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A study on the effect of lesions of area 7 of the parietal cortex on the short-term visual spatial memory of rhesus monkeys (Macaca mulatta)
Brain Research, 600 (1993) 187-192
187
© 1993 Elsevier Science Publishers B.V. All rights reserved 0006-8993/93/$06.00
BRES 18405
A study on the effect of lesions of area 7 of the parietal cortex on the short-term visual spatial memory of rhesus monkeys ( Macaca mulatta) Xiaochun Pu, Yuanye Ma and Jingxia Cai Kunming Institute of Zoology, Academia Sinica, Kunming, Yunnan 650107 (People's Republic of China) (Accepted 4 August 1992)
Key words: R h e s u s monkey (Macaca mulatta); Direct delayed response task; Prefrontal cortex; Lesion; Parietal cortex: Short-term visual spatial memory
This research is focused on the contribution of area 7 to the short-term visual spatial memory. Three rhesus monkeys (Macaca mulatta) were trained in the direct delayed response task in which 5 delay intervals were used in each session. W h e n each monkey reached the criterion of 90% correct responses in 5 successive sessions, two monkeys underwent a surgery while the other one received a sham operation as a control. In the first stage of the surgery, bilateral areas 7a, 7b and Tip of the parietal cortex of two monkeys were precisely lesioned. After 7 days of recuperation, the monkeys were required to do the same task. The average percentage of correct responses in the lesioned animals decreased from 94.7% to 89.3% and 93.3% to 82.0% respectively (no significance, P > 0.05, n = 2). In addition, the monkeys' complex movements were mildly impaired. The lesioned monkeys were found to have difficulty picking up food from the wells. In the second stage, bilateral area 7m was lesioned. In the 5 postoperative sessions, the average percentage of correct responses in one monkey, with a relatively precise 7m lesion, decreased from 94.7% to 92.2% (no significance, P > 0.05), while the other monkey, with widely spread necrosis of lateral parietal cortex, showed an obvious decline in performance, but still over the chance level. After 240 trials this monkey reattained the normal criterion. The results of this research suggest that the lesions of area 7 of the parietal cortex did not significantly affect the short-term visual spatial memory, which has been shown to be sensitive to lesions of the prefrontal cortex; they also support the notion of dissociation of spatial functions in the prefrontal and parietal cortices.
INTRODUCTION The typical visual spatial delayed response (VSDR) task was introduced by Jacobsen as a behavioral measure to study the function of primate prefrontal cortex 12. Many researchers showed that the performance of the VSDR task particularly depended on the integrity of the cortex in and around the principal sulcus. Bilateral lesions of this cortex produced severe impairments in the performance of the VSDR task 4'm. It may be concluded from the former study that the damages in the performance of the VSDR task reflect a difficulty in integrating behavioral acts which are based on spatially and temporally discontinuous events or stimuli. Because this task requires monkeys to keep the spatial information in memory for a short time, it seems overdetermined by virtue of the fact that both spatial and temporal dimensions are critical in this task.
The prefrontal cortex is reciprocally connected to several structures, such as the mediodorsal nucleus of the thalamus (MD), the hippocampus and the amygdala. If the hippocampus and amygdala are ablated, the short-term memory is affected and the ability to perform the VSDR task is markedly decreased ~6. On the other hand, with the aid of split-brain procedures, Glickstein and his collaborators 9 were able to show that at least some proportion of the sens6ry information that the animal uses for the performance of the delayed response task reaches the prefrontal cortex from the posterior areas of the hemisphere by way of transcortical connections. Yamaguchi and Myers 2° showed that the animals with a commissurotomy could transfer the learned experience of the delayed response task from one hemisphere to the other. This fact suggested that the cortico-cortical neural connections are very important for the performance of the
Correspondence." Xiaochun Pu, K u n m i n g Institute of Zoology, Academia Sinica, Kunming, Y u n n a n 650107, People's Republic of China.
188 VSDR task. It is also known that the activity of the neurons located at the principal sulcus can be affected by the angle of the gaze ~. The functional properties of these neurons resemble those of the neurons described in the posterior parietal association cortexr'2. Cavada and his colleagues also demonstrated that each areal subdivision of the posterior parietal cortex was preferentially connected to one specific portion of the principal s u l c u s 5. The prefrontal cortex does not directly receive information
from
the
primary
sensory cortex, while
the
p a r i e t a l a r e a 7 is a v i s u a l a s s o c i a t i o n a r e a r e c e i v i n g p r o j e c t i o n s f r o m b o t h the p r i m a r y visual cortex a n d t h e prefrontal
cortex.
