The projection of the auditory cortex upon the diencephalon and brain stem in the cat

305

BRAIN RESEARCH

Research Reports

T H E P R O J E C T I O N OF T H E A U D I T O R Y C O R T E X U P O N T H E D I E N C E P H A L O N AND BRAIN STEM IN T H E CAT

I. T. D I A M O N D , E. G. JONES AND T. P. S. POWELL

Department of Human Anatomy, University of Oxford, Oxford (Great Britain) (Accepted April 23rd, 1969)

INTRODUCTION

In the auditory cortex of the cat a number of subdivisions have been recognized on the basis of electrophysiological criteria as well as by their anatomical features and the boundaries defined by changes in architectonic structure correspond closely with those determined by the method of evoked potential32, as. Studies using the method of retrograde cell degeneration have demonstrated that the thalamic projection upon these fields also differs, either in arising from distinct parts of the medial geniculate nucleus or in being of a different nature2, a2. More recently these subdivisions of the auditory cortex have also been found to have different patterns of cortical connections, and this is particularly true of the commissural system 3. The present study concerns the projection of the individual subdivisions to subcortical structures, and especially to the relay nuclei of the ascending auditory pathway. The presence of such corticofugal fibers has already been demonstrated with axonal degeneration techniques and these fibers have been shown to arise from all subdivisionsl,12,z6,36, 37. However, little attention has been paid to possible differences in the projection of the various fields, and this is now of particular interest in ielation to the recent subdivision of the medial geniculate nucleus into several components which differ not only in their neuronal architecture but also in the nature and origin of their afferent fibers from lower levels of the auditory pathway 15,18. Furthermore, there is no information in regard to the termination of corticofugal fibers from the auditory cortex in the posterior group of the thalamus, which has been shown to be a part of the thalamic auditory systeml4, zz. MATERIALAND METHODS The brains of 19 cats have been used in this investigation; many of them were also used in previous studies on the association and commissural connections of the Brain Research, 15 (1969) 305-340

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auditory cortexa, 4 and the details of the operative procedure, fixation and histological techniques have been given. It may be noted that in all but 2 of the experiments the postoperative survival period was between 5 and 7 days, but 2 cats were killed 3 days after operation. The distribution of the fiber and terminal degeneration in subcortical structmes was studied in frozen sections stained by the Nauta and Gygax methodlL The rzsults will be conveyed by a series of drawings of thalamic and/or b~ain stem sections for each case with the locus and type of degeneration depicted. In drawing the thalamus an effort was made to indicate the various subdivisions of the principal division of the medial geniculate nucleus described by Morest 17. This was done partly by reference to Morest's maps, partly by an examination of adjacent Nissl sections, and partly by differences in the pattern of degeneration which different subnuclei displayed. Insofar as this last was part of the criteria for subdivision, the correlation between subdivision and type of degeneration is perhaps less precise than the lines in the drawing would suggest. It is our view that this qualification does not detract t¥om the main force of the findings. RESULTS

The sites of the lesions in the auditory cortex will be described in terms of the subdivisions of this sensory area proposed by Rose 3° on the basis of architectural features, and by Woolsey as in his synthesis of the available anatomical and electrophysiological data. Although there are certain differences in the extent of the fields, depending upon the criteria adopted, the differences do not appear to be very important for the present study; however, if any ambiguity in boundaries is considered to be of significance in the interpretation of the experimental findings, then attention will be called to the various criteria for subdivision. In regard to the terminology of the nuclei of the thalamus and brain stem the conventional classification has been followed s, and it is necessary only to state briefly our usage for the medial geniculate nucleus and the posterior group of the thalamus. For the medial geniculate nucleus the division into a lateral small-celled division and a smaller, medially situated large-celled part has been followed27,aL In addition, the subdivision of the small-celled or principal division by MoresO 5 has been found to be most impoltant for the interpretation of the distribution and form of the axonal degeneration after cortical lesions. On the basis of neuronal architecture and type of axonal plexus, Morest has described ventral and dorsal divisions, and within each of these there are subnuclei. In the ventral division there is a pars lateralis in which the neurons are arranged in curved, parallel lamellae, and a more medial pars ovoidea in which the laminae are coiled; superficial and ventrolateral to the ventral nucleus is a small ventrolateral nucleus ; in the dorsal division there is a dorsal nucleus, a deep dorsal nucleus and a superficial dorsal nucleus. The subdivisions labelled deep dorsal and superficial dorsal by Morest lie adjacent to the posterior group of tbalamic nuclei, and indeed whether they should be classed as part of the posterior group or part of the medial geniculate proper is difficult to determine. The subdivision labelled ventral by Morest probably corresponds largely with the rostral two-thirds of the principal division as this term has been used in Brain Research, 15 (1969) 305-340

