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Parietal and frontal eye field neglect in the rat
Behavioural Brain Research, 22 (1986) 227-231
227
Elsevier BBR 00610
PARIETAL AND FRONTAL EYE FIELD NEGLECT IN THE RAT
D O U G L A S P. CROWNE, C L A U D E T T E M. R I C H A R D S O N and KIM A. D A W S O N
Department of Psychology, University of Waterloo, Waterloo, Ont. (Canada) (Received 25 January 1986) (Revised version received 17 July 1986) (Accepted 17 July 1986)
Key words: Parietal cortex - Frontal eye field - Unilateral lesion - Contralateral neglect
Rats were given unilateral aspiration lesions of parietal, medial frontal, or dorsolateral frontal (motor) cortex and then tested for visual, auditory and tactile neglect, and for circling. All medial frontal lesion animals showed contralateral neglect in each modality and circled ipsiversively. The parietal lesion rats initially displayed contralateral visual and auditory neglect as severe as that in the medial frontal group. Three weeks after the lesions, the parietal group had a smaller residual deficit on the visual test than the medial frontal group. In the first week, parietal animals responded less than the medial frontals to stroking the vibrissae but were more responsive to mild pinching of a toe contralateral to the lesion side. In striking contrast to the medial frontal animals, the parietal group circled strongly to the contralateral side. No rat with a motor cortex lesion neglected or circled preferentially. Like medial frontal cortex, unilateral parietal lesions also produce neglect and circling, but there are important features distinguishing unilateral lesion effects in these two regions.
INTRODUCTION
Among the effects of damage to posterior parietal cortex in humans and monkeys is the syndrome affecting the contralateral side that Denny-Brown e t a l : called amorphosynthesis and that we commonly refer to as neglect. The person or animal does not attend to sensory events on the side opposite the lesion, infrequently moves the affected limbs spontaneously, and misdirects reaching 5-7"9"12. Unilateral lesions in other areas of the brain, cortical and subcortical, also produce contralateral neglect syndromes. Damage to the frontal eye fields, cingulate gyrus, the laminar nuclei of the thalamus, and the reticular formation result in symptoms of neglect ~°'~1. Heilman and c o l l e a g u e s 1°'11"13,14 consider posterior parietal cortex to be a critical region in neglect and in the emotional aberrations that frequently accompany it. Attention to impinging stimuli and affective responsb to them depend on
corticolimbic-reticular arousal loops in each hemisphere. Because of their input from limbic structures (cingulate cortex, lateral hypothalamus, substantia innominata) and reticular formation, and reciprocated projections to the cingulate area and reticular formation ~9"2°, the parietal cortices are dominant structures in those arousal l o o p s 14. In the rat, neglect has been shown to occur after unilateral lesions in several sites - among them, lateral hypothalamus 18, superior colliculus 16 and the frontal eye fields 1'2. In this experiment, we examine the effects of unilateral lesions of parietal cortex and compare them to the sequelae of medial frontal (frontal eye fields) and dorsolateral frontal (motor) cortical lesions. MATERIALS AND M E T H O D S
In 30 male Long-Evans hooded rats, we made unilateral aspiration lesions under sodium pentobarbital anaesthesia of parietal, medial frontal, or
Correspondence: D.P. Crowne, Department of Psychology, University of Waterloo, Waterloo, Ont. N2L 3G1, Canada. 0166-4328/86/$03.50 (© 1986 Elsevier Science Publishers B.V. (Biomedical Division)