These
discoveries
q u e s t i o n s . In the p e r f o r m a n c e
raised
several
of the VSDR
t a s k , is
a r e a 7 i n v o l v e d in t r a n s m i t t i n g v i s u a l s p a t i a l i n f o r m a t i o n t o t h e p r e f r o n t a l c o r t e x ? Is t h i s t h e o n l y p a t h w a y ? Is t h e i n t e g r i t y o f t h e a r e a 7 a n e c e s s a r y c o n d i t i o n f o r such transmission? This research aimed to investigate and answer these q u e s t i o n s by e x a m i n i n g the e f f e c t s on t h e p e r f o r m a n c e of the VSDR
lk)rced delay period of several seconds, the screen wa~, raised and the monkeys were allowed to choose either the right or left location. -1'o be rewarded the monkeys had to remember where the pcallu! had been placed prior to the enforced delay period. Incorrect choices were neither rewarded nor punished. After this prelimina~' training. the monkeys were required to perform the VSDR task during one session each day. A session consisted of 30 trials. Starting with a 0 s delay, the duration of the delay was increased with 1 s each time the monkeys reached 90% correct responses in 3 consecutive sessions. After 1,000 trials, the final delay duration (n) of each monkey was determined. We defined: A = 0, B = n / 3 , ( ' - 2B, D = n, E - - 4 B and used these 5 kinds of pseudorandom delays to train monkeys m each session. When the monkey reached 90% correct performance for 5 consecutive sessions, the first surgery" was performed in which bilateral areas 7a, 7b and 7ip were ablated. After a week of recuperation, the animals were retested in the same task with the same procedures as in the preoperative test until they reattained the criterion level. After reaching the criterion, the second operation, in which bilateral areas 7m were lesioned, was carried out. The test schedule after the second operation was essentially the same as that after the first operation. No. 3 received a sham surgery as a control. No. 4 was untrained and unoperated and served as a control in the electrophysiological investigation. The surgery was performed aseptically under anesthesia with hydrochloric acidulated ketamine (4 mg/kg) and sodium pentobarbital (20 mg/kg). The cortex was removed with the negative pressure method. After the removal was finished, the dura and skull were resutured.
Electrophysiological incestigations
task a n d t h e visual e v o k e d p o t e n t i a l s
c a u s e d b y t h e s e r i a l a b l a t i o n s o f a r e a s 7a, 7b, 7ip a n d 7m. MATERIALS AND METHODS
Animals and experimental design Four (Nos. 1-4) adult male rhesus monkeys (Macaca mulatta), supplied by the Animal Department of the Institute and previously untrained, served as the subjects in this experiment. Nos. 1-3 were trained in the VSDR task, while No. 4 remained untrained in this research and only served as a control in the electrophysiological investigation. All training was conducted in a modified Wisconsin General Testing Apparatus (WGTA). The monkeys were shown the location of a food morsel in the left or right well, after which the wells were immediately hidden from view by an opaque screen. After an en-
Nos. 1, 3 and 4 were comfortably seated in a primate chair and their visual evoked potentials were recorded at the prefrontal cortex with stainless scalp electrodes. The recording electrode was placed on the projection on the scalp of the caudal one-third of the principal sulcus; the reference electrodes were placed under the lobes of both ears. A flash light was located at 30 cm in front of the monkey. Each stimulus was a flash lasting for 1 ms with an amplitirude of 200 N, and the time between two stimuli was at least 90 s. The visual evoked potentials were recorded and averaged on a Macintosh II computer (30 times). After completion of the behavioral test, the monkeys were given a lethal dose of sodium pentobarbital and perfused intracardially with saline, followed by formaline (10%). The brains were removed, embedded in agar gel, and sectioned at 2 mm in the frontal plane. The sections were stained in accordance with the general method for brain staining 7. The behavioral data were treated with Student's t-test; a P value less than 0.05 was considered to be significant.
Post2nd0p
Post 1 s t Op
I No.3 No.2 .o.,
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,
,
60
120
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360
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Fig. 1. Trials necessary to reach the criterion after operation.
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180
210
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240
270
300
189 RESULTS Considerable experimental experience has demonstrated that the 90% correct response rate is a stable and reasonable criterion of performance in the VSDR task. Our preoperative monkeys were trained to reach this criterion; the postoperative monkeys were trained to reattain this same criterion. The necessary trials required to reach the criterion after the first and the second operations are shown in Fig. 1.
Results following the first operation Histological reconstruction showed that the lesions of areas 7a, 7b and 7ip were restricted to the intended scope (Figs. 2 and 3). Monkeys Nos. 1 and 2, with lesions of areas 7a, 7b and 7ip, showed a poor retention in the first few sessions, but still scored higher than chance level (see Fig. 4B): 4 sessions (120 trials) were required for No. 1 to reattain the 90% correct response rate and 5 sessions (150 trials) for No. 2. The preoperative and postoperative mean correct response rates descreased from 94.7% to 89.3% (No. 1), and from 93.3% to 82.0% (No. 2), but they were still not of significant difference ( P > 0.05). In contrast, No. 3, which had received sham surgery, did not show any decrease in the performance of the VSDR task.
Fig. 3. Lesions of areas 7a, 7b and 7ip in animal No. 2 on the left and right (B) sides.
This fact demonstrates that the ablations of areas 7a, 7b and 7ip, with an additional lesion of 7m, does not produce any significant lasting effect on the performance of the VSDR task (see Fig. 4C).
