Nonspatial conditional learning impaired in patients with unilateral frontal but not unilateral temporal lobe excisions

0028.3932 Yl~s300*000 1990 Perpamon Prers plc

NONSPATIAL CONDITIONAL LEARNING IMPAIRED IN PATIENTS WITH UNILATERAL FRONTAL BUT NOT UNILATERAL TEMPORAL LOBE EXCISIONS* MICHAEL PETRIDES Department of Psychology. H3A 1 Bl; and Montreal

McGill

University,

1205 Dr Penfield Avenue,

Montreal,

Quebec,

Canada,

Neurological Institute. McGill University, 3801 University Street. Montreal. Quebec. (Receired

20 Mar

Canada,

H3A 2B4

1989: accepred

21 Augusr

1989)

Abstract-The present study examined the effect of unilateral frontal- or temporal-lobe excisions on the acquisition of a conditional task requiring that the subjects respond to each one of six different coloured stimuli by selecting, from a set of six abstract designs, the correct design for each stimulus. Patients with excisions from the left or right frontal cortex were impaired in learning this task. whereas patients with left or right temporal-lobe excisions, with or without radical involvement of the hippocampal region, were not impaired. These findings demonstrate that the major role played by the frontal cortex in the acquisition of conditional responses is a general one and not restricted to situations involving different movements.

INTRODUCTION PATIENTS with unilateral excisions from the frontal cortex have been shown to be severely impaired in learning two conditional associative tasks [12]. In these tasks, there are a number of alternative responses that the subjects can perform, but the correct response is conditional upon the particular stimulus that is presented on any given trial. To master such a task, the subjects must learn the appropriate response for each one of a set of stimuli, so that when one of these stimuli is shown, the correct response will be produced. In the above conditional tasks. the patients were required to respond by pointing towards different positions or by producing various hand postures [ 123. Experimental work carried out with nonhuman primates has demonstrated that the posterior part of the dorsolateral frontal cortex is a critical region for the learning and performance of such tasks [4, 1I, 131. This work has further shown that the role of the posterior dorsolateral frontal cortex in the control of conditional responses is not restricted to situations requiring selection between different movements or different spatial responses. For instance, monkeys with lesions limited to this region were markedly impaired on a conditional task in which they had to respond to stimuli by selecting the appropriate one of two visually distinct boxes that varied randomly in position from trial to trial [13]. Since these boxes did not occupy a constant position, the animals could not successfully perform the task by learning to make different movements in the presence of the stimuli. Successful performance could only be achieved by learning to select the appropriate box. irrespective of its location. *Thts worh was prcacnted 1988.

at the 10th Annual

Conference

137

of the Cognitive

Science Society.

Montreal.

August

13x

MICHAEL PETRIDES

The purpose of the present study was to explore the possibility that, just as in nonhuman primates, the impairment on conditional tasks in patients with frontal-lobe excisions is a more general one, involving the control of responses that need not be distinct movements. To examine this question. a new conditional task was developed that was comparable in requirements to the one used with monkeys. In this task, the subjects had to respond to different coloured stimuli by selecting, from a set of abstract designs, the correct one for the particular stimulus that was shown. It was predicted that patients with left or right frontallobe lesions would be impaired in acquiring this task. In the earlier work on conditional tasks [12], patients with unilateral excisions of the temporal lobe that did not involve extensive damage to the hippocampal region were not impaired, whilst those with more radical involvement of the hippocampal region exhibited material-specific impairments that varied with the size of the excision. On the present conditional task, impairments were not expected from temporal lobectomies that did not encroach extensively on the hippocampal region or from excisions involving the hippocampus on the left side. However, for patients with damage to the right hippocampus no clear prediction could be made. It could be argued that a deficit might be observed in such cases because the responses that had to be learned, i.e. select the appropriate abstract design for the various stimuli, might require the right hippocampal system. On the other hand, the fact that these designs had to be associated with colours, which are stimuli that could be readily verbalized, might reduce the possibility of demonstrating an impairment after right hippocampal damage.