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earlier papers 32. The subdivision labelled dorsal by Morest is virtually identical to the caudal pole of the medial geniculate ~. The detailed descriptions of other workers14, 2a,3.a have been used for the delimitation of the posterior group, and the usefulness of dividing this complex into medial and lateral divisions 14 has been shown not only on the basis of the distribution of ascending fibers but also on the basis of the restricted sites of termination of fibers from the somatic sensory area of the cortex 9. From our own unpublished observations we would suggest that the medial division of the posterior group, as described by Moore and Goldberg 14, may be further subdivided into an intermediate part, lying more dorsally in relation to the ventral margin of the more posterior parts of the lateroposterior nucleus, and a medial part situated more ventrally and anteromedial to the magnocellular division of the medial geniculate nucleus and extending forwards dorsomedial to the ventroposterior nucleus. That these parts differ in their architectural features has already been reported 23. It should be mentioned that although the posterior group of nuclei usually includes the suprageniculate nucleus, the latter is sufficiently distinct to be identified and described separately; the nucleus limitans, however, has been included with the suprageniculate nucleus. Experiment 270 is an example of a large lesion which has involved several fields of the auditory area and in which the minimal involvement of white matter does not appear to have interrupted fibers passing to or from more dorsally situated areas such as the visual cortex. Fields A I, A I I , EP and the suprasylvian fringe have been damaged, but that part of the auditory cortex in the anterior ectosylvian gyrus and the insulotemporal area in front of and behind the pseudosylvian sulcus are not affected. In the horizontal sections of this brain (Fig. 1) the course and termination of the degenerating fibers are clearly seen. Dense degeneration is present in the posterior part of the head, the body and tail of the caudate nucleus and in the putamen. A few degenerating fibers enter the thalamus dorsal to the lateral geniculate nucleus and terminate in the posterior part of the pulvinar and more medially in the suprageniculate nucleus. A far greater number of coarse degenerating fibers leave the internal capsule ventral to the lateral geniculate nucleus and in front of the optic tract; as they pass through the reticular nucleus some fibers terminate as pericellular arborizations. On successive sections the degenerating fibers can be seen to pass posteriorly, medially and ventrally between the optic tract and small-celled part of the medial geniculate nucleus, laterally, and the ventroposterior nucleus and magnocellular division of the medial geniculate, medially. Intense fiber and terminal degeneration is found in the lateral component of the posterior group lying in the angle between the optic tract and the ventroposterior nucleus, and although a little extends more medially into the intermediate part of the posterior group, there is none in the most medial part (i.e. medial to the magnocellular division of the medial geniculate nucleus and dorsomedial to the ventroposterior nucleus). The degeneration in the lateral component is directly continuous posteriorly with similarly dense degeneration in the small-celled part of the medial geniculate nucleus. Numerous coarse degenerating fibers continue posteriorly in the brachium of the inferior colliculus, and many of these turn medially and laterally into both main parts of the medial geniculate nucleus. In the small-celled part of the nucleus there is a very dense plexus of degenerating fibers; near the brachium it is denser and has a high Brain Research, 15 (1969) 305-340

