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Multiple representation in the primate motor cortex
366
Brain Research, i 54 (1978) 366~ ~70 i ) Elsevier/North-Holland Biomedical P,-ess
Multiple representation in the primate motor cortex
P E T E R L. STRICK and JAMES B. PRESTON Research Service, Veterans Administration and Departments oj Neurosurgery and Physh~togy, Ispsrate Medical Center. Syracuse, N. Y. ( U. S. A. (Accepted May 18th, 1978)
The classical view of somatotopic organization in the motor cortex is that a single continuous representation of body parts exists within the primary motor area. This concept of cortical representation was derived from studies in a variety of species including man, in which movements were evoked following cortical surface stimulation a~, 15,16
Woolsey et al. summarized their findings by portraying the representation in primary motor cortex as a distorted map o f the body parts in which each part had a single representation. However, they were quick to note that such a diagram did not completely represent their findings 'since in a line drawing one cannot indicate the successive overlap which is so characteristic a feature of cortical representation' (see p. 252) 16. A number of models have been proposed in an attempt to better describe the fine structure of motor cortex output 1,3,4,6, s,9, r~. It occurred to us that multiple representations of a body part might be buried within the 'successive overlap" observed in these earlier studies. This concept of cortical organization finds support from recent studies which have challenged the classical concept of a single sensory representation within the primary somatosensory cortex 1° In order to explore the possibility that multiple representations exist within area 4, we elected to map the arm area of the primary motor cortex in the squirrel monkey using intracortical microstimulation 4. We chose the squirrel monkey because none of the arm or hand m o t o r representation is buried within a sulcus in this primate 13. The results of our experiments demonstrate that the wrist and hand are represented twice in area 4. Squirrel monkeys fSaimiri sciureusJ were anesthetized with 10 mg/kg ketamine hydrogen chloride given intramuscularly and 25 mg/kg ofpentobarbitat sodium given intraperitoneally. Supplemental i.m doses of ketamine hydrogen chloride were given as needed to maintain anesthesia. A plastic cylinder was fixed over the forelimb area of the motor cortex. The cylinder was filled with warm mineral oil and formed the base of a closed chamber system 5. The m o t o r cortex was mapped using intracortical microstimulation to evoke movements of the contralateral forelimb. Glass coated, platinum-iridium micro-
367 electrodes with impendances of 0.7 to 1.5 M ~ were driven into the motor cortex approximately perpendicular to its surface. As in the Cebus monkey a, the lowest threshold points for evoking muscle contractions were located approximately 1.5 mm below the surface of the cortex. Histology has confirmed this depth to be within the Betz cell layer. Stimulation consisted of a 50-60 msec cathodal pulse train delivered at a frequency of 300-400 Hz with a pulse duration of 0.2 msec. Thresholds for evoking movements varied between 1.0 and 25/~A (in most cases below I0 #A). The effects of microstimulation were determined by muscle palpation, visual inspection, and in some cases verified by E M G recording. Microstimulation in area 4, in the region rostral to area 3a, evoked movements of the hand (thumb and fingers). A zone from which predominately wrist and radioulnar joint movements were evoked (wrist flexion and extension, wrist ulnar and radial deviation, and forearm supination and pronation) was found just rostral to the hand zone. Rostral to this wrist zone there was an abrupt transition to a zone from which thumb and finger movements were once again evoked. The presence of this second zone of hand representation in area 4 does not conform to the classical viewpoint of motor cortex representation. Although classical maps of the motor cortex demonstrate some overlap in the representation of body partsa'5, t6, the basic pattern is one in which movements of more proximal portions of the limb are evoked from points rostral to a single area of hand representation. Thus, in contrast to maps derived from surface stimulation, our microstimulation studies have demonstrated a discrete second representation for the hand. Furthermore, immediately rostral to the second hand zone lies another zone in which movements of the wrist and radioulnarjoint are again evoked. Low intensity microstimulation did not evoke additional hand movements rostral to this second wrist representation. We will call the hand and wrist zones nearest the central fissure the caudal representation and the second hand and wrist zones, which are more remote from the central fissure, the rostral representation. In general the same muscles were activated at similar threshold currents in both representations. Histological analysis of the sites of lesions marking both caudal and rostral representations demonstrated that both were located in area 4. Fig. 1 illustrates some of our findings. Figure IA depicts an oblique view of the left hemisphere of the squirrel monkey. The parallelogram outlined on the cortical surface (labeled B) represents a segment of area 4. Located within this segment is the center of the hand-wrist region, as well as the transition between caudal and rostral representations. The line of transition between the two representations was 4 mm from the central fissure in the animal illustrated. In 4 other animals the line of transition was located from 3.7 to 4.2 mm rostral to the central fissure. Fig. 1B is an enlarged view of the parallelogram labeled B in Fig. I A. Each symbol shows the site of one microelectrode penetration made in this 2 ><, 2 millimeter area. The relatively large spaces where penetrations were not made were regions occupied by surface blood vessels. The filled circles represent sites from which thumb or finger movements were evoked and the open circles are sites where stimulation evoked movements of the wrist or radioulnar joint. Note the clustering of like responses which
