi[ive operations betíjud WCSI seoresbe re>aled Lo specific brain processes Unfortouate!y, noleven fMR] slucies, wilb Ibeir bigh spatia! resolotion, coutdsolve ¡his question without first isolatintz the cognitiveprocesses involved itt card sorling. Mos[ neuroiíííagingstodies tisled in Table 1 did nol even [ry ¡o control for anycognitive process wilb an appropriate experimenlal ¡askdesign. [u most cases roetabo!ic brain aclivity was avetagedbr ¡he whote dutation of ¡be íask, as if performance of IheWCST generaled a bonogenuos stale of ‘fronlatity’ wboseessence cuold be Oireclly cap¡¡u’ed by <he brain itnager¿ SLtcba cuorse of adtion denotes sorne iugenui¡y aboot <líe scieníificprocedures necessary [o tueasore cognilive processes.and tnay be responsible for mucb of ¡be “anatoníicatnonspecificity” of ncot’oimaging studies (Barceló & Cale,1997). On <op of jI, <bis problem parlty derivcs lrotií Ibecoarse temporal resolitíjon of rnany metabo[ic tecbniq¡tes,wbicb prevení Ibe double-dissociation of distincí palícrusof brain aclivalion as specificatly related lo particularopera¡ions ¡bat lypica!!y develop at a vet’y fasí pace (I3at’celó& Santomé, 2000; DEsposito, Zaraho, & Aguirre, ¡999)

itt donsequence, adequale experimental desigus anObigber temporal resolit[ion seem two itnporlan[ reqoirenieutsfor acbicving a close correspondence be[weeu brain analotiiy,pbysiology, and coguilion. tu ihis respecí. ERPs roay be asvahO as any olber fonclional imaging Iecbniqoe to assessprefrontal futícíjon. However, it is importaut lo keep ití minOboth [he strengths anO weaknesses of cadí iníaging lechniqtte[o avoid misiníerpre¡ations. Wilh regard lo ERPs, resoltscali be misleadiug when [be active neura! poptttalions areorgaríized in a closed ficíd, or whctí ptefrontal aclivalion isin [be form of a buid modulalion rather than a pbasicstimtt]us->ocked response (Barceló, Sttwazono, & Knigb<,2000). Figure 7 illustrates an esample of ERPs recordedfrom prefroníal scalp [bat were nol sensilive lo proven]esions in Ihe undertying brain [issue lustead, ¡he largesíERP anomalies were observed in Ibe pbasic stimotus-lockedresponses of [bose ipsitesional extrastriate areas <bat lackeda sustained modulatot’y inpuí doro prefrontal cortex (Barcetó,Sowazono, & Knigbl, 2000). 11 appears thaI ihe prefrontalcortex exerls a susíained modulalion ¡tpon extrastriale seíísoryareas thaI may nol be always reflecíed in ¡be ERPs.Nevet’lbeless, ¡he nexí section illustrates an esamp!e of bowERPs can become sensilive indexes of prefrontal bunctiouwhen combined wiíh appropriaíe task desigtís.

Wh’at’s wrong with WCST errors?

Ihe most direct way lo inlerface WCST perlormancewith brain fttnclion would be <o try lo isotate those brainresponses dial are s¡ricity associated with specific scor¡tígnorms, anO in particular, witb WCST errors. Surprisingly,viríually no neuroimaging study has so bar atletiíp[eO <oisolate ¡he locos uf brain Oysfunction related to <he

corlínuission of different lypes of WCSI errors. Ibisoulslanditig disregard for [líe analysis of llie neorocognitivetííechanistís bebirid WCST scot’ing tiorms paralícís a long—!asting disregard fo> the cognilive siguificance of WCSTerros ¡líeníselves. lo date, few authors seen te lave asked<bese si uíp!e qíestinus: Wba¡s ¡be cognitive meanitlg offait ing ¡o cotíplete a WCST category? AnO wbal’s <bemeanng of a ¡íotípetsevera¡ive error? itt oitr a[tcmp¡ lo tinkbraití physiotogy lo cognitiotí, it suon became apparen[ ihatoblaining a category score of ¡ero does uo¡ denote any

líarlico lar cogni tive or brai u dysbuuction. Tlíus, a bai 1 ore [oscot’e a catcgoty may retlect inabilily lo síu fI set, b¡tt alsoinabil <y lo mainlain set u <he face of stimulos interference(Barceló, [999). It was nucessaty ¡o ctarily llíis coticeplualconbounding ebfect ib 1 was ¡o cotnply with <be basic roleitt ERP research [bat ‘ontv EEC adlivity dom cognitivelysimilar Irjals sboutd be averaged toge[het’.’

