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Effects of caudate nuclei or frontal cortical ablations in kittens: Maze learning
EXPERIMENTAL
NEUROLOGY
Effects
of Caudate
63, 251-265 (1979)
Nuclei or Frontal Cortical Kittens: Maze Learning
CH. E. OLMSTEAD
Ablations
in
AND J. R. VILLABLANCA’
Departments of Psychiatry and Anatomy and the Mental Retardation Research Center, University of California School of Medicine, Los Angeles, California 90024 Received
May
9, 1978
Cats which had received bilateral lesions of the caudate nuclei and the frontal cortices during the first month of life were tested as juveniles on T-maze position habit and spatial reversal tasks. Intact and sham-operated littermates served as controls. All animals of all groups were capable of learning the spatial discrimination and to successfully reverse that habit. While maintaining many of the perseverative characteristics of adult-operated acaudates, the kitten-operated acaudates showed the fewest number of trials to acquire the position habit and to complete 30 reversals. There was a direct relationship between the size of the lesion and the number of perseverative errors made by the acaudate animals. The afrontal cats showed more reversal errors and were unmotivated and distractable. The data suggest for the tasks used here that although there may be similar qualitative deficits the overall effects on performance are not as great when the lesion is inflicted in the neonate compared to the adult. The data imply that many factors contribute to this recovery, e.g., early experience.
INTRODUCTION We recently described (7) the reversal aspects of T-maze learning in adult cats with extensive lesions of the caudate nuclei and frontal cortices. In that study, acaudate animals showed, on a spatial alternation task as well as on a black-white discrimination, errors best described as perseverative toward the site of last reward, whereas the afrontal animals did not persevere and 1 This research was supported by U.S. Public Health Service grants HD-05958, MH-07097, and HD-04612. We wish to thank I. Buckberg for her participation in the research and P. Atkinson of the UCLA Mental Retardation and Child Psychiatry Media Unit for his assistance in the illustrations. 257 0014-4886/79/020257-09$02.00/O Copyright All rights
0 1979 by Academic Press, of reproduction in any form
Inc. reserved.
258
OLMSTEAD
AND
VILLABLANCA
made more randomly distributed errors. The present paper reports similar studies on animals with caudate, frontal cortical, and sham lesions made in the first month of life, with emphasis on the acquisition and successive reversals of a position habit. Other studies have been conducted on these subjects in an attempt to define the effects produced by early caudatectomy (4, 9, 13, 14). METHODS The subjects were cats of either sex which had received bilateral lesions of the caudate nuclei (N = 7, three males and four females) or frontal cortices (IV = 9, five males and four females) at 9 to 36 days of age. Sham-operated (N = 5, two males and three females) and intact littermates (N = IS, 12 males and three females) served as controls. All animals were reared in the UCLA Mental Retardation Research Center kitten colony. A detailed description of the surgery, postoperative care, and histological procedures was given in the first three papers of this series (9, 13, 14). Beginning at 90 days of age, these animals were studied in a T-maze visual discrimination (4). From approximately 4 months of age until the termination of this experiment, the animals were housed individually in standard laboratory cages. All underwent bar press training at a median of 9 months of age (8). The subjects were fed sufficient canned cat food to maintain a body weight slightly below that of growing ad libitum feeding cats. Beginning at a median of 12 months of age they were trained 5 days/week. The maze was a standard T with a 1.25-m alley (15 cm wide x 45 cm deep) with two 60-cm arms of height and breadth equal to those of the alley. The tuna fish reward was available in recessed receptacles placed at the arm ends. The spatial learning and reversals were run in daily 20-trial blocks with the requirement that when the subject made five consecutive responses to the rewarded side (trials to initial spatial learning) this was reversed. Thereafter, each time five consecutive correct trials were made, the correct side was reversed (i.e., 5 x 5) for a total of 30 reversals. During these trials, the number of errors, the correct response, and their sequences were recorded to permit analysis of perseveration, spontaneous alternation, and other error topographies. Subject idiosyncracies were also noted. Error profiles were classified in the following manner: (a) any time five successive trials were followed by two or more incorrect trials in a row, the error was called perseverutive; (b) three or four correct trials followed by an error was called anticipatory; (c) any error occurring after one or two correct trials was called random ; and (d) perfect was five correct followed by five correct at the other arm. Nonparametric statistics (11) were used to analyze the results.