SUBJECTS Eighty-five pabents who had undergone a unilateral excision from the frontal- or anterior temporal-lobe at the Montreal Neurological Hospttal and 20 normal control subjects participated in this investigation. All subjects were rrght-handed except for three patients who were left-handed but had speech represented in the left hemrsphere as demonstrated by preoperative intracarotid Amytal* tests [S, 251. Most of the operations had been carried out for the relief of pharmacologically intractable epilepsy. The epileptogenic lesions had been well lateralized and had been static and atrophic except where stated. Patients with fast-growing tumours or with atypical speech representation. as well as those with a full-scale IQ under 80 on the Wechsler-Bellevue Adult Intelligence Scale or under 75 on the Wechsler Adult Intelligence Scale-Revised were excluded from the study. The IQ rating of any given patient was taken to be the one assessed nearest to the time of testing in the present investigation. Forty patients were tested m the early postoperative period (13. 15 days after operation) with the remaining patients tested from I to 24 years postoperatively. The distribution of sex. age, and full-scale IQ ratings for the various groups of subjects is shown in Table I.

Table Hrppocampal removal

Group Normal control Left frontal Right frontal Left temporal Left temporal Right temporal Rrght tcmpornl

*Sodrum

amobarbrtal

Small Large Small Large

Sodrum

Amytal,

I. Subjects

M

Sex F

Mean

Range

Wechsler IQ Mean Range

14 7 9 IO 9 7 9

6 3 4 7 6 9 5

32.0 32.1 33.8 25.1 23.9 25.5 30.3

13-58 1345 20 57 18.-36 14-37 1637 20-40

Not assessed loo.9 85 II’ 103.5 79 128 101.7 77- I22 102.3 755123 104.6 78 124 99.9 76 123

Age

Eli Lilly and Company.

Indianapolis,

Indiana.

U.S.A.

NDI’SPATIAL

CONDITIONAL

I39

LEARNISG

Frontal-lobe groups Le$ jrontal-lobegroup.The extent of removal m the 10 cases comprising

this group is illustrated in Fig. 1. Inspection of this figure shows that the lateral frontal cortex was involved. at least partially. in all patients and that Broca’s area on the posterior part of the inferior frontal gyrus was always spared. In some cases. the exciston extended to the medial surface of the frontal lobe. Four patients (HOSP.. Th.Fe.. Ti.Pa.. Wi.Wh.1 were tested in the early postoperative period: the other six patients were tested from 1 to 20 years postoperatively. The left frontal group included four cases of indolent cerebral tumour (Ho.Sp.. Lo.La.. Mi.Mi.. Wi.Wh.1 and one case of arteriovenous malformation (A.-M.Be.)

Case

Error Score

Case

Error Score

Error Score

Case

14

Ti. Pa. c

_‘ME_ _~

19

_.

Ho. Sp.

,

-~

62

19

Fig. I. Diagrams showing the esttmated extent ofcortical excisions in the left frontal-lobe casts. These diagrams are based on the surgeon’s drawing at the time of operation. On the medial surface. the excision extended down to the callosal sulcus in case Mi.Mi. The number of errors made by each patient IS indicated beside the appropriate brain map. For case HOSP., the cortical area marked wtth dots was disconnected hut not excised.

140

MICHAEL PETRIDES

$$tr frontul-lobe group. Figure 2 illustrates the exctsions of the 13 patients comprising thts group. All of the exctstons in the right frontal group involv’ed a considerable part of the dorsolateral frontal lobe with many of the excisions includmg parts of the media1 frontal cortex. Six patients (AI.Ma.. Br.Fe.. Cn.Cr.. ElSa.. Ro.Ma., SC.%.) were tested in the early postoperative period with the remaining patients tested from I to 24 years postoperatively. In this group, there were four patients (Br.Fe.. Gu.Vi.. Ro.Bo.. Ro.Ma.) with indolent cerebral tumour and two cases (Bo.Gr.. La.Ho.) of arteriovenous malformation. In one patient (AI.Ma). the excision involved the anteriormost part of the corpus callosum.

