THE ROLE OF FRONTAL AND PARIETAL CORTEX IN COGNITIVE PROCESSING

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1 ., _._,,,,-_.._---_..._-_..._.,, ---;, ----,..,.-,..,.-. - _---_....!)-)oo " Bran (1978), 101, THE ROLE OF FRONTAL AND PARETAL CORTEX N COGNTVE PROCESSNG TESTS OF SPATAL AND SEQUENCE FUNCTONS, by BETTY ANN BRODY and KARL H:PRBRAM 2 (From tm Department ofpsychology, Stanford Unversty. Stanford, Cal/omD 94305) NTRODUCTON SNCE Jacobsen frst demonstrated that monkeys wth resectons of the anteror frontal cortex are unable to learn delayed-response or spatal delayed-alternaton tasks (Jacobn, 1936; Jacobsen and Nss(n, 137), there have been many attempts to nterpret these,fndngs n order to formulate a mechansm for frontal cortcal control of complex behavour. Recent nterpretatons have emphaszed the fact that these tasks nvolve rght-left dscrmnatons and therefore mght tap spatal memory (Goldman and Rosvold, 1970; Goldman, Rosvold, Vest and Galkn, 1971). Although spatal cogntve processes have classcally been attrbuted to the doman ofthe posteror paretal cortex n humans (Crtchley, 1953), several studes n the:: clncal lterature have also noted certan types of spatal mparments followng frontal cortcal damage. These studes have provdedsuggestve evdence for a dchotomy between the nature ofthe spatalmparments produced by damage to the frontal and paretal cortex. Patents wth paretal cortcal damage were found to have dffculty n settng a lne to vertcal aganst a conflctng background (Teuber and Mshkn, 1954) and to be unable to make conceptual spatal rotatonsofmaps (Semmes, Wensten, GhentandTeuber, 1963) orvsual patterns (Butters and Barton, 1970; Butters, Barton and Brody, 1970); n contrast patents wth frontal damage had no such dffculty. Conversely, patents wth frontal cortcal damage were found to have dffculty n settng a lne to vertcal when ther own bodes were tlted wth respect to vertcal (Teuber and Mshkn, 1954), pontng to the parts ofther own body correspondng to those desgnated on a dagram (Semmes el al.1963)"ormakng a seres of rght-left dscrmnatons wth respect to varyng orentatons on a map dfferent from the orentaton ofther own bodes (Butters, Soeldner and Fedo, 1972). Patents wth paretal damage also had dffculty wth some of these latter tasks; however, fthe paretal damage was confned 1 Present address: Unversty ofpennsylvana. School ofmedcne. Box 192. Phladelpha. Pennsylvana % Requests for reprnts may be sent to Karl H. Prbram. Department of Psychology. Stanford Unversty. Stanford. Calforna

2 ".. - _. " '-' BETTY ANN BRODY AND KARL H. PRBRAM to the rght hemsphere, the patentswere unmpared.on the bass oftherfndngs Teuber and hs colleagues (Semmes et al., 1963; Teuber, 1964) characterzed the general mparment followng paretal damage as one nvolvng extrapersonal spatal orentaton, that s, a dffculty wth dscrmnatons nvolvng the spatal relatonshps among external stmul. n contrast, they characterzed the mparment followng frontal cortcal damage as one nvolvng personal spatal orentaton, thats, a dffculty wthdscrmnatonsdependent on theaccurate assessment of the body's orentaton n space. n orderto specfy the locus ofthedefct more accurately andto correlate these clncal fndngs wth the vast amount of nformaton obtaned from research wth nonhuman prmates, Pohl (1973) attemptedto testthedchotomy between personal and extrapersonal spatal orentaton usng monkeys wth dorsolateral frontal or wth posteror paretal ablatons. Snce t had been assumed that the salent feature of the tasks defued as measures of personal spatal orentaton was the necessty. of makng rght-left dscrmnatons, P0hl used the place reversal task (go left to a crteron-go rght to a crteron) as the measure ofpersonal spatal orentaton. For comparson he used a landmark dscrmnaton (go to the foodwell nearer the landmark) and a landmark dscrmnaton reversal task (go near the landmark to a crteron-go far from the landmark to a crteron) as measures ofextrapersonal spatal orentaton. The solutons for these latter spatal tasks were based on the spatal locaton of an external referent, the landmark. The monkeys wth frontal lesons were mpared on the place reversal but not the landmark reversal whle the oppostewas true for the monkeys wth paretallesons. Pohlnterpreted hs results to ndcate that the personal-extrapersonal dchtomy s approprate for monkeys as well as humans.. Despte the fact that both patents and monkeys wth frontal damage demonstratesgnfcant mparments oncertan tasksnvolvngrght-leftdscrmnatons, there remans somedffculty wthemphaszngrght-leftdsorentaton orthe more general concept of personal spatal dsorentaton as the prmary bass of the syndrome followng frontal damage. Frst, the clncal lterature ndcates that rght-left dsorentaton classcally follows paretal cortcal damage (Gerstmann, 1940; Crtchley, 1953) rather than frontal damage. Secondly, the most strkng effect offrontal cortcal damage n patents s ther tendency to perseverate prevous responses; aspects ofths syndrome have been tested emprcally wth card sortng (Mlner, 1963), a multple object search task (Poppen, Prbram and Robnson, 1965), and multstep nstructons (Lura, Prbrarl and Homskaya, 1964; Lura, 1966). An emphass on personal spatal dsorentaton cannot account for these fndngs. Thrdly, the expermental data obtaned on monkeys ndcate that f lesons are confned to the focus wthn dorsolateral frontal cortex attrbuted to be selectvely nvolved wth spatal functon, a rght-left dscrmnaton requrement s not suffcent by tself to produce the defct; memory must be taxed, ether wth mposed delays or wth alternatons or reversals of response requrements (Goldman and Rosvold, 1970; Goldman et a/., 1971).

