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Premotor cortex and instrumental behavior in monkeys
Physiology and Behavior, VoL 8, pp. 299-305. Brain Research Publications Inc., 1972 Printed in Groat Britain
Premotor Cortex and Instrumental Behavior in Monkeys J E A N D E L A C O U R ~, S I M O N E L I B O U B A N A N D M A R G O T M C N E I L *
Centre d'Etudes de Physiologie nerveuse, Paris (Received 6 M a y 1971) DELACOUR, J., S. LIBOUBANAND M. MCNEIL. Premotor cortex and instrumental behavior in monkeys. PHYSIOL.Bra-~v. 8 (2) 299-305, 1972.---Twenty monkeys were trained on two main tests, 1 and 2. Test 1 included both a conditioned avoidance response (CAR) and a food reinforced response (FRR) according to a random schedule of presentation. Test 2 consisted of a standard test of delayed response (DR) made in WGTA. A bilateral ablation of the dorsal part of the premotor cortex has provoked significant deficits in Test 1. The CAR and the FRR were unequally and differently affected according to the individual differences. The animals did not show the phenomena called by some authors the cue magneto reactions. They also did not show deficits in Test 2, (DR), nor any disturbances of the spontaneous locomotor activity or the orienting responses to neutral stimuli.
Monkey Premotor cortex Avoidance response Locomotor activity Orienting responses
THERE ARE a very large number of neuropsychological studies concerned with the frontal cortex of the primate, but, for the most part, these studies emphasize the role of the prefrontal areas and, particularly that played in delayed responses. However, due to certain work by Stepien [17, 18, 19] and to the theoretical discussion of Luria [10] attention has recently been drawn to the premotor cortex. A n d thus, the old debate concerning the specific character of the functions of the premotor cortex has been revived [2, 5, 7, 9, 14, 21, 22]. Questions are being reformulated: is this area only the most rostral part of the motor cortex or is it a distinct anatophysiological entity ? According to Stepien, the ablation of the premotor area in the dog produces effects which are different from those found after prefrontal or motor cortex impairment. Premotor destruction produces a stereotyped hyperactivity of the conditioned response which is dissociated from the conditionod stimulus (CS) and an exaggeration of the orienting responses provoked by the CS (cue magneto reactions). These findings are supported by the anatomical data obtained in the Macaque by Pandya et al. [12]. They studied the cortico-cortical connections of the premotor cortex, and more specifically the connections of afferents arising from the different sensory areas that converge toward this area. The premotor area would be the pathway whereby sensory information converges toward the motor cortex. This area, controlling the movement of the eyes, ears, head and neck, would play, according to Pandya et aL, a role of particular importance in the orienting responses.
Food reinforced response
Delayed response
In view of these data, we have studied the effects of premotor cortical lesions on instrumental behavior in the Macaque in an experimental situation which allowed us to show the relationship between the orienting response and the instrumental response. This experimental set-up, having both positive and negative reinforcements available in the same situation, also allowed us to verify whether or not the role of the premotor cortex could, with respect to instrumental behavior, depend on the type of motivation involved. METHOD Twenty Macaques (Macaca irus) were used during two different series of experiments. The first series was used to standardize the procedures, the second series was the actual experimental group. The animals were naive males, weighing from 2-5 kg. F r o m the time that the experiments were begun the animals always lived in individual cages. They received their food which consisted of fruit and standard dry food for monkeys ( U A R Aliment compose complet--107) at the same hour each day (between 4-5 p.m.). The food was rationed for each animal according to the requirements of the experiment. All the animals were in the laboratory for at least 6 weeks before the experiments began.
Procedure The animals were habituated to their transport cages and to the test apparatus for two weeks. They were submitted to three tests: 1, 2 and 3.
1This research was supported by grant No. 70.34.467 from D.R.M.E. We express our gratitude to Dr. P. Der6me for aid with the neurosurgery and to R. Footnick for the translation into English. aRequests for reprints should be sent to J. Delacour, Centre d'Etudes de Physiologic nerveuse du C.N.R.S., I~partement de Psychophysiolngie, 4, avenue Gordon-Bennett, 75-Paris 16e, France. spresent address: Stanford University School of Medicine, Stanford University, Medical Center, Stanford, California 94305. 299
~00 Test I. A Skinner-type box was used, which was 62 cm high, 48 cm wide and 62 cm long. One of the large sides was made of transparent Plexiglas and the other three sides were opaque plastic covered in aluminium. These walls could be electrified as well as the floor, which was made of brass bars electrically isolated from each other. On each of the smaller walls (A and D) was an identical pedal. On wall A, a food cup was above the pedal. A loud speaker and a 15 W bulb lamp w~th a frosted glass were attached to the opaque ceiling. The animals, having been placed on a rationed diet, first learned to press pedal A on a continuous reinforcement schedule in order to obtain a reward of a 1.0 g pellet (NoyesPrecision Food Pellet Banana). The cage was lit steadily by the interior bulb. Following this, the illumination would become intermittent and the responses on Pedal A were only reinforced during the lit intervals which played the role of the FDS (food discriminative stimulus). The first response made in the presence o f a FDS was reinforced (food reinforced response FRR). This response automatically extended the duration of the FDS to 1 sec beyond the moment when the response was given. Just as the other responses on Pedal A were without effect, so were all the responses on Pedal D. At the end of this phase of the experiment, the maximum duratton of the FDS was 5 sec and that of the average intertnal interval was 15sec (range 10-25). Thus, each session was made up of 20 trials. When the percentage of reinforced trials reached 80%, a second learning situation began. Then, the animals had to press Pedal D in order to avoid an electric shock (4-6 mA) delivered by a scrambler generator (Grason-Stadler E60 70B). White noise of 77 db above the human threshold, was the cue for the onset of the shock, thus having the role of the DDS (defensive discriminatory stimulus). The parameters of this last learning phase were: DDS--shock interval equal to 5 sec and the maximum duration of the shock was 2.5 sec. The DDS overlapped the shock. By pressing Pedal D, the subject terminated either just the DDS (conditioned avoidance response CAR), or both the DDS and the shock (escape response). Each session always included an alternation of the FDS (Trial A) and the DDS (Trial D). The number of Trials D, which at first were limited to 3 or 4, increased progressively until they became equal to those of Trials A. In the last learning phase, Test 1 comprised 30 trials (15 A and 15 D) presented in random order and separated by an average interval of 15 sec (range 10-25). The test apparatus was in a soundproof chamber. The installation for programming and recording was in an adjoining room from where the animals were observed all the time by the use of a closed circuit TV. Throughout each trial the initial position and the successive positions of the head of the animal were noted according to a code based on 6 directions: face turned upwards (ceiling), downwards, toward the right (wall D), toward the left (wall A), toward the front (transparent wall), toward the back (back walt). The animals particularities of movement and of posture were, according to each case, also recorded. The physical location of each of the two cues must be emphasized. Each one was placed on the ceiling on the side opposite to that of the corresponding pedal, that is, the source of the FDS (15 W lamp) was on the side D and the source of the DDS (loud speaker) was on side A. This arrangement facilitated the shaping of the CAR (the S fleeing the source of the aversive signal). On the other hand, it was also favourable for observing the orienting responses (OR) provoked by the