228 motor cortex. In each group, n = 10, 5 left and 5 right. Prior to the surgery, the animals were handled daily for one week. During the experiment, they were individually housed, fed ad libitum, and maintained on a normal 12h light-dark cycle. Postoperative testing for neglect of visual, auditory, and tactile stimuli and for circling toward the side of the lesion began 3 days after surgery. Our testing procedures followed those we have previously described 2,3. Briefly, sensory testing was conducted in a small, hemispheric enclosure. The animal was lightly held, and the stimuli (initial side randomly chosen) were presented as soon as it was quiescent and oriented straight ahead. The first test was visual; a sucrose pellet cemented to a 25.5 cm wand was brought into view from the rear and slightly moved for 5 s. The normal response is a vigourous head turn toward the stimulus; neglect is shown by ignoring the stimulus, turning toward the non-stimulated side (an allesthetic response), or turning toward the stimulus but overshooting and not responding to it. For the auditory test, scratching and tapping sounds were made to one side and then the other on the exterior surface of the enclosure. Responses were similar to the visual ones. In the tactile test, the perioral vibrissae were gently stroked with the wooden end of a cottan swab. A nociceptive test concluded the sensory measures. The swab stick was pressed on the outer toe of each forepaw just behind the nail. The normal animal responds by immediate withdrawal and often squeals, while the neglecting rat makes no effort to remove its paw. With the exception of the toe pinch, the stimuli were typically presented at least twice on each side unless a clear response was made. The responses to all of these tests were scored on a 3-point scale (0 = no response; 1 = weak or poorly targeted response; 2 = strong and well-directed response). Circling was assessed in a 2-min observation with the animal in its home cage atop an elevated platform. The number of left and right turns (to the nearest 5Lturn) was recorded. This set of tests was administered postoperatively on days 3, 4 and 5, and on corresponding days of the following 3 weeks. The experimenter was blind to lesion placement in all
A
B
Fig. l. A:dorsolateral view of the cortical lesions. P, Parietal; F, Medial Frontal; M, Motor. Bregma is at O, and the scale is in mm. B: stippling shows area of degeneration in laterodorsal (LD) and lateral posterior (LP) thalamic nuclei resulting from the parietal lesions (only 1 hemisphere shown).
animals throughout the course of testing. With the conclusion of the experiment, the animals were killed, the brains removed, and frozen sections taken for histological analysis. The medial frontal and motor cortex lesions replicated those on which we have previously reported 2'3. The parietal lesions included Brodmann's area 7 and the caudal portion of the region of corticospinal projections. These lesions were similar to case 12 in Jones and Leavitt ~5. Fig. 1 shows the lesion sites and areas of thalamic degeneration. RESULTS
The results, seen in Fig. 2, reveal strong contralateral neglect of the 4 test stimuli in the first postoperative week in the parietal and medial frontal lesion groups. Weak or poorly directed responses characterized the second week, especially on the visual and auditory tests, with some residual visual and auditory impairments lasting into the third week. There was no orienting deficit in the motor cortex l~sion group. Fig. 2 shows that circling did not diminish over 4 weeks. As described in our earlier reports 2'3, the circling of
229 []
Parietal
D
Frontal
[]
Molar
55
4
45
~
25
m or)
Week I
Vis
Aud
Vib
Toe lpsl Contra Clrc C~r¢
Week 5
Week 2
Vis
Aud
Vib
Toe Ipsi ConTra Clrc Clrc
Week 4
Fig. 2. Orienting and circling in the parietal, frontal, and motor cortex lesion groups. A mean orienting score of 6 signifies a complete response on each of the 3 test days in a week. The 4 sensory tests are identified as visual (Vis), auditory (Aud), vibrissae (Vib), and toe pinch (Toe). The ordinate for ipsiversive circling (Ipsi Circ) and contraversive circling (Contra Circ) is to the right.