3 .. -., "---'' '--'--'-----_ SPATAL AND SEQUENCE FUNCTONS 609 By contrast to these theores nvolvng spatal functons, some tme ago Prbram (1958, 1961) ponted out that the delayed-response and delayed-alternaton tasks requre the sequencng of behavours. He and hs co-workers suggested that the functon of the anteror frontal cortex s to provde a workng memory n whch these sequences can be flexbly ordered (Prbram, Ahumada, Hartog and Ross, 1964). The clncal lterature also provdes e.vdence that patents wth frontal damage have consderable dffculty wth the temporal organzaton of behavour, partcularly when flexblty s requred. The almost pathognomonc tendency of such patents to perseverate portons ofnstructons occurs most notably when they attempt to perform a sequence ofdfferent behavours (Lura et al., 1964; Mlner, 1964; Lura, 1966). Moreover, the dffculty smlar patents have shown n dentfcaton of body parts (Semmes et al., 1963), n a stylus maze task (Mlner, 1964), or n a path readng task (Butters et a., 1972) has been attrbuted to a defct n personal spatal orentaton, but the conflctng sequental response requrements are equally crtcal features of these tasks (Semmes et a., 1963; Mlner, 1971). Mlner (1971) has reported that her patents wth frontal damage could recognze prevously-seen tems but could not recall n what order they had been seen, suggestng Beffectve 'temporal taggng' of nfonnaton. Prbram had earler suggested that the dffculty monkeys wth frontal resectons have wth sequencng tasks such as delayed alternaton mght be due to an nablty to parse stmul nto useful patterns. He and hs students were able to mprove the performance 0f such monkeys on delayed alternaton by the smple expedent of mposng a temporal pattern to the stmul (Prbramand Tubbs, 1967; Prbram, Plotkn, Anderson and Leong, 1977). Also n Prbram's laboratory, Pnto-Hamuy and Lnck (1965) drectly examned the role of the frontal cortex n sequencng by teachng. monkeys to press dfferent stmulus-response panels n a partcular sequental order. On the bass ofearler work by Kmble and Prbram (1963) they nvestgated the possblty that sequences organzed by external cues and those dependng on nternal cues would be dfferentally nfluenced by frontal resectons. They found that f the sequental order was externally mposed such that the monkeys were always requred to choose the same unque sequence, those monkeys wth frontal ablatons were able to learn the problems at a normal rate. On the other hand, f the only rule mposed was that a sequence on anyone tral must contan no repettons, the monkeys wth frontal ablatons demonstrated a defct. These authors suggested that durng the latter type of sequence the monkey must nternally organze the sequence wthn each tral by mantanng a memory ofeach pror press; whereas, durng the externally-ordered sequence the external vsual cues contaned the nformaton needed to order the responses. They concluded therefore that the frontal cortex s necessary to order sequental behavours whenever such sequences requre organzaton wthn memory. However, another dfference between the two types of sequences mght have been an mportant varable n the study by Pnto-Hamuy and Lnck. The stmul were presented on a four-by-four stmulus-panel array such that the locatons of r-'--"--" [ J

4 ft', _.._... "..._-.., '- --:.. o...mwt...!,", 610 BETTY ANN BRODY AND KARL H. PRBRAM the stmul changed only between trals. The nternally-ordered sequence could correctly be completed by smply pressng each panel once, rememberng only the locatonofthe prevous press. n fact, one ofthe nternally-orderedsequences (red, red, red) requred such a spatal soluton. By contrast, n' the externally-ordered sequences the pattern as well as the locaton of the cued panel could be used to solve the problem. The defct on the nternally-ordered sequence s equally well nterpreted n terms of the hypothess that followng frontal resecton monkeys have a defct n spatal memory. An expermental analyss of both the spatal and the temporal theores was therefore undertaken and s reported here n two studes. The frst of the studes attempts to clarfy the relevance of a personal-extrapersonal spatal dchotomy to frontal and paretal cortcal functon. Monkeys wth blateral anteror frontal or wth blateral posteror paretal ablatons were traned on varatons ofa spatal task desgned to test the dchotomy as smply as possble whle avodng the use of ether rght-left dscrmnatons or reversal problems. As a test of personal spatal orentaton the monkey was requred to press the panel next to a panel he had prevously selected. As a test of extrapersonal spatal orentaton the monkey was requred to press the panel next to a green panel. The personal-extrapersonal spatal theory would clearly predct a double dssocaton of functon on these two tasks. The purpose of the second study was to determne f monkeys wth frontal ablatons have defcts whch are related to an nablty to organze sequences ndependent of a spatal component and to examne the monkeys' dependence on external.cues n learnng such sequences. Monkeys wth anteror frontal or wth posteror paretal ablatons wer!: tested on sequence problems whose solutons were completely ndependent of the spatal locatons of the stmul. We expected that monkeys wth frontal resectons would show a greater defct on nternallyordered sequences than on externally-ordered sequences. n contrast, we expected those wth paretal resectons to show a completely normal performance under both condtons. METHODS Subjcts Fourteen juvenle rhesus monkeys (Macaca mulatta) served as subjects; ther range or weght at operatonwas 2 8 to 3 6 kg. Three orthese remaned as normal controls (Normal Group), 4 sustaned blateral posteror paretal lesons (paretal Group), and 7 (or whch only 4 were used n the spatal tasks) sustaned blateral anteror frontal lesons (Frontal Group). Surgery and Hstology Pror to surgery all monkeys were tranquuzed wth Ketamne ( mg/kg.m.) and then anl!:sthetzed wth ntravenous sodum pentobarbtal untl eyeld reflexes were absent. A salne drp through an ntravenous catheter was mantaned throughout surgery durng whch addtonal doses or pentobarbtal were admnstered as requred. All ablatons were performed as a one-stage blateral aseptc