CAUDATE
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RESULTS Anatomy. The caudate lesions were extensive (median, 81%; range, 44 to 93%) and the exact histology of these animals was described in detail in the third paper of this series (8). Behavior. A Friedman two-way analysis of variance on the median errors per five reversal segments (Fig. 1) showed significant group differences (xrZ = 13.4, u” = 3, P < 0.002) and significant decreases in errors with successive reversal training (xr2 = 12.6, & = 5, P < 0.04). Individual group comparisons showed these effects to be restricted primarily to differences between the sham-operated animals and the other groups. Of the other groups, only the frontals showed significant differences from the intact and then only on the initial segments of the training. A chi-square analysis of the error distribution during reversals (shown as percentages in Table 2) showed an overall significant difference between groups at the 0.001 level (x2 = 8.75, df = 3). A presentation of the individual group results follows. The normal littermates readily acquired the initial position habit and in the 5 x 5 spatial reversal (Table 1) stabilized at two or three errors per reversal (Fig. 1). Note that there was a significant decrement in errors from the first five-trial block to the second. In these animals, the distribution of the types of errors (see Table 2) showed the majority to be anticipatory. Only two of the animals were exceptional in that they showed more random errors. The three females in this group were not significantly different from the 12 males on any of the measures. The sham-operated cats acquired the initial position habit in a median of 18 trials, but showed significantly fewer errors than the intact animals (P < 0.04) in doing so. On the reversal, however, they showed a sharp TABLE
1
Medians and Ranges of Correct (C) and Error (E) Trials for Acquisition, First Reversal, and First Five Reversals in the Maze Reversal Task” Acquisition C Intact ( 15)b 22(7-39) Sham (5)* 11(9-21) Afrontal (9)b 1q5-50) Acaudate (7)* 11(5-15)***
First reversal E
10(3-21) 7(1-18)* 8(0-67) 4(0-9)**
C 13(6-36) 10(9-26) 20(7-38) 8(6-17)
E 6(1-14) 14(4-36)*** 11(4-34)*** 3(1-9)
First five reversals C 57(36-113) 60(41-100) 55(42- 191) 47(32-62)
E 20(13-54) 53(12-65)* 30(22-81) 18(10-43)
o P by Mann-Whitney U-test: * cO.05, **<0.(X)8, ***<0.02, compared to intact animals. * Number of animals in parentheses.
OLMSTEAD AND VILLABLANCA
260
N=5
77 8 6
ShO BFr
; = t s g
40
5 =
30
N=9
BAc
INTACT
N=7 N=15
123456
‘-’I L. Successive
23456 Reversals
x 5
Fro. 1.Median number of errors and intraquartile ranges for the four kitten-operated groups during the 5 X 5 spatial reversal as a function of five trial blocks, ShO-sham-operated, BFr-afrontal, BAc-acaudate. (See text for statistical values.)
increase (Fig. 1, Table 1)in the number of errors on both the first (P < 0.02) reversal and the first five (P c 0.05) reversals. Although there was a sharp decline in errors as afunction of reversals, their rate in the final five reversal blocks was still higher, although not significantly, than that of the intact controls. More important, however, was the nature of these errors as 55% (Table 2) of them were of the rundom type. This distribution was uniform for all five animals, and no relationship was seenbetween either the number of errors or their type, the sex of the cat, or the extent of the lesion, Subjective notes were that the animals responded swiftly when the door was opened and corrected themselves rapidly and that the errors were made long before the choice point. None of the animals showed a preference for any particular arm of the maze or had turning biases. The qfrontal cats took approximately the same number of trials as the intact and sham-operated animals to acquire the initial spatial discrimination, but produced more errors than the intacts on both the first reversal
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(P c 0.012) and the first five (P < 0.002) reversals (Table 1). Thereafter, they were not significantly different from the controls. There was a preponderance of anticipatory and random errors distributed fairly closely to that seen in the sham-operated animals. It was interesting that this was the only group which showed a change in the type of error with training, in that between the first and last 10 reversals there was a doubling of the percentage of anticipatory at the expense of random and perseverative errors. Subjectively, these animals were more temperamental than the other groups, and nearly all stopped consuming the food reward before the end of the 20 trials, often in spite of severe deprivation. There were no specific traits that could be attributed to either the sex of the animal or the extent of the lesion. The acaudute animals took significantly (P < 0.002 compared to intact) fewer trials than any of the other groups to acquire the initial position habit (Table l), However, they were not distinguishable from the intact animals on either the first (P C 0.38) or the first five (P < 0.72) reversals (Table 1). In fact, only on the first reversal did they show significantlyfewer errors than the afrontal (P < 0.006) and sham-operated (P < 0.04) groups. As seen in Fig. 1, the acaudates stabilized at two or three errors per reversal, The distribution of these errors is of interest. As shown in Table 2, the acaudates had the most uniform distribution of all four classesof errors and actually showed the most perfect reversals as well as the most TABLE Distribution
2
of Errors on the Reversal Task” Percentage of error typeb
Group (N)
Anticipatory
Perseverative
Random
None
Kitten Intact (15) Sham (5) Afrontal (9) Acaudate (7)
63.3 30.0 32.1 34.5
0.0 9.3 10.7 13.8
33.3 54.1 42.9 20.6
.Q3 6.0 1483 31.0
Adult’ Intact and sham (5) Afrontal (4) Acaudate (7)
25.0 13.3 13.1
1S.l 21.6 40.4
28.9 22.5 19.2
30.9 42.5 27.2
a These are percentages of total number of animals times 30 reversals. ) See text for a description of the error types. c The previously unreported values for adult-operated animals were added for comparitive purposes.