animals with medial frontal lesions was predominantly ipsiversive. The parietal lesion group displayed an equally strong tendency toward contraversive circling. Significant lesion x week interactions were found for each of the sensory tests (visual: F = 70.22 [6,81], P < 0.001; auditory: F = 3 5 . 5 1 [6,81], P < 0 . 0 0 1 ; vibrissae: F = 26.05 [6,81], P < 0.001 ; toe pinch: F = 42.00 [6,81], P < 0.001). Individual comparisons on data of the first week revealed that the parietal and medial frontal lesion groups did not differ on the visual and auditory tests but did on the vibrissae and toe pinch tests (Fs = 4.40 and 13.99, Ps < 0.05 and 0.001 respectively). The parietal group responded slightly less to stimulation of the whiskers, but was not as affected as the medial frontal animals by pinching of the contralateral toe. The two lesion groups had orienting scores on all 4 tests that were significantly lower than the motor cortex group (P < 0.001 in each case). In the second week, the parietal and medial frontal groups again were not different on the visual and auditory tests but did differ, at P < 0.001, from the motor cortex lesion group. There was no between-groups difference on the vibrissae test. On toe pinch, however, the parietal animals, while differing significantly from the
motor cortex group (P < 0.02), made more consistent and accurate orienting responses on the side contralateral to their lesions to this mildly nociceptive stimulus than did the medial frontal group (P < 0.001). By week 3, the parietal and medial frontal groups had each recovered on the vibrissae and toe pinch tests. Compared to the motor cortex group, both these groups showed residual orienting deficits visually (Ps < 0.02); the medial frontal animals had not recovered as well as the parietals (P < 0.005). On the auditory test, the medial frontal group remained slightly impaired relative to the motor cortex group ( P < 0.005). The neglecting groups had fully regained responsiveness by the fourth week. There was no decrement in ipsiversive or contraversive circling by any of the groups over the month of testing. A significant lesion x directionof-circling interaction (F = 6.99 [ 3,81 ], P < 0.001) and analysis of simple main effects confirmed the potent ipsiversive turning preference of the animals with medial frontal lesions and the contraversive turning of those with parietal lesions. For the ipsiversive-contraversive comparison in the parietal group, F = 4.81 [ 1,81 ], P < 0.05. The same comparison in the medial frontal group gave F = 11.38 [1,81], P < 0.005. Individual comparisons of the lesion groups on each circling direction showed greater ipsiversive circling by the medial frontal animals than by either of the other groups (/med. frontal vs parietal 9.72 [1,53], P < 0.001) and more contraversive circling by the parietal g r o u p (lparietal vs .... ,,,r = 6.77 [1,531, P < 0.001). =
DISCUSSION
A strong contralateral neglect of visual, auditory, and tactile stimuli results from unilateral lesions of both frontal and parietal cortical areas in the rat, as it does in the monkey and in the human. The neglect syndrome from these lesions is more transient in the rat than it is in the monkey. The symptoms of frontal eye field lesions in the monkey typically endure for a month, although there may be long-lasting residual deficits 4'14"17. Extinction to simultaneous stimulation after posterior parietal lesions persists for 2-3
230
months, with some animals failing to recover s . The human typically requires months to show recovery, and some symptoms may last for years 14. Our data show that the contralateral neglect from lesions of parietal cortex closely resembles the orienting deficits following medial frontal damage. This semblance should not be surprising if parietal cortex in the rat has major connections with the frontal eye fields as it does in the monkey ~. There are distinctions, however. Although slight in absolute terms, 3 differences in contralateral responsiveness appeared. (1) Response to somatosensory stimulation was more affected by the parietal lesion, but recovery in both groups occurred rapidly. (2) The parietal lesions produced less impairment in response to mildly painful stimulation than the medial frontal lesions, although in this case too, neglect was short-lived. (3) There was a slightly longer-lasting residual impairment of visual and auditory responsiveness in the medial frontal lesion group. Several lines of evidence suggest that neglect in humans and monkeys is an attention or attentionarousal disorder and not a sensory loss - i.e. a failure of registration ~a°'14. Among them are the facts that neglect is not an absolute deficit ~7, that it frequently