Strio-Pallidal Projection in the Monkey

J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.29.5.426 on 1 October 1966. Downloaded from

J. Neurol. Neurosurg. Psychiat., 1966, 29, 426

Strio-pallidal projection in the monkey

W. M. COWAN AND T. P. S. POWELL From the Department of Human Anatomy, University of Oxford

The corpus striatum in the mammalian brain appears firmation of the organization of strio-pallidal and to receive only two major groups of afferents: from strio-nigral connexions, but also because they the intralaminar nuclei of the thalamus and from demonstrate the value of the study of the distribu- most areas of the cerebral cortex. A common feature tion ofgliosis as an analytical method in fibre systems of both groups of afferents is their well-developed in which the direction of conduction is known. topographical organization. Rostral and caudal The organized nature of the afferent and efferent parts of the thalamus and cortex are related to the connexions of the striatum has assumed greater corresponding parts of the striatum (Powell and significance with the demonstration by Nauta and Cowan, 1956; Webster, 1961, 1965; Carman, Cowan, Mehler (1966) that the small-celled external segment and Powell, 1963); in the medio-lateral dimension of the globus pallidus sends fibres only to the sub- the organization is more complex, and does not thalamic nucleus, whereas the large-celled inner conform, as might have been supposed, to the simple segment is related to the thalamus and midbrain.guest. Protected by copyright. division of the striatum into a medial caudate Their additional finding that part of the projection nucleus and a laterally placed putamen. Instead, the from the internal segment is to the centromedian available evidence suggests that the efferents from nucleus is of particular interest: first, because it may the greater part of the cerebral cortex and most of provide a 'circular pathway' from the striatum to the the intralaminar nuclei terminate on both sides of globus pallidus and thalamus, and back to the the internal capsule. Thus, for example, in the rabbit striatum; second, because of the substantial projec- the cortex on the dorso-lateral surface of the hemi- tion to the intralaminar nuclei of the thalamus sphere sends fibres both to the caudate and putamen (including the centromedian nucleus) from the (Carman et a!., 1963), and in the monkey, following cerebral cortex (Auer, 1956; Niimi, Kishi, Miki, a lesion in the centromedian nucleus degenerating and Fujita, 1963; Astruc, 1964; Petras, 1964; fibres can be traced into both the caudate and Mehler, 1966; Powell and Cowan, 1966). putamen (Mehler, 1966). In the present paper, on the basis of our own and In view of this evidence it was of some interest to other workers' findings on the strio-pallidal projec- determine whether the functional organization tion, an attempt will be made to synthesize some of imposed upon the architectonically homogeneous the recent anatomical work on the inter-relationships striatum by its afferents is reflected also in its between the cerebral cortex, thalamus, and the strio- efferent connexions. Our attention was drawn to this pallidum. question several years ago when studying the thalamo-striate connexions (Powell and Cowan, MATERIAL AND METHODS http://jnnp.bmj.com/ 1956) because in most of the material used in that study discrete areas of intense gliosis were observed The brains of 28 monkeys (Macaca mulatta) were avail- in different parts of the globus pallidus and sub- able for this study (cf. Powell and Cowan, 1956, 1966). stantia nigra with experiments involving varying In 26 of these brains lesions of varying size had been portions of the caudate nucleus and putamen. The placed in either the caudate nucleus or in the putamen. publication in 1960 and 1962 of papers by Voneida The lesions in the putamen were all placed stereotactically and by Szabo on the distribution of striatal efferents with the aid of Olszewski's Atlas (1952). Several of those showed a close correspondence between the pattern in the caudate nucleus were made in the same way, but a on September 24, 2021 by of the projection of the striatum as determined by number were placed under direct vision, through a trans- Nauta method and our own findings on the dis- callosal approach to the lateral ventricle. In a few of the the brains bilateral lesions had been placed, but they were tribution of gliosis in our earlier material and in always in distinctly different parts of the striatum on the several additional brains prepared since that time two sides. The remaining two brains had large neocortical (Powell and Cowan, 1966). It was considered worth- lesions, without involvement of the striatum, and were while, therefore, to put our observations on record used as controls to show that incidental involvement of not only because they provide independent con- cortical projection fibres does not contribute significantly 426 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.29.5.426 on 1 October 1966. Downloaded from

