B n The Hippocampal System and Recombinant Processing

Last night, during surgery, a graduate student, ill discussi~lg his future, made [lie c o ~ ~ l ~ l t e n t that the I~ippocampus was tlle black hole of the neurosciences. Surveying the four volun~es tllat lsaacson and I have edited OII the sul?ject, I Iwg;~n to wonder whether perhaps Ile was correct. especi;~lly when 1 recallrd 111at tl~esc four \*olunies d o uot convain their own re\liews of the prodigious eflbrts of Breada hlilner, Ross Adey. Jarlles Olds. Mortimer hlislikin, and the teanis of Squire and Zolir-Morgan and of O'Keefe and Nadell, all of ~\*lioni wcre a s k d but f i ~ r one re;rso~~ o r otllel- could not psnicipate. ,

As in the case of tile cosnlic I~lnck holes, ig~lorance is not the only f'allout (or s11vuld I sit)', fall in?) to result fro111 t l ~ e experinlenu and analyses t~lotivared by tlie "l>uzzlc wrapped in an e~~ig-ala," a11 older descril~tion of this beautiful piece or ~~euro;~rcliitectu~.e tlllrt is the I~ippocampus. 1 - w i ~ I I ~ ~ O ' L C I I C ~ can I)c discerned i r ~ tlie rcseairll. 011e of tllesr uses tllr hippo- carilpus as a model system to study generalizable functions o f neural nrt\vorks; t l l r other is add~.essed to the functions of the hippocampus per sf.

In this chapter. my concern is or~ly wi~h the secorld of tliese approaches, bvhic11 is implemented by t.evie~ving tile r x l ~ e r i ~ ~ ~ c l ~ t s performed iri rny

1. 1 1;rboratory and the theory developed OII tlic basis of' laloriltory discussions 3 of tl~c=sc esl,r~.ir~~cnts. Xly 11l1,tivation is si111l)le: tlcspile sc.\.cral t1ec;idc-s of ,

experinlentation using monkeys, there is almost no nientiori in the current literature of the data we obtained (e.g., see hlahut, and also Gray and Rawlins, this volume, and Zola-hlorgan t-t al., 1982). The reasons for this neglect may be many, but one possibility is that the data and conclusions were, presented in a form that could not be readily digested by those who did not participate in the experiments. In this chapter, I address this possibility.

Before reviewing this work in detail, the basic procedure by which the experiments were performed is set out briefly. Much of the work to be described was accomplished in the 1960s, when funding <or basic research was ample. Thus, each of the experiments described below involved two to three groups of at least 4 monkeys each. In a typical experiment, one group of morikeys was subjected to hippocampectomy arid another to amygdalec- tomy, and a third served as a control group, altogether a total of 12 monkeys. The experiments in which both the amygdala and the hippocampus were removed-the medial temporal lobe resections-used a minimum of 8 subjects. ( In these experiments, hi/~ocutnpe,erlomy refers to removal of the entire hippocampal gyrus and thus includes, in addition to the hippocampus, the sul)ic.ulum and the entorhirlal cortex. The control group was given surgery identical to that performed in the operated groups except that no tissue was removed.)

Behavior was assessed quantitatively in a coniputer-controlled system that allowed us to automate an extensive battery of tests (Pribram, 1969). This system, called DADTA (for Discriniination Apparatus for Discrete Trial Analysis), consisted of a portable chamber within wliich the monkey could niove about readily. The monkey was able to reach a 4 x 4 array of translucerit Plexiglas panels through bars along one side o.f tlie chamber. Underrrcath these patlels was a small food cup that delivered banana pellets. Visual pltterns were projected onto the panels by digital display units, controlled by computer. The computer also kept track of tlie panel presses rriade by the monkeys, their reaction times, and whether tlie responses had

, k e n reinlbrced. In col.rect trials, the pattern reappcarcci each tinie it1 a Iiew ltuation (another panel) alier a 5-s intertrial interval. incorrect responses niercly turried off the display without ttie delivery of a rei~~forcenient and irii~iatctl (ilfter 5 s) another trial. Si~riulti~neous deprcssior~ of IIVO pa~lcls was

'

1101 rcwarcled and delayed the next trial by 10 s. Fai1ut.c to press any panel \ c , i t t i i ~ l 5 s resulted in a timeout of' 10 s, during wliicll ttle house lights were clirnr~ied before the next trial was initiated.

For tlie most part, the tests were developed as modifications of paradigms that, i r i orher hands, had been thoroughly analyzed so that the variables c.~.itical to perforniance were known. Nonetlieless, niodification entails the r~eed for I-rir~~erpretation according to the sl,ccifics of the t;~sl;s as tlics are act~l:!ll\ I;r csented. As a result, ttie co~~clusic~ns deri\.c.tl f1-on1 the experiments . . . -

Hippocampal System and Recombinant Processing 33 1

the paradigins themselves can emerge that provide biological grounding to hypotheses held at the behavioral level.

2. Limbic versw Nonlimbic Learning and Alernoty

2.1. A l t m t i o n versus Discrimination

The historical roots of the work reported here were reviewed in the introductory chapter of the first volume of this series (Isaacson and Pribram, 1975). T h e use of monkeys as subjects was motivated by the work of Kliiver and Bucy (1938, 1939), who had removed the entire temporal lobe-and had found a dramatic change in behavior to result. The monkeys were tamed and sexy and put all sorts of objects in their mouths. These findings were not entirely new, as similar results from temporal lobeaomy in monkeys had been reported during the latter part of the nineteenth century by Sanger- Brown and Schafer (1888). These early results became the basis for sugges- tions by Economo and Koskinas (1929) and Pap& (1937) that Broca's grot& lobe lintbique (defined on the basis of a thick, and therefore white, first cortical layer) served as the forebrain system responsible for emotional experience and expression. In addition to these early findings, the Kliiver-Bucy monkey: showed what they termed "psychic blindness" (1938).

In order to relate the variety of these behavioral phenomena to more specific brain regions, I tiegan by making subtotal resections of various parts of the temporal lobe and was able to show that the visual disturbance was due to removal of the lateral portion of the temporal lobe (Blum rt al., 1950; Mishkin and Pribram, 1954). but that damage to the medial "limbic" structures, the amygdala and the hil)pocampus, produced taming (loss of fear as de~~ioilstrated by accelerated extinction in a conditioned avoidance procedure; Pribram and Weiskrantz, 1957); diminished aggression (as mea- sured in a dominance hierarchy; Ros\,old et al., 1954); and oral changes in behavior (as determined by a I'ol,l>elreuter preferance procedure and food intake measures; Pribram and Bagshaw, 1953).

The extent of the lateral temporal lesion was localized to the infero- ren~~xwal cortex by nleails of a multiple dissociation technique that involves the addition and sllbtracrion of overlaps of location in terms of behavioral outcome. l'llis technique is described in detail in Pribram (1954a, 19580,b. 19GOo; Pribram and Kruger, 1954). AIany of tlirse early experiments treere performed before automation and involved a variety of discrimination tasks administered in various apparatuses such as Yerkes (IVisconsin) boxes and s~looperscope television devices. We found that the entire posterior iiltritisic "associarion" cortex could be s~ibdivided according to sensory ~nod;~lity: Infcrct~rnlpol.al resections disrupted visual discrin~inations (Hlum rt ol., 1951); R f ; , l . l . : - ---I I > . ' : .,.- ..

res~~lted in dclicits in taste discrimination (I'l-ihram a l ~ d Bagsliaw, 1953); a ~ ~ d posterior parietal damage resulteti in ti~ctile discri~nination deficits (Blum c! al., 1950; Pribram and Barry, 1956; hl. \Vilson, 1957).

In clear contrast to the above results, resections of the aniygdala and the Iiil)l)oca~npus resulted in no discrimination deficit whatsocvcr. Instead, we f0urid marked changes in conditioned avoidance (I'ribran~ and M'eis- krantz, 1957), don~inance (Rosvold el al., 1954). and oral (I'ribram and Bagslla\c, 1953) behaviors. In addition, and most important for tlie analysis pursued here, there was a marked deficit in the learning and performance of the delayed alternation task (Pribram et al., 1962). Such deficits are also obtained when parts of the head of the caudate nucleus (Rosvold, 1972), the far-frontal (prefrontal; frontal granular), and cingulate cortices (Pribram el al., 1952) are resected. As no such deficit appeared as a result of any of the lateral cortical resections, the frontal and limbic formations, including the lie dial ten~poral lobe structures, the amygdala, and tlie hippocampus, were classified together as frontolimbic and juxtal~osed to the systems of the cortical convexity (Pribram 1954a,b; 19600,b; 1971).

-1'hr essential characteristic of tlie discrimination tasks that we enlployed - was thitt the monkey's choice of either one of two or more cues was consiste~itly reinli~r-ced (or consistently not reinforced), and equally important, tliat the cues were conti~luously present until a choice was made. S y contr;tst, in the del;tyetl alternation task, choice cannot be guided by tlie specific cues present at the time. T h e correct choice always depends on what was done on the previous trial. This means that the cue-reinforcement contingencies are inconsistent. Jacobsen and Nissen (1937) ternied this sort of task "one trial learning," and more recently, Mishkir~ (1978) referred to it as "trial unique."

Wliile these experiments were in orogress, a paradox ell~er-ged. \Pllcn we con~pared our data to the neuro~)sycl~ological studies on humans with far frotital lesions, as in the leukotornizeti (loboto~i~izcd) patients, there \\*rre

e'. co~lsistc~it ~~a~ . ;~ l l e l s betwee11 tlie effects i l l ~no~ikcys a11t1 those obti~ined \\.it11 I I I I I I ~ ~ I I S (see, e.g., Pribram, 1950, 1951; I 'oppe~~ 1.1 (11.. 1965). Tliere were ~ I I S O sir~lilarities I)ct\ceen the syndrome prodi~ced by an~ygdalectotny io

. I I I I I I I ; I I IS ;tnd rnonkc).~ (Pribram. 19(jla,b). Ho\vcver. \ \ . l l c~~ the e l~ t i~ .e niedial est~.tit of the I{-niporal lobe, including anlyg<l;tla ; I I I ~ I I ~ ~ ) ~ > ~ ( . ; I I I ~ ~ ) I I S , was rebcc.trcl i r i hurilirris, no cha~iges wcre obscr\'ed in kliaviors tliat could LK' descri1)cd as enlotiol~al or motiva~ional, such as in avoidance (fleeing), ;r~grt.ssion (fighting), feeding, o r sex (the Four Fs; see I'ribran~, 1960a.b). I~istcad, a very distressirlg and peculiar long-terrn defective memory was 1)1~uc111c.~tl (hiilner a ~ l d I'enfield, 1955; Scoville a ~ l d 3lilnrr. 1957; for a review 01 t I~c ~);iriidox, see I'ribra~n. 19GOb). hly perso~l;ll ct1c.ountc.r \virl i tl~is 11." ; i t l o \ came as folio\\-s:

.. .

Hiplwarnpal System and Recombi~\a~\r Prtxessi~lg 333

to take a look at H. hi. becairse he seemed sorilewhat peculiar. I was eager to examine such a patient witli a view to finding out how his emotional responses differed from those of unoperated subjects: we had just obtained our results in a conditioned avoidance experiment (Pribr.am, 1954a,b; Pribram and Lt'eiskrantz, 1957). which was the first quantiiative experin~e~ltal deficit obtained from lesioning the hippocampus. Much to my surprise. therefore, H. M. responded normally in all respects. He discussed his relationship with his family; we had an interesting conversatio~i about a subject we were both interested in, a possible trip from Capetown to Cairo, during which H. M. became quite animated. I tested him on recall of lists such as telephone numbers and again found him to be normal. At this point in the interview, I was called to the telephone. On my return, I tried to recall where we had left off, somewhat unsuccessfully, and so turned to H. M. for help. Had we been doing telephone numbers? O r were we doing subtractions? H. RI. stared at me for some time and then asked. with a puzzled expression; "Doctor, have I seen you before?"

The distraction caused by the interruption tiad apparently produced a coniplete amnesia. H. RI. had appeared so utterly normal to me that I had doubted that Scoville had succeeded in the surgery. I had seen no change in emotions, no change in memory (the Africa journey tiad been a pre- operative interest). Now the memory defect was striking. Distraction had, as i t were. wiped tlie slate clean. Before 1 left him. I suggested to H. M. that he, carry lists of activities to which he could refer whenever his memory failed him.

1 knew that Brenda Milner had found similar disturbances of memory in patients operated on by Wilder Penfield at the hlo~itreal Neurological Institute. I therefore asked hIortinler hIislikir~, who knew Milner, to alert her to the existence of H. RI. and to ask her if she might be interested.in studying him. The rest is history. It has now becn some 30 years that hlilrler has regularly interviewed and tested H. M. and obtained results that liad to be taken into accourit in all of the subsequent experiments on the functions of the amygdala and the hippocampus in 1u)tlr I I I I I I I ~ I I S and animals. I

I'tie paradox witli which 1.1. hf. ~,rese~ited us made i t necessary to ex;rnli~~e rlost.ly the diffirence betwben the d i sc r i~ni~~at ior~ tasks that so clearly set apart the effects of resectio~is of the posterior cercbral convexity and tlie alternation tasks that were disrupted by frontolinibic Icsions. Discri~iiir~atio~i tasks are particularly useful in the stucly of long-tern~ nleaiory, wl~ereas delayed alternation and related delay t;lsks such as delayed response had her1 the standard for exl)loririg st~ort-ter111 Illernory ever since their intro- ductior~ I > \ Hunrer (1913) ant1 t l~eir ;~l)l~lic.i~tior~ t o the ;cn;tl!.sis ul- 11rai11 l'~rt~ction 1,). ~arot>cc!i (l!!28, 1936; .]acobsrn r ! ul . , 1995) ;!!ltl ~l;:coljsrrl ;III(!

resections were especially sensitive to pro- and retrorlctive interfel-el~ce, a result that was extended by Prilranl (IYGI) and th;~t clarified considerably the nature of' the short-term nieniory defect. I t was possible that H. M.'s deficit reflected a reduction in an enlianced c;il~abilit). (compared with that of mollkeys) of the human brain to resist interference. On the other hand, the nianner in which we dichotomized memory into short-term and long- term may have been iricorrect (see. e.g., Pribram in Kimble, 1967).

\%'hen there is a sharp dichotomy between the effects of brain lesions on two types of behavioral tasks, it is important to discover where the boundary between them may be drawn. Discrimination .reversals in which animals must suddenly adjust to a new stimulus-reinforcement co~itiugency provide a tool for titrating such a boundary. What effects would medial temporal lobe resections have on the learning and performance of discrim- ination reversals? T h e answer to this question ought to bring us closer to underst;inding the deficit shown by H. M.-in the sense that a sudden reversal nlay serve the same function as the distraction wlletl I left the room. At the same time, a discriniination reversal deficit would relate the deficit in delayed alternation (a trial-to-trial reversal) to a wider range of beliaviors.

Our initial expectation in undertaking a series of discri~ilitiatiorl reversal experi~~lents was that medial teniporal lolx resectio~~s would i~iflue~ice [lie slope of the learnitig curve. This change in slope \could, in turn, be increased by reversal. We were at~empting to influellce wliat is known as a "one- element" (at a time) model of learning. I'hese niodels assume tliat ar~i~iials (or 1iuni;tns) attend to only one feature of a conlplex stir~iulus, sucli as color or the slope of a line, at a time. A multis~age niodel of this type propcrly tirscrilwd discrimination learning in unoperated, no~.rii;il ~ ~ ~ o l i k e y s (Bleliert, 1966, in our laboratory) as well as in l~umans (Zeanlan and H o ~ ~ s e , 1963). M'e fou~id in ou r study that nonrcinforced choices wcrc climino/td one a1 a time L'ro~l~ the respollse repertoire on a cue-by-cue b;lsis.

In [lie series of expeririients on discrimination reversal ill teniporal lolw Irsioncd animals, we used 1 I naive lllolike).s, wilt1 7 rno~lkcys scrviiig as

"..: c.or~trols ;lrid 4 receiving cxtcnsive rcscctio~~s of' tlic r11lil.e ~llrtlial ~ )o~ . t i o~ l ol tht. trrrll)oral lobe, including tlle hilqx)c;inq~;~l gyrus arid tllc ; ~ r i ~ y ~ d ; ~ l a . 'I'lie surgery was performrd LeI'or-e atty testing. 'I'he 111o11kcys \vc.l.r trained rollowilig surgc*~y i l l t t ~ c IIADI'A to disc.ri~iiiri;~tc bct\veel~ tlic ~ iu~nera l s 2 arid 4, \vllich ;~j)pearrd-irl d i f f c r c~~ t loc.;~tio~is (i.c., 011 tiif'tkrcilt 1);111cls) VII

each tri;~l. Tllc morikeys were trained to critrrion pc.rSor~ii;~rice and \\.ere ~l ien givt.11 another 100 ovcrtainiiig tri;ils? wcrr rested lor 3 ~vceks, and \\.ere tcstcd tin retent ion.

For the discrimination reversal task, 111e nuri~erals 0 and 5 wrre used, ;~rld rrvci.sal training was iristit~rted as so011 as t l ~ e rlio~~key re;~rlird criterion (90'; O I I I OO corisccuti\*e tri;~ls). \$'II;II 1t.r I'i~ut~cl \\.;is c011tr;iry to OLIT

~ \ l ~ ~ ' \ ; ~ l i , , n s : [ I l c of' [he l e a r l l i r l t r r . t tr-\ .r .c * , . , . * -#x I.....-*.'.. . . - - - . I . - . . - . I I . ' '

aspects o f these discrinlinatio~l-learning tasks are a function of the posterior isocortex.

However, the anlygdala-hippoca~tl~l resectiott lltarkedly s l u u w f learning ~ionetheless. The inlpairnte~lt was localized to ihe portion of the learning curve that is relatively flat (i.e., "stationary"). These periods of stationarity showed a ntarked prolongation, and even more severe disruption appeared during the cue-reinforcenient contingency reversals. M1e interpreted these results in terms o f an operant cottditioning framework, in that "behavior during discrimination learning and reversal is under the control of two competing variables: the patterned cues to be discriminated and the noncon- tingent schedule o f reinforcenlent" (Pribram et al., 1969, p. 770). Further, the insights derived front tltis analysis helped to establish a relationship between the behavioral deficit and theories on incentive motivation and hypothesis formation. An excerpt front the discussion of this study summa- rizes this relatio~tsllip:

hforlkeys w i th linilir lesions . . . sltow a l o ~ t g p la t ra t l a f te r t l reir pcrfornial ice reacl~cs a c l ta l l re 50% level. Despite tlris. t h r s l o p s o f t l l r r i t rvcs 011 eitltc.r siclr o f this platcall art. ronrl)arable t o tlrosc in o r iK i~~ ; t l I e a r ~ l i ~ ~ g . I t is d i l ' f i iu l t t o rnp la i l t t l ~ e s r results i n t r r n i s o f ' at1 inabi l i ty t o discri:nit~;ttc Iw twern s t i~ l tu l i .