90 80
v
b
I#preooerate
....{2""" 2=~reooerate
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J-
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40
CHANCE
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3
4
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SESSIONS
f
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,°° t
Results following the second operation The extent of the lesions of area 7m are shown in Figs. 5 and 6. For No. 1, the ablation on the right-hand side was slighter than that of the contralateral cortex, which were both accurately located. For No. 2, the ablation of the left cortex was more severe than that of the other side. In addition, the lateral parietal cortex with the lesions of areas 7a, 7b and 7ip showed an unexpectedly wide-spread necrosis (Fig. 7). After its second operation, No. 1 showed an obvious decrease of the correct response: only 83.3% in the first test sessions. However, in the following tests the animal rapidly reattained the normal criterion of 90%.
A
i O0
~]o,,°'" i =7a,7b,7 ~
7O
8
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CHANCE
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SESSIONS Fig. 2. Lesions of areas 7a, 7b and 7ip in animal No. 1 on the left (A) and right (B) sides.
Fig. 4. Correct responses in the V S D R task. A: preoperation. B: post 1st operation. C: post 2rid operation.
19{)
t i'
Fig. 5. Lesions of area 7m in animal No. 1. on the left (A) and right (B) sides.
50ms Fig. 8. The visual evoked potentials recorded at the prefrontal cortex.
Fig. 6. Lesions of area 7m in animal No. 2. on the left (A) and right (B) sides.
It can also be seen in Fig. 4C, that although No. 2 showed a lower correct response rate during the 7 consecutive test sessions, after its second operation, it still scored higher than the chance level. As many as 8 sessions (240 trials) were required for No. 2 to reattain and retain the normal criterion of 90%. This fact demonstrated that the ablations of areas 7a, 7b and 7ip in combination with lesion of the bilateral areas 7m and the wide-spread necrosis of the lateral cortex, could produce a marked impairment of the performance of the VSDR task; however, the monkey still reserved the ability to reattain the criterion. It is noteworthy that the deficiency of the performance of the VSDR task may not be attributed to a unidimensional factor, but the necrosis of the lateral parietal cortex was undoubtedly an important factor. Certainly, further study will be necessary.
This could be observed obviously in the awake state. No. 1 showed significant difference of the visual evoked potential from No. 4 (see Fig. 9). That No. 3 displayed lower amplitude may be due to its state of anesthesia. These results suggest that at least some amount of visual information is transmitted through the parietalprefrontal connections in the normal monkey.
Disorders of complex movement After removal of areas 7a, 7b and 7ip, the monkeys displayed some disorders in complex movement. Preoperatively, they picked up peanuts quickly from the food wells, but postoperatively they suffered from difficulties to varying degrees, ranging from trembling fingers to the inability to pick up food. Sometimes, even if they were able to pick up the food, they would soon drop it. In time, these movement disorders diminished to some degree. Visually guided research was carried out on No. 2 for 4 months. Because it misjudged the distances, it gazed at the peanut in the food well, stretched its hand to fetch the peanut, but its hand failed to reached the correct location.
Results of the electrophysiological investigation 60
Fig. 8 shows the visual evoked potentials recorded at the projection of the principal sulcus on the scalp. Compared with two control monkeys, either awake (No. 4) or under anesthesia (No. 3), the lesioned monkey (No. 1) shows the lowest amplitude (peak-to-peak).
5O
q~ :I
=
30-
1~
20-
.
10-
NO.1 (awake)
Fig. 7. The widely spread necrosis of the lateral parietal cortex in animal No. 2 on the left (A) and right (B) sides.
NO.3 (anesthetic)
140.4 (awake)
Fig. 9. Comparison of amplitude (peak-to-peak) in the visual evoked potentials of 3 monkeys.
