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The effect of pyramidal lesions on response latency in cats
BRAIN RESEARCH
207
THE EFFECT OF P Y R A M I D A L LESIONS ON RESPONSE L A T E N C Y IN
CATS*
ARNE MOSFELDT LAURSEN AND MARIO WIESENDANGER Institute of Neurophysiology, University of Copenhagen, Copenhagen (Denmark) and Institute of Brain Research, University of Zurich, Zurich (Switzerland)
(Received December 6th, 1966)
INTRODUCTION In a previous study we reinvestigated the effects of unilateral, pyramidal lesions in cats 4. Contralateral flexor reflexes were weak; the permanent loss of phasic activity observed by Tower 1°, however, was not confirmed and slowness was apparent only the first few days after the operation as reported by MarshallL In fact no defects were apparent when the cat walked, jumped and climbed 3 weeks after the operation. Whether any slowness remained when the cats attained stable recovery after 1-3 months could not be determined by general observation; the cats might have been only slightly slowed or slowed only when performing special tasks. The aim of the study to be reported was to investigate quantitatively response latency and speed in executing a motor act; this was achieved using programmed reinforcement schedules. Bilateral and unilateral lesions varying in extent were made in the medullary pyramids and control lesions were placed in the mesencephalon, thalamus and cortex. METHOD Animals
Sixteen male cats were selected because they liked the creamed fish used in the automatic feeder. Successful experiments were made on twelve cats (3.3-4.5 kg) in 3 experimental groups: Brightness discrimination training: pyramidal lesions (5); control lesions (5). Fixed ratio training: pyramidal lesions (2). * A preliminary report was published in the Bull. schweiz. Akad. med. Wiss., 22 (1966) 336-340. Brain Research, 5 (1967) 207-220
208
a . M. LAURSEN A N D M. W I E S E N D A N G E I t
Nozzle of
feeder
-
-
Perspex ~-partition
Fig. 1. Setup for measuring response latency. On the return from the feeder the cat lit the stimulus lights by stepping on the platform, closing the microswitch. The response latency was defined as the time from depression of the platform to depression of one or the other lever.
Apparatus Brightness discrimination. In a sound-insulated box two stimulus lights consisting of incandescent bulbs covered with translucent caps were lit when the cat stepped on a platform (Fig. 1). The lamps were supplied with different voltages to produce a brightness difference clearly noticeable to the human eye. The brighter light alone illuminated a selen photoelectric cell, placed at the position of the cat's eye, with 48 Lux (selen cell of 37 m m diameter facing the light at a distance of 15 cm). The weaker light alone produced 7 Lux and ambient light alone 0.1 Lux. In addition to the difference in brightness the lights were slightly different in hue. One or the other light was brighter in different trials in a preselected random sequence 2. Depression of the lever under the brighter light produced 0.3 g ( ~ 10%) of creamed fish mash from the automatic feeder. A nylon piston driven by compressed air through a steel cylinder moved bits of food through the nozzle when a solenoid valve was opened. The nozzle of the feeder was placed 30 cm away from the stimuli and levers, on the other side of a perspex screen. Returning from the feeder the cat stepped on the platform thereby activating a microswitch under the platform. The latency was defined as the time from activation of this microswitch to closure of the switch operated by the response lever. The latencies were measured in units of 0.25 sec; depression of the levers operated different counters depending on how many quarter seconds had elapsed since the cat had depressed the platform. An additional counter recorded all responses with latencies longer than 5 sec. Responses on the
Brain Research, 5 (1967) 207-220
RESPONSE LATENCY AFTER PYRAMIDAL LESIONS
209
lever under the brighter and the weaker light were measured separately. In this way the response latencies were recorded cumulatively. Successive latencies were recorded in selected sessions by reading off the counters after each response. Cumulative counters recorded the number of trials and reinforcements. Fixed ratio training. To measure the speed of a simple repetitive movement the cats were trained to depress a lever 30 times for each bit of food. The same box was used, but the stimuli and the platform were inoperative and one lever was covered. Responses and reinforcements operated a cumulative recorder. Stimuli and reinforcement contingencies were controlled by a system of relays and switches.
Procedure Brightness discrimination. In a day's session lasting 30 min a cat obtained about 100 reinforcements; during 2-3 weeks of initial training the weight was reduced 10-20 ~o, thereafter the session time was lengthened or shortened as required to maintain constant weight. The same session time was used after the operation. In the home cage water was available ad libitum. In addition, 20 mg of terramycin in 100 ml of milk was given daily to reduce the risk of respiratory infections. Training proceeded through the following stages: (1) The animal was placed in the box and the feeder operated at irregular intervals until the cat responded to the sound of the solenoid valve by going to the nozzle to eat. (2) By reinforcing appropriate spontaneous movements the cats were trained to depress one or the other of the two levers to obtain food. (3) Only responses alternating between the two levers were reinforced. (4) Discrimination training with one bulb switched off. Responses on the lever under the lighted bulb were reinforced. Responses on the other lever extinguished the stimulus light for 20 sec; the same bulb was lit again until the cat made a correct response. (5) Brightness discrimination. By stepping on the platform the cat lit the two stimulus lights with different brightness. Reinforcements and procedure were as in (4). Since response latencies were measured from depression of the platform to depression of a lever, responses following an incorrect response (under the weaker light) were disregarded; after an incorrect response the cat remained seated on the platform waiting for the lights to come on again. (6) Differential reinforcement of short latency responses (DRS). When the spontaneous latency distribution was stable, responses with short latencies only were reinforced during four days. The dividing latency was chosen arbitrarily in an early experiment (Cat 210), in later experiments reinforcement was obtained when the response came before the end of the quarter second interval which contained the median of the latency distribution. Retraining began I-2 weeks after the operation and continued in the same way as the preoperative training until the preoperative criterion was reattained. Fixed ratio training. Initial training was similar to stages 1 and 2 of the discrimination training. Then a fraction only of the responses on the lever was reinforced and the ratio between responses and reinforcements was gradually increased to 30.
Brain Research, 5 (1967) 207-220
210
A. M. LAURSEN A N D M. W I E S E N D A N G E R
Criteria of training Brightness discrimination. Before and after the operation the cats were trained until more than 80 ~ of the responses were correct on each of 10 consecutive days and until the difference between the median latency of any 2 of the 10 days was less than 0.25 sec. Fixed ratio training. Before and after the operation training proceeded until the cats obtained at least 60 reinforcements in 1 h (20 g of creamed fish, 1800 responses).
Cinematography Direct observation was not possible because the presence of the observer changed the animal's behavior. To study the pattern of movement three cats (309, 277, 196) were filmed in the experimental box on the last day of brightness discrimination training. Infrared sensitive film was used to prevent extra light in the box from disturbing discrimination. The camera was operated by the programming apparatus; it started when the platform was depressed and stopped when the response was performed.