0 t i e us). of ro l ls ider ing t l ic plateau is t o stragest t l ~ a t t t i r s i t ua~ ion dcx-s 1101 iur l l is lr s t ~ l f i c i e ~ ~ t it~ce:clrtire t o al ter t l lc 1n:lt;lvior ljf nicrnleys w i t l i Irsions. T h i s woi t ld rollfor111 - t o ideas t l iat t l ie l i i i tbic systcnr is a sulwtratr o f ~rtot ivat iol l . I lowever. n o si11111le r e k r e l ~ c e t o t t ~ e st inlulus situation p r se wi l l yioviclc a suf f ic i r t t t cx l~ lanat ion. T h e r i les renrain r t te same; t t ~ e ovel-all probal i l i t i rs df t l teir In-il~g r r i ~ l f o r c r d Irave 1101 ctrairged. \lf/rat ha\ rlaurtgfd duritry m * r r ~ a l h thr ~liurl-trn11 p m k ~ h i l i t ~ tlrot rllr rnotrhryi r r~ f~ot lc r u ~ i l l br rrirrjutrrd. A/~/m~rrrtly. u lh i rhh prulx~hility r ro rhn 50%. a di.~po.~itiun ur ~ t a t r b itrdurrd it! thr hi/#-atn

Inlotrhrp with rcsr r t io~~t of rlrr hip/watnpuc atad fhr nm~gdala] I~JUIIL~J, but trot llrr trort~u~h. u ~ l r i r l ~ Ira& tu a cottritruatiotr u f ' tlru r r l a t i ~ ~ r l j itirJfrrtilv pr jurmarrrr. Tltr qurstittt) b Ituu. b r ~ t to rha ru r t r r i v Bit .rtatr.

T l t c data a n d t l ~ r o r i e s o f Z r a n ~ a n a ~ t d I l o u s r (1!1(13) woul t l appear to be relevatlt . .

t o present findilrgs, a n d t o o l l i r a possible answer. T l ~ r o u ~ I ~ the use o f Imcliwards I r a r i ~ i ~ ~ g curves tliese invest ig ;~~ors hav r li11111tl results nrucl i l i L r ours. i t 1 l t t ~ ~ r l a n

r r ta rda te leartring. T h a t i,. discri t i i i~ia~ic)r i Jc;~rning apl)~.:trs 10 in\.olve a statit)lra;y i ~ c r i o d o f \aryil:g Ir t lgt l r itr wliiclr t l t r SIIIGCCI i s correct at t w l y a CII~IICC p~~Lab i l i t ) . .

l ' l i i s is I 'ol lowrd by a n abrupt ly r is ing c u r v r o l r r la t iv r l ) cotistaitt slope fro111 one Iwrrorr o t l ~ r ~ b l ~ l l l t o t l ~ c t l rxt. Tllrir data, a1111 o u r f i~lcl i l rgs wit11 Illarty ~ i o r l i i a l ~nonkcys. indicate. t l la l t l t r c f i fk l . r l ice ~.IH.CCII a d i l l i cu l t a l l t l a11 easy prob l r rn o r a lasl a l l d a SIIIW lt.;~r~ir~ i~ i n t l r r l c n g t t ~ of t11c SIAI~~III:II~ prriwl p ~ i c ~ r I~I 111r l a k c - t ~ f l IMI~III.

F t ~ r t l ~ c r i t i u r c . a stati1111ary pet-itkl is ~II~II So111id at tlrc. 5U% 1n,i111 i n rrvt.rs;~l Icar11i11~ i f 1 IIIIIII~II reurdaws . X r a n ~ a ~ t a ~ i d I ~ o u s ~ s u g ~ c s t ~II;II tltc s1xti1111ary l w r i t d i n a d i s r r i l t ~ i t ~ a t i r r ~ ~ - l r a r . l ~ i r ~ ~ ~) rob len i is onc in w h i c l ~ t l ~ r su l j cc t l rar t is a l l o b b r r v i t t ~ resp t l sc or. i n c~ t l t e r words. l c a r ~ l s w l l i c l ~ ~SOVCIS 01'tt:r c o t r t l ~ ~ i t ~ ~ d s t i t i ~ i i l i 10 a t t c ~ \ d to.

A l o n g 11;1t pritd niigl t t t t i r ~ ~ indicate i l lat t l ~ r i n s ~ r t ~ ~ i ~ e i t ~ ~ t l and cr l t~r rv i t ig r r ~ ~ m ~ t i ~ r s h a v r cot r l r i t~ idrr 111r c o t ~ t r o l of (III'SCIC~I as lxc ts of t l t r ~ r i t ~ f ' t ~ r c r ~ ~ ~ c ~ ~ t M~IIC~IIIIC. .lSl:c S~;II~IIII;I~) pc t . i~ut ~ I I I ,~ I I~ r rv r r sa l :I .t i~t i l~g tlttrs r r p ~ r3c11ts a11 c ~ ~ i ~ t t t i u t t tjf tltc p t r \ ic~ttdy :1l1111olwi~tc t~Lmr~.\'iii): rrsl,ollscb. kl~i l t . IIIC i l ~ \ l t t ~ r l ~ ( . t i l . t i II.~~*III\CS ;arc ~f l ; t i t~l .~i~rccl 1)). lllc ,?,of; s< llr(flllv. ,r\t?l,~rcl::!,. I\,,. ;,l,llri..l .., ,..I ... I.-.: I . . . . . . . . . . ;- ......I. 8 . . ' - . ' '

p ~ ~ l ~ l e l l ~ had bc.c~l plc.sc.trted. I t is in this srl~sc /"I give I I ~ ) " ] 1~rI1aps111;~t the lilr~bic s)stctn can be wid to play a role in incenti1.e t~~trtiva~ion.

The results can also be i~~terpreted in "l~ylw~tllcsis Tor~n;~tion" tcrtur if observing responses are take11 as indicators of I~ypvthesis tcstir~g. he^^ an orga~lisnr'r trbservi~rg (11 a dizti~~ctive leature or stin~ulus dinletlsiot~ is reit\f'orced. an hypothesis (attenlive state) Itlay br i~lduced which increases ~ l t r l i lel i l~wd tllat this frature will Iw olrservcd ajiain. 'l'his hypothesis will be either confirn~rd or disconfirn~ed on sul,seque~~t trials. As already noted. two separate factors seem to be r e sp l~~s i l l c Tor Irarl~ing ill tlle clixri~~tination selling. One is likely to be related to the stimulus dinlensio~~s per se and. thus. ~~obabilistically will distribute observing anlong dinlensions. \Yith t ~ o other n~ccha~~ i sm than this. an). subject could I n r r ~ any problem in whicll the ctrrrect stir~rulus dinrrnsi~~n has a finite probability of being observed. \{'it11 low prokability stin~ulus dirnct~sions. however. this learning could be extren~ely protrarted.

T h r second factor is likely to be related to the duration over wllirh any I~).lmtl~esis is Iwld ill the face of disconfirmation. It is this fac~or (a criterio~l for relitlquishing tlle hypvthcsis) which is nlost likely to be regulated by limbic structures.

l'his study and earlier ones thus rrriphasize the fact that tllr distribution oTattentiol~ is detr~.r~rincd by at least two factors. 011e is tlir-cc-11y relatrd to sti~nulus di~net~sio~ls; the other to the te~nlwral organization of the le;lr~~ing sitltation. OllIy tlre second of rl~ese. 111e duration over which an hypothesis is l~ r ld ill the ('ace of di>tracticrl~ and c l i s c~~ l l i~ nration. is critically afferted by anlygdalcc.tc)~~~y and I t i ~ ~ y r ~ a ~ ~ ~ p e r t o m y . 7')iis Inay rwl~lain why alri~rlals with hippocan~pal alrd ;~ l~~ygt l ;~ la 1csio11 (or k)tlt) I~a\.c tltrir c h:tr;lt.cc.ristic lear11i11~ ditliculties. and l ~ r h a p rclu;rllp i~lllwrta~lt. wily they can reatlily solve n~c~st discrimination problenis in whirl1 tllc t.cil~forcil~g rtr~ltir~jie~lc.i~s arc 1101

rarircl. (I'ribratn rt ul.. 1969, pp. 770-77 1 )

T h i s ;ttlalysis d i r ec t ly i nvokes t h e t1teoretic;tl f ~ . ; t t ~ r e w o r k of inceti t ive ~ t ~ o t i v ; ~ t i o t ~ and hypothe;is tes t ing . M'hat is s u g g e s t e d is th;rt the r l l o t~keys

with n tedia l t e m p o r a l lobe resec t ions are i t l s u f f i c i e ~ ~ t l y n ~ o t i v a t e d to m ; ~ i t ~ t a i n

;I I ~ y p o t l ~ r s i s in the face of d i sconf i rn t a t i on ; t o n la i t i ta in a k l t a v i o r (a l~c.l t ; tviori~l slance or se t ) in t h e face of d i s t ~ a c t i o t l ; and t o resort to obt;ri~lirrg

;I low-belleli t (50%) i n c i d e n c e o f r e i t ~ f o r c e n t e r ~ t 1\.11en the cost (d isc : r i~~l i t~ ; t t ing t l te c u e s ) l 'or o b t a i n i n g a greater benef i t (90%) b e c o ~ ~ ~ e s t o o h i g h 101. tlleril

(tltoug11 110t for contro ls ) . A n o t l ~ r r way of s t ; t t i ~ ~ g t h i s is t o s;ty t11;tt t h e dil'fc-retli.c 1)etween o b t a i n i n g a 50% and a 90% r e w a r d is i t ~ s u f ~ f i c i e t ~ t inceritive

libr t l t c t ~ ~ o n k e y s wit11 m e d i a l tempor ; t l lobe r e s e c t i o t ~ s : t l icy fail to "~>;ty" ;.:.-. s t t e t ~ t i o l t t o tire discr.ir~tin;itive stiriiuli irt o r t l e r t o ; tchicvc t l te itlrrcasccl

t.c.\\.;t~.d.

'l ' licse ior lc lus ions w e r e t e s t ed it] a final r s p e r . i t r ~ e t ~ t i r l t h e s c ~ . i e s invol\-i t ig

thr ct~tirc tttedial a spec t (alnygd;~l; t ~)l t rs h i p p o c a t n l ~ i r s ) of r l l r t r t r ~ p o r a l lobr. 111 th i s rx1)c.r-irnerlt. w e modified a s i g ~ i a l - d e t e c t i o n , d e c i s i o n - t l ~ e o r y paradigm i n ; ~ n a t t r t l l p t t o clearly separate I,ell;t\.iot. c.oli trollrd by t h e srimitlus ("de- tcc tior!") ; t t r d tli;tt c o r ~ t r o l l r d by t l ~ c r c i u t i ) ~ . c i u g c o n t i n g e t ~ c i e s ("bias"). Eight I I I O I I L V \ S \\c.re u sed : four stt l?jectrd t o 3urxc.r-y ; t t~d foitt. s r~ . \ . i t t g ;is t.ot11r01~.

' 1 111. I , I ~ ~ C C ( ~ ~ ~ I . C c~,IISiSted 01' I ) s ~ ~ t t c l c ~ l ~ ; l ~ l t l , ~ r v ~ l \ ~ rl;ct~l.,..;.r,- *...., ..:.....I: I '

Hippocampal Syste111 and Recombinant Prc~cssir~g 337

screen. Discrimination learning and reversal trainirig procedures were fol- lowed as in the previous experiment. One of the stimuli (3) was reinforced 90% of the t in~e; the other (8) was reinforced on the other 10% of the trials. Thus, stinlulus control was effected in a 90%. probability reinforceme111 situation, and spatial location (position bias) came under the control of a 50% noricontingent schedule of reinforcement. Because monkeys readily succumb to position biases, the incentive of the 90% rei~iforcement schedule (for attending to the visually displayed cues) had to overcome this bias. (See . - .

Fig. 1.) The results clearly demonstrated that the nionkeys with resections of

the medial portion of the temporal lobe (amygdala and hippocampus) succumbed to their position bias more readily than did the control subjects. T h e control monkeys learned more quickly to make the discrimination and accomplished the rGversals much m i r e qUickly than the monkeys with th.? medial temporal lobe resections. l'lle dif'ferences in behavior were lin~ited to those portions of the learning arid reversal cumes where the mollkeys were making a sufficient number of errors (niisscs) so that their schedule of reinforcement was around 50% (plus o r ~rlinus 10%). Once the behavior reached the point where a discrin~i~iative s t i~~iulus was reinforced over 60% (and its mate was nonreinforced 400&), the l e a r ~ ~ i n g and reversal curves of the lesioned and control nio~ikeys were essentially indistinguishable. \%'hen response operator charactrristic (ROC) curves were plotted, detect io~~ (d') IS sl~own intact. The deficit in leztrning atid reversal was due to a greater influe~ice of position bias in the munkrys wit11 the lesions tllan in r l ~ e control subjects (wl~ich did demonstrate this Ipias as well, howevel-). As in the previous exlxrinlent, the n~o~ikeys witli ~iiedial ~c~iipol-al lolx resections succu~nbed ~ I O I - e than their controls to the relatively effortless 50% nonco~it ioge~~t opportunity for ol)taining rei~lforce~i~ent. 'i'lir potentially Inore rewarding 90R./IO% probability schedule, co~lti~igent on "paying" attention to the appropriate stiniulus, failed to be as powerflrl an i~icenti\*e for- the lesioned morike).s as it was for their conrrols. The nio~ikeys wirli [lie lesions did not as rr;~dily expcnd the "effort" to at tc~id, a ~iiotivatiolial, intensive aspect of ntter~tion delineatrd by Berly~lr (19GY), atiiongotlirrs. 'l'he reasoning i~ivolved in reaching this conclusio~l was su111111ari7.kd ill the reporr of the experiment by Sl~rvircl; and lJr.ibraln (1973):

l'llih I~~lw~tl icris suggrsts tli;it the nldjor rllc.ct p~.oduced by I~ilateral am)-gd;ilrc~on,).~niy and I i i l ~ l x ~ a n ~ l x c ~ o r t ~ ~ niag be to alter 111r i~,re~\sive aspects of attention (Bcrlylir. 1969). I f hi11-an1 subjec~s expcnd less efli~rt (11at1 tlte illtart n~onlt-ys for obtaining reward. lie). will show psit ion preferences during a larger ponion of discrilllitlation and reversal trials liar^ d o in~act cor~trols. H'lir~iever there is a reduction in 111e incentive value acrruiri~ to IIIC srilnulits clir~~cnsiori-as durir~g tlic chat~cr reward pcriods of rcvcrsal-tl~r trperinie~\tal tiionkeys resort 111 ;I period cjf ~ x ) s i t i t ~ l ~ 11rrf(-r1.11(~ ( C I I B I ~ ~ C levcls of' rrs1)011di11~) 111ut.e rapidlv tl1:111 on,).!^^ tllc i ~ ~ t a c ~ C < I I I I I C ~ I > . 7 tic rc<\iItit~g pcrio~l 01 (l1;111re ~ * C . I ~ < I ~ I I I ~ I I C C is I I ~ C I ~ ~ 1>1olo11gc(l 1 1 1 1 111r C S ~ I I . I . ~ I I I I . ~ I ! ~ ~ i~~!irr:al\ b ~ a t ~ c !It ( . \ . . . . .

O Z L 6 0 1 O R Y ~ ~ 2 0 Trlole to criterion x (00

FIG. I. (Ahove) Number of trials rqui rcd for 10 percent i n c r e n ~ r ~ ~ l s ill pcrforma~lce attd t l ~ e acquisition of the strict criterion after the last criterion during paltcrn discrin~ination Iearni~~g

,,. arid the first two revrrwls. (M): hip-an1 n~or~lieys: (0---0): i111ac-1 rnclnkeys. (Facing page) -.-'

(:c1111p&riw111 using KOC curves of 111c pcrlbrmal~rcs of a ~ykical I~il)lwcampal and a t!.l)ical contrcll s\ll+j,jc~~ during pattern diwri~nination and the lirst two reversals.

dinlrt~sion. Even alter tllc 11ipa111 subjccts d o r\cr~tually I ~ g i ~ l ro ~ c s l u ~ n d on the Irvrir of tllc stiat~ulus d i ~ ~ ~ e n s i o n , prcsumably bc-causr 111r irltcnsi~y of' rl~eir a ~ ~ e ~ ~ t i o n a l state has LK-CII s u f l i c i~~~ t ly altered, they still relaill their increased tcndencics to give up a t t c r ~ d i ~ ~ g and resort to a position bias. This hypothesis also suggests an explanatio~l for the dlllicultics of t l ~ e hip-am monkeys to maintain a criterion level of performance. once thrv have already acl~icucd the lax critcrion. Tllr same bias Tor pr~sition preference which c;luxd the experirnenlal anir~lals to rrrllain at a chance Icvel of rcspvnding at thr Iw~irrr~ing of pattern dixriminacio~~ I,jcarni~tg ac~d at the er~d c ~ f I I I V r \ t i r t c~ ic~~~ ~ ~ r r i u d ( i f I C - ~ U I >.,I, a r ~ d 10 recard acllir\*i~lv ~ r i ~ t - r i o ~ ~ i, s ~ i l l -am**.*---* -c.-- --:---:--

Hippocampal System and Recombinant Processing 3 39

c 0- .O .20 .LO .60 80 i.00 p hiinq 8 whm 3 on riqht

a 0- 0 20 .LO M) a0 60.00 p hittinq 3 w h 8 on riqht

c 1 0 0 1 l 6 ) I I I 1 I I -l

4 - - .80 - -

o - A q u i e i t i o n - r) g .60 - - x - - I .LO - - CP

- g 2 0 -

- -

C - - o . 0 I I I I I I I I I

0 20 40 LO M) . 1.00 p hittinq 3 when 8 on riqht

0 20 1 0 60 80 1.00 0 20 .LO 60 BO 100 p hiltinq 6 when 3 on riqht p hittinq 8 when 3 on riqht

lo the stimulus dimension, have difficulties in maintainingcritcrion performance during three successive test days.

Signal dcteccion a;lalyscs. therefore, have dearly demonstrated that the niajor diricrcncc be~wcm the h ipam and the intact s u b j m is in the intensive rather than the selective dinlension of allention-or to put it more baldly. in thc monkeys' niotivation. Funher, the analysis has shown tllat this motivario~~;ll difference brlwcrn the experinlcnlal and unopentrd monkeys during discrimination and rrtcrsal Icar~~irlg. is a quantitative and not a qualitative one: the \.ince~ltizcd di~rirninatiot~ atld rrvrrsal

At tlie conclusion of these experiments, i t seemed to nle that we had narrowed the apparent gap between the effects of nicdial telnporal lobe resections in monkey and human. H,owever, the terriis trrotivariol~, inteluitle dituetuion, and ef!jorl (especially eflort, as any such term derived from verbal reports of introspection) may not fully convey their technical meanings as they were developed in the laboratory and may well convey surplus meanings that are not intended. Specifically, as I hope to make clear, an increase in motivation (the intensive dimension of processing) is not due just to more "drive" (see also Miller et 01.. 1960). In this instance, motivation involves an incentive to reorganize the processing capacity of the organism. Attention theorists use the term ej/ort to describe a process that comes into play in overcoming the limited capability, the limited "span," that characterizes attention and the results of this limitation on performance (see Kalineman, 1973, for review). Most attention theorists conceive of an organism as having a fixed limitation in processing "capacity," but on the basis of experitlienis described below, McGuinness and 1 tiatre argued that attention span is uot fixed : I I I ~ that both external and internal flexible constraints are operating so that span can be expanded and contracted. C U I I I ~ P ~ P ~ I C ~ is a more accurate term to describe the span and its'lir~~itations. Competence, conceptualized in comrn~lnication theory terms, is the reciprocal of equivocation, that is, the sum of' noise and redundancy. "Effort can then be defined as the measure of a t te~~tion to increase or maintain efficiency by reducing equivocation, that is enhancing competency" (Pribrani and McGuin~~ess. 1975. p. 135). As we shall see in the following sections, redu~lduncy a ~ i d t~oise translate into "fa~niliarity" and "novelty" with regard to the effects of aniygdalectomy and hi ppocarnpectomy.