results from lesions in other than classical sensory projection systems, and that it may occur in more than one sensory modality. Symptoms of contralateral neglect in the rat are produced by damage to cortical areas that are homologous to those regions in man where neglect follows injury. In rats, polymodal neglect from medial frontal lesions is prevented by a brief period of postoperative maintenance in the dark 3, an effect more consistent with the preservation of attention than with the recovery of sensory systems. Circling was distinguished in an important way from sensory responsiveness, and a striking difference between the parietal and medial frontal lesion groups appeared. While neglect had largely recovered by week 3, the tendency to circle preferentially had not. As long as we measured it, the lesion-produced change in circling remained. This constitutes a significant dissociation in the
rat between the sensory and motor symptoms of these lesions. Animals with medial frontal (frontal eye field) damage circle toward their lesions, perhaps, as Mesulam ~9 suggests, because this cortical region "may contain an inner representation of motor programs for the distribution of exploratory sequences within extrapersonal space" (p. 314). Neglect of one hemifield carries with it the tendency to move in the direction of the intact half of space. The relative persistence of circling would reflect an imbalance between the 2 hemispheres undetected by gross measures of sensory responsiveness. We may note, however, that circling disappears quite early in the recovery sequence in monkeys with frontal eye field lesions 4, and thus there may be a species difference in the persistence of the motor effects of the frontal lesion. Parietal lesions induced circling away from the damaged side, and this was virtually as pronounced as the ipsiversive frontal circling. Parietal, like frontal, cortex has a motor involvement 21. As Mountcastle et al. observe, "'The most obvious change in behavior of a monkey without parietal association cortex is his reluctance to move the contralateral limbs or to project them into extrapersonal space, and the errors he makes when he does so. We infer that these defects reflect the loss of a particular source of commands for movement" (p. 901 ). If we can extrapolate from the movements of contralateral limbs in space of monkeys with parietal lesions to the exploratory ambulations of parietal-damaged rats in their home cages, perhaps contraversive turning derives from a contralateral 'command' deficit that fails to produce adequate movements of the limbs opposite the lesion together with normal motor commands on the side of the lesion. As with the frontal lesion, the continuing tendency to circle would suggest the unequal capacities of the hemispheres. We note that on occasion we have observed contraversive circling in monkeys with unilateral posterior parietal lesions.
ACKNOWLEDGEMENTS
This research was supported by Grant A8262 from the Natural Sciences and Engineering
231
Research Council of Canada to D.P.C. We are grateful for the assistance with histology provided by Kathy Blom.
REFERENCES l Crowne, D.P., The frontal eye field and attention, Psychol. Bull., 93 (1983) 232-260. 2 Crowne, D.P. and Pathria, M.N., Some effects of unilateral frontal lesions in the rat, Behav. Brain Res., 10 (1982) 25-39. 3 Crowne, D.P., Richardson, C.M. and Ward, G., Brief deprivation of vision after unilateral lesions of the frontal eye field prevents contralateral inattention, Science, 220 (1983) 527-530. 4 Crowne, D.P., Yeo, C.H. and Russell, I.S., The effects of unilateral frontal eye field lesions in the monkey: visualmotor guidance and avoidance behaviour, Behav. Brain Res., 2 (1981) 165-187. 5 Denny-Brown, D., Meyer, J.S. and Horenstein, S., The significance of perceptual rivalry resulting from parietal lesion, Brain, 75 (1952) 433-471. 6 Denny-Brown, D. and Chambers, R.A., The parietal lobes and behavior. In The Human Brain and Behavior, Res. Publ. Assoc. Res. Nerv. Ment. Dis., 36 (1958) 35-117. 7 Duell, R.K., Loss of motor habits after non-sensorimotor cortical lesions in monkeys, Neurology, 19 (1969) 294. 8 Eidelberg, E. and Schwartz, A.S., Experimental analysis of the extinction phenomenon in monkeys, Brain, 94 (1971) 91-108. 9 Ettlinger, G. and Kalsbeck, J.E., Changes in tactile discrimination and in visual reaching after successive and simultaneous bilateral posterior parietal ablations in the monkey, J. Neurol. Neurosurg. Psychiatry, 25 (1962) 256-268. 10 Heilman, K.M. and Watson, R.T., Mechanisms underlying the unilateral neglect syndrome. In E.A. Weinstein and R.P. Friedland (Eds.), Advances in Neurology, Vol. 18, Raven Press, New York, 1977.
