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Thalamic projections from the precentral motor cortex inMacaca fascicularis
Brain Research, 105 (1976) 253-267
253
© Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
T H A L A M I C PROJECTIONS F R O M T H E P R E C E N T R A L M O T O R CORTEX IN MACACA FASCICULARIS
HEINZ K()NZLE
Institute for Brain Research, University of Zurich, CH-8029 Zurich (Switzerland) (Accepted August 29th, 1975)
SUMMARY
Radioactive amino acids were injected into area 4 in 7 monkeys (Macaca fascicularis). Ipsilateral corticothalamic projections were traced to Olszewski's nucleus ventralis lateralis pars oralis and pars medialis, the nucleus ventralis posterior lateralis pars oralis, the nucleus ventralis posterior medialis and inferior and to the nucleus reticularis. Some fibers appeared to terminate in the ipsilateral nucleus ventralis lateralis pars caudalis, the nucleus lateralis posterior and the nucleus subthalamicus. A bilateral representation was found in the nucleus centrum medianum, possibly in the paracentralis-centralis lateralis complex and in the paralamellar portion of the nucleus medialis dorsalis. The contralateral labeling was due to fibers crossing via the massa intermedia and was most intense in the cases following injections into the motor face region. A somatotopic arrangement was clearly present in the nucleus ventralis lateralis pars oralis, the nucleus ventralis posterior lateralis pars oralis and the nucleus ventralis posterior medialis. The origin of the projections to the nucleus ventralis posterior medialis needs further clarification.
INTRODUCTION
Few recent communications regarding thalamic connections from the monkey's area 4 exist~a,2s,43,44,s°; a detailed analysis of these projections, however, has not been published since the Marchi period (for review see Carpenter s and MettleraT). The results of silver degeneration studies of precentral projections to the nucleus (n.) lateralis posterior, the n. ventralis posterior lateralis and medialis have not been in agreement43, 5° and the exact terminations of projections to the n. paracentralis, n. para-
254 fascicularis, n. reticularis, the zona incerta and the fields of Fore113,43,44,5° are still obscure. Moreover, all 43,44,s° but one report 13 describe cortical projections to the ipsilateral thalamus exclusively. In view of the dominant role of the thalamus in sensorimotor mechanisms 14,z° a reinvestigation of the precentral corticothalamic projections has been undertaken, using the autoradiographic technique 1°,3°. Special attention has been given to topographic relationships, e.g., to the cortical ipsi- and bilateral body and face representation and their respective thalamic counterparts. MATERIALS AND METHODS
A detailed description of the present material and autoradiographic methods can be found in an earlier publication z6, where the same 7 adult monkeys (Macaca fascicularis) were used. A reconstruction of the injection fields and some parameters used for tracing the efferent connections from the area 4 are shown in Fig. 1. The identification and nomenclature of thalamic structures follows that of OIszewski 42, although we are aware of the fact that certain boundaries of the ventral lateral nuclear complex are based on somewhat arbitrary cytoarchitectonic criteria 34. RESUL'/S
Labeled axons represented as linear grain arrangements can be seen entering the thalamus from the ipsilateral capsula interna (ci) and terminating in patches of unequally distributed silver grains (Fig. 2). The projections are mainly restricted to 72- 449
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Fig. 1. Reconstruction of the injection fields and some parameters used for tracing the efferent connections from area 4. According to the criteria mentioned previously26, the cells lying within the filled circles (blackened area) have taken up, incorporated and transported radioactive amino acids into their terminal ramifications, while cells within the stippled area may have contributed to a faint labeling of the pathways, svt -- survival time.
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® Fig. 2. Darkfield light microscopic autoradiographs. A: unequally distributed grains in the n. ventralis lateralis p. oralis (VLo) and linear grain arrangements in the capsula interna (ci). Some unequally distributed grains within fiber-like grain arrangements passing from ci to VLo may also exist in the dorsal part of the reticular nucleus (RT), (exp. 72-451 'leg' injection). × 9. B: a crescent or comma shaped grain patch in the lateral part of the n. ventralis posterior lateralis p. oralis (VPLo). The broad dorsal portion becomes successively smaller ventrally and turns into the n. ventralis posterior inferior (VPI). A few unevenly distributed grains are also observed in R T and the n. paracentralis (Pcn), (exp. 72-451 'leg' injection), x 9. C: a similar grain pattern as in B. The tracer, however, is situated more medially (exp. 72-449 'trunk' injection), x 9. D : grain accumulations in VPLo and Pcn (exp. 72-448 'face' injection), x 28.
256
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Fig. 3. Drawings of the thalamic projections of the ‘leg’ (exp. 72-451) and ‘arm’ (exp. 72-450) area 4. Projections to the midbrain are not drawn. Fiber-like grain accumulations are indicated by lines, unequally distributed grain arrangements, probably representing terminal fields, by dots. The highest density (see key at the bottom left) and the most extensive distribution of grains are found in the ipsilateral VPLo and CM, the lowest in the ipsilateral VLc and St as well as in the contralateral CM. Grain patches in VLo/VPLo resulting from precentral ‘leg’ injections are lying laterally, those from ‘arm’ injections more medially. Abbreviations used in this and in the following figures: Cd, n. caudatus; ci, capsula interna; CL, n. centralis lateralis; CM, n. centrum medianum; CL, n. geniculatum laterale; HI, He, fields of Fore]; LP, n. lateralis posterior; MD, n. medialis dorsalis; mi, massa intermedia; Pen, n. paracentralis; R, n. ruber; RT, n. reticularis thalami; thi, tractus habenulo-interpeduncularis; SN, substantia nigra; St, n. subthalamicus; VA, n. ventralis anterior; VLc, n. ventralis lateralis p. caudalis; VLm, n. ventralis lateralis p. medialis; VLo, n. ventralis lateralis p. oralis; VPI, n. ventralis posterior inferior; VPLc, n. ventralis posterior lateralis p. caudalis; VPLo, n. ventralis post. lateralis p. oralis; VPM, n. ventralis posterior medialis; 21, zona incerta.