Co~nmunication theory is based on nieasl~ring how much infornlation in a cot~lmunication is necessary to reduce uncertai~~ty. Tlie measure of both uncertainty and irlformatio~~ is made in terms of the tiunitwr of alternatives that describe the communication. Shannon and Wcaver (1949) suggested

c,. . that this measure be made in terms of a bi11ar.y Uooli;~~i algebra, rhr bir (an acronym for bitlor). digit), and this suggestiori has been widely accepted. At the salile time, Shantion pointed out that a corno~i~nic;ition is oftcr~ mirde intrlligil~le by repetition. which in the jargon of the 11it.01-y is c;~lled rrdu?rdat~q. George Millcr and Iris collcagu~s performed an extensive series of' experi- nlrrits 011 thc role of redundancy in the intelligibility of a coliirliunication (see hliller, 1951) and the effect on memory and ease of processing of. "chur~kilig" o r packaging informatio~i (hliller, 1956). Garner (1962, 1969) exploretl the relationship between st~cli structuring and rrdu11d:rncy as exl>l;cr~arory of a host of perceptual iitld cognitive processes. I n i~~forniation rllcs;tsirl.elnent theoryprr-sr, this issue i~f 'con~l~ining ; I I ~ recot~~bi~i iug cl iunki~~g i s lt:i~~cii;.d by mealis of' t t ~ c COIIC-CIII (IS t)!x)vir!i~~;: ;lie ~ , , , t n ~ i t ; t ~ ~ ~ ~ t - i , ~ ~ ~

Hippocam pal System and Recombinant I'r-ocessi~~g 34 1

From the results of the c ~ ~ e r i r n e ~ l t s . which distitiguished the effects of resections of the posterior cerebral convexity from those of the frontolirnbic fortnations, and from the model derived fro111 them, it is possible to make a clear disiinction between the brain systems invol\*ed in processing information per se and the redundancy and structuring that enhance processing. J'ribram and Tubbs (1967) and Pribranl el at. (1966) showed that resections of far- frontal and medial temporal lobes affected the operations of the structuring and redundancy processes, and not those directly concerned with information processing.

T o illustrate this point, it is useful to cite an experiment seniinal in this distinction between information and structuring redundancy that was per- formed by Smets (1973). In this experiment, he compared the effect on alpha-wave blocking and skin conductance (measures of arousal) of changing the amount of information in a display with the effect of altering the "complexity," the structure of redundancy of the display. Increases in the amount of information (the nun lb r of features) had little relationship to the measures of arousal. By contrast, arousal varied directly with the coniplexity of arrangements among the features displayed. As we shall see in the following sections, the same measures of arousal were dramatically altered by far-fron~al and medial teniporal lobe resections (see also Pribram, - and McGuinness, 1975, and McGuinness and Pribram, 1980, for review):

In short. we suggest that the controls [on processing] operate on the n~cchanisrns of redundancy, on the constraints operating within and between char~neis rather than on the information being processed. The constraints . . . may be conceived of as operating on mmrur)' rather than on input information. Another way o f stating this is to say that the controls operate on tlte context in which the informational content is processed. (Pribram and McGuinness, 1975. p. 136)

Several paragraphs follow that cite supporting evidence from the work of Anderson and Fitrs (1958), Garner (1962). and Lindsay (1970), as well as from our own work (Pribram ct al., 1966).

T h e tecl~nical usc of the tern1 tjJfo~-t thus relates to the efficiency with wliich an input is processed and does tiot imply the inverse of laziness (a cotinotation in ordinary language). This efficiency is brougl~t about by the restructuring of )>roressirig chan~~els , a restructuring both within and between channels. Another tern1 for restructuring is recoditrg. Tl~us , the binary code of macliinr Iitnguage is recodcd into octal and assembly languages for more efficient processing under certain conditions (constraints). Furt her recoding into operating systems and word-prcxessing routines makes i t possible for me to use the binary-coded machine operatiotls to write this essay efficiently.

\$'hat appeared to be missing in h t h H. h i . and our nlonkeys \c.ith resections of the medial portions of tile tcnil)o~.al lobe was the ability to ~wovide \ , ;~r- ic .~) . in the constraints, tllc cot~~exts t l ~ i ~ t rnake cf?icient c o d i ~ ~ g of scns:)ry ~ I I ~ J L I I ~ j ~ j ~ ~ i l ~ l e . T t ~ e lcsiot~s it~i!):+i~eci ~>ci!!!cr :;!:c;::- iiGF : u ~ ~ ~ - t e ~ - ~ i i

a/ . (1968) for H. M., and by Pribram and Douglas, who tested monkeys on the retention of a visual discrimination two years after original learning and found no deficit. As reviewed in the final chapters of the first two volumes of this series by Weiskrantz and Warrington (1975), and by Pribram and Isaacson (1975), it was compe&tace (i.e., efficiency and processing span) that were impaired.

3. Hippocampus versus Amygdala: Novelty and Familiarity \

3.1. Factors That Injzuerue Processing Span

In the previous section, the effects of medial temporal lobe resections were cotlceptualized in terms of attention and information theory. This conceptualization helped to bring together to some degree the apparent discrepancies between the results of such resections in humans and in monkeys. Essentially, a distinction was made between information processing carried out by the neural systems of the posterior cerebral convexity, on the one hand, and the structuring of the context within which information is processed, which is carried out by the frontolimbic formations of the forebrain, on the other (see, e.g., Pribram, 1971, for review). T h e systems of the posterior cortical convexity were shown to be involved in processing invariants (which are the basis for alternatives, information) in organisrn- environment transactions. The frontolimbic formations, including the hip- pocampus and the amygdala of the medial surface of the temporal lobe, were shown to be involved in the competence (efficiency) with which processing proceeds. It was suggested that two factors influenced competence, redundancy and noise, and it was also suggested that competence involves structuring both the internal and the external constraints on the processing of information (in its technical meaning), producing flexibility in enhancing or limiting processing span.

The current section addresses the issue of what constitute rcdundancv and noise in the processing of span and whether these t w o aspects of competence can be teased apart by restricting the medial tem6ral lobe resection to either the amygdala o r the hippcamplrs. T o this end. a series of experillrents was undertaken in which amygdalectomized monkeys were compareti to those with hippocampcctomy and also to a sltam-operated group. Rlodifications of the discrimination paradigm werc used in which 70% versus 30% was substituted for [lie more usual 100% versus 0% scl~edule of reinforcement in order to make the tasks.sensitive to frontolimbic damage.

Hippocampal System and Recombinant Processing

reversal process consists of two stages; the loss of the familiar response and the acquisition of the new. In a new series of experinlents (Douglas and Pribram, 1966)cin\,olving a dozen monkeys, we found that tlie amygdalec-

,

tomized group of.monkeys had no difficulty in the first stage of discrimi- nation. During reversal, they were slighdy superior to the sham-operated monkeys in eliminating the familiar (previously correct) response but had some difficulty in acquiring the new response with consistency (much as in the acquisition phase of the extinction experiment; see below).

Hippocampectomized subjects were slow to initiate the extinction of responses to the familiar cue and were equally slow in initiating the learning of the new response, a pattern similar to that obtained in the monkeys with the combined "hip-am" medial-temporal-lobe resection. It thus appears that the effect on discrimination reversal obtained with the medial temporal lobe resection is largely a result of the hippocampal component of that lesion. When the reinforcement ratio approximates 50% during the intermediate range of revenal-that is, when the monkeys have given u p responding to the previously reinforced cue but have not as yet achieved responding correctly to the currently reinforced cue-the hippocanlpectomized monkeys remain stuck longer than d o amygdalectonlized monkeys and control subjects. Hippocampectomized monkeys apparently fail to process the change in the cue-reinforcement contingencies as efficiently as the other monkeys.

3.3. Learning, Extinctiotr, and Releanlitrg

From the fact that whenever the reinforcement ratio for performing without observing (discrimination) approaches chance, hippocampectomized but not amygdalectomized monkeys get stuck, we expected an even more marked and specifiable deficit in a discrin~ination procedure in which the reinforcements are distributed 70% versus 30% between the cues. Nornlal monkeys tend to maximize in the presence of such a probability distribudoa. This was also true of the monkeys with amygdalectomy and hippocampeci tolily. Duripg extinction, however, the hippocampectomized monkeys took 1011get than did the a~~tygdalectomized o r the control monkeys. M'liat the probability-matching procedure broughr out was the fact that the hippocam- pcctomizcd tnonkcys responded niost often to the nwre rewarded (70%) stin~ulus, whereas the amygdalectomized monkeys responded least often. This result provided a clue that was followed subseque~ltly in tests involving reaction to novel stimuli (see below). Finally, when reaction times were plotted, it was discovered that the hippocampectomized monkeys showed the shortest latency of responding throughout extinction, whereas the amygdalectomized monkeys showed the longest. In fact, the amygdalecton~- izcd subjecrs sho\ved more long-latency (over 2 s) reslw~nscs 111;ln did co~itrols. t~. l~c~-cas the l ~ i p p t ~ a i n ~ ~ r c t o n ~ i z e d ~ ~ ~ o n l e v s sho\c.ed fewer s ~ i r t ~ "t~esita~io~>"

'

tomy. At this point in the experimental analysis, the effects of medial temporal lobe lesions on orienting and its habituatiorl were clearly establislied:

The finding that the amygdalectomized Ss were more prone lo make long latency responses on the rewarded trials may be relalrd to Bateson's (unpublished data) obxwation that amygdalectomized monkeys cock tl~eir ears more often duri~tg the training procedure than do normal monkeys, which show a 111uch greater decrement in car movements as training progresses. This result niay also be relaled to the obsen.ation reported by Schwanzbaum and Pribram (1960) that aniygdalectomizcd Ss hesitate on test trials in a transposition task. (Douglas and Pribram, 1966. p. 210)

3.4. Paired versuc Scattered Stimuli \

The fact that hippocampectomized monkeys make few long-latency responses in our DADTA procedures was also demonstrated (Douglas arid Pribram, 1966) in an experiment in which the cues were either closely paired on the DADTA display panels o r displayed on panels more remote from each other. In this experiment, hippocampectoniized monkeys made signif- icantly more correct responses on the paired that1 on the scattered presen- tations, whereas no such effect was obtained in the anlygdalectomized and control nionkeys. When the stimuli were scattered, the hippocampectoniized monkeys pressed the cued panel that happened to be xithin their line of gaze irrespective of the nonreinforcement history of that cue. This was tlie second experiment in which medial temporal lobe resection o r hippocam- pectonly influenced the processing of notireinforced elenients in the stimulus array: the first was the experiment in whicli the multistage rnodel of learning was tested (see Section 2.3, "Discrimination Reversal"). M'e therefore under- took another experiment in which we directly collf'ronted the ariimal with a novel cue paired with a previously reinforced o r a pi-eviously nonreinforced cue.

3.5. Mused versus Spaced Trio& I

.- ' But before I report the results or1 the pail-ir~g of novel cues, arlotller "<'.

- relcvailt ~.rsult needs to be interposed. 111 this ew1)rrilncnt (Kitnble and I Pribram, 19G3). the effects on learning of anlygdalecton,y and hippocani- / prctorny were asscssed under the conditions of massed and spaced trials. I Cont1.01 and hippocampeciomizcd monkeys sho~\.ed a strady and equal : itt~provenit.~~t in performance as the intertrial interval is lengthened up to 6 min. Aniygdalectomized monkeys, on the other hand, learned more slo\csly as the i ~ ~ ~ c r r r i a l interval increased.

i t is assunled that, for normal subjects, the longer intervals reduce pro- a11d retroac.tive interference among successive reinforced and nonreiuforced : trii~ls; thus. learning is enhanced. The result that a~o!.gd;~lecton~y wiped out ~ltis aclv:~~~l;lgc supported earlier evidence ttl;!t a111ygdalectomi7ed morike)pc { . . . . \ i c . l - ~ c t~t~. ' i t i~~ak)l \ lrss s ~ I I < ; I ; \ , P 1- m--;-. . l- .:---- - .'

Hippocampal System and Recombinant Processing 345

fore, that the effects of medial temporal lobe resections on the redundancy factor that influences competence, the effect of pro- and retroactive inter- ference, are a function of t.he amygdalectomy rather than of the hippocam- pctomy portions of the lesion.

3.6. Reaction to Novel Stimuli

These results indicate that the two factors that influence competence, redundancy and noise, may be separately influenced by amygdalectomy and hippocampectomy. Interference among redundant trials was shown to be affected by amygdalectomy. In Pavlovian theory, the orienting reaction following a situation in which the organism has become habituated is paradigmatic for studying interference phenomena. The laboratory had \

undertaken a long series of experiments assaying the visceroautonomic components of the orienting reaction as a function of the effects of arnyg- dalectomy (Kaada rt al., 1949; Bagshaw rt al., 1965; Kimble et al., 1965; Bagshaw and Benzies, 1968; Bagshaw and Coppock, 1968) after we found that monkeys with these lesions failed to habituate to repetitions of a stimulus (Schwartzbaum el al., 1961). It was therefore a natural next step to insert a novel stimulus into the current series of discrimination studies.

In these experiments, we compared the effects of amygdalectomy to those of hippocampectomy on a task in which a novel cue was matched either to a cue that had been previously reinforced (70%) or previously norireinforced (30%) after the animal had reached a criterion of 90% in'l00 consecutive trials. w e found that, after amygdalectomy, the monkeys chose the novel cue and the previously reinforced cue at about 50% each, whereas llippocampectomized monkeys and control subjects chose the previously rewarded cue 80% of the time. Further, the amygdalectomized monkeys chose the novel rather than the previously nonreinforced cues about 70% of the time, as did the control monkeys, whereas hippocampectomized monkeys responded 50% to each. T h e amygdalectomized monkeys apparently at- I

tended to and remembered the nonreinforced cue as being nonreinforced, but they ignored o r forgot the previously reinforced cue. By contrast, hippwarnpectomized nlonkeys c h o ~ e the pre\.iously reirlforced cue more than 809% of the time over the novel one, but they cllose tlie novel and the previously nonreinforced cue about equally. The kppocampectomized mon- keys had attended to and remenhered the previously reinforced cue but had apparently failed to attend to the one that had been previously nonreinforced.

M'e concluded that amygdalectornized monkeys learued by attending to the nonreinforced member of a pair whereas hippocampectornized monkeys -learned by attending to the reinforced member. In the abse~lce of a 11ipl)oc2mnss, learning ?to/ to go,to a tlo,lrrit\fi~!-crd cur (i.r.. ;iciivelv iunorirlcr . 1 r . . . .

to tlre nrore rewarded (70%) sti~llulus, wl~rrras t l ~ e anr).gdalectonlized nion- keys responded least often.

3.7. Errors of Omissiuti and o/ Con~t~iissiotl

M'e tested our conclusion regarding the effect of hippocampectorny on norn~ally occurring active ignoring of nonreinforced elements in a task by presenting another group of monkeys a discrinlination in which there was only one reinforced cue, but in which the number of no~~reinforced cues varied from one to four. The control (and a~nygdakcton~ized) subjccts quickly learned to ignore the non reinforced cues; the hipl>ocanrpector~~ized monkeys did not (Douglas e! at., 1969).

4.1 . Orie~ltittg and Hahituutiotl

l ' l ~ e experimental analyses revirwed ia the previous section devolved on teasing apart the variables resporlsible for enl~ancing conljletellce a11d extel~dir~g span by increasing f1exil)ility in processing. As noted, irr illfor- 111atio11 nleasurernenc theory. tlre critical variables for controlling "req~~isire varicty" in the processing chan~rels are redundancy and noise. In the an;~lysis of the effects of resection of the n~edial tcn~poral lobe, these vari;ibles transl;~tc. into fanliliarity and novelty: We noted that \\.ith respect to familiarity, an~ygd;llecton~y reduces pro- and retroactive i~iterfcrence. Other -.stutlies usirlg tllc orie~lting reaction further specified the rrature of the involve~nent of the iiniygditl;r in processing farl~ili;~~.ity and are retiewed iu o t l~er publi- cations rather ~ I I ; I I I here LKr;~use this c l~a i~ t c r l)ri~r~;~rily addresses the I-unc- lions of the l~ipl)ocanrl)us (Bagslrat\+ rt ( I / . , 1965; Kin~ble PI ol., 1965; I'rib~.an~ rt ul., 1966, 1979; Bagslraw and Benzies, 1968; B;~gshirr+* and Coppock, 19(iH;

,-I" Yrihriier and AlcG~~inness. 1975). Or l~cr paradigr~~s cxploretl o t l~er t a ~ ~ t s ol' this r.cl;ttionship (S(.hwartzba~~n~ auri 1'ribr;im. I!l(iO; Ile;l~.s~ and Pribrar~r. 19G4a.b; Bagshaw a ~ ~ d Pribratn, 1965; Barr-err, 1969).

In c.ssrnce. tlirse studics showctl ~ I I ; I I tire viscero;~~~tono~r~ic c.orliporrcllts vl' or- ie~~~itrg wc.8.e nral-kedly attenuated by arnygd;~lectori~y and tl~at habitua- r i o ~ ~ of' rlle Iw.havio~.al cotllponenis failed ro takc plilce. I inte~-l)rcted tl~rsc l i ~ ~ c l i ~ ~ g s to mean that the novel stir~~ulus hacl failed to "register" (to bcomr h ~ n ~ i l i ; ~ ~ . ) and th:~c a visccroauto~~on~ic "lwostcr" was I-cquil-etl for registratiotl. Col~bidrrable convergence with the work- of hlcGaugll and Hertz (1972) on sorlle f;cters of "co~~solidarion" of t l ~ c .rrlelrlor). rrac.cs ha3 been pointed out (I ' I .~OI.;IIII . l9H4). F;rilu~.e to rcgisrrr ;j r~o\cl r.sl)e~.ietrcc. \\.;IS sIlo\\-~r to be 1.cI1t.1 rvt! ill a S :~ i l~~rc to tr.a~rsSt-r t r ; ~ i n i ~ ~ g i t 1 t r . ; i ~~>po \ i t i~ )~~ I J ; I I ~ ; ~ C I ~ ~ I ~ I ~ (liagd~aw ; I I I , I 1'1~il~1.an1, l!lf.i5); 21 t l ~ c S ~ I I I I C tj111t.. S I I I I I I ~ ~ I ~ ~ t~*.~,~~v:~li.,:atio*~ ~ * - * ~ ~ . J ~ * ~ ~

Hippocampal Systern and Kecorlibinant Processing 347

This section coricerrls the relationship between the hippocampus and the other component of competence, the processing of "noise." As we shall see, hippocampectomy influences monkeys' respolises to distraction and in general reduces the flexibility of behavior in problem-solving situations. In a sense, the momentarily irrelevant aspects of a problem-solving situation constitute its noise. Changes in the situation, in the contexts that enhance their relevance, constitute novelty. Thus, in any situation that is characterized by variability, effort is expended in processing momentary irrelevancies and their subsequent emergence as novelties. T h e experimental analysis reviewed in this and the following sections is aimed at showing that hippocampectomy influences a process that operates on irrelevancy, a mechanism that is involved in the development of a context, the internal and external constraints, that defines novelty. The flexibility provided by this mechanism alloivs the same stimulus, the same memory, and the same intent to be experienced as novel when, under other conditions, it is experienced as familiar. ?'he reasoning that led to this collclusion did not proceed sinlply but canie as a result of testing hypotheses illat were, in several critical instances, disconrirmed.