Originally, my inlentiotí was lo ofíer a lopograpbicalanatysis of tbe brain’s etectrical changes associated witb ¡becotnníissiou of purseverative anO uonpet’sevurative errorslrom a nonclinical sample of youug vo!uuleers. It wasassuníed thaI WCST enors jo normal participanís probabtyrellecí tratísitoty dysfonctioos itt ¡be satie ricura! mecbatíismsdisrupled hy neurological or psycliiatric clisease. ¡u spite ob¡be tesser incidence ob errors jo nonclinical samples, Iheirtuote honogetícuos causation rnakes Itero casier Iii pinpoin¡anO s[udy. It was predicled <bat perseverative audnonperseveta[ive errors woold evoke dis¡inct palterns of ERPaclivation. Ibese ERP palterus were also expected lo dibferfrom [beir “correcí’ coou<erpar[s. Again, [bis cogniliveanalysis soon rcvealed thai ¡be convenlional scoringobnonpetsevetative WCST errots was serio¡tsly flawed. Wbeuparticipanís are itt [be process of shifting set, lhcy cauno[anlicipate Ihe nex¡ con’ec¡ caiegory, anO ¡ence, ¡bey ate forced¡o make notíperseverative errors u order lo finO <be new roteearly itt a new WCS’¡’ series (Barce!ó, 1999; Barceló &Knighl, in press). Ibis is a very efbicien¡ tria]-and-eu’orprocess in normal individuals, wbo can keep track of al! pasíincorreeb rotes lo quickly finO Ibe new corred une. Inconseqoence, <be tíonperseveratve error scott ití <be WCSIis a heícrogeneous mixture of Ibose errors relaled ¡o ¡beefficietí< tesí of hypotheses doriug sel-shibtitíg (j.c., “efficieíterrors ), as welt as of raudoro failures ¡o maintain set (j.c.,“randorn errors”). WiLh [he porpose of averaging brainrespotíses un a cognitive!y meanitígbu] way. eft’icien[ er¶orswere compo<eO separately froro raudom errors. Efbicienterrorsea’ty u <he WCST series were laken as [he corrcctconaterpail of perseverative eurors. la [ura, random errorsin Ibe tasI Irial of a WCST series coutd be referred lo asOislraclions, anO were compared wilti correcbly sor[ed Irjals.

Figure 8 illustrates ¡bis comparison. Ibese dala confirmíba¡ <be ERP pa¡¡ern evoked by perseveralive crxors anOOistractions deviate from ¡heir respeclive correc[ co¡tuterparls.Moreover, both perseverative aad randoní errors wercassociated wí[h Oistinct ERP anornalies encompassing

TIfF WCST AND PRFFRONTRALFUNCTION 91

IpsilesionalERPs

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Figure 7. Seíísitivity of ERPslo changes itt brain activation. Eventrelated potentíals were recorded from frontal (E) anO temporo-occipital (10) seatp regions u bolb prefrontal pa[ients anO conírols Ouring perlormance of a visoa] altention task ERPs recorOed

over <he tesioned frontal arce) Oid nol show siguificaní anoniaties tusteaO, importaut ERP anomaties were ubserved in <he phasicstimotus-tocked ERPs recorded over <he intact temporo-occipilal region of ¡he tesioned bemisphere Sthuíolus-lockeo ERPs may notbe sensitive lo Ibe <ype of sustained modotatiun of prefruntal cortex tpou visual cortical areas in visual alíention lasks (see niain Iextfor a futí esplanalion)