DJzLAC()UR, LIBOt)BAN AND NIt NI II discrimlnattve stimulus and their eventual dts~octauo~ l rom the instrumental response. In general, the learning of the CAR was dominated, at the beginning, by a blockage that was more or less complele of the food reinforced response (FRR). This blocking effect disappeared as the CAR was better controlled The food ration was decreased which also faclhtated the recovery of the FRR. When during the course of the same session each of the two responses reached the 80/°o level, the learning of Test 2 began. Test 2. In another test apparatus, W G T A type, whtch was in the same soundproof chamber as the first one, the ammals were submitted to a delayed response test according to the classical W G T A procedure. After a period of shaping the procedure was as follows: at the beginning of each trial, the opaque screen was raised when the transparent screen was kept in a lowered position and through it the animal could see which of the two food cups received the reinforcement. This phase was standardized by the following procedure: the reward, which consisted of a fragment of dry food btscu~t (standard monkey food) was held for an mstant just above one of the two food cups then released and this being done three times. The food cups were then covered again. According to random order, one of the two cups was chosen for reinforcement from one trial to another. For th~s last phase, the delay of the response was 10 sec. and the session had 30 trials which were separated by intervals of 15 20 sec. A non-corrective method was used. The ammal did Test 1 and 2 alternatively, from one day to the next, until they reached a certain criterion. For Test 1, the number of CAR and of F R R could not be, on the average, less than 14 (the maximum being 15) per session, for 5 consecutive sessions. In Test 2, the number of correct responses was not less than 25 (the maxnnum being 30) for any of the 5 consecutive sessions. After a systematic adjusting of the food rationing, intended to obtain a stable level of performance, the animal's weights were maintained at a constant value, not varying more than ± 2 ° ° . Test 3. This takes place in the enclosure of the WGTA. In the course of th~s test three types of data were collected. (a) For 30 min the locomotor activity was measured by a system of photoelectric cells, and the manipulative actiwty by a chain-pulling device. One of the partmons of the WGTA was the transparent screen and the apparatus occupied a fixed position insMe of the soundproof chamber which was lit by a 150 W bulb on the ceding. (b) At the end of this 30 mm period, some visual stimuli were presented to the animal. These stimuh consisted of the illumination of three 3.5V bulbs placed on the d~fferent partitions. These stimuh were presented m random order. They were lit during the t~mes when the animal was immobile and as much as possible in the peripheral region of h~s visual field. Twenty stimuli were presented in each session. For each one the presence or absence of an orienting response was noted. The latter being defined by the movement of the eyeball which may or may not have been accompanied by a head movement. (c) Simple reaching response. The experimenter, seated in front of the W G T A with only the transparent screen m place, put a pmce of biscuit in the center of the tray which held the two food cups. Then the transparent screen was raised and the experimenter recorded which hand the animal used to seize the biscuit and the latency of this response. This was done for 5 successive trials. The latency of this response revealed itself to be a sensitive measure of the emotional state of the
PREMOTOR CORTEX AND BEHAVIOR animal. Some observations on the motor capacity of the animal could also be made on this occasion. During the pre-operative period, all the animals had 6 sessions of Test 3. Operation The experimental group of 14 animals (7 from the first experimental series and 7 from the second) underwent bilateral ablation of the dorsal region of the premotor cortex. These animals were placed in a stereotaxic apparatus under general anesthesia. A flap, 25 mm long and 30 mm wide, was cut in the skull cap above the posterior half of the frontal lobe. After opening the dura mater, the ablation was made by sub-pial suction. The designated zone was limited caudally by the precentral dimple, ventrally by the superior brachium of the arcuate sulcus. It continued toward the front at least to the end of the superior brachium of the arcuate sulcus. Only the most dorsal part of the inter-hemispheric cortex was included in the designated zone. The dura was then put back into place but not resown. The injured zone was covered over with a thin layer of Spongel then the flap was put back into place and fixed by twisting 4-6 silver wires into closed rings. Then the opening made in the skin and muscles was closed. At the end of the operation the animals received 500,000 units of a bi-penicillin intramuscularly (Didromycin bi-penicillin--Pfizer) and 200 mg of terramycin --Pfizer. In half of the animals the general anesthesia was a intravenous dose of 80 mg/kg of chloralose and in the other half it was 45 mg/kg of nembutal given intraperitoneally. In the first group the delimitation of the injured zone relied on electrophysiological data: the cortical evoked potentials provoked by 1--4 V electric shocks to the limbs of the animals. They were observed on a cathode-ray oscilloscope. Bilateral responses of large amplitude were typically seen at the precentral dimple [1]. The recovery period was at least 6 full days. During this period the animals were weighed regularly and observed in their home cages. F o r at least three days, they received orally a dose of 250 mg of penicillin (ampicillin) Delagrange. At the end of this period, they immediately had 5 consecutive sessions of Test 2, then 5 consecutive sessions of Test 1. The reason for this order of retesting without alternation of the two tests was that the animals, who had a deficit in the C A R (Test 1), would receive a number of strong shocks. By testing the delayed response (Test 2) before Test 1 we avoided the possibility that the over-all behavioral d~sturbance provoked by the electric shocks would affect Test 2. After following 5 learning sessions in each of the two principal tests, the animals continued to be tested at the rate of one session per week for each test, for 5 weeks. Thus, the animals were submitted to 10 post-operative sessions for Test 1 and Test 2. And alternated with these tests, they also had 7 sessions of Test 3. The post-operative period had therefore a length of 9 to 12 weeks. During this period the animals weight was maintained, as much as possible, at a value (about =t=2%) equal to the stable value reached at the end of the pre-operative period. The animals were sacrificed by an over-dose of nembutal at the end of the post-operative period and perfused by an intracarotidical injection of 10% neutral formalin solution. A group of 6 animals were the non operated control group. These animals, after having reached an average performance level comparable to that of the experimental group, had an interruption in their training, the length of which was the same as the period of recovery of the experimental animals
301 after the operation. Then, they were retested following exactly the same procedure as was used on the experimental animals. Statistics Two-tailed non-parametric tests were used for statistical treatment, i.e., the Mann-Whitney test, the Wilcoxon test [16]. A parametric test (Student t) was also used [11]. RESULTS
Only the results obtained from 13 animals of the second experimental series (6 controls and 7 experimental animals) have been kept here, given that the first series of experiments were intended to set up the techniques and the protocol. Therefore, their results were not obtained in perfectly standardized conditions. Due to this fact, they were separated although on the whole the results of the two series were very comparable. 1. Description o f the Lesion The average limits of the destroyed zone are indicated in Figs. 1 and 2. In one case, of the monkey Ne, the lesion extended toward the front, beyond the arcuate, reaching the posterior part of the principal sulcus. In all the animals the inter-hemispheric cortex was touched only in the dorsal-most region. 2. Non-standardized Observations There has not been an interaction between the effects of the lesion and the anesthesia used (chloralose or Nembutal). In 4 out of 7 cases, edema appeared 48 hr after the operation.