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proportion of coarse fragments, but further away from the brachium it becomes progressively less dense and finer, which is in accord with descriptions of such fibers in Golgi-impregnated materially, 24. The anterior two-thirds of the nucleus are severely affected but there is an abrupt diminution about the junction of the middle and posterior thirds of the nucleus; the latter is not completely clear, however, as there are a few fine degenerating fibers present. Within the anterior two-thirds of the nucleus there is also less degeneration dorsally and laterally; differences in the orientation of the fibers can also be seen, changing from being predominantly horizontally disposed as they enter the nucleus from the brachium, to being cut transversely in more lateral parts. In the magnocellular part, lying medial to the brachium, coarse degenerating fragments are seen, but they are not as numerous as in the small-celled component nor is there such an obvious pericellular plexus. At more ventral and posterior levels terminal degeneration is also found in the interstitial nucleus of the brachium of the inferior colliculus and in the suprapeduncular nucleus; this degeneration is continuous anteriorly with that in the medial geniculate. No degeneration is seen in any other thalamic nucleus. In the brain stem degeneration is found in several structures. In the superior colliculus fiagmented fibers are present in the deeper layers throughout most of its anteroposterior extent, but pericellular plexuses of fine degeneration are seen only in the posterior part. Numerous coarse degenerating axons continue caudally in the brachium of the inferior colliculus and are more numerous in its lateral parts. In the parabrachial region, medial to the brachium, quite marked terminal pericellular plexuses are present, and some of these encroach upon the adjoining midbrain tegmentum. When the degenerating fibers in the brachium reach the inferior colliculus they take different courses. Many continue into the external or lateral nucleus, and although some may terminate around the cells of this part of the colliculus, few or none appear to penetrate the lateral margin of the central nucleus; the majority of the fibers continue to the posterior surface where they break up into numerous fine fibers which appear to run transversely in the posterolateral part of the central nucleus. Other fibers of the brachium continue into the 'cortex' on the dorsal surface of the colliculus where they terminate in all layers. Yet others sweep medially across the anterior surface of the colliculus to reach its medial edge. Here some cross the midline in the commissure while others remain on the ipsilateral side. The latter either terminate in the 'cortex' on the medial surface or pass backwards, as a band of fine fibers in the medial part of the central nucleus, to again reach the posterior surface. On the posterior surface therefore, there are two distinct bands coming in from the medial and lateral margins and these cover the entire dorsoventral and mediolateral extent. Apart from this degeneration in its medial and posterior parts there is surprisingly little in the central nucleus. In the contralateral colliculus the pattern of degeneration is similar, except that it is sparser, and in particular there is only an occasional fiber in the lateral nucleus. Although some degeneration is found immediately ventral to the colliculus, it is lateral to the lateral lemniscus and none is present in the nuclei of this tract, nor in any other more caudally placed nucleus of the auditory pathway. It is of interest that in this experiment in which all divisions of the auditory Brain Research, 15 (1969) 305-340

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Fig. 3. Photomicrographs showing: (A) degeneration of fine fibers and terminal degeneration in the dorsal nucleus of the small-celled part of the medial geniculate nucleus, in experiment 211, x 550; (B) degenerating axons of medium size and pericellular fragmentation in the deep dorsal nucleus in experiment 202, × 550; (C) the parallel arrangement of the degenerating cortico-geniculate fibers in the ventral nucleus of the medial geniculate body in experiment 202, x 550; (D) axonal and terminal degeneration in the lateral division of the posterior group in experiment 206, × 580. Nauta-Gygax method.

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cortex except the insular area and anterior ectosylvian gyrus were damaged little degeneration was found in the caudal third of the medial geniculate nucleus, in the most medial part of the posterior group nor in the central nucleus of the inferior colliculus. These findings are confirmed in experiment 202 (Fig. 2) in which the surface extent of the lesion is similar but, because of an extension into the white matter, fibers from more dorsal areas of the cortex are interrupted. The total distribution of the degeneration in subcortical structures will not be described, but the coronal sections show certain additional features in the medial geniculate nucleus and the inferior colliculus. In the geniculate nucleus there is intense degeneration, and again it is more marked and the fragments are finer in the small-celled than in the magnocellular division. Such dense degeneration is found throughout the anterior two-thirds of the small-celled part, but in its posterior third only occasional fragmented fibers are seen and these are more numerous ventrally. This brief description of the degeneration in the medial geniculate nucleus is a general account, but there are important variations in the extent and nature of the degenerating fragments which can be correlated closely with the subdivisions of the nucleus described by MorestlL In the anterior third of the nucleus the entire cross-sectional area is affected, but dorsally, in the part corresponding to the dorsal division, it is less dense, more loosely arranged and irregular than in the ventral division; in the latter the fibers are slightly larger, more tightly packed around the perikarya and tend to have a vertical, parallel arrangement. At the junction of the anterior and middle thirds, opposite the posterior end of the lateral geniculate nucleus, the intensity begins to diminish, particularly in the dorsal division, and the differences between the various parts become more distinct. As these can be clearly seen on the same section they are not due to variations in staining. In the dorsal division both the deep dorsal and superficial dorsal nuclei are affected, and here there is moderately severe degeneration of medium and fine fibers which are loosely arranged (Fig. 3). In the ventral division the medium-sized degenerating fibers are more clearly arranged in parallel rows in between the curved columns of cells, but with cross branches between them (Fig. 3). At progressively more posterior levels the degeneration becomes less dense and more ventrally situated so that the deep dorsal and ventral division are mainly affected. Finally, in the caudal tip of the medial geniculate body, made up entirely of the dorsal nucleus, there is only an occasional degenerating fiber. The magnocellular division is affected throughout its anteroposterior extent, and all parts of the lateral and intermediate components of the posterior group, including the suprageniculate nucleus, are involved; only the most medial part, anteromedial to the magnocellular division of the geniculate is free. The pattern of degeneration in the inferior colliculus is the same as in the previous experiment and the degeneration in all layers of the 'cortex' on the dorsal and medial aspects is seen more clearly. There is a band of degenerating fibers just within the medial edge of the central nucleus; from this, fibers penetrate a little further into the dorsal part of the nucleus at anterior levels and progressively more ventrally at posterior levels. These fibers clearly run in parallel rows, downwards and laterally between the cells which are arranged in similarly orientated columns (Fig. 4). The greater part of the central nucleus is clear, however, and no degenerating fibers enter its lateral aspect from the lateral nucleus; on the Brain Research, 15 (1969) 305-340