191 TABLE I
Preoperative and postoperative errors Animal
Percentage of errors Preopera tion
No. 1 No. 2
Postoperation
Left
Right
Left
Right
59.5 43
40.5 57
15.2 23
84.8 76.2
Spatial neglect The statistics for the preoperative and postoperative errors of each animal are given in Table I. The postoperative data were significantly different from the random error percentage. Both animals favored their left hand sides; the errors caused by choosing the left location while the peanut was placed on the right side were more numerous. This fact suggests that the lesions caused a contralateral neglect of the favored hand. To test this assumption, a row of peanuts was arranged in front of a lesioned monkey. The monkey always started to pick up peanuts on the left-hand side, while normal monkeys pick the peanuts up randomly. The right side of the lesioned monkey was indeed not paid attention to. However, this inattention to the right side was neither absolute nor long-lasting. DISCUSSION
The most significant discovery in the present study was that area 7 of the parietal cortex is not essential for the performance of the V S D R task. In light of our results, it seems that area 7 does indeed transmit visual information to the prefrontal cortex in the performance of the V S D R task. It seems possible that when a monkey observes a peanut being placed in one of two food wells, the parietal cortex is activated by a flood of incoming sensory data which are transformed into spatial coordinates. It may be the prefrontal cortex, however, that integrates the spatial signals relevant to the task at hand. Thus the lesions of areas 7a, 7b and 7ip produced a decline in correct responses, but after several days. the affected animals reattained the 90% correct criterion. This was also the case for lesions of area 7m. After the second operation, correct responses did indeed decrease, but the 90% correct criterion could be reattained and remained stable. This indicated that the pathway from area 7 to the prefrontal cortex is not the only one that is important for the performance of the V S D R task. The electrophysiological study also provided an important insight into this
problem. Lesions of area 7 partially block the visual pathway from primary visual cortex across parietal cortex to prefrontal cortex; amplitudes of the visual evoked potential recorded at prefrontal cortex are lower than those of normal monkeys. This suggests that some of the visual information may be transmitted from the medial dorsal nucleus, temporal cortex and optic papilla. This may be the reason why no significant effect was produced on the performance of the V S D R task after the lesions. Reciprocal projections from the temporal cortex and optic papilla to the prefrontal cortex probably also play an important role in the spatial visual process; therefore this function does not depend on the integrity of area 7. It has been reported that when the lateral parietal cortex was cooled, animals showed no significant difference from normal animals in the performance of the V S D R task 3. Both these results and ours support the proposal that the visual spatial process of the prefrontal cortex is not significantly affected by lesions of the parietal cortex, and support the idea of dissociation of spatial functions of the prefrontal and parietal cortices 13'~4"1s. The V S D R task, as a behavioral insight into the short-term spatial memory, is only sensitive to the integrity of the principal sulcus of the prefrontal cortex. The lesions of the parietal cortex, temporal cortex or the periarcuate or premotor areas, did not produce significant effects on the performance of the V S D R task ~°-12. We speculate that the parietal cortex is an important cortical center for integrating the spatial somatosensory information. The motor deficiency that the monkeys could not accurately pick up food, may be due to lesions of the parietal cortex. This was obviously the case in No. 2, in which necrosis of the lateral parietal cortex had occurred. Certainly, the determination of the spatial functions of the parietal cortex still requires the use of other more effective behavioral measures. The disorders of complex movements seen in the two lesioned monkeys may be due to the lesion of area 7b. Contrary to areas 7a, 7m and 7ip, area 7b receives few, if any, projections from the visual association areas w. The main input of area 7b is from the primary and secondary somatosensory areas. Area 7b projects selectively to the ventral rim of the principal sulcus, and neurons on the rim of the principal sulcus project to the anterior supplementary motor cortex, where the hand and upper-body representations are located, and also to the mouth and hand areas of the premotor cortex. The lesion of area 7b results in a decline in the amount of sensory information received by the prefrontal cortex and this may contribute to the disorders of movement observed.
192 In this research, the appearance of spatial neglect was also noteworthy. Spatial neglect has been reported in a clinical study in man ~9. For monkeys, it has been reported that unilateral lesion of the parietal cortex produced neglect on the contralateral side ~', and the functional and anatomical asymmetries of the two hemispheres in rhesus monkeys have also been reported ~5. In the present study, it was observed that lesions of the bilateral parietal cortex resulted in contralateral neglect of the favored hand. In our paper, lesions of area 7 produced an imbalance in attention to the left- and right-hand sides. The information from the left side attracted more attention than that from the right. In other words, the right side was neglected. This neglect was not absolute, but was statistically significant. This is undoubtedly an interesting phenomenon worthy of further study. Acknowledgements. This research was supported by National Nature and Science Grant 38970298. Thanks are due to L. Xu. X.T. Hu. K,Y. Xiao and W. Su for their kind help.
REFERENCES 1 Andersen, R.A., Essick, G.K. and Siegel, R.M., The encoding of spatial location by posterior parietal neurons, Science, 230 (1985) 456-458. 2 Andersen, R.A. and Mountcastle, V.B., The influence of the angle of gaze upon the excitability of the light-sensitive neurons of the posterior parietal cortex, J. Neurosci., 3 (1983) 532-548. 3 Bauer, R.H. and Fuester, J.M., The effect of ambient illumination on delayed-matching and delayed-response deficits from cooling dorsolateral prefrontal cortex, Behac. Biol., 22 (1978) 60-66. 4 Butters, N. and Pandya, D., Retention of delayed-alternation: effect of selective lesions of sulcus principalis, Science. 165 (1969) 1271-1273.