11 Heilman, K.M. and Watson, R.T., The neglect syndrome - a unilateral defect in the orienting response. In S. Harnad, R.W. Doty, L. Goldstein, J. Jaynes and G. Krauthamer (Eds.), Lateralization in the Nervous System, Academic Press, New York, 1977. 12 Heilman, K.M., Pandya, D.N. and Geschwind, N., Trimodal inattention following parietal lobe ablations, Trans. Am. Neurol. Assoc., 95 (1970) 259-261. 13 Heilman, K.M., Schwartz, H.D. and Watson, R.T., Hypo-arousal in patients with the neglect syndrome and emotional indifference, Neurology, 28 (1978) 229-232. 14 Heilman, K.M., Watson, R.T. and Valenstein, E., Neglect and related disorders. In K.M. Heilman and E. Valenstein (Eds.), ClinicalNeuropsychology, Oxford University Press, New York, 1985, pp. 243-293. 15 Jones, E.G. and Leavitt, R.Y., Retrograde axonal transport and the demonstration of non-specific projections to the cerebral cortex and striatum from thalamic intralaminar nuclei in the rat, cat and monkey, J. Comp. Neurol., 154 (1974) 349-378. 16 Kirvel, R.D., Greenfield, R. and Meyer, D.R., Multimodal sensory neglect in rats with radical unilateral posterior isocortical and superior collicular ablations, J. Comp. Physiol. Psychol., 87 (1974) 156-162. 17 Latto, R. and Cowey, A., Visual field defects after frontal eye-field lesions in monkeys, Brain Res., 30 (1971) 1-24. 18 Marshall, J.F., Turner, B.H. and Teitelbaum, P., Sensory neglect produced by lateral hypothalamic damage, Science, 174 (1971) 523-525. 19 Mesulam, M.-M., A cortical network for directed attention and unilateral neglect, Ann. Neurol., 10 (1981) 309-325. 20 Mesulam, M.-M., Van Hoesen, G.W., Pandya, D.N. and Geschwind, N., Limbic and sensory connections of the inferior parietal lobule (area PG) in the rhesus monkey: a study with a new method for horseradish peroxidase histochemistry, Brain Res., 136 (1977) 393-414. 21 Mountcastle, V.B., Lynch, J.C., Georgopoulos, A., Sakata, H. and Acuna, C., Posterior parietal association cortex of the monkey: command functions for operations within extrapersonal space, J. Neurophysiol., 38 (1975) 871-908.
227
Elsevier BBR 00610
PARIETAL AND FRONTAL EYE FIELD NEGLECT IN THE RAT
D O U G L A S P. CROWNE, C L A U D E T T E M. R I C H A R D S O N and KIM A. D A W S O N
Department of Psychology, University of Waterloo, Waterloo, Ont. (Canada) (Received 25 January 1986) (Revised version received 17 July 1986) (Accepted 17 July 1986)
Key words: Parietal cortex - Frontal eye field - Unilateral lesion - Contralateral neglect
Rats were given unilateral aspiration lesions of parietal, medial frontal, or dorsolateral frontal (motor) cortex and then tested for visual, auditory and tactile neglect, and for circling. All medial frontal lesion animals showed contralateral neglect in each modality and circled ipsiversively. The parietal lesion rats initially displayed contralateral visual and auditory neglect as severe as that in the medial frontal group. Three weeks after the lesions, the parietal group had a smaller residual deficit on the visual test than the medial frontal group. In the first week, parietal animals responded less than the medial frontals to stroking the vibrissae but were more responsive to mild pinching of a toe contralateral to the lesion side. In striking contrast to the medial frontal animals, the parietal group circled strongly to the contralateral side. No rat with a motor cortex lesion neglected or circled preferentially. Like medial frontal cortex, unilateral parietal lesions also produce neglect and circling, but there are important features distinguishing unilateral lesion effects in these two regions.
