Brain Research, 177 t1979) 176-182 "!~ Elsevier/North-Holland Biomedical Press
176
Frontal lobe inputs to primate motor cortex: evidence for four somatotopically organized 'premotor' areas
K A M E L F.
MUAKKASSA and PETER L. STRICK*
Research Service, Veterans Administration Medical Center and Departments of Neurosurgery and Physiology, Upstate Medical Center, Syracuse, N.Y. 13210 (U.S.A.)
(Accepted July 19th, 1979)
One of the classical concepts concerning the cortical control of movement is that ~premotor' areas exist in the frontal lobe which have direct access to the primary motor cortex. These "premotor' areas are thought to contribute to the structuring of skilled movement and the programming of motor cortex output. There is, however, both controversy and confusion concerning the location as well as the function of these cortical areas 4,9,12,14,16,1s-~0. Most authors agree that the supplementary motor area (SMA), which in the rhesus monkey ties in the medial part of area 62°, projects bilaterally to the motor cortex3,12.16. Inputs to the motor cortex from the frontal lobe. and in particular from other parts of area 6. have not been as precisely defined (see, however. refs. 7, 10 and 16). The present experiments sought to define more clearly the origin of frontal lobe inputs to the face, arm and leg areas of the primate motor cortex (area 4). Our methods have been described in detail elsewhere 13,17. Briefly, small (0.05-0.1 .ut) multiple injections of 30 % H R P (Boehringer, dissolved in distilled water) were made into the arm (4 animals), face (3 animals) and leg (3 animals) areas of the motor cortex of 10 monkeys (Macaca mulatta, and fascicularis). In 6 animals, the injections were placed using the maps of Woolsey et al. 2°. in 4 animals the injections were placed using intracortical microstimulation (ICMS) to determine the arm, face or leg area and to delimit each from cortical regions representing other body parts (see Asanuma and Rosen 2 for stimulation methods). Following the H R P injections the animals were allowed to survive for 24 h and then perfused with a solution containing 1% paraformaldehyde and 1.25% glutaraldehyde in a 0.1 M phosphate buffer. Brain sections (50 ~m) were processed for H R P using standard techniqueslL Animals were accepted for analysis only if the local spread of H R P from the injection site remained at least l mm away from the motor cortex borders with areas 6 and 3a. Seven animals met these criteria. Fig. ! demonstrates the distribution of labeled neurons in arhesus monkey with multiple injections of H R P in the arm area of the motor cortex. The 6 H R P injections in this animal (black dots in Fig. 1B) were made at points where stimulation evoked * To whom correspondence should be addressed.
177
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Fig. 1. A : two views of the cortical surface from the right hemisphere of a rhesus monkey. Lateral view (bottom) and medial view reflected upwards (top). B: enlarged view of cortical area included within the dotted rectangle of Fig. 1A. Cortical injections are indicated by 6 black dots. The continuous line surrounding the injection sites indicates the region containing dark H R P reaction product, and the dotted line the maximum spread of visible HRP reaction product. The distribution and relative density of cortical neurons in the frontal lobe labeled by retrograde H R P transport is indicated by the location and thickness of the straight lines. Arrow heads point to the location of labeled neurons in sulci (e.g. arcuate: posterior bank; superior precentral: medial bank; and cingulate: ventral bank). C: contralateral hemisphere of the same monkey. The distribution and relative density of neurons labeled by HRP transport are as in Fig. 1B. D and E: coronal sections at the levels labeled D and E in Fig. 1B. Each dot represents the location of a labeled neuron found in a 50/~m thick section. ArS, arcuate sulcus (IL ~ inferior limb, SL ~ superior limb); CS, central sulcus; CgS, cingulate sulcus; CC, Corpus callosum; IPcS, inferior precentral sulcus; IpS, intraparietal sulcus; PrS, principal sulcus; SPcS, superior precentral sulcus.