5 Cavada, C. and Goldman-Rakic, P.S., Parieto-prefrontal connections in the monkey: topographic distributicm within the prc frontal cortex of sectors connected with the lateral and medial posterior parietal cortex, Soc. Neurosci. Abstr., 11 (1985) 323. 6 Deuel, R.K. and Regan, D..I., Parietal hemineglect and motor deficits in the monkey, Neuropsychology, 23 (1985) 305-314. 7 Du, Z.M., Practical Techniques in Histology, Publishing House of People's Health, China, 1981, pp. 197-198. 8 Funahashi, S., Bruce, C.J. and Goldman-Rakic, P.S.. Visual properties of prefrontal neurons, Soc. Neurosci. Abstl:, l 1 (1985) 525. 9 Glickstein, M., Arora, H.A. and Sperry, R.W., Delayed-response performance foUowing optic tract section, unilateral frontal lesion and commissurotomy, J. Comp. Physiol. Psychol., 56 (1963) 11-18. 10 Goldman, P.S. and Rosvold, H.E., Localization of function within the dorsolateral prefrontal cortex of the rhesus monkey, E.tp. NeuroL, 27 (1970) 291-3//4. 11 Goldman, P.S., Developmental determinants of cortical plasticity, Acta Neurobiol. Exp., 32 (1972) 495-511. 12 Jacobsen, C.F., Studies of cerebral function in primates, Comp. Psychol. Monogr., 13 (1936) 1-68. 13 Kesner, R.P., Farnsworth, G. and DiMattia, B.V, et al., Double dissociation of egocentric and allocentric space following medial prefrontal and parietal cortex lesions in the rat, Behalf. NcuroscL, 103 (1989) 956-961. 14 Kolb, B., Buhrman, K. and Mcdonald, R., Dissociation of prefrontal, posterior parietal and temporal cortical regions to spatial navigation memory in the rat, Soc. Neurosci. Abstr., 1 (1989) 15. 15 Ma, Y.Y., Cai, J.X. and Tian, Y.F., The comparative study of brain asymmetry in six species of living nonhuman primates and tree shrews distributed in China, Acta Anthropol. Sin., 10 (1992). 16 Mishi, M., Degree of memory impairment in monkeys related to amount of conjoint damage to amygdaloid and hippocampal systems, Soc. Neurosci. Abstr., 5 (1979) 320. 17 Pandya, D.N. and Seltzer, B., Intrinsic connections and architertectonics of posterior parietal cortex in rhesus monkeys, J. Comp. Neurol., 204 (1982) 196-210. 18 Semmes, J., Weinstein, S., Ghent, L. and Teuber, H.L., Correlates of impaired orientation in personal and extrapersonal space, Brain, 86 (1963) 747-772. 19 Springer, S,P., Left Brain, Right Brain, Freeman, New York, pp. 159-164. 20 Yamaguchi, S. and Myers, J.E., Prefrontal lobe functions and the neocortical commissures in monkeys, Exp. Brain Res., 18 (1973) 119-130.
187
© 1993 Elsevier Science Publishers B.V. All rights reserved 0006-8993/93/$06.00
BRES 18405
A study on the effect of lesions of area 7 of the parietal cortex on the short-term visual spatial memory of rhesus monkeys ( Macaca mulatta) Xiaochun Pu, Yuanye Ma and Jingxia Cai Kunming Institute of Zoology, Academia Sinica, Kunming, Yunnan 650107 (People's Republic of China) (Accepted 4 August 1992)
Key words: R h e s u s monkey (Macaca mulatta); Direct delayed response task; Prefrontal cortex; Lesion; Parietal cortex: Short-term visual spatial memory
This research is focused on the contribution of area 7 to the short-term visual spatial memory. Three rhesus monkeys (Macaca mulatta) were trained in the direct delayed response task in which 5 delay intervals were used in each session. W h e n each monkey reached the criterion of 90% correct responses in 5 successive sessions, two monkeys underwent a surgery while the other one received a sham operation as a control. In the first stage of the surgery, bilateral areas 7a, 7b and Tip of the parietal cortex of two monkeys were precisely lesioned. After 7 days of recuperation, the monkeys were required to do the same task. The average percentage of correct responses in the lesioned animals decreased from 94.7% to 89.3% and 93.3% to 82.0% respectively (no significance, P > 0.05, n = 2). In addition, the monkeys' complex movements were mildly impaired. The lesioned monkeys were found to have difficulty picking up food from the wells. In the second stage, bilateral area 7m was lesioned. In the 5 postoperative sessions, the average percentage of correct responses in one monkey, with a relatively precise 7m lesion, decreased from 94.7% to 92.2% (no significance, P > 0.05), while the other monkey, with widely spread necrosis of lateral parietal cortex, showed an obvious decline in performance, but still over the chance level. After 240 trials this monkey reattained the normal criterion. The results of this research suggest that the lesions of area 7 of the parietal cortex did not significantly affect the short-term visual spatial memory, which has been shown to be sensitive to lesions of the prefrontal cortex; they also support the notion of dissociation of spatial functions in the prefrontal and parietal cortices.
INTRODUCTION The typical visual spatial delayed response (VSDR) task was introduced by Jacobsen as a behavioral measure to study the function of primate prefrontal cortex 12. Many researchers showed that the performance of the VSDR task particularly depended on the integrity of the cortex in and around the principal sulcus. Bilateral lesions of this cortex produced severe impairments in the performance of the VSDR task 4'm. It may be concluded from the former study that the damages in the performance of the VSDR task reflect a difficulty in integrating behavioral acts which are based on spatially and temporally discontinuous events or stimuli. Because this task requires monkeys to keep the spatial information in memory for a short time, it seems overdetermined by virtue of the fact that both spatial and temporal dimensions are critical in this task.