257 the ipsilateral thalamus: some fibers, however, cross the midline via the massa intermedia to the contralateral side. The highest density of grains is found in the n. ventralis posterior lateralis pars oralis, and in the n. centrum medianum. Patches of lowest density, on the other hand, exist in the n. ventralis lateralis pars caudalis and in the n. subthalamicus.
Ventral and lateral nuclear group (VLo, VLe, VLm, VPLo, VPM, VPI, LP) Precentral projections to the ventral and lateral nuclear group are restricted to the ipsilateral side. Dense patches of unequally distributed grains are found in all eases along the whole extent of the n. ventralis lateralis pars oralis (VLo) and the n. ventralis posterior lateralis pars oralis (VPLo) (Figs. 3 and 4). The patches have the shape of a crescent or of a comma (Fig. 2A-C). The broad dorsal portion is most intense in VPLo and may be subdivided into two patches. Ventrally the patches become successively smaller and turn into the n. ventralis lateralis pars medialis (VLm) or the n. ventralis posterior inferior (VPI) (Figs. 2B, 3, 5A). Injections into the precentral face area (exp. 72-448 and 73-320) do not seem to label VPI (Fig. 4). Instead, the silver granules marking the projections of the basal part of the precentral gyrus are found in the n. ventralis posterior medialis (VPM), more pronouncedly in the dorsolateral than in the ventromedial portion (Figs. 4, 5B and 6D). No label can be observed in the parvocellular part of VPM and in VPL pars caudalis. In VLo and VPLo the grain clusters are situated laterally in the 'leg'* (exp. 72-451 and 73-319; Figs. 2A, B and 3), intermediate in the 'arm-trunk'* (exp. 72-449, 72-450 and 73-475; Figs. 2C and 3) and medially in the 'face'* cases (exp. 72-448 and 73-320: Figs. 2D and 4). In VLm and VPI, on the other hand, unequally distributed grain accumulations, although less evident, lie ventrally in the 'leg' and dorsally in the 'arm-trunk' experiments (Fig. 3). An additional grain patch of low density is seen in the n. ventralis lateralis pars caudalis (VLc) in exp. 72-449, 72-450 and possibly in exp. 72-451 (incomplete material) (Fig. 3). The spot is rather small and restricted to the ventrocaudal and lateral part of VLc. It seems partly continuous with the grain accumulations in the n. lateralis posterior (LP), found in exp. 72-449, 72-450, 72-451 and 73-319 (Figs. 3 and 5A). This aggregate is of moderate density, somewhat larger, but also restricted to the ventrolateral portion of LP and without obvious differential topographic arrangement following 'arm' or 'leg' injections. Some tracer can also be observed in the most medial zone opposite to the laterally labeled region in VLc and LP in exp. 72-448 to 72-451. This zone (arrow, Fig. 4) is a transitional region in or between VLc, LP, VPL, CL and CM. The grain patch seems confluent with that in CM rather than with that in LP or VLc. Other nuclei of the lateral nuclear group are not affected.
* For the sake of simplicity the injections into the precentral 'leg-tail', 'arm-trunk' or 'face' area (anatomically defined according to the map of Woolsey e t al. 57) are called 'leg', 'arm-trunk' and 'face' cases.
258
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Fig. 4. Drawing of the thalamic projections of the precentral 'face' area (exp. 72-448). Note the intense labeling of the contralateral CM and the accumulation of grains in an unidentified region lateral to the intralaminar nuclei (arrow). Abbreviations and symbols as in Fig. 3.
259
Fig. 5. Darkfield light microscopic autoradiographs. A: grain accumulations of low to moderate density in the n. lateralis posterior (LP), the n. ventralis posterior inferior (VPI) and the n. subthalamicus (St). A grain patch of high density is seen in the most dorsolateral portion of the n. centrum medianum (CM) (exp. 72-449). x 9. B: the bilateral projection field in the ventrolateral portion of CM and fibers crossing via the massa intermedia (mi) following precentral 'face' injections. The ipsilateral n. ventralis posterior medialis (VPM) and the n. medialis dorsalis (MD) are partially labelled (exp. 72-448). x 9. C: a section from Fig. 5B showing the crossing fibers in the massa intermedia at higher magnification, x 21.
Intralaminar and medial nuclear group (Pcn, CL, CM, MD) Grain arrangements of low to moderate density are found ipsilaterally in a transitional zone within the ventral portion of the n. paracentralis (Pcn)-centralis lateralis (CL) complex (Figs. 3 and 4). The rostral dorsal and ventral parts of the ipsilateral Pcn, in addition, have been slightly labeled in exp. 72-448 to 72-451 (Figs. 2B, 2D, 3 and 4). There may be a few granules on the contralateral side within the ventral P c n - C L complex in exp. 72-448 and 73-320 (Fig. 4). A differential distribution of label according to different injection sites is not evident in the rostrocaudal nor in the dorsoventral plane. The silver grains in the caudal two-thirds of the n. medialis dorsalis (MD) are restricted to the ventral and lateral zones including pars multiformis ( M D m f ) and pars parvocellularis (MDpc) (Figs. 3, 4, 5B and 6). There m a y be a differential distribution of tracer rostrally, indicated by grains lying more dorsally in exp. 72-449, 72-450, 72-451, 73-319 and 73-475, and more ventrally in exp. 72-448 and 73-320. Some particles may be observed in the contralateral ventral zone of M D in exp. 72448 (Fig. 4). The grain patch lying within the ipsilateral n. centrum medianum (CM) is most
261 dense in the cases with large injection fields and long survival time (exp. 72-448 to 72-451; Figs. 3 and 4), moderate in the others. A clear contralateral grain pattern can be found in the cases injected into the motor 'face' area (exp. 72-448 and 73-320). The grain count in the contralateral CM - - although 3-5 times less than ipsilaterally-reveals an up to 20 times higher density than that of the background. In the ' b o d y ' eases only a few (exp. 72-449 to 72-451) or no grains (exp. 73-319 and 73-475) lie in the contralateral CM. Linear or fiber-like grain accumulations passing to the contralateral CM can be followed from the ipsilateral CM across the midline (Fig. 5B and C), but not from the contralateral capsula interna. Apart from the density of particles the bilateral grain pattern is symmetrical, involving CM along its whole rostrocaudal extent. The tracer is restricted to the ventrolateral parts of the ipsi- and contralateral CM in exp. 72-448 (Figs. 4, 5B and 6D) and exp. 73-320. While in these two cases as well as in exp. 73-475 (with granules lying somewhat more dorsally) the grain patches form slightly curved bands throughout C M (Fig. 6D), the grain arrangements in the other cases vary considerably (Fig. 6A-C). The tendency to form bands seems to be restricted to the rostral parts of CM, where they are situated in its dorsomedial portion. The density of grains, however, changes from one section to the other, resulting from rostral to caudal in ring-like, crescent-shaped (open side towards the midline) or irregular patches. At the caudal level the main grain cluster seems to extend into adjoining regions ventrolateraJly to CM. A p a r t from some fiber-like grain arrangements passing from CM to the midbrain, the parafascicular nucleus is almost free of silver particles.