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preironlal as well as nonfronlal brain regiotís. This evideocesuggests tbat [hesetwo lypes of error resutt froní a differenttype ob di sroption in [he neural nelworks thaI controlatíentiona! set-shifting (Harcetó, 1999; Fuster, 1997; O\seuel al., >993). Wbereas perseverative ei’rors wer’e related <osigni bi caní y reduced extrastriate Nl anO prefrontal P2conípotíenís, tandom errors were associated witb att increasedamplitode of [líe bronto-ceníra! P2 componeul. Theíopographical distribotion of Ibese effects suggests actisrttptiou u near fietd generators for perseveralions, aucíu deeper, bar bield generalors for random euTurs (Barcetó.¡999). Note ¡he tatge P3b responses evoked by pet’sevetativeerror trials llíat are similar lo those evoked during [he tasIcorrect trials of a WCST series, wherc Ihere is no changeití Ihe altenlional set. Tbos, a normal P3Lí can be expectedwhen participanís fail tu opdate <he oíd set in <he preseoceob changing conlextoal cies (j.c., aher a negalive beedback).These nove! ERP resolís await confirmation froní fastmetabolic netroimaging roethods wiltí a betíer spaíialreSO]ulion.

The neorocogxíitive analysis of errors broní normalparticipanís revealed a serious fautí in tbe scoring ofnoriperseveralive WCST errurs thai, itt bm, rnigb¡ helpinterpret pasí inconsistetícies iii WCSI research under a newligbt. It is beasible dial <bis cunfounding effect rnay baveweakened Ihe sensitiviíy of ihe WCST bor detecting btaindysfunetion, particularly wbeu u¡her scoring uorrns arederived brom noriperseverative errors (j.c., number obcalegories completed, perceptoal level responses; Heaton etal., 1993; Lezak, 1995; Spreen & Slrauss. 1998) Inreirospect, Ibis has slraigb[borward consequences for <beIraditional interpretalion of WCST resulís For lustance,tbis inherení confoonding effect itt Ibe scoring ofnuoperseverative errors may have lcd tnany aolhors loover]ook <he tule of raudoní crrors as iudicalors of prefruntalbbc pa¡hotogy (Heaton et al. 1993; Lezak, 1995). Ibetationale for [bis byputhesis is based bolb on <be importanceof dPFCx for holding itíborníation online itt workiog rnemory(Knigh¡ & Grabowecky, 21)00; Robbins, 1998b; Smith &Jonides, 1999), anO un ¡he susceptibi!ity obpt’ef’t’ontat palieu¡s¡o distraction anO interberence broní external stiroulation(Fuster. 1997; Lezak, 1995).

For instance, soppose a parlicipaní faces <líe 7~~<> carO oba new WCST series, just afta haviag been pronípted ¡o shiftcategory by [be

1s~ ¡rial error. An ideal participaní wouldhotO pasí informalion ontine lo dEscarO Ihe now-irretevantcaiegory anO selcct une ob ihe ¡wo rernainiug calegories.Socb an ideal participant wou!d be expecíed ¡o níake eblicieníerrors itt hatf of al! 211(1 ¡daIs. Any deviation froní ¡bis idealpatlern migbl reflecí a disruption in ¡be set-sbifting operatiorisinvolved in card sor¡ing (Keele & Rafal, 2000; Owetí et al.,1993; Rogers e¡ al., 1998). Itt any perscveraiivc behavior,[he previoosty esíablisbed sel rigidly deteunities í.líe responsein <be early tria¡s ob a new series despile disconfirníingfeedback (j.c., a “sluck-in-se¡” <endeucy; Miluer, 1963).

Howevc¡; patietiis wittí lesiotís in ¡beir OPFCx are sosceptib!elo distraction anO esternal interference ¡bat tiíigbt lead ¡odifficu!ties ti set níaitílenance. Por instanee, rapid degradatiunof information fruní ¡he previos trizO dee to s¡imutrtsinterferenee caOs <o puor petfuriance otí sobsequení tria[s.¡u extreme cases. !oss of oní tic information cuold caO lo araudoro error itt [líe sctec¡iotí of <líe nesí carO. Huwever, ¡líeinberent confoondittg ebfect betweeu randoííí anO efficienterrors íiíiglit inípair llie sensitivity ob [líe conventiotíal WCSTtu (lifberetices bebween efficient errurs anO tatídom eu’otsIbis issue has been reeentty addressed itt a saníple ofpieltontal paticnts itt cotl¿tboraíive ‘esearcb witb Dr. Robert1. Kniglí¡ a¡ <he Universily of Califomia, Berkeley (see Figure9). tnlerestingty, OPFCx palienís .sbowed higbty Oeviautnumbers of randoto errors that were <wide as targe as ibosebr perseveralive errors, Ihus rcvealing consíaní shifls ot’fboctuatinus ti iheir eboice of sorling principIe (see Figure¡0; Barceló & Knight, in press).