The prefrontal cortex is reciprocally connected to several structures, such as the mediodorsal nucleus of the thalamus (MD), the hippocampus and the amygdala. If the hippocampus and amygdala are ablated, the short-term memory is affected and the ability to perform the VSDR task is markedly decreased ~6. On the other hand, with the aid of split-brain procedures, Glickstein and his collaborators 9 were able to show that at least some proportion of the sens6ry information that the animal uses for the performance of the delayed response task reaches the prefrontal cortex from the posterior areas of the hemisphere by way of transcortical connections. Yamaguchi and Myers 2° showed that the animals with a commissurotomy could transfer the learned experience of the delayed response task from one hemisphere to the other. This fact suggested that the cortico-cortical neural connections are very important for the performance of the
Correspondence." Xiaochun Pu, K u n m i n g Institute of Zoology, Academia Sinica, Kunming, Y u n n a n 650107, People's Republic of China.
188 VSDR task. It is also known that the activity of the neurons located at the principal sulcus can be affected by the angle of the gaze ~. The functional properties of these neurons resemble those of the neurons described in the posterior parietal association cortexr'2. Cavada and his colleagues also demonstrated that each areal subdivision of the posterior parietal cortex was preferentially connected to one specific portion of the principal s u l c u s 5. The prefrontal cortex does not directly receive information
from
the
primary
sensory cortex, while
the
p a r i e t a l a r e a 7 is a v i s u a l a s s o c i a t i o n a r e a r e c e i v i n g p r o j e c t i o n s f r o m b o t h the p r i m a r y visual cortex a n d t h e prefrontal
cortex.
These
discoveries
q u e s t i o n s . In the p e r f o r m a n c e
raised
several
of the VSDR
t a s k , is
a r e a 7 i n v o l v e d in t r a n s m i t t i n g v i s u a l s p a t i a l i n f o r m a t i o n t o t h e p r e f r o n t a l c o r t e x ? Is t h i s t h e o n l y p a t h w a y ? Is t h e i n t e g r i t y o f t h e a r e a 7 a n e c e s s a r y c o n d i t i o n f o r such transmission? This research aimed to investigate and answer these q u e s t i o n s by e x a m i n i n g the e f f e c t s on t h e p e r f o r m a n c e of the VSDR
lk)rced delay period of several seconds, the screen wa~, raised and the monkeys were allowed to choose either the right or left location. -1'o be rewarded the monkeys had to remember where the pcallu! had been placed prior to the enforced delay period. Incorrect choices were neither rewarded nor punished. After this prelimina~' training. the monkeys were required to perform the VSDR task during one session each day. A session consisted of 30 trials. Starting with a 0 s delay, the duration of the delay was increased with 1 s each time the monkeys reached 90% correct responses in 3 consecutive sessions. After 1,000 trials, the final delay duration (n) of each monkey was determined. We defined: A = 0, B = n / 3 , ( ' - 2B, D = n, E - - 4 B and used these 5 kinds of pseudorandom delays to train monkeys m each session. When the monkey reached 90% correct performance for 5 consecutive sessions, the first surgery" was performed in which bilateral areas 7a, 7b and 7ip were ablated. After a week of recuperation, the animals were retested in the same task with the same procedures as in the preoperative test until they reattained the criterion level. After reaching the criterion, the second operation, in which bilateral areas 7m were lesioned, was carried out. The test schedule after the second operation was essentially the same as that after the first operation. No. 3 received a sham surgery as a control. No. 4 was untrained and unoperated and served as a control in the electrophysiological investigation. The surgery was performed aseptically under anesthesia with hydrochloric acidulated ketamine (4 mg/kg) and sodium pentobarbital (20 mg/kg). The cortex was removed with the negative pressure method. After the removal was finished, the dura and skull were resutured.
Electrophysiological incestigations
task a n d t h e visual e v o k e d p o t e n t i a l s
c a u s e d b y t h e s e r i a l a b l a t i o n s o f a r e a s 7a, 7b, 7ip a n d 7m. MATERIALS AND METHODS
Animals and experimental design Four (Nos. 1-4) adult male rhesus monkeys (Macaca mulatta), supplied by the Animal Department of the Institute and previously untrained, served as the subjects in this experiment. Nos. 1-3 were trained in the VSDR task, while No. 4 remained untrained in this research and only served as a control in the electrophysiological investigation. All training was conducted in a modified Wisconsin General Testing Apparatus (WGTA). The monkeys were shown the location of a food morsel in the left or right well, after which the wells were immediately hidden from view by an opaque screen. After an en-
Nos. 1, 3 and 4 were comfortably seated in a primate chair and their visual evoked potentials were recorded at the prefrontal cortex with stainless scalp electrodes. The recording electrode was placed on the projection on the scalp of the caudal one-third of the principal sulcus; the reference electrodes were placed under the lobes of both ears. A flash light was located at 30 cm in front of the monkey. Each stimulus was a flash lasting for 1 ms with an amplitirude of 200 N, and the time between two stimuli was at least 90 s. The visual evoked potentials were recorded and averaged on a Macintosh II computer (30 times). After completion of the behavioral test, the monkeys were given a lethal dose of sodium pentobarbital and perfused intracardially with saline, followed by formaline (10%). The brains were removed, embedded in agar gel, and sectioned at 2 mm in the frontal plane. The sections were stained in accordance with the general method for brain staining 7. The behavioral data were treated with Student's t-test; a P value less than 0.05 was considered to be significant.
