Brain Research, 169 (1979) 183-188 © Elsevier/North-Holland Biomedical Press

183

Role of frontal polyseneory cortex in guidance of limb movements

RUTHMARY K. DEUEL and NANCY L. DUNLOP Departments o f Pediatrics and of Neurology and Neurosurgery, Washington University School oJ Medicine, St. Louis Children's Hospital, P.O. Box 14871, St. Louis, Mo. 63178 (U.S.A.)

(Accepted February 8th, 1979)

In the rhesus monkey, fields in both parietal and frontal cortex have been demonstrated to receive projections from modality specific sensory association zones in preoccipital (visual), temporal (auditory), and parietal (somesthetic) cortex4,11,14,19. When these fields are viewed (disregarding their many other known anatomical and functional features1,2,9,16) as recipients of cortically originating polysensory input, and simultaneously as cortical origins of pathways to motor outflow systemsS,13,19, 23, a role for them in sensory guidance of cortically mediated movements seems plausible. We made bilateral removals of these regions, which we have termed frontal and parietal polysensory cortex (FPC and PPC) to distinguish them from other specified fields in frontal and parietal association cortex, and have previously reported the abnormalities of motor behavior we found 6,s. While primary motility was normal, the abnormalities, profound in FPC animals and mild in PPC animals, were found in retention of the complex motor task of latchbox opening. As manipulation of three separate latches in a fixed sequence was required to open the latchbox, the FPC animals' failure could have been due to their inability to produce a sequence of movements, or to a more basic inability to perform even single movements under some conditions. Our investigation of the effects of FPC and PPC removals on a single contingent movement of the upper extremity forms the basis of this report. To test whether damage in these fields would lead to a deficit in a single purposive motion, we taught the monkey, seated in a primate chair, to respond to a red placard displayed at eye level by raising its left hand from the waistpiece of the chair to its left ear within 10 sec. Following contact of the animal's hand with its ear or fur of the temple on the left side, the animal could obtain a bit of fruit from the center of the bottom of the red placard. During a 10-sec display of a white placard at eye level, the animal was to make no response. Correct withholding of response in this condition was not rewarded. Five seconds were allowed between trials. There were 30 trials daily, with positive and negative trials interspersed in a pseudorandom order so that in every block of 10, there were 5 trials when the animal was required to touch its ear and 5 when it was to withhold response. Subjects were 15 naive rhesus monkeys who were housed in individual cages and fed after their daily test sessions. The 8 animals that subsequently formed the bilateral FPC and PPC groups were first trained

184 and tested on the latchbox and another task6, 8 while the remaining animals were taught only the present task. All animals were first rewarded for removing a small clip from the left ear with the left hand. Soon they touched the ear in the absence of the clip, at the sight of the red placard. After they had mastered all of the task contingencies, waited two weeks, and then undergone retention testing to demonstrate they could maintain performance, they were operated. They weighed from 4.6 to 6 kg at that time. Grey matter was removed by subpial resection from association cortex. The intended FPC removal is shown in Fig. l. It includes both banks of the arcuate sulcus, both banks of the posterior one-third of the principal sulcus plus a triangular portion of cortex dorsomedial to the superior limb of the arcuate sulcus. The FPC overlaps the granular cortical region that is sometimes called 'dorsal prefrontal cortex '1 as well as the agranular areas designated 'periarcuate', 'premotor,' and 'frontal eye field' regions 5,22. Four animals had bilateral FPC removals, 3 left FPC (ipsilateral to the trained hand) only, and 4 right FPC (contralateral to the trained hand) only. Four animals had bilateral PPC (the same as Brodmann's area 7) ~, removals including the

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f Fig. 1. Diagram of the dorsal surface of the intended frontal polysensory cortex lesion with crosssections at the indicated approximate sterotaxic levels to demonstrate the grey matter removals in the depths of the principal and arcuate sulci.