5 '. ',-- '...;,..,... " ",_-'-" "--'---'.' _._... --_...._-.-._-_._--..._._ SPATAL AND SEQUENCE FUNCTONS 611 procedure. The cortex was exposed wth a full calvarum ftap whch crossed the mdlne and was hnged on one set of temporal muscles. Concal gray matter was removed blaterally by subpal aspraton usng a 19-9auge Prbram Sucker desgned to avod damage to underlyng whte matter. Bleedng was controlled by gentle packng wth cottonod pattes or, rarely, electrocauterzaton. The dura was closed wth ndvdual slk sutures; and muscle, subcutaneous tssues, and skn were closed n layers. Followng surgery, long-actng bclln (300,000 U Lm.) was routnely admnstered to au of the monkeys, and dexamethasone (2 mg.m.) was also gven.to those sustanng frontal ablatons. The anteror frontal leson was defned by von Bonn and Baley's (1947) areas FD, FDtl, and FDy, extendng from the mdlne to the lp of the lateral surface through both banks of the sulcus prncpals, and from the depth ofthe anteror bank of the arcuate sulcus rostraly to nclude the entre frontal pole. The posteror paretal leson was defned by von Bonn and Baley's areas PF, PC, PE, and the more dorsal portons of areas OA and TA on the lateral surface. The leson ncluded the anteror bank of the lunate sulcus and extended rostrally from the lunate through both banks of the dorsal porton of the superor temporal sulcus to nclude both banks of the ntraparetal sulcus. A several-rom-square area superor to the ntraparetal sulcus at the preoccptal notch was also removed. The ventral lmt ofthe leson was defned bya lne drawn frol'. the t1>ofthe ntraparetal sulcus to a pont several mllmetres below the tpofthe Sylvan fssure and then drectly n a lne perpendcular to the lunate sulcus. On the medal surfa the leson was defned by areas PE and OA extendng ventrally almost to the calcarne fssure and ncludng the anteror bank of the pareto-occptal sulcus and all of the tssue rostral to that sulcus for approxmately 10 mm. Followng completon of behavoural testng, the monkeys were perfused ntracardally under deep barbturate anoesthesa wth salne and 10 percent formaln, and the brans were blocked stereotaxcally n the coronal plane. They were hardened n formaln and 30 per cent sucrose-formaln, embedded n gelatn-albumn, and frozen; 50 f'm sectons were taken n the coronal plane, then mounted and staned wth cresyl volet for mcroscopc analyss of the lesons. Lateral and medal vews ofthe lesons were reconstructed from enlarged tracng usng seral sectons every mm. Reconstructons ofthe ndvdual brans wth. representatve coronal sectons through the anteror frontal and posteror paretal lesons are presented n fgs. and 2 respectvely. Apparatus All tranng was carred out usng a PDP-8 computer-controlled DADTA (Dscrmnaton Apparatus for Dscrete Tral Analyss; Prbram, 1969). Durng tranng the monkey sat n a testng cage measurng cm x cm x em, one sde of whch conssted of bars spaced at cm ntervals. Ths cage was placed n a small enclosure llumnated by a S-watt house lght n the celng. The monkey faced a c;m x em square panel on whch there was embedded a four-by-four regular array of clear round plastc push-panels, 2'54 cm n dameter. Mcroswtches mounted behnd each of the response panels sgnalled the presses to the computer, and lee dgtal dsplay projectors back-projected the stmul through these panels. A computer program controlled the sequence ofstmulus locaton, the ntertral nterval, rewards, and the teletype whch recorded the responses. A correct response caused a mechancal feeder to delver the banana pellet food reward to.a sngle foodwell centred just below the array of response panels. A large one-way mrror permtted observaton of the monkey durng tranng. Procedure Pre-operatvely all monkeys were ntally shaped to press only lt panels n the DADTA and were then traned on a colour dscrmnaton problem and ts reversal. Post-operatvely all monkeys learned three vsual dscrmnaton problems (Brody, Ungerleder and Prbram, 1977); each monkey was then assgned to one of four tranng groups (see Tables 1-4). Each tranng group learned four sets ofproblems: Personal Spatal (P-Sp); Extrapersonal Spatal (EP-Sp); nternally-ordered Sequences (-a Sq); Extemally-ordered Sequences (E-O-Sq). The tranng of these problemswas counterbalanced such that fr-"-

6 ...,. '...---_..,.. -._._..._.._..._.._--_.._..._-_._ ; _.""'.._. --_.. "'" 612 BETTY ANN BRODY AND KARL H. PR'BRAM.!.,, FG.. Antmor frontal lesons. The extent of the ndvdual lesons on the lateral surface was reconstructed from enlarged tracngs of the coronal sectons taken every mm. Four representatve coronal sectons are presented for each bran. The dark lne on the coronal sectons ndcates the extent of damaged or absent tssue. FG. from e n tl!. ; - "-"" '."".'.- Ol."

7 -----_._...._-_._._--_._---_.,. SPATAL AND SEQUENCE FUNCTONS 613!, ; FG. 2. Posteror paretal lesons. The lateral and medal extents of the ndvdual lesons were reconstructed from enlarged tracngs ofthe coronal sectons taken every mm. Representatve coronal sectons are presented as n fg.. r