Surgery In seven cats under pentobarbital sodium anesthesia the pyramids were exposed by a ventral approach 7, were viewed through an operating microscope, and a lesion was made with a fine forceps and scissors in one (3 cats) or both (4 cats) pyramids at the level of the trapezoid body. In four cats an electrolytic lesion (2.5 m A DC, 20 sec) was placed in the mesencephalon or thalamus with a stereotaxically inserted needle bared at the tip. In one cat tissue was removed from the middle suprasylvian gyri with a blunt spatula. The animals were treated with penicillin and terramycin until they were afebrile, for 3-10 days. They were then left with food and milk ad libitum for a week before training was resumed.
Histology The subcortical lesions were verified histologically (Fig. 2). After the experiments the brains were perfused and fixed in 10% formalin. Frozen sections were cut at 20 #, every tenth section was stained by the Spielmeyer method and a section adjacent to each of these was stained with thionine. The volume of the lesions was calculated after measuring the area of the damaged tissue on sections 0.2 m m apart; the areas were determined by planimetry after 20 times enlargement in a projector. The cortical lesions were drawn from a photograph of the dorsolateral surface of the fixed brain.
Brain Research, 5 (1967) 207-220
0
0
c
~
/,50
SS
LEFT
Fig. 2. Histological findings. Upper row: Extent of pyramidal lesions in cats trained to discriminate brightness. The response latency was increased in all except Cat 432 in which only 10 % of the fibers of one pyramid were interrupted. M i d d l e row: Extent of pyramidal lesions in cats trained on a fixed ratio schedule (p. 216). The response rate was unchanged although the lesions were larger than those which produced slowing in the discrimination task. L o wer row: Control lesions in cats trained to discriminate brightness. The response latency was unchanged in all except cat 273 which had lesions involving about 50 ,%0 of the medial lemniscus on both sides and the medial geniculate body on the left. C M : centrum medianum. G M : corpus geniculatum mediale. GSS: gyrus suprasylvius. L M : lemniscus medialis. LP: nucleus lateralis posterior. M D : nucleus medialis dorsalis. N C P : nucleus of the posterior commissure. N O : Nucleus olivaris inferior. SN: substantia nigra.
CM
RIGHT
to
212
A. M. LAURSEN A N D M. W I E S E N D A N G E R
RESULTS
( A ) Pyramidal lesions (1) General observation Three cats had the transient motor signs described4: diminished flexor reflexes and deficient contact placing in contralateral extremities for 1-3 weeks after the operation. Thereafter no abnormality was apparent, especially no slowing of motion was observed. In four cats the lesions were smaller than those previously studied by us and even transitory reflex changes were absent.
(2) Brightness discrimination All cats executed the lever pressing response with precise placement of the paw and normal coordination; the movements filmed before and after the operation were indistinguishable. Different forepaws were used in different trials in the earlier training stages. Later the pattern of movements became more stereotyped and only one paw was used for pressing the lever. A cat (277) with a 50 ~o unilateral lesion used the contralateral paw for responding on the last criterion day both before and after the operation. Whether pyramidal lesions had ipsilateral effects was not determined. Response latencies were increased by unilateral and bilateral pyramidal lesions of different sizes in four cats. The mean increase was largest after the largest lesions and amounted to 0.8 (P < 0.01)*, 0.4 (P < 0.03), 0.4 (P < 0.01) and 0.1 (P < 0.06) sec (Table I, Figs. 3 and 4). The smallest lesion which produced the slowing involved 30 ~ of one pyramid and the only pyramidal lesion which failed to produce the slowing involved 10 ~ of one pyramid. This cat (432) responded faster after the operation, the mean latency being reduced 0.4 sec (P < 0.01). The longer response latencies observed postoperatively were not associated with a shift to the paw which was not preferred in manipulation preoperatively. This was ascertained by cinematographic observation of one cat with a bilateral (309) and one with a unilateral (277) pyramidal lesion; these cats had the largest lesions in their experimental group. The three cats with the largest pyramidal lesions obtained fewer reinforcements per session and lost 1 0 - 1 5 ~ in weight (P < 0.01). The two cats with lesions smaller than 3 0 ~ of one pyramid, on the other hand, obtained more reinforcements and kept or gained weight. The number of reinforcements per session changed because the cats spent more or less time between trials; the sum of the changes in response latency amounted to only I min or 3 ~ of the length of the session. In different animals the latencies towards the end of the session were 10-100 longer than those in the beginning and no systematic change was produced by the operation. The material on this point is, however, too scarce for statistical treatment because successive latencies were recorded only in selected sessions, the ordinary way of recording being cumulative. * A non-parametric rank-order test11 was used to calculate probabilities (P) of chance occurrence.
Brain Research, 5 (1967) 207-220
213
RESPONSE LATENCY AFTF~ PYRAMIDAL LESIONS
DISTRIBUTION OF LATENCIES (CAT 309) Before p y r a m i d a l
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.r~
51 days after pyramidal l e s i o n
lesion
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2
3
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sec
Fig. 3. Histograms from a cat with short response latencies in brightness discrimination. (a) Distribution of latencies during the last criterion session before the lesions of the pyramids. (c) After
bilateral pyramidal lesions the mcdian latency was increased and the distribution flattened. The striped columns contain the median latency. (b) Before the operation differential reinforcement of responses with latencies shorter than 0.75 sec (dotted line) was without effect because the cat already responded rapidly. (d) After pyramidal lesions differential reinforcement of responses with short latency was still without effect although the cat was slowed.
DISTRIBUTION OF L A TE N C I E S (CAT 210) Before pyramidal lesion 76 days af ter pyramidal lesion
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I Errors
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2
3
4
0
1
2
3
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sec sec Fig. 4. Histograms from a cat with long response latencies in brightness discrimination. (a) Distribution of latencies during the last criterion sessions before the lesions of the pyramids. (c) After bilateral pyramidal lesions the median latency was slightly increased and the distribution flattened. The striped columns contain the median latency. (b) Before the operation differential reinforcement of responses with latencies longer than 1.5 sec (dotted line) was very effective. (d) After bilateral pyramidal lesions the cat could no longer be trained to respond faster.
Brain Research, 5 (1967") 207-220
Ixa
I
o~
Responses per session Reinforcements per minute Mean latency in seconds Per cent reinf., in interval with median
Before DRS
Afte~ operation :
Days to postoperative criterion
Lesion, per cent, right/left
After DRS Responses per session Reinforcements per minute Mean latency in seconds Per cent reinf., in interval with median Latency reduced
Responses per session Reinforcements per minute Mean latency in seconds Per cent reinf., in interval with median
Before DRS
Before operation:
Cat No.
