Cortico-cortical efferents of primary motor and somatosensory regions of the cerebral cortex in Macaca fascicularis

Neuroscience.

1978. Vol. 3. pp. 25-39.

Pcrpmon

Press. Pnnted

in Great Britain.

CORTICO-CORTICAL EFFERENTS OF PRIMARY MOTOR AND SOMATOSENSORY REGIONS OF THE CEREBRAL CORTEX IN MACACA FASCICULARIS H. KCJNZLE’ Institute for Brain Research, University of Ziirich, Ziirich, Switzerland Abstract-The cortical efferents of the primary somatic sensory and motor areas were traced autoradiographically in 13 monkeys (Macaca fuscicularis). Precentral fibers were traced bilaterally to the first and second somatic sensorimotor areas (MIJI, S,,,), to the rostra1 and caudal half of area 5 as well as into the ventral bank of the sulcus cingularis within area 24. The projections to area 5 and the cingulate gyrus appeared to arise only from precentral areas representing trunk and limbs. Furthermore, ipsilateral connections were demonstrated to the caudal parts of area 6 on the lateral aspect of the hemisphere. The existence of ipsilateral postcentral projections to the primary and secondary sensorimotor cortex was confirmed whereas a bilateral projection was found to S,, (all cases), S, (all but the ‘arm’ cases) and MI (only ‘face’ cases). Bilateral connections were also traced to the opercular-insular cortex. The distribution of fibers of the postcentral trunk and limb regions to the superior parietal lobulus appeared to be restricted to the ipsilateral and rostra1 parts of area 5. Apart from the well-known somatotopic and homotopic organization of S, and M[ efferents, heterotopit intra- and interhemispheric projections could be demonstrated. It was suggested that cortical regions representing proximal as well as distal body regions might be transcallosally interconnected. The relationship between primary sensorimotor regions and the cingulate, opercular and insular cortex was discussed, and the implications of the predominant precentral input to area 5 were considered. THE RECIPROCAL connections

of the primary motor (M,) and somatosensory (S,) regions of the macaque’s cerebral cortex and their connections to the second motor (M,,) and somatosensory (S,,) areas have been extensively investigated. Ipsilateral projections of M, to areas 6 and 8, and from ~3,to area 5 have also been described (JONES& POWELL, 1969~; 1970; PAN-

ties and the shortcomings of the fiber-degeneration methods. This autoradiographic analysis is an attempt to re-evaluate the cortical connections of the pericentral region of the primate brain. Preliminary results of this study have been reported elsewhere (K~~NzLE, 19766).

DYA & KUYPERS, 1969; PANDYA & VIGNOLO, 1971;

BOYD, PANDYA & BIGNALL, 1971). However, there is disagreement as to intra-area1 fibers interconnecting the face, trunk and limb regions of MI and S, respectively. Furthermore, it is not clear if ipsilateral efferents from MI or SI (extra-area1 connections) and interhemispheric projections are heterotopic, and if the hand and foot areas receive commissural fibers at all (JONES & POWELL, 1969a,b; PANDYA & VIGNOLO, 1969; 1971; BOYD et al., 1971; SHANKS, RIDCKEL& POWELL, 1975; JONES, BURTON & PORTER, 1975). Many discrepancies may be due to technical difficul-

EXPERIMENTAL PROCEDURES Twelve adult monkeys (Macaca fascicularis) were given single local injections of radioactive amino acids into the pericentral cortex. A triple injection was given in experiment 75-334. The injection sites were anatomically defined according to the maps of Woolsey and his collaborators (WOOLSEY,MARSHALL& BARD, 1942; WCJOLSEY & FAIRMAN, 1946; WOOLSEY,SETTLAGE,MEYER, SENCER,HAMURY & TRAVIS, 1952). Accordingly, injections were aimed at

sites representing the major regions of the body. In the subsequent description the respective cases are referred to as ‘leg‘, ‘trunk’, ‘arm’, or ‘face’ cases. While either C3H]pro1ine or C3H]leucine were used for the precentral cases (for a detailed description of the technical procedures of these cases see K~~NZLE,19756), various of Neuroscience, ’ Present address: Department mixtures of [‘H]proline (L-(5-3H) proline or 3,4(n)3H-proChildren’s Hospital Medical Center, 300 Longwood line, specific activity 18 or 54 Ci/mmol, Radiochemical Avenue, Boston, MA 02115, U.S.A. Centre, Amersham), [‘H]leucine (L(4,5-3H) leucine, Abbreviations: FA, FB, FC, etc., cortical regions accordspecific activity 38 and 51 Ci/mmol) and C3H]arginine ing to the nomenclature of VON BONIN & BAILEY (1947); (L-(5-3H) arginine, specific activity 16Ci/mmol) were inMI, MI,. primary and secondary motor regions according jected into the postcentral cortex. After evaporation and to WOOLSEY et al. (1952): 01, opercular-insular cortex; PA, redilution of the original solution, the precursors were inPC, PEm, PE, cortical regions according to the nomenclajected by a syringe needle driven by a micromanipulator ture of VON BONIN & BAILEY (1947); !3,, S,,, primary and at an injection rate of about 0.2 pl/min. The total volume secondary somatosensory regions according to W~~LSEY and activity applied varied between 0.6 and 5.2 4 and 40 et a/. (1942, 1946); 24B, ventral bank of the sulcus cinguand 100 &i. The needle was withdrawn 10 min after the laris lying within area 24 of BRODMANN(1905). end of each injection. 25