8 ---._------_.._ _..._----, 614 BETTY ANN BRODY AND KARL H. PRBRAM Groups A and C learned the spatal problems frst and Groups B and D learned the sequences frst. The order of tranng was further counterbalanced as follows: Tranng Group A: EP Sp p Sp E-O-Sp 1.Q-Sq Tranng Group B: E.O-Sq.Q.Sq EP Sp p Sp Tranng Group C: P-Sp Ep-5p.Q-Sq E-O-Sq Tranng Group D: -Q.Sq E.Q-Sq P-Sp EP-Sp Three ofthe 7 monkeys gven frontal resectons were traned as members ofgroup B for the dscrmna ton and sequence problems only; all the other monkeys completed au problems. All monkeys worked 100 trals a day, sx days a week to a crteron of90 correct out of 100 consecutve sets of 10 trals (100 trals) for e8(;h problem. Detaled descrpton of the testng procedure follows: E.'Ctrapersonal Spatal Ta.sks: FreStart. The monkey was requred to press consecutvely two (or n the case of the 3-element task, three) contguous panels n anyone horzontal row ofthe array n order to obtan a pell.:t. For the ntal tasks the monkey was permtted to start anywhere, press a panel, then press the panel next to the one he had just pressed. All actve and lt panels dsplayed the stmulus '' (a whte pattern aganst a dark feld). Aftereach correct press the stmul dsappeared, then mmedately reappeared as before, except that the pq1lel the monkey hadjust pressed turned green. The tral ended and an eght-second ntcrtral nterval began whenever the monkey made an ncorrect press or successfully completed the two or three consecuve presses requred. There was no tme lmt for respondng at any pont durng the tral, but rewards occurred only followng the last correct press. The monkeys were traned n successve steps begnnng wth just two contguous panels lt. Snce repeat presses were gnored, no errors were possble and only 50 trals were gven. The monkeys were then traned to the 90 per cent crteron wth 4, 8. and 16 panels lt, begnnng wth a 2-element verson n whch they were permtted to start anywhere and then requred to press one panel next to ther start ng panel. They were then traned to the 90 per cent crteron agan wth 4, 8, and 16 panels lt on a 3-element verson n whch they were requred to press three panels startng anywh. The thrd press was correct f t was made drectly next to ether the frst or the set:ond panel just pressed. Three correct presses were therefore not necessarly contguous presses, but any correct press after the frst one was always next to a green panel. Extrnpersonal Spatal Tasks: Forced Random-Start. n order to avod the tendency ofthe anmals to smply press the same two or three panelseach tral, at the begnnng ofthe tral only two panels appeared lt wth the '' stmul n random postons on the array. A press on ether panel caused 15 of the panels to dsplay the ''stmul and oneofthe panels to dsplay a green crcle. The monkey was then requred to press the pq1lel next to' the green panel n the same horzontal row. Ths 2-element verson was also followed by a 3-element verson n whch the frst correctpress caused all panels to be extngushed and then reappear mmedately wth 14 of the panels lt wth '\'s and two consecutve panels lt wth green crcles. The monkey was agan requred to pressone panel next to etherofthe green ones. Pressngether a green panel or any other ncorrect panel tennnated the tral wthout reward. The ntal two ''s, the green cue, and the two consecutve green cues n the 3-element verson all appeared n dfferent locatons from tral to tral accordng to three ndependent pseudo-random sequences, That s. the locaton ofthe llccn cue was ndependent of the ntal press. Thus, all monkeys learned eght versons oftheextrapersonal 'next-to' task to the same90 percentcrteron n the followng order: 2-4, 2 8, 2 16, 3-4,3-8,3-16, 2-2R, 3-2R. The tnt number ndcates the number of responses requred wthn one tral, the second number ndcates the number of conset:utve panels ntally lt, and the 2R ndcates two panels ntally lt n random locatons on each tral. Personal Spatal Tasks: FreStart. Ths task had exactly the same requrements as the free-start extrapersoffal ta.sk. The monkey was permtted to start anywhere on the array and then" requred to press two or three consecutve panels n a horzontal lne. The thrd press of the 3-element verson was permtted to be next to ether the frst or the set:ond panel just pressed. However, n ths task when the monkey pressed a panel. all ofthe pq1lel lghts dsappeared then reappeared exactly as before, that s all dsplayng' 1's.

9 ------_ _._---.. "' '-_.,,'-- SPATAL AND SEQUENCE FUNCTONS 6lS Pers01lQ Spatal Tasks: Forced Random-Start. As n the extrapersonal random-start verson the ntal dsplay conssted of only two randomly lt panels. A press on ether of these panels caused all 16 panels to dsplay ''s. The monkey was then requred to press the panel next to whchever ofthe panels he had chosen ntally. For 'the 3-element verson he was requred to press three contguous panels startng wth whchever panel he chose ntally, and agan the thrd press was permtted to be next to etherthe frst orsecond panel pressed. n addton, repeat presses were not permtted. Any repeat press as well as any other ncorrect press termnated the tral wthout reward. Agan all monkeys learned all eght versons ofthe personal'next.to' tasks n the same order: 2-4,2 8,2 16,3-4,3-8,3-16, 2-2R, 3 2R. Thus n both the personal and extrapersonal 'next-to' tasks the monkeys were frst traned usng a seres ofdsplays n whch all ofthe possble response panels were ntally lt (free start versons). The appearance of the dsplay was stable and the monkeys were permtted to establsh stable response patterns. They were then transferred to random-start versons of the task n whch the relevant stmul shfted spatal locaton from tral to tral. Ths change prohbted the monkeys from usng stable response patterns wth the same sets of panels every tral. Externally-ordered Sequental Task. The three problems n the order n whch all monkeys learned them were 'red green' (large soldly coloured crcles); '0' '2'; and '0'-'2'-'6' (whte patterns aganst a dark feld). On each tral the two stmul (or three n the caseofthe 3-element sequence) appeared n randomly.placed locatons on the four by four panel array. n order to receve a reward the monkey pressed frst the red and then the green panel rrespectveof ther locaton. The stmul dsappeared after each press wthn a tral and reappeared mmedately n a new random confguraton accordng to a programmed 100 tral pseudo-random sequence, thereby makng spatal strateges rrelevant. The trl! ended and an g:second ntertral nterval began when the monkey ether made an ncorrect press or successfully completed the sequence. There was no tme lmt for respondng at any pont n the sequence, but rewards occurred only at the end of a complete sequence. llternally-ordered Sequental Task. The three problems n the order n whch all monkeys learned them were 'blue'.'yellow' (a blue flled plus and a yellow flled trangle); '4'.'5'; and '4' '5'-'7' (whte patterns aganst a dark feld). Ths task was presented n exactly the same manner as the externallyordered sequence task except that the monkey was permtted to choose dfferent orders from tral to tral as long as any gven sequence contaned no repettons. Thus, for the 2-element 'blue'-'yellow' sequence task ether the order ofresponses blue yellow or yellow-blue was acceptable. For the 3-element sequence on any gven tral there were sx acceptable orders: 4-5-7, 4-7-5,5-4-7,5 7-4,7 5-4, and Because ofts dffculty, ths last problem was traned for a mnmum of5,000 trals and a maxmum of 10,000 trals. Spatal Tasks RESULTS The data obtaned from the varous 'next-to' tasks reveal four strkng results: Frst, there were no sgnfcant dfferences among any ofthe groups n the ntal free-start verson ofether the personal or the extrapersonal task (Table 1). Secondly, on the random-start verson ofthe personal task (fg. 3) the Frontal Group had { defct compared to both the Normal and Paretal Groups, whle the monkeys n the Paretal Group performed' well wthn the normal range Ths dfference only attaned sgnfcance for the 3-element verson of the task. The Kruskal-Walls nonparametrc one-way analyss of varance by ranks (Segel. 1956) for three ndependent samples gave a nonsgnfcant H = 0 89 for the twoelement verson and an H=6 05, P<0 05 for the three-element verson. Pared