FIG. 1. Dorsal view of Macaca Irus cortex. Representation of experimental group's lesions (7 animals) superimposed.
302
I)ELACOUR, LIBOUBAN A N t ) MCNEIl
not slgmficantly d~fferent from those ol the pre-op b,.olcs (47.7 as compared to 43.7). These scores were equally as stable m the controls (38.1-40.4). The test of mampulatlvc actlvlty was not sensitive enough and d~d not g~ve usable results. The average number of ORs provoked by the visual stimuli in the enclosure of the W G T A did not vary s~gnificantly after the operation in the experimental animal (6.7 as opposed to 8.6). The same for the controls, this number was not very modified by the interruption of the training (8.9 to 10.2). The latency of the simple reaching response and the hand preferentially used for th~s response were not modified by the lesion. 4. Test 2 (Delayed Response)
The performances of the experimental ammals decreased shghtly after the operation (Table 1), but this was essentially due to the performance of one animal. In this animal (Ne) the lesion extended bdaterally to the posterior part of the principal sulcus and his scores were at the level of chance (50%). Nevertheless, even taking into account this performance the post-op average results of the experimental animals were not significantly diminished and did not differ from those of the controls.
"1A B L E
I
MEAN PERFORMANCESIN TESI 2
Pre-op
6 FIG. 2. Diagrams showing by means of cross sections the depth of lesions of two typical experimental animals.
It was reabsorbed in 3-5 days. The observaUons made during the recovery period on the animal in his home cage did not reveal a sensory deficit. The animal had normal reactions to stimuli such as food, gestures of the experimenter, gestures or cries of the other animals. By contrast, the motor activity was slowed down and clumsy for an average period of two weeks. During several days immediately following the operation, some animals showed apathic and hypokinetic behavior. These signs were in general very attenuated, if not obliterated, from the time of the beginning of the learning tests. 3. Standardized Observations on Sensori-motor Capabilities An examination of the sensori-motor capabilities (Test 3) did not reveal a large deficit in the experimental animals. The average scores of the post-op locomotor activity were
Post-op Range
Group
Mean
Range
Mean
E
27.9
(29.6-25.0)
25.4
(29.3-15.3)
C
28.2
(29.5-27.2)
28.6
(30.0-25.4)
Te~t 2 (Delayed response). Mean number of correct responses per session (30 trials) for the experimental Group E and the control Group C. The post-op phase in Group E corresponds to the phase following the interruption of training in Group C.
5. Test 1
In th~s test, by contrast, the ablation of the pre-motor cortex has provoked clear deficits in the CAR and in the F R R (Table 2). The difference between the pre- and post-op scores of the C A R reached the p < 0.02 level and between the pre- and post-op levels of the F R R it was at the p < 0.01 level. The performances of the experimental animals were equally as inferior to those of the controls during the retraining phase, that is, p < 0.02 level for the C A R and for the F R R . In Crr.E., the dtfference between the post-op scores of the C A R and F R R is not significant, therefore the action of the lesion did not differentiate between the two types of responses. Yet an examination of the individual scores reveals very great differences: two animals do not demonstrate clear deficit (An and Je). In the case of two othors (Ma and XY) the C A R is almost perfectly intact while the F R R is practically completely blocked. Lastly, in the other three animals (Ph, Ac and Ne), the two responses are dearly depressed without however being completely blocked (Table 3). The intra- and inter-session evolution of the experimental animals' behavior shows that these deficits appear in various
PREMOTOR CORTEX AND BEHAVIOR
303
TABLE 2
TABLE 4
MEAN PERFORMANCF~ IN TEST I
MEAN LATENCIESIN TEST 1
Group
Response
C E E C
CAR CAR FRR FRR
Pre-op Mean Range
Post-op Mean Range
I00 I00 96.5 96.4
99.6 72.5 56.9 96.9
(98.6--92.1) (100-94.6)
(100-98.0) (100-34.0) (94.5-6.3) (98.0-95.4)
Group
Response
C E E C
CAR CAR FRR FRR
Pre-op Mean Range 0.76 0.89 1.85 2.07
(0.62-0.98) (0.40-1.49) (1.41-2.14) (1.48-2.60)
Post-op Mean Range 0.81 1.40 2.36 2.01
(0.64-1.02) (0.68-2.15) (1.65-3.51) (1.53-2.37)
Test 1. Mean percentage, with respect to the number of trials of the CAR (conditioned avoidance response) and of the FRR (food reinforced response). Same conventions used as for Table I.
Test 1. Mean latency in sec of the CAR and of the FRR. Same conventions used as in above tables.
TABLE 3
particularly clear with regard to Pedal D due to the behavior of bar-holding which developed on this pedal. After the operation, the average number of intertrial responses on Pedal A of the experimental animals showed a non-significant decrease, although the frequency of intertrial responses on Pedal D changed little. In contrast one finds these two categories of response remained stable in Group C (Table 5).
INDIVIDUAL PERFORMANCES IN TEST l
Subjects
An Ma Ph Ac XY Ne Je
CAR
Pre-op FRR
100 100 100 100 100 100 100
97.4 97.4 97.2 98.6 92.1 95.9 97.1
Post-op CAR 100 85.9 46.7 34.0 99.3 41.9 99.3
FRR 94.5 6.3 48.0 72.7 15.4 72.4 89.2
Test 1. Individual performances of the animals from Group E expressed in mean percentages of the number of trials. Same conventions used as for the preceding tables.
ways. The blockage of the F R R may be due to the deficit of the CAR, i.e. to the shocks received owing to this deficit (Ph, Ac, Ne). The blocking of the feeding response can manifest itself right away (Ma and XY) and can continue in spite of an elevated level of the CAR. These deficits could be linked to mistakes of commission, that is, responses on the Pedal D in the presence of the F D S and reciprocally, but these errors were rare. Most often the deficit was noticed by the complete absence of all manipulatory responses in the presence of the signal. In the presence of the DDS, the animal did not remain immobile but executed a series of jumps and runs in circles which were sometimes accompanied bycries. When the F D S w a s present, the animal very frequently remained immobile; in many cases he then displayed a barholding behavior on Pedal D. The latency of the C A R increased significantly (p < 0.01) in Gr. E. after the operation, likewise for the F R R (p < 0.02). On the contrary, the latency of the two categories of responses remained stable in G r o u p C (Table 4). The observations made on the animals seem to show that this augmentation was not due to a slowing down of the manipulatory gesture itself, but rather to other factors, such as, slowing down the postural adjustment necessary for the response, a difficulty in releasing the pedal used for the preceding trial or by responses during the intertrial interval. This difficulty in releasing was
TABLE 5 INTERTRIAL RESPONSES IN TEST 1
Group
Pedal
C E E C
D D A A
Pre-op Mean Range
Post-op Mean Range
7.1 5.6 40.3 44.7
6.4 8.5 15.7 40.9
(2.2-20.6) (0.4-19.2) (1.8-137.0) (4.3-97.8)
(1.7-28.1) (2.9-19.6) (1.5-43.8) (5.1-94.7)
Test 1. Mean number of intertrial responses on Pedal D and on Pedal A per session. Same conventions used as for above tables.
