Percep~uala7zd Mocor Skills, 1975, 41,407-410. @ Perceptual and Motor Skills 1975
FURTHER EVALUATION OF A SENSITIVE METHOD FOR DETECTING EXPERIMENTAL BRAIN LESIONS1
TERRY J. HO'JTMAN, ROBERT E. SANDERS, CHRISTINE M. RINCK AND CHARLES L. SHERIDAN Universi~yof Missoasi at Kansas City and Vetman's Administration Hospital Kansar Cicy, Missouri Summary.-Small, unilateral cortical lesions were placed in either medialanterior, lateral-anterior, or posterior cortex of 20 male, Sprague-Dawley, albino rats. In addition, unilateral sham operations were performed on 8 rats from the same stock. All subjects had been trained prior to surgery with diametrically opposed visual habits mediated by opposite cerebral hemispheres. The opposing habits were, insofar as poss~ble,evenly matched prior to surgery. After surgery, lesioned hemispheres, regardless of locus of lesion, were slower in acquiring the habit they mediated, t h a n were unlesioned hemispheres. Further, unlesioned hemispheres dominated in test trials in which subjects chose one of the two cue doors with both eyes open. These findings confirm that the "interocularly conflicting discrimination" baseline detects a role of extrastriate cortex in mediation of pattern discrimination habits. They further indicated that losses occur without regard to the various locations of lesion employed. Besley and Sheridan (1973) described an unusually sensitive merhod for the detection of experimental brain lesions. For over 40 yr., attempts have been made to detect an influence of extrastriate cortical lesions o n visual pattern discriminations in rats (Lashley, 1931; Horel, Bettinger, Royce, & Meyer, 1966); successful identification of such effects was not reported in papers prior to that of Besley and Sheridan (1973). Previous investigators uniformly employed a technique of imposing bilateral lesions on some behavioral baseline involving binocular performance of pattern discriminations. Besley and Sheridan (1973) used a behavioral baseline, previously described by Sheridan (1965 ), i n which diametrically opposite discriminations are established via opposite eyes, and they introduced unilateral extrastriate lesions. Since their subjects were albino rats, in which the uncrossed visual pathways are virtually absent (Lund, 1965) and nonfunctional (Creel & Sheridan, 1966; Sheridan & Shrout, 1966), the effectiveness of their technique was probably due to the existence of a close balance between the opposing discriminations which were presumably mediated by opposite hemispheres. Even a small unilateral lesion was enough to shift the balance in favor of the unoperated hemisphere. Since the study of Besley and Sheridan (1973) stands alone in having demonstrated a deficit in the performance of pattern discrimination following . 'Supported by Research Funds from the United States Veteran's Administration.
408
T. J. HOTTMAN, ET AL.
lesions of extrastriate cortex, the present study was designed to replicate it. Further, the location of the lesions was varied in this study rather than restricted to cortex near the cerebral midline as it had been in the case of Besley and Sheridan (1973).
METHOD Twenty-eight male, Sprague-Dawley albino rats, about 90 days old at the beginning of the experiment, served as subjects. They were trained with diametrically opposite discriminations mediated by opposite eyes until, when challenged, they immediately performed at 90% correct on the original discrimination with the original eye open and at 90% correct on the reversal discrimination with the second eye open. After this training, all subjects were retired to their home cages for 3 wk. and were then retrained on the same schedules. This latter training session (termed the "pre-surgical retraining session") permitted assessment of the effects on the conflicting habits of a protracted lapse in training, and also afforded a degree of overtraining to stabilize each of the habits. After the pre-surgical retraining session, subjects were given unilateral cortical lesions. Most animals underwent both meningeal incision and subpial aspiration of anterior or posterior cortex, but some received only the meningeal insult. Small areas of cortical degeneration following meningeal damage necessitated placing some of the "sham" operated subjects into one of the lesion groups, because the behavioral baseline proved to be sensitive even to such small lesions. Lesioned groups were formed after extensive post-mortem histological examination of the brains. It was of particular interest in this study to determine whether anterior lesions might have interrupted underlying fibers which project to the visual syscem. For subjects with anterior lesions, dorsal lateral geniculate nuclei were examined carefully for cellular asymmetries between right and left geniculates. N o degeneration was detected in any of the subjects reported here. Subjects were divided into a lateral anterior (LA) group ( N .= 6 ) , a medial anterior (MA) group ( N = 7 ) , a posterior (P) group ( N = 7 ) and a sham (S) group ( N = 8). Even the largest lesions did not approach the sizes which failed to impair pattern discrimination in earlier studies. After surgery, animals were given 10 to 12 days recovery time, and then were retrained to criterion just as they had been in the pre-surgical retraining session. This retraining period after recovery from surgery provided post-surgical dependent measures with respect to the learning task. In order to control for any residual, pre-surgical differences in performance, pre-surgical retraining errors were subtracted from post-surgical retraining errors to form a dependent measure. (Effects reported here were even stronger with the simple postsurgical scores.)