10 , _._ "-' -.,_.._---- _._- -_._--_._.--_._-_ _..._. 616 BETTY ANN BRODY AND KARL H. PRBRAM. :-". comparsons usng the Mann-Whtney U test for two ndependent samples (Segel, 1956) ndcated that ths overall group dfference was due to, the poor performance of the monkeys wth frontal lesons. The comparson of the Frontal and Paretal Groups gave a U = 0, P = 0 014, and the comparson of Frontal and Normal Groups gave au =, P= TABLB 1. TRALS TO 90 PeR CENT PERFOUANCB LevEL 'NeXT-To' FREE-START TASU Tranng Extrapersofl41 Personal Subjects Group 2-press 3-press.2-press 3-press N-w A SO 70 N-Zld B N-Gld C Mean P Brc A P Tbs B Grf C P-Tag ::: Mean F-Ose A F-Pp. B F-Smn C F-Clb D Mean N = Normal Group; P= Paretal Group; F = Frontal Group. Thrdly, on the random-start versons of the extrapersonal task (fg. 4) both the Frontal and Paretal Groups demonstrateda sgnfcant mparment comparedto the normal performance. The Kruskal-Walls analyss of varance ndcated sgnfcant overall dfferences among the three groups for both the two-element and threeelement versons of the task. For the 2-element verson H == 6 20, P < 0 05, and for the 3-element verson H = 6 40, P < For the 2-element verson the Mann Whtney U test gave a U = 0, P < for comparsons between both the Frontal and Normal Groups and between the Paretat and' Normal Groups. For the 3-element versons the comparson between the Paretal and Normal Groups gave. a nonsgnfcant U = 2, P = There was complete overlap between the Frontal and Paretal groups on both versons of the extrapersonal 'next-to' tasks. Fourthly, on the random-start tasks, the performance ofall monkeys, ncludng the mparment shown by the Frontal Group, was ndependent of the level of testng sophstcaton they had attaned pror to begnnng these tasks. On the free-start

11 ..,.._._----._... _ ; '---_..-.--_ SPATAL AND SEQUENCE FUNCTONS 617 &--4 FlDfT.U. (tf-.) Cl---G!f1]RJ!AL (f-]) o---e P.tRETAL (f-.) 2500 :!.. " \: :l!l z ;:.... "" :.l '- 8 P!R CElT PER70RlAYC LEV!. 't1fo PRESS 80 PER CllT-.:Jl L&nL TlU Pll8 FG. 3. Personal 'next-to' task. The cumulatve number of trals requred to reach each successve performance level (percentagecorrect) durng acquston oftwo versons ofthetaskare presentedfor eachexpermentalgroup. Two-press verson-ntalze press, then press the panel next to the panel just pressed. Three press versonntalze press, then press the panel next to he panel just pressed, then press the panel next to ether one of the two panels just pressed. All monkeys learned the two-press verson frst and then the three press venon. oool FRlfTAL (11-.) o-._o\ll S01llW. (:<-3' 1400 Qo- PtalETAL Cf-.) :l. " '" " ẉ. z ;:;!! " 1200 ṇ.. :! 80.. w '" : "e ;:: f PEa CDT PElFOtlllAlfC1 LYL no PRESS Pa ClfT PlOlWlC LllYlL mr11 PRUS FG. 4. Extrapersonal 'next-to' task. Learnng curves are presented as n fg. 3. Two-press verson-ntalze press. then ress he panel next to thesngle green panel. Three-press verson-ntalze press, then press he panel next 10 the smgle green panel, hen press the panel next to ether one ofthe two adjacent green panels. All monkeys learned the wo-press verson frst and then the three-press verson.

12 ._ _._----_.--.._------_.._--._ _---._ BETTY ANN BRODY AND KARL H. PRBRAM f f1.! - r t tasks there was a sgnfcant tendency for the monkeys who learned the extrapersonal tasks before the personal tasks (Tranng Groups A and B) to reach crteron more slowly (U = 2, P =0,02, N 1 '2 = 6,5 two-taled) on the extrapersonal tasks and more quckly on the personal tasks (U = 1, P = 0'008) than those who learned the tasks n the reverse order (Tranng Groups C and D). However, there were no dfferences among the leson groups n ths tendency, and the effect became nsgnfcant by the 3-element verson of each task. Smlar comparsons for the random-start tasks ndcated extensve overlap among the performances of the tranng groups (Table 2). TABLE 2. TRALS TO 90 PER CENT PERfORMANCE LEVEL 'NEXT-To' RANDOM-START TASKS Tranng Exrrapersonal Personal Sflbjects group 2.press 3-press 2-press 3-press N-Lns A N-Zld B N-Gld C Mean P Bn: A P Ths B P-Orf C P-Tag Mean S F Ose A F-Pp B F Snn C F-Clb Mean Tranng stopped after 80 per cent but before 90 per cent crteron attaned. n order to detect any further dfference n the nature of mparments produced by frontal or paretal cortcal damage, several types of error analyses were performed on the data from the random-start versons of both 'next-to' tasks. Whle learnng the personal task the monkeys made many of ther errors by pressng the other one ofthe two 'ntalze' panels. The number ofncorrect presses on the 'other-ntalze' panel was talled for the frst 100 non-repeat errors made n learnng the 2-element verson. The expected frequency of such an error n 100 trals s 7. The means of the observed frequences for the Normal, Paretal, and Frontal Groups gave Z scores respectvely of 9,04, 16,7, and -0,2. That s, both the monkeys of the Paretal and Normal Groups, but not the Frontal Group, made sgnfcantly more of such errors than would be expected by chance., ' ; ''' '''J._... Ll