Ventral thalamus and subthalamus (RT and St) Besides fiber-like structures, obviously passing through the n. reticularis thalami (RT), a clear pattern of unequally distributed grains can be seen within this nucleus (Fig. 2A-C). It is involved ipsilaterally along the rostrocaudal extent of VLo/ VPLo (Figs. 3 and 4). The dorsal half is labeled in the cases injected into the motor 'leg' area (exp. 72-451 and 73-319), the ventral, when radioactive amino acids have been injected into the motor 'face' and 'finger' regions (exp. 72-448, 73-320 and 73475). The'arm-trunk' cases (exp. 72-449 and 72-450) resulted in a grain patch within the whole dorsoventral extent of RT. Grains in the zona incerta are rather sparse: those in the fields of Forel (H1, H2 and H) are more abundant, but mainly arranged in a linear or fiber-like fashion.
Fig. 6. Darkfield autoradiograph demonstrating the various grain arrangements in the ipsilateral centrum medianum. Column A represents grain patterns following injection into the motor 'leg' area (exp. 72-451), B, 'trunk' (exp. 72-449), C, 'arm' (exp. 72-450), and those from D are due to a labeling of the precentral 'face' area (exp. 72-448). The upper pictures are taken from rostral, the lower from caudal sections (not necessarily at the same level). Note that the small grain spots to the right in the upper half of each column are in the n. medialis dorsalis (arrow). In column D grain accumulations to the left are in the n. ventralis medialis. Compare also with Fig. 5B. x 7.
262
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263 In the lateral portion of the n. subthalamicus (St) grain patches of low density can only be seen in the experiments with large injection fields and long survival time (Figs. 3, 4 and 5A). There may be a differential projection since grains resulting from injections into the precentral body region (exp. 72-449 to 72-451) are located more dorsally, those from the 'face' injection (exp. 72-448) more ventrally.
DISCUSSION VLo- VPLo- VPM The present results (summarized in Fig. 7) are consistent with Sakai's findings5° in Macaca mulatta and fuscata, demonstrating precentral projections to VLo and VPLo. These regions are therefore reciprocally and topographically interconnected with area 41,2,25,43,5°,53 and receive cerebellar afferents34. VPLo, however, differs from VLo as to its additional postcentra121 and lemniscaP 5,45 inputs: it may also project to area 3a2t, 2z. In man 19 and chimpanzee s4 the region corresponding to Olszewski's VPLo 42 is called n. ventralis intermedius. This term az expresses best the notion of a separate anatomical and functional entity situated in the rostrocaudal direction between VLo and VPL pars caudalis (VPLc) 22'34'36. According to the lemniscal input 3a and the postcentral connections 21,48 on the other hand, VPM is regarded as the analog to VPLc, representing 'sensory' face and body regions respectively. A cortical input from the primary motor area to VPM, but sparing VPLc, would be in contrast to this concept. Precentral fibers terminating in VPM have already been shown previously29,~°; however, in the present material we cannot exclude the possibility of a direct minimal labeling of postcentral somatosensory cortex, especially in exp. 72-448, one of the more extensive injections (see Fig. 1, Kiinzle26). The situation is also complicated by the fact that sensory cortex of the facial representation swings forward into the precentral region48. VLm- VPI/ VLc-LP No detailed descriptions of precentral projections to VLm and VPI are available. Our positive findings are consistent with the termination areas of cerebellar 34, nigral 9 and pallida127,39 afferents to VLm, suggesting that this nucleus contributes to sensorimotor control mechanisms. It is interesting that corticofugal fibers to VPI have been reported from the postcentral fore- and hindlimb areas 21, and a similar projection from the precentral 'body' region to VPI was also found in the present material. Apart from an unidentified region dorsal to CM (Fig. 4, arrow) the terminal field in VLc and LP is confined to the lateral portion and clearly separated from the main projection field in VLo/VPLo. The fibers seem to originate from the precentral body region. Sakai 5° made similar observations concerning LP. The sparse precentral projections to VLc, apparently in contrast to other investigators43,44,s°, may be explained by delineation difficulties. The boundary between VLo and VLc was assumed to be slightly more dorsal than originally describe& 2. It corresponds to the rather sharp dorsal edge of the grain patch in VLo/VPLo resulting from precentral injections.