INTRODUCTION
Among the effects of damage to posterior parietal cortex in humans and monkeys is the syndrome affecting the contralateral side that Denny-Brown e t a l : called amorphosynthesis and that we commonly refer to as neglect. The person or animal does not attend to sensory events on the side opposite the lesion, infrequently moves the affected limbs spontaneously, and misdirects reaching 5-7"9"12. Unilateral lesions in other areas of the brain, cortical and subcortical, also produce contralateral neglect syndromes. Damage to the frontal eye fields, cingulate gyrus, the laminar nuclei of the thalamus, and the reticular formation result in symptoms of neglect ~°'~1. Heilman and c o l l e a g u e s 1°'11"13,14 consider posterior parietal cortex to be a critical region in neglect and in the emotional aberrations that frequently accompany it. Attention to impinging stimuli and affective responsb to them depend on
corticolimbic-reticular arousal loops in each hemisphere. Because of their input from limbic structures (cingulate cortex, lateral hypothalamus, substantia innominata) and reticular formation, and reciprocated projections to the cingulate area and reticular formation ~9"2°, the parietal cortices are dominant structures in those arousal l o o p s 14. In the rat, neglect has been shown to occur after unilateral lesions in several sites - among them, lateral hypothalamus 18, superior colliculus 16 and the frontal eye fields 1'2. In this experiment, we examine the effects of unilateral lesions of parietal cortex and compare them to the sequelae of medial frontal (frontal eye fields) and dorsolateral frontal (motor) cortical lesions. MATERIALS AND M E T H O D S
In 30 male Long-Evans hooded rats, we made unilateral aspiration lesions under sodium pentobarbital anaesthesia of parietal, medial frontal, or
Correspondence: D.P. Crowne, Department of Psychology, University of Waterloo, Waterloo, Ont. N2L 3G1, Canada. 0166-4328/86/$03.50 (© 1986 Elsevier Science Publishers B.V. (Biomedical Division)
228 motor cortex. In each group, n = 10, 5 left and 5 right. Prior to the surgery, the animals were handled daily for one week. During the experiment, they were individually housed, fed ad libitum, and maintained on a normal 12h light-dark cycle. Postoperative testing for neglect of visual, auditory, and tactile stimuli and for circling toward the side of the lesion began 3 days after surgery. Our testing procedures followed those we have previously described 2,3. Briefly, sensory testing was conducted in a small, hemispheric enclosure. The animal was lightly held, and the stimuli (initial side randomly chosen) were presented as soon as it was quiescent and oriented straight ahead. The first test was visual; a sucrose pellet cemented to a 25.5 cm wand was brought into view from the rear and slightly moved for 5 s. The normal response is a vigourous head turn toward the stimulus; neglect is shown by ignoring the stimulus, turning toward the non-stimulated side (an allesthetic response), or turning toward the stimulus but overshooting and not responding to it. For the auditory test, scratching and tapping sounds were made to one side and then the other on the exterior surface of the enclosure. Responses were similar to the visual ones. In the tactile test, the perioral vibrissae were gently stroked with the wooden end of a cottan swab. A nociceptive test concluded the sensory measures. The swab stick was pressed on the outer toe of each forepaw just behind the nail. The normal animal responds by immediate withdrawal and often squeals, while the neglecting rat makes no effort to remove its paw. With the exception of the toe pinch, the stimuli were typically presented at least twice on each side unless a clear response was made. The responses to all of these tests were scored on a 3-point scale (0 = no response; 1 = weak or poorly targeted response; 2 = strong and well-directed response). Circling was assessed in a 2-min observation with the animal in its home cage atop an elevated platform. The number of left and right turns (to the nearest 5Lturn) was recorded. This set of tests was administered postoperatively on days 3, 4 and 5, and on corresponding days of the following 3 weeks. The experimenter was blind to lesion placement in all
A
B
Fig. l. A:dorsolateral view of the cortical lesions. P, Parietal; F, Medial Frontal; M, Motor. Bregma is at O, and the scale is in mm. B: stippling shows area of degeneration in laterodorsal (LD) and lateral posterior (LP) thalamic nuclei resulting from the parietal lesions (only 1 hemisphere shown).