178 contractions of wrist musculature (4-10 ,uA threshold). The subsequent spread of H R P remained within the cortical area from which only contractions of forelimb musculature could be evoked. A ring of labeled neurons which varied in density surrounded the injection site. In addition, 4 spatially separate regions in the ipsilateral frontal lobe contained labeled neurons. The labeled neurons surrounding the injection site were separated from those in the frontal lobe by a zone, 1-2 mm wide, which lacked labeled neurons. The 4 regions in the frontal lobe which contained labeled neurons included: (1) the surface and caudal bank of the arcuate sulcus; (2) the lateral bank of the superior precentral sulcus: (3) the SMA on the medial wall of the hemisphere; and (4) the ventral bank of the cingulate sulcus. Similar observations recently have been reported by Matsumara and Kubota 1~. Although the density of labeled neurons varied from animal to animal, a greater number of labeled neurons was always found in the regions of the arcuate sulcus and SMA than in the regions of the cingulate and precentral sulci (Fig. ID and 1E). All 4 cortical regions, however, contained labeled neurons, even following a single, small H R P injection (spread of less than 1 ram) into motor cortex wrist representation. A similar pattern of labeled neurons was also seen in the motor cortex and the 4 frontal lobe areas contralateral to the injection sites (Fig. 1C). However. the number of labeled neurons in the contralateral hemisphere was always tess than that observed in the comparable ipsilateral region. The low density of labeled neurons observed in the contralateral hemisphere may be due in part to the relatively short survival time employed. Labeled neurons were found in both the deep and superficial cortical layers(3) of all 4 frontal lobe regions following the motor cortex H R P injections. The highest density of labeled neurons was found in layer II1 (see Fig. ID and IEJ. The size of labeled neurons varied considerably in layer III, and included both the largest and smallest pyramidal-shaped cells found in that layer. The results of experiments in which H R P injections were made into either the face, arm or leg representation of motor cortex are summarized in Fig. 2. Fig. 2A, from Wootsey 2°, shows the body representation in both the primary motor cortex and SMA. The location, spatial extent and somatotopic organization of the 4 frontal lobe regions which project to the primary motor cortex are indicated by the symbols in Fig. 2C and 2D. For example, following H R P injections into the face area of the motor cortex, labeled neurons were observed in: (1) the lateral bank of the inferior precentral sulcus; (2) the inferior limb of the arcuate sulcus (caudal bank); (3) rostrally in the SMA; and (4) rostrally in the ventral bank of the cingulate sulcus. In contrast. following H R P injections into the leg area of the motor cortex, labeled neurons were observed in: (1) the medial bank of the superior precentral sulcus: (2) the superior limb of the arcuate sulcus (caudal bank); (3) caudally in the SMA; and (4) caudally in the ventral bank of the cingulate sutcus. All animals contained symmetrical patterns of labeling in the contralateral frontal lobes. Our results indicate that there are 4 spatially separate and somatotopically organized regions in the frontal lobe which project directly to the primate motor cortex of both hemisperes. The most significant of these inputs appears to originate
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Fig. 2. Location and somatotopic organization of 4 'premotor' areas. A: body representation and location of the primary (vertically oriented figurine) and supplementary (horizontally oriented figurine) motor areas in the rhesus monkey according to Woolsey et al. 2°. The rostral bank of the central sulcus and the dorsal bank of the cingulate sulcus have been included in order to illustrate the total body maps. B: enlarged view of cortical area included within the dotted rectangle of Fig. IA. Neither the cingulate sulcus nor the central sulcus have been opened in this view. C: location and approximate spatial extent of the 4 'premotor' areas which project to the primary motor cortex are indicated by symbols (posterior arcuate, filled circles; precentral sulci, triangles; SMA, squares; cingulate sulcus, open circles ;). Note that the projection from the arcuate sulcus originates largely from its caudal bank while the projection from the cingulate sulcus originates from its ventral bank. D: body representation in each of the 4 'premotor' areas depicted in Fig. 2C is indicated by the words 'face', 'arm', and 'leg' in each region. See text for further details.