FIG. 1. Reconstruction of site and extent of the injection fields and some parameters used for tracing the cortical connections. According to the criteria mentioned previously (KUNZLE,19756) the cells lying within the filled circles (blackened areas) 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. Experiment 73-475 (L/45 pCi/2d) with an injection into the precentral 'finger' region (in the depth of the rostra1 bank of the sulcus centralis at a level opposite experiment 75-333) is not indicated (see KUNZLE,19756, Fig. 1). A: C3H]arginine, L: [3H]leucine, P: [3H]proline, d days of survival. After a survival time of 1-8 days, the animals were per- (SHANKSet al., 1975; JONES et al., 1975; K ~ ~ z L E , fused either with 4% (w/v) buffered paraformaldehyde or 1976a; GOLDMAN& NAUTA, 1977). The present with a buffered solution of paraformaldehyde (4% w/v) and account will, therefore, not further elaborate the genglutaraldehyde (2.5% w/v). The brains were removed from eral pattern of terminations, but rather concentrate the skull, postfixed and cut into serial frontal sections (car- on the details of cortical topography of the projection bowax sections in the precentral cases, frozen sections in fields. the postcentral cases). Depending on the regions investigated, sections taken at intervals of 75-300pm were Projections of the precentral gyrus (MI) mounted on glass slides and dipped in Kodak NTB 2 or Although grain accumulations of high density may NTB 3 nuclear emulsion, diluted 1: 1 with water. After an exposure time of 8-12 weeks, the sections were developed, occur throughout all cortical layers, labeling within fixed and stained for cell bodies with cresyl violet (KUNZLE, areas receiving fibers from the precentral gyrus is par19756). ticularly dense in layers I, VI and, t o a lesser extent, A detailed description of the injection site has been given 111. Regional preferences of certain cortical layers may elsewhere (KUNZLE,19756; 1977). Reconstructions of the occur, too: In the superior parietal lobule, for injection fields and some parameters used for tracing the example, the highest grain density is found in layer efferent connections from the pericentral cortex are shown I, but in the depth of the dorsal bank of the sulcus in Fig. 1. The cortical areas in the frontal and parietal lateralis, layer VI is most densely labeled. There is lobes were denoted according to the nomenclature of BRODMANN (1905) and VON BONIN& BAILEY(1947). The rather sparse preterminal labeling of layer IV in the opercular-insular regions were subdivided according to the dorsal bank of the ipsilateral sulcus lateralis in cases 72-449, 72-450 and 72-451, a n d in the rostralmost & AKERT(1963). cytoarchitectonic map of ROBERTS portion of the inferior parietal lobule in case 72-448. This activity may be due to a faint contact-labeling RESULTS of postcentral areas by the injection field (see below). Frontal cortex. Precentral efferents within the ipsiThe cortical fields of termination are characterized by homo- and heterogeneous grain arrangements of and contralateral frontal lobe project t o areas 4, 6 varying density, concentrated in different layers of the and 24 (FA, FB, FC, FBA and LC). In other words, cortex a n d giving the impression of more or less pro- MI and MI, (medial and adjacent convexity portion nounced vertically and/or horizontally oriented of area 6 a s well as the dorsal bank of the sulcus bands. An example of this organization is shown in cingularis in area 4 ) are particularly involved. The labeling in the remaining dorsolateral a n d ventrolaFig. 6. The priniciple of these 'columns' or 'zones' has been dealt with in several previous studies teral fields of area 6 a s well a s area 24 is considerably