Ibis tutidency uf sorne OPFCs pa¡iet¡s tu suri al raudomíííay bave gone undetected One ¡o bbc inherení confouudingebfect iii ¡he scoring of oonperseverative errors, anO <beesíctíded ¡tse of <líe tiumber of categories compleled as asommary seore lor WCSI perbormance. Ihus, [líe abseiíccof significaul grott~í dilberences iii notiperseverative erosmay tíave niotivaled <bat any debicil iii <be category scorebe altributed tu perseveralive errors alune (Kimberg et al.,1997; Miluer, 1963). [u turu, ¡he present results suggest thaiextreme perseveralive tendeucies leading bu a “slock-in-set’score m:ty uut atways acenuní br Ibe ow WCSI caiegoryscore of OPFCs patienís. Mote obten, patienis may simptylose írack of ibe ongoing category iii Ihe presence ofdistracíing stimulus beatures.

Implicatiotís for ¡he Assessníent of Prefruntal Funetion

In recení years, research into Ibe neoral aud cognitiveprucesses ob atíenlional set-shifling bave discloscd newinsigbts fur Ibe assessmeut of prefrunlal funclion. Ihesenew tindiíígs are rclevan¡ tu botlí the clinical aiídexperimental contexts. Ibe relative uovelly uf <he preseníresults makes it Oifficutt lo eslablish a definite íiíodcl ofatientional seí—shifting at Ibis titííe. From ¡he variouscoguilive coustructs lappcd by thc conveiííiouat WCSY wechuse [o fucus un altentiunal set-shiftiag, a pmocess obtenrelaled tu Ibe esecolive systetí of altenlion Ibe prcsentfindings bave a utímber of iníplicatiutís bor ¡heíeuropsycho]ogical assessmeut of bigher fonctíons

WCSI perlormance activates a widespread networkof uettrat arcas [u line with cvery ueuroimaging study,our ERP findings confirm thai carO sorting tnodutatesbrain adlivity over a widespread iietwurk of brain arcas(Hernian et al.. >995; Konishi et al. 1998: Nagahama etal., 1996). In normal individoals, tbc musí couspicuousuf ¡bese FRP rnodolalions influenced <he target P3b

TItE WCST AND PIZEFRONTRAL FUNCTION 93

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Figure 9. Lesion reconsiroeliotí is shown for 6 patieuts wiíh tesious <o tbcir teR Ootsotateta! prcltotitat c<.rtex [u alt cases, prefrontal datííagewas doc tu cetebral stroke ¡u an¡etior branches of tbc teít middte eceebral attety Leshisis ate transeritíed otilo ax¡at tetiíptates ositig 5—tutucute’, Eactí tnw stiows ¡líe extetír ot darnage u att itt di vidual patietíl. Alt lesione’ overtappeO over posterior ;íottiotis 01 Hrodtnanu arcas 9 anO45 Pie average tissue toss was 414 cuí3 per paticnt Suftwatc permitíecí reuonsttoctiou of ¡líe aretal petspeetive of [betesion. de¡ctuíinaliouof tusion vn> ¡e nc. une> pie mii ~‘ec’y¶o~ocbitectorí u oeca daníaged Lcsionert ateas ¿nc enci ruteeI witi ttíicle 1 luce’ ala> fil lee> iu ‘Vi th ji ray

response, whose putative gniíeraiors bave beeií proposedat lemporo—parieta! aud níesi al tetuipural associ ah uncortices (Harceté & Rubia, 1998; Ha]gren. Handena,Ctarke, Heit. Liégeois. el al., [995; Halgren, flaudena.Clarke. ucd, Marinkovic. e¡ al.. [995: 1-Mt et al.. 1990;Knight, >997<>; Knight cl ¿tI., 1995: Kniglit & Scabiui,1998). A fcw fMRI s¡odies have reporteO bilateral OPFCx

acle vation iriReO <o specific set-shi ftirig operatious, buty arv ng atíío o nís of ací i val ion tiave also bccn ubservedal postertor assoeia<iou corlices (Kou isb i el al., ] 999;Konisbi et al.. 998). t’tiis apparent analotíiicatnonspecifiuity correspouds witb <he svidely distributedorranizati un of neural ne<wurks onderly ing ¿etíentiutí(Posuer & Debaene, 1994: Rubbins, ]998b). anO renders