4.2. Allenuition versus Deluyed Response

An in~portant early finding seminal in the analyses reviewed in t11is section is the fact that the effects of brain resections can dissociate variarior~s of the delayed response and the delayed alternation procedures and can even produce a dissociation between delayed response and delayed alterna- tion in their classical form. Mishkiri and 1 had used the delayed response task in our early localization experinients (Mislikin. 1954; ' ~ i s h k i n and Pribrani, 1'354) and had found no deficit afier hippocanipal resection. Ttie classical forni (also called tlie dircct fonn) of delayed response performance (which is severely affected by far-frontal resections) consists of having a ~llonkey recall which of two boxes had been baited 5 s previously with a peanut while it watcl~ed. A screetl is i~lterlwsed during the delay. As noted earlier, hl:rlrno (1942) had ~ l i c ) \ ~ n that i t \\'as this screen that acted as a distractor (resulting in pro- a ~ l d I-etroactive interference), because when rlle Jrlay is created by da~.krrii~ig the testi~tg ch;lnll>er for 5 s, the monkeys with f'ront;~l resec-tions show no deficit.

l'lle classical form of delayed alternation cot~sists of initially baiting bolt1 boxes out of sight of the nlo~ikey. The nlonkey cliooses one box and is rewal-dcd. After the impositio~~ of an opaque screen, tlic monkey has ano~lier choice and, in order to receive the reward, nlust ctloose tlie box it had not emptied oli the previous trial. T o d o this, it must Icarn a \\,in-stlift strategy. On successi\~e trials, alternate Imses are baited ~ L I I of vie\\ of the rno~iliry (i.r.. while t l ~ v screcjr is dowr~). A co1.1.cictio11 procedure i s tr\;t.d: !he szmr I)ox rcillai~is biiirrd \111til the mottkcy ~.!looscs it. (.\l:crri;i1iorr \ \ . i r i ~ o c l r c.cwc.rc- . .

Rrsections of far-frotital cortex result i r i deficits i l l the Icar~ii~ig and per- li~~.rii;~~ice ol' these forms of the delayed alternatiori as well as ot' (lie delayed resl)ollse task. BUI hil~pocan~pectolny, altlio~rgh it produces a co~l~l)lete deficit in this classical form of deli~yed alter~lation (Pribrani ut o l . , l'.lG2), fails to impair de,layed response learning or perforniance (htishki~i and Pribrain, 1954; Maliut, 1971).

Because all frontoliriibic (far-frontal, cingulate, orbitofrontal, temporal ix)lar, and amygdala, as well as hippocampal) lesio~is pi-oduce defective performarice in delayed alternation tasks, 1 had collie to tlie hypothesis that such lesio~is interfere with the sequencing of (instrumental) behavior (Pri- bran^, 19546; 195(Ja,b). Performance on the delayed response? task demands the carrying out of a sequence (observing and reaching), althougll limited to a single trial. There was therefore the need to distinguish between the types of seque~rcing involved in the two tasks.

The thrt-that k) th tasks involve a delay seemed to rule out this elenlent as critical to the disti~iction. Nonetheless, because the ~ncnlorv loss in H.hl .

I

alq>eared to partake of all interniediate-rar~ge short-term (prinlary) nielllory, ;111d because b t l i delayed response and alternation irl\tolve sllort-tel-111 ulrtnory, we perforllied two rattler different exl)crin~rr)ts in wlricll inter- tr~ediate Ieligths of' delay were a factor. As reviewed earlicr, in an experinier~[ \rsing the 1)ADI-A. we investiga~ed tlie effect of 1lil)l~ocarnpectoniy o ~ i discriniillation lear~ii~ig under n~itssed verstrs sp;~cetl trial co~iditions. There wi~s 110 effect (Kin~ble and I'ribran~, 11163). 111 the otllcr c.xperi~~lent, J used a 1.5-nii~l fixed-interval procedure a ~ i d agilin obtained rlo eflkcr (Pribr;tm, l\)ti3u,b). Clearly, the delay factor per sr could not accoullt for the deficit ~~roduccd by hippoca~iil>rctorny in n~onkeys.

4.3. ltitmtally versus Extm~ully Orderrd S ~ q u u t ~ c ~ s

We IICSI inquired directly ir~co the distinction I)ct\\*een it scqi~e~lce wlierr ol)scr\'i~~g is followed by one instrumer~tal resporise and a sequence tliat rrquires t w o d i f l i r e ~ ~ t instrua~ental resporlses. The ciisti~ictio~\ aplxared to .-

-.'-' drpc11d OII \ \ . l le~l~e~. the sequet~cing \\.as cued esrr~.~i;tlly (visu;illy) to tllc org;~~iisni or wlletller ; I I ~ i~iternal (i.e., kiricsthetic) cue was c~itical. -1-0 this ellti. we tested monkeys in the DA1)l.A 011 our t;lsl; (\vl~irli we I;~l,clcd us/r.r~~ccr/ly ort lrrd) i l l \\.liicl~ the sequence of' ~) ; t~ l r l presses ~iec~ss;~i.y to ~.ct:ri\.c a 1.rw;trd \\.i~l~in ~ l la t trial was sperilictl 1)); tlie sti~iiult~s rlisl)l;~y, a ~ ~ d O I I

;~r~otlicr (which we called i ~ l t ~ t ~ i u l l j ordrrrd) ill wliicll tllr nlo~ikrys \c.ere 11.ee to cleterr~li~~r their own sequence, 1)rovidcd they did not choose a sti~iiulus t l i ; ~ t . duririg ~liat 11-ial, they hat1 rliosen pl.eviously. \Ye l b u ~ ~ d tliat 1iil)pocarn- ~)ecton~y clisrupted perforlliance on both the interr~;illy ;tlid tlie exter~l;rlly orclrrcd secltlence (Ki~iible and I'ribrani, 1963) \\ . l~er~ the ~~~orikc) .s \\.ere rel;cti\.rl\ it~r\l>erie~\ced, I~ut not wllen they Il;id bee11 ove~.t~.~li~ied.

S ~ I I I ~ I ~ I I . !.est~lts were ol)t;ti~~cd \ \ , l~c~i I . ~ S ~ C . I I ~ I I S \+.ere I I I N I ~ . 111. l-ll*-*.

Hippocampal Sys~enl and Reconlbillallt P~.occssing 349

alysis of the factors involved in producing the deficit (Brody ~t al., 1977; Urody and Pribram, 1978) showed that a continu;ll shift in the spatial location of the stimuli (the pseudorandon~izativn of cues across the 12 panels of DADTA) distracted all subjects, but especially those with frontolinlbic resec- tions (Douglas and Pribram, 1965; Grueninger and Pribram, 1969).

T h e results of these experiments focused our attention once again on the distraction caused by distributing cues among the 12 panel locations of DADTA. This dutracting eflect had both good and bad consequences: l~anl ing was ofkn slowed but the range of prubleitrr that the monkrys could kanl was enhanced considerably by the fact that the resort to position habits ulas discouraged. Distraction, when properly processed, as in the exptrienced motlk~y, etilranres competptlce.

4.4. Spatial versus Nonspatial Tasks

Alterations in the processing of distractors underlie the deficits in both attention and learning discussed so far. Suc l~ alterations also confound arlotller issue that has plagued the study of the effects of Iiippocanipectomy: the relevance of spatial as opposed to nonspatial cues. I wish therefore to present in some detail a set of exper i~ i le~~ts perfor~ned over 15 years ago that remained unpublished because spatial effects and distractibility were confounded. The reason for detailing them now is that, more recently, others have come u p against this difficult problem, and their studies as well as ours have provided plausible explanations for [lie findings (see, e.g., Mahut and hloss, Chapter 8, this volume).

The spatial aspect of the dcficit followillg I~ i l~pt~anipec tomy has been repeatedly e~nphasized by O'Keefe and Nadel (1978) and by hiahut (see Cllapter 8, this volunle). In fact, Schifer, in the 1900 edition of his Text-book ofPlrysiology, devoted over three pages to this issue. He rel>ol-ted that Ferrier arid hlunk had described changes in tiictile sensibility following lesions of tlie hil>pocaml)us and the gyrus fornicatus (ilicluding the cingulate cortex). I4owever. working will) Iiorsley and wit11 Sanger-Brown. Schifer was unable to confisnl thesc resulcs.

In ou r exl>erirnents, t ~ t . used niodifica~ions of delayed alternation and sensory discrin~in;~tior~ procedures. As rloled earlier, such nlodilications allow inquiry into thc. basic v;rriables t1i;it rllal-i~ctcrize the deficit produced by the cerebral resectiorls, variables tllat arc only supcl.licially represerited in tlre i~npa i r~ncnt of task pel-forn~arlce. Specifically, tvllen the successive (go, no- go) fo1.111 of the dalayed altcrnatiorl procedure is used in addition to the classical spatial (rigtit-lef't) form, frontal arid a~nygdala resectiotls produce different results: frontal lesions drastically imp;lir right-left delayed alter- nation, leaving go. no-go alternation vistually i~ltact, \\.he~-eas a~liygdalec~olny has a greater effect on prrforma~lce of tile go, 110-go versioli tllitn of the 5p.itial fo rm of tllc task (hfisllLin P~-il)r;rrn. l!#.i.i Iq5f i . I + i l ~ r : ~ m et 01

t o ~ ~ ~ y nri~lrt also be different when different versio~is of the delayed alter- rration 1)rocedure were used. This expectation was enhanced by the fact that perfornla~rce of spatial delayed response is spared by this lesion. Our results hacl shown that neither the delay nor the spatial aspect of the spatial delayed alternation cask appeared to be the critical variable basic to the deficit produced by the resection.

This finding left the possibility that alternation per SP is the basic variable disrupted by hippwampectomy. To test this hypothesis, we returned to the delayed alternation and visual discrimination tasks, but we used them not only in their classical spatial guise but also in a successive go, no-go form. hionkeys were trained on both alternation and discrimination tasks, each given in both spatial and go, no-go versions.

Eight rhesus monkeys were divided into two groups of four subjects each. One group was given bilateral hi1)pocampal resections; the other received tlre identical surgery except that no tissue was removed. The testing was performed in the DADI'A. For the simultaneous discrinlinations and reversal, a red and green circle (or, for the second tcst, the numerals 3 and 8 ) were distributed in pseudorandom sequence (no more than four repcti- tions) over the 12 panels. For the classical spatial alternation. white zeros were displayed in the two center panels of the DADTA. For the successive (go, no-go) discrirnination, both panels were illur~linated by the same pattern (red circle or green circle), and the correct response consisted of pressing either (go for green)-or nn'thtr- (no-go for red)-panel. In the go, no-go alternation, the panels were always illur~rinated with white zeros, and the ~llonkey Irad to alternately press either panel o r withholcl a response for 5 s. For all tasks, incorrect responses were followed by a repetition of theqrial (correction procedure).

The behavior of the nlonkeys was shaped before surgery so that they would sust;tin panel pressing at a 5 0 2 overall reinforccaletlt scl~cdule. After surgery. the tests were administered in the following order (no attempt was tir;lde to balance for order effects): simultaneous red-versus-green discrimi- 11;1tiorr; t.eversal of the red-green discritninatio~); go, no-go red-green dis- c.~.i~r~i~r;rtiorr and its reversal. Then the classical rigl11-left spatial alternation was presented, followed by the go, no-go alternation.

A dcfic-it in the spatial, simultaneous form of the r ~ d - ~ r e e n discrin~ination \\;IS lxodi~c.ed by hilqmcampcctomy. Thus, the p~ssibility arose that such ;I

tlrficit w;rs due to invasion of or dantage to the adjacent inferotemporal cortex. 111 order to assess this possibility, a more difficult discrimination (a 3-versus-$) was adn~inistered, as were a set of discrimirlatiorr reversals to thi-se cues. Damage to the inferoteni~wral cortex produces severe deficits on suc.11 dil'ficult discriminiltion tasks and in~p;~irs the develol)menr of reversal Ir;rriri~~): .sets (Clrristia~lsetr atrd lir.ibri~rn. l!)f9).

' 1 ' 1 1 ~ ~.c.,ulu of the first set of tllcsc. rsl)cri~nrnts are cleal-cut, as can be .,.,,,, I , .,,,,, 'I'zlrlrr I -,,A ') u:...-- . I

Hippocampal System and Recombi~lant Processing

Spatial Alternatioo, Discrimination, and Reversal

Right-left red-versus- Right-left Rigl~t-left

Right-left green disc 3-versus-8 Higl11-left alternation discriminadon reversal discrimination reversals

Control N N

352 1150 200 4 50 352 100 1100 353 750 200 200 953 100 700 354 1100 150 SO0 354 150 600 36 1 800 350 450 36 1 250 650

alternation nor with the discrimination, or its reversals. U y contrast, the monkeys that had been given hippocanlpal resections failed spatial right-left alternation conipletely (in 1500 trials) and were retarded (no overlap with the sham-operated control group) in the initial simultaneous red-versus- green discrimi~iation. which they also failed to reverse (in 600 trials). This deficit in simultiineous discrimination learning was confirnied with subse- quent more difficult 3-versus4 discriminanda. However, the deficit was no more severe than on the initial msk, despite the greater difficulty of the 3- versus4 discrimination. In fact, one subject had no deficit at all.

Spatial Altertlation. Discrinlination. and Hrs-ersal

Ca, n v p GI. 110-go Go, no-go rctl-rcrsus-gl.ec11 disc altert~iltio~~ disrrimi~~ation revcrsal

Con I rol 1800 4 00 2.50 600 200 200

1050 150 I SO 900 250 I O U

I + i l ~ l ~ ( ~ a ~ ~ ~ p a l 1200 300 15(1

POI1 6, &.#I1 :. I ' -11

Tlris deficit in discrimination perfbrmance was surprising (the study by Mahut, 1971, was carried out at my urging to confirm or disconfirm this result) and discomforting in view of the repeated failure to find such a deficit when the testing was done in the spatial, simultaneous fashion with only two nlanipulanda. Only when we performed the paired-versus-scattered-cue experiment described above (Douglas and Pribram, 19G6) and compared the performance of the same nlonkeys in the classical (Yerkesl\l'isconsin) appa- ratus and showed that the deficit was due to the randomizatio~l of cues across the 12 panels of the DADTA (Brody et al., 1977) did we obtain a plausible explana~ion for our result.

As noted, the possibility also existed that the visual discrinlination deficit was due to an unintended invasion of the inferotemporal cortex. Against this interpretation are (I) the histological findings, which showed that invasion of the inferotemporal cortex was minimal; (2) the excellent performance on the successive form of the discrimination; and (3) the relatively good ~~crfornlance on the 3-versus-8 discrimin;rtion, which monkeys with infero- temporal resectio~ls ordinarily find extrenlely difficult (e.g., Mislrkitl and I'ribram, 1954; Pribranl $1 at., 196G).

An alternative, more parsinlonious description is that the hippocampal rcsection kriled to interfere with go, no-go perfor~lr;ir~ces while producing tlranlatic irllpairrnents of spatial tasks, whether discri~ui~iation or alternation. I'aken in isolation, the obvious interpretatio~~ of this findit~g is that the Ilippocan~pal lesion impairs perforniance in which sl~atial cues must be learned. This is the interpretation espoused by O'KeeSe and Nadel (1978) in their extensive and penetrating review of the results of experinlents 011

~ a t s . Agairlst this interpretation is the fact th;rt l~ippocan~pal lesions fail-to impair delayed response performance, which has a strong spatial component. Furthern~ore, explanations in terms of spatial lea~.rri~~g I1;1ve been invoked to explain defertin: behavior follo\r.ing frontal (Oscar arid i\'ilso~i, 1966; hlishkin rt crl., 1969; Oscar-Ber~~ian, 1975) and pariet;il (H. Pribranl artd

. ... .B;rrry, 1951;; Cl'ilson, 1957) lesions. If, in fact, t l ~ e effccts 01' Iiippocanlpal *-'. Irsior~s are to be explained in terms of spi~tial learning, i~ will still be necessary to tlisli~~guisl~ the type of spatial ~,rocessing d is r~~ptcd by these lcsiorls as corrtlastrd to those of otller brain reb' T I~ I IS .

A possil)le sltel-native explanatiorl of the sclrcti\~c cl'fects o r tllc I~ippo- car~lpi~l rc.scc.tions that does not ignore the spatial ;rrtril)utrs of si~l~ultarleous taAs co~rld l)e made in terms of processi~ig distractors. As ~loted, Douglas ;rrrti Pribranl (1969) showed that hi~~pocaniyecto~ny alters a 111cb11key's susccp- til.)ility to distraction. In ~llose exl,erinle~lts, it was also deniorlstrated that, in these tasks, spatial cues were more distracting to all monkeys ~ I I ; I I I visual (or ;ruditory) rucs. Because the spatial factor lays such a large role wllen tasks ;IIT ~ ) I ' C S C I I I C . ~ in llle sinlultaneous for~ll, tile ~,rol)o"nl III;I!' I)e errtrrt;~incd !II.!I rltc cffi-cts of tllc Ilil)l)uc;~r~ll~;rl lesic.111 are ~)rin~;ll.ily or1 rl~r ; t l ) i l i ty ro , ., . . .. :..-- t!i.*i I .tctors ;4ll~i, I)CC;ILISC 01. 1/1t: !!>o!!!:!*~:s' :~:i<!~.iii.i I J ~ + % ~ I ~ I 111 ix~i~i l \

Hippocampal System and Reconibinant Processii~g 353

All of the experiments reviewed in tlie previous section had pointed to an obvious conclusion: hlonkeys with hippocari~pal lesions are impaired when problem solving depends on actively ignoring (processing) a nonreinforced cue (a potential distractor). How, t l~en, do we explain the fact reviewed in the present section that learning and performance on the go, no-go versions of alternation and discrimination remain intact? An answer may be derived from two observations: Normal subjects make a very large number of repetitive errors on the no-go trials, so that the difference between them and the hippocampectomized monkeys is washed out. (In the tables, non- repetitive errors are presented; the monkeys in this experiment and those in others with frontolimbic lesions made approximately twice as many repetitive errors as did their controls; however, the learning curves of elimination of the repetitive errors were essentially parallel; i.e., tlie difference in the curves was early, before the process of elimination, much as in the effects on discrimination and reversal described in the previous section; see. e.g., Pribram, 1962.) Also, the nature of the no-go trials niakes then1 difficult to ignore. These results also clearly demonstrate the fact illat it is not the withholding of responses that is impaired by hippocampectoniy; it is active ignoring.

Only in the spatial situation is there a cue that initially acts as a distractor in the performance of the task. Control subjects learn to eliminate the errors due to nonreinforcement because their hippocampus is involved in learning to actively ignore nonreinforced events. Hippocan~pectomized subjects con- tinue to be distracted by the spatial cues until the elimination process has had a charice to work.

4.5. Hippocamnpal Eleciricul Activity

The hypotl~esis that the hippoc:u~tpal deficit on spatial allernation and discrimination could be accounted fur by a deficiency in processing spatial distractors received support L'ron; several other expcrilnents performed in tlre lahratory. For insrance, it was sl~own that the effects of resection of,far- frontal cortex resultcd in a silililar deficiency, especially in the presence of spatial distractors (Grireni~lger and Pribram, 1969). Hotvever, as in the case of' frontal lesions in humans, the failure to adequately process distractors can lcad to perseveratioli as well as to distractibility, depending on the situation (Pribram rl al., 1964). Thus, we needed to discover what the conditions were in which hippocamprctomy enhanced distractibility. Ob- viously, the spatial forms of the alternation and discriniination tasks were critical. Could i t be, as suggested in the previous section. that witliholding a response, as in the go, no-go versiorls, produces such a striking liehavioral effect that ignoring is fostered and distraction is prevented? I n order t o tcst this l~ypothesis, we exanlined the electrical activity gc~ierr?tcd in r!ie hij~po- c!rr!l?~!s I durir;g spatial iiiid.fi',, rro-go iti~ern;irior~ ~~c-r.forrriaricr. Hi\)})ocanipal

; I I I ~ "i~ilentional" activity in rats and dogs (Vander\~olf, 1969; Black el ul., 1950). I lowever, theta acti\,ity was not apparent in the ordinary recordings that hat1 been reported from mot~key hippocampus.