Sixty-two patients with excisions from the left or the right anterior temporal lobes were tested. These subjects were also classified according to the extent of damage to the hippocampal system. This resulted in four temporal-lobe groups: a left temporal-lobe group with limited (LTh) and one with extensive (LTH) damage to the hippocampal system, as well as a right temporal-lobe group with limited (RTh) and one with extensive damage to thts system (RTH). These classifications were based on the surgeon’s drawings and reports at the time ofoperatton. A temporal-lobe excision was considered to involve limited damage to the hippocampal system if. in addition to the antertor temporal neocortex. only the amygdala or the amygdala and pes hippocampi were ablated. An excision was considered to include extensive damage to the hippocampal complex if, in addition to the anterior temporal neocortex. amygdala. and pes htppocampi, there was damage to the body of the htppocampus and.or further damage to the parahippocampdl gyrus. In the left temporal-lobe group. the corttcal excisions ranged from 4.0 to 6.0 cm along the Sylvian fissure and from 3.5 to 6.5 cm along the base ofthe temporal lobe. In the right temporal-lobe group. the excisions ranged from 4.5 to 7. I cm along the Sylvian fissure and 5.0 to 7.0 cm along the base. The lateral extent ofexcision m three pattents of the LTh and !hree of the RTh group is illustrated in Fig. 3. Ten patients in the LTh group. six in the LTH group. six in the RTh group, and etght in the RTH group were tested in the early postoperative period: the remaining 32 patients were tested from I to 21 years postoperattv,ely. Four cases of indolent cerebral tumour and five cases of arteriovenous malformation were included in the temporallobe cases that were tested.

This group comprised 20. rtpht-handed. normal subjects. These subjects were chosen to be similar to those m the pattent groups m age and socioeconomic background: some of the control subjects were relattves of patients. Table I includes the distribution of sex and age for the control subjects.

TEST MATERIALS

AND PROCEDURE

In the present expertment. the subjects were presented with a stack of I8 cards (20.4 x 25.3 cm). Each one of these cards had six abstract destgns printed on It (see Fig. 4). The same six designs appeared on each card m varying posittons in a 2 x 3 array. These abstract designs were the same as those used in one of the test conditions (Ltst 6 of Abstract Destgns) of an earlter tnvestigatton that examined the effect of frontal- and temporal-lobe lesions on selfordered tashs Llh]. The destgns were drawn in such a way that they would be easy to distingutsh from one another but difficult to code verbally. This stmulus material posed no difficulties in discriminability for patrents with either frontal- or temporal-lobe excistons (see [ 161 I and it is precisely for this reason that it was used in the present study. At the hegtnntng of the testing scssmn. the subject and the experimenter sat at the table facing each other (see Ftg. 51. The stach of cards was placed on the table in front of the subject and the experimenter drew the subject’s attention to the fact that each card had the same designs printed on it hut that their positions varted from card 10 card.Thesuh.jcct ma:, then told that theexpertmentcr would point tooneofthedesignsonacardand that thesubject would then have to turn this card face dovvnwarda and. on the next card. point to the same design that the cxperimcnter had touched. The caperimenter would then point to another design and the subject again had to turn to the next card and touch the same one. This procedure continued until all six destgns had been touched. The purpose of thts part k>fthe test ~;ts to familiartze the subjects with the material and to establish that they had no dtlticulty tn dtscrtmtnattnf hctucen the stx diflerent destgns and in locating. within a new array and from memory. a parttcular dcstgn All subjects ft~und thts part of the test extremely) easy and errors were rarely made. If a subject made any crrots. tht\ procedure was repeated ~oensure that all designscould be readily dtscrimtnated before testmg on the condrtronal rash. On iomplett~>r> of thr\ rmtial stage of tcstmg. the expertmenter placed six differently coloured light-caps (red. yellow. whttc. hrovr n. blue. and green) on the table. in front of the stack of cards and close to the small screen that provented the suhjecl from scctng the scortng sheet (see Fig. 5). The subject was told that each one of the coloured \trmult ~a\ assocratcd H tth one and only one of the abstract designs and that his task was to learn whtch design was the correct one f
34

Error Score

44

Br.

or

121

19

Error Score

Ca.