The continual observations of the animals through the closed-circuit TV did not give any evidence for the existence of a phenomenon analogous to the cue magneto reactions. The patterns of postural adjustment of the body and the orienting movements of the head remained unchanged in the two animals not having clear deficits. In the others, these reactions were modified in various ways, especially in the animals receiving a large number of shocks. The absence of response was accompanied, most often in the presence of the DDS, by only poorly orientated locomotor responses or by a complete immobility in the presence of the FDS. The postural adjustments and the ORs preceding the responses were above all marked by a certain slowness or perseverance of motor patterns in the course of execution (inter-trial responses). DISCUSSION
The lack o f deficit in the experimental animals on the delayed response test confirms earlier results of Jacobsen [8]
q)4
DELACOUR, LIBOUBAN AND M(.NFII
and Pmbram [13J. Likewise the absence of notable changes m the locomotor actiwty agrees with the data of French [4]. Finally, neither the ORs to neutral stimuli, nor the simple reaching response tested in Test 3 were disturbed by the lesion. These negahve results do not allow the deficits observed in Test 1 to be attributed to an over-all dlsturbance of the behavior, from the sensori-motor and emotional point of view. These deficits present a problem which is difficult to interpret owing to the ambiguity of the very notion of the premotor cortex. Two main conceptions may be considered with regard to the role of the premotor cortex: that of a purely motor function and that of an integrator role. 1. According to the first of these two concepts, the motor cortex would only consist of the most rostral part of the motor area [14, 22]. The transitory maladroitness, the slowness of the spontaneous movements and the augmentation of the latency of the conditioned responses are arguments m favour of this idea. The observed increase in latency appears to be due more to the slowness of the postural adjustments rather than to the manipulatory motion itself. This fact seems to confirm the idea of a rostro-caudal organization of the motor area. The most rostral region of this area would control the proximal and axial articulations which would be particularly set into action by the postural adjustments [22]. The motor trouble following an injury of this zone would be especially sensitive to such a task as Test 1. This is due to two character~stics of the test: (a) limited time of response (maximum duration of the FDS or of the DDS--shock interval) (b) alternation between two responses, thus setting into action different and incompatible postural adjustments (Pedal A and Pedal D are placed on the two opposite partitions). There was no effect on the locomotor achwty or manipulatory responses displayed when the ammal was m a constant posture (Test 2). In Test 1 the CAR and the F R R were unequally and differently affected according to the mdiwdual differences of the animal. This data could also be explained within the framework of the purely motor conception of the premotor cortex. The utilizahon of a hmb affected by a pre-central lesion could depend on the level of motwatlon [2, 3]. The relative respectwe levels of the food and defensive rnotivat~on were probably not equal m all the animals.
This would be the result of very large differences betv~een individuals, notwithstanding the comparable and stable pre-op performance levels for each of the two responses. Nevertheless, Schwartz' results [15] obtained m conditions s~milar to ours, do not confirm the existence of an interaction between the level of motivation and deficits following the precentral lesions. 2. For several authors, the functions of the premotor cortex would be distinct from those of the motor cortex. The premotor cortex would play a role in the programmahon of movement [10]. It could exert an mh~biting action on the patterns of instinctive reaction depending on the pallidonigral system [2]. And a third hypothesis has it controlling the relations between the CS and the conditioned response [19]. Only this latter hypothesis has been able to be tested directly by our experiments. Our results did not show the cue magneto reactions nor a significant increase of the hum bet of rater-trial responses observed in the dog by Stephen. One must note that this same author did not find the cue magneto reactions again when she looked at the monkey in a s~tuatlon quite comparable to the one she has used for the dog [20]. Nevertheless, the phenomena of stereotype and of perseverat~on observed by Stepien after a lesion in the premotor cortex could be at the origin of the deficits obtained m Test 1. The situation would be characterized by the interaction of two motivations mobilizing two spatially distract responses. The capacity of shifting (between averswe and approach responses) reqmred by this situation would have been diminished in the experimental animals. A support of this hypothesis could be the lengthening of the latencies and above all the errors of commission sometime emitted. These latter errors ~ere nevertheless rare, the deficit of the responses consisted for the most part of a complete blockage. There is another objection to this interpretation, which is that the test of the delayed response, tested in the WGTA, is equally as sensitive to the phenomena of perseveratlon. But, the animals of the experimental group have not shown a deficit in this test. The results presented here are too incomplete to allow a choice between the motor concephon and the integrator hypothes~s of the premotor cortex. It seems, nevertheless, that with regard to our results, the first of these two concepts ~s the most economical explanation.
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chimpanzees. Res. Publ. Ass, Nerv. Ment. Dts. 13: 225-247, 1934. Jacobsen, C. F. and G. M. Haslerud. A note on the effect of motor and premotor area lesions on delayed response m monkey. Comp. PsychoL Monogr. 13: 66-68, 1936. Kennard, M., H. R. V~ets and J. F. Fulton. The syndrome of the premotor cortex in man. Brain 57: 69-84, 1934. Lurm, A. R. Human Brain and Psychological Pro~esaes. New York and London: Harper and Row, 1966. Mac Nemar, Q. Psychological Statistics. New York: Wiley, 1955. Pandya, D. N. and H. G. J. M. Kuypers. Cortico-corhcal connections in the rhesus monkey. Brain Res. 13: 13-36, 1969. Pribram, K. H., L. Kruger, F. Robinson and A. J. Berman. The effects of precentral lesions on the behaviour of monkeys. Yale J. Biol. and Med. 28: 428-443, 1955-1956. Pribram, K. H. Neocortical function in behavior. In: Biological and Biochemical Bases of Behavior, edited by H. F. Harlow and C. N. Woolsey. Wisconsin: University of Wisconsin Press, pp. 151-172, 1958.