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Fig. 1. A: oblique view of squirrel monkey left hemisphere. Parallelogram (labeled B) represents a 2 ~ 2 mm segment of area 4 at the center of the hand-wrist representation. The line caudal (to the right) and medial to (above) the parallelogram indicates the location of the central fissure. B: enlarged view of parallelogram in Fig. 1A. Symbols indicate sites of microelectrode penetrations. Filled circles are sites where thumb and finger movements were evoked. Open circles are sites where wrist or radioutnar movements were evoked, The dashed line indicates the border between the two motor representations. C: graph of results from 3 animals. Comparable 2 x 2 mm parallelograms from 3 animals were divided into 8 equal mediolateral bands. Parallelograms were aligned on the border between the two representations (dashed line). Each bar represents the percentage of hand (above) and wrist (below) responses seen in each band. See text.
t e n d to orient in mediolateral bands, a n d the a l t e r n a t i o n of the h a n d a n d wrist bands. The dashed line was placed by eye a n d is the b o r d e r between the caudal a n d rostral representations i n this animal. Fig. 1C is a n a t t e m p t to represent the results f r o m several e x p e r i m e n t s i n a semiq u a n t i t a t i v e fashion. I n order to summarize results from different animals, the border between the rostral a n d caudal representations was used to align the maps of 3 animals. I n these a n i m a l s a sufficient n u m b e r of p e n e t r a t i o n s were made a r o u n d t h e b o r d e r region to unequivocally define it. In each animal, s t i m u l a t i o n sites n e a r the center o f the forelimb r e p r e s e n t a t i o n a n d within a 2 x 2 m m area c o n t a i n i n g the border between the rostral a n d caudal representations were used in c o n s t r u c t i n g the graph i n Fig. 1C. In all, 134 s t i m u l a t i o n sites were c o n t a i n e d within these three 2 × 2 m m areas of cortex. Each of the 2 x 2 m m areas was divided into eight 250 # m mediolateral b a n d s a n d the
369 number of sites from which we elicited movements of thumb-fingers and wrist-radioulnar joint were separately totaled for each band. In Fig. 1C the vertical bars represent the eight bands. The length of the bar above the horizontal '0' line represents the percentage of thumb-finger responses and the length below represents the percentage of wrist-radioulnar joint responses. Although there are hand and wrist responses in each band, this overlap is not sufficient to mask a clearly defined double representation even when the results from 3 animals are lumped together. There has been controversy concerning the interpretation of results from microstimulation studies I 4,v,s,14. Regardless of the neuronal elements activated by microstimulation, our results indicate that the concentrations of points from which hand movements are evoked peak in two spatially separated zones within area 4. The same is true for wrist movements. This observation most likely reflects a similar spatial distribution of output neurons. K wan et al.9 recently have reexamined the representation of the body,particularly the forelimb, in the motor cortex of the stump-tailed monkey. Our findings in the handwrist representation differ from theirs in that they did not report a double representation which we have found in the squirrel monkey. In the stump-tailed monkey, the difficulty in reconstructing the topography within the depths of the central sulcus may account for this difference. The demonstration of a double representation within the forearm region of area 4 in the squirrel monkey raises several questions. First, is multiple representation in the motor cortex limited to the forearm motor representation? As yet we have not explored other regions of the motor cortex. Second, is this pattern of multiple representation species specific or is it a general feature of motor cortex organization? Evidence from microstimulation studies in the cat suggests that a multiple representation of the forelimb also exists in the motor cortex of this species (Pappas and Strick, submitted for publication). Finally, what is the functional significance of multiple representations in area 4? Our hypothesis is that the double representation reflects two motor control systems within area 4 that deal with different components of motor behavior. While it would be surprising if these systems are completely independent, they may have been anatomically separated to facilitate differential control over their input and/or output. The study was supported in part by funds from the Veterans Administration Medical Research Fund and USPHS Grant NS02957.