264 This definition is consistent with studies demonstrating pallidal afferents to VLo, but not to VLc 27,39 and efferents from VLo to area 4 ~,2,a8,53 and from VLc to area 62,48. Pcn-CL-MD-CM Precentral projections to Pcn, CL and to paralaminar regions of M D have been reported by several investigators13,43,44, s°. A differential input to Pcn (from prefrontal and premotor regions) and CL (from premotor and motor cortex) is not obvious ~3 in our material. Conceivably, Pcn receives a more pronounced projection from the rostral parts of area 4 and from area 6 s°. The most intense precentral projection terminates in the ventral portion of a transitional region between Pcn-CL. This region may correspond to the area described to receive spinal and cerebellar afferents34,a5 and to send fibers to area 425,53. The involvement of the paralamellar portion of MD in sensorimotor mechanisms is suggested by its precentral, cerebellar and spinal afferents31,34,35. The dorsal paralamellar portion, predominantly connected with the precentral body region, is in addition reciprocally interconnected with the so-called frontal eyefield3,52, while the ventral paralamellar portion receiving mainly fibers from the precentral 'face' area projects to the orbitofrontal opercular cortex 48. There are several recent studies about the center median-parafascicular complex 4,6,33,35,36. AS to the topographic organization, the present results are consistent with those of Kuyper's 28, De Vito 13 and Petras 43. Different types of precentral fibers terminating in CM (thin pyramidal tract collaterals, CM-destined axons branching into fibers of small and medium size) have recently been reported s. Their intricate arrangement within CM may be the basis for the uncommonly dense and complex neuropi117,~8,5~,55. RT-St Fiber degeneration following precentral lesions has been mentioned in RT, ZI, St and in the fields of Fore143,44. A clear distinction between fiber and preterminal degeneration, however, has previously not been established. Using the autoradiographic technique, grain patterns suggesting a terminal field are found in RT and St, but not in ZI or in the fields of Forel. Contralateral thalarnic projections A symmetrical bilateral projection field (n. ventralis anterior, medialis and lateralis, VPL, VPI, VPM, MD, Pcn, CL, CM, Pf and RT) has been reported in cats, following lesions of the medial wall of the rostral hemisphere 46,4v. The bilaterality, however, has been restricted to the posterior part of the n. ventralis following lesions of area 4 and 6at and to CM and CL after destruction of the sensorimotor cortex 24. Fibers to the contralateral thalamus have been reported in various lower mammals to decussate in the massa intermediaT,24, sl, the anterior commissure 46,47 and the corpus callosum 46. The present results are similar to those described by Kawana and Kusama 24 in cat and support the sparse findings in monkeys, mentioned by De Vito 13. This
265 conformity favors the idea that the massa intermedia in primates does not only represent a commissure is but also a decussation. Transneuronal transport 16,56 of radioactive material within the ipsilateral CM and a further transport to the contralateral side, however, cannot be excluded. The role of the massa intermedia in motor performance has recently been suggested in monkeys a2. In man, however, the massa intermedia seems to lack commissural fibers 2a, is of variable size and frequently absent lx,49. The regressive tendency within the phylogenetic scale of thalamic commissures and the evolutionary progression of the centre median33, 4° are seemingly in conflict and render an interpretation of the function of the massa intermedia rather difficult. The demonstrated bilateral representation of the primary motor cortex within the medial thalamus and the preferred localization of the monkey's precentral face region within the contra- and ventrolateral CM should stimulate further research; this in turn may clarify the functional role of the massa intermedia concerning face and body movements in monkey and man. ACKNOWLEDGEMENTS The author thanks Prof. K. Akert for his support and encouragement throughout the course of the experiment, and Prof. J. de Groot and Prof. J. M. van Buren for their instructive advice on the manuscript. The skillful technical assistance of Mrs. S. Benguerel, R. Emch, E. Knecht and E. Schneider is appreciated as well as the help of Mrs. U. Fischer and Messrs. H. T. Aschwanden, A. F~ih and J. B. Frei, Supported by grants from the Swiss National Foundation for Scientific Research Nos. 3.823.72 and 3.124.73 and the Dr. Eric Slack-Gyr-Foundation, Ziirich.
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267 ing anterolateral cordotomy. An experimental study in the monkey, Brain, 83 (1960) 718-750. 36 MEnLER, W. R., AND NAUTA, W. J. H., Connections of the basal ganglia and of the cerebellum, Confin. neuroL, 36 (1974) 205-222. 37 METrLER, F. A., The corticothalamic projection: the structural substrate for the control of the thalamus by the cerebral cortex. In T. L. FR1GY~I, E. RINVlK AND M. D. YAHR (Eds,), Corticothalamic Projections and Sensorimotor Activities, Raven Press, New York, 1972, pp. 1-19. 38 MOUNTCASTLE,V. B., ANDHENNEMAN,E., The representation of tactile sensibility in the thalamus of the monkey, J. comp. Neurol., 97 (1952) 409-440. 39 NAUTA, W. J. H., AND MEHLER, W. R., Projections of the lentiform nucleus in the monkey, Brain Research, 1 (1966) 3-42. 40 NIIMI, K., KATAYUMA,K., KANASEKI,T., AND MORIMOTO,K., Studies on the derivation of the centre median nucleus of Luys, Tokushima J. exp. Med., 6 (1960) 261-268. 41 NnMI, K., KaSHI, S., MIKI, M., AND FUJITA,S., An experimental study of the course and termination of the projection fibers from cortical areas 4 and 6 in the cat, Folia psychiat, neuroL jap., 17 (1963) 167-216. 42 OLSZEWSrO,J., The Thalamus o f the Macaca mulatta. An Atlas for Use with the Stereotaxic Instruments, Karger, Basel, 1952. 43 PETRAS, J. M., Some efferent connections of motor and somato-sensory cortex of Simian primates and Felid, Canid and Procyonid carnivores. In J. M. PETRASAND C. R. NOBACK (Eds.), Comparative and Evolutionary Aspects of the Vertebrate Central Nervous System, Ann. N.Y. Acad. Sci., 167 (1969) 469-505. 44 PETRAS,J. M., Corticostriate and corticothalamic connections in the chimpanzee. In T. L. FRIGYESI, E. RINVIK AND M. D. YAHR (Eds.), Corticothalamic Projections and Sensorimotor Activities, Raven Press, New York, 1972, pp. 201-216. 