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sulcus (this region corresponds approximately to that less. Area 8 and 9 (FD) do not exhibit any labeling in the ‘arm’ case). The contralateral projection inon either side. volves all these target areas in case 72-451 (including Case 72-450, with an injection in the precentral the distal limb regions in the rostra1 bank of the ‘arm’ region exemplifies the bilateral frontal projecsulcus centralis), but only those within MI in experition pattern. (Fig. 2): Ipsilateral grain accumulations ment 73-319 (case with short survival time and restricbegin rostrally (Fig. 2, section 1) within the medial ted injection field). Further ipsi- and contralateral and adjacent dorsolateral portion of area 6. This projections to the intermediate third of the lateral labeling corresponds to Woolsey’s arm, trunk and possibly face region of the supplementary motor cor- convexity of area 4 are found in case 72-451. These labeled regions, clearly separated from the main protex. The activity extends caudalwards (Fig. 2, section jection fields, lie adjacent to the caudal end of the 2) into the dorsolateral (supra-arcuate) and ventrolateral (infra-arcuate) area 6 as well as into the ventral arcuate sulcus, corresponding to the precentral upper bank of the cingulate sulcus. While the labeling of trunk region (Fig. 4, section 1) as well as within the this area (hereafter to be called 24B) continues caudaldepth of the sulcus centralis, possibly representing wards as far as the level of the middle precentral motor finger areas (Fig. 4, section 2; for their contragyrus (Fig. 6A and B), the labeling in the convexity lateral representation see KCJNZLE, 1976a, Fig. 1, secpart of area 6 becomes confluent with heavy grain tion 4). Grain accumulations within the ipsilateral accumulations within area 4 (Fig. 2, section 3). At area 6 appear only in case 72-451. They lie within this frontal level the grain pattern involves the dorsal the caudal half of the medial aspect of area 6 (MI1 bank of the cingulate sulcus (supplementary motor arm and trunk, Fig. 4, section 1) and within the dorleg region), the medial aspect as well as the two dorsal solateral convexity adjacent to the sulcus arcuatus thirds of the lateral convexity of the precentral gyrus and area 4. (Fig. 2, sections 3-5; Fig. 6A) along its whole rostra In addition to the bilateral projection to the motor caudal extent (neck, trunk, arm and leg regions of face region (Fig. 5, section 2), the precentral ‘face’ M,). In comparison with the injection field, its immeregion projects into the caudal third of the ventroladiate surround (MI arm and upper trunk) and the teral area 6 (bilaterally in case 72-448, ipsilaterally dorsal bank of the cingulate sulcus (MI1 leg), the grain in case 73-320), as well as into the outer and inferior density is relatively low in the medial and most dorsofaces of the ipsilateral opercular cortex (areas 3, 1 lateral aspect of the hemisphere (M, leg). and 2, Fig. 5, sections 2 and 3). Labeled in case The contralateral projections in this case, although 72-448, furthermore, is a rather sparse projection to the depth of the upper dorsal third of the ipsilateral less dense and somewhat less extensive, are similar sulcus centralis (representing primary motor distal leg to those on the ipsilateral side. The contralateral region, Fig. 5, section 5) as well as bilaterally into labeling in particular appears to involve regions the most dorsolateral and rostra1 half of area 6 (Fig. representing trunk, proximal as well as distal limbs in both MI (note the labeling of the rostra1 bank of 5, section 1). This latter region extends somewhat more rostrally than the corresponding area in the the sulcus centralis in Fig. 2, section 4 and 5) and MI,. Apart from its transition zone with area 4, the ‘arm’ case, but may similarly involve both supplementary face and arm regions. The main Ma face and contralateral area 6 on the lateral convexity is unlabeled. arm representations on the medial aspect of area 6, While the labeled frontal projections in case 73-475 however, are much less prominently involved in the (so-called precentral ‘finger’ case with short survival ‘face’ than in the ‘arm’ experiments. Projections to area 24B cannot be detected in the ‘face’ cases. time and small injection field) are restricted ipsilaterally to the immediate surrounding of the injection Parietal cortex. Precentral projections to the ipsifield and the homotopic contralateral area 4, case and contralateral parietal lobe terminate within the 72-449 with an injection of the precentral trunk postcentral gyrus (areas 3, 1 and 2/PA, PB and PC region exhibits a labeling pattern as extensive as that or S,) and the rostra1 and caudal portion of the superobserved in case 72-450. The focus of the bilateral ior parietal lobule including the adjacent ventral bank projection pattern, however, is somewhat more of the sulcus cingularis (area S/PEm and PE). Labelmedially situated in this case than in case 72-450, and ing of Sir will be dealt with below. in contrast to the latter case only a few grains appear In the precentral ‘arm’ case (case 72-45O/Fig. 2) the to involve the supplementary motor trunk region (but grain distribution within the ipsilateral postcentral Mri arm and leg regions also are labeled). Furthergyrus is as extensive as, but less dense than it is in more, the labeling of area 24B is somewhat more cauthe precentral gyrus. Woolsey’s neck, trunk, proximal dally situated than it is in the ‘arm’ case. and distal arm and leg regions lie within this projecIn the precentral ‘leg’ cases (case 72-451, Fig. 4, tion. Caudally the grain accumulations continue into section 1 and 2, and case 73-319) the grain accumuthe superior parietal lobule (Fig. 2, sections 6-8) parlations are densest in the dorsolateral and medial ticularly its medial convexity and-separated by an aspect of the precentral gyrus (M, and M,, leg area) unlabeled zone-in the dorsal bank of the sulcus inand in area 24B at a level caudal to an imaginary traparietalis. While the labeled region of the dorsolavertical line through the posterior pole of the arcuate teral convexity becomes progressively smaller, the

FIG. 2. Drawings of frontal sections of experiment 72-450 demonstrating the bilateral distribution of silver grains due to a precentral 'arm' injection (blackened areas). The level of the sections is indicated at the upper left comer. Linear or fiber-like grain accumulations are indicated by lines, evenly distributed grain arrangements, representing terminal fields and/or transversely cut fibers within the cortical grey by dots. The region labeled by a question mark could not be investigated. Abbreviations: ai, sulcus arcuatus inferior; ar, sulcus arcuatus; as, sulcus arcuatus superior; ce, sulcus centralis; ci, sulcus cingularis; ip, sulcus intraparietalis; la, sulcus lateralis; pr, sulcus principalis; ts, sulcus temporalis superior.