M'e fouod, however, that spectral analysis of hippocampal activity by conilluter established beyond doubt that a considerable amount of theta activity occurred in the record of priniate hippocanipal activity. Further, we found that the amount of theta was different during the go and the no-go trials of' alternation performance: during the no-go trials (correctly per- for~ned), theta was distinctly more prominent. This pronlinence of theta activity tleveloped gradually during learning. Further, the theta increase was present inin~ediately after stimulus presentatio~l and did nbt persist; hiplm- caoipal electrical activity recorded later in the trial did not show any systenlatic differences between trial categories or problems.

Mre fully expected that the electrical activity recorded during the spatial version of the task would resemble tlie activity recorded during the go trials of the go, no-go 1)rocedure. After all, tlie spatial task delllanded a go respotise on each trial. But once again, we were surprised. Hi] )p~anipa l theta activity recordecl during trials on the spatial task resembled that recorded d u r i ~ ~ g no-go triiils. \llith respect to hil~pocan~l~dl function (11ot the fu~ictiori ol' tlie rest of the brain, however), spatial alternatio~~ is a diKere11tiatio11 of no-go Icl~avior (Crowlie ct al., 1972). Clearly, tlie hipl>ocanlpus is invol\.ed in tliose aspects of processing tllat lead to active ignot-irig and no~iresl,oridi~ig, the context witllin which selective (infornlatio~~) processing occurs. 'l'lie colnpre- l~et~sive progranl of research undertake11 by Ricliard I'hornpsor~ and his collalw~-ittors is relevant here (see Berger et 01.. tliis volume). The results of this resc;rrch sllow tliat a "neuronal model" of the t in~e course of a response is constr-r~cted in the hippocampus, a nlodel uccess;iry to the perforniarlre of' a classical (l'art\*lovian) condition;il response 1141rtrt7~rr tltr1-r is pro1oirpc.d rlrlr~? Iwtwcen t l ~ e conditional stiniulus (CS) and tlie u~ico~iditio~ial sti~i~ulus (LJCS). 'I'he II~UI-onal model apparently serves as a teml~oral bridge to e ~ i l ~ a t ~ r c \vitlil~olclit~g a premature response, to e~illancc the sl)atl over \cel~icli the

&J*' c.ouditio~~i~ig process car1 proceed. I'erl~;rl)s. tile co~~struct io~l of' this sol-I of' - ~ ~ c u r o ~ ~ a l ~nodcl is tile bi~sis of the effort expended to c t ~ l ~ a ~ i c e tlie processing

span ill t lir more cogr~itive types of perfirrniances reviewed Iiere.

'I'lrcsc exl)eritl~ental results pointed once again, ;IS liad tile earlic*r ones. t o tlit* I~i]q)ommpus as a structure involved in ~>roccssing tliosc aspects ol' siruatiol~s that dcn~and active ignoring. I'avlov had conceptualized s1rc.11 ~I.OCCSSC*S ;is resul~i~ig from "inter~~al i ~ ~ l ~ i l ~ i t i o ~ i " and Kinible ( 1 9651) dcvcloped ;I r~rodrl c s l Itily,oc;rnll>al f'i~rictio~l b;rscd or1 this totic-ept. L)oul;l;ts (I!l(ifi) a~itl 1'1 il1ri1111 ( 1969h) cstr~ldcd this n1odrl 11) i~~c-Jude r.cl(.v;i~~t I I C \ ~ . ~ ; I I ; I f'ror11 t l ~ e 1,1!14bl i l t + % l \ .

Hippocampal System and Recombi~~ant Processing 355

Frontotemporal Sensory specif ic- intr lnslc

Lateral I n h l b l t t o n

11 S e l f

Inhibition

FIG. 2. Diagram of the relationship among excitatory and inhibitory neural intcraaio~u and h e place o f the hippocampus in this scheme. See text for Lhc database upon which the diagram is constructed.

primary projection syster~is were controlled by the frontolinlbic forni;~tions and by the precentral motor and intrinsic as so cia ti or^ systenls of [lie posterior cerebral convexity. The corltrols on processirlg were demonstrated by the corticofugal effects of electrical excitation of these systems on recovery cycles within the sensory channels ;IS assayed by successive sensory stimulations (Spinelli and Pribram, 1967). The dependent variables used were variability it1 the amplitudes of the channel response to sensory stiniulation, as well as the speed of recovery.

'I'he effects werc interpreted (l'ribrarn, 1967) as operating on reciprocal inllibitory rnechanisnis within the setlsory channels: lateral inhibition (cor- responding to I'avlov's external irlhilition) arid self-inhibition (corrcspondi~~g to l'avlov's inrerilal inl~ibitio~i). Four controllirig processes were delineated: those of the pt.rcenrral motor and intrinsic systen~s of the posterior cerebral convexity operated by enIi;inc-i~~g self- and lateral inhibition respectively; those of tllc frontoten~po~-id (;~r~iygdala) a ~ i d the hippocampus produccd disinhibitio~i of the basic i~~l~ibi tory processes (see Fig. 2). Note t11;tt the ef'fect of f~ippocan~pal excitation operates to disinhibit self-inhibition (inferred from [lie fact that the variability of tile se~lsory evoked response is increased). Uisinhibition of internal i~;hibition allows -the processir;g of situations that would ordinarily induce i~iterrlal inlti1)ition; tllat is, i~lhibitory proqess \seould gate out these situ;\tions. Incr.c;~scd v;rriability i~icrrases the op~~ortunit y for flesibiliry in processi~ig.

I'are~itlic.tic;ill~ disi~ihibitio~i of 1;lrer;tl inhibi!io~) 1)). ckc-it;jlior~ of' rile aril\pdala ilnti rrl;t!ec! !'ror:t;t! c.oi.irx: 1v~t111s i l l tilt r.c.gis~r.;~tio~i of';ir> -r.ict~tirifi -. :... 1 . . .

rlrptrd 1)). arnygdala or I'rontal lesions, \\.irll tllc r.csult that habituation (tiniilia~-ization) of the be11avior.al conlponelits Failed to take place (l'ribrain, 1975). . - I'o sunlmarize: T h e deficits produced by frontolilnbic resections and the el'lkcts of electrical excitation of.frontolin~bic f'orrnatior~s (Kaada et ul., 1949) can I)e readily distinguished from the effects of resecrion and of electrical excitation of the sensorimotor and associated systetiis of the posterior cortical convexity. Manipulations of [he posterior convexity influ- ence behaviors that are characterized by invariant relationships between the organism a r ~ d the environment. Manipulations of frontolinl5c fornlations i~ifluence bcl~aviors that are characterized by the more evanescent relation- sflips of familiarity and novelty in the relationship between organism and c~lvironn~eni. Thus, habituation of the orienting response is actively pro- n)ot.ed tiy .(lie amygdala and related frontal cortex. Once habitua~ior~ has tak;.l.i.~@l&e,.rhe hippocampal systeln nlakes possil)lc the active processing of the hi6itua~ttd, ostensibly ignored stimulus.

fictive.ignoring arid the active processirig of ostensibly ignored siruations ~OI.III the pr:c~essing span, tllat is, the context, the set(tiiig), a i d the alq)cr- ccpiive mass within which the invariances tllar make up pel-crivcd exl,criei~c-e and ordirlarj. behavior take place. With respeck lo tile Iiippocan~pus. tl~ese r e s~~ l t s of arlalysis were stated iri the sualniary of the first two volurnes of ' this series as follows:

l'ril~rartl (I!l7 I ) has distiltguisltrd tlte or-gat~iz~tic~tl o ~ ~ ~ I ~ K ~ ~ ~ ~ ~ c - ~ I I I I s \ I I I I ~ ~ I I ~ ~ ) ~ artd otltrr well-itl~rait~cd habirual bel~aviors whirlc depctctl otl t l~e bawl fi;u~filia fm1d 1 1 1 ~ 11igrc1- st~.iatal syblc.ln) front atier~tio~ral-it~tet~tic~~cal h.luvic~rs wl~irh dc.l>c~itl OII ~ l t e ttil)lxw.ac~~pal attd c c ~ c l ~ l l ~ r circuits for their c u t ~ ~ r o l l i t ~ ~ (11~ratic111~. Isadcsi>tt (1974) e111pItasi1t.1l illc sartlc distittt tion by altributiltg illstittctivc atrcl well-tl-;ti~ied In- l tavi~~~s to tllc "rrl~tilia~t c c ~ ~ t ~ ~ ~ l e x " ol the braill (as the kern\ was usetl by hfaclxatt. 1!)71t) wltit-It iltcltt(l~s t l ~ r 11.rsal ~ a t ~ g l i a artd aswciated brain systrtns. hp~wtit ivr-c.oc~s~c~~~;c~c~r~ attcl Itabir~tal Ix.. It.cviors arc re~ulatt-d pritlrarily by closed-lrxq). Iro111rosl:rlir ICC'llbdck t t ~ r i ~ l t ; ~ ~ ~ i ~ t t ~ s . .~\ttcrttiollal 411d icl~~t\tiot~;tl ln.11avi01~ are rl~al-artcrizrd br pa~-.cllc.l ~)~.occ,sitty. ol)cct- I I M I ~ I . fectllc~rward re111trol systems. Ilal)ituatiott car1 Iw coltcri\rtl ;IS a clcanjir 1111 t11c I I ~ ~ I ~ Y M ~ I I I ~ N I \ , atlIwlK IIII>CI. systrn~s) Itonr all "attd" gate statc. ( i t 1 \ \ . l t i c 11 a I ~ S ~ H I I I ~ C

. ... ,.- cI~~n~c\cls OIL I I IC C O ~ \ ~ ~ I N C I I I ar1iu11 CIS it111\11s] I I I art "(11.' ~ A I C (111 ~vlcic~l~ tc~s~n~ttsrs (11 . < ~ I I I \ ~ I I ~ . X ~ I I L V cells ;*re activated 13). atty varivry 111 itcputs c ~ c u r r i ~ ~ ~ ;I! d i l l ~ r c r ~ r ri~ttes).

C.swc~li.tll> t l l i < t~>eatcs 11111 i l l ~ t l r prcsrttcr ol tlcrla cell i~~l t i l~ i tc~r) . ;trti\.it!. 111r ~ I I I I I ~ ) ~ I . L spike tllat~lti Is ale Lt-111 ic~dr~~rrtclell~ o f pac 11 otltrt.. Tllc s!scrrll is I I ~ ; I Y ~ ~ I I ; I ~ ~ ! ~ S C I I S ~ I ~ V C .

, I I O I I I I ~ >!strtIt> cat1 111t-rcSotr a1.1 i t t patallcl. ( I ' I I ~ I I . I I I I :IIICI 1~a:1isc111, l!li.5. 11. 433)

i\s itttlicared by the review thus f i r , tile ttleoretical 1,itsis for our results c.c.n~c.rc.tl f i ~ r ille rnost part on i~~ f i~ r i i~ ; t t i o t~ rl1easurelllcl)l 111i-ory, or1 signal tl,.rci I ~ I I I I ;rtlcl sair~l~lirlg tlleories, o n 1';tvlovi;lit tlleor\.. ; I I I ( I OII r~lodels dcrived ~ I ~ I I I I ~ - I I I I I I I \ I I I . I . - ~ I - ~ ~ ~ ; I I ~ I I I I ~ I I ~ I ) I . ~ C ~ ( ~ L J I . C S . \\\'Ira1 II;IS ~ . I I I C I . ~ C . ~ is a cot~sidcr- ;;:I~.II (11 l t i l ~ ~ ~ : ~ ~ ~ a i ~ ~ p ~ 1 f ~ ~ i ~ c t i v i ~ in [ct.it~s of' tlie I . O I I ( . ~ - I I I ot 2 ~ ~ t - a w e ~ ~ i - * - <*>.>*-

Hilqwc.an~pal System and Recon~billant Processilig 357

virtue of processing by an arnygdala-frontal system. Coding was conceived of as a process, concomitarlt with storage, that "packaged" information into more-or-less redundant "chunks" that could be variously cornbined and recombined to facilitate retrieval. Possibilities we considered anlong the laboratory group as niodels of this process were "hash coding" in computer programming, the pagination necessary to store and retrieve information in a computer program, bandwidth li~iliting in holography, and the "parsing" of a comniunication, all of which were conceived of as providing a context within which infornlation is processed. Without such contextual aids, input into the brain would be processed into one set of programs by sheer repetition, and into other programs that were responsible for skilled performances but that failed to allow the flexibility necessary for retrieval triggered by 'a particular need or episode.

For the most part. these concepts were developed with regard to the very similar, if not identical, functions of the far-frontal cortex and were related to the work of others in review articles arid books: The concept of a working memory was introduced in Plum and thr Structurr of B ~ l m ~ i o r (Miller et al., 1960) to describe the process invol\led in performing delayed alterna- tion. Olton has since applied this concept extensively to the functions of the hippocampus (see Chapter 9, this volunie). Shortly after its introduction, this concept was made niore precise by specifying that tlie nature of working memory was a list structure tliat could be flexibly rearranged, a "flexible noticing order" (Pribram, 1961~). Somewhat later, these flexible noticing orders were developed into executive routines in tinie-sharing systenls used with large "niain-frame" computers, and "working memory" was conceived of as operating as an executive process for the fu~ictions of the rest of the brain (Pribram, 1973).

1-he distiiictiol~ l>ct\vee~l thc n1enlo1-y-processing f'unctio~is of the fronto- lirribic formations arid tlie i~ifor~nation processing performed by the systems of the posterior cerebral convexity was initially franied in terms of context- dcpenderit and sensory-spec-ilic 1)r.ocessing niecl~anisnis (Pribrani, 1966, 197 1). More receritly, the evidence I'or a hierarchical organization of com- p ~ i e n t s of tliese c;itegoriCs of Inelllory and learning was revieacd: The co~ilpone~its of sensory-specific processing. 110w itlr~itificd as referenti;rl learning and illemory, include serisory arid niotor skills, search, san~l)ling, ;~nd categorizing. 'l'he canipurrents of'contextu:~l processing il-rclude rcgistra- tiori of orie~itirig to an episode and its subsequerit I~al~ituatiori (or extinction. if conditioning or learning has taken place), processes co~isidered basic to "eveat" or "episodic memory." T o this forin of processing was added probability estimation to complete tlie roster of colliponents of ca~ltcxt- dependelit processing (Pribram, 1984; see Fig. 3).

One of the more infl~~etltiitl of tllese ;tttr~rll)ts ;it niodcli~~g tilt. ~~lecllarlisril i~~voli-ed i l l c.c,~~tex~u;~liza~iot: has:d or1 rl\c I;il,c,i.;ii<,r\-'~ ~ i \ . i ~ i ~ . \ \\.a< thxt (4'

(Declarat ive) Syntact ic

Con tex tua l Re fe ren t ia l

Executive '\ Spatlotemporal Episodic Automatic Search & Sampling

Probabil i t ( S k i l l ) [ ~ a r ~ r o n t a l ! / \ , , [Poster lor (Procedural I n t r i n s i c ] )

Re i s t r a t i o n a l Recombinant Hotor Perceptual f h y g d a l a l [Hip~ocampal I [Motor] [Sensory]

FIG. 3. A tentative diavam of relationships among various forms of memory processing to indi~ate the place of hippocampal mechanisms in a larger context. Brackcu indicate anatomical structures: parentheses enclose other terms which have been utcd tr) I:~bcl the process.

cue \vhich refers to but is not necessarily described within the information that is retrieved." Such itiforniation is stored directly as a function of the inwriant relatiotisllips bctween cues and responses, as in the discriniination tasks given to our nlonkeys. Hirsh went on to describe what is meant by cotllexl:

T h i s concept has strong implications fo r theories o f how the brain controls behavior. Understanding these implications requires def in ing and exploring the mctaphysiological concept o f the performance line. A pc r fo r~nance l ine is defined as a system mediating the series o f events o r processes init iated by the ovenly observable stimulus and resulting in the occurrence o f the o v e r ~ l y observable response. I t is considered t o exist in real tirne and real space, and ultimately be pllysiologically observable.

S-R theories, as usually interpreted by pl~ysiologicdl psycl~ologists, ho ld that m e ~ ~ l o r y is stored u p o n the performance line. T h e stimulus is defined as activated by a n cnvi ronnl rn la l event o f a neural system sensitive to it. hlemory. o r more exactly, Iearnilrg, is he ld t o result f r o m the formation o f a funaional connection between t l ~ c neural elen~cnts sensitive t o t l l r s t in~ulus and tllose responsible for p rod t~c ing t l ~ e response. Th is connection beco~ l~es the key part of thc performance l ine for that part icular co~nbinat ion o f stimulus and reslwllse e l c m r ~ ~ t s and is unique to it.

Retrieval o f i t ~ f o r m a t i o n stored upon the prrfornlance l i t ic can tK d c ~ r i l x d with assvciativc logic. T h e memory consists o f S-R. and the wcurrence o f tile S, described wi th in the i n f o r n ~ a t i o n t o be retrieved, results i n performance o l t h r described k l ~ a v i o r . T h e conrepts o f retrieval a n d description are uscful Ilere only for con~parati \*c purposes. I t suffices t o say that the occurrence o f the st in~ulus causes the occurrence o f the response. Contextual retr ieval has n o ro lc in suctl a system.

W l ~ e n contextual retrieval is present i t is n o b ~ n g c r necessary t o store acquired information upon the pcr for tnat~ce line. I ~ ~ r o r m a t i o n can be stored in a scquestrred place o r state free f r o m interference by in format ion processing k i n g carried out o n the performance line. T h e next paragraplts d e x r i k how this happens af ier first discussing the nature o f i n fo rmat io~ t storage. (Hirsh, 1974. 11p. 422-423)

The relatioriship of this formulation to hippocampal function is tlien deli~ieated by boll1 experinlent and further theorizing by Hirsh (1970, 1973. 1974; Hirs l~ and Segal, 1972). hfahut (Chapter 8, this volunie), and Mislikin (hlishkin and Petri. 1984; bfislikin rl a!., 1984). 01ie inference to be macle from this q u o ~ a ~ i o n is usually ignored, however: If processing of. tlie ~wrforniancc line occur,s it1 real time, contextualizaiion must proceed ia fast tinie, that is, ahead of processir~g tlie perforniance line (sec Pribratli, 1971). l'liis inference is supported by the data obtained by Richard I'lionipson (Chapter 7, this vulume), which demoristratr that the temporal shape of t l t r nictitatirig response is constructed within die liippocanipus btfol-e its emer- gerice in tlie periplieral response.