180 from the regions of the arcuate sulcus and the SMA. Behavioral and neuron recording studies have suggested that the 'premotor" arcuate area is involved in the visual guidance of limb movementg, 14. Inputs to the arcuate area f r o m posterior parietal cortex (area 7)6,7,16 may be responsible in part for the visuo-motor properties of this region. Like the arcuate region, neurons have been observed in area 7 which are preferentially active during limb movements under visual controP a,15. Therefore, the arcuate area may be part of a circuit by which area 7 influences motor cortex output during movements guided by vision. As noted earlier the SMA has long been known to project bilaterally to area 4. Its somatotopical organization, observed in this study, correlates well with the maps derived from the stimulation studies of Woolsey 2° and the results of recent neuron recording studies in SMA of awake monkeys 4,18. A number of functions have been suggested for the SMA including its involvement in the control of posture, gating motor cortical reflexes, and initiating motor cortex output and movement '1,16, ~ 20 Although the SMA is included in the medial part of area 6. our results suggest that it is anatomically separate from "premotor' areas in the lateral part of area 6. A comparison of neuron activity m arcuate and SMA "premotor" areas suggest that they are functionally distinct as well 4-9.1s. The labeled neurons observed in the ventral bank of cingulate sulcus (area 24j were spatially separate from labeled neurons m the SMA in every animal. This observation was independenl of whether the H R P injection was made inlo the face. arm or leg motor cortex. Further evidence that the ventral bank of the cingulate sutcus is separate from the SMA comes from stimulation studies 2°. The representation in SMA of axial and body musculature in these studies was found to extend into the dorsal but not the ventral bank of the cingulate sulcus. Based on the limited information available, the connexions of the ventral bank of the cingutate sulcus suggest that it may be a route by which the limbic system has access to the motor cortex. The location of the precentral sulci, labeled SPcS and IPcS in Figs. 1 and 2. varies from animal to animal. Some authors include the cortex around these sulci within area 4 while othels place these regions in area 63,5. Our reason for considering the labeled neurons near the precentrat sulci as separate from those which immediately surround the injection site is that labeled neurons in these regions were separated from one another by a l-2 m m zone of unlabeled neurons. We have grouped the labeled neurons around the inferior and superior precentral sulci together as a fourth 'premotor' area. By doing so, a complete, though discontinuous, body representation is formed. It remains to be determined whether the functional properties of the neurons in the two regions are comparable. Stimulation near the precentral sutci evokes contractions of proximal and axial body musculature 2°. The inputs from the precentral sulci to regions of area 4 near the central sulcus may represent a cortical mechanism for integrating postural adjustments with limb movement (see also ref. 1). Recently, there has been some controversy concerning the means by which the basal ganglia influences motor output. Anatomical studies have demonstrated little overlap of basal ganglia input onto thalamic regions which in turn project to area 4
18l (see ref. 17 for discussion). Basal gangliaprojections do terminate, however, in thalamic regions which project to area 68,17. Thus ' p r e m o t o r ' areas, in a d d i t i o n to being involved in cortico-cortical loops, also appear to be a route by which the basal ganglia influence the activity of area 4 neurons. Which one or all of the 4 ' p r e m o t o r ' areas d e m o n s t r a t e d in this study is the m a i n terminus of the basal g a n g l i a - t h a l a m o c o r t i c a l pathway is presently u n d e r investigation. The d e m o n s t r a t i o n of multiple frontal lobe inputs to the m o t o r cortex potentially defines the terminal stages of various subsystems controlling motor cortex o u t p u t and m o t o r behavior. While the functions of these frontal lobe regions are not well defined, it is hoped that the present anatomical study will provide a framework for their future analysis. The authors t h a n k Ms. C a t h r y n Skretch for invaluable technical assistance, Dr. James B. Preston for reviewing this m a n u s c r i p t a n d Dr. Robert B. K i n g for his generous support. This project has been supported in part by the Veterans A d m i n i s t r a t i o n and funds from the Neurosurgery D e p a r t m e n t .