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Fig. 4. Photomicrograph to show the parallel arrangement of the degenerating cortico-tectal fibers in the central nucleus of the inferior colliculus in experiment 202; A, × 430; B, × 750. Nauta-Gygax method.

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been described in the nuclei of the brain stem of these 2 experiments is orthograde in nature, it is possible that the degeneration in the medial geniculate nucleus is retrograde, particularly as the distribution of the severe degeneration in the anterior twothirds is in accord with retrograde cellular degeneration studies of the projection of the nucleus upon the cortex ~2. In 2 experiments, therefore, a survival period of only 3 days was allowed after placing large and deep lesions in the auditory cortex, one in A I and the other in A II, since at this shorter survival period the degeneration is less likely to be retrograde in nature 7,9. In both brains unequivocal degeneration is present in the medial geniculate nucleus and in the posterior group; it is more dense and the fragments coarser in the magnocellular than in the parvocellular divisions, and in the latter there is more fine granularity than at 7 days. The insulo-temporal area was also spared in these experiments, and in the caudal part of the medial geniculate body the degeneration is again found only in the deep dorsal and ventral nuclei, the dorsal nucleus being clear. Experiment 211 (Fig. 5) demonstrates that damage of the insulo-temporal region, in addition to A I and A II, results in severe fiber and terminal degeneration throughout the anteroposterior extent of the medial geniculate nucleus. The lesion is in the form of a narrow strip extending almost vertically downwards from the middle suprasylvian sulcus above to the rhinal sulcus below; it involves approximately the middle of the anteroposterior extent of A I, the posterior part of A II and the cortex adjoining the anterior and posterior banks of the pseudosylvian sulcus; there is no extension into the white matter. Terminal degeneration is present in the same nuclei of the thalamus and brain stem as in the previous experiment with large lesions of the auditory cortex, but only that in the medial geniculate nucleus and posterior group need be considered. In the parvocellular part of the geniculate nucleus there are several features of the degeneration which are of interest. The first of these is that marked degeneration extends throughout the anteroposterior extent of the nucleus, and there is no abrupt difference in the intensity or distribution of the degeneration in the caudal third as compared with that in more rostral parts. The second feature is its distribution and nature in the various subdivisions of Morest15; it affects 5 of these subdivisions, the pars lateralis and medialis of the ventral division, the ventrolateral nucleus, the deep half or so of the deep dorsal nucleus and the dorsal nucleus, but there is very little in the superficial dorsal nucleus. Although the degeneration in these divisions is in continuity, there is a definite gradient in the size of the degenerating fragments. Those in the ventral nuclei are of medium-sized fibers, in the deep dorsal of medium and fine, and they are sparser than in the ventral, while in the dorsal nucleus they are of very fine fibers (Fig. 3). The third point is the distribution of the degeneration in the mediolateral dimension as it forms a slightly oblique band of quite severe degeneration occupying the middle third of the mediolateral extent of the deep dorsal and ventral nuclei; there is sparser fragmentation in both parts medial to this band, but the lateral parts are clear. In the dorsal nucleus, in the caudal third of the medial geniculate body, degeneration is again in a band, but this is orientated more obliquely, from dorsolateral to ventromedial, and there is sparse degeneration both medial and lateral to it. The final point is that in the ventral nucleus the fragmented fibers are Brain Research, 15 (1969) 305-340