DETECTING EXPERIMENTAL BRAIN LESIONS
Table 1 shows the mean numbers of corrected post-surgical retraining errors to criterion for each of the groups. In each group, more errors were associated with the lesioned than with the unlesioned hemisphere. Further; there were more errors associated with lesioned hemispheres than with their sham-operated controls. (Negative numbers indicate thac post-surgical performances were better than pre-surgical performances.) With respect to unoperated hemispheres, post-surgical performances were better than pre-surgical ones in aU but the medial anterior lesioned group, but the deviation of this group was probably due to surgical artifact. Microscopic examination of brains with medial anterior lesions indicated that, because of the midline location of these lesions, some damage was done to the unlesioned hemisphere. TABLE 1 CORRECTED MEANPOST-SURGICAL RETRAINING ERRORS TO CRITERIONFOR LESIONED AND UNLESIONED H ~ I S P H E ROF E SFOUR SURGICAL TREATUENT GROUPS
Group
Sham
Lesioned Unlesioned
-3.63 -3.00
Lateral Anterior Medial Anterior
12.17 - 0.50
8.00
Posterior
10.42 3.00
-
4.28
Results of a 2 X 4 analysis of variance done on corrected post-surgical error data are presented in Table 2. Factor A represents lesioned vs unlesioned hemisphere and Factor B represents the 4 surgical treatments. Main effects were statistically reliable, but the second-order interaction was not. Individual comparisons indicated thac operated hemisphere performances for each lesioned TABLE 2
ANALYSIS OF VARIANCE FOR POST-OPERATIVE RETRAINING Source SS df MS F A (Hemisphere) 651.4 1 651.4 6.66 B (Surgical group) A X B Within Groups Total
876.3
5 10.9 4693.4 6732.0
3 3 48 55
292.1 170.3 97.8
2.99 1.74
P C.05 C.05
group were inferior to performances associated with sham-operated hemispheres (aU ps < .05 ), (all p values presented in this paper are 2-railed). Lesioned groups did not differ reliably from each other with respect to performances associated with the lesioned hemisphere. Despite the inflated error for medial anterior lesioned subjects associated with the unlesioned hemispheres, there were no significant differences between surgical treatment groups with respect to the unlesioned hemisphere.
T. J. HOTTMAN, ET AL.
410
The finding of a deficit in rerention of a pattern discrimination discovered by Besley and Sheridan (1973) was thus replicated. W e confirm the great sensitivity of the "interocularly conflicting discrimination" baseline. Even the tiny lesions incidental to sham operations often proved detectable with this baseline. The baseline should provide an interesting supplement to the usual methods of involving bilateral sensory input and bilateral lesioning. The basis or bases of the deficits has not been determined. Considerable further research will be needed to delineate such bases. Though the present findings suggest equiporentiality of different loci, the bases for the deficiencies following lesions in various loci might differ. Deficits due to posterior lesions are not surprising, since these subjects presumably suffered a scotoma due to impingement on primary visual cortex. I t is grossly improbable that the deficits in remaining groups were due to sensory loss. Analyses of the behavioral deficits are needed, now that the phenomenon has been well established. REFERENCES SHERIDAN,C. L. Sensitive method for the detection of experimental brain lesions. Perceptual and Motor Skills, 1973,36, 584-586. CREEL,D. J., & SHERIDAN,C. L. Monocular acquisition and interocular transfer in albino rats with unilateral striate ablations. P~ychonomicScience, 1966, 6 , 89-90. HOREL,J. A., B E ~ N G EL.R A., , ROYCE,G. J., & MEYER,D. R. Role of neocortex in the learning and relearning of two visual habits by the rat. Journal of Comparative and Physiological Psychology, 1966,61,66-78. LASHLEY, K. S. The mechanism of vision: IV. The cerebral areas necessary for pattern vision in the rat. Jourml of Comparative Neurology, 1931, 53, 419-478. LUND, R. D. Uncrossed visual pathways of hooded and albino rats. Science, 1965, 149,
BESLEY, S. S.,
&
1506-1507.
SHERIDAN, C. L. Interocular interaction of conflicting discrimination habits in the albino rat: a preliminary report. Psychonomic Science, 1965, 3, 303-304. SHERIDAN,C. L., & SHROUT, L. L. Differences in the effecriveness of optic uncrossed fiber systems in albino and hooded rats. Psychonomic Science, 1966,4, 177-178.