103 3.0 2.1 11 (7)
34
60/60
132 3.9 1.3 34 (3) no P>0.10
115 3.4 1.3 27 (3)
309
97 3.1 2.2 8 (8)
74
40/30
149 4.8 1.2 44 (4) yes P<0.01
145 4.7 1.8 17 (6)
210
Pyramidal lesions
67 2.1 2.7 9 (10)
77
0/50
121 4.0 1.5 21 (6) yes P<0.01
85 2.7 2.3 11 (7)
277
158 6.2 1.3 40 (5)
73
30/0
158 6.1 1.2 42 (5) no P>0.10
119 4.5 1.2 42 (5)
330
92 3.0 1.6 22 (6)
38
10/0
60 1.8 1.7 44 (5) yes P<0.01
74 2.4 2.0 14 (7)
432
77 3.1 2.2 14 (7)
243
103 4.9 1.3 14 (5) (yes) P=0.07
119 4.6 1.5 16 (5)
273
110 3.7 1.4 28 (5)
50
97 3.2 1.5 33 (5) yes P<0.01
72 2.4 1.9 17 (7)
415
Control lesions
71 2.7 1.0 39 (3)
165
124 4.6 1.3 24 (4) yes P<0.01
114 4.6 1.9 5 (7)
196
86 1.9 0.9 50 (3)
59
94 2.4 1.1 36 (4) yes P<0.03
86 2.2 1.2 39 (4)
406
123 3.4 1.1 46 (4)
17
137 3.7 1.0 53 (4) yes P<0.01
114 3.2 1.2 43 (4)
450
Before DRS (differential reinforcement of short latency responses): the figures are means from the 10 consecutive criterion days. After DRS: the figures are from the first day of testing. Per cent reinforcements in the interval with the median: the figure in parentheses is the 0.25 sec interval which contains the median.
R E S P O N S E L A T E N C I E S A F T E R P Y R A M I D A L LESIONS OF D I F F E R E N T SIZES
TABLE I
7" ~7 77"
rll
7' ~7
7'
70
t"
t,~
o
o
2"
273
Medial geniculate Formatio reticulafis Substantia nigra
Response latency after operation Increased
Other structures damaged
Involvement of the medial lemniscus in per cent, fight/left 60/40
Volume of the lesions in microliters
Cat No.
CATS WITH CONTROL LESIONS
TABLE II
17
slower P<0.01
After DRS
* Latency increased; P < 0.01.
slower P<0.01
139 4.5 2.0 9 (7) no P~0.10
Before DRS
Change after operation:
After DRS Responses per session Reinforcements per minute Mean latency in seconds Per cent reinf., in interval with median Latency reduced
slower P<0.01
slower P<0.01
100 3.1 2.7 12 (10) no P>0.10
Decreased
161 6.2 1.1 43 (5) yes P<0.01
Nster P<0.01
84 2.5 1.6 12 (6) no P>0.10
slower P<0.01
124 4.9 1.8 17 (7) (yes) P=0.08
Decreased
Medial geniculate Formatio reticularis Substantia nigra
10/25
11
415
~ster P<0.01
P<0.01
~s~r
134 4.5 1.1 35 ~ ) yes P<0.01
Nster P<0.01
Nster P<0.01
85 2.9 0.9 59 (3) no P>0.1
Decreased
Thalamus Pretectal area Nucl. post. commiss.
0/0
11
406
nochan~nochangeslower P>0.10 P>0.10 P<0.01
slower P=0.06
Formatio reticularis Substantia nigra Pes pedunculi
30/20
11
196
slower P<0.01
slower P=0.03
107 3.5 2.3 27 (9) no P>O.lO
450
Decreased
Gyrus suprasylvius medius
0/0
35
N~er P<0.01
P<0.01
yes
147 4.0 0.9 46 (3)
nochan~ N~er P > 0 . 1 0 P<0.01
N~er P<0.01
96 1.3 1.2 20 O) no *
to
O Z
t"
216
A. M. L A U R S E N A N D M. W I E S E N D A N G E R
Differential reinforcement of short latency responses (DRS) reduced the mean response latency of the three slowest cats about 0.5 sec, to as little as 1.2 sec. This seemed to be about the fastest a cat could respond under the circumstances because two cats with mean response latencies of 1.2 and 1.3 sec were not speeded up significantly by the DRS procedure. After interruption of 40-60 % of one or both pyramids the DRS was ineffective (P > 0.1) although the mean latencies of the three cats were between 2 and 3 sec. The procedure reduced the mean response latencv (P < 0.01) of the cat which had the smallest effective lesion (Cat 330, 30 % unilateral lesion) and the least slowing. The cat which was unaffected by the lesion (Cat 432, 10 % unilateral lesion) responded faster after the operation and was not speeded up any further by the DRS procedure. Performance of the discrimination task was unaffected by the operation in all cats. (3) Fixed ratio tra&ing To determine if pyramidal lesions produced slowing in a general way two cats were trained to repeat a simple movement rapidly and many times. The first 250 responses on the 18th day after the pyramidal lesion were made at a rate of 2.4/sec (Cat 380) and 2.0/sec (381), for both cats the same as before the operation. The lesions were the largest in the series involving 70 % of the left and 60 % of the right pyramid in Cat 380; the cumulative record of this cat's performance (Fig. 5) exemplifies both. Later in the sessions the mean rate declined because rapid runs were mixed with pauses in an irregular fashion. Descriptively, the cat may be said to tire sooner after the pyramidal lesion because pauses were more frequent and lasted longer, but the fatigue seems to be of a special kind since rapid response sequences occurred throughFixed Before
ratio schedule
30 (cat 380) 18 days a f t e r
pyramidat lesion
pyrarnidal lesion
/
,
/
A
/V
5 min
/
' :
/ t
Fig. 5. (Cumulative record of performance of the fixed ratio schedule. The short slanted lines at an angle to the main record indicate reinforcements. The record between two successivereinforcements
represents 30 responses on the lever. After bilateral pyramidal lesions the preoperative response rate of 2.4/sec was maintained for 100 to 200 responses at a time. The pauses (horizontal parts of the record) were not preceded by gradual slowing.
Brain Research, 5 (1967) 207-220
RESPONSE LATENCY AFTER PYRAMIDAL LESIONS
217
out the record. A similar change was not detectable during discrimination training because the cats ate and "rested" between responses on the lever.
(B) Control lesions (1) General observation To determine if slow responding to discriminative stimuli was specific of pyramidal lesions bilateral control lesions were placed in the midbrain, thalamus, and association cortex (Fig. 2). General behavior, spinal reflexes and coordination were unaffected.