45 POGGIO, G. F., AND MOUNTCASTLE, V. B., The functional properties of ventrobasal thalamic neurons studied in unanesthetized monkeys, J. Neurophysiol., 26 (1963) 775-806. 46 RINVIK, E., The corticothalamic projection from the gyrus proreus and the medial wall of the rostral hemisphere in the cat. An experimental study with silver impregnation methods, Exp. Brain Res., 5 (1968) 129-152. 47 RINVlK,E., Organization of thalamic connections from motor and somatosensory cortical areas in the cat. In T. L. FRIGYESI, E. RINVIK AND M. D. YAHR (Eds.), Corticothalamic Projections and Sensorimotor Activities, Raven Press, New York, 1972, pp. 57-90. 48 ROBERTS, T. S., AND AKERT, K., Insular and opercular cortex and its thalamic projection in Macaca mulatta, Schweiz. Arch. NeuroL Neurochir. Psychiat., 92 (1963) 1-42. 49 ROSALES,R. K., LEMAY, M. J., AND YAKOVLEV, P. I., The development and involution of the massa intermedia with regard to age and sex, J. Neuropath. exp. NeuroL, 27 (1968) 166. 50 SAKAI, S., Some observations on the corticothalamic fiber connections in the monkey, Proc. Jap. Acad., 43 (1967) 822-826. 51 SCHEIBEL, M. E., AND SCHEIBEL, A. B., Patterns of organization in specific and non-specific thalamic fields. In D. P. PURPURA AND M. D. YAHR (Eds.), The Thalamus, Columbia University Press, New York, 1966, pp. 13-46. 52 SCOLLO-LAvIZZARI,G., AND AKERT, K., Cortical area 8 and its thalamic projection in Macaca mulatta, J. comp. NeuroL, 121 (1963) 259-269. 53 STRICK, P. L., Multiple sources of thalamic input to the primate motor cortex, Brain Research, 88 0975) 372-377. 54 VAN BUREN, J. M., AND BORKE, R. C., A reevaluation of the nucleus ventralis lateralis and its cerebellar connections. A study in man and chimpanzee, Int. J. Neurol., 8 (1971) 155-177. 55 VOGT, C., UND VOGT, O., Thalamusstudien I-III, J. PsychoL Neurol. (Lpz.), 50 (1941) 32-154. 56 WIESEL, T. N., HUBEL, D. H., AND LAM, D., Autoradiographic demonstration of ocular dominance columns in the monkey striate cortex by means of transsynaptic transport, Brain Research, 79 (1974) 273-279. 57 WOOLSEY,C. N., SETTLAGE,P. H., MEYER,D. R., SENCER,W., HAMUY,T. P., ANDTRAVIS,A. M., Patterns of localization in precentral and 'supplementary' motor areas and their relation to the concept of a premotor area. In Patterns of Organization in the Central Nervous System, Res. Publ. Ass. nerv. ment. Dis., 30 (1952) 238-264.
253
© Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
T H A L A M I C PROJECTIONS F R O M T H E P R E C E N T R A L M O T O R CORTEX IN MACACA FASCICULARIS
HEINZ K()NZLE
Institute for Brain Research, University of Zurich, CH-8029 Zurich (Switzerland) (Accepted August 29th, 1975)
SUMMARY
Radioactive amino acids were injected into area 4 in 7 monkeys (Macaca fascicularis). Ipsilateral corticothalamic projections were traced to Olszewski's nucleus ventralis lateralis pars oralis and pars medialis, the nucleus ventralis posterior lateralis pars oralis, the nucleus ventralis posterior medialis and inferior and to the nucleus reticularis. Some fibers appeared to terminate in the ipsilateral nucleus ventralis lateralis pars caudalis, the nucleus lateralis posterior and the nucleus subthalamicus. A bilateral representation was found in the nucleus centrum medianum, possibly in the paracentralis-centralis lateralis complex and in the paralamellar portion of the nucleus medialis dorsalis. The contralateral labeling was due to fibers crossing via the massa intermedia and was most intense in the cases following injections into the motor face region. A somatotopic arrangement was clearly present in the nucleus ventralis lateralis pars oralis, the nucleus ventralis posterior lateralis pars oralis and the nucleus ventralis posterior medialis. The origin of the projections to the nucleus ventralis posterior medialis needs further clarification.
INTRODUCTION
Few recent communications regarding thalamic connections from the monkey's area 4 exist~a,2s,43,44,s°; a detailed analysis of these projections, however, has not been published since the Marchi period (for review see Carpenter s and MettleraT). The results of silver degeneration studies of precentral projections to the nucleus (n.) lateralis posterior, the n. ventralis posterior lateralis and medialis have not been in agreement43, 5° and the exact terminations of projections to the n. paracentralis, n. para-
254 fascicularis, n. reticularis, the zona incerta and the fields of Fore113,43,44,5° are still obscure. Moreover, all 43,44,s° but one report 13 describe cortical projections to the ipsilateral thalamus exclusively. In view of the dominant role of the thalamus in sensorimotor mechanisms 14,z° a reinvestigation of the precentral corticothalamic projections has been undertaken, using the autoradiographic technique 1°,3°. Special attention has been given to topographic relationships, e.g., to the cortical ipsi- and bilateral body and face representation and their respective thalamic counterparts. MATERIALS AND METHODS
A detailed description of the present material and autoradiographic methods can be found in an earlier publication z6, where the same 7 adult monkeys (Macaca fascicularis) were used. A reconstruction of the injection fields and some parameters used for tracing the efferent connections from the area 4 are shown in Fig. 1. The identification and nomenclature of thalamic structures follows that of OIszewski 42, although we are aware of the fact that certain boundaries of the ventral lateral nuclear complex are based on somewhat arbitrary cytoarchitectonic criteria 34. RESUL'/S
Labeled axons represented as linear grain arrangements can be seen entering the thalamus from the ipsilateral capsula interna (ci) and terminating in patches of unequally distributed silver grains (Fig. 2). The projections are mainly restricted to 72- 449
73- 319
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Fig. 1. Reconstruction of the injection fields and some parameters used for tracing the efferent connections from area 4. According to the criteria mentioned previously26, the cells lying within the filled circles (blackened area) have taken up, incorporated and transported radioactive amino acids into their terminal ramifications, while cells within the stippled area may have contributed to a faint labeling of the pathways, svt -- survival time.