1 Armand, J. and Aurenty, R., Dual organization of motor corticospinal tract in the cat, Neurosci. Lett., 6 (1977) 1-7. 2 Asanuma, H. and Rosen, l., Topographical organization of cortical efferent zones projecting to distal forelimb muscles in the monkey, Exp. Brain Res., 14 (1972) 243 256. 3 Bonin, G., Von and Bailey, P., The Neocortex ofMacaca mullata Urban, Illinois University Press, 1947, XII, p. 163. 4 Brinkman, J. and Porter, R., Supplementary motor area of the monkey. Activity of neurons during performance of a learned motor task, J. Physiol. (Paris), 74 (1978) 313 316. 5 Bucy, P. C., A comparative cytoarchitectonic study of the motor and premotor areas in the primate cortex, J. camp. Neural., 62 (1935) 293 332. 6 Chavis, D. A. and Pandya, D. N., Further observations on cortico-frontal connections in the rhesus monkey, Brain Research, 117 (1976) 369-386. 7 Jones, E. G., Coulter, J. D. and Hendry, S. H., Intra-cortical connectivity of architectonic fields in the primate somatic sensory, motor and parietal cortex of monkeys, J. comp. Neurol., 181 (1978) 291 348. 8 Kievit, J. and Kuypers, H. G. J. M., Organization of the thalamocortical connexions to the frontal lobe in the rhesus monkey, Exp. Brain Res., 29 (1977) 299 322. 9 Kubota, K. and Hamada, I., Visual tracking and neuron activity in the post-arcuate area of monkeys, J. Physiol. (Paris), 74 (1978) 297 312. 10 Kunzle, H., An autoradiographic analysis of the efferent connections from premotor and adjacent prefrontal regions (areas 6 and 9) in Macacafascicularis, Brain Behav. Evol., 15 (1978) 185 234. 11 Leinonen, L., Hyvarinen, J., Nyman, G. and Linnankoski, I., 1. Functional prolzerties of neurons in lateral part of associative area 7 in awake monkeys, Exp. Brain Res., 34 (1979) 299 320. 12 Matsurnara, M. and Kubota, K., Cortical projection of hand arm motor area from post-arcuate area in macaque monkey: a histological study of retrograde transport of horseradish peroxidase, Neurosci. Lett., I I (1979) 241 246. 13 Mesulam, M. M., Tetramethyl benzidine for horseradish peroxidase neurohistochemistry: a non-carcinogenic blue reaction product with superior sensitivity tot visualizing neural afferents and efferents, J. Histochem. Cytochem., 26 (1978) 106-I 17. 14 Moll, L. and Kuypers, H. G. J. M., Premotor cortical ablations in monkeys: contralateral changes in visually guided reaching behavior, Science, 198 (1977) 317 319. 15 Mountcastle, V. B., Lynch, J. C., Georgopoulos, A., Sakata, H. and Acuna, C., Posterior parietal association cortex of the monkey : command functions for operating within extrapersonal space, J. Neurophysiol., 35 (1975) 871-908.
182 16 Pandya, D. N. and Vignolo, L. A., lntra and inter-hemispheric projections of the precentral, premotor and arcuate areas in the rhesus monkey, Brain Research, 26 (1971) 217- 233. 17 Strick, P. L., Anatomical analysis of ventrolateral thalamic input to the primate motor cortex. J. NeurophysioL, 39 (1976) 1020-1031. 18 Tanji, J. and Tanaguchi, K., Does the SMA play a part in modifying motor cortex reflexes?. J. Physiol. (Paris), 74 (1978) 317-318. 19 Wiesendanger, M., Seguin, J. J. and Kuenzle, H., The supplementary motor area, a control system for posture? In R. B. Stein, K. Pearson, R. Smith and J. Redford {Eds.). Control o[" Posture and Locomotion, Plenum Press, New York, 1973, pp. 331-346. 20 Woolsey, C. N., Settlage, P. H., Meyer, D. R., Sencer, W., Hamery, T. P. and Travis, A. M., Patterns of localization in precentral and 'supplementary' motor areas and their relation to the concept of a premotor area, Res. Publ. Ass. herr. ment. Dis., 30 (1952) 238-264.