Accepted ] m e 25,1975.
FURTHER EVALUATION OF A SENSITIVE METHOD FOR DETECTING EXPERIMENTAL BRAIN LESIONS1
TERRY J. HO'JTMAN, ROBERT E. SANDERS, CHRISTINE M. RINCK AND CHARLES L. SHERIDAN Universi~yof Missoasi at Kansas City and Vetman's Administration Hospital Kansar Cicy, Missouri Summary.-Small, unilateral cortical lesions were placed in either medialanterior, lateral-anterior, or posterior cortex of 20 male, Sprague-Dawley, albino rats. In addition, unilateral sham operations were performed on 8 rats from the same stock. All subjects had been trained prior to surgery with diametrically opposed visual habits mediated by opposite cerebral hemispheres. The opposing habits were, insofar as poss~ble,evenly matched prior to surgery. After surgery, lesioned hemispheres, regardless of locus of lesion, were slower in acquiring the habit they mediated, t h a n were unlesioned hemispheres. Further, unlesioned hemispheres dominated in test trials in which subjects chose one of the two cue doors with both eyes open. These findings confirm that the "interocularly conflicting discrimination" baseline detects a role of extrastriate cortex in mediation of pattern discrimination habits. They further indicated that losses occur without regard to the various locations of lesion employed. Besley and Sheridan (1973) described an unusually sensitive merhod for the detection of experimental brain lesions. For over 40 yr., attempts have been made to detect an influence of extrastriate cortical lesions o n visual pattern discriminations in rats (Lashley, 1931; Horel, Bettinger, Royce, & Meyer, 1966); successful identification of such effects was not reported in papers prior to that of Besley and Sheridan (1973). Previous investigators uniformly employed a technique of imposing bilateral lesions on some behavioral baseline involving binocular performance of pattern discriminations. Besley and Sheridan (1973) used a behavioral baseline, previously described by Sheridan (1965 ), i n which diametrically opposite discriminations are established via opposite eyes, and they introduced unilateral extrastriate lesions. Since their subjects were albino rats, in which the uncrossed visual pathways are virtually absent (Lund, 1965) and nonfunctional (Creel & Sheridan, 1966; Sheridan & Shrout, 1966), the effectiveness of their technique was probably due to the existence of a close balance between the opposing discriminations which were presumably mediated by opposite hemispheres. Even a small unilateral lesion was enough to shift the balance in favor of the unoperated hemisphere. Since the study of Besley and Sheridan (1973) stands alone in having demonstrated a deficit in the performance of pattern discrimination following . 'Supported by Research Funds from the United States Veteran's Administration.
408
T. J. HOTTMAN, ET AL.
lesions of extrastriate cortex, the present study was designed to replicate it. Further, the location of the lesions was varied in this study rather than restricted to cortex near the cerebral midline as it had been in the case of Besley and Sheridan (1973).
METHOD Twenty-eight male, Sprague-Dawley albino rats, about 90 days old at the beginning of the experiment, served as subjects. They were trained with diametrically opposite discriminations mediated by opposite eyes until, when challenged, they immediately performed at 90% correct on the original discrimination with the original eye open and at 90% correct on the reversal discrimination with the second eye open. After this training, all subjects were retired to their home cages for 3 wk. and were then retrained on the same schedules. This latter training session (termed the "pre-surgical retraining session") permitted assessment of the effects on the conflicting habits of a protracted lapse in training, and also afforded a degree of overtraining to stabilize each of the habits. After the pre-surgical retraining session, subjects were given unilateral cortical lesions. Most animals underwent both meningeal incision and subpial aspiration of anterior or posterior cortex, but some received only the meningeal insult. Small areas of cortical degeneration following meningeal damage necessitated placing some of the "sham" operated subjects into one of the lesion groups, because the behavioral baseline proved to be sensitive even to such small lesions. Lesioned groups were formed after extensive post-mortem histological examination of the brains. It was of particular interest in this study to determine whether anterior lesions might have interrupted underlying fibers which project to the visual syscem. For subjects with anterior lesions, dorsal lateral geniculate nuclei were examined carefully for cellular asymmetries between right and left geniculates. N o degeneration was detected in any of the subjects reported here. Subjects were divided into a lateral anterior (LA) group ( N .= 6 ) , a medial anterior (MA) group ( N = 7 ) , a posterior (P) group ( N = 7 ) and a sham (S) group ( N = 8). Even the largest lesions did not approach the sizes which failed to impair pattern discrimination in earlier studies. After surgery, animals were given 10 to 12 days recovery time, and then were retrained to criterion just as they had been in the pre-surgical retraining session. This retraining period after recovery from surgery provided post-surgical dependent measures with respect to the learning task. In order to control for any residual, pre-surgical differences in performance, pre-surgical retraining errors were subtracted from post-surgical retraining errors to form a dependent measure. (Effects reported here were even stronger with the simple postsurgical scores.)