Additiorial relationships between this forrnulatioti and olher data sets and rlieir analyses liave been pointed out. One interpretation close to t l~at ~xesrnted lirre is developed by Jeffrey Gray (see this voluri~e for review). 'The variables tlrat define "anxie~y" i ~ r Gray's tl~cor-y a r e al~iiost idc.ntica1 to tlir oilcs tll;i~ dzlitlc "crlfo~-1" i t 1 t l t r work reportrd 1irt.e. I'ltrr(* are so!!ic difi'cr.ellc.rs ;ts j,.c!!: )l~,\r.l.\.rl.. ;!!!<! :i.c;c i-c..,.ii-i,-i:il i r l i:;XC; i n . i ) , . ; i ~ r : , n r

inhibition" theory: "The safest co~~clusion for the nlonlent. then, is that the septo- I~ippocanr)~al system anlong its functions includes participatior~ in the behavioral inhibition system." In fact, anxiety is defined in terms of "behavioral inhibition." Cray - docs suggest, however, that perhaps it is not "behavior" per.se that is "inhibited by the system but motor programs or plans." Talland (1965). by contrast, had suggested that the hipyocampus is involved in the orfivr construction of phcrs. Several pieces of evidence stlppon Talland against Cray. The first is the fact that whether hippocam- pectomized subjects are more distractible than control subjects depends on whether they are already engaged in carrying out a task. If reslwrrse inhibition refers to inhibition of distraction, then in at least some situations the subjects with hippocampal resections show an itrrreusr in response inhibition. Even more clear-cut is the finding in nonhuman primates [Pribram, this volume; Mahut. 1971; Chapter 8. this volume] andvther species that hippocampcctomized subjects. while deficient in performing spatial alternation, show absolutely no deficiency whatsoever in godno-go alterr~ation. They show no increase in errors on no-go trials. which of all msk responses dcnland behavioral inlribition ill its clearest form. Finally, there is Richard Thonlpsot~'~ (C:lrapter 7, this \olun~e) elrctro-physiological evidence, which shows that a ncuronal nlodel of the nictiuting tesponse of rabbits is forrned prior to the occurrence (IWI the itrhibition) of that rrsporlse.

The queslion t l~en arises of how to relate t l ~ e Talland "co~lslruction of plans" to "anxirty" or "cffort" (and also to menrory) rather tlrat~ an "inlli1)ition of plans." This prol~lenl is ciealt wit11 in a step-by-step rasllion (tllr strps are takrrl from one set of data to tile next) by Pribran~ and Isxacson (1075). Critical to tltis a~l;llysis is a view of the I I ~ I I ~ ~ ~ I ~ I I S as acornparator betweet) "attentional" ( i~~put- regul ;~~i~lg) ;rnd "intet~tio~~al" (bclla\,ior-rcgulati~~g) systenrs. Cmmparison ma) take elTort as in "l~aying" atte~~tion; "tl~ougl~tful" retrievals from memory; or "inte~~tional" inl~ihitio~l of an iml~ulsivc r c s p r n ~ to distractors.

Perhaps. as shown by these exanlples, the major fault in .4?uirtj lies ill its narrowness of fucus. As Pribram and McGuinness (1975) detailed. t l ~ e I~iplnx-anlpal systenr cannot be ut~derstw)d without reference to two systems represented in tile lorebrain by several .,. basal ganglia: the anrygdala orthe lin~bic formations and tlle striatu~n (caudatclputa~r~e~r). I t is these systems wl~ich are ~~rimarily involved in orie~tting reactions (distraction) and their habitu;~tion-the stop [and go] mecllanisn1s wlricl~ Gray att~.il~utrs tcl the I~il~lrcr- . ~

o-anrpus. 1 ' 1 1 ~ h ip ln~an~pus . by contrast, nrtrdirtrs htwccn stu11 a ~ ~ c i go. The key concepts (stop a~rd go) rclate to <;ray's discussiol~ crf t l ~ e two tl~corirs

regardir~g ~ r l o ~ ~ o a ~ n i ~ l e trat~sn~itten involvi~lg sel-c~totlin and 111r dorsal ascc.1loli11~ .: c~oradretr'r~ic bundlc. \$'e sug~ested that tile prc~l~crtirs of 111or I h c ~ systrnls Itlay Ix.st

;,_I. IJC cc~~~(~ept~; l l izrd as an intrrrupt or stop systcrn ~llcdi;ltcd via IIIC sr~c~~orr~crgic. patl~w;~y and act activatil~p go system ~t~ediatcd by ~ ~ u t e ~ ~ i ~ l c l r l ~ r i ~ ~ e a~lol dcr1)arninc. l 'l~esc tlesigc~ators lit the data reviewed hy (;ray . . . and are in acrold wit11 llis co~rrlusio~~s. Iiowrvrr. 111r ana~on~ic-al and ~rhysiolo~ical d:~ta ~ H B ~ I I I to I W O srl~;~ratc systr111s wl~icl~ r t ~ ~ r \ t - t ~ c 011 IIIC 11i~~~wcar11~111s rather than S ~ I I I I C u11itar) s e ]~~o- l~ ip l )~n it1111x~l k41avior- int~it~itico~~ I~~ t~c t ion . In ;rdditio~~. Itewer data sllow tllat tlle I I ~ ~ ~ ~ . L I I I I I I I S . tllvre t11;1n ;111y o t l~cr 511 ircturc in t l ~ e braill. contait~s rrccptors f i~ r adrecrvcortical I~ornrot~rs. \VIlile llle slop d l l i l go fu~lcliolrs are primarily indole (setcrto~ncrgit-) and catrrhol (nclrcl~inr- ~~l i r i~l r rgic and dopamir~i-~gic) anrinergic and so are 11c11r-urcgularor! , I I IC I~iplx~a~rllrus is seen as plalil~g a critical role in t l ~ e pituita~ladre~ral-"strers" systclll wI1i~l1 n~udulates. I]!. wily of .J(:?'H and related pcptides derived Sronl lipvtropin (stre-11 as the f3- r.nLel~lrali~l\). IIIC arnicler~ic t~euroregulator). n~ech;~llih~~ls. Hrcausr c ~ l tllis higher older 1 8 1 - nlttclrllatic~~~ tile fu~rztior~s of- the hilqxcarl~lwl s!-strr~l ale tlillic 1111 to d i ' r e t ~ t ; ~ ~ ~ ~ l c 11-111 I!I**\v i! ~I~KI\I ISICS. .l 'l~is. wc contelld. is I I IC I ~ . A S ~ I I wli) all 111r d ~ ~ a tc.vicwc.tl II! l . ~ : t \ ~ ) s > ~ f i t a tlrcory h s ~ d ,uIcl! OII I ~ C S C ~ I I ~ ~ . ~ I I I I ~ I ~ M : I ~ I I I ~ . ! ! b t + ! t ~ ~ t ;e prv!:!!,!?! . . .

Hippocampal System and Recombinant Processing

5. Whither Now?

5.1. Issues

Experimental and theoretical analyses can never be completely 'disso- ciated: The data reviewed above were all guided by theory in the sense that the choice of the experimental paradigm tied the results to a body of knowledge in the behavioral sciences. Thus, the use of a fixed-interval task and the issue of whether the behavior of the hippocampectomized monkeys is under the control of the discriminative stimulus or a 50% schedule of reinforcement imply the response-reinforcement theory of operant condi- tioning. When probability-matching techniques are used and the data are presented in terms of response to previously reinforced versus previously nonreinforced cues, the sets of positive and negative instances of mathe- niatical psychology come to mind. And when response operator characteristic (ROC) curves are used to determine whether d' (detection) or B (bias) is influenced by hippocampectoniy, the tlieory of signal detection is invoked.

The probleni for neuropsycliology is essentially a twofold. problem: ( I ) the reconciliation of disparate databases (in tlie case of medial teniporal lobe lesions, the difference between what is found in humans and what is found in different species of animals) arid (2) the reconciliation of the different tlieoretical frames within which the data were gathered. These problems, though they create a nuniber of pitfalls arid difficulties, also present oppor- tunities for reaching a new level of understanding.

l'he pitfalls and opponunities are illustrated by the recent surge of iuterest elicited by experimental results obtained with monkeys, which appear to reconcile the animal and human data sets. Mahut and hcr ro-workers (hlaliut et ol., 1982; Mahut, 1985: hlaliut and hloss. Chapter 8, this volunic), Garfar1 (1974, 1985), and h.1ishkin (hlishkin rt al:, 1984; hfishkin and Petri, 1984) have used several modificatioris of a task tliat t l tey adapted fl-oni liunian cognitive experinietltal ~)sycl~ology. a task that purports to test "recognition." Fol- tlie monkey, this task is a trial-u~~iqur delaycd nonniatching I'rorn sample. As such, it is a cross between the indirect version of delayed response (delayed matching from sample) and delayed altcrllation (the rionrnatching aspcct) and tlius partakes of all the factors involved in solving those tasks: delay per se, alternation (i.e., learning a will-sliiSt str;tteg).). response to ~iovelry, and pro- and retroactive interference. l ' l ~ c rcsl~lts obtaillcd \villi this task are moi-r-or-less il~terniedi;~te I~ r~~ \ . c r r i those ol~tairlccl with delayed response and tliosr ctbtaillcd wit11 drlit!.cd a l i r r t ~ ~ ~ i t ~ ~ ~ . ;IS ~nighc l)t- rsl?cctcd.

For example. Gaffin (ISRfi), in a sectiori elititled "1iiil)airt.d Habit Formation after Fornix 'I'ransection." concluded ttiat

111 111c cxan~l)lcs discussed so far fornix trartscctiol~ impaired cl~r alliliry lo r11;lngr all

c ~ ~ a l ~ l i s l ~ c d habit. Some further observations suggesc chat this i r~ t l ) a i r~~~rn t can h sclbsunred ultdcr a niorc general defecc, namely in~paired lcartli~tg ability when otw 11;rbic is to bc formed in one scc of circurnsiances and a dit.fererlt llabit is to tK. forn~ed ill a different set of circumstances that is similar to thc first and cherclorc liable to be C O I I ~ U K ~ wit11 it. (p. 95)

-1'llis description fits with what 1 have here and elsewhere (e.g., I'ribram, 197 1 ) been c;tlling the competence for reconlbinant context-se'nsitive pro- cessirig. Further, Gaffan suggested that it is "instructive to consider the hypothesis that habits unmediated by memories are one of the direct products

%of 'learning." Here. Gaffan's analysis is reminiscent of Hirsh's. However, .A'C;af'f;tri used the term tnmory in a technically specific n1;lliner as i t is used by -'.cognitive psyc.hologists and in human neuropsycl lolo (wllere tlie term ~ a m r r ~ . ~ i a is siri~ilarly restricted and does not cover the "agliosias," whicl~ are

deficits in "re-cognizing" tlie use to which objects are put). Filially, GafS;r~i c~iil)liasizcd [Ire relatio~iship between response and rew;trd in the productio~i of 11;tbits in a fashion similar to that sirggested in one of tlie h'ebr;cska

':.Syniposia ~ I I hloti\*ation, where 1 (19636) referred to it as "addictiori;~nce" (see itlso Priljram, 1980, "Cognition and I'erforniance: ?'he Relatior1 to

:. Neur;rl Rlecliariisms of Consequence, Confidence and Conipetence). -1'hese c-o~~siderations enabled Gaffan (1985) to distinguish htween rec;tll

iilitl t l t r n1otiv;ition for it: "The habit of clioosirig stimuli that are associated i l l nlr6nlory with non-reward in preference to stinluli associated in rneniory witli reward can tlierefore proceed without any corlfusion o r interferelice betwcen the recall task and the motive for it" (p. 93). Was lie here not prol)osii~g a f0rniulation similar to tllat of Jeffrey Gray and colisonarit \\.it11 tliat pt~rsued i l l the analysis o f t h e work of this 1ab)ratory-but with certai~i diI'fercnces as wcll? 130th Gray's and our interpretation would groutid recall i l l ill(-critive ~r~otivation, wliere Gaffan wishes to separate tllr two.

&.I 13). coi~t~.;tst, hlishkitl f r al. (1984) clc;trly sep;~ratrd "u~eniories" ; i~i t l

"habirs." kit11 tlre I~ippoca~nl)us and arnygdala being i~i\:olved olily ill nlcniory procc-~.\cs. 111 Oiis, IIC follos\.ed Hirsh and tlie other a~~alyses steninling S ro~~ i ( I ~ I I . I ; tOo~.;~tt)i .y liiore clusel y than those ol' G a f t i ~ ~ :

'I ltr lirst 1or111 of learc~i t t~ to Iw rol~sidr~cd. t l~r otlr here I;llw:lc~cl IIICIIIVI-). fo~.t~latit)tt.

is tllc OIIK that by t~early u~~i\.rrsal agreement I ~ a s LK.L.II ; ~ t ~ r i b u ~ c d t o I I IC t ~ i p p w i l ~ l ~ l ~ ; ~ l s\stern excl~trively. Tltis attribution is cxplic-it in tl~r ct~lr~tcs frc1111 Iiir.11. Tllr evidc~lce I I C I I I I our rrsc.arch on the n ~ r ~ r ~ l e y , however. suggests rllar nienlnry tornlation ltas a 11ro:ccIcr Ii1111)ic substrate than this. one that i~~cludes ' t l tc ant!.gcl;llc~icl s).strtn as wcll. (3tisl1Lit1 rf ell.. 1982)

Hut i l ~ l l l l s t ' l e made clear 11i;rt hfislikiti used the t ~ ~ t . 1 1 1 7~(*11107? i n i ~ s 1c~-lir1~(.11 $ ( . I I \ I . as i t is developed in co~r~itivc. t>st.c.hc~lc,a\. . I ' I IV c . cq~l i t ivc*

Hiplmampal System and Recornbinar~t Processing 363

guish new (i.e., the novel) from old (i.e., the familiar as this is displayed in . tasks in which recetlfb presented stimuli are inibedded in ones not recently

presented). As a rule, tlie presentations are made with words or pictures that are clearly "re-cognized" as such in the terminology of neurology.

Where hlishkin and the analyses presented here disagree is in the characterization of discrimination learning as a process which he calls habit formation. Discrimination learning involves categorization and decision mak- ing (see Pribram, 1971, for review). Further, hfishkin (as 1 did in earlier formulations) lumps together the caudate nucleus and the putamen, which constitute the strialal (basal ganglia) system, when the evidence indicates that the head of the caudate nucleus is concerned with the learning and perform- ance of delayed alternation (the basis of allocating "memory" to the fronto- limbic systems), whereas the putamen is concerned with discrimination (reviewed by Mahut and Moss, Chapter 8, this volume; and by Pribram, 19771).

5.3. Thcorelical Frames and llre Probkt~~ of Cotrrciour Cognizance

I t is therefore wort11 asking whether there is anything fundamental being currently added to our utlderstariding of hippocampal function or to relating the animal database to that obtained on hunlans? l believe that there is but that the issue that is k i n g addressed must still be niade transparent. The dam reviewed and the analyses performed here that relate medial teniporiil lobe lesions to changes in "con~petence," an enhanced processing span, go a long way toward explaining the fact that Brenda hlilner's H. Af. has failed to recognize her for the past 30 years. O u r job now is to relate conipetence and processing span, as well as their basis in learning and performing trial-unique tasks, to rotun'ous cognizance.

The fact is that hippoca~iipecton~ized monkeys "re-cognize" a discrimi- native stiriiulus in an instrumental situation two years after having been last exposed to the stimulus, better t11a11 d o their controls (YG% vs. 87%) arid that H. M. "re-cognizes" instru~iic~ltally a task that he has learncd: he simply has 110 introspective cogoiza~ice oftlle fact. Finally, H. R I . , whcn not distracted by long lists i l l tcl~ich two- and retl-oactive interference operate, has littlc diificully i l l per-fornling tlie type of short- tern^ nleniory ~ s k s that characterize tlie trial-unique situations used in the nloiilrey experimer~ls. There may be, and 1 txlie\*e there probably is, a relationstlip between this failure in introspecti\,e cognizance aiid failure on trial-unique lasks, but this connection lias not yet been adequately developed. On close scrutiny, tlie current surge of interest in the effects of mediill temporal lobe resection stems as much fro111 verbal magic centered on the tenn rrcopri~iotr as it does from tlie intuition that we may h on thr thrrshold of e s p l a i r ~ i ~ ~ g reflective (irltro- spec.tive) conccious!?ess.

. .

exl)erimc.ntal ~~sychology (PI-ibram, l97Sa,b, 1981; -I'ulving, 1985). Just d i a t is tllc rclatiolisl~ip between the observing response oirhe operant colidi~ioning paradignl and a d ' obtained in a decisiorial paradigm? \Ithat is the relationship between research on short-term memory and research on attention? When we use a particular technique developed by experimental psychologists and obtain a change in behavior as a function of a neur-ological manipulation, how are we to interpret the data? With respect to hippocanipal fu~iction, just how do we go about deciding which theoretical frame-and thus, which paradigol-is the most cogent? Only when we answer these questions will the layers of puzzles that wrap tlie enigma of the hippocdmpus be further removed. And perhaps in the process, the relationships between theoretical frames in the behavioral sciences will also become clarified.

At i t )k~sot i . N. S., AND Fn-1s. P. M. A n i o u n ~ o f in format ion gained d u r i n g b r i e f r x l w j s u r o of n l ~ n ~ c r a l s and co lon. Journal of Expm'rnrnlal I'~~rlcolug.. 1958. 56. 962-369.

HA~;~IIAH.. M. H.. AND BE~~ZIES. S. Mul t ip le nicasures o f the or ient ing rear l ion at id ~ l t c i r dissc*.ia~ion a f t c r anlygdalectorny in monkeys. Exprrimriltal A1ruro lo~. 1968. PO. 175- 187.

BAGSI~AH., ht. H.. AN!) GIFF(X:K. H. W. Galvanic skin response condi t ion i l lg dc l i c - i~ i n arnygda- Iec.toniizcd t t t o~~keys . Exprrirnrntal h'rurcrlu~y, 1968. 40, 188- 196.

B ~ c s t t ~ u . . M. H., A t i n PYIHRAM. K. H. f f f c c t o f aniygdalrc.tonly o n ~ r a t t s f c r of t ra i t l ing i n nionkcys. Juunral of Cotn/mratitr a t d P h y i u l c ~ p ~ ~ a l Pr).rhulofi?.. 1965. 59, 1 18- 12 I.

BA~;*IIAH., hf. H.. K ~ n t s t x . D. P.. AND PRIBRAM. K. H. T h e GSK o f monkeys d u r i ~ c g o r i rn t i t rg ancl 11;lbituation a n d af ter ablation o f the an~ygtlala. I~ ipp twan t l~us a n d in lkroten1p)ra l cortex. .\'ruropsyholo+. 1965, 11. 1 1 1 - 1 19.

BAUY~-I.I.. I'. Mr. Studies of t l ~ e fu~lcc ion o f the amygdaloid co~t ip len i n h l a c a ~ r a h l~ l lacta. Srurupj~rhologia, 1969. 7, 695-697.

B~:RI.YNF. 1). E. l h e d e v e l o p ~ ~ ~ e n ~ o f t l ie C O I ~ C C ~ I c > f a t t e n ~ i ~ ) ~ i i n 1~sycliole)gy. 11) C . K . Evans and T. I S . . \ l t~l l iol land (Eds.). Allrrrliotr i n t r rurc~pl r )~ i r~ lo~. h'cw York: . ~ ~ ~ ~ I C I ~ I ~ - ( : ~ I I I I I ~ ) . - ( : ~ ~ I I ~ . I!ltiY. IJP. 1-26.

t)t.Ac:r. A. 11.. Sotr~c:. c;. A., AM) BAT-t : t ic t~ur . C. T l t c avoicfatic-r [ ra in ing of i t i p l n ~ a n ~ l ) a l ~ l t c l a ha\cs it1 f laxcdi l izcd dogs a n d i ts 1,elation t o skeletal n m v r n i c n ~ . Jounrol oJ (:otcr~uccr~it+r utcd

.I.