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189 RESULTS Considerable experimental experience has demonstrated that the 90% correct response rate is a stable and reasonable criterion of performance in the VSDR task. Our preoperative monkeys were trained to reach this criterion; the postoperative monkeys were trained to reattain this same criterion. The necessary trials required to reach the criterion after the first and the second operations are shown in Fig. 1.
Results following the first operation Histological reconstruction showed that the lesions of areas 7a, 7b and 7ip were restricted to the intended scope (Figs. 2 and 3). Monkeys Nos. 1 and 2, with lesions of areas 7a, 7b and 7ip, showed a poor retention in the first few sessions, but still scored higher than chance level (see Fig. 4B): 4 sessions (120 trials) were required for No. 1 to reattain the 90% correct response rate and 5 sessions (150 trials) for No. 2. The preoperative and postoperative mean correct response rates descreased from 94.7% to 89.3% (No. 1), and from 93.3% to 82.0% (No. 2), but they were still not of significant difference ( P > 0.05). In contrast, No. 3, which had received sham surgery, did not show any decrease in the performance of the VSDR task.
Fig. 3. Lesions of areas 7a, 7b and 7ip in animal No. 2 on the left and right (B) sides.
This fact demonstrates that the ablations of areas 7a, 7b and 7ip, with an additional lesion of 7m, does not produce any significant lasting effect on the performance of the VSDR task (see Fig. 4C).
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Results following the second operation The extent of the lesions of area 7m are shown in Figs. 5 and 6. For No. 1, the ablation on the right-hand side was slighter than that of the contralateral cortex, which were both accurately located. For No. 2, the ablation of the left cortex was more severe than that of the other side. In addition, the lateral parietal cortex with the lesions of areas 7a, 7b and 7ip showed an unexpectedly wide-spread necrosis (Fig. 7). After its second operation, No. 1 showed an obvious decrease of the correct response: only 83.3% in the first test sessions. However, in the following tests the animal rapidly reattained the normal criterion of 90%.
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SESSIONS Fig. 2. Lesions of areas 7a, 7b and 7ip in animal No. 1 on the left (A) and right (B) sides.
Fig. 4. Correct responses in the V S D R task. A: preoperation. B: post 1st operation. C: post 2rid operation.
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Fig. 5. Lesions of area 7m in animal No. 1. on the left (A) and right (B) sides.
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Fig. 6. Lesions of area 7m in animal No. 2. on the left (A) and right (B) sides.
It can also be seen in Fig. 4C, that although No. 2 showed a lower correct response rate during the 7 consecutive test sessions, after its second operation, it still scored higher than the chance level. As many as 8 sessions (240 trials) were required for No. 2 to reattain and retain the normal criterion of 90%. This fact demonstrated that the ablations of areas 7a, 7b and 7ip in combination with lesion of the bilateral areas 7m and the wide-spread necrosis of the lateral cortex, could produce a marked impairment of the performance of the VSDR task; however, the monkey still reserved the ability to reattain the criterion. It is noteworthy that the deficiency of the performance of the VSDR task may not be attributed to a unidimensional factor, but the necrosis of the lateral parietal cortex was undoubtedly an important factor. Certainly, further study will be necessary.
This could be observed obviously in the awake state. No. 1 showed significant difference of the visual evoked potential from No. 4 (see Fig. 9). That No. 3 displayed lower amplitude may be due to its state of anesthesia. These results suggest that at least some amount of visual information is transmitted through the parietalprefrontal connections in the normal monkey.
Disorders of complex movement After removal of areas 7a, 7b and 7ip, the monkeys displayed some disorders in complex movement. Preoperatively, they picked up peanuts quickly from the food wells, but postoperatively they suffered from difficulties to varying degrees, ranging from trembling fingers to the inability to pick up food. Sometimes, even if they were able to pick up the food, they would soon drop it. In time, these movement disorders diminished to some degree. Visually guided research was carried out on No. 2 for 4 months. Because it misjudged the distances, it gazed at the peanut in the food well, stretched its hand to fetch the peanut, but its hand failed to reached the correct location.
Results of the electrophysiological investigation 60
Fig. 8 shows the visual evoked potentials recorded at the projection of the principal sulcus on the scalp. Compared with two control monkeys, either awake (No. 4) or under anesthesia (No. 3), the lesioned monkey (No. 1) shows the lowest amplitude (peak-to-peak).