area of labeling in the dorsal bank of the sulcus intraparietalis increases as the sulcus deepens in more caudal cross-sections. The whole dorsal and a small adjacent portion of the ventral bank are labeled along the rostra1 half of the sulcus intraparietalis, while more caudally the labeling withdraws from the depth of the sulcus intraparietalis to the surface. The areas of labeling in the upper dorsal bank of the sulcus intraparietalis and in the medial convexity of the superior parietal lobule (including the dorsal and adjacent ventral bank of the sulcus cingularis), however, extend caudalwards as far as indicated in Fig. 2, section 8. The grain distribution is bilateral, but the contralateral projections are less dense and more restricted; scarcely any activity is found in the caudal bank of the sulcus centralis (Woolsey's distal limbs). In comparison to this 'arm' labeling pattern, the

grain distribution in the precentral 'trunk' case (experiment 72-449) is similar, but somewhat more dorsally situated. The lateral convexity of the superior parietal lobule is more extensively affected, while the dorsal bank of the sulcus intraparietalis is somewhat more sparsely labeled. In the 'finger' experiment (case 73-475, injected with [3H]leucine, short survival time and restricted injection field), on the other hand, the parietal labeling is restricted to the ipsilateral postcentral gyrus a t a level caudal to the injection field. There is no labeling of the superior parietal lobule. In the precentral 'leg' case (case 72-451) the postcentral projections mainly cover the trunk and leg regions bilaterally. Furthermore, there is an ipsilateral projection, sparse but clearly separated from the main postcentral target region to the middle third of the lateral convexity just caudal to the sulcus centralis

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FIG. 3. Drawings of frontal sections of experiment 75-334 demonstrating the bilateral distribution of silver grains due to a postcentral ‘trunk’ injection. Abbreviations and symbols as in Fig. 2.

(!$ finger region). The superior parietal lobule is most heavily affected on the Iateral and medial convexity, while the labeling of the dorsal bank of the sulcus intraparietalis is less dense and more restricted than in the precentral ‘arm’ case (Fig. 4, sections 3-5). While the grain accumulations in experiment 72-451 extend bilaterally from the sulcus centralis c.audaIward almost to the caudalmost part of the superior parietal lobule they are restricted to the ipsilateral half of the superior parietal Iobule in case 73-319, the postcentral ‘leg’ case with short survival time and restricted injection field. In contrast to the precentral body regions (legtrunk-arm cases), the precentral ‘face’ region (cases ‘72-448 and 73-320) appears not to project to the superior parietal lobule. There may, however, be a sparse dorsally directed projection into the depth of the ipsilateral sulcus centralis in case 72-448 (Fig. 5, section 5), possibly involving the postcentral toe region. The focus of the ‘face’ projections involves the

ventrolateral third of the ipsilatera1 postcentral gyrus (inclu~ng the outer opercular face), with a few grains found in the rostralmost parts of the inferior parietal lobule (Fig. 5, sections 3-6). The contralateral postcentral labeling is rather sparse (less than in the ‘leg’, ‘trunk’, or ‘arm’ experiments with similarly long survival time), and not obvious in case 73-319 [as in the other cases with a survival time of less than 4 days). Opercular, insular and related cortical regions. Based on the pre- and postcentral projection pattern to the opercular and insular cortex and the dorsal and ventral bank of the sulcus lateralis, one may subdivide these regions into three areas: (I) the rostral, outer, inferior and adjacent inner opercular faces (caudal boundary approximately at a Ievel where the inferior and inner opercular faces fuse) representing primary sensory areas (ROBERTS& AKERT,1963); (2) a caudal region involving particularly the dorsal bank of the sulcus lateralis and its adjacent lateral convexity of

FIG.4. Drawings of selected sections of the ipsilateral hemisphere of experiment 72-451 (precentral 'leg' injection) and 74-677 (postcentral 'leg' injection). Note the different extent of pre- and postcentral connections into the superior parietal lobule. Abbreviations and symbols as in Fig. 2.

the inferior parietal lobule often referred to as SII (WOOLSEY & FAIRMAN,1946; ROBERTS& AKERT, 1963; JONES& POWELL,1973; but see Discussion); (3) the insular cortex and adjacent dorsal parts of the inner opercular face here to be called 01. Apart from the labeling of sub-area 1 (mentioned above in connection with the 'face' cases), the precentral efferents particularly involve sub-area 2. The labeling pattern is bilateral and again most extensive in the precentral 'arm' case 72-450 (Figs. 2 and 7). It involves the dorsal bank of the sulcus lateralis along its whole rostrocaudal extent as well as adjacent parts of the lateral convexity of the inferior parietal lobule, the ventral bank of the sulcus lateralis and the caudalmost parts of the insula. The activity is more restricted and mainly confined to the ipsi- and

contralateral depth of the sulcus lateralis in cases 72-451rleg' (Figs. 4 and 7) and 72-499rtrunk' (Fig. 7). In case 72-448rface' the labeled area comprises the ipsilateral outer caudal operculum and the adjacent lateral convexity of the inferior parietal lobule (Fig. 5, sections 4 and 5; the labeled part of the inferior opercular face in Fig. 7 largely corresponds to sub-area 1). An additional projection involves the caudal and dorsalmost insula as well as the ventral bank of the sulcus lateralis (Fig. 5, section 6 and Fig. 7). This latter projection cannot be traced in the other 'face' case (73-320), and no sub-area 2 labeling at all appears in cases 73-319 and 73-475 (the 'leg' and 'arm' cases with short survival time and restricted injection field). Sub-area 3 (01) appears not to be affected in the