Case

Case

_,

Error

50

28

25

SCOW

El. Sa.

63

17

26

Error Score

the excision extended down lo the cingulale fig. 2. Diagrams showing the estimated extent of cortical excisions in the right frontal-lobe cases. On the media! surface, errorsmade by these patients is indicated beside the appropriate brain map. gyrus in case J-P.Bi. The number

Case

z

142

MlCHAtL

PETRIDES

Case

Error Score

Case

Ph. Iv.

5

Er. Bo.

11

Do. VI.

Bo. Gr

Da. Br

_-_ ‘\

,---.

Error Score

,

12

,-.

/,’

--_

\

13

1’

10

Li. Bi.

,,/---‘ ,’

*\

7

Fig. 3. Diagrams showing the estimated lateral extent ofcortical excisions in three left and three right temporal-lobe cases. The number oferrors made by these patients is indicated beside the appropriate brain map.

he was told whether he had pointed to the correct design or not. lfan incorrect response was made. the subject had to point to other designs on the card until he found the correct one. The light-cap that was the stimulus for that trial was then placed back among the others and the subject turned the card to which he had just responded face downwards. thereby exposing the next card. The relative position of the light-caps was then changed, and the next trial was initiated by placing one of the light-caps m front ofthe others. The order of stimulus presentation was random. with the restriction that all six stimuli would be presented once in every set of six trials and that no sttmulus would be repeated on two consecutive trials. Testing continued until the subject reached the criterion of learning (1X consecutive correct responses) or until 1X0 trials had been administered. When testing had been completed, IO trials were run as follows. The experimenter pointed to one of the designs on a card. the subject was asked to look away from the card and count up to 20 and the card was covered. When the subject had finished counting. he had to point on a new card to the design that theexperimenter had touched. Errors in this final phase of the test were extremely rare in all groups of subjects. demonstrating that the designs could bc readtly idcntrfied from memory.

RESULTS The mean error scores made on this task by the various groups of subjects is illustrated in Fig. 6. In calculating the error scores only the first error made by a subject on each incorrect trial was counted. Thus. the error score of a subject refers to the number of incorrect trials before criterion. These data were analysed by means of appropriate nonparametric statistical tests because of the unequal number of subjects in the various groups in combination with heterogeneity of variance. A one-way analysis of variance by means of the KruskalPWaliis test performed on the error scores indicated the existence of significant differences between the various groups (H= 39.24, d.f. =6. P
NONSPATIAL

Fig. 4. The abstract

CONDITIONAL

143

LEARNING

designs used in the nonspatial

conditional

task.

NONSPATlAL

Fig, 5. Schematic

drawing

CONDITIONAL

145

LEARNING

of the experimental

arrangement

whether there was any relation between these two variables. None of these correlation coefficients (Pearson’s Product Moment) was significant. In addition. for each one of the two impaired groups. a direct comparison (Mann-Whitney test) was carried out between the error scores of patients tested in the early postoperative period and those of patients tested one or more years after operation. These comparisons were not significant, indicating that the impairment was just as evident in the cases seen a year or more postoperatively as in the cases that were examined in the immediate postoperative period. Figures I and 2 illustrate the excisions of patients in the left and right frontal groups together with the corresponding error scores. Definite statements regarding critical foci within the frontal lobe for this impairment cannot yet be made because the various excisions are restricted to particular regions of the frontal cortex in only a few cases. Nevertheless, it is worth noting that a number of patients with lesions invading the posterior dorsolateral frontal cortex (e.g. Ti.Pa. Wi.Wh. in Fig. I and Ca.Cr., Br.Fe. in Fig. 2) were severely