Strio-pallidal projection in the monkey 427 to the gliosis seen in the globus pallidus after striatal gliosis in distinctly different parts of the globus lesions. pallidus. In the brain of monkey OM 21 a narrow The animals were allowed to survive for periods rang- lesion was placed in the ventro-lateral part of the ing from one to four months after operation, following putamen; the damage extends from just behind the which the brains were removed, fixed either in 70% alcohol and 20% acetic acid or in 10 % formalin and rostral end of the putamen back to the level of embedded in paraffin wax. From the serial sections cut junction of its rostral and middle halves (Fig. 1). throughout the extent of the cerebral hemisphere a In the globus pallidus there is a focus of intense regular one-in-five or one-in-ten series was routinely gliosis in the ventral and lateral parts of the external mounted and stained with thionin. segment beginning just behind the caudal limit of the lesion and extending back to about the middle RESULTS of the antero-posterior extent of that segment. The gliosis reaches as far laterally as the junction be- As the lesions in the striatum and the distribution of tween the putamen and globus pallidus, and medially the resulting gliosis in the globus pallidus in several for a short distance into the internal segment; just of the brains are similar both in their site and extent, as its medio-lateral and supero-inferior limits are only a small number of representative experiments sharply defined so it stops quite abruptly over the will be described in detail. The first two experiments space of a few sections at both its rostral and caudal demonstrate that localized lesions, either in the ends. It may be noted that witliin the area of gliosis putamen or in the caudate nucleus, result in heavy there does not appear to be any appreciable change guest. Protected by copyright.

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FIG. 1. Diagram to show the site and extent of the lesion in the putamen in experiment OM 21 and the distribution of the resulting gliosis in the globus pallidus. In this and the subsequent illustrations in which only one lesion is shown, the area of the striatal damage is indicated in solid black and the pallidal gliosis marked by bold arrows andfilled-in circles. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.29.5.426 on 1 October 1966. Downloaded from

428 W. M. Cowan and T. P. S. Powell

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FIG. 2. The lesion in the head of the caudate nucleus together with the pallidal gliosis in experiment OM 18. in the number, size, or staining of the pallidal posteriorly it comes to involve the dorso-lateral part neurones, although, of course, they are more com- of the internal segment. The similarity in the antero-

pactly arranged than normal. posterior extent of the gliosis in the pallidum in these http://jnnp.bmj.com/ The findings in this brain may be compared with two brains is almost certainly correlated with the those in experiment OM 18 in which the lesion is fact that the lesions in the two cases are more or less situated in the head of the caudate nucleus. Again, co-extensive in this dimension. In the medio-lateral the damage begins just behind the rostral end of the dimension, on the other hand, there is a distinct caudate as a small, oval area of destruction close to topographical difference in the distribution of the the ventricular margin; further posteriorly the lesion gliosis within the pallidum as a whole. occupies a more lateral position at thejunction of the The next group of six experiments has been

middle and medial thirds of the nucleus, but at no selected to illustrate in more detail the principles of on September 24, 2021 by point does it encroach upon the internal capsule the organization of the projection of the putamen (Fig. 2). In the rostral half of the globus pallidus upon the globus pallidus. The site and extent of the there is a dense band of gliosis along the dorso- lesions in the first two of these experiments are medial border of both the external and internal shown in Figure 3. In experiment OM 9 the lesion segments immediately adjoining the internal capsule. occupies a considerable part of the dorso-lateral Anteriorly the gliosis occupies only the dorso-medial region of the putamen from just in front of the corner of the external segment, but when traced middle of its antero-posterior extent back almost to J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.29.5.426 on 1 October 1966. Downloaded from