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FIG. 5. Drawings of the ipsilateral cortical connections of the pre- (72-448) and postcentral (75-333) ‘face’cases. Abbreviations and symbols as in Fig. 2. precentral ‘body’ cases (cases 72-449, 72-450, 72-451, 73-319 and 73-475) and may or may not be involved ipsiiateralIy in the postcentral ‘face’ cases (cases 72-448 and 73-320). In these Iatter cases it is not clear if the grains in the rostra1 and dorsalmost part of the inner opercular face and adjacent insular cortex (Fig. 5, sections 2 and 3 and Fig. 7) are due to direct the spread of activity from the injection field or to intra-axonal transport of label.

After injection into the postcentral sensory cortex, labeling of high density appears in particular in layer IV (parietal and opercular-insular regions) and/or 111~ (frontal regions). A few grains also appear in

supragranular layers. This supragranular labeling is relatively more pronounced in frontal (particularly Ib and II) than in parietal target areas. The labeling of layer VI is quite variable, in general of Iow density, and scarceiy visible on the contralateral side. Parietal cortex. The ipsilateral efferent connections from S, distribute within the postcentral gyrus as well as in the rostra1 portion of the superior parietal lobule (approximately corresponding to PEm). Contralateral projections are distributed only to S, (in~lu~ng a transitional zone of the rostralmost parts of the superior parietal lobule); none can be traced from injection sites in the postcentral ‘arm’ regions. The most extensive grain distribution appears after a triple injection into the postcentral ‘trunk’ region

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(case 75-334, Fig. 3). Grain accumulations around the injection fields cover the dorsolateral two-thirds of the postcentral gyrus including the rostralmost dorsal bank of the sulcus intraparietalis. A few grains are also observed in its medial convexity and in particular in the dorsal bank of the sulcus cingularis. These areas of labeling represent Woolsey’s trunk, proximal and distal limb regions. Contralateral projections of low density are traced to homotopic regions of the injection fields and their immediate surroundings, as well as into the depth of the rostra1 sulcus intraparietalis (Fig. 3, section 6) regions mainly representing trunk. Only on the ipsilateral side do the grain ‘accumulations continue into the superior parietal lobule caudalwards as far as a level just caudal to that shown in Fig. 3, section 7. They mainly involve the dorsolateral convexity, adjacent to the sulcus intraparietalis as well as the dorsal bank of the sulcus cingularis. The ipsilateral grain distribution in the postcentral ‘leg’ case (case 74-677) is slightly more restricted in its rostrocaudal extent than that just described (Fig. 4, sections 3 and 4) and it mainly involves the most dorsolateral and medial convexity of the parietal lobe representing Woolsey’s leg and trunk regions. A further separate projection of low to moderate density can be traced into the ipsilateral postcentral ‘hand area (Fig. 4, section 2). The few grains in the contralateral postcentral gyrus occupy trunk and proximal leg regions. The projections of the postcentral ‘arm’ cases (cases 74-464 and 74-978) are restricted to the ipsilateral side and involve the area around the injection field and approximately the rostra1 third (in case 74-464 even less) of the superior parietal lobule (particularly the dorsal and an adjacent part of the ventral bank of the sulcus intraparietalis). The ventrolateral half (case 75-333, Fig. 5) and ventrolateral third (case 74-872) of the ipsilateral postcentral gyrus, including outer and inferior opercular faces. are marked by label in the ‘face’ cases. While the superior parietal lobule is free of grains, the areas of labeling extend into the rostralmost parts of the inferior parietal lobule. An additional projection into the ipsilateral postcentral ‘leg’ region can be traced in case 75-333 (Fig. 5, section 5). Discrete contralateral patches of labeling are observed in both ‘face’ cases in homotopic regions as well as in the outer and inferior opercular faces (in parts belonging to ‘S,,‘, see below). Frontal cortex. Projections from the postcentral gyrus to the frontal lobe are distributed in area 4 (Ml and MI,), the medial aspect of area 6 (M,,) and from the ‘trunk’ region only, to area 24B. The projections appear to be only ispilaterally represented except in the ‘face’ cases, where a few fibers can be traced to the contralateral agranular cortex adjacent to area 3. Following a triple injection into the postcentral ‘trunk’ region (case 75-334. Fig. 3. for example) label-