MICHAEL

PETHIDES

50!-

40

-

E g

30-

w 5 al I

m-

Group

NC

LTh

LTH

RTh

RTH

LF

RF

N

20

17

15

16

14

10

13

*p<

001

**

p<

0.001

Fig. 6. Mean error scores for the various groups on the conditional task. NC = LTh = left temporal-lobe group, little hippocampal involvement: LTH = left extensive hippocampal invoivement: RTh = rght temporal-lobe group. little ment: RTH =right temporal-lobe group. extensive hippocampal involvement: group: RF = right frontal-lobe group.

impaired,

Dw.Mi.

whilst others. with this region spared, performed in Fig. I and Sc.Sa.. Jo.Ed. in Fig. 2).

normal control group: temporal-lobe group. hippocampal ~nvolvcLF= left frontal-lobe

quite well (e.g. Ho.Sp..

Mi.Mi..

DISCUSSION The critical role of the human frontal cortex for mastering conditional tasks was first demonstrated with responses that were either distinct movements of the hand or pointing responses to different locations [12]. The present study examined the effect of unilateral excisions from the frontal or temporal lobes on the acquistion of a conditional task in which the subjects had to respond to various coloured stimuli by pointing to abstract designs. Since the position of these designs varied randomly on different trials, the correct responses were neither directed towards particular points in space nor were they distinct movements, but rather responses that could only be defined in terms of the goal that had to be achieved {e.g. select design X). As predicted and in agreement with work carried out with nonhuman primates, patients with excisions from the frontal cortex were impaired on this task. These findings extend previous work with patients by demonstrating that the role of the human frontal cortex in conditional learning is a general one and not limited to situations requiring selection between distinct movements. The deficit observed on the present task in patients with excisions from the frontal cortex cannot be due to difficulties in discriminating between the coloured stimuli or the different abstract designs; nor can it be ascribed to difficulties in scanning the display of six designs in order to locate the required one. For instance. these patients could readily name the different coloured stimuli and could identify any design from among the set of six designs. This was clearly shown in the initial phase of the experiment in which, after the experimenter had pointed to one of the designs, the subject had to turn over to the next card and locate, within the new arrangement. the one that the experimenter had touched. Thus, the patients with

frontal-lobe excisions, despite the fact that they could locate, from memory, any one of the designs on the different cards. were markedly impaired in iearning to select the particular one that was being cued by the different coloured stimuli. Work carried out with nonhuman primates has identified the posterior part of the dorsolateral frontal cortex (i.e. the periarcuate cortex) as a critical region for the learning and performance of conditional tasks [4, 11, 131. It has been demonstrated that animals with lesions restricted to this region can learn and perform without difficulty different responses. can discriminate between different stimuli, but are severely impaired when they have to select one or the other response conditional upon the particular stimulus presented [see 151. The posterior dorsolateral frontal cortex can be distinguished from other frontal regions on the basis ofcertain anatomical characteristics, such as the fact that it is linked directly with the visual, auditory and somatosensory cortical areas that are adjacent to the primary sensory cortices [e.g. 1, 2, 17, IS]. In addition. the anatomical evidence indicates that different parts of this region are preferentially linked to particular sensory systems. Investigation of the effects of selective lesions within the posterior dorsolateral frontal cortex has demonstrated differences according to the type of response required on various conditional tasks. Lesions restricted to the anterior part of the periarcuate region (area 8). which is preferentially connected with the visual system. resulted in a severe impairment on a conditional task in which the appropriate response (open the lit or the unlit box) could only be determined on the basis of the visual characteristics of the manipulanda. By contrast, lesions restricted to the more posterior part (rostra1 area 6) which is closely linked with the motor cortex and the somatosensory system. caused a severe impairment on a conditional task requiring selection between two distinct movements [see IS]. In both the work with patients and work with nonhuman primates on conditional tasks. it was shown that the subjects knew what the alternative responses were and could perform them without any difficulty. but were severely impaired in retrieving the particular ones that were being cued by the various stimuli. The importance of selection between alternative responses was well illustrated in experiments in which there was only one possible action to be performed. In such experiments, monkeys with periarcuate lesions could acquire the task at a normal rate, even if many different stimuli were involved and the monkeys had to learn which ones of these different stimuli were the cues for the response (Experiment 5 in ref. [ 143 ). Yet these same animals exhibited severe impairments when they had to choose between two alternative responses, even though they now had to consider only two stimuli. On the present conditional task, patients with temporal-lobe excisions with or without extensive involvement of the hippocampal complex were not impaired. By contrast, in an earlier investigation [ 121 patients with temporal-lobe excisions including an extensive part of the hippocampal complex exhibited impairments that varied with the side of the excision. Extensive damage of the right hippocampal system impaired acquisition of a conditional task with spatial responses, whereas left hippocampal damage resulted in a deficit on a task in which the responses were different hand postures. We know that the limbic areas in the mesial part of the temporal lobe are indispensable for adequate performance on many memory tasks and that their bilateral destruction will result in a severe amnesic syndrome [557, 91. We also know that significant inputs from many cortical areas, including the frontal cortex, reach this region 13, 10. 19-241. These findings suggest that the mesial region of the temporal lobe may be a critical part of a memory circuit serving many different cortical systems. The results ofthe earlier investigation on conditional tasks [ 121 were in agreement with this interpretation. It is therefore of considerable interest