PREMOTOR CORTEX A N D BEHAVIOR 15. Schwartz, A. S. Recovery from motor deficit under d~fferent motivational conditions. Physiol. Behav. 4: 57-60, 1969. 16. Siegel, S. Non-parametric Statistics for the Behavioral Sciences. New York: McGraw-Hill, 1956. 17. Stepien, I., L. Stepien and J. Konorskl. The effects of bdateral lesions in the premotor cortex on type 11 conditioned reflexes in dogs. Acta Biol. Exp. 20: 225-242, 1960. 18. Stepien, I., L. Stepien and J. Kreiner. The effects of total and partial ablation of the premotor cortex on the instrumental conditioned reflexes in dogs. Acta Biol. Exp. 23: 45-59, 1963. 19. Stepien, I., L. Stepien and B. Sychowa. Disturbances of motor conditioned behavior following bdateral ablations of the precruciate area in dogs and cats. Acta Biol. Exp., Warsaw 26: 323-340, 1966.
305 20. Steplen, 1. and J. S. Stamm. Impairments of locomotor task involving spatial opposition between cue and reward in frontally ablated monkeys. Acta Neurobtol. Exp. 30: 1-12, 1970. 21. Walshe, F. M. R. On the syndrome of the premotor cortex and the definition of premotor and motor areas. Brain 58: 49-80, 1935. 22. Woolsey, C. N., P. H. Settlage, D. R. Meyer, W. Spencer, T. P. Hamuy and A. M. Travls. Patterns of locahzation in precentral and supplementary motor areas and their relation to the concept of premotor area. In : Patterns oJ Organization in the Central Nervous System. Res. Publ. Ass. Nerv. Ment. Dis. 30: 238-264, 1952.
Premotor Cortex and Instrumental Behavior in Monkeys J E A N D E L A C O U R ~, S I M O N E L I B O U B A N A N D M A R G O T M C N E I L *
Centre d'Etudes de Physiologie nerveuse, Paris (Received 6 M a y 1971) DELACOUR, J., S. LIBOUBANAND M. MCNEIL. Premotor cortex and instrumental behavior in monkeys. PHYSIOL.Bra-~v. 8 (2) 299-305, 1972.---Twenty monkeys were trained on two main tests, 1 and 2. Test 1 included both a conditioned avoidance response (CAR) and a food reinforced response (FRR) according to a random schedule of presentation. Test 2 consisted of a standard test of delayed response (DR) made in WGTA. A bilateral ablation of the dorsal part of the premotor cortex has provoked significant deficits in Test 1. The CAR and the FRR were unequally and differently affected according to the individual differences. The animals did not show the phenomena called by some authors the cue magneto reactions. They also did not show deficits in Test 2, (DR), nor any disturbances of the spontaneous locomotor activity or the orienting responses to neutral stimuli.
Monkey Premotor cortex Avoidance response Locomotor activity Orienting responses
THERE ARE a very large number of neuropsychological studies concerned with the frontal cortex of the primate, but, for the most part, these studies emphasize the role of the prefrontal areas and, particularly that played in delayed responses. However, due to certain work by Stepien [17, 18, 19] and to the theoretical discussion of Luria [10] attention has recently been drawn to the premotor cortex. A n d thus, the old debate concerning the specific character of the functions of the premotor cortex has been revived [2, 5, 7, 9, 14, 21, 22]. Questions are being reformulated: is this area only the most rostral part of the motor cortex or is it a distinct anatophysiological entity ? According to Stepien, the ablation of the premotor area in the dog produces effects which are different from those found after prefrontal or motor cortex impairment. Premotor destruction produces a stereotyped hyperactivity of the conditioned response which is dissociated from the conditionod stimulus (CS) and an exaggeration of the orienting responses provoked by the CS (cue magneto reactions). These findings are supported by the anatomical data obtained in the Macaque by Pandya et al. [12]. They studied the cortico-cortical connections of the premotor cortex, and more specifically the connections of afferents arising from the different sensory areas that converge toward this area. The premotor area would be the pathway whereby sensory information converges toward the motor cortex. This area, controlling the movement of the eyes, ears, head and neck, would play, according to Pandya et aL, a role of particular importance in the orienting responses.
Food reinforced response
Delayed response
In view of these data, we have studied the effects of premotor cortical lesions on instrumental behavior in the Macaque in an experimental situation which allowed us to show the relationship between the orienting response and the instrumental response. This experimental set-up, having both positive and negative reinforcements available in the same situation, also allowed us to verify whether or not the role of the premotor cortex could, with respect to instrumental behavior, depend on the type of motivation involved. METHOD Twenty Macaques (Macaca irus) were used during two different series of experiments. The first series was used to standardize the procedures, the second series was the actual experimental group. The animals were naive males, weighing from 2-5 kg. F r o m the time that the experiments were begun the animals always lived in individual cages. They received their food which consisted of fruit and standard dry food for monkeys ( U A R Aliment compose complet--107) at the same hour each day (between 4-5 p.m.). The food was rationed for each animal according to the requirements of the experiment. All the animals were in the laboratory for at least 6 weeks before the experiments began.
Procedure The animals were habituated to their transport cages and to the test apparatus for two weeks. They were submitted to three tests: 1, 2 and 3.