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predominantly orientated in parallel with each other between the curved cell columns with the pericellular terminal degeneration in between. In the dorsal division there is no such arrangement. Thus the findings in this brain, which are confirmed by others with small lesions, suggest that the degeneration in the dorsal and ventral divisions differs both in intensity and in the orientation of the fibers. Quite marked fragmentation is also distributed throughout most of the extent of the magnocellular division of the geniculate. In the posterior group degeneration is found in the lateral division, lying in front of and merging with the rostral end of the geniculate, and there is also a little in the more dorsal, intermediate part and in the suprageniculate nucleus. Again, the medial, somatic portion, lying anterior and medial to the magnocellular division, is clear. It may also be noted that following this lesion which is restricted to the auditory cortex there is degeneration in the dorsolateral and paramedian groups of the pontine nuclei; this is intense on the ipsilateral side with a little also in the contralateral nuclei. That severe degeneration only occurs in the caudal third of the medial geniculate nucleus after involvement of the insulo-temporal region is confirmed by other experiments in which deep lesions in this part of the cortex have resulted in a pattern of degeneration in the nucleus very similar to that of the previous experiment. There is one feature of the distribution of the degeneration in these brains with damage of the insulo-temporal region which has not been observed in the other experiments which have been described. At about the level of junction of the anterior and middle thirds of the medial geniculate body a band of dense fiber and terminal degeneration is seen passing medially from the brachium of the inferior colliculus. This degeneration lies between the magnocellular medial geniculate nucleus above and the substantia nigra below; some of the fibels traverse the medial lemniscus before sweeping dorsally to become continuous with the degeneration in the suprageniculate nucleus. The experiments which have been described have shown the total distribution of the efferent fibers of the auditory cortex to the diencephalon and brain stem, and have suggested that those gging to the medial geniculate nucleus reciprocate the projection of this nucleus upon the cortex. All the lesions have been large and have involved more than one of the subdivisions of this sensory ar2a. The remaining experiments, with lesions virtually restricted to one or other field, indicate that each subdivision projects to all structures found to be affected after the larger lesions; they also provide further evidence of a reciprocal cortico-geniculate relationship. In view of the similarity of the findings to those already presented only certain points will be considered. Area A I

In 3 brains small lesions involve slightly different parts of this area. In cat 200 the damage is restricted to this field and lies just in front of the middle of its anteroposterior extent; there is no extension into the underlying white matter (Fig. 6). In cat 206 the lesion is situated more dorsally and extends further anteriorly and posteriorly than in experiment 200; it is a narrow strip along the ventral bank of the middle Brain Research, 15 (1969) 305-340

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suprasylvian sulcus and a slight extension into the white matter undercuts the posterolateral part of the suprasylvian fringe in the lateral wall of the sulcus (Fig. 7). The damage in A I in experiment 209 is in the posterior part of the field, but in addition, there is a small focus of necrosis in the middle suprasylvian gyrus immediately dorsal Brain Research, 15 (1969) 305-340

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to the suprasylvian sulcus (Fig. 8). In each of these brains there is marked degeneration in the lateral component of the posterior group, and in cats 206 and 209 there is additional degeneration in other parts of this complex. Thus, in the latter 2 brains Brain Research, 15 (1969) 305-340

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there is degeneration in the lateral part of the suprageniculate nucleus and in the dorsally placed intermediate part of the posterior group; this additional degeneration is presumably due to the undercutting of the suprasylvian fringe in 206 and to the additional focus of damage in the suprasylvian gyrus in 209. In the small-celled principal division of the medial geniculate nucleus severe fiber and terminal degeneration is present. The distribution of this degeneration differs in the 3 brains, being most anterior and medial in experiment 206 and most lateral and posterior in 209, while that in 200 is in between and overlaps that in the other 2. In all 3 brains degeneration is found in the pars lateralis and pars medialis of the ventral nucleus and in the deep dorsal nucleus. The intensity of degeneration and extent of involvement of the latter vary, however; it is least in experiment 200, with the smallest lesion and with the damage unquestionably restricted to area A I, and here only the ventral edge of the nucleus contains degeneration; it is greatest in 206 with the additional involvement of the suprasylvian fringe, and in this brain and in experiment 209 the degeneration extends into the superficial dorsal nucleus. The appearance of the degeneration in these nuclei is the same as that described in the previous brains, the fragmenting fibers being of medium diameter, having a clearly parallel course and greater density in the ventral nucleus. The ventrolateral and dorsal nuclei are both clear in these 3 experiments. In the magnocellular element there is less degeneration of coarse fibers, and while only part of the cross-sectional area appears to be affected in each experiment it does extend throughout the greater part of the anteroposterior extent of the nucleus. There is degeneration in the inferior colliculus of both sides in the 3 brains, and the nature and disposition of this in the 3 parts of the colliculus - - the external nucleus, the dorsomedial cortex and the central nucleus - - is the same as that already described. The course of the fine fibers between the cell columns in the posterior part of the central nucleus is quite clear, and it may be noted that here the degeneration is again restricted to a relatively narrow band, with that in 209 being situated more dorsolaterally, that in 206 more ventromedially, and that in 200 in between. There are again clear loci of degeneration in the dorsolateral and paramedian pontine nuclei. Area A H