185 inferior bank of the intraparietal sulcus, the anterior bank of the superior temporal sulcus, and grey matter extending rostrally from the convergence of these two sulci to a line perpendicular to the intraparietal sulcus where the Sylvian fissure joins the superior temporal sulcus. For the first 10 weeks after operation animals received only neurological examinations and short retention tests. In the first week, differences among groups were obvious. Animals with bilateral FPC lesions sat at the front of their cages, made little spontaneous movement or vocalization, did not reach for food with their hands, but instead slowly brought their mouths to the food. They had increased reflexes in upper and lower extremities, bilateral grasp and magnet reaction (visually induced grasp) of the hands, and impaired dexterity. Strength in the extremities was normal as were eye movements (both in tracking and in voluntary gaze) and response to pinprick and thermal stimuli. When they began to reach for food, they preferred the preoperatively trained hand. Unilateral FPC animals, in contrast, vocalized and moved frequently (often circling to the side of the lesion). There were severely constricted visual fields contralateral to the lesion, with decreased responsiveness to painful, thermal, and sometimes auditory stimuli on that side. Eye movements were normal toward the side of the lesion, but conjugate gaze away from that side was limited in three animals. Preference was for the hand ipsilateral to the lesion in all cases (the untrained hand in four and the trained hand in 3). Animals with bilateral PPC removals appeared normal, except for misreaching with both hands and difficulty in coordinated use of the two hands for reeling in string baited at the end. These behavioral abnormalities showed progressive recovery in neurological examinations performed at two week intervals, and had resolved in all groups by 10 weeks after operation. Brief retention tests on the learned motor response two weeks after surgery (approximately 16 days after the preoperative retention test) showed that 7 of the 8 animals with an FPC lesion contralateral to the trained hand did raise that (left) hand when the red placard was presented, but 6 of these 7 reached directly for the placard instead of the ear. Their responses, as incorrect, were not rewarded, but did serve to demonstrate that these animals were still capable of distinguishing the red ('respond') from the white ('withhold response') placard, and that memory for at least a fragment (raising the trained hand) of the correct movement was intact. In contrast, animals with only ipsilateral FPC removals performed correctly in 98 % of trials, and bilateral PPC animals performed correctly in 99 % of trials. Beginning 10-weeks after operation, animals that had not shown perfect retention of the task were retrained to criterion: 100 % correct 'response' trials, and 67 % correct 'no response' trials in a given 30 trial session. For the first three sessions of retraining (90 trials), correction was given for errors on 'response' trials. If an animal failed to touch its ear when the red placard was displayed, the red placard was displayed again, but at the same time the clip that had been used in preoperative training was put on the ear. When the animal removed the clip with the left hand, a reward was given as for a correct response. Animals always correctly removed the clip; thus repeatedly demonstrating their ability to carry out the entire correct movement. After the first 90 trials, corrections were eliminated, but daily 30 trial sessions continued until reattainment of criterion.

186 PRE- AND POST-OPERATIVE LEARNING OF LEFT HAND GESTURE TASK 700

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Fig. 2. Pre- and postoperative learning of the 4 groups of animals in terms of trials to reach criterion. Bars represent group medians, with the score of each individual animal shown by a small horizontal line. Group differences, shown in Fig. 2 in terms of trials to criterion postoperatively, were striking. The contralateral FPC group required significantly more trials to relearn than the ipsilateral FPC group (P = 0.01), and the bilateral frontal group more than the parietal (P = 0.01), as evaluated by the Mann-Whitney U test. Errors made by the deficient contralateral and bilateral FPC groups were primarily during 'respond' trials. The contralateral group made errors in 36 ~ , and the bilateral group in 32 ~ of such trials. In contrast the PPC group made errors in only 2 ~ of 'respond' trials, and the ipsilateral group in none. After sacrifice, microscopic examination of brain sections showed relatively uniform removals of the FPC with variation at the anterior edge, where the depths of the sulcus principalis were spared in some brains, and at the inferior border of the arcuate sulcus. Retrograde degeneration was seen in the nucleus medialis dorsalis (the lateral aspects of the multiform and parvocellar regions) and in nuclear area X of Olszewski in the thalamus is. After PPC lesions degeneration was seen where the nucleus pulvinaris abuts lateralis posterior, involving both of these nuclei in all 4 brains. In two, mild lateral geniculate degeneration consequent to invasion of the optic radiations was found. The findings show that the FPC animals can perceive the positive cue, recognize its imperative to act, and can even perform the entire required upper extremity movement. They also show that the animals' memory is intact, or, if not, the memory

187 deficit is highly specific and does not include either recognition of the cue or use of the correct hand and arm for responding. Because the task demands only a single motion to a single response site, a failure of sequencing cannot be basic to this abnormal performance; nor can an attentional or akinetic deficit, since such deficits nonspecifically affect all movements of a given limb 9,7,2z, and even immediately postoperatively the trained limb performed a movement on cue, but this movement was inappropriately directed. Our hypothesis concerning the nature of the deficit derives from the fact that it depends not only on a contralateral FPC removal, but also upon the absence of a simultaneously presented sensory target (the clip). In the absence of the clip, the FPC animals make a movement in the wrong direction and over too short a distance. Thus, the spatial characteristics of the response are impaired. This finding is in accord with physiological evidence that single cells in the FPC are active during delayed alternation and other spatial tasks. Much behavioral evidence for an effect of frontal lesions on use of spatial frames of reference, both in monkey and man 2°,21,24 has already been advanced12,17. Our present findings add the suggestion, at least for the frontal region we removed, that the role it plays in guiding learned spatially directed motor responses is conditional: only when no sensory target is present, or when several equivalent sensory targets are present (as in our latchbox task), need the FPC come into play to program the spatial dimensions of the purposive movement that is about to be performed. This hypothesis not only helps to explain the deficit of our animals with bilateral FPC lesions in our latchbox task, but also offers a new interpretation of deficits after dorsolateral prefrontal removalsg, 15 on spatial discrimination tasks. More experiments are needed to test this hypothesis, and to elucidate the FPC animals' propensity to reach toward the cue when responding incorrectly. The present experiments do, however, indicate that the response abnormality is limited to the limb contralateral to the cortical removal, and thus strongly suggest that if FPC contributes to higher order motor activities, the contribution, in macaques at least, is primarily to activities of the contralateral limb. This work was supported by USPHS Research Grant R01 NS 10601, to Dr. Deuel and by the Allen P. and Josephine B. Green Foundation. A preliminary report of this investigation was presented at the 4th Annual Meeting of the Society for Neurosciences. The authors wish to thank Dr. Mortimer Mishkin for his helpful suggestions. 1 Akert, K., Comparative anatomy of frontal cortex and thalamofrontal connections. In J. M. Warren and K. Akert (Eds.), The Frontal Granular Cortex and Behavior, McGraw-Hill, N.Y., 1964, pp. 372-396. 2 Bianchi, L., The functions of the frontal lobes, Brain, 18 (1895) 497-522. 3 Brodmann, K., Beitr/ige zur histologischen Lokalisation der Grosshirnrinde, 5 Mitteilung. Ober den allgemeinen Bauplan des Cortex Pallii bei den Mammaliern und zwei homologe Rindenfelder im besonderen. Zugleich ein Beitrag zur Furchenlehre, J. Psychol. NeuroL (Leipz.), 6 (1905-1906) 275-400. 4 Chavis, D. A. and Pandya, D. N., Further observations on corticofrontal connections in the rhesus monkey, Brain Research, 117 (1976) 369-386.