148

MICHAEL PETRIDES

that. on the present task, patients with temporal-lobe excisions with extensive involvement of the hippocampal system were not impaired. This finding highlights the importance of the material to be learned in the demonstration of an impairment after unilateral damage of the hippocampal complex (see [6, 73). The use of coloured stimuli, which the subjects could readily verbalize, may have minimized the extent to which performance on this relatively easy task could be affected by unilateral hippocampal damage. Acknowledqemenrs--I am grateful to Dr A. Ohvier. Dr J.-G. Villemure and Dr W. Femdel and their associates at the Montreal Neurological Hospital for the opportunity to study their patients, to Mrs R. Amsel for statisucal advIce. and to Dr Brenda Milner for her comments during the preparation of this paper.

REFERENCES BARBAS.H. and MESULAM.M.-M. Organization ofafferent input to subdivisions ofarea 8 in the rhesus monkey. J. camp.Nrurol. 200,40743 1, 198 1. CHAVIS. D. A. and PANDYA. D. N. Further observations of cortico-frontal connections in the rhesus monke!. Brain Re,y. 117, 369- 386. 1976. GOLDMAN-RAKK, P. S.. SELEMON, L. D. and SCHWARTZ, M. L. Dual pathways connecting the dorsolateral prefrontal cortex with the hippocampal formation and parahippocampal cortex in the rhesus monkey. Neuroscience 12, 719-743. 1984. 4. HALSBAND, U. and PASSINGHAM,R. The role of premotor and parietal cortex in the direction of action. Bra& Res. 240. 368 -372, 1982.