THE WCSI AND PREFRONIRALFUNCTION 95

PREFRONTALPATI ENTS

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as illusory auy attemp[s lo design pure tes¡s of prefronlalfotíctiun Ihe probleen resides witlí tbe vcry uatterc ofprefronlal (“executive’) furiction, wbicb involves [hemanageníení of a variely of hierarctíicafiy tower-tiereds[imutus anO response processes (Rabbitt, 1997), eaehwilb <heir distiuct ana¡oíííicat stebslraíes. Nevertbeless,<bis anaíoeeíical nouspecificily of neuroitiíaging resuttsmigb¡ also reflecí lechuical anO nielbodotogical itíímat.¡erityof (mr measuremcnt devices anO protocots ralber [han anirretrievable conceptual hurdle for linking sírodlure lofutíction. Current neura! uetwork models postulale thaIdifferent divisions of [líe prefrontal cortes cumpuleOibferent coguitive operations (Debaene & Changeus.1991; Parks e¡ al.. [992) Sucb an organizalional principIeob altentional uetworks also iiííplies Ihat an improvedresotution in both Ibe spatial anO temporal measurerneulof brain foncíjone’ witl betp us lo detineate a spccificmappiug beí.ween cogeíitive upera<ions anO brain anatomyAny socb lechuical itííprovements shoutd go ¡ogether wi[hme¡hodotogica! refiuereíents in lask design, uecessary inorder lo isotate ¡he cuguitive operatiosís of interesí(Mazzioita, >996; Fosne> & Dehaene, 1994: Robbins,1998b)

At[entioriat set-sbibtitíg ití <be WCST modotates [he targe¡P3b response Altlíuugh partly onexpecled, tbis uovcl feudinghas opened a proenisiug patbway fue integrating a largedatabase of neuropsycbologicat anO psychophysiotogicalresearetí into [bebraiu rnectíanisms of working meniury anOalteution Ibe new evidence has propitiated a frteitb¡lintegralion uf Ihe “cuntexí updating’ model of ibe P3bresponse (Donchin & Coles. 1928) svith foreíía! niodets ofvisoa[ atlenti nel au(l alteo tianal set—sh i ing (A! [pon et al,1994; Bundesen, [990; Debaene & Changeos, 199];

[)esimoue& Duncan, ¡995; Robbius, ]995a; Rogers &Monsell, 1995; Sbaltice, 1994). Altentional sel-shifting haslong been regarded as an eseculive futíction of alteutionthai is regulated by prefroutal cortes (Baddeley & DellaSala, 1998; Mituer, 1963; Robbins, 1998b). This binding iscunsistenc with tbe bypo[hesis [bat prefrontal coríexiííodulaíes ¡líe activity of posterior associalion arcas (Ftester,Bauer. & Jervey, 1985; lomita, Obbayasbi, Nakabara,Hasegawa, & Miyasbiía, 1999), anO witb reporteOdisroptioris in [be aeíípliludc of <be [argel P3b responsesecondary ¡o Oeficiís in prebrontal modu!aíiuu (Barcetó,Stewazono, & Keíigbt, 2000). On ¡he ulber bariO, rnost pastP3b research has oscO simple odObatí tasks witb a fixed,pre-establisbed set (Donchin & Coles, 1988; Ford, 1999).Itícrefore, Iask-se¡-sbifliug paradigms socb as [líe MCSTi’epíesetít a new metbodologicat approaeh bor exploe-iug Iheinteractiotí of prefrontal anO posterior association corticesonder clíanging atteíítionat demands. Indeed, correníneurocognilive modets of cognitive fuuctions empbasize [here]evauce of Oynaoíie inlerac¡ions among distaul braití arcas(Posuer & Dehaene. 1994). 1’he MCST rnay also help osexplore <he concep¡na> links between cons[rodts snch asaltentiun. woe’king memory, aad sel-sbifliug, as welt as ¡beirinlerdepende’ícc wjtlí various divjsiuns of prefrontal cottex(D’Esposito cl al.. 1995; Robbins, 1998b). Ibis goal wit[¡‘equire [be combinatiun of ERPs anO IMRL tecliniques, aííd[be manipulalion aud control of a number of variablesaffectiug alteutiunal set-sbifíing in order tu parcel uut ¡hecontribution lo <líe P3b modulation frtím vaniotís sub-operatiotts siecb as memory access, iribibition of interference,visual searcb. response evatuation, aud bypoíhesis teslitte(HadOeley & Della Sala, 1998: Hayes el al., [998: Keete& Rafal. 2000)