255
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® Fig. 2. Darkfield light microscopic autoradiographs. A: unequally distributed grains in the n. ventralis lateralis p. oralis (VLo) and linear grain arrangements in the capsula interna (ci). Some unequally distributed grains within fiber-like grain arrangements passing from ci to VLo may also exist in the dorsal part of the reticular nucleus (RT), (exp. 72-451 'leg' injection). × 9. B: a crescent or comma shaped grain patch in the lateral part of the n. ventralis posterior lateralis p. oralis (VPLo). The broad dorsal portion becomes successively smaller ventrally and turns into the n. ventralis posterior inferior (VPI). A few unevenly distributed grains are also observed in R T and the n. paracentralis (Pcn), (exp. 72-451 'leg' injection), x 9. C: a similar grain pattern as in B. The tracer, however, is situated more medially (exp. 72-449 'trunk' injection), x 9. D : grain accumulations in VPLo and Pcn (exp. 72-448 'face' injection), x 28.
256
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Fig. 3. Drawings of the thalamic projections of the ‘leg’ (exp. 72-451) and ‘arm’ (exp. 72-450) area 4. Projections to the midbrain are not drawn. Fiber-like grain accumulations are indicated by lines, unequally distributed grain arrangements, probably representing terminal fields, by dots. The highest density (see key at the bottom left) and the most extensive distribution of grains are found in the ipsilateral VPLo and CM, the lowest in the ipsilateral VLc and St as well as in the contralateral CM. Grain patches in VLo/VPLo resulting from precentral ‘leg’ injections are lying laterally, those from ‘arm’ injections more medially. Abbreviations used in this and in the following figures: Cd, n. caudatus; ci, capsula interna; CL, n. centralis lateralis; CM, n. centrum medianum; CL, n. geniculatum laterale; HI, He, fields of Fore]; LP, n. lateralis posterior; MD, n. medialis dorsalis; mi, massa intermedia; Pen, n. paracentralis; R, n. ruber; RT, n. reticularis thalami; thi, tractus habenulo-interpeduncularis; SN, substantia nigra; St, n. subthalamicus; VA, n. ventralis anterior; VLc, n. ventralis lateralis p. caudalis; VLm, n. ventralis lateralis p. medialis; VLo, n. ventralis lateralis p. oralis; VPI, n. ventralis posterior inferior; VPLc, n. ventralis posterior lateralis p. caudalis; VPLo, n. ventralis post. lateralis p. oralis; VPM, n. ventralis posterior medialis; 21, zona incerta.
257 the ipsilateral thalamus: some fibers, however, cross the midline via the massa intermedia to the contralateral side. The highest density of grains is found in the n. ventralis posterior lateralis pars oralis, and in the n. centrum medianum. Patches of lowest density, on the other hand, exist in the n. ventralis lateralis pars caudalis and in the n. subthalamicus.
Ventral and lateral nuclear group (VLo, VLe, VLm, VPLo, VPM, VPI, LP) Precentral projections to the ventral and lateral nuclear group are restricted to the ipsilateral side. Dense patches of unequally distributed grains are found in all eases along the whole extent of the n. ventralis lateralis pars oralis (VLo) and the n. ventralis posterior lateralis pars oralis (VPLo) (Figs. 3 and 4). The patches have the shape of a crescent or of a comma (Fig. 2A-C). The broad dorsal portion is most intense in VPLo and may be subdivided into two patches. Ventrally the patches become successively smaller and turn into the n. ventralis lateralis pars medialis (VLm) or the n. ventralis posterior inferior (VPI) (Figs. 2B, 3, 5A). Injections into the precentral face area (exp. 72-448 and 73-320) do not seem to label VPI (Fig. 4). Instead, the silver granules marking the projections of the basal part of the precentral gyrus are found in the n. ventralis posterior medialis (VPM), more pronouncedly in the dorsolateral than in the ventromedial portion (Figs. 4, 5B and 6D). No label can be observed in the parvocellular part of VPM and in VPL pars caudalis. In VLo and VPLo the grain clusters are situated laterally in the 'leg'* (exp. 72-451 and 73-319; Figs. 2A, B and 3), intermediate in the 'arm-trunk'* (exp. 72-449, 72-450 and 73-475; Figs. 2C and 3) and medially in the 'face'* cases (exp. 72-448 and 73-320: Figs. 2D and 4). In VLm and VPI, on the other hand, unequally distributed grain accumulations, although less evident, lie ventrally in the 'leg' and dorsally in the 'arm-trunk' experiments (Fig. 3). An additional grain patch of low density is seen in the n. ventralis lateralis pars caudalis (VLc) in exp. 72-449, 72-450 and possibly in exp. 72-451 (incomplete material) (Fig. 3). The spot is rather small and restricted to the ventrocaudal and lateral part of VLc. It seems partly continuous with the grain accumulations in the n. lateralis posterior (LP), found in exp. 72-449, 72-450, 72-451 and 73-319 (Figs. 3 and 5A). This aggregate is of moderate density, somewhat larger, but also restricted to the ventrolateral portion of LP and without obvious differential topographic arrangement following 'arm' or 'leg' injections. Some tracer can also be observed in the most medial zone opposite to the laterally labeled region in VLc and LP in exp. 72-448 to 72-451. This zone (arrow, Fig. 4) is a transitional region in or between VLc, LP, VPL, CL and CM. The grain patch seems confluent with that in CM rather than with that in LP or VLc. Other nuclei of the lateral nuclear group are not affected.
* For the sake of simplicity the injections into the precentral 'leg-tail', 'arm-trunk' or 'face' area (anatomically defined according to the map of Woolsey e t al. 57) are called 'leg', 'arm-trunk' and 'face' cases.
258
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Fig. 4. Drawing of the thalamic projections of the precentral 'face' area (exp. 72-448). Note the intense labeling of the contralateral CM and the accumulation of grains in an unidentified region lateral to the intralaminar nuclei (arrow). Abbreviations and symbols as in Fig. 3.