5. MILNER, B. Disorders of learning and memory after temporal lobe lesions in man. Ch Neurosury. 19.42 I 446. 1972. of memory. In Cerebral Correlafes of Cmscious Eupurimcc~. 6. MILNER. B. Clues to the cerebral organization INSERM Symposium No. 6. P. BUER and A. ROUGEUL-BUSER (Editors), pp. 139-153. Elsevier. Amsterdam. 1978. functional specializations of the human cerebral hemispheres. In &‘wre Ctp//\. 7. MILNEK. B. Complementary Transmirters and Behariour. R. LEVI-MONTALCINI (Editor). pp. 601-625. Elsevier, Amsterdam. 1980. injections of sodium 8. MILNEK. B.. BRANCH. C. and RASSMUSSEN.T. Study of short term memory after intracarotid Amytal. Truns. .4m. neural. ilss. 87, 224 226. 1962. 9. MISHKIX. M. A memory system in the monkey. Phil. Trms. R. Sm. Land. B298, 85-95, 1982. of the cingulate gyrus in the 10. PANDYA. D. N.. VAN HOESEN. G. W. and MFSILAM. M.-M. EfTerent connections rhesus monkey. Exp. Bruit, Rrs. 42, 319-330. 19x1. associative-learning after selechve prefrontal lesions in the monke!. Brhr II. PETKIL)ES.M. Motor conditlonal Braill Res. 5, 407413. 1981. tasks after frontal- and temporal-lobe lesions in man. 12. PETRIIXS. M. Deficits on conditional associative-learning Nrurop.\~~/to/o[/lu 23, 601 -6 14. 19X5. In non-spatial condltlonal assoclatibe learnmg after periarcuate lesions in the monhq. 13. PI.TRILXS. M. D&Its Bch. Brtrirl Re.\. 16, 95 101. 1985. lesions In the monkey on the performance of symmctrlcally and 14. PFTRIIXS. M. The effect of pcriarcuale as>mmetrlcall\ rclnforced visual and auditory go. no-go tasks. J. ,Vuurosci. 6, 2054-2063, 1986. learning and the prlmate frontal cortex. In Tile Frorltal Lohrs Rrrisiled, E. PERIX‘hlA2. 15. PETRIIXS. M. Conditional (Editor), pp. 91 10X. The IRBN Press. Nc\r Yorh. 1987. 16. PTTKIIXS. hl. and MIL.NI-K. B. Deficit\ on %uhJcct-ordered tasks after frontal- and temporal -lohe lesions in man Ncurops l~~~hr>/~~(qir~ 20. 249 262. 1982. to the frontal cortex from the posterior parletal region m the 17. PCrHiI)i:s. M. and PSUI>\ A. D. ii Prqectlons rhesus monkc!. .I co,l1/) :\c~rrr~/. 228. IO5 116. 1984. fiber pathways to the frontal cortex from the superior temporal IX. PI~TRII)Is. M and P.\\t)\ 4. D. N. A\\ouratlon region tn the rhebuh monhq. .I. ump :Veuro/. 273, 52 66. 198X. area in the rhcsua monkq. I’). SI:LT~I:R. B. and PA~UYA. D. N. Some cortical pro_@tlonr to the parahippocampal

Evp. .VcwtJ/.

SO. I46

160. 1476.

in the ‘0. SI ~771 R, B. and V %I HOI SI X. <; W A direct Inferior parlctal lobule projection to the presuhiculum rhesus monhey. Bnrru Rc\. 179. I57 161. 197Y. 21. VA\ HOI SI X. G. W. and PAXI)) 4. D. N. Some connecllons of the entorhinal (area 28) and perirhinal (arca 351 cortices of the rhesus monhe!,. I. Temporal lohc ;&rents. Brcun Ru. 95, I-24, 1975. of the entorhinal (area 2x1 and ‘2. VA\ HOI:SI-3. G W.. P~\I)YA. D N. and Bt TTI KS. K Some connections perirhinal (arca 35) cortlce\ of the rhesus monkey. Il. F-rental lobe alTerents. Bruijl Rrs. 95, 25 3X. 1975.

NONSPATIALCONI1ITIONALLEARNING;

149

23. VAN HOESEN. G. W. and PANDYA, D. N. Some connections of the entorhinal (area 28) and perirhinal (area 35) cortlces of the rhesus monkey. III. Efferent connections. Brain Res. 95. 39-59. 1975. 24. VAN HOESEN. G. W., PANDYA. D. N. and BUTTERS. N. Cortical afferents to the entorhinal cortex of the rhesus monkey. Science 175, 1471-1473, 1972. 25. WADA, J. and RASMUSSEN,T. Intracarotid injection of sodium Amytal for the lateralization of cerebral speech dominance. Experimental and clinical observations. J. Neurosurq. 17, 266. 282, 1960.