1 Anderson, P., Hagan, P. J., Phillips, C. G. and Powell, T. P. S., Mapping by microstimulation of overlapping projections from area 4 to motor units of the baboon's hand, Proc. roy. Soc. B, 188 (1975) 31-60. 2 Asanuma, H. and Arnold, A. P., Noxious effects of excessivecurrents used for intracortical microstimulation, Brain Research, 96 (1975) 103-107. 3 Asanuma, H. and Rosen, I., Topographical organization of cortical efferent zones projecting to distal forelimb muscles in the monkey, Exp. Brain Res., 14 (1972) 243-256.
370 4 Asanuma, H. and Sakata, H., Functional organization of a cortical efferent system examined with focal depth stimulation in cats, J. Neurophysiol., 30 (1967) 35 54. 5 Davies, P. W., Chamber for microelectrode studies in the cerebral cortex, Scieltce, t 24 (1956) 179 180. 6 Evarts, E. V., Representation of movements and muscles by pyramidal tract neurons of the precentral motor cortex. In M. D. Yahr and D. P. Purpura (Eds.) Neurophysiological B~isi., O/+~rmatand Abnormal Motor Activities, Raven Press, New York, 1967, pp. 215-254. 7 Jankowska, E., Padel, Y. and Tanaka, R., The mode of activation of pyramidal tract cells by intra+ cortical stimuli, J. Physiol. (Lond.), 249 (1975) 617-636. 8 Jankowska, E., Padel, Y. and Tanaka, R., Projections of pyramidal tract cells to a-motoneurones innervating hindlimb muscles in the monkey, J. Physiol. (Lond.), 249 (1975) 637~667. 9 Kwan, H. C., MacKay, W. A., Murphy, J. T. and Wong, Y. C., An intracortical microstimulation study of output organization in precentral cortex of awake primates, J. Physiol. (Paris), in press. 10 Paul, R. L., Merzenich, M. and Goodman, H., Representation of slowly and rapidly adapting cutaneous mechanoreceptors of the hand in Brodmann's areas 3 and 1 of Mocaea mulatto, Brain Research, 36 (1972) 229-249. 11 Penfield, W. and Rasmussen, T., The Cerebral Cortex o/Mon, MacMillan, New York, 1950, pp. I1 65. 12 Phillips, C. G., The Ferrier Lecture. Motor apparatus of the baboon's hand, Proe+ roy: Soc. B, 173 (1969) 141 174. 13 Sanides, F., The architecture of the cortical taste nerve areas in squirrel monkey (Saimiri sciureus) and their relationships to insular, sensorimotor and prefrontal regions, Brain Research, 8 (I 968) 97--124. 14 Stoney, S. D., Jr., Thompson, W. D. and Asanuma, H., Excitation of pyramidal tract Cells by intra~ cortical microstimulation: Effective extent of stimulating current, J. Neurophysiol., 3 i (1968) 659+: 669. 15 Welker, W. I., Benjamin, R. M., Miles, R. C. and Woolsey, C. N., Motor effects of stimulation of cerebral cortex of squirtet monkey (Saimiri seiureus), J. Neurophysiol., 20 (1957) 347- 364. 16 Woolsey, C. N., Settlage, P. H., Meyer, D. R., Sencer, W., Pinto Hamuy, T. and Travis, A. M., Patterns of localization in precentral and +supplementary' motor areas and their relation to the c0n, cept of a premotor area, Res. Publ. Ass. nerv. ment. Dis., 30 (1952) 238-264.