Strio-pallidal projection in the monkey 429

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FIG. 3. The site and extent ofthe lesions in experiments OM 9 (solid black) and OM 7 (cross-hatching) and the ensuing gliosis in thepallidum (filled-in and open circles, respectively). its caudal end, while that in OM 7 is in the most putamen projects to the corresponding part of the ventral part of the putamen extending over approxi- globus pallidus while dorsal parts of the putamen mately the caudal one-fourth of its antero-posterior are related to more dorsal regions within the extent; in OM 7 the most ventral part of the lesion pallidum. But it should be noted that the most also extends through the white matter inferior to the dorsal quarter of the globus pallidus is free of putamen to involve the tail of the caudate nucleus. gliosis in OM 9 despite the fact that the lesion in this In both brains areas of dense gliosis are found in the case extends right up to the dorsal margin of the That to more of will globus pallidus. due the dorsal lesion putamen. The significance this observation be http://jnnp.bmj.com/ in OM 9 occupies a wedge-shaped area, the base of discussed more fully later, but it may be recalled which coincides with the junction between the puta- that the gliosis resulting from the lesion in the men and pallidum, while the apex reaches for a caudate in experiment OM 18 occupies this area, short distance into the internal segment of the but at a slightly more rostral level. That there is a globus pallidus (Fig. 4). The gliosis is found over comparable medio-lateral organization in the pro- approximately the middle three-fifths of the antero- jection of the putamen is illustrated by the findings posterior extent of the globus pallidus which corre- in the next two experiments.

sponds reasonably well with the relative antero- In experiment OM 8, there is a narrow electrolytic on September 24, 2021 by posterior extent of the lesion in the putamen. The lesion along the lateral edge of the putamen involving gliosis in OM 7, on the other hand, is confined to a approximately the middle third of its antero- triangular area in the most ventral part of the globus posterior extent (Fig. 5). The resulting gliosis in the pallidus over its caudal one-fourth. Together, these globus pallidus is restricted to a small area in the two experiments establish one feature of the pattern external segment only from about the level of the of the projection of the putamen upon the globus posterior limit of the lesion back to about the middle pallidus in showing that the ventral part of the of its antero-posterior extent leaving the most 5 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.29.5.426 on 1 October 1966. Downloaded from

430 W. M. Cowan and T. P. S. Powell

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FIG. 4. A low-power photomicrograph to show the intensity of the gliosis in the lateral part of the globus pallidus in experiment CM 9. The margins of the affected area are indicated by the arrows. P-putamen; GP-globus pallidus; IC-internal capsule. x 28.

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FIG. 5. Tracings ofrepresentative sections through the basalganglia in experiment OM 8 to show the extent ofthe lesion and the distribution ofthe resulting gliosis in this brain (solid black andfilled-in circles, respectively), together with super- imposed tracings of the lesion and gliosis in experiment OM 23 (hatching and open circles). J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.29.5.426 on 1 October 1966. Downloaded from

Strio-pallidalprojection in the monkey 431 anterior part of the external segment and the whole putamen, are consistent in showing quite clearly of the internal segment free of gliosis. In the other that the putamino-pallidal projection is distinctly experiment, OM 23, the ventro-medial edge of the organized in all dimensions and that it is confined to putamen has been damaged in its caudal half, and in the ventro-lateral two-thirds to three-quarters of the this brain the gliosis involves both segments of the globus pallidus. The experiments which follow globus pallidus but only in their most ventral parts. demonstrate a similar degree of organization within Again, as Fig. 5 shows, the antero-posterior extent the projection of the caudate nucleus to the dorso- of the gliosis corresponds quite closely to that of medial part of the pallidum. the lesion. The first of these experiments, OM 34, is described In Fig. 6 a composite diagram is shown of the for two reasons. First, it is the largest lesion of the extent of the lesions at one level, together with the caudate nucleus which we have been able to place resulting gliosis, in two additional experiments, without additional involvement of the internal OM 5 R and OM 22, together with OM 23. This capsule, and secondly, because a comparison of the clearly indicates that with lesions which are situated findings in this case with others in which there are progressively more medially in the putamen, the smaller, centrally placed lesions in the caudate head gliosis in the globus pallidus comes to occupy pro- strongly suggests that with small central lesions a gressively more of its medio-lateral extent, and in considerable number of fibres from the peripheral particular, comes to involve the internal as well as part of the caudate are inevitably interrupted. The the external pallidal segment. Whether the gliosis large lesion in the head of the caudate nucleus in in the external segment after a medially placed lesion, experiment OM 34 was placed by way of a trans- such as OM 23, is due solely to the interruption of callosal approach. The damage extends from the

fibres from more peripheral parts of the putamen or anterior end of the striatum back almost to the level guest. Protected by copyright. whether the medial part of the putamen projects to of the junction of the head and body of the nucleus both segments cannot be resolved. The above and is greatest at about the middle of the antero- experiments, and all others with lesions in the posterior extent of the lesion where all but the lateral http://jnnp.bmj.com/ on September 24, 2021 by 0M22 f--f 6M23 8 _o 1 FIG. 6. A composite diagram to show the extent ofthe lesions at the level ofcrossing ofthe anterior commissure and the distribution of the gliosis in the rostral third of the pallidum, in experiment OM 5(R), OM 22, and OM 23. For con- venience, all the tracings appear as though on the left side. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.29.5.426 on 1 October 1966. Downloaded from