1This research was supported by grant No. 70.34.467 from D.R.M.E. We express our gratitude to Dr. P. Der6me for aid with the neurosurgery and to R. Footnick for the translation into English. aRequests for reprints should be sent to J. Delacour, Centre d'Etudes de Physiologic nerveuse du C.N.R.S., I~partement de Psychophysiolngie, 4, avenue Gordon-Bennett, 75-Paris 16e, France. spresent address: Stanford University School of Medicine, Stanford University, Medical Center, Stanford, California 94305. 299
~00 Test I. A Skinner-type box was used, which was 62 cm high, 48 cm wide and 62 cm long. One of the large sides was made of transparent Plexiglas and the other three sides were opaque plastic covered in aluminium. These walls could be electrified as well as the floor, which was made of brass bars electrically isolated from each other. On each of the smaller walls (A and D) was an identical pedal. On wall A, a food cup was above the pedal. A loud speaker and a 15 W bulb lamp w~th a frosted glass were attached to the opaque ceiling. The animals, having been placed on a rationed diet, first learned to press pedal A on a continuous reinforcement schedule in order to obtain a reward of a 1.0 g pellet (NoyesPrecision Food Pellet Banana). The cage was lit steadily by the interior bulb. Following this, the illumination would become intermittent and the responses on Pedal A were only reinforced during the lit intervals which played the role of the FDS (food discriminative stimulus). The first response made in the presence o f a FDS was reinforced (food reinforced response FRR). This response automatically extended the duration of the FDS to 1 sec beyond the moment when the response was given. Just as the other responses on Pedal A were without effect, so were all the responses on Pedal D. At the end of this phase of the experiment, the maximum duratton of the FDS was 5 sec and that of the average intertnal interval was 15sec (range 10-25). Thus, each session was made up of 20 trials. When the percentage of reinforced trials reached 80%, a second learning situation began. Then, the animals had to press Pedal D in order to avoid an electric shock (4-6 mA) delivered by a scrambler generator (Grason-Stadler E60 70B). White noise of 77 db above the human threshold, was the cue for the onset of the shock, thus having the role of the DDS (defensive discriminatory stimulus). The parameters of this last learning phase were: DDS--shock interval equal to 5 sec and the maximum duration of the shock was 2.5 sec. The DDS overlapped the shock. By pressing Pedal D, the subject terminated either just the DDS (conditioned avoidance response CAR), or both the DDS and the shock (escape response). Each session always included an alternation of the FDS (Trial A) and the DDS (Trial D). The number of Trials D, which at first were limited to 3 or 4, increased progressively until they became equal to those of Trials A. In the last learning phase, Test 1 comprised 30 trials (15 A and 15 D) presented in random order and separated by an average interval of 15 sec (range 10-25). The test apparatus was in a soundproof chamber. The installation for programming and recording was in an adjoining room from where the animals were observed all the time by the use of a closed circuit TV. Throughout each trial the initial position and the successive positions of the head of the animal were noted according to a code based on 6 directions: face turned upwards (ceiling), downwards, toward the right (wall D), toward the left (wall A), toward the front (transparent wall), toward the back (back walt). The animals particularities of movement and of posture were, according to each case, also recorded. The physical location of each of the two cues must be emphasized. Each one was placed on the ceiling on the side opposite to that of the corresponding pedal, that is, the source of the FDS (15 W lamp) was on the side D and the source of the DDS (loud speaker) was on side A. This arrangement facilitated the shaping of the CAR (the S fleeing the source of the aversive signal). On the other hand, it was also favourable for observing the orienting responses (OR) provoked by the
DJzLAC()UR, LIBOt)BAN AND NIt NI II discrimlnattve stimulus and their eventual dts~octauo~ l rom the instrumental response. In general, the learning of the CAR was dominated, at the beginning, by a blockage that was more or less complele of the food reinforced response (FRR). This blocking effect disappeared as the CAR was better controlled The food ration was decreased which also faclhtated the recovery of the FRR. When during the course of the same session each of the two responses reached the 80/°o level, the learning of Test 2 began. Test 2. In another test apparatus, W G T A type, whtch was in the same soundproof chamber as the first one, the ammals were submitted to a delayed response test according to the classical W G T A procedure. After a period of shaping the procedure was as follows: at the beginning of each trial, the opaque screen was raised when the transparent screen was kept in a lowered position and through it the animal could see which of the two food cups received the reinforcement. This phase was standardized by the following procedure: the reward, which consisted of a fragment of dry food btscu~t (standard monkey food) was held for an mstant just above one of the two food cups then released and this being done three times. The food cups were then covered again. According to random order, one of the two cups was chosen for reinforcement from one trial to another. For th~s last phase, the delay of the response was 10 sec. and the session had 30 trials which were separated by intervals of 15 20 sec. A non-corrective method was used. The ammal did Test 1 and 2 alternatively, from one day to the next, until they reached a certain criterion. For Test 1, the number of CAR and of F R R could not be, on the average, less than 14 (the maximum being 15) per session, for 5 consecutive sessions. In Test 2, the number of correct responses was not less than 25 (the maxnnum being 30) for any of the 5 consecutive sessions. After a systematic adjusting of the food rationing, intended to obtain a stable level of performance, the animal's weights were maintained at a constant value, not varying more than ± 2 ° ° . Test 3. This takes place in the enclosure of the WGTA. In the course of th~s test three types of data were collected. (a) For 30 min the locomotor activity was measured by a system of photoelectric cells, and the manipulative actiwty by a chain-pulling device. One of the partmons of the WGTA was the transparent screen and the apparatus occupied a fixed position insMe of the soundproof chamber which was lit by a 150 W bulb on the ceding. (b) At the end of this 30 mm period, some visual stimuli were presented to the animal. These stimuh consisted of the illumination of three 3.5V bulbs placed on the d~fferent partitions. These stimuh were presented m random order. They were lit during the t~mes when the animal was immobile and as much as possible in the peripheral region of h~s visual field. Twenty stimuli were presented in each session. For each one the presence or absence of an orienting response was noted. The latter being defined by the movement of the eyeball which may or may not have been accompanied by a head movement. (c) Simple reaching response. The experimenter, seated in front of the W G T A with only the transparent screen m place, put a pmce of biscuit in the center of the tray which held the two food cups. Then the transparent screen was raised and the experimenter recorded which hand the animal used to seize the biscuit and the latency of this response. This was done for 5 successive trials. The latency of this response revealed itself to be a sensitive measure of the emotional state of the
PREMOTOR CORTEX AND BEHAVIOR animal. Some observations on the motor capacity of the animal could also be made on this occasion. During the pre-operative period, all the animals had 6 sessions of Test 3. Operation The experimental group of 14 animals (7 from the first experimental series and 7 from the second) underwent bilateral ablation of the dorsal region of the premotor cortex. These animals were placed in a stereotaxic apparatus under general anesthesia. A flap, 25 mm long and 30 mm wide, was cut in the skull cap above the posterior half of the frontal lobe. After opening the dura mater, the ablation was made by sub-pial suction. The designated zone was limited caudally by the precentral dimple, ventrally by the superior brachium of the arcuate sulcus. It continued toward the front at least to the end of the superior brachium of the arcuate sulcus. Only the most dorsal part of the inter-hemispheric cortex was included in the designated zone. The dura was then put back into place but not resown. The injured zone was covered over with a thin layer of Spongel then the flap was put back into place and fixed by twisting 4-6 silver wires into closed rings. Then the opening made in the skin and muscles was closed. At the end of the operation the animals received 500,000 units of a bi-penicillin intramuscularly (Didromycin bi-penicillin--Pfizer) and 200 mg of terramycin --Pfizer. In half of the animals the general anesthesia was a intravenous dose of 80 mg/kg of chloralose and in the other half it was 45 mg/kg of nembutal given intraperitoneally. In the first group the delimitation of the injured zone relied on electrophysiological data: the cortical evoked potentials provoked by 1--4 V electric shocks to the limbs of the animals. They were observed on a cathode-ray oscilloscope. Bilateral responses of large amplitude were typically seen at the precentral dimple [1]. The recovery period was at least 6 full days. During this period the animals were weighed regularly and observed in their home cages. F o r at least three days, they received orally a dose of 250 mg of penicillin (ampicillin) Delagrange. At the end of this period, they immediately had 5 consecutive sessions of Test 2, then 5 consecutive sessions of Test 1. The reason for this order of retesting without alternation of the two tests was that the animals, who had a deficit in the C A R (Test 1), would receive a number of strong shocks. By testing the delayed response (Test 2) before Test 1 we avoided the possibility that the over-all behavioral d~sturbance provoked by the electric shocks would affect Test 2. After following 5 learning sessions in each of the two principal tests, the animals continued to be tested at the rate of one session per week for each test, for 5 weeks. Thus, the animals were submitted to 10 post-operative sessions for Test 1 and Test 2. And alternated with these tests, they also had 7 sessions of Test 3. The post-operative period had therefore a length of 9 to 12 weeks. During this period the animals weight was maintained, as much as possible, at a value (about =t=2%) equal to the stable value reached at the end of the pre-operative period. The animals were sacrificed by an over-dose of nembutal at the end of the post-operative period and perfused by an intracarotidical injection of 10% neutral formalin solution. A group of 6 animals were the non operated control group. These animals, after having reached an average performance level comparable to that of the experimental group, had an interruption in their training, the length of which was the same as the period of recovery of the experimental animals
301 after the operation. Then, they were retested following exactly the same procedure as was used on the experimental animals. Statistics Two-tailed non-parametric tests were used for statistical treatment, i.e., the Mann-Whitney test, the Wilcoxon test [16]. A parametric test (Student t) was also used [11]. RESULTS
Only the results obtained from 13 animals of the second experimental series (6 controls and 7 experimental animals) have been kept here, given that the first series of experiments were intended to set up the techniques and the protocol. Therefore, their results were not obtained in perfectly standardized conditions. Due to this fact, they were separated although on the whole the results of the two series were very comparable. 1. Description o f the Lesion The average limits of the destroyed zone are indicated in Figs. 1 and 2. In one case, of the monkey Ne, the lesion extended toward the front, beyond the arcuate, reaching the posterior part of the principal sulcus. In all the animals the inter-hemispheric cortex was touched only in the dorsal-most region. 2. Non-standardized Observations There has not been an interaction between the effects of the lesion and the anesthesia used (chloralose or Nembutal). In 4 out of 7 cases, edema appeared 48 hr after the operation.