13 ;'".l'.o.._ 00._.-. _... -_-.. _._.!.._ SPATAL AND SEQUENCE FUNCToNS 619 For the extrapersonal 'next-to' task where the Frontal Group was as mpared as the Paretal Group, none of the error analyses revealed any dffetences n behavoural strateges. The frst 100 trals n whch each monkey made exactly 50 correct responses were talled accordng to the locaton to the rght or left of the green cue for the correct responses and the spatal locaton for the ncorrect responses. The data ndcated that all monkey dstrbuted ther correct responses relatvely equally to the rght and left of the green cue, and there were no group dfferences. There were no dfferences among the groups n the tendency to ncorrectly respond to the green cue tself, to ncorrectly press panels that were on the same horzontal row but separated from the cue by one panel, or to ncorrectly press panels that were vertcally or dagonally next to the cue. Furthermore, there were no dfferences among the groups n the. tendency to contnue ncorrectly pressng the panel next to the 'ntalze' panel.,, Sequence Tasks The data from both the externally-ordered and nternally-ordered sequence problems reveal several strkng results. Frst, the level ofsophstcaton was qute clearly the most mportant varable n determnng the ease wth whch rhesus monkeys were able to learn such sequences regardless ofthe type ofbran damage they sustaned. Second, the monkeys wthfrontal ablatons showed a strkng mparment whch was dependent on ther level ofsophstcaton. However, sophstcaton apparently needs to be defned dfferently for the two types of sequences. n the case of the externally-ordered sequences, any extended experence wth the automated apparatus produced sophstcaton. Not only dd the two tranng groups (C and D) whch had learned the nternally-ordered sequences frst perform well on the externally-ordered sequences, but the monkeys n Group A, who had fnshed the spatal tasks, also performed equally well despte the fact that the externally-ordered sequences were the frst sequences they experenced (Table 3). n the case of the nternally-ordered sequences, general sophstcaton apparently dd not suffce. Only those two tranng Groups (A and B) whch had prevously learned externally-ordered sequences were able to learn the two 2-element sequences sgnfcantly faster than ether of the other two tranng groups regardless ofther level ofgeneral sophstcaton (Table 4). The learnng curves of the monkeys wth paretal damage showed complete overlap wth the curves of the normal monkeys at each crteron level; ths was true for both the sophstcated and the nave monkeys (see Tables 3 and 4), There-' fore, n order to determne whch factors were contrbutng to the dfferences between the groups, two-way analyses ofvarance were calculated on each ofthe sequences at the 90 per cent crteron level wth the Paretal and Normal Groups combned to form a sngle Control Group. The two factors analysed were (a) level of sophstcaton and (b) presence or absence offrontal cortcal damage. A sgnfcant effect due to level of sophstcaton was obtaned on the three easest of the sx sequences traned; that s, the 'red'-'green' (F=4808, d.f.= 1/10, P<O OO) _.._.r '_..., 4

14 r._ _ _.,,,..-,."_.._...._._-_.. _.-...._--- _.-_... _ BETTY ANN BRODY AND KARL H. PRBRAM TABLE 3. TRALS TO 90 PER CENT PERFORMANCE LEVEL EXTERNALLY ORDERED SEQUENCE TASKS Tranng Subject! group Red-green O-Z o-z Nave N Z1d B P-Ths B Mean 188S S F-ss B 2420 lloo 5160 F Pp B F Al B S F-Mdb B Mean S 6998 Sophstcated _N-Lus A 610 S N-Gld C S N-Bn: A 370 SSO 2830 p Orf C P Tag D S70 Mean 748 S F Dse A F-Smn C F-Clb D Mean and the 'O''2' (F = 14, d.f. = 1/10, P < 0'004) extemally-ordered sequences and the 'blue' 'yellow' (F = 42, d.f. = 1/10, P < 0,001) ntemally-ordered sequence. There was both a sgnfcant leson effect and a sgnfcant nteracton between level of sophstcaton and leson for the '0'-'2' sequence (F = 7'1, d.f. = 1/10, P<0 024; and F=9 3, d.f. = 1/10, P<0 012 respectvely) and for the 'blue' 'yellow' sequence (F=12 9, d.f.=l/lo, P<0 005; and F=lO, d.f.=l/lo, = < respectvely). Specfc- comparsons ndcate that nave monkeys wth frontal ablatons had a sgnfcant defct n reachng the 90 per cent crteron compared to the nave controls; for 'red' 'green' (t=2'56, d.f.=4, P<0 05); for '0' '2' (t=3 12, d.f. = 4, P < 0'05); and for 'blue' 'yellow' (t = 2 54, dj. = 3, P < 0'05). n con trast, the sophstcated monkeys wth frontal ablatons performed extremely well. Ther learnng scores were completely wthn the range of those of the sophstcated monkeysfrom the Paretal and Normal Groups. The dfferences between the mean scores of the nave and sophstcated monkeys wth frontal ablatons were hghly sgnfcant; for 'red' 'green' (t = 7 44, d.f. = 5, P < 0 005); for '0' '2' (t = 4,09, d.f. = 5, P < 0'005); and for 'blue'-'yellow' (t = 5,01, d.f. = 5, P < 0,005).

15 _... _ ,..._. ;;.:,"_ '..-.-'''''''.--'-.. -:<',?-.-;..-= SPATAL AND SEQUENCE FUNCTONS 621 TABLE 4. TRALS TO 90 PER CENT PERFORMANCE LEVEL NTERNALLY ORDERED SEQUENCE TASKS Tranng Subjects group Yellow-blue 4-5 Nave N-Gld C P-Grf C P-Tag D Mean F Smn C F-Clb D Mean Sophstcated N Lns A N-Zld B P-Brc A P-Ths B Mean F-Dse A F-ss B 20 F Pp B F AJ B F-Mdb B 1830 Mean The learnng curves for the three externally-ordered sequences (fg. 5) suggest that the nave controls became sophstcated faster than the nave monkeys wth frontal ablatons. However, there were too few subjects n the Control Group for the nteracton effect to attan statstcal sgnfcance n a three-way analyss of varance wth repeated measures on the three sequence problems. The ease wth whch each monkey was able to solve the nternally-ordered sequences correlated hghly wth the degree to whch the monkey lmted the number ofpossble sequences he actually used durng a sesson. The monkeys were ranked accordng to the number of tmes each monkey used the same one of the two possble.correct sequences durng the frst 100 trals n whch he made exactly 90 correct responses. The Spearman rank correlaton (two-taled) between that rankng and the ranks on trals to a 90 per cent crteron was Rho = 0,68, P < 0 01 for 'blue' 'yellow' and Rho = 0 63, P < 0 05 for '4'-'5'. The sophstcated monkeys had means of 88 and 87 responses of the same order for the 'blue'-'yellow' and '4'-'5' seq uences respectvely whle the nave monkeys had respectve means of only 62 and 69 responses of the same order. Moreover, those monkeys who had prevously learned the fxed sequence 'red' 'green' began the 'blue'-"yellow' sequence.. '

16 , _... ;;;;;:;... --;;;;;;;;;;-E":;:;::' ""'" _.. -, l::!. 3500, j... oc «to Ẇ A '"w > ;:! u 0--0 nonal N..V R-4) COTlL N"VE N-2)...-..,lOTAL PSTCATD N-3) COTlOL 8DPlSTCATE 111-:11 " " /'.-...,...".tr',1:)".,- PEl CEHT PERFOUNCE un:!. aeuee,0 /,/ 1250 ; 10 a 150' ;:: oc 5 u,,'/ /,/ PS CENT PEU0811AHCE Ln:!, 0-2 / / ; = ::,.. = S :10 '-0-1 pa CElT PE...ORANCB LEVEL FG. S. EXlernally.ordered cquence tasks. The cumulatve number of trals requred to reach each successve performance cvel (percenlage correct) durng acquston orthe three sequence problems arc presented separately for the nave lnd sophstcatcd Frontal and Control Groups. The Control Group conssts of the monkeys wlh paretal lesons and the norm;al monkeys. All monkeys learned all three problems n tbe order 'red' 'green'; '0' '2'; '0' '2' '6'. 0-a-8 't:ll tr -< > ZZ t:ll ;ll o o-< > Zo >;ll t'" ;: 'U - ;ll t:ll ;ll > S' _...