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96 BARCELÓ

The convenlional WCST !acks sofbicient cons[ructvalidi¡y. ¡u is curreul burro, sonie WCS’I’ scores do tiol iufouííabuu[ any specific type of cognitive iaípaireiíeat. asid olbeusreflecí a he¡erogeneoos roixtute ob very diverse pt’oeesses.These íypes of confuonding effecís prubably ondertie sonieof Ihe criticisnis abouí Ihe lack of validi¡y anO reliabi!i¡y of¡líe WCSI for pinpointing Oaeííage in prefiuntal corles(Buwden et al., 1998; Muontain & Snuw, 1993).Neverthetess, une níigh¡ s¡ill want ¡o ose WCS’F seures asindeses of <he general status of Ihe pa[ienl’s execulive systemof atíenliun, rcgardtess of jIs anatomical iníplicatiuns (Lezak.[995). Unforlunatety, a Ocíaited neurucognilive analysis ufWCSI scores, s¡ecb as perseveralive anO nonperseverativeert’urs, reveals [bat very lieterogetícuos or evetí antagonisíprocesses are seored as eqoivatent. Ibis is ¡he case wlíenefficieeít anO random et’e’urs are coeííbiued wjtlíiri ¡he broadclass of nuriperseverative errors. Furihermose. dic ambiguityinherení ¡u many WCST responses molivaled an artifcial>ycornplex scuring syslem witb arbitrary rules sucb as Ihe“sandwich rule” (Heaton el al., [993), wbicb níakes itinípussibte ¡o pinpoin¡ specific cognilive dysfuncíiuns inretation lo breakdowns in perforriiarice. Quite un [he cunlrary,tecetil cuntribotions lo llie cugnitive str¡ectore aud anatomicalsubsírates of altentional seí-sbibtirig bave shuwed op by usingbelíavioral íasks [bat avoid ¡be conceploal cutífu¡tndieíg ebfectpreseul in ¡he original WCST design (Barceló, 1999; l3arcetó& Santorné, 2000; Dias, Robbins, & Roberts. 1997; Robbins,1998b).

Appropriate task Oesigns rnay he!p os ¡o pinpuiíí¡ braindamage. Atthough [be uveral! pidtore of WCSI residísappears ralber mixed np, it is iroporlaní lo empbasize ibala few new last< desigris have sbown thaI specific WCSIerrors can eventualty piupuiní disruplions in prefrontalfutictiun. Froní [he foreguing discussion, it transpires íhat¿en iritact OPFCx is neccssary fo> accotiíptislíiug ¡be operatiunof shifting tite attcational set, buí is ¶ío¡ sufficien[ for acorred execuliun of otber operaíions. nur for <be corredcomplelion of [he tesí. A kcy issoe is wbelber <be scoringfornís uf ¡be WCST ur i¡s analogues can pruvide os witboseful infurnialion about [be cugnitive opera¡ionscompromised by a lesiun, nr cIsc about [he damagedeletuenís in [he network. ‘Phis is esactly <be conclusion thaIderives irom [be work of Dr. Trevur Robbins al <beUtiivet’siíy uf Caííbridge. Fur inst:tucc, usieíg att ati¿Oogoeob Ibe WCST, [bey fuond <bat buth OPFCx palienís anOParkinson’s disease patienís failcd tu sbibt elfuciently aínongslirnultes categories. Howevee, ¡líe type of errors, and hetíce,Ihe urider!ying cognitive debicil. differed itt eacb groop.Whereas dPFCs paiien¡s failed lo inbibit Ibeir responses tua previoos]y ee!evaeíl calegory-ie., persevetation-. Parkinsun’spatients bad difficot¡y sbifting tu a previoosty irrelevantOimension-j.e., carneO irretevance (Oseen el al, 1993)Experimental slodies boíh itt boeííau patienis (Hayes el al,1998; Kee!e & Rafal, 201)0; Owen, Monis, Sabakian, Po]key.& Rubbins. 1996; Ruberís el al., 1988). ¿es welt as ití todenís

anO nonhoman priniates (Dias el al., 1997; Roberís el al.,1994). Iceid sopport tu llie hyputbesis ¡bat even a relativelysimple csíguutivc peocess such as attentiuaat scl-sbiftisíg isregolateO by a cumples reciprocal irileradtion ob inhibitory(j.c., dopaminergic) anO exciialory (je.. ebotinergie) circojísin dPFCs anO orbitofrotulal cottices (huslee; 1997; Goldnian-Rakic, 1999: Rubbins, 1998b). [lis feasible thai Ibesereciprocal in<eractions belween dislant brain regiuns wittevent¡tally be Oisc!osed using fas¡ measures of braití ad[ivilyitt cotríbination wi¡b appropriale task designe’