262
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perseverative responding. A closer analysis showed there was an indirect relationship (r, = +.68, P < 0.05) between the size of the lesion and the number of anticipatory errors and a direct relationship (r, = +.71, P < 0.05) between the lesion and the perseverative errors. Although no such significant relationship could be demonstrated for the other types of errors, there was a trend (r, = -.58, P < 0.10) for the animals with the larger lesions to show fewer perfect reversals. All in all, the acaudates showed the mostperseverative and the fewest random errors. Once again, no specific sex-related idiosyncracies or side preferences were seen. No relationships could be readily established between any noncaudate surgical damage and the behavior of the cats. In summary, all animals of all groups were capable of learning a position habit (a spatial discrimination) and were able to successively reverse that habit. Overall, animals with sham lesions showed the greatest number of reversal errors followed by those with lesions of the frontal cortices. Acaudate cats showed the fewest overall errors and took, by far, the fewest number of trials to complete the acquisition of the position habit and the thirty reversals. The type of errors was significantly different between groups. DISCUSSION As stated previously (8), it is impossible to compare the results in the animals with caudate lesions with the literature because no such studies have been successfully carried out [see (2, 5, 8, 12) for a discussion]. We can, however, compare this work with our previous experiments in adult animals (7). The striking difference between the kitten-operated and the adultoperated groups was a marked decrease in the amount of perseveration in the former. As shown in Table 2, the perseverative errors in the adult-operated animals in the discrimination reversal task totaled 40.4%, a value which was almost double that for any other group. In the kitten-operated animals, the acaudates still showed the highest amount of perseveration, but this time by a much narrower margin. In relation to the learning of the initial position habit, the perseveration appeared to have a favorable influence because both kitten-operated (Table 1) and adultoperated acaudates took fewer trials and much fewer errors to acquisition. Furthermore, the adults, with the larger perseveration, produced fewer errors than the kittens. However, when the effects on the reversal of the spatial discrimination were examined in the adult-operated, the influence of perseveration resulted in a significantly increased production of errors (7). The result was to be expected because impairments of a similar nature were seen in other behavioral tasks (4, 8, 9, 14) applied to these animals, both
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263
kitten- and adult-operated, in which alternation or reversal of a performance was involved. In contrast, for the kitten-operated, mere error count during the maze reversal was not a sensitive enough indicator to differentiate the groups (Fig. 1) in this specific task. Therefore, we can conclude that although qualitatively both the kitten- and adult-operated acaudates shared the same basic defect, i.e., persistence in responding at the site of last reward, quantitatively in the kittens this defect was not large enough to be detected by the reversal aspect of the task. An obvious question is what caused the marked decrease relative to the adults in the perseverative tendency of the kittens. This question is pertinent, particularly because in other tests we have used, this differential recovery was not seen (8, 9). An important factor, which was not present for any of our other tasks, was that the kitten-operated animals had received earlier training (between 3 and 8 months of age) in a T-maze. In that early maze, perseveration significantly impaired reversal learning. Unfortunately, the maze and the experimental paradigm (4) used were not exactly the same as the one here, and therefore, any strict comparison is impossible. There are other, although few, reports in the literature (1, 3,6) suggesting beneficial effects of postlesion training upon impairments resulting from early brain damage. Repetition of the present experiments under more stringent conditions, i.e., an identical paradigm for both early and late maze testings, appears to be indicated in order to verify whether this variable can account for a decrement in the perseveration. It is interesting (Table 2) that the kitten-operated subjects showed a somewhat more restricted distribution of the types of errors than the adults. This concentration on anticipatory and random types of errors in the kitten might also represent an effect of the previous experience with a black-white discrimination (4), whereas that of the adult would indicate a shifting of the strategies as training progresses, as it was actually observed (7). In the latter study, the adults showed most random errors in the early reversals and anticipatory errors in the late reversals, whereas the kittens of all groups showed the anticipatory and random errors to be distributed throughout the 30 reversals. Regarding kitten- and adult-operated afrontals, only nonsignificant differences were seen between the two groups. As in the adults, the kittens showed a larger percentage of random errors, although not as marked and with an increase in anticipatory errors as training progressed (which brought them closer to their intact littermates). More important, perhaps, was that the kitten-operated afrontals were almost equally unmotivated, distractable, and irregular performers as were their adult counterparts. For hypotheses concerning the behavioral differences between acaudate and afrontal cats, we refer the readers to our previous papers (7, 8, 13, 14).