Brain Research, i 54 (1978) 366~ ~70 i ) Elsevier/North-Holland Biomedical P,-ess
Multiple representation in the primate motor cortex
P E T E R L. STRICK and JAMES B. PRESTON Research Service, Veterans Administration and Departments oj Neurosurgery and Physh~togy, Ispsrate Medical Center. Syracuse, N. Y. ( U. S. A. (Accepted May 18th, 1978)
The classical view of somatotopic organization in the motor cortex is that a single continuous representation of body parts exists within the primary motor area. This concept of cortical representation was derived from studies in a variety of species including man, in which movements were evoked following cortical surface stimulation a~, 15,16
Woolsey et al. summarized their findings by portraying the representation in primary motor cortex as a distorted map o f the body parts in which each part had a single representation. However, they were quick to note that such a diagram did not completely represent their findings 'since in a line drawing one cannot indicate the successive overlap which is so characteristic a feature of cortical representation' (see p. 252) 16. A number of models have been proposed in an attempt to better describe the fine structure of motor cortex output 1,3,4,6, s,9, r~. It occurred to us that multiple representations of a body part might be buried within the 'successive overlap" observed in these earlier studies. This concept of cortical organization finds support from recent studies which have challenged the classical concept of a single sensory representation within the primary somatosensory cortex 1° In order to explore the possibility that multiple representations exist within area 4, we elected to map the arm area of the primary motor cortex in the squirrel monkey using intracortical microstimulation 4. We chose the squirrel monkey because none of the arm or hand m o t o r representation is buried within a sulcus in this primate 13. The results of our experiments demonstrate that the wrist and hand are represented twice in area 4. Squirrel monkeys fSaimiri sciureusJ were anesthetized with 10 mg/kg ketamine hydrogen chloride given intramuscularly and 25 mg/kg ofpentobarbitat sodium given intraperitoneally. Supplemental i.m doses of ketamine hydrogen chloride were given as needed to maintain anesthesia. A plastic cylinder was fixed over the forelimb area of the motor cortex. The cylinder was filled with warm mineral oil and formed the base of a closed chamber system 5. The m o t o r cortex was mapped using intracortical microstimulation to evoke movements of the contralateral forelimb. Glass coated, platinum-iridium micro-
367 electrodes with impendances of 0.7 to 1.5 M ~ were driven into the motor cortex approximately perpendicular to its surface. As in the Cebus monkey a, the lowest threshold points for evoking muscle contractions were located approximately 1.5 mm below the surface of the cortex. Histology has confirmed this depth to be within the Betz cell layer. Stimulation consisted of a 50-60 msec cathodal pulse train delivered at a frequency of 300-400 Hz with a pulse duration of 0.2 msec. Thresholds for evoking movements varied between 1.0 and 25/~A (in most cases below I0 #A). The effects of microstimulation were determined by muscle palpation, visual inspection, and in some cases verified by E M G recording. Microstimulation in area 4, in the region rostral to area 3a, evoked movements of the hand (thumb and fingers). A zone from which predominately wrist and radioulnar joint movements were evoked (wrist flexion and extension, wrist ulnar and radial deviation, and forearm supination and pronation) was found just rostral to the hand zone. Rostral to this wrist zone there was an abrupt transition to a zone from which thumb and finger movements were once again evoked. The presence of this second zone of hand representation in area 4 does not conform to the classical viewpoint of motor cortex representation. Although classical maps of the motor cortex demonstrate some overlap in the representation of body partsa'5, t6, the basic pattern is one in which movements of more proximal portions of the limb are evoked from points rostral to a single area of hand representation. Thus, in contrast to maps derived from surface stimulation, our microstimulation studies have demonstrated a discrete second representation for the hand. Furthermore, immediately rostral to the second hand zone lies another zone in which movements of the wrist and radioulnarjoint are again evoked. Low intensity microstimulation did not evoke additional hand movements rostral to this second wrist representation. We will call the hand and wrist zones nearest the central fissure the caudal representation and the second hand and wrist zones, which are more remote from the central fissure, the rostral representation. In general the same muscles were activated at similar threshold currents in both representations. Histological analysis of the sites of lesions marking both caudal and rostral representations demonstrated that both were located in area 4. Fig. 1 illustrates some of our findings. Figure IA depicts an oblique view of the left hemisphere of the squirrel monkey. The parallelogram outlined on the cortical surface (labeled B) represents a segment of area 4. Located within this segment is the center of the hand-wrist region, as well as the transition between caudal and rostral representations. The line of transition between the two representations was 4 mm from the central fissure in the animal illustrated. In 4 other animals the line of transition was located from 3.7 to 4.2 mm rostral to the central fissure. Fig. 1B is an enlarged view of the parallelogram labeled B in Fig. I A. Each symbol shows the site of one microelectrode penetration made in this 2 ><, 2 millimeter area. The relatively large spaces where penetrations were not made were regions occupied by surface blood vessels. The filled circles represent sites from which thumb or finger movements were evoked and the open circles are sites where stimulation evoked movements of the wrist or radioulnar joint. Note the clustering of like responses which