432 W. M. Cowan and T. P. S. Powell

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FIG. 7. The extent of the lesion in the head and the caudate nucleus in experiment OM 34 and the distribution of the gliosis in the dorsomedial part of the globus pallidus. /I I C

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FIG 8 A photomicrograph of the rostral part of the external segment of the globus pallidus in experiment OM 34' to show the intensity of the gliosis (marked by bold arrows) in its dorso-medial one-third adjacent to the internal capsule. IC internal capsule GP globus pallidus x 28 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.29.5.426 on 1 October 1966. Downloaded from

Strio-pallidal projection in the monkey 433 part of the caudate nucleus has been destroyed OM 5 the damaged area is limited to the anterior (Fig. 7). Ventrally, the lateral edge of the lesion abuts one-third of the head of the caudate, while that in upon the internal capsule, but as far as can be deter- OM 12 extends over the posterior half of the head of mined the fibres of the capsule have not been the caudate and the anterior one-third of the body. involved, nor is there any damage on this side to In neither brain has there been any involvement of other structures except for the dorsal part of the white matter except over the very limited area of the septum, a small area of the cingulate gyrus, and the electrode track. The difference in the antero-posterior rostral half of the corpus callosum. The gliosis in positions of the lesions is reflected in the distribution the globus pallidus in this case is found in its dorso- of the gliosis in the globus pallidus in the two brains. medial part over the anterior two-thirds of its extent Following the more anterior lesion of OM 5 there (Fig. 8). Anteriorly the area of gliosis occupies is a small area of gliosis in the dorso-medial corner approximately the dorso-medial third of the cross- of the external segment of the pallidum extending sectional area of the external segment of the globus from its anterior end to a level just in front of the pallidus, but posteriorly it becomes progressively appearance of the internal segment. In experiment restricted, so that near its caudal end it is confined OM 12, the gliosis is limited to the internal segment, to the margin of the internal segment. beginning a little behind its anterior end and extend- In the next two experiments, OM 5(L) and OM 12, ing back to about the level ofjunction of its anterior small electrolytic lesions were placed along the and middle thirds. Although in both cases the medial edge of the caudate nucleus (Fig. 9). In gliosed area is limited to the dorso-medial part of guest. Protected by copyright.

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FIG. 9. The caudate lesions in experiments OM 12 and OM 5(L) (shown in solid black and cross-hatching, respectively) and the ensuing gliosis (filled-in and open circles). J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.29.5.426 on 1 October 1966. Downloaded from

434 W. M. Cowan and T. P. S. Powell the pallidum, that in OM 5 extends somewhat more confined to its body and tail), from many experi- ventrally than the narrow band-like area of gliosis ments with lesions in different parts of the head of in OM 12. Perhaps the most important feature of the nucleus it is clear that there is a medio-lateral these experiments is not simply that the gliosis is at organization within the projection of this part of the different antero-posterior levels in the globus pallidus caudate upon the dorso-medial sector of the pal- but that it is found differentially in the two segments lidum; thus, a comparison of experiments OM 18 of the pallidum. Although we do not have lesions on the one hand, and OM 5 and OM 12 on the in all parts of the caudate (and, in particular, any other, shows that the more lateral lesion in OM 18 guest. Protected by copyright. http://jnnp.bmj.com/ A ,'-'- OM 23 on September 24, 2021 by I FIG. 10. A series oftracings ofequally-spaced sections through the substantia nigra in experiments OM 34 (above) and OM 23 (below) to illustrate the difference in distribution of the gliosis after a large lesion in the head of the caudate nucleus (OM 34) andfollowing a lesion in the ventro-medial part of the putamen (OM 23), In each case the gliosis is indicated by coarse dots and the affected area marked by bold arrows. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.29.5.426 on 1 October 1966. Downloaded from