17 " "N l--.'._.-_._-'--'- _.,.-_ _._ _ SPATAL AND SEQUENCE FUNCTONS 623!, ; j \. l ;. j!! '. ;.. J. 10 ', j,!0!!j usng almost exclusvely the yellow-blue order even though ether order was correct. There was no partcular tendency for the monkeys wth frontal ablatons to lmt the number of possble sequences they used more or less than the control monkeys. Only 3 (one monkey each from the nave Frontal, sophstcated Frontal, and sophstcated Paretal Groups) of the monkeys traned on the 3-element nternally-ordered sequence showed any tendency to lmt therchoces among the sx correct possble sequences. Each of these 3 showed a sgnfcant tendency to begn the tral wth the stmulus '5'. Moreover, these 3 plus one addtonal normal sophstcated monkey were the only monkeys able to reach an 80 per cent crteron wthn the allotted 10,000 trals. The remanng 8 monkeys requred between 7,000 and 10,000 trals to reach a performance level of70 percent correct, and there was complete overlap n the learnng curves of all tranng groups regardless of leson or level of sophstcaton. For the 3-element externally ordered sequence there were sx possble ncorrect responses: '2', '6', '0'-'0', '0'-'6', '0'-'2'-'0', and '0'-'2'-'2'. For the 3-element nternally-ordered sequence there were three types of ncorrect responses: XX, XYY, orxyx. An analyss ofthe type oferror made at the 50 percent performance level for both sequences also faled to reveal any consstent dfferences among groups. DSCUSSON Spatal Tasks The purpose ofths partofthe study was to re-examne the relevance ofa personalextrapersonal spatal dchotomy to frontal and paretal cortcal functon by tranng monkeys on conceptually smple 'next-to' tasks. The results dd not provde the doubledssocaton predcted by ths dchotomy: whle the Paretal Group was mpared only on the extrapersonal 'next-to' task, the Frontal Group was mpared on both the personal and extrapersonal 'next-to' tasks, but only under a randomstart condton..the fact that the monkeys ofthe Paretal Group were sgnfcantly mpared on a task whch requred them to press a panel next to'a green cue but were unmpared on a more dffcult task whch requred them to press the panel next to ther own prevous press supports the usefulness of the extrapersonal-personal spatal dstncton wth respect to paretal functon. t s true that the Paretal Group dd not show the expected defct on the ntal free-start verson of the extrapersonal task. However, n that verson the 'ntalze' panel tself became green so that the task could be solved by gnorng the green cue and smply pressng the panel next to the 'ntalze' panel, that s, by treatng the task as ft were a personal 'next-to' task. t s nterestng that these fndngs from monkeys parallel the fndngs from patents wth paretal damage confned to the rght hemsphere. Such patents show only extrapersonal spatal defcts even though patents wth left paretal damage show both personal and extrapersonal spatal defcts (Semmes et al., 1963; Teuber, 1964; Butters et al., 1973)..

18 0- _._._. --_..._._-_... "" _ '---'.---_ BETTY ANN BRODY AND K.ARL H. PRBRAM J'j!j,' The surprsng result n ths study was that the Frontal Group was as mpared as the Paretal Group on the random-start extrapersonal 'next-to' task. Nether an emphass on spatal memory mparments (Goldman et al., 1971) nor on personal. spatal orentaton (Semmes et al., 1963; Pohl, 1973) would have predcted that monkeys wth frontal damage should have any defct on a task whch smply requred the monkey to press a panel next to a vsble green cue. The task requred nether memory nor personal orentaton. The mportance of the spatal factor wth respect to frontal cortcal control mechansms was frst suggested by Mshkn and Prbram (1955, 1956) when they found that several non-spatal varatons of the delayed-response and delayedalternaton tasks mproved the performance ofmonkeys wth frontal resectons. Although a spatal hypothess became less tenable when they next demonstrated that frontal resectons produced defcts onan extremely dffcult rght-left alternaton task that were as severe as those on spatal alternaton, an unusually good performance on object alternaton by one monkey n the Frontal Group called for further analyss (Prbramand Mshkn, 1956). To ths end, Prbram (1961) devsed a multple locaton object alternaton test whch was more readly learned by monkeys. Hewever, he contnued to fnd a defct after frontal lesons although performance (70 per cent) was better than on spatal alternaton (50 per cent). Mshkn, Vest, Waxler and Rosvold (1969), usng Prbram's new test, tben found a dssocaton between object and spatal alternaton by makng more restrcted resec'tons wthn the frontal cortex. They demonstrated that monkeys wth lateral frontal resectons. confned more dorsally to the regon of the sulcus prncpals contnued to have a profound defct on spatal alternaton but were able to attan a performance level of80 per cent on object alternaton. n contrast ther monkeys wth more 'ventral' resectons, ncludng both orbtofrontal and ventrolateral frontal cortex showed profound defcts on both the spatal and object alternaton tasks suggestng the monkeys were dsturbed by the reversal factor nvolved n both tasks. These results ndcate that dfferent functons may be dfferentally localzed wthn the frontal cortex. Despte ths, we chose to utlze the larger dorsolateral resecton defned by"tle projecton of the parvcellular porton of the nucleus medals dorsals (Prbram, Chow and Semmes, 1953) thus nvadng the ventrolateral cortex. Ths choce was made because we wanted to evaluate both spatal facton (on the bass of tbe above data presumably located around the sulcus prncpals) and temporal factors (possbly located more ventrally). As we were nterested n analysng the nature of the defct rather than ts localzaton, we utlzed the small number of subjects avalable to such a study to control for test., varables rather than to subdvde the group accordng to a varety of lesons..: However, because the resectons dd nclude the entre anteror lateral surface,,j possble effects specfcally due ether to damage to the frontal eye felds (area 8) j or to nvason of the ventrolateral surface must be consdered. Results of earler studes ndcate that an explanaton n terms of perpheral j.-,...,"...''!"...:':"',-.-.