FIG. 1. Dorsal view of Macaca Irus cortex. Representation of experimental group's lesions (7 animals) superimposed.
302
I)ELACOUR, LIBOUBAN A N t ) MCNEIl
not slgmficantly d~fferent from those ol the pre-op b,.olcs (47.7 as compared to 43.7). These scores were equally as stable m the controls (38.1-40.4). The test of mampulatlvc actlvlty was not sensitive enough and d~d not g~ve usable results. The average number of ORs provoked by the visual stimuli in the enclosure of the W G T A did not vary s~gnificantly after the operation in the experimental animal (6.7 as opposed to 8.6). The same for the controls, this number was not very modified by the interruption of the training (8.9 to 10.2). The latency of the simple reaching response and the hand preferentially used for th~s response were not modified by the lesion. 4. Test 2 (Delayed Response)
The performances of the experimental ammals decreased shghtly after the operation (Table 1), but this was essentially due to the performance of one animal. In this animal (Ne) the lesion extended bdaterally to the posterior part of the principal sulcus and his scores were at the level of chance (50%). Nevertheless, even taking into account this performance the post-op average results of the experimental animals were not significantly diminished and did not differ from those of the controls.
"1A B L E
I
MEAN PERFORMANCESIN TESI 2
Pre-op
6 FIG. 2. Diagrams showing by means of cross sections the depth of lesions of two typical experimental animals.
It was reabsorbed in 3-5 days. The observaUons made during the recovery period on the animal in his home cage did not reveal a sensory deficit. The animal had normal reactions to stimuli such as food, gestures of the experimenter, gestures or cries of the other animals. By contrast, the motor activity was slowed down and clumsy for an average period of two weeks. During several days immediately following the operation, some animals showed apathic and hypokinetic behavior. These signs were in general very attenuated, if not obliterated, from the time of the beginning of the learning tests. 3. Standardized Observations on Sensori-motor Capabilities An examination of the sensori-motor capabilities (Test 3) did not reveal a large deficit in the experimental animals. The average scores of the post-op locomotor activity were
Post-op Range
Group
Mean
Range
Mean
E
27.9
(29.6-25.0)
25.4
(29.3-15.3)
C
28.2
(29.5-27.2)
28.6
(30.0-25.4)
Te~t 2 (Delayed response). Mean number of correct responses per session (30 trials) for the experimental Group E and the control Group C. The post-op phase in Group E corresponds to the phase following the interruption of training in Group C.
5. Test 1
In th~s test, by contrast, the ablation of the pre-motor cortex has provoked clear deficits in the CAR and in the F R R (Table 2). The difference between the pre- and post-op scores of the C A R reached the p < 0.02 level and between the pre- and post-op levels of the F R R it was at the p < 0.01 level. The performances of the experimental animals were equally as inferior to those of the controls during the retraining phase, that is, p < 0.02 level for the C A R and for the F R R . In Crr.E., the dtfference between the post-op scores of the C A R and F R R is not significant, therefore the action of the lesion did not differentiate between the two types of responses. Yet an examination of the individual scores reveals very great differences: two animals do not demonstrate clear deficit (An and Je). In the case of two othors (Ma and XY) the C A R is almost perfectly intact while the F R R is practically completely blocked. Lastly, in the other three animals (Ph, Ac and Ne), the two responses are dearly depressed without however being completely blocked (Table 3). The intra- and inter-session evolution of the experimental animals' behavior shows that these deficits appear in various
PREMOTOR CORTEX AND BEHAVIOR
303
TABLE 2
TABLE 4
MEAN PERFORMANCF~ IN TEST I
MEAN LATENCIESIN TEST 1
Group
Response
C E E C
CAR CAR FRR FRR
Pre-op Mean Range
Post-op Mean Range
I00 I00 96.5 96.4
99.6 72.5 56.9 96.9
(98.6--92.1) (100-94.6)
(100-98.0) (100-34.0) (94.5-6.3) (98.0-95.4)
Group
Response
C E E C
CAR CAR FRR FRR
Pre-op Mean Range 0.76 0.89 1.85 2.07
(0.62-0.98) (0.40-1.49) (1.41-2.14) (1.48-2.60)
Post-op Mean Range 0.81 1.40 2.36 2.01
(0.64-1.02) (0.68-2.15) (1.65-3.51) (1.53-2.37)
Test 1. Mean percentage, with respect to the number of trials of the CAR (conditioned avoidance response) and of the FRR (food reinforced response). Same conventions used as for Table I.
Test 1. Mean latency in sec of the CAR and of the FRR. Same conventions used as in above tables.
TABLE 3
particularly clear with regard to Pedal D due to the behavior of bar-holding which developed on this pedal. After the operation, the average number of intertrial responses on Pedal A of the experimental animals showed a non-significant decrease, although the frequency of intertrial responses on Pedal D changed little. In contrast one finds these two categories of response remained stable in Group C (Table 5).