Strio-pallidal projection in the monkey 435 has resulted in gliosis situated further laterally in the parts of the pars reticulata of the substantia nigra, pallidum than the two more medial lesions of the and together these serve to confirm the general other experiments. organization of the strio-nigral projection described In some of the experiments which have been by Szabo (1962). The findings in two experiments described the area of gliosis in the pallidum has will be described and these clearly illustrate the extended as a band across most of its medio-lateral difference in the projection of the caudate nucleus extent, but we have not observed gliosis occupying and the putamen upon the substantia nigra. In its full dorso-ventral extent after lesions restricted to OM 34, in which the lesion has destroyed a large either the caudate nucleus or the putamen. How- part of the head of the caudate nucleus (Fig. 7), ever, in a number of brains with large lesions involv- quite severe gliosis is found in the anterior half of ing both the caudate and putamen (together with the substantia nigra. Anteriorly, the gliosis occupies the intervening part of the internal capsule) the the medial two-thirds of the cross-sectional area of whole dorso-ventral extent of either the external or the nucleus, but more posteriorly it decreases, to fill internal segments shows gliosis. In those cases in first, the medial half of the nucleus and then, an which the lateral parts only of the caudate and intermediate segment as shown in Figure 10. While putamen are damaged the external segment alone is there is slight gliosis in the pars compacta, the most filled with dense gliosis; after lesions which damage marked change is seen in the pars reticulata extend- the medial parts of the caudate and putamen both ing throughout its whole thickness (Fig. 11). The pallidal segments show gliosis, possibly due to the findings in this experiment may be compared with interruption of fibres originating in more peripheral those in experiment OM 23 in which the lesion is in parts of the striatum. the postero-medial part of the putamen, and gliosis

The gliosis in the substantia nigra after lesions has occurred in the most lateral part of the substantia guest. Protected by copyright. restricted to the striatum is less intense than that nigra over rather more than the posterior half of the found in the globus pallidus, but in the majority of nucleus (Fig. 10); again, the gliosis is primarily in the experiments which have been used in this study the pars reticulata, and at its maximum extent foci of gliosis have been readily detected in different occupies no more than its lateral one-fifth. These . S T- v .-e - .

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FIG. I l. A low-powerphotomicrograph to show the extent ofthe gliosis (marked by arrows) in the rostral part of the substantia nigra in experiment OM 34. ST-subthalamic nucleus; SN-substantia nigra; CP-cerebral peduncle; OT optic tract. x 28. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.29.5.426 on 1 October 1966. Downloaded from

436 W. M. Cowan and T. P. S. Powell two experiments by themselves indicate that in the this is the added difficulty of delimiting with con- striatal projection upon the substantia nigra there is fidence the boundary between an affected area and a well-defined organization in both the antero- the surrounding normal neuropil since the gradient posterior and medio-lateral dimensions, and the of change is usually not sharp. For these reasons it findings in other experiments with lesions in different is likely that the actual areas of termination of strio- parts of the striatum are all consistent with this pallidal fibres may be more or less extensive than our conclusion. findings suggest, but with this qualification it may reasonably be concluded that the margin of error DISCUSSION inherent in the use of this technique is not very great, because the gliosis in the globus pallidus after Before going on to discuss the present findings on the a striatal lesion is so intense and generally very organization of the projection of the striatum upon sharply localized. Moreover, it is worth pointing out the globus pallidus and its significance in regard to that there is remarkably close agreement between the the afferent and efferent connexions of these basal present findings and those of other studies based ganglia, it is necessary first to assess the validity of upon the Nauta method (Johnson and Clemente, the technique which has been used. As we have 1959; Voneida, 1960; Szabo, 1962; Nauta and pointed out above, this study arose from observa- Mehler, 1966). tions which were made quite incidentally during the The findings in this and earlier studies (Voneida, course of a study of the cellular degeneration in the 1960; Szabo, 1962; Nauta and Mehler, 1966) are thalamus after lesions in the striatum and all the consistent in showing that the efferents from the material which has been used was in fact collected corpus striatum project radially 'like the spokes of a with that purpose in view. Had our primary intention wheel' (Papez, 1942) upon the globus pallidus andguest. Protected by copyright. been to study the efferent connexions of the striatum that within the strio-pallidal projection as a whole the method of choice would undoubtedly have been there is a considerable degree of organization. the axonal degeneration technique of Nauta (1957). However, they are inconclusive as to the relation- The use ofgliosis as an indication offibre connexions ship of different parts of the striatum to the two may be criticized on the grounds of the relative pallidal segments, and two alternative possibilities insensitivity of the method and the impossibility of must be considered. First, the projection may be distinguishing between gliosis which is secondary to organized upon a simple topographical basis, so that degeneration of fibres of passage and that which is the two segments of the pallidum receive fibres from found at the site of terminal degeneration. Readily different parts ofthe striatum as shown inFigure 12A. detectable gliosis probably only occurs when there Secondly, all parts of the striatum may project in has been substantial fibre loss, and associated with an organized manner upon both the external and