DETECTING EXPERIMENTAL BRAIN LESIONS
Table 1 shows the mean numbers of corrected post-surgical retraining errors to criterion for each of the groups. In each group, more errors were associated with the lesioned than with the unlesioned hemisphere. Further; there were more errors associated with lesioned hemispheres than with their sham-operated controls. (Negative numbers indicate thac post-surgical performances were better than pre-surgical performances.) With respect to unoperated hemispheres, post-surgical performances were better than pre-surgical ones in aU but the medial anterior lesioned group, but the deviation of this group was probably due to surgical artifact. Microscopic examination of brains with medial anterior lesions indicated that, because of the midline location of these lesions, some damage was done to the unlesioned hemisphere. TABLE 1 CORRECTED MEANPOST-SURGICAL RETRAINING ERRORS TO CRITERIONFOR LESIONED AND UNLESIONED H ~ I S P H E ROF E SFOUR SURGICAL TREATUENT GROUPS
Group
Sham
Lesioned Unlesioned
-3.63 -3.00
Lateral Anterior Medial Anterior
12.17 - 0.50
8.00
Posterior
10.42 3.00
-
4.28
Results of a 2 X 4 analysis of variance done on corrected post-surgical error data are presented in Table 2. Factor A represents lesioned vs unlesioned hemisphere and Factor B represents the 4 surgical treatments. Main effects were statistically reliable, but the second-order interaction was not. Individual comparisons indicated thac operated hemisphere performances for each lesioned TABLE 2
ANALYSIS OF VARIANCE FOR POST-OPERATIVE RETRAINING Source SS df MS F A (Hemisphere) 651.4 1 651.4 6.66 B (Surgical group) A X B Within Groups Total
876.3
5 10.9 4693.4 6732.0
3 3 48 55
292.1 170.3 97.8
2.99 1.74
P C.05 C.05
group were inferior to performances associated with sham-operated hemispheres (aU ps < .05 ), (all p values presented in this paper are 2-railed). Lesioned groups did not differ reliably from each other with respect to performances associated with the lesioned hemisphere. Despite the inflated error for medial anterior lesioned subjects associated with the unlesioned hemispheres, there were no significant differences between surgical treatment groups with respect to the unlesioned hemisphere.
T. J. HOTTMAN, ET AL.
410
The finding of a deficit in rerention of a pattern discrimination discovered by Besley and Sheridan (1973) was thus replicated. W e confirm the great sensitivity of the "interocularly conflicting discrimination" baseline. Even the tiny lesions incidental to sham operations often proved detectable with this baseline. The baseline should provide an interesting supplement to the usual methods of involving bilateral sensory input and bilateral lesioning. The basis or bases of the deficits has not been determined. Considerable further research will be needed to delineate such bases. Though the present findings suggest equiporentiality of different loci, the bases for the deficiencies following lesions in various loci might differ. Deficits due to posterior lesions are not surprising, since these subjects presumably suffered a scotoma due to impingement on primary visual cortex. I t is grossly improbable that the deficits in remaining groups were due to sensory loss. Analyses of the behavioral deficits are needed, now that the phenomenon has been well established. REFERENCES SHERIDAN,C. L. Sensitive method for the detection of experimental brain lesions. Perceptual and Motor Skills, 1973,36, 584-586. CREEL,D. J., & SHERIDAN,C. L. Monocular acquisition and interocular transfer in albino rats with unilateral striate ablations. P~ychonomicScience, 1966, 6 , 89-90. HOREL,J. A., B E ~ N G EL.R A., , ROYCE,G. J., & MEYER,D. R. Role of neocortex in the learning and relearning of two visual habits by the rat. Journal of Comparative and Physiological Psychology, 1966,61,66-78. LASHLEY, K. S. The mechanism of vision: IV. The cerebral areas necessary for pattern vision in the rat. Jourml of Comparative Neurology, 1931, 53, 419-478. LUND, R. D. Uncrossed visual pathways of hooded and albino rats. Science, 1965, 149,
BESLEY, S. S.,
&
1506-1507.
SHERIDAN, C. L. Interocular interaction of conflicting discrimination habits in the albino rat: a preliminary report. Psychonomic Science, 1965, 3, 303-304. SHERIDAN,C. L., & SHROUT, L. L. Differences in the effecriveness of optic uncrossed fiber systems in albino and hooded rats. Psychonomic Science, 1966,4, 177-178.
Accepted ] m e 25,1975.