176
Frontal lobe inputs to primate motor cortex: evidence for four somatotopically organized 'premotor' areas
K A M E L F.
MUAKKASSA and PETER L. STRICK*
Research Service, Veterans Administration Medical Center and Departments of Neurosurgery and Physiology, Upstate Medical Center, Syracuse, N.Y. 13210 (U.S.A.)
(Accepted July 19th, 1979)
One of the classical concepts concerning the cortical control of movement is that ~premotor' areas exist in the frontal lobe which have direct access to the primary motor cortex. These "premotor' areas are thought to contribute to the structuring of skilled movement and the programming of motor cortex output. There is, however, both controversy and confusion concerning the location as well as the function of these cortical areas 4,9,12,14,16,1s-~0. Most authors agree that the supplementary motor area (SMA), which in the rhesus monkey ties in the medial part of area 62°, projects bilaterally to the motor cortex3,12.16. Inputs to the motor cortex from the frontal lobe. and in particular from other parts of area 6. have not been as precisely defined (see, however. refs. 7, 10 and 16). The present experiments sought to define more clearly the origin of frontal lobe inputs to the face, arm and leg areas of the primate motor cortex (area 4). Our methods have been described in detail elsewhere 13,17. Briefly, small (0.05-0.1 .ut) multiple injections of 30 % H R P (Boehringer, dissolved in distilled water) were made into the arm (4 animals), face (3 animals) and leg (3 animals) areas of the motor cortex of 10 monkeys (Macaca mulatta, and fascicularis). In 6 animals, the injections were placed using the maps of Woolsey et al. 2°. in 4 animals the injections were placed using intracortical microstimulation (ICMS) to determine the arm, face or leg area and to delimit each from cortical regions representing other body parts (see Asanuma and Rosen 2 for stimulation methods). Following the H R P injections the animals were allowed to survive for 24 h and then perfused with a solution containing 1% paraformaldehyde and 1.25% glutaraldehyde in a 0.1 M phosphate buffer. Brain sections (50 ~m) were processed for H R P using standard techniqueslL Animals were accepted for analysis only if the local spread of H R P from the injection site remained at least l mm away from the motor cortex borders with areas 6 and 3a. Seven animals met these criteria. Fig. ! demonstrates the distribution of labeled neurons in arhesus monkey with multiple injections of H R P in the arm area of the motor cortex. The 6 H R P injections in this animal (black dots in Fig. 1B) were made at points where stimulation evoked * To whom correspondence should be addressed.
177
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Fig. 1. A : two views of the cortical surface from the right hemisphere of a rhesus monkey. Lateral view (bottom) and medial view reflected upwards (top). B: enlarged view of cortical area included within the dotted rectangle of Fig. 1A. Cortical injections are indicated by 6 black dots. The continuous line surrounding the injection sites indicates the region containing dark H R P reaction product, and the dotted line the maximum spread of visible HRP reaction product. The distribution and relative density of cortical neurons in the frontal lobe labeled by retrograde H R P transport is indicated by the location and thickness of the straight lines. Arrow heads point to the location of labeled neurons in sulci (e.g. arcuate: posterior bank; superior precentral: medial bank; and cingulate: ventral bank). C: contralateral hemisphere of the same monkey. The distribution and relative density of neurons labeled by HRP transport are as in Fig. 1B. D and E: coronal sections at the levels labeled D and E in Fig. 1B. Each dot represents the location of a labeled neuron found in a 50/~m thick section. ArS, arcuate sulcus (IL ~ inferior limb, SL ~ superior limb); CS, central sulcus; CgS, cingulate sulcus; CC, Corpus callosum; IPcS, inferior precentral sulcus; IpS, intraparietal sulcus; PrS, principal sulcus; SPcS, superior precentral sulcus.