(2) Brightness discrimination In contrast with the pyramidal lesions control lesions, in four of five cats, were without effect on response latencies in the brightness discrimination task. The mean response latency was, in fact, shortened (P < 0.01) 0.5 sec on the average after retraining which lasted 17-165 days. The control lesions were bilateral in the midbrain, thalamus and suprasylvian gyrus of the cortex and were placed differently in the different cats (Fig. 2). A cat with bilateral lesions involving the medial lemniscus, medial geniculate and to a small extent the substantia nigra and reticular formation was slowed (P < 0.01; Cat 273; Table I; Fig. 2). Interruption of the medial lemniscus on one or both sides and may he also the damage to the medial geniculate produced the slowing because damage to the substantia nigra and reticular formation was as extensive in another cat (415, Fig. 2) which was faster after the operation (P < 0.01), and the total volume of the lesions in the slowed cat was exceeded by the volume of the lesions in another cat (450, Table I1) which was also faster (P < 0.01). A reduced level of alertness is believed to explain the slowing observed in the cat with damage to specific afferent pathways in the midbrain s. This cat took 4 times as many days to reach postoperative criterion performance as the other cats (average 65 days, Table I) and it was the only animal to gain weight in spite of reduced food intake. Differential reinforcement of short latency responses ( DRS) was less effective after the lesions because retraining by itself reduced the mean response latencies of four of the five cats. In this respect their behavior was similar to the cat with the smallest pyramidal lesion (Cat 432). After DRS the mean latencies of the four control cats were from 0.9 to 1.2 sec and in only two of the cats had the DRS produced a statistically significant change (P > 0.01). Performance of the discrimination task was unaffected in four cats with control lesions; one failed to discriminate after the operation (Cat 406, Table I). The lesion was in the nucleus of the posterior commissure and pretectal area of one side and on the other it extended into the pretectal area and the nuclei lateralis posterior and suprageniculatus of the thalamus. The pretectal damage was probably responsible for the failure to discriminate6,9. Brain Research, 5 (1967) 207-220
218
A. M. LAURSEN A N D M. W t E S E N D A N G E R
(3) Fixedratio training Cats with control lesions were not trained on this schedule because in four of the five response latency was unaffected. DISCUSSION
The experiments show that incomplete interruption of one or both pyramidal tracts make cats respond slower in a discrimination task. Nor could their responses be speeded up: differential reinforcement of short latencies was without effect. A repetitive movement was executed at the same rate before and after the operation and no slowness was noticed by inspection of gait and play. The increase in response latency was small; most cats with control lesions, however, were speeded up. Fatigue probably did not cause the slowing because the training schedule in brightness discrimination provided rest periods between single responses while the cat ate. On the fixed ratio schedule, which provided no rest periods, interresponse times for hundreds of successive responses were unaffected although irregular pauses occurred later in the sessions. That the operated cats were less hungry and therefore responded with increased latency is unlikely; the small loss of weight of cats with pyramidal lesions is explained by the fixed session time within which the slowed cats made fewer responses. Cats which were not slowed did not loose weight. The effect of the lemniscal control lesions emphasizes the need to avoid lemniscal damage in studies of the effects of pyramidotomy. In cats the medial lemniscus is adjacent to the pyramids in the medulla oblongata and complete pyramidotomy may damage the lemniscus by gliosis in a chronic experiment. In this investigation incomplete lesions changed the cats behavior and intact tissue of the pyramids remained to protect lemniscal fibers from damage. Complete section of one or both pyramids in cats abolished conditioned rubbing of the cheek whereas conditioned button pressing remained but was less precisea. Tasks requiring pushing with the forepaws were most seriously affected. That motor impairment was absent in our cats may be explained by their smaller lesions. Ablation of the sensorimotor cortex increased the mean response latency of cats trained to press a lever to get food when clicks or flashes were presented 1. The operated cats were handicapped by hyperactivity without purpose, episodes of disorientation and difficulties in executing the instrumental response; sometimes the cats made the response in the air and occasionally a response was made which looked normal. The response latencies were highly variable, some were 40 sec. Thus, the results of pyramidal lesions and ablation of the sensorimotor cortex are not the same. A small decrease in response latency may, at first sight, seem a minor contribution of the pyramidal tract to the capacities of the nervous system. However, a cat solving the visual discrimination problem of detecting mice in darkness gets more mice, the faster she responds. The survival value of rapid execution of complex tasks and of the ability to learn to respond faster may have contributed to the special development of the pyramidal tract in higher mammals.
Brain Research, 5 (1967) 207-220
RESPONSE LATENCY AFTER PYRAMIDALLESIONS
219
SUMMARY Cats walked, jumped and climbed with no apparent defects 3 weeks after transection of a pyramid in the medulla oblongata. To determine if a precisely defined task was executed with reduced speed, cats were trained to press a lever under the brighter of two light bulbs to obtain bits of food. The bulbs were lit when the cat stepped on a platform and the time from depression of the platform to depression of a lever was measured for about 100 consecutive responses on each of 10 consecutive days. The measurements were made after the cat had attained stable performance before and about 3 months after incomplete lesions in one or both medullary pyramids. Unilateral and bilateral lesions involving more than 30 ~ of one pyramid increased the mean response latency from 0.1 to 0.8 sec and the largest lesions produced the largest increase in latency. Differential reinforcement of responses with short latency made the slowest cats respond faster before pyramidotomy. After the operation the cats could no longer be speeded up. The pyramidotomized cats depressed the lever with normal coordination and one cat used the same paw for responding before and after a contralateral lesion interrupting 50 ~o of the fibers. The slowing was not duc to general m o t o r impairment: 3 weeks after large lesions of both pyramids the cats made hundreds of responses in succession ( F R schedule) at the same rate as before the operation. O f five cats with bilateral control lesions in mesencephalon, thalamus or association cortex four were unaffected. Slowing of the fifth cat is attributed to damage of specific afferent pathways; the cat relearned slowly, gained weight in spite of reduced food intake and presumably had a reduced level of alertness. ACKNOWLEDGMENTS This work was made possible through the support and sponsorship of the U. S. A r m y through its European Research Office. Dr. M. W. was supported by a grant from the Swiss National Foundation (No. 2903). We gratefully acknowledge the assistance of Mr. Thomas Nissen and Mr. Vagn Hansen in training the animals. REFERENCES 1 BUSER,P., ET ROUGEUL, A., Observations sur le conditionnement instrumental alimentaire chez le chat. In J. F. D~LAFRESNAW(Ed.L Brain Mechanisms and Learning, Blackwell, Oxford, 1961
p. 527. 2 GELLERMAN, L. W., Chance orders of alternating stimuli in visual discrimination experiments, J. genet. Psychol., 42 (1933) 207-208. 3 GORSKA,T., JANKOWSKA,E., AND MOSSAKOWSKI,M., Instrumental conditioned reflexes after section of the pyramids in cats, Bull. Acad. pol. Sci. CI. 2, 12 (1964) 413-416. 4 LALrRSEH,A. M., ANDWmSEHI~ANGER,M., Motor deficits after transection of a bulbar pyramid in the cat, Acta physiol, scand., 68 (1966) 118-126. 5 MARSHALL,C., Experimental lesions of the pyramidal tract, Arch. Neurol. Psyehiat. (Chic.), 32 (1934) 778-796. 6 MCNEw, B. g., AND THOMPSON,R., Effect of posterior thalamic lesions on retention of a brightness discrimination motivated by thirst, J. comp. physiol. Psyehol., 62 (1966) 125-128. Brain Research, 5 (1967) 207-220
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7 ScrnrF, J. M., Lehrbuch der Physiologie des Menschen, Lahr, Schauenburg, 1858-1859, p. 305. 8 SPRAGUE, J, M., LEVITT, M., ROBSON, K., LIU, C. N., STELLAR, E., AND CHAMBERS, W. W., A neuroanatomical and behavioral analysis of the syndromes resulting from midbrain lemniscal and reticular lesions in the cat, Arch. ital. Biol., 101 (1963) 225-295. 9 THOMPSON,R., AND RICH, 1., A discrete diencephalic pretectal area critical for retention of visual habits in the rat, Exp. Neurol,, 4 (1961) 436--443. 10 TOWER, S. S., The dissociation of cortical excitation from cortical inhibitioa by pyramid section and the syndrome of that lesion in the cat, Brain, 58 (1935) 238-255. 11 WILCOXON, F., Some Rapid Approximate Statistical Procedures, American Cyanamid Co., New York, 1949, p. 4.