259
Fig. 5. Darkfield light microscopic autoradiographs. A: grain accumulations of low to moderate density in the n. lateralis posterior (LP), the n. ventralis posterior inferior (VPI) and the n. subthalamicus (St). A grain patch of high density is seen in the most dorsolateral portion of the n. centrum medianum (CM) (exp. 72-449). x 9. B: the bilateral projection field in the ventrolateral portion of CM and fibers crossing via the massa intermedia (mi) following precentral 'face' injections. The ipsilateral n. ventralis posterior medialis (VPM) and the n. medialis dorsalis (MD) are partially labelled (exp. 72-448). x 9. C: a section from Fig. 5B showing the crossing fibers in the massa intermedia at higher magnification, x 21.
Intralaminar and medial nuclear group (Pcn, CL, CM, MD) Grain arrangements of low to moderate density are found ipsilaterally in a transitional zone within the ventral portion of the n. paracentralis (Pcn)-centralis lateralis (CL) complex (Figs. 3 and 4). The rostral dorsal and ventral parts of the ipsilateral Pcn, in addition, have been slightly labeled in exp. 72-448 to 72-451 (Figs. 2B, 2D, 3 and 4). There may be a few granules on the contralateral side within the ventral P c n - C L complex in exp. 72-448 and 73-320 (Fig. 4). A differential distribution of label according to different injection sites is not evident in the rostrocaudal nor in the dorsoventral plane. The silver grains in the caudal two-thirds of the n. medialis dorsalis (MD) are restricted to the ventral and lateral zones including pars multiformis ( M D m f ) and pars parvocellularis (MDpc) (Figs. 3, 4, 5B and 6). There m a y be a differential distribution of tracer rostrally, indicated by grains lying more dorsally in exp. 72-449, 72-450, 72-451, 73-319 and 73-475, and more ventrally in exp. 72-448 and 73-320. Some particles may be observed in the contralateral ventral zone of M D in exp. 72448 (Fig. 4). The grain patch lying within the ipsilateral n. centrum medianum (CM) is most
261 dense in the cases with large injection fields and long survival time (exp. 72-448 to 72-451; Figs. 3 and 4), moderate in the others. A clear contralateral grain pattern can be found in the cases injected into the motor 'face' area (exp. 72-448 and 73-320). The grain count in the contralateral CM - - although 3-5 times less than ipsilaterally-reveals an up to 20 times higher density than that of the background. In the ' b o d y ' eases only a few (exp. 72-449 to 72-451) or no grains (exp. 73-319 and 73-475) lie in the contralateral CM. Linear or fiber-like grain accumulations passing to the contralateral CM can be followed from the ipsilateral CM across the midline (Fig. 5B and C), but not from the contralateral capsula interna. Apart from the density of particles the bilateral grain pattern is symmetrical, involving CM along its whole rostrocaudal extent. The tracer is restricted to the ventrolateral parts of the ipsi- and contralateral CM in exp. 72-448 (Figs. 4, 5B and 6D) and exp. 73-320. While in these two cases as well as in exp. 73-475 (with granules lying somewhat more dorsally) the grain patches form slightly curved bands throughout C M (Fig. 6D), the grain arrangements in the other cases vary considerably (Fig. 6A-C). The tendency to form bands seems to be restricted to the rostral parts of CM, where they are situated in its dorsomedial portion. The density of grains, however, changes from one section to the other, resulting from rostral to caudal in ring-like, crescent-shaped (open side towards the midline) or irregular patches. At the caudal level the main grain cluster seems to extend into adjoining regions ventrolateraJly to CM. A p a r t from some fiber-like grain arrangements passing from CM to the midbrain, the parafascicular nucleus is almost free of silver particles.
Ventral thalamus and subthalamus (RT and St) Besides fiber-like structures, obviously passing through the n. reticularis thalami (RT), a clear pattern of unequally distributed grains can be seen within this nucleus (Fig. 2A-C). It is involved ipsilaterally along the rostrocaudal extent of VLo/ VPLo (Figs. 3 and 4). The dorsal half is labeled in the cases injected into the motor 'leg' area (exp. 72-451 and 73-319), the ventral, when radioactive amino acids have been injected into the motor 'face' and 'finger' regions (exp. 72-448, 73-320 and 73475). The'arm-trunk' cases (exp. 72-449 and 72-450) resulted in a grain patch within the whole dorsoventral extent of RT. Grains in the zona incerta are rather sparse: those in the fields of Forel (H1, H2 and H) are more abundant, but mainly arranged in a linear or fiber-like fashion.
Fig. 6. Darkfield autoradiograph demonstrating the various grain arrangements in the ipsilateral centrum medianum. Column A represents grain patterns following injection into the motor 'leg' area (exp. 72-451), B, 'trunk' (exp. 72-449), C, 'arm' (exp. 72-450), and those from D are due to a labeling of the precentral 'face' area (exp. 72-448). The upper pictures are taken from rostral, the lower from caudal sections (not necessarily at the same level). Note that the small grain spots to the right in the upper half of each column are in the n. medialis dorsalis (arrow). In column D grain accumulations to the left are in the n. ventralis medialis. Compare also with Fig. 5B. x 7.
262
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Fig. 7. Diagrammatic representation of the bilateral thalamic projections following differentially localized, unilateral injections into the precentral motor cortex. For the reservations concerning VPM projections, see text.
263 In the lateral portion of the n. subthalamicus (St) grain patches of low density can only be seen in the experiments with large injection fields and long survival time (Figs. 3, 4 and 5A). There may be a differential projection since grains resulting from injections into the precentral body region (exp. 72-449 to 72-451) are located more dorsally, those from the 'face' injection (exp. 72-448) more ventrally.