178 contractions of wrist musculature (4-10 ,uA threshold). The subsequent spread of H R P remained within the cortical area from which only contractions of forelimb musculature could be evoked. A ring of labeled neurons which varied in density surrounded the injection site. In addition, 4 spatially separate regions in the ipsilateral frontal lobe contained labeled neurons. The labeled neurons surrounding the injection site were separated from those in the frontal lobe by a zone, 1-2 mm wide, which lacked labeled neurons. The 4 regions in the frontal lobe which contained labeled neurons included: (1) the surface and caudal bank of the arcuate sulcus; (2) the lateral bank of the superior precentral sulcus: (3) the SMA on the medial wall of the hemisphere; and (4) the ventral bank of the cingulate sulcus. Similar observations recently have been reported by Matsumara and Kubota 1~. Although the density of labeled neurons varied from animal to animal, a greater number of labeled neurons was always found in the regions of the arcuate sulcus and SMA than in the regions of the cingulate and precentral sulci (Fig. ID and 1E). All 4 cortical regions, however, contained labeled neurons, even following a single, small H R P injection (spread of less than 1 ram) into motor cortex wrist representation. A similar pattern of labeled neurons was also seen in the motor cortex and the 4 frontal lobe areas contralateral to the injection sites (Fig. 1C). However. the number of labeled neurons in the contralateral hemisphere was always tess than that observed in the comparable ipsilateral region. The low density of labeled neurons observed in the contralateral hemisphere may be due in part to the relatively short survival time employed. Labeled neurons were found in both the deep and superficial cortical layers(3) of all 4 frontal lobe regions following the motor cortex H R P injections. The highest density of labeled neurons was found in layer II1 (see Fig. ID and IEJ. The size of labeled neurons varied considerably in layer III, and included both the largest and smallest pyramidal-shaped cells found in that layer. The results of experiments in which H R P injections were made into either the face, arm or leg representation of motor cortex are summarized in Fig. 2. Fig. 2A, from Wootsey 2°, shows the body representation in both the primary motor cortex and SMA. The location, spatial extent and somatotopic organization of the 4 frontal lobe regions which project to the primary motor cortex are indicated by the symbols in Fig. 2C and 2D. For example, following H R P injections into the face area of the motor cortex, labeled neurons were observed in: (1) the lateral bank of the inferior precentral sulcus; (2) the inferior limb of the arcuate sulcus (caudal bank); (3) rostrally in the SMA; and (4) rostrally in the ventral bank of the cingulate sulcus. In contrast. following H R P injections into the leg area of the motor cortex, labeled neurons were observed in: (1) the medial bank of the superior precentral sulcus: (2) the superior limb of the arcuate sulcus (caudal bank); (3) caudally in the SMA; and (4) caudally in the ventral bank of the cingulate sutcus. All animals contained symmetrical patterns of labeling in the contralateral frontal lobes. Our results indicate that there are 4 spatially separate and somatotopically organized regions in the frontal lobe which project directly to the primate motor cortex of both hemisperes. The most significant of these inputs appears to originate
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Fig. 2. Location and somatotopic organization of 4 'premotor' areas. A: body representation and location of the primary (vertically oriented figurine) and supplementary (horizontally oriented figurine) motor areas in the rhesus monkey according to Woolsey et al. 2°. The rostral bank of the central sulcus and the dorsal bank of the cingulate sulcus have been included in order to illustrate the total body maps. B: enlarged view of cortical area included within the dotted rectangle of Fig. IA. Neither the cingulate sulcus nor the central sulcus have been opened in this view. C: location and approximate spatial extent of the 4 'premotor' areas which project to the primary motor cortex are indicated by symbols (posterior arcuate, filled circles; precentral sulci, triangles; SMA, squares; cingulate sulcus, open circles ;). Note that the projection from the arcuate sulcus originates largely from its caudal bank while the projection from the cingulate sulcus originates from its ventral bank. D: body representation in each of the 4 'premotor' areas depicted in Fig. 2C is indicated by the words 'face', 'arm', and 'leg' in each region. See text for further details.