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In spite of the differences between kitten- and adult-operated animals, which we discussed above, it must be pointed out that there were many features seen in both age groups. Specifically, the tendencies of the kitten-operated acaudates and afrontals to make errors qualitatively identical to those of their adult counterparts indicated some unitary effect of the lesion which was independent of the age at surgery as well as of the handling and testing during ontogeny. Also, the fact that, at least in the acaudate subjects, there was a strong correlation between the lesion size and the parameters of the deficit points to a surviving neural defect not overcome by other developmental factors. An additional point for discussion is the reason for the high level of error production by the sham-operated group. Although we initially speculated that the effect was due to the estrous females in the group as was seen in the bar pressing task (8, lo), it was not possible to statistically verify this hypothesis. For the present time, since the sham operation involved a lesion of the cingulum, we should consider this, preliminarily at least, as a true lesion effect and a subject for further investigation. The lack of such effects in our adult series is against this possibility, but we should, perhaps, consider whether or not the cingulum has a different role in the adult versus the developing cat. Finally, although the present data indicate that animals with caudate and frontal cortex lesions inflicted as kittens are qualitatively similar to adult-operated cats, the kitten-operated are behaviorally more labile than the adults. The role of such factors as early experience, sex, and the tasks used for evaluation-all of which may, according to our results (4,8,9,13, should provide a fertile ground for further 14), influence that labilityinvestigation. REFERENCES 1. BENJAMIN, R. M., AND R. F. THOMPSON. 1959. Differential effects of cortical lesions in infant and adult cats on roughness discrimination. Exp. Neural. 1: 305-332. 2. GOLDMAN, P. S. 1976. Maturation of the mammalian nervous system and the ontogeny of behavior. Pages l-90 in J. S. ROSENBLATT, R. A. HINDE, E. SHAW, AND C. BEER, Eds., Advances in the Study of Behavior. Academic Press, New York. 3. GOLDMAN, P. S., AND M. J. MENDELSON. 1977. Salutary effects of early experience on deficits caused by lesions of frontal association cortex in developing rhesus monkeys. Exp. Neural. 51: 488-602. 4. LEVINE, M. S., J. R. VILLABLANCA, C. D. HULL, N. A. BUCHWALD, AND CH. E. OLMSTEAD. 1976, Maze learning in kittens with caudate or frontal cortical lesions. Sot. Neurosci. Abstr. 2: 65. 5. KLING, A., AND T. J. TUCKER. 1968. Sparing of function following localized brain lesions in neonatal monkeys. Pages 121- 145 in R. L. ISAACSON, Ed., The Neuropsychology of Development. Wiley, New York. 6. NONNEMAN, A. J., AND R. ISAACSON. 1973. Task dependent recovery after early brain damage. Behav. Biol. 8: 143-172.
CAUDATE 7.
8.
9.
10. 11. 12. 13. 14.
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C. E., J. R. VILLABLANCA, R. J. MARCUS, AND D. L. AVERY. 1976. Effects of caudate nuclei or frontal cortex ablations in cats. IV. Bar pressing and maze learning and performance. Exp. Neural. 53: 670-693. OLMSTEAD, CH. E., AND J. R. VILLABLANCA. 1979. Effects of caudate nuclei or frontal cortical ablations in kittens: Bar pressing performance. Exp. Neurol. 63: 244-256. OLMSTEAD, CH. E., AND J. R. VILLABLANCA. 1979. Effects of candate nuclei or frontal cortical ablations in kittens. Paw usage. Comparisons with adults. Exp. Neurol. (in press). SCOTT, P. P. 1970. Cats. Pages 192-207 in E. S. E. HAFEZ, Ed., Reproduction and Breeding Techniques for Laboratory Animals. Lea and Febiger, Philadelphia. SIEGEL, S. 1956. Nonparametric Statistics for the Behavioral Sciences. McGraw-Hill, New York. TEUBER, H.- L. 1973. Recovery of function after lesions of the central nervous system: History and prospects. Neurosci. Res. Progr. Bull. 12: 197-211. VILLABLANCA, J. R., CH. E. OLMSTEAD, M. S. LEVINE, AND R. J. MARCUS. 1978. Effects of caudate nuclei or frontal cortical ablations in kittens: neurology and gross behavior. Exp. Neurol. 61: 615-634. VILLABLANCA, J. R., CH. E. OLMSTEAD, AND I. DE ANDRE. 1978. Effects of caudate nuclei or frontal cortical ablations in kittens: responsiveness to auditory stimuli and comparisons with adult-operated littermates. Exp. Neurol. 61: 635-649. OLMSTEAD,
NEUROLOGY
Effects
of Caudate
63, 251-265 (1979)
Nuclei or Frontal Cortical Kittens: Maze Learning
CH. E. OLMSTEAD
Ablations
in
AND J. R. VILLABLANCA’
Departments of Psychiatry and Anatomy and the Mental Retardation Research Center, University of California School of Medicine, Los Angeles, California 90024 Received
May
9, 1978
Cats which had received bilateral lesions of the caudate nuclei and the frontal cortices during the first month of life were tested as juveniles on T-maze position habit and spatial reversal tasks. Intact and sham-operated littermates served as controls. All animals of all groups were capable of learning the spatial discrimination and to successfully reverse that habit. While maintaining many of the perseverative characteristics of adult-operated acaudates, the kitten-operated acaudates showed the fewest number of trials to acquire the position habit and to complete 30 reversals. There was a direct relationship between the size of the lesion and the number of perseverative errors made by the acaudate animals. The afrontal cats showed more reversal errors and were unmotivated and distractable. The data suggest for the tasks used here that although there may be similar qualitative deficits the overall effects on performance are not as great when the lesion is inflicted in the neonate compared to the adult. The data imply that many factors contribute to this recovery, e.g., early experience.