In experiments 203 and 205 the damage is mainly, if not entirely, within A II. In experiment 203 the lesion is in 2 parts; the smaller involves the cortex of the upper part of the anterior ectosylvian gyrus while the larger extends obliquely downwards and backwards over the middle sylvian gyrus (Fig. 9). There is no extension into the white matter. On the basis of the architectonic subdivisions of Rose 3° this lesion would be entirely within area A I I , but the part of the lesion in the anterior ectosylvian gyrus would be in the suprasylvian fringe according to the revised map of Woolsey 3s. In experiment 205 there is a narrow strip of damage extending from the anterior to the posterior ectosylvian sulcus; at the middle of its anteroposterior extent it involves the banks of the pseudosylvian sulcus, but there is virtually no encroachment upon the white matter (Fig. 10). The lower margin of A I1 is therefore affected, together with the Brain Research, 15 (1969) 305-340

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in A I, only that in the posterior group of the thalamus, the medial geniculate nucleus and the inferior colliculus will be described. In both experiments there is well marked terminal degeneration in the lateral part of the posterior group, a few degenerating fibers passing through the intermediate part, and definite degeneration in the suprageniculate nucleus; in experiment 203 the degeneration in the latter is clearly localized to its most ventral part. In the small-celled division of the medial geniculate nucleus there is degeneration in both the dorsal and ventral subdivisions of Morest, but the intensity of the degeneration in the ventral nucleus is appreciably less than that in the dorsal, in cat 203 it is mainly concentrated in a curved band occupying approximately the middle third of the mediolateral extent of these nuclei. In experiment 205 it is more medially situated and reaches more posteriorly, and at both its anterior and posterior ends it is sparser than in the middle. The difference in the nature of the degeneration in the dorsal and ventral subdivisions is particularly clear in these brains. The fragmenting fibers in both parts are of medium size, are clearly orientated in curved, parallel rows in the ventral part, but are sparser and irregularly arranged in the dorsal part. The almost inverse proportion in the extent of the dorsal and ventral subdivisions at anterior and posterior levels of the geniculate body is reflected in the extent of the 2 types of degeneration, medium and fine, in experiment 205. Both 203 and 205 cause degeneration in the 2 subnuclei of the ventral division and in the deep dorsal nucleus. In certain respects, however, the distribution of the degeneration in the medial geniculate nucleus differs; thus in experiment 203 the degeneration extends dorsally into the lateral part of the superficial dorsal nucleus, but the dorsal nucleus and the ventrolateral nucleus are unaffected. In experiment 205, on the other hand, there is definite degeneration in the dorsal nucleus, extending right to the caudal t i p of the geniculate body. This degeneration is in approximately the middle of the mediolateral extent of the nucleus and is the characteristic fine fragmentation seen in earlier experiments. In addition, the ventrolateral nucleus is full of degenerating fragments, but the superficial dorsal nucleus is clear. There is definite, but less marked, degeneration in the magnocellular division in both experiments. The degeneration in the inferior colliculus is well marked, is distributed to all 3 parts and is bilateral. The only point to note is that at the posterior end of the central nucleus there are 2 distinct areas of degeneration, each continuous with degenerating fibers entering from the medial and lateral aspects respectively. Again, the fact that, as in the brains with lesions in A I, the degeneration is localized to parts of the posterior end of the central nucleus suggests that an organization is present in the cortical projection upon this part, at least, of the colliculus. Foci of fragmented fibers are also present in the dorsolateral and paramedian pontine nuclei. Insulo-temporal area