FIG. 12. Diagram to illustrate the two possible arrangements of strio-pallidal fibres as discussed http://jnnp.bmj.com/ in the text. CN-caudate nucleus; P-putamen; GPe-external segment of globus pallidus; GPi-internal pallidal segment. on September 24, 2021 by

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Strio-pallidal projection in the monkey 437 internal segments as suggested in Figure 12B. In cytoarchitectural differences between the two parts support of the first of these views are the observa- of the pallidum must be looked for in their efferent tions that certain parts of the caudate nucleus and connexions. On the other hand, if the two pallidal putamen project exclusively to either the internal or segments are in fact connected with different parts external pallidal segment. For example, lesions in of the striatum (and the balance of evidence seems to the peripheral part of the putamen, as in experiment favour this position), this difference in the afferent OM 21 of the present series, result in gliosis only in connexions must be regarded as a contributory the external segment of the globus pallidus whereas factor to the cytoarchitectural distinction. While lesions confined to the medial part of the caudate this point must remain sub judice until more con- give rise to preterminal degeneration (Voneida, clusive evidence becomes available, there is un- 1960; Szabo, 1962) or gliosis (experiment OM 12 of equivocal experimental evidence that the two seg- the present series) limited to the internal pallidal ments of the globus pallidus differ markedly in their segment. The main reason for considering the second efferent projection. The most detailed study of these view is the finding that lesions in the putamen and in connexions is that of Nauta and Mehler (1966) who the greater part of the head of the caudate nucleus have shown that the external segment sends fibres appear to result in preterminal degeneration in both only to the subthalamic nucleus whereas the internal segments of the pallidum (Szabo, 1962; Nauta and segment projects widely upon the thalamus and mid- Mehler, 1966). Whether or not this extensive de- brain tegmentum. Depending upon which view of generation is due to the interruption of fibres from the organization of the strio-pallidal connexions more peripheral parts of the striatum is difficult to proves to be correct it would follow that either the determine, but it is significant that both Voneida peripheral parts of the striatum may influence the