188 5 Crosby, E. C., Humphrey, T. and Lauer, E. W., Chapter 7. In Correlative Anatomy of the Nervous System, MacMillan, N.Y., 1962, pp. 480~97. 6 Deuel, R. K., Loss of motor habits after nonsensorimotor cortical lesions in monkeys, Neurology (Minneap.), (1969) 294. 7 Deuel, R. K., Unilateral periarcuate lesions cause loss of motor habit, Proc. Soc. Neurosci. 4th Ann. Meet., 1974, 19. 189. 8 Deuel, R. K., Loss of motor habits after cortical lesions, Neuropsychologia, 15 (1977) 205-215. 9 Goldman, P, S. and Rosvold, H. E., Localization of function within the dorsolateral prefrontal cortex of the rhesus monkey,, Exp. Neurol., 27 (1970) 291-304. 10 Johnson, T. N., Rosvold, H. E. and Mishkin, M., Projections from behaviorally defined sectors of the prefrontal cortex to the basal ganglia septum and diencephalon of the monkey, Exp. Neurol., 21 (1968) 20-34. 11 Jones, E. G. and Powell, T. P., Connexions of the somatic sensory cortex of the rhesus monkey, Brain, 92 (1969) 477-502. 12 Kubota, K., Prefrontal unit activity during delayed-response and delayed-alternation performances, Jap. J. PhysioL, 25 (1975) 481-493. 13 Mettler, F. A., Corticofugal fiber connections of the cortex of Macaca mulatta. The frontal region, J. comp. Neurol., 61 (1935) 509-542. 14 Mesulam, M. M., VanHoesen, G. R., 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 Research, 136 (1977) 393-414. 15 Mishkin, M., Effects of small frontal lesions on delayed alternation in monkeys, J. Neurophysiol., 20 (1967) 615-622. 16 Mountcastle, V. B., Lynch, J., Georgopoulis, A., Sakata, H. and Acuna, C., Posterior parietal association cortex of the monkey, J. NeurophysioL, 38 (1975) 871-908. 17 Niki, H. and Watanabe, M., Prefrontal unit activity and delayed response: Relation to cue location versus direction of response, Brain Research, 105 (1976) 79-88. 18 Olszewski, J., The Thalamus of the Macaca Mulatta, Karger, N.Y., 1952, 86 pp. 19 Pandya, D. N. and Kuypers, H. G., Corticocortical connections in the rhesus monkey, Brain Research, 13 (1969) 13-36. 20 Pohl, W., Dissociation of spatial discrimination deficits following frontal and parietal lesions in monkeys, J. comp. physiol. Psychol., 82 (1973) 227-229. 21 Semmes, J., Weinstein, S., Ghent, L. and Teuber, H. L., Correlates of impaired orientation in personal and extrapersonal space, Brain, 86 (1963) 747-772. 22 Smith, W. K., The Frontal Eye Fields, In Buoy, P. C. (Ed.), The Precentral Motor Cortex, University of Illinois Press, Urbana, Ilk, 1964, pp. 307-342. 23 Strick, P. L., A horseradish peroxidase study of connections of motor cortex, in preparation. 24 Ungerleider, L. G. and Brody, B. A., Extrapersonal sl:atial orientation: The role of posterior parietal, anterior frontal, and inferotemporal cortex, Exp. Neurol., 56 (1977) 265-280. 25 Watson, R. T., Miller, B. D., Heilman, K. M., Non-sensory neglect, Ann. NeuroL, 3 (1978) 505-508

Role of frontal polysensory cortex in guidance of limb movements.

Brain Research, 169 (1979) 183-188 © Elsevier/North-Holland Biomedical Press 183 Role of frontal polyseneory cortex in guidance of limb movements R...
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