In experiment 221 (Fig. 11) the lesion involves the cortex lying in front of and behind the pseudosylvian sulcus, and itis quite superficial. Of the subdivisions of the auditory cortex only the insular area is therefore affected, but the posterior part of the lesion between the pseudosylvian and posterior ectosylvian sulci is in the temporal Brain Research, 15 (1969) 305-340

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cortex which may also be included within the target of the caudal medial geniculate 2. There are several features of interest in the distribution of the subcortical degeneration in this brain. Although there are bundles of degenerating fibers passing through the Brain Research, 15 (1969) 305-340

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lateral division of the posterior group there is only a little terminal degeneration, but in the medial divisions of this complex there is more degeneration and this affects the more posterior levels of the intermediate part and the suprageniculate nucleus; that area just anteromedial to the magnocellular part of the medial geniculate nucleus, which has been shown to receive fibers from the ascending somatic sensory pathway and from the somatic sensory cortex, is quite free. In the medial geniculate nucleus there is degeneration in both the magno- and parvocellular parts. In the latter the only degeneration in the ventral division is found close to the ventrolateral margin, in the ventrolateral nucleus. In the dorsal division, however, there is severe degeneration; and this extends through most of the anteroposterior extent of the medial geniculate nucleus. In the anterior half or so of its extent it is in the deep dorsal nucleus, and fills its entire mediolateral extent. In the caudal third of the medial geniculate body the area of degeneration expands ventrolaterally to fill the dorsal nucleus and it has the fine fragmentation characteristic of this nucleus; it is quite severe and reaches to the caudal tip of the geniculate. Just medial and ventral to the magnocellular division and dorsal to the substantia nigra there is a band of degeneration which is continuous from the brachium of the inferior colliculus to the suprageniculate nucleus; this lies ventral to and overlaps the part of the medial division which receives fibers from the somatic sensory cortexL There is degeneration in all 3 parts of the inferior colliculus of the ipsilateral side, and this has the same features as in the other brains; on the opposite side, however, only an occasional fragmented fiber is seen. Posterior ectosylvian area (EP)

In 2 experiments, 201 and 204, small superficial lesions were placed in the posterior ectosylvian gyrus with the intention of damaging field EP. The site of this field differs, however, according to the criteria used: on the basis of architectonic features Rose 30 considered it to occupy the dorsal half of the posterior ectosylvian gyrus, but Woolsey 3s and Sindberg and Thompson a4, using the evoked potential method, found it to lie more ventrally. The lesions of both these experiments are in EP as delimited by Rose, that of 201 being in the upper part of the area and that of 204 near the lower end; according to the revised map of Woolsey, however, only that of 204 would be in EP and that of 201 would involve the unspecified region of cortex near the dorsal end of the gyrus. The distribution of the subcortical degeneration in these 2 brains is essentially similar (Fig. 12), and in the nature of the degenerating fibers they share a feature in common which is in contrast to all the other experiments. In most sites the degenerating fibers are extremely fine, and are the thinnest that we have observed in any thalamic nucleus after a lesion of the cerebral cortex; in addition, the degeneration is sparser than in the brains with lesions in other parts of the auditory cortex. The degeneration is quite definite, however, and in distribution and appearance it is uniform through all sections, including those from several series stained at different times. There is little, if any, degeneration in the lateral part of the posterior group; on the other hand, there is degeneration in the more dorsal, intermediate part of its extent and there is further degeneration in the pulvinar in 201, and in the suprageniculate Brain Research, 15 (1969) 305-340

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Y:";:3.

201

Fig. 12. The lesions in the posterior ectosylvian gyrus in experiment 201 and experiment 204 with the distribution of the fiber and terminal degeneration in the thalamus and inferior colliculus. nucleus in both experiments. Both the magno- and parvocellular parts of the medial geniculate nucleus contain degeneration, and this extends throughout most of their anteroposterior extent; as in the previous experiments, the fragments are coarser in the magnocellular element. In the small-celled division the degeneration is dorsally situated, in the deep dorsal nucleus and in the adjoining dorsal part of the ventral nucleus; in both experiments the degeneration is in the medial halves of the nuclei. Although the degeneration extends into the posterior third of the nucleus it does not reach its caudal end. The degeneration in the inferior colliculus is sparse and is dorsally situated on both sides. In the final experiment to be described, cat 271, there is a small area of damage, Brain Research, 15 (1969) 305-340

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3",

Fig. 13. To show the extent of the damage of the anterior ectosylvian gyrus in experiment 271 and the 2 loci of degeneration in the thalamus.