INTRODUCTION We recently described (7) the reversal aspects of T-maze learning in adult cats with extensive lesions of the caudate nuclei and frontal cortices. In that study, acaudate animals showed, on a spatial alternation task as well as on a black-white discrimination, errors best described as perseverative toward the site of last reward, whereas the afrontal animals did not persevere and 1 This research was supported by U.S. Public Health Service grants HD-05958, MH-07097, and HD-04612. We wish to thank I. Buckberg for her participation in the research and P. Atkinson of the UCLA Mental Retardation and Child Psychiatry Media Unit for his assistance in the illustrations. 257 0014-4886/79/020257-09$02.00/O Copyright All rights
0 1979 by Academic Press, of reproduction in any form
Inc. reserved.
258
OLMSTEAD
AND
VILLABLANCA
made more randomly distributed errors. The present paper reports similar studies on animals with caudate, frontal cortical, and sham lesions made in the first month of life, with emphasis on the acquisition and successive reversals of a position habit. Other studies have been conducted on these subjects in an attempt to define the effects produced by early caudatectomy (4, 9, 13, 14). METHODS The subjects were cats of either sex which had received bilateral lesions of the caudate nuclei (N = 7, three males and four females) or frontal cortices (IV = 9, five males and four females) at 9 to 36 days of age. Sham-operated (N = 5, two males and three females) and intact littermates (N = IS, 12 males and three females) served as controls. All animals were reared in the UCLA Mental Retardation Research Center kitten colony. A detailed description of the surgery, postoperative care, and histological procedures was given in the first three papers of this series (9, 13, 14). Beginning at 90 days of age, these animals were studied in a T-maze visual discrimination (4). From approximately 4 months of age until the termination of this experiment, the animals were housed individually in standard laboratory cages. All underwent bar press training at a median of 9 months of age (8). The subjects were fed sufficient canned cat food to maintain a body weight slightly below that of growing ad libitum feeding cats. Beginning at a median of 12 months of age they were trained 5 days/week. The maze was a standard T with a 1.25-m alley (15 cm wide x 45 cm deep) with two 60-cm arms of height and breadth equal to those of the alley. The tuna fish reward was available in recessed receptacles placed at the arm ends. The spatial learning and reversals were run in daily 20-trial blocks with the requirement that when the subject made five consecutive responses to the rewarded side (trials to initial spatial learning) this was reversed. Thereafter, each time five consecutive correct trials were made, the correct side was reversed (i.e., 5 x 5) for a total of 30 reversals. During these trials, the number of errors, the correct response, and their sequences were recorded to permit analysis of perseveration, spontaneous alternation, and other error topographies. Subject idiosyncracies were also noted. Error profiles were classified in the following manner: (a) any time five successive trials were followed by two or more incorrect trials in a row, the error was called perseverutive; (b) three or four correct trials followed by an error was called anticipatory; (c) any error occurring after one or two correct trials was called random ; and (d) perfect was five correct followed by five correct at the other arm. Nonparametric statistics (11) were used to analyze the results.