ing of moderate intensity extends in front of the injection field from the depth of the sulcus centralis along two-thirds of the length of the precentral gyrus (Fig. 3, sections 3-5). This region may affect areas representing trunk, proximal and distal arm and leg. Another target area appears to cover the precentral neck and face region (see grain patches in Fig. 3. sections 2 and 3. extending from a level just caudal to the sulcus arcuatus towards and into the sulcus centralis). A third grain accumulation of low density can be observed at the dorsal edge of the superior frontal lobule extending slightly into the rostra1 precentral gyrus (Fig. 3, sections 2 and 3). It may reflect an s,MU (arm) projection. Further labeling of the frontal lobe is confined within the depth of the sulcus cingularis. Appearing at a level somewhat rostra1 to the posterior pole of the sulcus arcuatus, it mainly involves the ventral bank of the sulcus cingularis (area 74B, Fig. 3, sections 24) while at caudal levels it also involves the dorsal bank of the sulcus (supplementary ‘leg’ region, Fig. 3, section 5). The frontal projections of the other postcentral cases are less extensive than those described but similar with respect to the precentral grain accumulations anterior to the injection field. They involve approximately the caudal two-thirds of the precentral gyrus in the ‘leggarm’ cases, and reach the sulcus arcuatus and its adjacent ventral regions in the ‘face’ experiments (Fig. 5. section 2). Projections from the postcentral gyrus to the supplementary motor region are distributed to Woolsey’s face region (Fig. 5. section 1) in the ‘face’ case 75-333, to its caudal trunk or proximal leg region in the ‘leg’ (case 74-677, Fig. 4. section I) and ‘arm’ cases (case 74-978). No such projection is labeled in case 74-464 (‘arm’) and 74-872 (face’). Apart from the labeling of the dorsal and ventral depth of the sulcus cingularis (labeling of banks is questionable) in case 74-978 at a similar level as mentioned above, no further activity is found in area 24. Opercular, insular und related cortical regions. The postcentral projections to the opercular, insular and related cortical regions involve all of the three subareas defined above. Projections to Sr,’ (sub-area 2) appear bilateral in all cases while ipsi- and contralateral labeling of 01 (sub-area 3) appears mainly in the ‘face’. ‘trunk’, and ‘leg’ cases. Labeling of sub-area I (S,) as described above is found only in the ‘face’ cases. Sub-area 2 in particular the dorsal and an adjacent zone of the ventral bank of the sulcus lateralis is involved in all ‘leg’, ‘trunk’, and ‘arm’ cases (Fig. 7). The area of labeling lies somewhat more rostrally (involving the adjacent inferior and inner opercular faces) in the ‘arm’ cases (experiments 74-464 and 74-978) than in the ‘leg’ case (experiment 74-677. Figs. 4 and 7). The caudal opercular and/or adjacent lateral convexity of the inferior parietal lobule are labeled most prominently in the ‘face’ experiments (74-872 and 75-333. Figs. 5 and 7). In the latter case, however,

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FIG. 6. Darkfield autoradiographs demonstrating vertically and/or horizontally oriented bands of varying grain density. (A) Vertically oriented bands(arrowheads) within the precentral gyrus medially to the injection field of experiment 72-450. Arrow indicates the grain accumulation of low density in the ventral bank of the sulcus cingularis (area 248) given at higher magnification in B. 10x. (B) Cinguiate projection of Fig. 6A at higher magnifi~tion. Silver grains predomin~dy he within layer I, III and VI. 19 x . (C) Hetero- (hyer III) and homogeneous (layer I and VI) grain a~umulations within the caudaf postcentral gyrus following a precentral ‘leg’ injection (experiment 72-451). 8 x . (D) Insular projection of experiment 74-677 (postcentral ‘leg’ case). Grains mainly he in layer IV. 11x. Abbreviations: ci, sulcus cingularis; Cl, claustrum; la, sulcus lateralis; Pu, putamen.