animals throughout the course of testing. With the conclusion of the experiment, the animals were killed, the brains removed, and frozen sections taken for histological analysis. The medial frontal and motor cortex lesions replicated those on which we have previously reported 2'3. The parietal lesions included Brodmann's area 7 and the caudal portion of the region of corticospinal projections. These lesions were similar to case 12 in Jones and Leavitt ~5. Fig. 1 shows the lesion sites and areas of thalamic degeneration. RESULTS
The results, seen in Fig. 2, reveal strong contralateral neglect of the 4 test stimuli in the first postoperative week in the parietal and medial frontal lesion groups. Weak or poorly directed responses characterized the second week, especially on the visual and auditory tests, with some residual visual and auditory impairments lasting into the third week. There was no orienting deficit in the motor cortex l~sion group. Fig. 2 shows that circling did not diminish over 4 weeks. As described in our earlier reports 2'3, the circling of
229 []
Parietal
D
Frontal
[]
Molar
55
4
45
~
25
m or)
Week I
Vis
Aud
Vib
Toe lpsl Contra Clrc C~r¢
Week 5
Week 2
Vis
Aud
Vib
Toe Ipsi ConTra Clrc Clrc
Week 4
Fig. 2. Orienting and circling in the parietal, frontal, and motor cortex lesion groups. A mean orienting score of 6 signifies a complete response on each of the 3 test days in a week. The 4 sensory tests are identified as visual (Vis), auditory (Aud), vibrissae (Vib), and toe pinch (Toe). The ordinate for ipsiversive circling (Ipsi Circ) and contraversive circling (Contra Circ) is to the right.
animals with medial frontal lesions was predominantly ipsiversive. The parietal lesion group displayed an equally strong tendency toward contraversive circling. Significant lesion x week interactions were found for each of the sensory tests (visual: F = 70.22 [6,81], P < 0.001; auditory: F = 3 5 . 5 1 [6,81], P < 0 . 0 0 1 ; vibrissae: F = 26.05 [6,81], P < 0.001 ; toe pinch: F = 42.00 [6,81], P < 0.001). Individual comparisons on data of the first week revealed that the parietal and medial frontal lesion groups did not differ on the visual and auditory tests but did on the vibrissae and toe pinch tests (Fs = 4.40 and 13.99, Ps < 0.05 and 0.001 respectively). The parietal group responded slightly less to stimulation of the whiskers, but was not as affected as the medial frontal animals by pinching of the contralateral toe. The two lesion groups had orienting scores on all 4 tests that were significantly lower than the motor cortex group (P < 0.001 in each case). In the second week, the parietal and medial frontal groups again were not different on the visual and auditory tests but did differ, at P < 0.001, from the motor cortex lesion group. There was no between-groups difference on the vibrissae test. On toe pinch, however, the parietal animals, while differing significantly from the
motor cortex group (P < 0.02), made more consistent and accurate orienting responses on the side contralateral to their lesions to this mildly nociceptive stimulus than did the medial frontal group (P < 0.001). By week 3, the parietal and medial frontal groups had each recovered on the vibrissae and toe pinch tests. Compared to the motor cortex group, both these groups showed residual orienting deficits visually (Ps < 0.02); the medial frontal animals had not recovered as well as the parietals (P < 0.005). On the auditory test, the medial frontal group remained slightly impaired relative to the motor cortex group ( P < 0.005). The neglecting groups had fully regained responsiveness by the fourth week. There was no decrement in ipsiversive or contraversive circling by any of the groups over the month of testing. A significant lesion x directionof-circling interaction (F = 6.99 [ 3,81 ], P < 0.001) and analysis of simple main effects confirmed the potent ipsiversive turning preference of the animals with medial frontal lesions and the contraversive turning of those with parietal lesions. For the ipsiversive-contraversive comparison in the parietal group, F = 4.81 [ 1,81 ], P < 0.05. The same comparison in the medial frontal group gave F = 11.38 [1,81], P < 0.005. Individual comparisons of the lesion groups on each circling direction showed greater ipsiversive circling by the medial frontal animals than by either of the other groups (/med. frontal vs parietal 9.72 [1,53], P < 0.001) and more contraversive circling by the parietal g r o u p (lparietal vs .... ,,,r = 6.77 [1,531, P < 0.001). =
DISCUSSION