CAUDATE
OR FRONTAL
ABLATIONS
259
IN KITTENS
RESULTS Anatomy. The caudate lesions were extensive (median, 81%; range, 44 to 93%) and the exact histology of these animals was described in detail in the third paper of this series (8). Behavior. A Friedman two-way analysis of variance on the median errors per five reversal segments (Fig. 1) showed significant group differences (xrZ = 13.4, u” = 3, P < 0.002) and significant decreases in errors with successive reversal training (xr2 = 12.6, & = 5, P < 0.04). Individual group comparisons showed these effects to be restricted primarily to differences between the sham-operated animals and the other groups. Of the other groups, only the frontals showed significant differences from the intact and then only on the initial segments of the training. A chi-square analysis of the error distribution during reversals (shown as percentages in Table 2) showed an overall significant difference between groups at the 0.001 level (x2 = 8.75, df = 3). A presentation of the individual group results follows. The normal littermates readily acquired the initial position habit and in the 5 x 5 spatial reversal (Table 1) stabilized at two or three errors per reversal (Fig. 1). Note that there was a significant decrement in errors from the first five-trial block to the second. In these animals, the distribution of the types of errors (see Table 2) showed the majority to be anticipatory. Only two of the animals were exceptional in that they showed more random errors. The three females in this group were not significantly different from the 12 males on any of the measures. The sham-operated cats acquired the initial position habit in a median of 18 trials, but showed significantly fewer errors than the intact animals (P < 0.04) in doing so. On the reversal, however, they showed a sharp TABLE
1
Medians and Ranges of Correct (C) and Error (E) Trials for Acquisition, First Reversal, and First Five Reversals in the Maze Reversal Task” Acquisition C Intact ( 15)b 22(7-39) Sham (5)* 11(9-21) Afrontal (9)b 1q5-50) Acaudate (7)* 11(5-15)***
First reversal E
10(3-21) 7(1-18)* 8(0-67) 4(0-9)**
C 13(6-36) 10(9-26) 20(7-38) 8(6-17)
E 6(1-14) 14(4-36)*** 11(4-34)*** 3(1-9)
First five reversals C 57(36-113) 60(41-100) 55(42- 191) 47(32-62)
E 20(13-54) 53(12-65)* 30(22-81) 18(10-43)
o P by Mann-Whitney U-test: * cO.05, **<0.(X)8, ***<0.02, compared to intact animals. * Number of animals in parentheses.
OLMSTEAD AND VILLABLANCA
260
N=5
77 8 6
ShO BFr
; = t s g
40
5 =
30
N=9
BAc
INTACT
N=7 N=15
123456
‘-’I L. Successive
23456 Reversals
x 5
Fro. 1.Median number of errors and intraquartile ranges for the four kitten-operated groups during the 5 X 5 spatial reversal as a function of five trial blocks, ShO-sham-operated, BFr-afrontal, BAc-acaudate. (See text for statistical values.)
increase (Fig. 1, Table 1)in the number of errors on both the first (P < 0.02) reversal and the first five (P c 0.05) reversals. Although there was a sharp decline in errors as afunction of reversals, their rate in the final five reversal blocks was still higher, although not significantly, than that of the intact controls. More important, however, was the nature of these errors as 55% (Table 2) of them were of the rundom type. This distribution was uniform for all five animals, and no relationship was seenbetween either the number of errors or their type, the sex of the cat, or the extent of the lesion, Subjective notes were that the animals responded swiftly when the door was opened and corrected themselves rapidly and that the errors were made long before the choice point. None of the animals showed a preference for any particular arm of the maze or had turning biases. The qfrontal cats took approximately the same number of trials as the intact and sham-operated animals to acquire the initial spatial discrimination, but produced more errors than the intacts on both the first reversal
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(P c 0.012) and the first five (P < 0.002) reversals (Table 1). Thereafter, they were not significantly different from the controls. There was a preponderance of anticipatory and random errors distributed fairly closely to that seen in the sham-operated animals. It was interesting that this was the only group which showed a change in the type of error with training, in that between the first and last 10 reversals there was a doubling of the percentage of anticipatory at the expense of random and perseverative errors. Subjectively, these animals were more temperamental than the other groups, and nearly all stopped consuming the food reward before the end of the 20 trials, often in spite of severe deprivation. There were no specific traits that could be attributed to either the sex of the animal or the extent of the lesion. The acaudute animals took significantly (P < 0.002 compared to intact) fewer trials than any of the other groups to acquire the initial position habit (Table l), However, they were not distinguishable from the intact animals on either the first (P C 0.38) or the first five (P < 0.72) reversals (Table 1). In fact, only on the first reversal did they show significantlyfewer errors than the afrontal (P < 0.006) and sham-operated (P < 0.04) groups. As seen in Fig. 1, the acaudates stabilized at two or three errors per reversal, The distribution of these errors is of interest. As shown in Table 2, the acaudates had the most uniform distribution of all four classesof errors and actually showed the most perfect reversals as well as the most TABLE Distribution
2
of Errors on the Reversal Task” Percentage of error typeb
Group (N)
Anticipatory
Perseverative
Random
None
Kitten Intact (15) Sham (5) Afrontal (9) Acaudate (7)
63.3 30.0 32.1 34.5
0.0 9.3 10.7 13.8
33.3 54.1 42.9 20.6
.Q3 6.0 1483 31.0
Adult’ Intact and sham (5) Afrontal (4) Acaudate (7)
25.0 13.3 13.1
1S.l 21.6 40.4
28.9 22.5 19.2
30.9 42.5 27.2
a These are percentages of total number of animals times 30 reversals. ) See text for a description of the error types. c The previously unreported values for adult-operated animals were added for comparitive purposes.