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191 TABLE I
Preoperative and postoperative errors Animal
Percentage of errors Preopera tion
No. 1 No. 2
Postoperation
Left
Right
Left
Right
59.5 43
40.5 57
15.2 23
84.8 76.2
Spatial neglect The statistics for the preoperative and postoperative errors of each animal are given in Table I. The postoperative data were significantly different from the random error percentage. Both animals favored their left hand sides; the errors caused by choosing the left location while the peanut was placed on the right side were more numerous. This fact suggests that the lesions caused a contralateral neglect of the favored hand. To test this assumption, a row of peanuts was arranged in front of a lesioned monkey. The monkey always started to pick up peanuts on the left-hand side, while normal monkeys pick the peanuts up randomly. The right side of the lesioned monkey was indeed not paid attention to. However, this inattention to the right side was neither absolute nor long-lasting. DISCUSSION
The most significant discovery in the present study was that area 7 of the parietal cortex is not essential for the performance of the V S D R task. In light of our results, it seems that area 7 does indeed transmit visual information to the prefrontal cortex in the performance of the V S D R task. It seems possible that when a monkey observes a peanut being placed in one of two food wells, the parietal cortex is activated by a flood of incoming sensory data which are transformed into spatial coordinates. It may be the prefrontal cortex, however, that integrates the spatial signals relevant to the task at hand. Thus the lesions of areas 7a, 7b and 7ip produced a decline in correct responses, but after several days. the affected animals reattained the 90% correct criterion. This was also the case for lesions of area 7m. After the second operation, correct responses did indeed decrease, but the 90% correct criterion could be reattained and remained stable. This indicated that the pathway from area 7 to the prefrontal cortex is not the only one that is important for the performance of the V S D R task. The electrophysiological study also provided an important insight into this
problem. Lesions of area 7 partially block the visual pathway from primary visual cortex across parietal cortex to prefrontal cortex; amplitudes of the visual evoked potential recorded at prefrontal cortex are lower than those of normal monkeys. This suggests that some of the visual information may be transmitted from the medial dorsal nucleus, temporal cortex and optic papilla. This may be the reason why no significant effect was produced on the performance of the V S D R task after the lesions. Reciprocal projections from the temporal cortex and optic papilla to the prefrontal cortex probably also play an important role in the spatial visual process; therefore this function does not depend on the integrity of area 7. It has been reported that when the lateral parietal cortex was cooled, animals showed no significant difference from normal animals in the performance of the V S D R task 3. Both these results and ours support the proposal that the visual spatial process of the prefrontal cortex is not significantly affected by lesions of the parietal cortex, and support the idea of dissociation of spatial functions of the prefrontal and parietal cortices 13'~4"1s. The V S D R task, as a behavioral insight into the short-term spatial memory, is only sensitive to the integrity of the principal sulcus of the prefrontal cortex. The lesions of the parietal cortex, temporal cortex or the periarcuate or premotor areas, did not produce significant effects on the performance of the V S D R task ~°-12. We speculate that the parietal cortex is an important cortical center for integrating the spatial somatosensory information. The motor deficiency that the monkeys could not accurately pick up food, may be due to lesions of the parietal cortex. This was obviously the case in No. 2, in which necrosis of the lateral parietal cortex had occurred. Certainly, the determination of the spatial functions of the parietal cortex still requires the use of other more effective behavioral measures. The disorders of complex movements seen in the two lesioned monkeys may be due to the lesion of area 7b. Contrary to areas 7a, 7m and 7ip, area 7b receives few, if any, projections from the visual association areas w. The main input of area 7b is from the primary and secondary somatosensory areas. Area 7b projects selectively to the ventral rim of the principal sulcus, and neurons on the rim of the principal sulcus project to the anterior supplementary motor cortex, where the hand and upper-body representations are located, and also to the mouth and hand areas of the premotor cortex. The lesion of area 7b results in a decline in the amount of sensory information received by the prefrontal cortex and this may contribute to the disorders of movement observed.
192 In this research, the appearance of spatial neglect was also noteworthy. Spatial neglect has been reported in a clinical study in man ~9. For monkeys, it has been reported that unilateral lesion of the parietal cortex produced neglect on the contralateral side ~', and the functional and anatomical asymmetries of the two hemispheres in rhesus monkeys have also been reported ~5. In the present study, it was observed that lesions of the bilateral parietal cortex resulted in contralateral neglect of the favored hand. In our paper, lesions of area 7 produced an imbalance in attention to the left- and right-hand sides. The information from the left side attracted more attention than that from the right. In other words, the right side was neglected. This neglect was not absolute, but was statistically significant. This is undoubtedly an interesting phenomenon worthy of further study. Acknowledgements. This research was supported by National Nature and Science Grant 38970298. Thanks are due to L. Xu. X.T. Hu. K,Y. Xiao and W. Su for their kind help.
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