F.. I ' lc~.str~l~~pral P ~ j r h o l r t ~ . 1970, 7 0, 15-24, UI.~.IIIYI. 5. I(. Pat t r rn d i s r r i t t~ ina t ion learning wi th tllcstts n l o l ~ l r y s . I'syrlr~dtr~ic.rrl Hrputf.~. 1966.

19, 31 1-924. H1.t:~. J . S., Ctiow, K. L.. AXD J~UIBRAM, K. H. A l ~ l ~ a v i c ~ r ; t l a~t:aIysis c i f t l i c c~r~t t~ iz . :a t ie~t i of 111c

~~~~~~irl~~~~ernporn-pr~~uci~,ital cortex. Juuncol r4 (.'onc/rccturit* .\iutcrluh?. I!l50. 93, 53- 100. U a c ~ l ~ v . H. ..\.. ANII P l c t n v ~ ~ . K. H. T h e role o f front:tl ancl 11;lric-tal cortex i n r-c~gttitive ~)rcucssing:

' I 'czts ~ ~ l ' s p a ~ i a l ar id s c q u e ~ ~ c c fu~tcric~ns. Braill. 1978, 101. (iI17-633. Ht to~)r , B. .4.. USC:LULEIUER. L. G.. AND PUIBYALI. K. ti. 1'11~. r f fects o f ins~abi l i t ) of [he visual

tlisl)lar- on pat tern d i x r i n ~ i n a t i o n lcart l ing I)y tt~ottkrys: Disswiat ion prcx111( c d a l t c r rrsec- rions 111. l r u ~ ~ t a l a n d i t l l e ro te t l~pora l and prestriatr lesions. Ex/~r~ imrt r lu l trraitr Hr jmrrh. 1977. 27,257-269.

(:IIYIsI~I.~\~~s, C. A,. AXIJ PRIHRALI. K. 11. T h c cll'ect o f i ~ ~ f r r c ~ ~ c t ~ t p v r a l c ~ r fc~vra l ~ ~ r c s t r i ; ~ t e AIII~II~III un serial r c v e r ~ a l Ieat -n i t~g 111 niv~iheys. J V r c c i ~ ~ / ~ ~ ~ r ~ ~ ~ ~ l ~ ~ ~ i r ~ . 1979. 17, I - 1 0 .

( :M~*K\ I . 1) l'., Kosuu., A, . ! h . 4 r ~ , K. . I . . AXI) I 'M I I<K~~, K . H . l l i p ~ ~ w a ~ ~ i p : t l ~11.1-1riral activit) i t8 11s~ III~~IILC) d u r i ~ t g delayed a I t c t ~ ~ ; t r i < t ~ ~ p ~ ~ t l ~ l c t l ~ s . ;V~I~IU~~J\\;/:~S/~J; 1977 lfi. 15'4-lti ')

H i p p o c a n l p a l Sys tem a n d R e c o l ~ ~ b i r ~ a r l t Processir lg 365

DOL:GLAS, R. J. 1'hr hippocanlpus and behavinr. Jctunial ufConrpurafivt and Phj~iulugiral P~JI hulugy. 1966. 64. 354-357.

Douc:ms. R. J.. ASD PUIBYAM. K. t l . Distractioll and l iabituation i n monkeys wit11 l i n i l~ i c lesions. Jounwl ofComparatir*e a i d Phyiulugual Pljchulogy, 1969. 69, 473-480.

Dou t ims . R. J.. f l ~ u a r n , T. W., PYI~RAM. K. H., AND CERHI.. M. C. Limbic lesions and e r ro r reduction. Jounwl of Comparati~w a i d Ph~riulogical P~cholugy. 1969. 68,437-44 1.

E~UNOMO VON. C., AHD KOSRINAS. C. H. The rytoarclrdcclui~ics of thr human c o r k . (Trans. by S. Parker.) London: O x f o r d University Press. 1929.

CATFAN. D. Recognit ion impai red and association intact in the memory o f monkeys after [ransection o f the fornix. Journalof Comprat iw P h ~ ~ i o l u g u a l Psyholog?., 1974.86,1100-1109.

CAFTAN. D. Hippocampus: memory, habit and voluntary nlovement. Philosophical Tranurctioiu of (lu Royal Socirty of Lmdoir. 1985, BSO8, 87-99

GARNER. W. R. Uncrrfainy and stnvturr ac prycholugical cunrrpts. N e w York: Wiley, 1962. GARNER, W. R. T h e st imulus in in format ion processing. Amrricon Pryrholugist, 1969, 45, 350-

358. <;REUNINCER, W., AN[) PWIIIRAM. K. H. l ' h r effects o f spatial atlcl nonspatial distractors o n

pcrforntance latency o f monkeys wit11 frontal Iesio~ls. Jounwl of Cutnparufitr o r d Ph~siological P~ychology. 1969. 68,203-204.

HURST, E.. ANII PWIBRALI. K. H. A p ~ ~ e ~ i t i ~ r and avrrsivr ~ e ~ l e r a l i z a t i u n gradients ill a~l~ygclalrc- to l i~ i zed monkeys. Jounral of Coirr/mrolitw a d Phy~iolugiral I '~?rl iolug~ I!)C,4o. 58, 296-298.

Ht .~us i . . E.. ANI) PYIBKAM. K. H. F a r i l i t a t i o ~ ~ o f avoidancr bcl lavior by u~~a\*o ida l ) lc s l ~ w k s ill riornial and a~nygdalectomized n ~ o t ~ k r y s . I ~ r h u l u p ' r a l Rrpurts. 19Crlb. 14, 99-42.

H~us t r , K. The ro& o/ thr hippocampuc i t t i r l j un r~d iu i~ rrtrinurl. U n l ~ u M i s h c d dcwtoral dissertation, S u n f o r d University. 1970.

HIUII. R. I'rcvious stiniulus c x l n . r i r ~ ~ c r ddelays c o n d i t i o n i ~ ~ g - i ~ l d u c e d changes i t ) I ~ i p l w a l i ~ p a l un i t rcspunses i n rats. JUU~UII of Cumparatitw a r d Pl i~s iu lug~ra l Psycholug. 1975. 85. 337-345.

J~IUSII. R. I'llr hippocanlpus a n d con~ex tua l rrlrie\,al of i r l forn lat ion front memory: A tllcory. Brhaln'rwctl Biology, 1974. If, 421-444.

HIRSII. R.. AHI) SLGAL. M. Complctc t r a ~ ~ s c u t i o ~ ~ of t l ie fo r r i i r a n d rcvcrsal pusitioll liabit ill the rat. I ' h j r i o l u ~ arid Brlmvwr. 1972, 8, 1051-1054.

H u ~ ~ . r r . W. S. T h e delayed reaction in aninials and c l l i l c l re~~ . Aiiintal Hrhatriur Monopuph. 1913, 0. 1-86.

~SAAL:W.*;. R. L. Tlrr 11mbir spfrm. New Scr~.k: I ' l r t lum I'rcss. 1974. ISAA~SON. R. L.. ASU YYIHKAM. K. H. Sunlniary statrlnent. Thr hippucan~pu, \!ol. 2: A'rurcqlr~riokrg).

o i ~ d l cha~ iu r . N e w York: P l r n u ~ n Press. 1975. 1)p. 429-44 1. J~c:omst .~. C. F. RCCCIII c x l w r i n ~ r n t s o t ~ t l l r I ' u~ l r t i on o f t l ~ c f ronta l lobes. P~~rlrulrrgiral Hullt~itr.

19?H. 25. 1-11. J*cr~*\i~h., C. F. Studies ufccrebra l f l rnrt ion ill ~ ~ r i l ~ l a t r s . I. Tlir f u ~ l c t i o n of tile frontal a s v ~ i a t i o r ~

areas in mot i lcys. Cumfmratitv P . t ~ r h u l u ~ r a l 4~luiro~vophr. lY3(i, IS, 3-60. J~c:clnst N. (1. F.. ~ s t i Nlsscs. ti. \V. S~udies o l 'c . r r r l~ra l f ~ t n r t i o ~ ~ i t i primates. I\'. T l ~ e r f k c t s of

I r o ~ ~ t a l lok. lrsiol ls OII tlre drl ; tyrd a l t e r ~ i a l i o ~ ~ lrvbit i n nic~t~kcys. Jounurl uf G,rn/Hlrafi~r P g c h u l u ~ . 1997. 23, 101-1 12.

J~c:oust.x. <:. F.. \\'OI.TL. J. H.. ASII J ~ c : ~ g i ( ) s . 1. A. St~td ics of ccrrbra l f u n c t i o l ~ i t 1 ~ ~ r i ~ ~ l a t e s . 1. T h e f u ~ l c t i o n of l l l e frorl tal asscwiatio~~ arcas ill niot l lcys. Cnrr~/m~afi tr P~~r i tu lug i ru l hfaio- g111p1o. 1935. 13, 3-60.

KAAIIA. B. K.. ~'RILIRAM. K. H. . ANI) EWI t IS. J. A. KCSIJ~~PIOI.!. allel vascular respoltsrs i t1 ~ i l o l ~ l c y s f r o m te~ t lpo ra l pole. irlsula. orbilill s l ~ t Tarr and r i ~ ~ # u l i ~ l r gyrus. Jouriiul u j h'rutul,/i~lio/~l~~, 1949. 12, 347-356.

K~II.S~.MAS, I). .4tfrri1;1,ri arid tffur!. EII~ICWLI~KI CIiSls. K1: I ' r r ~ ~ t i ~ c - l i . * l l . 1973. KI\II,I.~., 1). 1'. T/:r VI~~III~XI~~C,II u j t r ~ ~ r l l . !ict\ Y ~ I I ~ : X c t i Y c ~ r l .%~~;I<I~III~ 111 ~ C ~ C I I C C S , lYtj7. ,.__ . .,.. .. ... . . . . . .

KIMILK. I). P.. ANI) PYIBRAM, K. H. Hippvcampvrto~~ly a l ~ d klla\.ior sequences. Scir~rrr. I!I(iJ. 139, H24-825.

K I M ~ U , D. P.. BAC;SHAW, hl. H.. A N D PRIIRAY. K. H. T h e GSK of rrro~tkeys (luring or ic~~t i t lg and habituation after selecd\*e partial ablations o f cingulate and frolr~al cortex. ~\'c.rriup~j- cholop. 1965.3. 121-128.

KLC.\,LR, H.. AND BUC:Y. P. C. An analysis of cenain effects of' bilateral temporal lolicctorny in the rltrsus monkey. with special reference to "psychic blindness." Jounurl ofPsycholo~, 19SB. 5. 33-54.

K ~ i . v r a . H.. A N D Bucv. P. C. Preliminary analysis o f functions of the temporal lobes in nlonkeys. Archiwr of Nrurology and Psychiatry, 1939. 44, 979- 1000.

LINDSAY. P. H. Multichannel processing in perception. In D. I. hlostofsky (Ed.). Anrnfiun: C o n h p o r o v I h q and a ~ l y s u . New York: Appleton-Gntury-Crofu, 1970. pp. 149- 17 1.

M A C : ~ A N . Y. D. T h e triune brain, emotion and scientific bias. In F. 0: Schmiti (Ed.), 7'hr Nrurorrmrcr~. S r c d ~ I d y program. New York: Rockefeller University Press. 1970, pp. 336- 349.

h f ~ t t c ~ . H. Spatial and object reversal learning in monkeys w i ~ h partial ten~poral lobe ablations. Nrur~.t~chulugia. 197 I. 9.409-424.

hl~l tur- . ti . Dissociation of two behavioral fut~ctions in t l ~ c monkey after early h i l > p r a t ~ l l ~ a l ablalic~r~r. In 6 . Will, P. Schimitt; and J. Dalry11111le-AIford (Eds.), Hrait~ plasfirifj. l r o n ~ h ~ g and mrttiory. New York: Plertum Press, IYH5.

h f ~ ~ t ~ r r . H.. ~ ~ L A - M ~ Y ~ : A s . S.. AN) MOSS, M. t l i l ~ l ~ ~ a ~ n p a l resections impair associative I r : ~ r t ~ i r ~ g and rrcc~g~~it ion nlcmory in the monkey. Juunurl of h'ruro>rirrrrr. 1982, 2, 1214-1229.

L~AI.MO, R. 5. Interfcret~ce factors i r ~ delayed reslmnsc in nlorrlrys after rrmoval of I'ror~tal lobes. J t ~ u m l oJ N r u r ~ l ~ ~ ~ i u l u ~ , 1942, 5, 295-3013.

hlcf:t.t.~uv. K. A. Response specificity in the behavioral e f i c t s ell' l i r~~bic system Icsions it1 tile cat.]uutrlol o/ Comparoritr and Phjsiolugicul I'syrhulogi. 1961. 54, 605-61 3.

M ~ C A U G I I . 1 . L.. AND HLYIZ, M. J . Mrmor) rwuuliduliun. Sat1 F~atlcisco: Albion. 1972. h f ~ G u t s h ~ x \ . D.. A N U P Y I ~ ~ K A M . K. H. T h e 11euro1)syc1101~~gy of attetttio~~: Etllotiottal 3 r d

motivati~~r~alcontrols. In M. C. H'ittrvcL (Ed.). 7kr btoiii 011dpzytbul1,gy. New York: Acadc~nic Press. 1!180. 95- 139.

h1l1.1.t.~. <;. A. L o n p g r atrd romrnunicotion New York: hlc.Graw-llill. 1951. MILLER. G. A. T h e t~~agica l nunlbcr severt, plus o r n ~ i r ~ u s two, or, some linlits on o u r capacity

for prcrcssilrg information. P~chologicol Hr~irua. 1956. 63, 01-97. hl~u.ru. (;. A.. CAUNTEK, E.. A N D PKIBRAM, K. 14. I'hitu atld Ihr .cl~uclltrr ~J I~r l io t~ tu~ . h'cn york:

IhJIt. I!ltiO. hlt~tit.a. H.. ~ N D P ~ N V I ~ I D . W. T h e cflect ~ I ' I I ~ ~ ~ ~ H K ~ I I I ~ I ~ I lesions 011 rrretlt ~l~cnrory. Ttuiorrrliuirj

of Ihr Aninicon Nrurulogiral Auucioliun, 1955. 80. 42-48. MISIIEIN, hl. \'isual dixrinlination p c r t i ~ r n ~ a ~ ~ c e Ii~llowing partial al)l;~tioris of t l ~ e t r r t ~ p ~ r ; ~ l I c ~ l r .

,;.:."' 11. \ ' c ~ ~ r r r l surlace vs. h i p p w a ~ ~ , p u s . Jounu~l I,/ Cumprufilr otrd I'lr~~~~~l~r~itulI's~rhol~~~~, li154. 140. 187-193.

h l ~ s t ~ a ~ u . hi. 5lemory ill nlorrkeys severel) i ~ ~ ~ p a i r r d by c.e~li~t)it~ed IJUI ttclr by sclraratc re111t)\al o l ' a n ~ \ ~ ~ l a l a and I ~ i p p ~ a n ~ p u s . h'ururr. 1!17H. 473, 297-298.

S l t s~ t r ;~s . 51.. AND P~:.I.RI. H. L. hfen~ories and Iral>itz: S ~ I I I I C inil>liratiot~s Sot t l ~ e a~r:~lyhis C I I learrii~tg and r r t c ~ i t i o ~ ~ . In R. Squire and N. M I I I I C ~ S (l:(is.), A'r~t tc$~~rl icrf t~~ u j nirnio?. N1.w Ye~rk: (;uillbtd I'ress. 1984. pp. 287-2%.

h f ~ s ~ t w ~ s . 51.. ANII PMIHRAM. K. 11. Visual dixritnir~arion perlorl~rar~c.c. followi~ifi jrarirtal abla~iotrs of tllc t c r ~ ~ p r a l lobe. 1. \'entral vs. lateral. Jttrrv~trrl ufConpora!it-r atul Phjrio!rgcul I'iyhr,lub?. 1954. 47, 14-20.

hftsltrts. hf.. AND P K I B K A ~ ~ . K. H. Analysis of ttlr rf'licts of frcll~lal Irsior~s in t i ~ o ~ ~ k e ) . : 1. \'ariatic~rts of dclaycd al t rrr~arior~. jounrol I,/ Cu~n/mwrr~,r and PI~s?ic~lup~rul t's)rholufi?, 19.55, 48. .I!)?-495.

~ t ~ ~ l l h l ~ . \ I . ANn P~tnu .4~1 . k. t i . A t i ~ l ~ $ i s 111 t11v efcrtt5 t ~ ! frc~t!r :!I lcsit~tl% it1 t i ~ ~ t t ~ h ~ ! . 1 1 . \ . I 1 ~ . I ~ ~ . , l I \ ~ r d ~ l ~ \ ~ ~ ( T ~ S ~ Y \ ~ ) C F I,..,,..../ ..I I ' . . - , . - . -a : - . - -...' ' I ' . ' ' I' ' '"-' '"

Hipl>oc"n~lul Sys~e tn a n d R e c o ~ u b i t ~ a t ~ t Processing 367

~ ~ I S I I K I N . ht.. \'IST. B.. \VAXI.LY, kt.. A N I I ROSVOUI. H. E. A r e - e x a ~ ~ ~ i ~ ~ a t i o r ~ of the effec~s of frontal lesions on objec~ alternation. Nrurops).rholugia. 1969. 7. 357-963.

MISIIKIN, M.. SI~IFSUR, tl. J., S . A ~ ~ N ~ I ~ R S . R. C.. ASU ~ ~ A I . A L I \ . . I . B. 1. An aninla1 mcdel ol global amnesia. In S. Corkin. K. L. Dh.*id. J. H. Crowden, E. Usdin, and H. J. M'urtn~an (Eds.). AlzJ~rit~rr's ~UWC: A rrpmi (I/proprs~. New Yorl;: Raven Press. 1982.

MISIIKIK, h!., MALAMVI, 8.. A N D BACI~LVAI.IER. J. hfe~nories and habits: TWO neural systenls. In G. Lynch. J. L. hfcGaugh, and N. M. Weinberger (Eds.). A'curubiolo6)' of tianting a ~ d ntrmolp. New York: Cuilford Press. 1984. pp. 65-77.

0 'Krr~c .J . . AND NADU, L. Thr hi\+ucampu ar a cogrrhirtr map. London: Oxford University Press. 1978.

OSCAR. M.. A N D \VIWIN. M. Tactual and visual discrimination learning in monkeys wit11 frontal lesions. Jounml o/ Conlparativr and Ph~siological P~)c/rologr, 1966. 64, 108-1 14.

OX:AR-BERMAN. hi. Thc effects of dorsolateral-frontal and ventrolateral onibofrontal lesions on spatial discrimination learning and delayed response in two modaliiies. h'ruropyrhologia, 1975. IS, 297-246.

PAPW.. J. W. A proposed mechanisn~ of enlotion. Archivo o/ h ' rurolu~ attd f'syrhiatr)., 1937, 38, 725-743.

PIN.I.O-HAMUY. T.. A N D LINK, P. Effect of frontal lesions on performal~ce of scque~ltial casts by monkeys. Erpm'mrntal hr rurolu~, 1965. 14, 96- 107.

POPPEN. R.. PRILIIUM. K. H.. ANII R~IRINSON. R. S. Tllc effects of frontal lolnrlomy ill nlan on perfcrl.n~ance of a n~ultiple choice task. &xpm.mo:tal A'rurukr~. 1965. 11, 2 18-229.

I'RIIIRAM. H.. A N I I BAIIRY. J. Fur111cr lx.l~avioral atlalysis of the par ic to- te l~~~nrro-~~~ '~c~cip i ta I conex. Jounlnl o/ h'ruruphysiolog)., 1956. 19, 99- 106.

Putnlc~u, K. H. Psychosurgery in midcentury. Surgrr).. Cplr ru lu~ atul OLtrlrLJ, 1950, 91, 364- 967.

I'RIHRAM, K. H. Sonlc aspects of exlwrinle~~tal ps).rl~c~s~~rgcry: The cffcrt of scarring fron~al conex on conlplex hl~avitrr . Sutk,lrol Forut::. 1951. 36, 565-575.