A strong contralateral neglect of visual, auditory, and tactile stimuli results from unilateral lesions of both frontal and parietal cortical areas in the rat, as it does in the monkey and in the human. The neglect syndrome from these lesions is more transient in the rat than it is in the monkey. The symptoms of frontal eye field lesions in the monkey typically endure for a month, although there may be long-lasting residual deficits 4'14"17. Extinction to simultaneous stimulation after posterior parietal lesions persists for 2-3
230
months, with some animals failing to recover s . The human typically requires months to show recovery, and some symptoms may last for years 14. Our data show that the contralateral neglect from lesions of parietal cortex closely resembles the orienting deficits following medial frontal damage. This semblance should not be surprising if parietal cortex in the rat has major connections with the frontal eye fields as it does in the monkey ~. There are distinctions, however. Although slight in absolute terms, 3 differences in contralateral responsiveness appeared. (1) Response to somatosensory stimulation was more affected by the parietal lesion, but recovery in both groups occurred rapidly. (2) The parietal lesions produced less impairment in response to mildly painful stimulation than the medial frontal lesions, although in this case too, neglect was short-lived. (3) There was a slightly longer-lasting residual impairment of visual and auditory responsiveness in the medial frontal lesion group. Several lines of evidence suggest that neglect in humans and monkeys is an attention or attentionarousal disorder and not a sensory loss - i.e. a failure of registration ~a°'14. Among them are the facts that neglect is not an absolute deficit ~7, that it frequently results from lesions in other than classical sensory projection systems, and that it may occur in more than one sensory modality. Symptoms of contralateral neglect in the rat are produced by damage to cortical areas that are homologous to those regions in man where neglect follows injury. In rats, polymodal neglect from medial frontal lesions is prevented by a brief period of postoperative maintenance in the dark 3, an effect more consistent with the preservation of attention than with the recovery of sensory systems. Circling was distinguished in an important way from sensory responsiveness, and a striking difference between the parietal and medial frontal lesion groups appeared. While neglect had largely recovered by week 3, the tendency to circle preferentially had not. As long as we measured it, the lesion-produced change in circling remained. This constitutes a significant dissociation in the
rat between the sensory and motor symptoms of these lesions. Animals with medial frontal (frontal eye field) damage circle toward their lesions, perhaps, as Mesulam ~9 suggests, because this cortical region "may contain an inner representation of motor programs for the distribution of exploratory sequences within extrapersonal space" (p. 314). Neglect of one hemifield carries with it the tendency to move in the direction of the intact half of space. The relative persistence of circling would reflect an imbalance between the 2 hemispheres undetected by gross measures of sensory responsiveness. We may note, however, that circling disappears quite early in the recovery sequence in monkeys with frontal eye field lesions 4, and thus there may be a species difference in the persistence of the motor effects of the frontal lesion. Parietal lesions induced circling away from the damaged side, and this was virtually as pronounced as the ipsiversive frontal circling. Parietal, like frontal, cortex has a motor involvement 21. As Mountcastle et al. observe, "'The most obvious change in behavior of a monkey without parietal association cortex is his reluctance to move the contralateral limbs or to project them into extrapersonal space, and the errors he makes when he does so. We infer that these defects reflect the loss of a particular source of commands for movement" (p. 901 ). If we can extrapolate from the movements of contralateral limbs in space of monkeys with parietal lesions to the exploratory ambulations of parietal-damaged rats in their home cages, perhaps contraversive turning derives from a contralateral 'command' deficit that fails to produce adequate movements of the limbs opposite the lesion together with normal motor commands on the side of the lesion. As with the frontal lesion, the continuing tendency to circle would suggest the unequal capacities of the hemispheres. We note that on occasion we have observed contraversive circling in monkeys with unilateral posterior parietal lesions.
ACKNOWLEDGEMENTS
This research was supported by Grant A8262 from the Natural Sciences and Engineering
231
Research Council of Canada to D.P.C. We are grateful for the assistance with histology provided by Kathy Blom.
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