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Fig. 1. A: oblique view of squirrel monkey left hemisphere. Parallelogram (labeled B) represents a 2 ~ 2 mm segment of area 4 at the center of the hand-wrist representation. The line caudal (to the right) and medial to (above) the parallelogram indicates the location of the central fissure. B: enlarged view of parallelogram in Fig. 1A. Symbols indicate sites of microelectrode penetrations. Filled circles are sites where thumb and finger movements were evoked. Open circles are sites where wrist or radioutnar movements were evoked, The dashed line indicates the border between the two motor representations. C: graph of results from 3 animals. Comparable 2 x 2 mm parallelograms from 3 animals were divided into 8 equal mediolateral bands. Parallelograms were aligned on the border between the two representations (dashed line). Each bar represents the percentage of hand (above) and wrist (below) responses seen in each band. See text.
t e n d to orient in mediolateral bands, a n d the a l t e r n a t i o n of the h a n d a n d wrist bands. The dashed line was placed by eye a n d is the b o r d e r between the caudal a n d rostral representations i n this animal. Fig. 1C is a n a t t e m p t to represent the results f r o m several e x p e r i m e n t s i n a semiq u a n t i t a t i v e fashion. I n order to summarize results from different animals, the border between the rostral a n d caudal representations was used to align the maps of 3 animals. I n these a n i m a l s a sufficient n u m b e r of p e n e t r a t i o n s were made a r o u n d t h e b o r d e r region to unequivocally define it. In each animal, s t i m u l a t i o n sites n e a r the center o f the forelimb r e p r e s e n t a t i o n a n d within a 2 x 2 m m area c o n t a i n i n g the border between the rostral a n d caudal representations were used in c o n s t r u c t i n g the graph i n Fig. 1C. In all, 134 s t i m u l a t i o n sites were c o n t a i n e d within these three 2 × 2 m m areas of cortex. Each of the 2 x 2 m m areas was divided into eight 250 # m mediolateral b a n d s a n d the
369 number of sites from which we elicited movements of thumb-fingers and wrist-radioulnar joint were separately totaled for each band. In Fig. 1C the vertical bars represent the eight bands. The length of the bar above the horizontal '0' line represents the percentage of thumb-finger responses and the length below represents the percentage of wrist-radioulnar joint responses. Although there are hand and wrist responses in each band, this overlap is not sufficient to mask a clearly defined double representation even when the results from 3 animals are lumped together. There has been controversy concerning the interpretation of results from microstimulation studies I 4,v,s,14. Regardless of the neuronal elements activated by microstimulation, our results indicate that the concentrations of points from which hand movements are evoked peak in two spatially separated zones within area 4. The same is true for wrist movements. This observation most likely reflects a similar spatial distribution of output neurons. K wan et al.9 recently have reexamined the representation of the body,particularly the forelimb, in the motor cortex of the stump-tailed monkey. Our findings in the handwrist representation differ from theirs in that they did not report a double representation which we have found in the squirrel monkey. In the stump-tailed monkey, the difficulty in reconstructing the topography within the depths of the central sulcus may account for this difference. The demonstration of a double representation within the forearm region of area 4 in the squirrel monkey raises several questions. First, is multiple representation in the motor cortex limited to the forearm motor representation? As yet we have not explored other regions of the motor cortex. Second, is this pattern of multiple representation species specific or is it a general feature of motor cortex organization? Evidence from microstimulation studies in the cat suggests that a multiple representation of the forelimb also exists in the motor cortex of this species (Pappas and Strick, submitted for publication). Finally, what is the functional significance of multiple representations in area 4? Our hypothesis is that the double representation reflects two motor control systems within area 4 that deal with different components of motor behavior. While it would be surprising if these systems are completely independent, they may have been anatomically separated to facilitate differential control over their input and/or output. The study was supported in part by funds from the Veterans Administration Medical Research Fund and USPHS Grant NS02957.