180 from the regions of the arcuate sulcus and the SMA. Behavioral and neuron recording studies have suggested that the 'premotor" arcuate area is involved in the visual guidance of limb movementg, 14. Inputs to the arcuate area f r o m posterior parietal cortex (area 7)6,7,16 may be responsible in part for the visuo-motor properties of this region. Like the arcuate region, neurons have been observed in area 7 which are preferentially active during limb movements under visual controP a,15. Therefore, the arcuate area may be part of a circuit by which area 7 influences motor cortex output during movements guided by vision. As noted earlier the SMA has long been known to project bilaterally to area 4. Its somatotopical organization, observed in this study, correlates well with the maps derived from the stimulation studies of Woolsey 2° and the results of recent neuron recording studies in SMA of awake monkeys 4,18. A number of functions have been suggested for the SMA including its involvement in the control of posture, gating motor cortical reflexes, and initiating motor cortex output and movement '1,16, ~ 20 Although the SMA is included in the medial part of area 6. our results suggest that it is anatomically separate from "premotor' areas in the lateral part of area 6. A comparison of neuron activity m arcuate and SMA "premotor" areas suggest that they are functionally distinct as well 4-9.1s. The labeled neurons observed in the ventral bank of cingulate sulcus (area 24j were spatially separate from labeled neurons m the SMA in every animal. This observation was independenl of whether the H R P injection was made inlo the face. arm or leg motor cortex. Further evidence that the ventral bank of the cingulate sutcus is separate from the SMA comes from stimulation studies 2°. The representation in SMA of axial and body musculature in these studies was found to extend into the dorsal but not the ventral bank of the cingulate sulcus. Based on the limited information available, the connexions of the ventral bank of the cingutate sulcus suggest that it may be a route by which the limbic system has access to the motor cortex. The location of the precentral sulci, labeled SPcS and IPcS in Figs. 1 and 2. varies from animal to animal. Some authors include the cortex around these sulci within area 4 while othels place these regions in area 63,5. Our reason for considering the labeled neurons near the precentrat sulci as separate from those which immediately surround the injection site is that labeled neurons in these regions were separated from one another by a l-2 m m zone of unlabeled neurons. We have grouped the labeled neurons around the inferior and superior precentral sulci together as a fourth 'premotor' area. By doing so, a complete, though discontinuous, body representation is formed. It remains to be determined whether the functional properties of the neurons in the two regions are comparable. Stimulation near the precentral sutci evokes contractions of proximal and axial body musculature 2°. The inputs from the precentral sulci to regions of area 4 near the central sulcus may represent a cortical mechanism for integrating postural adjustments with limb movement (see also ref. 1). Recently, there has been some controversy concerning the means by which the basal ganglia influences motor output. Anatomical studies have demonstrated little overlap of basal ganglia input onto thalamic regions which in turn project to area 4
18l (see ref. 17 for discussion). Basal gangliaprojections do terminate, however, in thalamic regions which project to area 68,17. Thus ' p r e m o t o r ' areas, in a d d i t i o n to being involved in cortico-cortical loops, also appear to be a route by which the basal ganglia influence the activity of area 4 neurons. Which one or all of the 4 ' p r e m o t o r ' areas d e m o n s t r a t e d in this study is the m a i n terminus of the basal g a n g l i a - t h a l a m o c o r t i c a l pathway is presently u n d e r investigation. The d e m o n s t r a t i o n of multiple frontal lobe inputs to the m o t o r cortex potentially defines the terminal stages of various subsystems controlling motor cortex o u t p u t and m o t o r behavior. While the functions of these frontal lobe regions are not well defined, it is hoped that the present anatomical study will provide a framework for their future analysis. The authors t h a n k Ms. C a t h r y n Skretch for invaluable technical assistance, Dr. James B. Preston for reviewing this m a n u s c r i p t a n d Dr. Robert B. K i n g for his generous support. This project has been supported in part by the Veterans A d m i n i s t r a t i o n and funds from the Neurosurgery D e p a r t m e n t .
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