~'UlNWAM, K. 14. Cmncerning lltrec rhinet~cepl~dlic systenls. E~rr t r .ur t~t~fu~lvpoph~ a t d Cliriical Nrurophyjiolu~. 19540. 6, 708-709.

I'UIHRAM. K. H. Toward a science of ~~europsyc-l~ology (t~lrthod and data). 111 R. A. I 'a~lot~ (Ed.). Cumnit trndc in pgrholcr~ ottd fhr brha~riurul scintrrr. Picbburgh: University of I'ittsburgl~ Press, 19546, pp. 1 15-142.

PRI~IWAM, I. H. Cornparalive neurology and thr evolution of brl~avior. In Simproll. <;. <;. (Ed.). E1~oluriot1 and brhaldur. New kla\.et~: Yale Uni\.ersity Press. 195th. 1111. 1.10-164.

PYIHWAM. K. Ii. N ~ ~ ~ o r t i c a l futlction it] IK.l~laviw In I!. F. Harlow and C. N. Wtn~lsry (Eds.), Biulr~fiirul and biorhrmiral h w r cflchalrior. Madison: Univcnity of M'isco~~sin Press. 195Rb. pp. 151-172.

I'UIIWAH. K . 11. ~ ' I I c inlrillsic S ~ S I C I I I S of 111r forebrain. In J . )'icld. I{. M'. htagoun, a11d V. E. llall (Eds.). Iluirdlwok uf p/rv,iulu~ aitd t~ruruph~ric*lcrg?. 11. Washington, 1). C:.: A~ncricat~ I'l~ysiolc~gicrl Svcirty. 1!)60a. pp. 1323- 1324.

I ' I I I~IUAM. K. 11. A review ol' tllrory ill ~rlr)~sicrlc~gical psychology. Atit~unl Rn~iru, 4 I '~jrhulu~~. I9ti0L. 11, 1-40,

I 'ultlu&~. K. 11. .4 furt l~er espcrirnc~l~;rl onal!.sir ol' tltr Inl~a\ioral deficit chat iollows ~ I ~ U I ) tu the pri111ate frontal rctrtex. Es\nrii~iri:lul A'rurulug~, I!l(ilo. 3, 492-466.

I ' U ~ H R A L ~ . K. H. Implicati~ns for systct~la~ic studies of Ir.luvior. 111 E. Sl~eer (Ed.). Etirtriral ~~irnulo~iurt nJrhc htuitr. Austin: University crf Tcxas l'rrss, 1961b. I I ~ . 563-574.

I'ulaa~hc. K. H. Limbic s).stem. 111 D. L. Sl~rer (Ed.). Elrrtriral sttmulaliuii uf rhr braitc. Auslin: Lllliversity of Tcxas Press. I 9fi I r. pp. 3 1 1-320.

I 'MIHKAL~. K. H . <i)ncrol syslrlns i l td I~l lavie~t . I I I hi. A. I). Hiaric-r (Ed.). Mluiri rrrrd brhalioi. I'ul. 2. \Vasliir~glt~~~. I)(:: A~ncrican Illstitc~tc trf Miokrgital Scirtltcs. IWi'L. 1111. 371-387.

I'm I P R ~ ~ I , K . 14. .+ r~r~:rc~p~yrI~r~logical r11trlc.1: % J I I I ~ ~ J L L ~ I . ~ : I I ~ ~ I I I \ 1111 I I IC slrttc.Iut c 111 11s)~ l~~llugi~itl , . , , . . . I , P I ...... . \ 8 . . ; r ., . < . . . . . . . . . .

I'IIIHKALI. K. H. Keinforcement revisited: A struc~ural view. In ht. J c ~ l ~ r s (Ed.). h ' c b m r b S>mposiurn utr hfofi~urtion. Linroln: Universiry of Ncbrash Press. IYGSh. pp. 1 13-159.

PRIMYAU. K. H. Some dimensions of r r ~ ~ ~ r n l b c r i ~ ~ g : Steps toward a neuropsychological n~odcl of memory. In J. Gaito (Ed.), Macromo&cu&s and brluviur. New York: Acadenlic Press. 1966. pp. 165- 187.

Pitlaruu. K. ti. Thc.limbic systems. cferent control of neural inhibition and bchavior. 111 W. R. Adey and T. Tokimnc (Eds.). Progress in broin rrsrarrh. Amsterdam: Elsevier, 1967. pp. 318- 336.

PRIUUM. K. H. DADTA 111: An on-line con~putcrized system for the experimental analysis of bcllavior. Prrcrptual and Motm Ski&. 1969a. 29, 599-608.

P R ~ ~ U A M . K. H. The primate frontal conex. Nruropsychologio. 19696. 7. 259-266. Pnlnluu. K. H. La~'guogcs o/ h e brain: Expm'mrn&( parodazcs and pntrciph in nruruppchology (3rd

cd.). New York: Prenticc-Hall. 1971. \

P U I ~ K A M . K. ti. T h e primate frontal cortex-Exccuti\~e of thc brain. In K. H. Pribram and A. R. Lurid (Eds.). ;PsJ;chophYsio~gy o/ Ilu/ron&l lobs. New York: Academic Press. 1973, pp 293-3 14.

PRIMRAM. K. H. The primate froncal concx: Progress report. Arfo h'ruruhiologiral Exprrirnnr~olu, 1975. 95, 609-625. <

PYIRWM. K. H. Alternate states of consciousness: Somc observations on the organiza~ion of studies of 111ind. brain and behavior. In N. E. Zinkrg (Ed.). A l l m f t stofrs ofronsciournru. New York: Frcc Press. 19770, pp. 220-229.

Pulnn~u. K. 11. New dimensions in the functions o f th r basal ganglia. In C. Shagrass, S. Gcrsl~on. and A. J. Friedhoff (Eds.). PsfiopofJwbgy and brain djsfunc~ion. New York: Raven Press, 19770. pp. 77-95.

I'U~HRAM. K. H. Cbgnition and performance: T h e relation 10 neural nlrchanisn~s ofconsequc~~ce. conlidence and conqxteslcc. In A. Wourtcnkrg (Ed.). Biology o/ rrin/orrrmnrt: Far& o/ brain ~t~nruhlrorr rcuord. New York: Academic Press. 1980, pp. 11-36.

PRIHUAM. K. H. I'sychology as a scicnce; Three fundan~ental approaches. In K. A. Kosschau and C. W. Colrr (Eds.). Psychdogyirrcond cnrtury, Huclstot: Symposiutn 2. New York: Praeger. 1981. [#I). 2 18-296.

PRIBUAM. K. It. Rrain systems and cognitive learning prvccsscs. In ti. L. Koitblat. T. G. Bcver, a l ~ d H. S. l'rrracc (Eds.). Animalcognition. Hillsdale. NJ: Erlbac~m, 1984, pp. 627-656.

P R I ~ U A M . K. 11.. AND BAGSHAW. M. Further analysis of the ten~poral lobe syt~drome utilizing t runto-tcs~~[n)ral ablaiions.]ounrd of Compororitv Nrurology. 1953. 99, 347-375.

PRIHRAM. K. 11.. AND KRUGER. L. Functions of the "olfaclory brain." AtrnoLr of tlrr h h 1 1 )$d .4radrmy 01 St imrr. 1954, 58, 109-1%.

PUIHRAM. K. H.. A N D MCGUINKW. D. Arousal, activation. and cffon in the contrul of atlention. P~rholuAiral R M ~ u . 1975. 82, 1 16-149.

,- .Pdlnuau. K. H.. A N D MLCUINKESS. D. Commentary on Jeffrey Gray's 'Thr ncu~~ol~sycl~ology of . allxirt): AII cnquiry inlo the functions of the seprof~ippocampal system.' Tlrr firhouiorol and

Btoirc Srinrrrr. 1982. 5, 496-498. POIHUM, K. H.. . ~ V D TL'B~s, W. Short-tcr~r~ memory. parsing and printate irol~tal cortex. Scirnrr.

l!*ti?. 156. 1165. I'RII~IIAM. K. H.. *so WLISKRANSZ. 1. A comparison of the effects of medial a11d lateral cerebral

rrsectiorts a111 conditic~ncd avoidance bellavior in o ~ o ~ ~ l c y s . lounrnl o/Comparotizr and Yhjb- ulugiral i's>rhrrlogy, 1957. 50, 74-80:

Ynteu~u. hi. H.. A N D ISAACSOS. R. L. Sun~mary. In R. H. lsaacson and I(. H. Pribram (Eds.). Thr Ifipyorompur, 1'01. 2. Ntw York.: Plenum Press. 1975, pp. 429-441.

Pa lna~u . K . H.. ~ ~ I S H K I N . M.. ROS\.(IU). H. E.. AN11 KAI'L~N. S. J. Effects on delayed-respc~nsc prl 'orn~ant r on lesions ofdorsolateral and vrr~tromedial fron~al cortex of batrwns. Jounlnl t J f.'unpr~utr:*r ond Phyiohgud P~yrhology, 1952. 45, 565-575.

I'u~lir \ \ I . K. I I . . \ \ ' t t su~ . \+'. A.. A N I I GJSSOIIS. 1 . T h r clficts nf I r r i c ~ ~ ~ \ ctf tllr me-di;~l forrbrain ,sn . I ~ I C I ; i ; s r l : r ~ t k l ~ a v i c ~ r of rhrsc~s mor~kevs. Exfiri7mrrr1ol .V~rrt,*h,#.r i(Jf;'J 6 'w- 4 7

Hippocampal System and Recombinant Processing 369

dprocess disturbed by frontal lesions in primates. In S. M. Warren and K. Akan (Eds.). The fronlal granulor cotinr and brhavior. New York: McCraw-Hill. 1964, pp. 28-55.

Parsruu. K. H.. BLLHERT. S. R.. AND SPINCLLI. D. N. The effects on visual discrimination of crosshatching and undercutting the infcroteniporal conex of monkcys. Journal ofCamparativc and Phy~wlogical Psychology, 1966, 64. 358-364.

PRIBRAM, K. H., LIM, H., POPPLN, R., A N D BAGSHAH'. M. H. Limbic lesions and the temporal structure of redundancy. Journal of Compararivc and Physidogud P~rprholo~, 1966.61,365- 373.

PRIBUM, K. H., D o u c ~ ~ s , R. J.. AND PRIERAM, B. J. The nature of nonlimbic learning. Journal of Comparariur and Physiological Psychology, 1969, 69.765-772.

PRIBUM. K. H., Rctn , S., McNrt~. M.. AND SPLVACK. A. A. The e f f m of amygdalcaomy on orienting and classical conditioning. Pavhnbn Jmtmal of Bid0g i .d Scimct. 1979. 14. 203- 217.

ROSVOLD, H. E. The frontal lobe system: Cortical-subcortical interrelationships. Acba h1c11robiologinr Exptrimmlalic, 1972,34,439-460.

R o s v o ~ ~ . H. E.. M~RSKY. A. J.. AND PRIBRAM. K. H. Influence on amygdalcctomy on social behavior in monkcys. Journal of Comporafitw and Phy~wlogical Pvcholo~, 1954,47, 179- 178.

SANCCR-BROWN. S., AWD SCIIATLR. E. A. Functions of the occipital and tcn~poral lobes of the monkey's brain. Philosophiral Trawartiom of& Royal Sorirty of London, 1888. 179. 303-327.

SctiAr-CR, E. A. (Ed.). Tat-book ojphjsiology. Edinburgh: Y. J. Pentland. 1900. S c ~ r w ~ n r r e r r u ~ . J. S. Change in reinforcing properties of stimuli followiiig ablation of the

amygdaloid coniplex in monkeys. Jmrnurl of Comporah'tu and I'hj~wlogiral Psychology. 19GOa. 59,388-395.

S~IIH.ARTZBAUM. J. S. Response to changes in reinforcing conditions of bar-pressing after ablation of the amygdaloid conlplex in monkcys. Psydrologicol Rrpmtr. 1960b. 6,215-221.

S c t ~ w ~ ~ n n ~ u ~ , J. S. Some characteristics of "amygdaloid hypcrphagia" in monkcys. A d a n Journal of Psych01ug-y. 1961.14.252-259.

SCHWARRBAUM. J. W.. AND PRIBRAM. K. H . The effects of amygdalec~omy in monkeys on transposition along a brightness continuutn. journalof Cmnporafiw andPhj~wlogira1 Psyrhology. 1960. 53,535-539.

S~HWARRBAUM, J. W.. WIWN. W. A., JR.. AND ~ ~ ~ I R U I S E T T E . J. R. The cffeas olamygdalcaomy on locon~otor activity in monkeys. Jmrnutl o/Conrpnratiw and Physiologicaf Pvrhobgy, 1961. 54,335-336.

SCO~ILIX. W. 8.. ASD h f t t . ~ ~ ~ . B. LOSS of recent memory after bilateral hippocanlpal lesions. 'Journal o j hrrurolog). N~urorurgn): and Ps~chiatty. 1957.40, 1 1-2 1.

SHANNON. C. E.. AND WLAVTR. W. Thr mathrmafical throty 4 communiratwru. Urbana: University of Illinois Prcss, 1949.

SI~)MAN, hl.. ST.ODLIARD. L. T., A N D hfutt~. J. P. Sonic additional quantitative observations of imrncdiati memory in a patient with bilateral hippcampal lesions. h'rurof~chulogia. 1968. 6,245-254.

Sh4t:ls. C. A r ~ h t i r judprnt and arousal. Leuvcn. Belgium: Lcuven L!cliversily Press, 1973. SPCVAC:K. A. A.. ANI) PW~BRAM. K. H. A decisioiral analysis of the erfccts of lirnbir lesions on

Iearniti~ in monkeys. Juurnnl o/Comparutizu and PhysidoK;d P~?r/rolog?, 1973. 82, 21 1-226. SPINLUI. D. N.. ANU PRIBRAM. K. H. Changes in visual recovery funaions and unit activity

produced by frontal and temporal conex stimulation. Ehtrumrrphalugraphy arrd Clinical h'ruroph~si~bg), 1967.12, 143-149.

TALLAND, G. A. Drrangrd mq. New York: Academic Prcss. 19G5. TLILVINC;, E. On the classification problem in learning and mcnlory. In L.-G. Nils.mn and T.

Archer (Eds.). Pmprctivr~ in Iramitcg a id trrrmn~. Hillsdale. KJ: Erlbal~rn. 1985. VAS~II.RH.OL~. C. H. tlippocampal electrical activity and \ t ~ l ~ r r l u n nio\.cnirnt i r l l l ~ r rat.

Ehrtrortlc-rpAulu~~uphj arid Clrrrirul ,'t'rurolnfi? IYG9, 26. 4117-4 1 b. \,.). ,<,- Y.,..,7 1 ..... I..." .... .. - .. .. - . .

M'trsc~s. hf. Effects of circumscribed cortical lesions UIHIII wn~rstl~etic discrin~illation ill the rr~onkcy. jr.unwl o/ Cvmparatiw otd Phpiologiral Psyrl~ulu~. 1957. 50. 630-635.

ZI.AYAS. D.. ASIJ HOL.SL. B.J. The role of attention in retartlate discril~linx~iun l e a r ~ ~ i r ~ g . In N. K. Lllis (Ed.). Hat~dluoh of mrtital deficiency. New York: McGraw llill. 1963.

Z(JI.A-Mouc;~s, S.. Syutff, L. K.. A N D MISHKIN The nruroanatorny of amnesia: A~~\ )gJa l a - hipprwal~lpus versus temporal stern. S&tur, 1982, 418, 1337- 13339.

Index

ACTH: ser Adrenocorticotropin hormone Acc~ylcl~olinc, 44-45.62. 137- 140, 152

receptors, 46, 139, 228 Acetylcholincsterase, 44. 66 3-amtylpyridine, 99. 120 Acquisition: rrr k a r r ~ i n g Adipsia. 112 Adrenal medulla, I36 Adrenal steroids: rrr Glucocorticoids.

Corticcosterone, Mit~eraloconicoids Adrcnalcctor~~y, 140. 154 Adrenocorticotropin hortnonc (ACTH). 14 1,

SGO Afterllyperpolariza~ion, 222 Alcol~ol. 160, 162 Alpha-adrenergic rrreptors. 89 Alveus. 95.97 Alzhein~er's dixasc. 65-66, 121. 282 An~r~csia. 31-32, 35. 170. 191. 193, 241-243,

265.273. 881-282,289.299.310. 324. 325. 333

At~~l~hetarrl inc. 13 1 Amygdala. 96. 318. 3?1

Ichic~ns of. 24 1. 28H. 330-346. 330-364 A m y g d a l c ~ l ~ i p ~ a n ~ p a l lesions. 246, 250, 27.7,

275 .4nterior ro~n~~~ issure . 59 At~xirty. ItiU. 164. IRO. 359-360

and a~~t ianx ic~) . drug action, 160- 164. 180. 186. 188-IYO. 193, 195

Apl~agia. 1 12 .4pomorpliit1e. 133 Arousal. 2 18-219. 325 Association cortex. 3 16 Atrupinc, 44. 46

and t11t.u rliythm. l t i i - 169, 177 A ~ t c n ~ i o l ~ . IM, 216-219, 337, :i:39-340. :i42,

JJ!I. 3% 'Gfl ?f.2

Barbiturnla. 160. 162, 189 Basal ganglia. 130- 133. 151-153. 356, 360.

363 srr ulro Caudate ~lucleus

Bcllavioral inhibition syslenl. 160- 164. 171- 172. 187

Bcl~avioral prin~ing: Jrr Ixarning He~~zodiazcpi~~rs. IG0. 193- 194

srr aLw specific drugs rmeptors. 162. 189

Blud-brain barrier. IS9 Bretylium, 144- 151. 141-153

Caudatr IIUCI~US. 2. 5-7. 9. 28, 31-32.95, 130- 135.274.332.360, 363

srr oLo Basal ganglia Cwrekllum. 229-232 Chlordiazcpoxidc Itydrorhloride. 164. 190-

193 P-C'l~loroampf~cl;rtl~ine, 84 C l lo l i~~e acetyltransfcrase, 44. 66 Cholinc cl~loride, 135-140. 151- 152 Cingula~z conex, 2, 5-9. 11-20, S5,95-96,

I(ili. 175- 176, 231-232. 317-3 18. 321, 332

Icsions of, 1 1 - 17.24-27,332, 348-349 Cirradian cycle. 129 Classical ronditionitig. 65. 160. 203-235.

294-295. 302.322 Claunruni. 98 Curf~lear t~uclcus. 2 5 . 234 Colcliici~~e. 99. 104. 1 17 Co11ditio1lc.d a\oicIa~~ce khavior, 97. 120,

198. 134. 170.322-323, 352-333 JN. a110 L r a n ~ i r ~ g ar~t l disrrir~lir:aliot~. 11-6. 10- I I. 14- 16. 20 11rural corrcl>trs of. 1-35 ,. . . . .