1 Anderson, P., Hagan, P. J., Phillips, C. G. and Powell, T. P. S., Mapping by microstimulation of overlapping projections from area 4 to motor units of the baboon's hand, Proc. roy. Soc. B, 188 (1975) 31-60. 2 Asanuma, H. and Arnold, A. P., Noxious effects of excessivecurrents used for intracortical microstimulation, Brain Research, 96 (1975) 103-107. 3 Asanuma, H. and Rosen, I., Topographical organization of cortical efferent zones projecting to distal forelimb muscles in the monkey, Exp. Brain Res., 14 (1972) 243-256.
370 4 Asanuma, H. and Sakata, H., Functional organization of a cortical efferent system examined with focal depth stimulation in cats, J. Neurophysiol., 30 (1967) 35 54. 5 Davies, P. W., Chamber for microelectrode studies in the cerebral cortex, Scieltce, t 24 (1956) 179 180. 6 Evarts, E. V., Representation of movements and muscles by pyramidal tract neurons of the precentral motor cortex. In M. D. Yahr and D. P. Purpura (Eds.) Neurophysiological B~isi., O/+~rmatand Abnormal Motor Activities, Raven Press, New York, 1967, pp. 215-254. 7 Jankowska, E., Padel, Y. and Tanaka, R., The mode of activation of pyramidal tract cells by intra+ cortical stimuli, J. Physiol. (Lond.), 249 (1975) 617-636. 8 Jankowska, E., Padel, Y. and Tanaka, R., Projections of pyramidal tract cells to a-motoneurones innervating hindlimb muscles in the monkey, J. Physiol. (Lond.), 249 (1975) 637~667. 9 Kwan, H. C., MacKay, W. A., Murphy, J. T. and Wong, Y. C., An intracortical microstimulation study of output organization in precentral cortex of awake primates, J. Physiol. (Paris), in press. 10 Paul, R. L., Merzenich, M. and Goodman, H., Representation of slowly and rapidly adapting cutaneous mechanoreceptors of the hand in Brodmann's areas 3 and 1 of Mocaea mulatto, Brain Research, 36 (1972) 229-249. 11 Penfield, W. and Rasmussen, T., The Cerebral Cortex o/Mon, MacMillan, New York, 1950, pp. I1 65. 12 Phillips, C. G., The Ferrier Lecture. Motor apparatus of the baboon's hand, Proe+ roy: Soc. B, 173 (1969) 141 174. 13 Sanides, F., The architecture of the cortical taste nerve areas in squirrel monkey (Saimiri sciureus) and their relationships to insular, sensorimotor and prefrontal regions, Brain Research, 8 (I 968) 97--124. 14 Stoney, S. D., Jr., Thompson, W. D. and Asanuma, H., Excitation of pyramidal tract Cells by intra~ cortical microstimulation: Effective extent of stimulating current, J. Neurophysiol., 3 i (1968) 659+: 669. 15 Welker, W. I., Benjamin, R. M., Miles, R. C. and Woolsey, C. N., Motor effects of stimulation of cerebral cortex of squirtet monkey (Saimiri seiureus), J. Neurophysiol., 20 (1957) 347- 364. 16 Woolsey, C. N., Settlage, P. H., Meyer, D. R., Sencer, W., Pinto Hamuy, T. and Travis, A. M., Patterns of localization in precentral and +supplementary' motor areas and their relation to the c0n, cept of a premotor area, Res. Publ. Ass. nerv. ment. Dis., 30 (1952) 238-264.