Cunclodirig remarks

Ttíe empirical evidence suníiarized ir Ibis review isconsislení witb esisting clinical anO experimental literatureja thaI dic WCSI is sícilber a specibic aur a reliable test ofprefruntal fonclion. Even more iníportant, ¡he evidencesogges Is ihal Ibe original WCST sttffers brorn a number ufdeliciencies ¡bat tíí¿eke it less <han adeqoale bor rneasoringcugnitive processes reheleO tu atietitional sel-shifting, a keyaspecí of <be execolive system uf atíention (Sballice, 1988).In retruspeel. Ibis is rol al alí sorprising for ¿en instrumenídevised froeií att olO-fashioncd view uf cognitive anO braitifuncíjon. I-luwever. fur maay years, bliud reliance un ¡bescores of Ihe original WCSI rnay bave acloalty arresledoor understanding uf huw cugnitive processes rehile tuprefeuntal funcliun (Muontain & Snuw, 1993; Reitan &Wolfsoti, >994).

[u genera], <bere seeme’ lo be Iwu diffcrent, alíhougbrelated, problenís whcn it comes tu iuterpre<iug tesulís fromneoropsycbolugical tesIs ti terms uf brain anaíomy. Firstly,it is Oifbicult tu isutale anO measure ihe neuruphysiologicalcorrel¿e<es of fas¡ cugeíitive prucesses thai succeed al a verytapiO pace duritig task perforeííance. Second!y. diere is <heproblem of faully designe’ dial shed reasunabie doubt un thereliabitity anO va!idity of tes¡s devetoped froni ootdatedviews of cognitive anO bt’ain fonclion. Tberefore. prublemsmese nol only broní techuical liníjiatiuris in assessing basíbrain prucesses in aterí human sobjecís. buí also fromlirnií.a¡iuns di dic conceptual franíewurk aboní tIte nautre of¡be neurocogniti ve fund ious thai. i u bm, g ve risc <omethodolugicat deficiencies in task design anOimp!emeníation. A sototiun tu <be first prublení demandsieííproved temporal resutolion of fienetiunal neoroiníagiugtedtiniqLtes tu títunitor ¡he fasí pace uf cugeíitive processes.The sotulion ¡u ¡be second prubleen involves Ihe use ofappropria¡e task desigus u otOer lo ubíain itiore vatiO anOreliable measores of ¡bose cugnitive processes respunsiblebor breakdowns in perforriíance. Mureover. task designsbould rety un reatistic modele’ of bijiher brain fotíctione’.Evetí if more vahO, sensilive, anO reli¿ebte tesis of prefrutítalfuriction were eventoatty devised, ji wuold be illusury tucxpect <bern lo be able ¡o specifically activale prebrualalcueles ¿done. An essetítial funclion of prefeuntal associa<ion

THE WCST AND PREFRONTRAL FUNCTION

ateas is tu cuatro! aad modulate activatiun uf o¡hcr corticalanO sobeortica! regions, anO hence, prefroníal adlivation isprobably associatcd wi[h activation of distaní brain strtectures.

la (bis review, Ibe principies frum cognilive neurosciencebave been applied lo sulve a long-stauding prublení inclinical anO esperimenla! neurupsycho!ogy. It is feasib!e<bat Ihe same principIes will continne tu hetp os Oesignappropriale lesís fur assessing [be linkage belween romOanO brain processes. Abter Ihe beydays ob behaviurisrn anOcogni¡ivisrn, cognitive neuruscience seenis tu bave takenover in [be search for a fruitful integration of hieníanneorubiulogy anO psychology. Ihis endeavur witt liketydemand llie co>laburative ebbort ob difberení professiunatssucb as psychologists, tícurologisís, anO cumpoter sceentsl.s.

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Received June 22, 2000Revision received November 16, 2000

Accepted January 12, 200]