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207
THE EFFECT OF P Y R A M I D A L LESIONS ON RESPONSE L A T E N C Y IN
CATS*
ARNE MOSFELDT LAURSEN AND MARIO WIESENDANGER Institute of Neurophysiology, University of Copenhagen, Copenhagen (Denmark) and Institute of Brain Research, University of Zurich, Zurich (Switzerland)
(Received December 6th, 1966)
INTRODUCTION In a previous study we reinvestigated the effects of unilateral, pyramidal lesions in cats 4. Contralateral flexor reflexes were weak; the permanent loss of phasic activity observed by Tower 1°, however, was not confirmed and slowness was apparent only the first few days after the operation as reported by MarshallL In fact no defects were apparent when the cat walked, jumped and climbed 3 weeks after the operation. Whether any slowness remained when the cats attained stable recovery after 1-3 months could not be determined by general observation; the cats might have been only slightly slowed or slowed only when performing special tasks. The aim of the study to be reported was to investigate quantitatively response latency and speed in executing a motor act; this was achieved using programmed reinforcement schedules. Bilateral and unilateral lesions varying in extent were made in the medullary pyramids and control lesions were placed in the mesencephalon, thalamus and cortex. METHOD Animals
Sixteen male cats were selected because they liked the creamed fish used in the automatic feeder. Successful experiments were made on twelve cats (3.3-4.5 kg) in 3 experimental groups: Brightness discrimination training: pyramidal lesions (5); control lesions (5). Fixed ratio training: pyramidal lesions (2). * A preliminary report was published in the Bull. schweiz. Akad. med. Wiss., 22 (1966) 336-340. Brain Research, 5 (1967) 207-220
208
a . M. LAURSEN A N D M. W I E S E N D A N G E I t
Nozzle of
feeder
-
-
Perspex ~-partition
Fig. 1. Setup for measuring response latency. On the return from the feeder the cat lit the stimulus lights by stepping on the platform, closing the microswitch. The response latency was defined as the time from depression of the platform to depression of one or the other lever.
Apparatus Brightness discrimination. In a sound-insulated box two stimulus lights consisting of incandescent bulbs covered with translucent caps were lit when the cat stepped on a platform (Fig. 1). The lamps were supplied with different voltages to produce a brightness difference clearly noticeable to the human eye. The brighter light alone illuminated a selen photoelectric cell, placed at the position of the cat's eye, with 48 Lux (selen cell of 37 m m diameter facing the light at a distance of 15 cm). The weaker light alone produced 7 Lux and ambient light alone 0.1 Lux. In addition to the difference in brightness the lights were slightly different in hue. One or the other light was brighter in different trials in a preselected random sequence 2. Depression of the lever under the brighter light produced 0.3 g ( ~ 10%) of creamed fish mash from the automatic feeder. A nylon piston driven by compressed air through a steel cylinder moved bits of food through the nozzle when a solenoid valve was opened. The nozzle of the feeder was placed 30 cm away from the stimuli and levers, on the other side of a perspex screen. Returning from the feeder the cat stepped on the platform thereby activating a microswitch under the platform. The latency was defined as the time from activation of this microswitch to closure of the switch operated by the response lever. The latencies were measured in units of 0.25 sec; depression of the levers operated different counters depending on how many quarter seconds had elapsed since the cat had depressed the platform. An additional counter recorded all responses with latencies longer than 5 sec. Responses on the
Brain Research, 5 (1967) 207-220
RESPONSE LATENCY AFTER PYRAMIDAL LESIONS
209
lever under the brighter and the weaker light were measured separately. In this way the response latencies were recorded cumulatively. Successive latencies were recorded in selected sessions by reading off the counters after each response. Cumulative counters recorded the number of trials and reinforcements. Fixed ratio training. To measure the speed of a simple repetitive movement the cats were trained to depress a lever 30 times for each bit of food. The same box was used, but the stimuli and the platform were inoperative and one lever was covered. Responses and reinforcements operated a cumulative recorder. Stimuli and reinforcement contingencies were controlled by a system of relays and switches.
Procedure Brightness discrimination. In a day's session lasting 30 min a cat obtained about 100 reinforcements; during 2-3 weeks of initial training the weight was reduced 10-20 ~o, thereafter the session time was lengthened or shortened as required to maintain constant weight. The same session time was used after the operation. In the home cage water was available ad libitum. In addition, 20 mg of terramycin in 100 ml of milk was given daily to reduce the risk of respiratory infections. Training proceeded through the following stages: (1) The animal was placed in the box and the feeder operated at irregular intervals until the cat responded to the sound of the solenoid valve by going to the nozzle to eat. (2) By reinforcing appropriate spontaneous movements the cats were trained to depress one or the other of the two levers to obtain food. (3) Only responses alternating between the two levers were reinforced. (4) Discrimination training with one bulb switched off. Responses on the lever under the lighted bulb were reinforced. Responses on the other lever extinguished the stimulus light for 20 sec; the same bulb was lit again until the cat made a correct response. (5) Brightness discrimination. By stepping on the platform the cat lit the two stimulus lights with different brightness. Reinforcements and procedure were as in (4). Since response latencies were measured from depression of the platform to depression of a lever, responses following an incorrect response (under the weaker light) were disregarded; after an incorrect response the cat remained seated on the platform waiting for the lights to come on again. (6) Differential reinforcement of short latency responses (DRS). When the spontaneous latency distribution was stable, responses with short latencies only were reinforced during four days. The dividing latency was chosen arbitrarily in an early experiment (Cat 210), in later experiments reinforcement was obtained when the response came before the end of the quarter second interval which contained the median of the latency distribution. Retraining began I-2 weeks after the operation and continued in the same way as the preoperative training until the preoperative criterion was reattained. Fixed ratio training. Initial training was similar to stages 1 and 2 of the discrimination training. Then a fraction only of the responses on the lever was reinforced and the ratio between responses and reinforcements was gradually increased to 30.
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A. M. LAURSEN A N D M. W I E S E N D A N G E R
Criteria of training Brightness discrimination. Before and after the operation the cats were trained until more than 80 ~ of the responses were correct on each of 10 consecutive days and until the difference between the median latency of any 2 of the 10 days was less than 0.25 sec. Fixed ratio training. Before and after the operation training proceeded until the cats obtained at least 60 reinforcements in 1 h (20 g of creamed fish, 1800 responses).
Cinematography Direct observation was not possible because the presence of the observer changed the animal's behavior. To study the pattern of movement three cats (309, 277, 196) were filmed in the experimental box on the last day of brightness discrimination training. Infrared sensitive film was used to prevent extra light in the box from disturbing discrimination. The camera was operated by the programming apparatus; it started when the platform was depressed and stopped when the response was performed.