19 ,_..._-----'._--' -.. -_.._---"'--_.;--..._ "_.--- ".,,-.., SPATAL AND SEQUENCE FUNCTONS ,'-'! l, j,, J, l!! ', 0 0 J.}!, f1 '1 t j, : t t nattenton or neglect due to damage to the frontal eye feld s unlkely to account for the observed data. Monkeys wth unlateral damage to area 8 do demonstrate transent neglect of the contralateral vsual feld, but they do not show neglect after blateral damage (Kennard, 1939; Prbram, 1955). Presumably f frontal damage caused an attentonal neglect ofthe perpheral feld of vson, the errors made by the Frontal Group would centre around whatever pont on the response panel array the partcular monkey tended to fxate.' Fxaton ponts were not measured n ths study; however, the Frontal Group demonstrated the same error patterns as dd the Paretal and Normal Groups on the extrapersonal 'next-to' task. Ths pattern oferror was n fact random wth respect to both the green cue and the 'ntalze' panel. Mshkn and others have postulated that the ventrolateral surface s part of the frontal cortcal regon n whch damage produces perseveratve nterference (Mshkn, 1964; Butter, 1969; versen and Mshkr., 1970; Passngham, 1972). n the present study, the method oftranng the monkeys to learn the extrapersonal 'next-to' task nvolved a shft from the free-start verson n whch the green cue appeared on the panel the monkey had just pressed (necesstatng a response to the panel nxt to the frst press) to a random-start verson n whch the green cue appeared n random locatons (generally necesstatng responses away from the 'ntalze' panel). Ths shft n the response pattern requrement could have created defcts due to perseveratve response tendences. However, error analyses revealed that there were no dfferences among groups n the tendency to perseverate the response next to the 'ntalze' panel. By the tme the monkeys had attaned a 50 per cent correct performance level such perseveratve errors consttuted less than 15 per cent of the errors for each group. Furthermore, when the monkeys from ths studywere traned ona landmarkreversal problem, the Frontal Group demonstrated a normal performance (Unger:leder and Brody, 1977). Reversal learnng tasks n general have been shown to be extremely senstve to perseveratve nterference errors (Mshkn, 1964; versen and Mshkn, 1970). Therefore, f the monkeys had sustaned suffcent damage to the ventrolateral surface to account for ther defcts on the bass ofperseveratve nterference, they. should also have demonstrated sgnfcant perseveratve nterference on the landmark reversal task. Thus nether a perpheral nattenton hypothess nor a perseveratve nterference hypothess adequately accounts for the data. However, other detals of the performance ofthe monkeys wth frontal lesons suggest an alternate explanaton for the unexpected dffculty the Frontal Group had wth the random-start extrapersonal task. Frst, the data ndcate that the Frontal Group demonstrated an mparment on the personal 'next-to' tasks only f the 'ntalze' cues shfted spatal locaton randomly. from tral to tral and only durng the 3-element verson of the task. Observaton of the monkeys durng the learnng of ths task ndcated that ths. mparment was due to ther nablty to flexbly shft ther response patterns from <),. :

20 '''' ' ",,' , , ,. _._ _.-,, a-,'..," ;,j ' 't! 626 BETTY ANN BRODY AND KARL H, PRBRAM. ', a left-rght movement to a rght-left movement, or vce versa, when the locaton of the 'ntalze' cues on the response-panel dsplay demanded the drecton ofmovement opposte to the ndvdual monkey's preferred drecton. Only the 3-element verson n whch three consecutve panels had to be pressed wthn a four-panel row requred frequent shfts n the response pattern. n addton, stll other aspects of the data ndcate that the Frontal Group mght have been relyng heavly on movement stereotypes to solve the personal 'next-to' task. When the monkey's were frst learnng the task, the Frontal Group made sgnfcantly fewer errors by pressng the other one of the two 'ntalze' panels than ether the Normal or Paretal Groups. Unlke the other monkeys, they made that error at chance frequency. The occurrence of such an error at a level greater than would' be expected by chance mples that the monkey remembered correctly where the locaton ofthe stmulus was before all the panels became dentcally lt. lbe fact that the Frontal Group howed no evdence of rememberng where the ntalze cues had been strongly suggests that ther normal performance on the random-start 2-element personal task was dependent on movement stereotypes learned n the ntal free-start versons. Moreover, the lack of a sgnfcant group effect n the 2-element random-start task was due more to the ncreased varance ofthe ablty ofthe Normal Group to solve ths more dffcult task than to a partcularly nspred performance by the Frontal Group. Thus, the ablty of the monkeys n the Frontal Group to depend on movement stereotypes could expla ther normal performance on the free-start and the 2-element random-start personal task. These movement patterns faled n the 3-element verson of the personal 'next-to' task specfcally because flexblty of response was requred. Perhaps then the defcts of the Frontal Group were unrelated to spatal processes n both the personal and extrapersonal 'next-to' task. Recent neurophysologcal fndngs provde evdence relevant to ths queston. There s a populaton of sngle unts n posteror paretal cortex whch responds when arm movements towards relevant stmul are co-ordnated wth vsual fxaton ofthose stmul n space (Hyvarnen and Poranen, 1974; Mountcastle, Lynch, Georgopoulos, Sakata and Acuna, 1975). These data support the vew that the posteror paretal regon s specfcally concerned wth spatal orentaton. n contrast sngle unts n dorsolateral frontal cortex do not respond n relaton to arm movements but rather respond when the monkey must hold relevant nformaton n memory pror to makng a response n a delayed response ordelayed alternaton paradgm (Fuster, 1973; Kubota and Nk, 1971; see also Stamm and Rosen's macr.oelectrode analyss, 1969). Thus neurophysologcal data as well as the behavoural data ofths study suggest that the frontal cortex s nvolved n hgherorder control functons. Such functons are easly tapped by personal spatal tasks but may also be tapped by other problems, such as the extrapersonal 'next-to' task and the sequence tasks whch consttute the other part of ths report.