INDIVIDUAL PERFORMANCES IN TEST l
Subjects
An Ma Ph Ac XY Ne Je
CAR
Pre-op FRR
100 100 100 100 100 100 100
97.4 97.4 97.2 98.6 92.1 95.9 97.1
Post-op CAR 100 85.9 46.7 34.0 99.3 41.9 99.3
FRR 94.5 6.3 48.0 72.7 15.4 72.4 89.2
Test 1. Individual performances of the animals from Group E expressed in mean percentages of the number of trials. Same conventions used as for the preceding tables.
ways. The blockage of the F R R may be due to the deficit of the CAR, i.e. to the shocks received owing to this deficit (Ph, Ac, Ne). The blocking of the feeding response can manifest itself right away (Ma and XY) and can continue in spite of an elevated level of the CAR. These deficits could be linked to mistakes of commission, that is, responses on the Pedal D in the presence of the F D S and reciprocally, but these errors were rare. Most often the deficit was noticed by the complete absence of all manipulatory responses in the presence of the signal. In the presence of the DDS, the animal did not remain immobile but executed a series of jumps and runs in circles which were sometimes accompanied bycries. When the F D S w a s present, the animal very frequently remained immobile; in many cases he then displayed a barholding behavior on Pedal D. The latency of the C A R increased significantly (p < 0.01) in Gr. E. after the operation, likewise for the F R R (p < 0.02). On the contrary, the latency of the two categories of responses remained stable in G r o u p C (Table 4). The observations made on the animals seem to show that this augmentation was not due to a slowing down of the manipulatory gesture itself, but rather to other factors, such as, slowing down the postural adjustment necessary for the response, a difficulty in releasing the pedal used for the preceding trial or by responses during the intertrial interval. This difficulty in releasing was
TABLE 5 INTERTRIAL RESPONSES IN TEST 1
Group
Pedal
C E E C
D D A A
Pre-op Mean Range
Post-op Mean Range
7.1 5.6 40.3 44.7
6.4 8.5 15.7 40.9
(2.2-20.6) (0.4-19.2) (1.8-137.0) (4.3-97.8)
(1.7-28.1) (2.9-19.6) (1.5-43.8) (5.1-94.7)
Test 1. Mean number of intertrial responses on Pedal D and on Pedal A per session. Same conventions used as for above tables.
The continual observations of the animals through the closed-circuit TV did not give any evidence for the existence of a phenomenon analogous to the cue magneto reactions. The patterns of postural adjustment of the body and the orienting movements of the head remained unchanged in the two animals not having clear deficits. In the others, these reactions were modified in various ways, especially in the animals receiving a large number of shocks. The absence of response was accompanied, most often in the presence of the DDS, by only poorly orientated locomotor responses or by a complete immobility in the presence of the FDS. The postural adjustments and the ORs preceding the responses were above all marked by a certain slowness or perseverance of motor patterns in the course of execution (inter-trial responses). DISCUSSION
The lack o f deficit in the experimental animals on the delayed response test confirms earlier results of Jacobsen [8]
q)4
DELACOUR, LIBOUBAN AND M(.NFII
and Pmbram [13J. Likewise the absence of notable changes m the locomotor actiwty agrees with the data of French [4]. Finally, neither the ORs to neutral stimuli, nor the simple reaching response tested in Test 3 were disturbed by the lesion. These negahve results do not allow the deficits observed in Test 1 to be attributed to an over-all dlsturbance of the behavior, from the sensori-motor and emotional point of view. These deficits present a problem which is difficult to interpret owing to the ambiguity of the very notion of the premotor cortex. Two main conceptions may be considered with regard to the role of the premotor cortex: that of a purely motor function and that of an integrator role. 1. According to the first of these two concepts, the motor cortex would only consist of the most rostral part of the motor area [14, 22]. The transitory maladroitness, the slowness of the spontaneous movements and the augmentation of the latency of the conditioned responses are arguments m favour of this idea. The observed increase in latency appears to be due more to the slowness of the postural adjustments rather than to the manipulatory motion itself. This fact seems to confirm the idea of a rostro-caudal organization of the motor area. The most rostral region of this area would control the proximal and axial articulations which would be particularly set into action by the postural adjustments [22]. The motor trouble following an injury of this zone would be especially sensitive to such a task as Test 1. This is due to two character~stics of the test: (a) limited time of response (maximum duration of the FDS or of the DDS--shock interval) (b) alternation between two responses, thus setting into action different and incompatible postural adjustments (Pedal A and Pedal D are placed on the two opposite partitions). There was no effect on the locomotor achwty or manipulatory responses displayed when the ammal was m a constant posture (Test 2). In Test 1 the CAR and the F R R were unequally and differently affected according to the mdiwdual differences of the animal. This data could also be explained within the framework of the purely motor conception of the premotor cortex. The utilizahon of a hmb affected by a pre-central lesion could depend on the level of motwatlon [2, 3]. The relative respectwe levels of the food and defensive rnotivat~on were probably not equal m all the animals.
This would be the result of very large differences betv~een individuals, notwithstanding the comparable and stable pre-op performance levels for each of the two responses. Nevertheless, Schwartz' results [15] obtained m conditions s~milar to ours, do not confirm the existence of an interaction between the level of motivation and deficits following the precentral lesions. 2. For several authors, the functions of the premotor cortex would be distinct from those of the motor cortex. The premotor cortex would play a role in the programmahon of movement [10]. It could exert an mh~biting action on the patterns of instinctive reaction depending on the pallidonigral system [2]. And a third hypothesis has it controlling the relations between the CS and the conditioned response [19]. Only this latter hypothesis has been able to be tested directly by our experiments. Our results did not show the cue magneto reactions nor a significant increase of the hum bet of rater-trial responses observed in the dog by Stephen. One must note that this same author did not find the cue magneto reactions again when she looked at the monkey in a s~tuatlon quite comparable to the one she has used for the dog [20]. Nevertheless, the phenomena of stereotype and of perseverat~on observed by Stepien after a lesion in the premotor cortex could be at the origin of the deficits obtained m Test 1. The situation would be characterized by the interaction of two motivations mobilizing two spatially distract responses. The capacity of shifting (between averswe and approach responses) reqmred by this situation would have been diminished in the experimental animals. A support of this hypothesis could be the lengthening of the latencies and above all the errors of commission sometime emitted. These latter errors ~ere nevertheless rare, the deficit of the responses consisted for the most part of a complete blockage. There is another objection to this interpretation, which is that the test of the delayed response, tested in the WGTA, is equally as sensitive to the phenomena of perseveratlon. But, the animals of the experimental group have not shown a deficit in this test. The results presented here are too incomplete to allow a choice between the motor concephon and the integrator hypothes~s of the premotor cortex. It seems, nevertheless, that with regard to our results, the first of these two concepts ~s the most economical explanation.
REFERENCE~
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