Surgery In seven cats under pentobarbital sodium anesthesia the pyramids were exposed by a ventral approach 7, were viewed through an operating microscope, and a lesion was made with a fine forceps and scissors in one (3 cats) or both (4 cats) pyramids at the level of the trapezoid body. In four cats an electrolytic lesion (2.5 m A DC, 20 sec) was placed in the mesencephalon or thalamus with a stereotaxically inserted needle bared at the tip. In one cat tissue was removed from the middle suprasylvian gyri with a blunt spatula. The animals were treated with penicillin and terramycin until they were afebrile, for 3-10 days. They were then left with food and milk ad libitum for a week before training was resumed.
Histology The subcortical lesions were verified histologically (Fig. 2). After the experiments the brains were perfused and fixed in 10% formalin. Frozen sections were cut at 20 #, every tenth section was stained by the Spielmeyer method and a section adjacent to each of these was stained with thionine. The volume of the lesions was calculated after measuring the area of the damaged tissue on sections 0.2 m m apart; the areas were determined by planimetry after 20 times enlargement in a projector. The cortical lesions were drawn from a photograph of the dorsolateral surface of the fixed brain.
Brain Research, 5 (1967) 207-220
0
0
c
~
/,50
SS
LEFT
Fig. 2. Histological findings. Upper row: Extent of pyramidal lesions in cats trained to discriminate brightness. The response latency was increased in all except Cat 432 in which only 10 % of the fibers of one pyramid were interrupted. M i d d l e row: Extent of pyramidal lesions in cats trained on a fixed ratio schedule (p. 216). The response rate was unchanged although the lesions were larger than those which produced slowing in the discrimination task. L o wer row: Control lesions in cats trained to discriminate brightness. The response latency was unchanged in all except cat 273 which had lesions involving about 50 ,%0 of the medial lemniscus on both sides and the medial geniculate body on the left. C M : centrum medianum. G M : corpus geniculatum mediale. GSS: gyrus suprasylvius. L M : lemniscus medialis. LP: nucleus lateralis posterior. M D : nucleus medialis dorsalis. N C P : nucleus of the posterior commissure. N O : Nucleus olivaris inferior. SN: substantia nigra.
CM
RIGHT
to
212
A. M. LAURSEN A N D M. W I E S E N D A N G E R
RESULTS
( A ) Pyramidal lesions (1) General observation Three cats had the transient motor signs described4: diminished flexor reflexes and deficient contact placing in contralateral extremities for 1-3 weeks after the operation. Thereafter no abnormality was apparent, especially no slowing of motion was observed. In four cats the lesions were smaller than those previously studied by us and even transitory reflex changes were absent.
(2) Brightness discrimination All cats executed the lever pressing response with precise placement of the paw and normal coordination; the movements filmed before and after the operation were indistinguishable. Different forepaws were used in different trials in the earlier training stages. Later the pattern of movements became more stereotyped and only one paw was used for pressing the lever. A cat (277) with a 50 ~o unilateral lesion used the contralateral paw for responding on the last criterion day both before and after the operation. Whether pyramidal lesions had ipsilateral effects was not determined. Response latencies were increased by unilateral and bilateral pyramidal lesions of different sizes in four cats. The mean increase was largest after the largest lesions and amounted to 0.8 (P < 0.01)*, 0.4 (P < 0.03), 0.4 (P < 0.01) and 0.1 (P < 0.06) sec (Table I, Figs. 3 and 4). The smallest lesion which produced the slowing involved 30 ~ of one pyramid and the only pyramidal lesion which failed to produce the slowing involved 10 ~ of one pyramid. This cat (432) responded faster after the operation, the mean latency being reduced 0.4 sec (P < 0.01). The longer response latencies observed postoperatively were not associated with a shift to the paw which was not preferred in manipulation preoperatively. This was ascertained by cinematographic observation of one cat with a bilateral (309) and one with a unilateral (277) pyramidal lesion; these cats had the largest lesions in their experimental group. The three cats with the largest pyramidal lesions obtained fewer reinforcements per session and lost 1 0 - 1 5 ~ in weight (P < 0.01). The two cats with lesions smaller than 3 0 ~ of one pyramid, on the other hand, obtained more reinforcements and kept or gained weight. The number of reinforcements per session changed because the cats spent more or less time between trials; the sum of the changes in response latency amounted to only I min or 3 ~ of the length of the session. In different animals the latencies towards the end of the session were 10-100 longer than those in the beginning and no systematic change was produced by the operation. The material on this point is, however, too scarce for statistical treatment because successive latencies were recorded only in selected sessions, the ordinary way of recording being cumulative. * A non-parametric rank-order test11 was used to calculate probabilities (P) of chance occurrence.
Brain Research, 5 (1967) 207-220
213
RESPONSE LATENCY AFTF~ PYRAMIDAL LESIONS
DISTRIBUTION OF LATENCIES (CAT 309) Before p y r a m i d a l
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51 days after pyramidal l e s i o n
lesion
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2
3
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Fig. 3. Histograms from a cat with short response latencies in brightness discrimination. (a) Distribution of latencies during the last criterion session before the lesions of the pyramids. (c) After
bilateral pyramidal lesions the mcdian latency was increased and the distribution flattened. The striped columns contain the median latency. (b) Before the operation differential reinforcement of responses with latencies shorter than 0.75 sec (dotted line) was without effect because the cat already responded rapidly. (d) After pyramidal lesions differential reinforcement of responses with short latency was still without effect although the cat was slowed.
DISTRIBUTION OF L A TE N C I E S (CAT 210) Before pyramidal lesion 76 days af ter pyramidal lesion
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2
3
4
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sec sec Fig. 4. Histograms from a cat with long response latencies in brightness discrimination. (a) Distribution of latencies during the last criterion sessions before the lesions of the pyramids. (c) After bilateral pyramidal lesions the median latency was slightly increased and the distribution flattened. The striped columns contain the median latency. (b) Before the operation differential reinforcement of responses with latencies longer than 1.5 sec (dotted line) was very effective. (d) After bilateral pyramidal lesions the cat could no longer be trained to respond faster.
Brain Research, 5 (1967") 207-220
Ixa
I
o~
Responses per session Reinforcements per minute Mean latency in seconds Per cent reinf., in interval with median
Before DRS
Afte~ operation :
Days to postoperative criterion
Lesion, per cent, right/left
After DRS Responses per session Reinforcements per minute Mean latency in seconds Per cent reinf., in interval with median Latency reduced
Responses per session Reinforcements per minute Mean latency in seconds Per cent reinf., in interval with median
Before DRS
Before operation:
Cat No.