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cortex

35

body regions is compatible with anatomical and physiological results suggesting an involvement of the opercular-insular cortex in limbic and visceral sensorimotor systems (HOFFMAN& RASMUSSEN, 1953; FRONTERA, 1956; SHOWERS& LAUER, 1961; ROEERT~& AKERT, 1963; BENJAMIN& BURTON, 1968; WIRTH, 1973; BURTON& JONES, 1976). On the basis of its cortico-cortical connectivity (Fig. 8), the region affected (01) appears to represent a distinct functional area receiving fibers from S,, while the labeled region in the posterior opercular faces and the dorsal and ventral banks of the sulcus lateralis receives input from S, as well as M, and may represent Woolsey’s !$,,. Based on thalamic projections upon the opercular-insular cortex (BURTON& JONES,1976) this caudal region, however. is interpreted to represent S,+ of WHEEL., PETRUCEL~I& WERNER(1969), while Stlfr is situated more rostrally, in part overlapping the labeled area indicated in the present study as 01. In this context it is worth mentioning that OI’s corticocortical relationships are, in a sense, the converse of those of the claustrum, as the latter receives a heavy precentral input (K~~NzLE, 1975b) but only sparse postcentral fibers (KUNZLE, 1977). While the postcentral projection of 01 appears to be separated partly at least from S, and S,,, it is an DISCUSSION open question whether the precentral projection to Variability of results the cingulate cortex (as well as the projection to the cingulate gyrus from the postcentral ‘trunk’ region) A major problem in this study of cortico-cortical outlines an extension of the supplementary motor connations has been the va~ability of the results. area or alternatively, a motor-sensory area in its own In Mme cases, one or other well-known connections right (SHOWERS,1959; KAADA, 1960). Judged by its could not be demonstrated (e.g. the projection from the precentral cortex to MI, and $I, in case 73-475), localization within the ventral bank of the sulcus while an unexpected and extensive intra- and extra- cingularis, the region in question could correspond area1 connection was found labeled in some cases, to the primitive gigantopyramidal area recently debut not in others. As described previously (KiiNZLE, scribed in man (BRAAK,1976). 1975a) the extent of the injection field, the amino acid lntra- and interhemispheric connectivity of the primary applied, as well as the varying survival times may and secondary sensorimotor regions account for these differences. The often very restricted One impressive feature of the present findings lies band-like grain accumulations (some less than 200 pm wide) representing a particular cortical projection, on in the wide spread of intrahemispheric cortic+cortithe other hand, may pose a further di~culty in trac- cal connections, relationships which confirm the gening sparse connections through a series of sections eral notion that primary motor and ~~to~n~ry spaced 75%300pm apart. Negative results such as areas are reciprocally connected and that both project those regarding the precentral projections to area 8 to the secondary motor and somatosensory areas (PANDYA& KUYPERS,1969; JONES& POWELL,1969a; and the surprisingly sparse labeling of fibers project1973; PANDYA& VIGNOLO,1971). Of equal interest, ing from MI to area 6 (apart from Ml,) should therefore be taken with some caution (PANDVA & however, is the evidence that intra-area1 connections are not restricted to the immediate surroun~ngs of KUYPERS, 1969; JONES& POWELL, 1970; PANDYA & each injection site but may, instead, spread widely VIGNOLO,1971). in both the sag&al and transverse direction. Most Opercular, insular and cingulate projections characteristic in this respect are the results of injecProjections from the postcentral cortex to the ipsi- tions locaiized to the dorsal or ventrolateral parts of the hemisphere (‘leg’ and ‘face’ regions). In such cases and contralateral insular cortex, on the other hand, band-like grain a~umulations could be found that have not been demonstrated by silver d~eneration were clearly separated from the injection site and its techniques except for fibers to its most dorsolateral labeled surroundings in the ‘arm’ (cases 72-451 and aspect interpreted as being part of the ‘trunk’ area of S,, (see JONES& POWELL, 1973; POWELL, 1977). 74-677) and ‘leg’ (cases 72-448 and 75-333) region respectively. The present evidence of a topographically organized Similar, though less extensive heterotopic relationprojection originating mainly from axial or midline

there is also a projection to the ventral bank of the sulcus lateralis (Fig. 5, section 6 and Fig. 7). All projections described can be traced to both sides. In the ‘trunk’ and ‘face’ cases the contralateral grain distribution is more restricted but of almost similar density as its ipsilateral counterpart. By contrast, in the ‘leg’ and ‘arm’ cases, labeling is much less dense on the contralateral than on the ipsilateral side. As to sub-area 3 (01), labeling in the ‘face’ cases (74-872 and 75-333) bilaterally involves the rostra1 two-thirds of the inner opercular face and to a lesser extent the insula (Fig. 5, sections 2-4 and Fig. 7). The area of labeling is either locally continuous (case 74-872) or entirely separated (case 75-333) from the labeled region in sub-area 1. Labeling of 01 in the ‘arm’ cases is sparse, and limited to the intermediate third of the region on the ipsilateral side (inner opercular face and insula in case 74-464, insular cortex only in case 74-978, Fig. 7). Dense bilateral projections can be traced into the caudal insular cortex in the ‘trunk’ (case 75-334, Fig. 3, sections 4 and 5, and Fig. 7) and ‘leg’ cases (case 74-667, Fig. 4, section 2 and Figs. 6 and 7). In case 75-334, in particular, these grain a~umulations are continuous with those in sub-area 2.

H.

36

KDNZLI

--

face Ice

s, bank tr. bank

74 - 677

74 - 978

72 - 448

75 -333

FIG. 7. Diagrammatic drawings of the pm- and postcentral projections (shaded area) into a reconstruction of the opercular and insular cortex, redrawn and sfigbtfy modified according to Roaa~rs & AKERT (1963) (upper left). In addition to the area of labelling within the caudal operculum and the dorsal and ventral banks of the sulcus iateralis by pre- and postcentral fibers, there is a further opercularinsular projection (01) from the postcentral gyrus. Ahhreuiatiotts: Allo, allocortex; Ins a, cortex insularis agranutaris; Ins d, cortex insularis dysgranuiaris; Ins g, cortex insularis granularis; OFO, cortex orbitofron~lis; PrCO, cortex opercularis praecentralis: tr, transitionai zone.