DISCUSSION VLo- VPLo- VPM The present results (summarized in Fig. 7) are consistent with Sakai's findings5° in Macaca mulatta and fuscata, demonstrating precentral projections to VLo and VPLo. These regions are therefore reciprocally and topographically interconnected with area 41,2,25,43,5°,53 and receive cerebellar afferents34. VPLo, however, differs from VLo as to its additional postcentra121 and lemniscaP 5,45 inputs: it may also project to area 3a2t, 2z. In man 19 and chimpanzee s4 the region corresponding to Olszewski's VPLo 42 is called n. ventralis intermedius. This term az expresses best the notion of a separate anatomical and functional entity situated in the rostrocaudal direction between VLo and VPL pars caudalis (VPLc) 22'34'36. According to the lemniscal input 3a and the postcentral connections 21,48 on the other hand, VPM is regarded as the analog to VPLc, representing 'sensory' face and body regions respectively. A cortical input from the primary motor area to VPM, but sparing VPLc, would be in contrast to this concept. Precentral fibers terminating in VPM have already been shown previously29,~°; however, in the present material we cannot exclude the possibility of a direct minimal labeling of postcentral somatosensory cortex, especially in exp. 72-448, one of the more extensive injections (see Fig. 1, Kiinzle26). The situation is also complicated by the fact that sensory cortex of the facial representation swings forward into the precentral region48. VLm- VPI/ VLc-LP No detailed descriptions of precentral projections to VLm and VPI are available. Our positive findings are consistent with the termination areas of cerebellar 34, nigral 9 and pallida127,39 afferents to VLm, suggesting that this nucleus contributes to sensorimotor control mechanisms. It is interesting that corticofugal fibers to VPI have been reported from the postcentral fore- and hindlimb areas 21, and a similar projection from the precentral 'body' region to VPI was also found in the present material. Apart from an unidentified region dorsal to CM (Fig. 4, arrow) the terminal field in VLc and LP is confined to the lateral portion and clearly separated from the main projection field in VLo/VPLo. The fibers seem to originate from the precentral body region. Sakai 5° made similar observations concerning LP. The sparse precentral projections to VLc, apparently in contrast to other investigators43,44,s°, may be explained by delineation difficulties. The boundary between VLo and VLc was assumed to be slightly more dorsal than originally describe& 2. It corresponds to the rather sharp dorsal edge of the grain patch in VLo/VPLo resulting from precentral injections.
264 This definition is consistent with studies demonstrating pallidal afferents to VLo, but not to VLc 27,39 and efferents from VLo to area 4 ~,2,a8,53 and from VLc to area 62,48. Pcn-CL-MD-CM Precentral projections to Pcn, CL and to paralaminar regions of M D have been reported by several investigators13,43,44, s°. A differential input to Pcn (from prefrontal and premotor regions) and CL (from premotor and motor cortex) is not obvious ~3 in our material. Conceivably, Pcn receives a more pronounced projection from the rostral parts of area 4 and from area 6 s°. The most intense precentral projection terminates in the ventral portion of a transitional region between Pcn-CL. This region may correspond to the area described to receive spinal and cerebellar afferents34,a5 and to send fibers to area 425,53. The involvement of the paralamellar portion of MD in sensorimotor mechanisms is suggested by its precentral, cerebellar and spinal afferents31,34,35. The dorsal paralamellar portion, predominantly connected with the precentral body region, is in addition reciprocally interconnected with the so-called frontal eyefield3,52, while the ventral paralamellar portion receiving mainly fibers from the precentral 'face' area projects to the orbitofrontal opercular cortex 48. There are several recent studies about the center median-parafascicular complex 4,6,33,35,36. AS to the topographic organization, the present results are consistent with those of Kuyper's 28, De Vito 13 and Petras 43. Different types of precentral fibers terminating in CM (thin pyramidal tract collaterals, CM-destined axons branching into fibers of small and medium size) have recently been reported s. Their intricate arrangement within CM may be the basis for the uncommonly dense and complex neuropi117,~8,5~,55. RT-St Fiber degeneration following precentral lesions has been mentioned in RT, ZI, St and in the fields of Fore143,44. A clear distinction between fiber and preterminal degeneration, however, has previously not been established. Using the autoradiographic technique, grain patterns suggesting a terminal field are found in RT and St, but not in ZI or in the fields of Forel. Contralateral thalarnic projections A symmetrical bilateral projection field (n. ventralis anterior, medialis and lateralis, VPL, VPI, VPM, MD, Pcn, CL, CM, Pf and RT) has been reported in cats, following lesions of the medial wall of the rostral hemisphere 46,4v. The bilaterality, however, has been restricted to the posterior part of the n. ventralis following lesions of area 4 and 6at and to CM and CL after destruction of the sensorimotor cortex 24. Fibers to the contralateral thalamus have been reported in various lower mammals to decussate in the massa intermediaT,24, sl, the anterior commissure 46,47 and the corpus callosum 46. The present results are similar to those described by Kawana and Kusama 24 in cat and support the sparse findings in monkeys, mentioned by De Vito 13. This
265 conformity favors the idea that the massa intermedia in primates does not only represent a commissure is but also a decussation. Transneuronal transport 16,56 of radioactive material within the ipsilateral CM and a further transport to the contralateral side, however, cannot be excluded. The role of the massa intermedia in motor performance has recently been suggested in monkeys a2. In man, however, the massa intermedia seems to lack commissural fibers 2a, is of variable size and frequently absent lx,49. The regressive tendency within the phylogenetic scale of thalamic commissures and the evolutionary progression of the centre median33, 4° are seemingly in conflict and render an interpretation of the function of the massa intermedia rather difficult. The demonstrated bilateral representation of the primary motor cortex within the medial thalamus and the preferred localization of the monkey's precentral face region within the contra- and ventrolateral CM should stimulate further research; this in turn may clarify the functional role of the massa intermedia concerning face and body movements in monkey and man. ACKNOWLEDGEMENTS The author thanks Prof. K. Akert for his support and encouragement throughout the course of the experiment, and Prof. J. de Groot and Prof. J. M. van Buren for their instructive advice on the manuscript. The skillful technical assistance of Mrs. S. Benguerel, R. Emch, E. Knecht and E. Schneider is appreciated as well as the help of Mrs. U. Fischer and Messrs. H. T. Aschwanden, A. F~ih and J. B. Frei, Supported by grants from the Swiss National Foundation for Scientific Research Nos. 3.823.72 and 3.124.73 and the Dr. Eric Slack-Gyr-Foundation, Ziirich.
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