103 3.0 2.1 11 (7)
34
60/60
132 3.9 1.3 34 (3) no P>0.10
115 3.4 1.3 27 (3)
309
97 3.1 2.2 8 (8)
74
40/30
149 4.8 1.2 44 (4) yes P<0.01
145 4.7 1.8 17 (6)
210
Pyramidal lesions
67 2.1 2.7 9 (10)
77
0/50
121 4.0 1.5 21 (6) yes P<0.01
85 2.7 2.3 11 (7)
277
158 6.2 1.3 40 (5)
73
30/0
158 6.1 1.2 42 (5) no P>0.10
119 4.5 1.2 42 (5)
330
92 3.0 1.6 22 (6)
38
10/0
60 1.8 1.7 44 (5) yes P<0.01
74 2.4 2.0 14 (7)
432
77 3.1 2.2 14 (7)
243
103 4.9 1.3 14 (5) (yes) P=0.07
119 4.6 1.5 16 (5)
273
110 3.7 1.4 28 (5)
50
97 3.2 1.5 33 (5) yes P<0.01
72 2.4 1.9 17 (7)
415
Control lesions
71 2.7 1.0 39 (3)
165
124 4.6 1.3 24 (4) yes P<0.01
114 4.6 1.9 5 (7)
196
86 1.9 0.9 50 (3)
59
94 2.4 1.1 36 (4) yes P<0.03
86 2.2 1.2 39 (4)
406
123 3.4 1.1 46 (4)
17
137 3.7 1.0 53 (4) yes P<0.01
114 3.2 1.2 43 (4)
450
Before DRS (differential reinforcement of short latency responses): the figures are means from the 10 consecutive criterion days. After DRS: the figures are from the first day of testing. Per cent reinforcements in the interval with the median: the figure in parentheses is the 0.25 sec interval which contains the median.
R E S P O N S E L A T E N C I E S A F T E R P Y R A M I D A L LESIONS OF D I F F E R E N T SIZES
TABLE I
7" ~7 77"
rll
7' ~7
7'
70
t"
t,~
o
o
2"
273
Medial geniculate Formatio reticulafis Substantia nigra
Response latency after operation Increased
Other structures damaged
Involvement of the medial lemniscus in per cent, fight/left 60/40
Volume of the lesions in microliters
Cat No.
CATS WITH CONTROL LESIONS
TABLE II
17
slower P<0.01
After DRS
* Latency increased; P < 0.01.
slower P<0.01
139 4.5 2.0 9 (7) no P~0.10
Before DRS
Change after operation:
After DRS Responses per session Reinforcements per minute Mean latency in seconds Per cent reinf., in interval with median Latency reduced
slower P<0.01
slower P<0.01
100 3.1 2.7 12 (10) no P>0.10
Decreased
161 6.2 1.1 43 (5) yes P<0.01
Nster P<0.01
84 2.5 1.6 12 (6) no P>0.10
slower P<0.01
124 4.9 1.8 17 (7) (yes) P=0.08
Decreased
Medial geniculate Formatio reticularis Substantia nigra
10/25
11
415
~ster P<0.01
P<0.01
~s~r
134 4.5 1.1 35 ~ ) yes P<0.01
Nster P<0.01
Nster P<0.01
85 2.9 0.9 59 (3) no P>0.1
Decreased
Thalamus Pretectal area Nucl. post. commiss.
0/0
11
406
nochan~nochangeslower P>0.10 P>0.10 P<0.01
slower P=0.06
Formatio reticularis Substantia nigra Pes pedunculi
30/20
11
196
slower P<0.01
slower P=0.03
107 3.5 2.3 27 (9) no P>O.lO
450
Decreased
Gyrus suprasylvius medius
0/0
35
N~er P<0.01
P<0.01
yes
147 4.0 0.9 46 (3)
nochan~ N~er P > 0 . 1 0 P<0.01
N~er P<0.01
96 1.3 1.2 20 O) no *
to
O Z
t"
216
A. M. L A U R S E N A N D M. W I E S E N D A N G E R
Differential reinforcement of short latency responses (DRS) reduced the mean response latency of the three slowest cats about 0.5 sec, to as little as 1.2 sec. This seemed to be about the fastest a cat could respond under the circumstances because two cats with mean response latencies of 1.2 and 1.3 sec were not speeded up significantly by the DRS procedure. After interruption of 40-60 % of one or both pyramids the DRS was ineffective (P > 0.1) although the mean latencies of the three cats were between 2 and 3 sec. The procedure reduced the mean response latencv (P < 0.01) of the cat which had the smallest effective lesion (Cat 330, 30 % unilateral lesion) and the least slowing. The cat which was unaffected by the lesion (Cat 432, 10 % unilateral lesion) responded faster after the operation and was not speeded up any further by the DRS procedure. Performance of the discrimination task was unaffected by the operation in all cats. (3) Fixed ratio tra&ing To determine if pyramidal lesions produced slowing in a general way two cats were trained to repeat a simple movement rapidly and many times. The first 250 responses on the 18th day after the pyramidal lesion were made at a rate of 2.4/sec (Cat 380) and 2.0/sec (381), for both cats the same as before the operation. The lesions were the largest in the series involving 70 % of the left and 60 % of the right pyramid in Cat 380; the cumulative record of this cat's performance (Fig. 5) exemplifies both. Later in the sessions the mean rate declined because rapid runs were mixed with pauses in an irregular fashion. Descriptively, the cat may be said to tire sooner after the pyramidal lesion because pauses were more frequent and lasted longer, but the fatigue seems to be of a special kind since rapid response sequences occurred throughFixed Before
ratio schedule
30 (cat 380) 18 days a f t e r
pyramidat lesion
pyrarnidal lesion
/
,
/
A
/V
5 min
/
' :
/ t
Fig. 5. (Cumulative record of performance of the fixed ratio schedule. The short slanted lines at an angle to the main record indicate reinforcements. The record between two successivereinforcements
represents 30 responses on the lever. After bilateral pyramidal lesions the preoperative response rate of 2.4/sec was maintained for 100 to 200 responses at a time. The pauses (horizontal parts of the record) were not preceded by gradual slowing.
Brain Research, 5 (1967) 207-220
RESPONSE LATENCY AFTER PYRAMIDAL LESIONS
217
out the record. A similar change was not detectable during discrimination training because the cats ate and "rested" between responses on the lever.
(B) Control lesions (1) General observation To determine if slow responding to discriminative stimuli was specific of pyramidal lesions bilateral control lesions were placed in the midbrain, thalamus, and association cortex (Fig. 2). General behavior, spinal reflexes and coordination were unaffected.