(1960) and Szabo (1962) found degeneration limited subthalamus while the central region of the striatum guest. Protected by copyright. to the inner segment when the lesions involved only plays upon the thalamus and midbrain tegmentum, the medial part of the caudate nucleus. Unfor- or alternatively the whole striatum may act upon the tunately, there is no report of the distribution offibre entire pallidal projection field. degeneration in experiments with lesions in the The ordered arrangement of the strio-pallidal peripheral parts of the putamen. It would be interest- projection fibres is only of interest when seen as a ing to know if a lesion in the peripheral part of the part of a larger system of similarly organized con- putamen, similar to those in OM 8 and OM 22, nexions involving the afferents to the corpus striatum would result in fibre degeneration only in the external on the one hand, and the further connexions of the segment of the pallidum, and if this is so, to deter- globus pallidus on the other. From an anatomical mine with the Nauta method at what point in the point of view the striatum and globus pallidus may latero-medial extent of the putamen a lesion would be regarded as lying at the centre of a complex produce preterminal degeneration in the internal interrelationship between the cerebral cortex and segment. It is clearly impossible with available the thalamus, subthalamus, and midbrain teg- neurohistological techniques to resolve the problem mentum. For an understanding of the functional as to whether the central parts of the striatum significance of the connexions between the striatum project differentially upon the two pallidal segments and the pallidum it is, therefore, necessary to con- or to both segments, but the observation that the sider briefly some of the recent evidence on the gliosis occupies a progressively more internal posi- connexions of these basal ganglia. tion within the globus pallidus after more centrally Although the detailed relationship between the http://jnnp.bmj.com/ placed lesions strongly suggests that these parts of cerebral cortex and the corpus striatum has not yet the striatum project upon the pallidum in essentially been determined in the Primate brain, it is clear from the same manner as the peripheral portions. work on lower mammals (Webster, 1961; 1965; The question of the relationship of the striatum Carman et al., 1963; Carman, Cowan, Powell, and to the two segments of the globus pallidus has been Webster, 1965) that the cortex is undoubtedly a considered at some length because of the obvious major source of afferents to the caudate nucleus cytoarchitectural differences between the internal and putamen. Four features of this projection are of and external pallidal segments, and because of the particular relevance in the present context. First, it on September 24, 2021 by recent evidence that the two segments differ signi- is not limited to certain cortical areas (e.g., the ficantly in their efferent connexions. If cytoarchi- motor cortex or the so-called 'suppressor areas') tectural variations reflect differences in connexions, but appears to be contributed to by the entire as has been demonstrated in several other regions cerebral cortex; secondly, the fibres from the cortex of the central nervous system, it would follow that converge in a well-organized topographical manner if all areas of the striatum project upon both parts of upon the striatum as a whole, so that cortical areas the pallidum the significant factor underlying appear to be related to a medio-laterally disposed J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.29.5.426 on 1 October 1966. Downloaded from

438 W. M. Cowan and T. P. S. Powell band within the striatum often including parts of both the caudate nucleus and the putamen; thirdly, all parts of the caudate nucleus and putamen receive cortical afferents, and, fourthly, there is a bilateral projection to the striatum from the sensori-motor cortex. This means that different regions within the striatum are under the influence of cortical areas having distinctly different functions and this must be reflected also in the strio-pallidal projection. The question of the nature of the relationship of the intralaminar nuclei of the thalamus and the striatum is still unresolved, but there is a substantial body of evidence to suggest that they form a second important source of afferents to the striatum (Mehler, 1966; Powell and Cowan, 1956, 1966). This thalamo-striate projection resembles that from the cortex in at least two respects: it is topographic- ally organized and it is known that certain of the nuclei (notably the centromedian) send fibres into both the caudate nucleus and the putamen. At present, the significance of these connexions is rather obscure, but it may be important for an understanding of the strio-pallidal projection to guest. Protected by copyright. point out that the intralaminar nuclei themselves receive fibres in an ordered manner from wide- spread areas of the cerebral cortex and that some of these nuclei are also connected with the dentate nucleus of the cerebellum (Mehler, 1966). Through these various pathways there is a considerable convergence of cortical, thalamic, and cerebellar in- fluences upon the striatum. It follows from the nature of the strio-pallidal projection that there is even greater convergence of effects upon the cells of the globus pallidus, and because of the organized nature FIG. 13. A diagrammatic illustration to show some ofthe of these connexions, it is clear that parts of the major connexions between the cerebral cortex, striatum, globus pallidus (and probably even the two pallidal globus pallidus, and thalamus. For sake ofclarity the con- are influenced one or nexions with the motor cortex have been emphasized (see segments) predominantly by text) and those with the subthalamus, substantia nigra and other area of the cortex or intralaminar nuclei of the midbrain tegmentum have been omitted. It should be thalamus. pointed out that the cortico-striate projection in the upper One conclusion to be drawn from these studies is part of the figure shows only its general topographical that the is placed to strio-pallidum strategically organization with respect to the striatum as a whole, and http://jnnp.bmj.com/ sample the activity of the entire cerebral cortex should not be taken to imply that any specific area of the (through the cortico-striate connexions), to integrate cortex projects to either the caudate nucleus or to the this with the resultant activity of the intralaminar putamen. nuclei of the thalamus, and to affect in turn the activity of one component of the intralaminar system seems very probable that both the centromedian (the centromedian nucleus) and the motor area of the nucleus and the motor cortex project upon those cortex (through the pallidal projection to the ventral parts of the caudate nucleus and putamen which nuclei of the thalamus). In this connexion it may be send their fibres into the internal pallidal segment. on September 24, 2021 by noted that the thalamic nuclei to which the internal Some of these interrelationships are summarized in pallidal segment projects are both closely related to Fig. 13; although this shows some of the major the motor cortex, the ventral nuclei being reci- interconnexions within the forebrain, the total procally connected to the motor area while the system of connexions of the strio-pallidum is clearly centromedian nucleus receives a substantial projec- much more complex as it includes an important tion from it (Astruc, 1964; Petras, 1964; Mehler, descending influence upon the subthalamus and 1966; Powell and Cowan, 1966). Furthermore, it brain-stem. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.29.5.426 on 1 October 1966. Downloaded from