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perseverative responding. A closer analysis showed there was an indirect relationship (r, = +.68, P < 0.05) between the size of the lesion and the number of anticipatory errors and a direct relationship (r, = +.71, P < 0.05) between the lesion and the perseverative errors. Although no such significant relationship could be demonstrated for the other types of errors, there was a trend (r, = -.58, P < 0.10) for the animals with the larger lesions to show fewer perfect reversals. All in all, the acaudates showed the mostperseverative and the fewest random errors. Once again, no specific sex-related idiosyncracies or side preferences were seen. No relationships could be readily established between any noncaudate surgical damage and the behavior of the cats. In summary, all animals of all groups were capable of learning a position habit (a spatial discrimination) and were able to successively reverse that habit. Overall, animals with sham lesions showed the greatest number of reversal errors followed by those with lesions of the frontal cortices. Acaudate cats showed the fewest overall errors and took, by far, the fewest number of trials to complete the acquisition of the position habit and the thirty reversals. The type of errors was significantly different between groups. DISCUSSION As stated previously (8), it is impossible to compare the results in the animals with caudate lesions with the literature because no such studies have been successfully carried out [see (2, 5, 8, 12) for a discussion]. We can, however, compare this work with our previous experiments in adult animals (7). The striking difference between the kitten-operated and the adultoperated groups was a marked decrease in the amount of perseveration in the former. As shown in Table 2, the perseverative errors in the adult-operated animals in the discrimination reversal task totaled 40.4%, a value which was almost double that for any other group. In the kitten-operated animals, the acaudates still showed the highest amount of perseveration, but this time by a much narrower margin. In relation to the learning of the initial position habit, the perseveration appeared to have a favorable influence because both kitten-operated (Table 1) and adultoperated acaudates took fewer trials and much fewer errors to acquisition. Furthermore, the adults, with the larger perseveration, produced fewer errors than the kittens. However, when the effects on the reversal of the spatial discrimination were examined in the adult-operated, the influence of perseveration resulted in a significantly increased production of errors (7). The result was to be expected because impairments of a similar nature were seen in other behavioral tasks (4, 8, 9, 14) applied to these animals, both
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kitten- and adult-operated, in which alternation or reversal of a performance was involved. In contrast, for the kitten-operated, mere error count during the maze reversal was not a sensitive enough indicator to differentiate the groups (Fig. 1) in this specific task. Therefore, we can conclude that although qualitatively both the kitten- and adult-operated acaudates shared the same basic defect, i.e., persistence in responding at the site of last reward, quantitatively in the kittens this defect was not large enough to be detected by the reversal aspect of the task. An obvious question is what caused the marked decrease relative to the adults in the perseverative tendency of the kittens. This question is pertinent, particularly because in other tests we have used, this differential recovery was not seen (8, 9). An important factor, which was not present for any of our other tasks, was that the kitten-operated animals had received earlier training (between 3 and 8 months of age) in a T-maze. In that early maze, perseveration significantly impaired reversal learning. Unfortunately, the maze and the experimental paradigm (4) used were not exactly the same as the one here, and therefore, any strict comparison is impossible. There are other, although few, reports in the literature (1, 3,6) suggesting beneficial effects of postlesion training upon impairments resulting from early brain damage. Repetition of the present experiments under more stringent conditions, i.e., an identical paradigm for both early and late maze testings, appears to be indicated in order to verify whether this variable can account for a decrement in the perseveration. It is interesting (Table 2) that the kitten-operated subjects showed a somewhat more restricted distribution of the types of errors than the adults. This concentration on anticipatory and random types of errors in the kitten might also represent an effect of the previous experience with a black-white discrimination (4), whereas that of the adult would indicate a shifting of the strategies as training progresses, as it was actually observed (7). In the latter study, the adults showed most random errors in the early reversals and anticipatory errors in the late reversals, whereas the kittens of all groups showed the anticipatory and random errors to be distributed throughout the 30 reversals. Regarding kitten- and adult-operated afrontals, only nonsignificant differences were seen between the two groups. As in the adults, the kittens showed a larger percentage of random errors, although not as marked and with an increase in anticipatory errors as training progressed (which brought them closer to their intact littermates). More important, perhaps, was that the kitten-operated afrontals were almost equally unmotivated, distractable, and irregular performers as were their adult counterparts. For hypotheses concerning the behavioral differences between acaudate and afrontal cats, we refer the readers to our previous papers (7, 8, 13, 14).