Corticocortical

efferents of sensorimotor

I FB (61

I-

FIG. 8. Diagrammatic representation of the ipsilateral connections from M, (above) and S, (below) as revealed in the present study. The cortical grain pattern most consistently observed after pre- and postcentral injection is represented at the bottom right of each diagram. Projections to area 5 only concern the pericentral areas representing body regions. The postcentral input to area 24B (interrupted line) is limited to the ‘trunk’ case. With the exception of the precentral input to the dorsolateral area 6 (FB), efferents originating from M, are represented on both sides. Bilateral projections from S, were traced to Sr, Srr and 01 and to the precentral ‘face’ region. For further details see text. ships appear to exist also in the extra-area] connections. Evidence of such heterotopy was more marked

in the labeled projections from the precentral cortex to S, (e.g. from the precentral ‘leg’ area to the postcentral ‘finger’ region in case 72-451 or from the precentral ‘face’ area to the postcentral ‘toe’ region in case 72-448) than in reciprocating connections. The considerable overiap between the various pre- and postcentral projections to M,, or S,,, as well as the small size of the target regions, rendered an interpretation with respect to a topographic organization of the secondary sensorimotor areas rather difficult. While a somatotopic organization within Mu and $, appears possible with respect to the face versus body representation, we can neither confirm nor exclude such an organization within the body representation (e.g. arm vs leg). Interhemispheric projections from M,, according to

cortex

37

our findings, terminate within MI, MI,, St, and Sn, while projections from S, were traced to the contralateral S, (for exceptions see below), Stt and only in the postcentral ‘face’ cases to Mr. The interhemispheric projections from the precentral gyrus appear to have a rostrocaudal and mediolateral distribution as wide as that of their ipsilateral counterparts, and to involve the rostra1 bank of the sulcus centralis (representing distal arm and ieg). Such a mirror-like grain distribution is less evident in the contralateral projection of the postcentral cortex, although heterotopic distributions are not entirely lacking in their connections either. In the postcentral ‘arm’ cases, interhemisphe~c projections were found labeled to St,, but not to St. Due to the complexity of the postcentral body representation (WOOLSEYet al., 1942; PAUL, MERZENICH& GOODMAN,1972; WERNER& WHITSEL,1973) and the difficulties in delineating injection fields (GRAYBIEL, 1975; KUNZLE, 1975b; HUNT & KUNZLE, 1976) it is questionable whether or not the injection fields were restricted to regions representing the distal arm. The present failure in tracing connections from the S, ‘arm’ region to the contralateral coronally cut area Sr, but not to the tangentially cut area Sn is remarkable in view of the findings of SHANKSet al. (1975) who demonstrated interhemispheric connections to distal arm and leg regions of Sr in sections cut sagitally. However this may be, even should projections from S, to the contralateral distal-arm and distal-leg regions be lacking, the present study has shown projections to such distal regions from the contralateral precentral gyrus, and thus confirms earlier evidence that distal limb regions of the sensory-motor cortex do have callosal afferents (SHANKSet al., 1975; INNO_ CENT&MANZONI& SPIDALIERI,1974). Projections

to the superior

parietal

lobule

The present results indicate that the body regions (trunk and limb cases) of the precentral gyrus project to area 5 bilaterally, whereas the body regions of the postcentral gyrus have only ipsilateral projections to area 5. The somatotopic organization in the coronal plane is similar to that described by JONES& POWELL (1969~~).Furthermore, in some pre- and postcentral cases (72-449, 72-450, 75-334) there are two separate projection fields within the dorsolateral and medial aspects of area 5. These fields may correspond to the two topographically organized fields of peroxidasepositive neurons identified in the same two regions of area 5 after cervical and lumbar spinal cord horseradish peroxidase injections (M. P. BIBER, L. W, KNEISLEY & J. H. LAVAIL,unpublished observations). Precentral projections to the superior parietal lobule are controversial. While JONES & POWELL (1969a, 1970) denied such connections, PANDYA & VIGNOLO (1971) demonstrated that the precentral trunk region does project ipsilatemily to PEm and PE, suggesting that these regions may represent axial body structures. The unexpected finding that precen-

38

H.

KDNzLt

tral projection extends even further caudally (PEm That area 5 on the other hand takes part in the proand PE) than the postcentral efferents (approx PEm) cessing of active motion has recently been demonmay be attributable to the fact that the postcentral strated (AREZZO & VAUGHAN. 1975; MOUNTCASTLEet injection fields did not involve the most caudal region al.. 1975). The present anatomical data may well supof St; alternatively, it may indicate that the caudal port the command hypothesis with a corollary disregions of the superior parietal lobule are particularly charge in the posterior parietal association cortex as involved in motor functions. suggested by Mountcastle and his co-workers. Up until the present single-neuron analyses have failed to reveal significant differences in the spatial Acknowlrdgemmts-The author thanks Prof. K. AKERT for distribution of functionally different neuron populations in the superior parietal lobule (MOUNTCASTLE, his support and encouragement as well as Dr M. P. BIRER LYNCH, GEORCOFQULOS,SAKATA & ACUNA. 1975). It is, however, worth mentioning that the neurons most likely to be involved in high order processing of

somesthetic information are situated in that part of area 5 (see SAKATA,TAKAOKA, KAWARASAKI& SHIBUTANI, 1973, Fig. 1) which in the present material was found to receive afferents from the postcentral gyrus.

and Dr S. BRANDfor their constructive help on the manuscript. He gratefully acknowledges the skillful technical assistance of M. DUTTLE, R. EMCH, A. F~;H, H. HAUSER, D. SAVINI, E. SCHNEIUER and A. E. WATERMAN. This work was supported by grants from the Swiss National Foundation for Scientific Research Nos 3.368.74 and 3.124.73 and the Dr Eric Slack-Gyr Foundation, Zurich.

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(Accepted 29 August 1977)