(2) Brightness discrimination In contrast with the pyramidal lesions control lesions, in four of five cats, were without effect on response latencies in the brightness discrimination task. The mean response latency was, in fact, shortened (P < 0.01) 0.5 sec on the average after retraining which lasted 17-165 days. The control lesions were bilateral in the midbrain, thalamus and suprasylvian gyrus of the cortex and were placed differently in the different cats (Fig. 2). A cat with bilateral lesions involving the medial lemniscus, medial geniculate and to a small extent the substantia nigra and reticular formation was slowed (P < 0.01; Cat 273; Table I; Fig. 2). Interruption of the medial lemniscus on one or both sides and may he also the damage to the medial geniculate produced the slowing because damage to the substantia nigra and reticular formation was as extensive in another cat (415, Fig. 2) which was faster after the operation (P < 0.01), and the total volume of the lesions in the slowed cat was exceeded by the volume of the lesions in another cat (450, Table I1) which was also faster (P < 0.01). A reduced level of alertness is believed to explain the slowing observed in the cat with damage to specific afferent pathways in the midbrain s. This cat took 4 times as many days to reach postoperative criterion performance as the other cats (average 65 days, Table I) and it was the only animal to gain weight in spite of reduced food intake. Differential reinforcement of short latency responses ( DRS) was less effective after the lesions because retraining by itself reduced the mean response latencies of four of the five cats. In this respect their behavior was similar to the cat with the smallest pyramidal lesion (Cat 432). After DRS the mean latencies of the four control cats were from 0.9 to 1.2 sec and in only two of the cats had the DRS produced a statistically significant change (P > 0.01). Performance of the discrimination task was unaffected in four cats with control lesions; one failed to discriminate after the operation (Cat 406, Table I). The lesion was in the nucleus of the posterior commissure and pretectal area of one side and on the other it extended into the pretectal area and the nuclei lateralis posterior and suprageniculatus of the thalamus. The pretectal damage was probably responsible for the failure to discriminate6,9. Brain Research, 5 (1967) 207-220
218
A. M. LAURSEN A N D M. W t E S E N D A N G E R
(3) Fixedratio training Cats with control lesions were not trained on this schedule because in four of the five response latency was unaffected. DISCUSSION
The experiments show that incomplete interruption of one or both pyramidal tracts make cats respond slower in a discrimination task. Nor could their responses be speeded up: differential reinforcement of short latencies was without effect. A repetitive movement was executed at the same rate before and after the operation and no slowness was noticed by inspection of gait and play. The increase in response latency was small; most cats with control lesions, however, were speeded up. Fatigue probably did not cause the slowing because the training schedule in brightness discrimination provided rest periods between single responses while the cat ate. On the fixed ratio schedule, which provided no rest periods, interresponse times for hundreds of successive responses were unaffected although irregular pauses occurred later in the sessions. That the operated cats were less hungry and therefore responded with increased latency is unlikely; the small loss of weight of cats with pyramidal lesions is explained by the fixed session time within which the slowed cats made fewer responses. Cats which were not slowed did not loose weight. The effect of the lemniscal control lesions emphasizes the need to avoid lemniscal damage in studies of the effects of pyramidotomy. In cats the medial lemniscus is adjacent to the pyramids in the medulla oblongata and complete pyramidotomy may damage the lemniscus by gliosis in a chronic experiment. In this investigation incomplete lesions changed the cats behavior and intact tissue of the pyramids remained to protect lemniscal fibers from damage. Complete section of one or both pyramids in cats abolished conditioned rubbing of the cheek whereas conditioned button pressing remained but was less precisea. Tasks requiring pushing with the forepaws were most seriously affected. That motor impairment was absent in our cats may be explained by their smaller lesions. Ablation of the sensorimotor cortex increased the mean response latency of cats trained to press a lever to get food when clicks or flashes were presented 1. The operated cats were handicapped by hyperactivity without purpose, episodes of disorientation and difficulties in executing the instrumental response; sometimes the cats made the response in the air and occasionally a response was made which looked normal. The response latencies were highly variable, some were 40 sec. Thus, the results of pyramidal lesions and ablation of the sensorimotor cortex are not the same. A small decrease in response latency may, at first sight, seem a minor contribution of the pyramidal tract to the capacities of the nervous system. However, a cat solving the visual discrimination problem of detecting mice in darkness gets more mice, the faster she responds. The survival value of rapid execution of complex tasks and of the ability to learn to respond faster may have contributed to the special development of the pyramidal tract in higher mammals.
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RESPONSE LATENCY AFTER PYRAMIDALLESIONS
219
SUMMARY Cats walked, jumped and climbed with no apparent defects 3 weeks after transection of a pyramid in the medulla oblongata. To determine if a precisely defined task was executed with reduced speed, cats were trained to press a lever under the brighter of two light bulbs to obtain bits of food. The bulbs were lit when the cat stepped on a platform and the time from depression of the platform to depression of a lever was measured for about 100 consecutive responses on each of 10 consecutive days. The measurements were made after the cat had attained stable performance before and about 3 months after incomplete lesions in one or both medullary pyramids. Unilateral and bilateral lesions involving more than 30 ~ of one pyramid increased the mean response latency from 0.1 to 0.8 sec and the largest lesions produced the largest increase in latency. Differential reinforcement of responses with short latency made the slowest cats respond faster before pyramidotomy. After the operation the cats could no longer be speeded up. The pyramidotomized cats depressed the lever with normal coordination and one cat used the same paw for responding before and after a contralateral lesion interrupting 50 ~o of the fibers. The slowing was not duc to general m o t o r impairment: 3 weeks after large lesions of both pyramids the cats made hundreds of responses in succession ( F R schedule) at the same rate as before the operation. O f five cats with bilateral control lesions in mesencephalon, thalamus or association cortex four were unaffected. Slowing of the fifth cat is attributed to damage of specific afferent pathways; the cat relearned slowly, gained weight in spite of reduced food intake and presumably had a reduced level of alertness. ACKNOWLEDGMENTS This work was made possible through the support and sponsorship of the U. S. A r m y through its European Research Office. Dr. M. W. was supported by a grant from the Swiss National Foundation (No. 2903). We gratefully acknowledge the assistance of Mr. Thomas Nissen and Mr. Vagn Hansen in training the animals. REFERENCES 1 BUSER,P., ET ROUGEUL, A., Observations sur le conditionnement instrumental alimentaire chez le chat. In J. F. D~LAFRESNAW(Ed.L Brain Mechanisms and Learning, Blackwell, Oxford, 1961
p. 527. 2 GELLERMAN, L. W., Chance orders of alternating stimuli in visual discrimination experiments, J. genet. Psychol., 42 (1933) 207-208. 3 GORSKA,T., JANKOWSKA,E., AND MOSSAKOWSKI,M., Instrumental conditioned reflexes after section of the pyramids in cats, Bull. Acad. pol. Sci. CI. 2, 12 (1964) 413-416. 4 LALrRSEH,A. M., ANDWmSEHI~ANGER,M., Motor deficits after transection of a bulbar pyramid in the cat, Acta physiol, scand., 68 (1966) 118-126. 5 MARSHALL,C., Experimental lesions of the pyramidal tract, Arch. Neurol. Psyehiat. (Chic.), 32 (1934) 778-796. 6 MCNEw, B. g., AND THOMPSON,R., Effect of posterior thalamic lesions on retention of a brightness discrimination motivated by thirst, J. comp. physiol. Psyehol., 62 (1966) 125-128. Brain Research, 5 (1967) 207-220
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7 ScrnrF, J. M., Lehrbuch der Physiologie des Menschen, Lahr, Schauenburg, 1858-1859, p. 305. 8 SPRAGUE, J, M., LEVITT, M., ROBSON, K., LIU, C. N., STELLAR, E., AND CHAMBERS, W. W., A neuroanatomical and behavioral analysis of the syndromes resulting from midbrain lemniscal and reticular lesions in the cat, Arch. ital. Biol., 101 (1963) 225-295. 9 THOMPSON,R., AND RICH, 1., A discrete diencephalic pretectal area critical for retention of visual habits in the rat, Exp. Neurol,, 4 (1961) 436--443. 10 TOWER, S. S., The dissociation of cortical excitation from cortical inhibitioa by pyramid section and the syndrome of that lesion in the cat, Brain, 58 (1935) 238-255. 11 WILCOXON, F., Some Rapid Approximate Statistical Procedures, American Cyanamid Co., New York, 1949, p. 4.
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