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In spite of the differences between kitten- and adult-operated animals, which we discussed above, it must be pointed out that there were many features seen in both age groups. Specifically, the tendencies of the kitten-operated acaudates and afrontals to make errors qualitatively identical to those of their adult counterparts indicated some unitary effect of the lesion which was independent of the age at surgery as well as of the handling and testing during ontogeny. Also, the fact that, at least in the acaudate subjects, there was a strong correlation between the lesion size and the parameters of the deficit points to a surviving neural defect not overcome by other developmental factors. An additional point for discussion is the reason for the high level of error production by the sham-operated group. Although we initially speculated that the effect was due to the estrous females in the group as was seen in the bar pressing task (8, lo), it was not possible to statistically verify this hypothesis. For the present time, since the sham operation involved a lesion of the cingulum, we should consider this, preliminarily at least, as a true lesion effect and a subject for further investigation. The lack of such effects in our adult series is against this possibility, but we should, perhaps, consider whether or not the cingulum has a different role in the adult versus the developing cat. Finally, although the present data indicate that animals with caudate and frontal cortex lesions inflicted as kittens are qualitatively similar to adult-operated cats, the kitten-operated are behaviorally more labile than the adults. The role of such factors as early experience, sex, and the tasks used for evaluation-all of which may, according to our results (4,8,9,13, should provide a fertile ground for further 14), influence that labilityinvestigation. REFERENCES 1. BENJAMIN, R. M., AND R. F. THOMPSON. 1959. Differential effects of cortical lesions in infant and adult cats on roughness discrimination. Exp. Neural. 1: 305-332. 2. GOLDMAN, P. S. 1976. Maturation of the mammalian nervous system and the ontogeny of behavior. Pages l-90 in J. S. ROSENBLATT, R. A. HINDE, E. SHAW, AND C. BEER, Eds., Advances in the Study of Behavior. Academic Press, New York. 3. GOLDMAN, P. S., AND M. J. MENDELSON. 1977. Salutary effects of early experience on deficits caused by lesions of frontal association cortex in developing rhesus monkeys. Exp. Neural. 51: 488-602. 4. LEVINE, M. S., J. R. VILLABLANCA, C. D. HULL, N. A. BUCHWALD, AND CH. E. OLMSTEAD. 1976, Maze learning in kittens with caudate or frontal cortical lesions. Sot. Neurosci. Abstr. 2: 65. 5. KLING, A., AND T. J. TUCKER. 1968. Sparing of function following localized brain lesions in neonatal monkeys. Pages 121- 145 in R. L. ISAACSON, Ed., The Neuropsychology of Development. Wiley, New York. 6. NONNEMAN, A. J., AND R. ISAACSON. 1973. Task dependent recovery after early brain damage. Behav. Biol. 8: 143-172.
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10. 11. 12. 13. 14.
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C. E., J. R. VILLABLANCA, R. J. MARCUS, AND D. L. AVERY. 1976. Effects of caudate nuclei or frontal cortex ablations in cats. IV. Bar pressing and maze learning and performance. Exp. Neural. 53: 670-693. OLMSTEAD, CH. E., AND J. R. VILLABLANCA. 1979. Effects of caudate nuclei or frontal cortical ablations in kittens: Bar pressing performance. Exp. Neurol. 63: 244-256. OLMSTEAD, CH. E., AND J. R. VILLABLANCA. 1979. Effects of candate nuclei or frontal cortical ablations in kittens. Paw usage. Comparisons with adults. Exp. Neurol. (in press). SCOTT, P. P. 1970. Cats. Pages 192-207 in E. S. E. HAFEZ, Ed., Reproduction and Breeding Techniques for Laboratory Animals. Lea and Febiger, Philadelphia. SIEGEL, S. 1956. Nonparametric Statistics for the Behavioral Sciences. McGraw-Hill, New York. TEUBER, H.- L. 1973. Recovery of function after lesions of the central nervous system: History and prospects. Neurosci. Res. Progr. Bull. 12: 197-211. VILLABLANCA, J. R., CH. E. OLMSTEAD, M. S. LEVINE, AND R. J. MARCUS. 1978. Effects of caudate nuclei or frontal cortical ablations in kittens: neurology and gross behavior. Exp. Neurol. 61: 615-634. VILLABLANCA, J. R., CH. E. OLMSTEAD, AND I. DE ANDRE. 1978. Effects of caudate nuclei or frontal cortical ablations in kittens: responsiveness to auditory stimuli and comparisons with adult-operated littermates. Exp. Neurol. 61: 635-649. OLMSTEAD,