Strio-pallidal projection in the monkey 439

SUMMARY , , and Webster, K. E. (1965). A bilateral cortico-striate projection. J. Neurol. Neurosurg. Psychiat., 28, 71-77. Johnson, T. N., and Clemente, C. D. (1959). An experimental study of the fiber connections between the putamen, globus pallidus, The projection of the corpus striatum upon the ventral thalamus, and midbrain tegmentum in cat. J. comp. globus pallidus and substantia nigra has been deter- Neurol., 113, 83-101. Mehler, W. R. (1966). Further notes on the Centre Median Nucleus of mined by an analysis of the distribution of gliosis in Luys. In Thalamic Integration of Sensory and Motor Activities, these structures after a variety of lesions in the edited by D. P. Purpura, M. B. Carpenter, and M. D. Yahr. nucleus and putamen. The strio-pallidal Columbia University Press, New York. (In Press.) caudate Nauta, W. J. H. (1957). In New Research Techniques ofNeuroanatomy, projection appears to be organized upon a rather pp. 17-26. Edited by W. F. Windle. Thomas, Springfield, Ill. simple topographical basis; 'peripheral' parts of the , and Mehler, W. R. (1966). Projections of the lentiform nucleus in the monkey. Brain Res., 1, 3-42. striatum project upon the external segment of the Niimi, K., Kishi, S., Miki, M., and Fujita, S. (1963). An experimental pallidum, but whether the more 'central' parts of study of the course and termination of the projection fibers upon internal from cortical areas 4 and 6 in the cat. Folia psychiat. neurol. the striatum project exclusively the jap., 17, 167-216. segment or upon both segments cannot be resolved. Olszewski, J. (1952). The Thalamus of the Macaca mulatta: An Atlas of this ordered projection is dis- for Use with the Stereotaxic Instrument. Karger, Basel. The significance Papez, J. W. (1942). A summary of fiber connections of the basal cussed in relation to other recent evidence on the ganglia with each other and with other portions of the brain. connexions of the basal ganglia. Res. Publ. Ass. nerv. ment. Dis., 21, 21-68. Petras, J. M. (1964). Some fiber connections of the precentral cortex (areas 4 and 6) with the diencephalon in the monkey (Macaca This work was supported by a grant from the Medical mulatta). Anat. Rec., 148, 322. Research Council. Powell, T. P. S., and Cowan, W. M. (1956). A study of thalamo-striate relations in the monkey. Brain, 79, 364-390. -,- (1966). The interpretation of the degenerative changes in the intralaminar nuclei of the thalamus. J. Neurol. Neurosurg. REFERENCES Psychiat., in the Press. Szabo, J. (1962). Topical distribution of the striatal efferents in the guest. Protected by copyright. Astruc, J. (1964). Corticofugal fiber degeneration following lesions monkey. Exp. Neurol., 5, 21-36. of area 8 (frontal eye field) in Macaca mulatta. Anat. Rec., 148, Voneida, T. J. (1960). An experimental study of the course and des- 256. tination of fibers arising in the head of the caudate nucleus Auer, J. (1956). Terminal degeneration in the diencephalon after in the cat and monkey. J. comp. Neurol., 115, 75-87. ablation of frontal cortex in the cat. J. Anat. (Lond.), 90, 30-41. Webster, K. E. (1961). Cortico-striate interrelations in the albino rat. Carman, J. B., Cowan, W. M., and Powell, T. P. S. (1963). The J. Anat. (Lond.), 95, 532-544. organization of the cortico-striate connexions in the rabbit. (1965). The cortico-striatal projection in the cat. Ibid., 99, 329- Brain, 86, 525-562. 337. http://jnnp.bmj.com/ on September 24, 2021 by