only a few millimeters in size and confined to the cortex, in the upper part o f the anterior ectosylvian gyrus (Fig. 13). This is above the level of overlap of auditory and somatic responses and is in area A I I according to Rose 8° but in what Woolsey as considers to be the anterior part of the suprasylvian fringe. Following this small lesion there is only a small amount of degeneration in the thalamus; this is present in the dorsolateral part of the small-celled division of the medial geniculate, which could be either the most lateral part of the ventral nucleus or the superficial dorsal nucleus, in the intermediate p a r t of the posterior group and in the most ventral corner of the suprageniculate nucleus. Only a few scattered fibers are seen in the first 2 of these sites, but they are present in the relevant sections of several series; in the suprageniculate nucleus, however, there is a ventral focus of quite severe fragmentation. DISCUSSION

The results of the present study confirm earlier accounts of the sites in the diencephalon and brain stem in which fibers from the auditory cortex terminate12,24i and also earlier findings that all subdivisions of the auditory area contribute to this projection 12,36. Thus, all parts of the auditory cortex send fibers to the corpus striatum, the reticular nucleus, the medial geniculate nucleus and posterior group of the dorsal thalamus, the superior colliculus, the nucleus of the brachiOm of the inferior colliculus, the parabrachial region and adjoining parts of t h e midbrain:tegmentum and the inferior colliculus. In particular, the projections to the medial geniculatenucleus, the posterior group, and the inferior colliculus warrant further discussion because of the importance of these centers in the afferent auditory pathway and because newer observations, made since the time of the previous studies o f cortical projections to them, provide an unusual opportunity to improve our understanding of the relation between the afferent and the efferent projection systems. First, concerning the projection of the auditory cortex upon the medial geniculate nucleus, all subdivisions of the auditory cortex are similar in sending fibers to both the magnocellular division and to one or more of the subnuclei within the parvocelluBrain Research, 15 (1969) 305-340

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lar division, but they differ in that the majority of them send different patterns of fibers to the subdivisions 15 of the parvocellular component. In addition to differences in distribution, the fibers to the ventral nucleus, from A I and A II, are well organized and arranged in distinct parallel order between the cell columns seen in this nucleus in Nissl sections and particularly in Golgi preparations as described in detail by Morest 17. Secondly, all parts of the auditory cortex project to one or more parts of the posterior group of the thalamus, and it will be suggested that there is a definite correlation between the portion of this group which is affected, the particular subdivision of the medial geniculate in which degeneration is present and the source of the ascending fibers to these two regions. Thirdly, the auditory cortex sends fibers to all 3 major subdivisions of the inferior colliculus - - the dorsomedial cortex, the lateral or external nucleus and the central nucleus; those to the latter have a definite relation to the cell columns present in it. Finally, the auditory cortex sends fibers back, not only to the medial geniculate nucleus from which it receives ascending fibers, but also to those sites in the midbrain from which the geniculate nucleus itself receives ascending afferent connections. These points will be discussed separately. Medial geniculate nucleus

It is now well established that the medial geniculate nucleus is the major source of afferent fibers from the thalamus to the auditory cortex, and evidence from studies using the method of retrograde cell degeneration 2,32 indicate that the nucleus projects in a differential manner upon the various subdivisions of this sensory area. In addition to the division of the medial geniculate nucleus into 2 clearly separable parts, consisting of large and small cells, Morest 15 has recently proposed a further parcellation of the small-celled division. These subdivisions are based upon the examination, in Golgi material, of the form and arrangement of the constituent neurons and of the nature of the axonal plexuses; furthermore, there is experimental evidence that the ascending afferents to these subdivisions differ both in their origin in the brain stem and in their size and terminal arborizations within the nuclei is. The present observations add further experimental evidence for the significance of these subdivisions in showing that they receive fibers from different fields of the auditory cortex, and also that the corticogeniculate fibers vary in their size and terminal pattern in a manner closely related to those shown by the ascending afferents to these nuclei. In view of the agreement between the present findings and those of Morest it should be mentioned that we started this investigation with certain reservations about the possibility of correlating the degeneration found in Nauta-stained sections with the fine subdivisions based upon the appearances seen in normal Golgi material. However, the distribution, orientation and size of the degenerating fragments in these subdivisions in the Nautastained sections are so different that the subdivisions can be identified and delimited on the basis of their characteristic plexuses of degeneration. The conclusion that all fields of the auditory cortex send fibers to the medial geniculate nucleus, to the magnocellular element and to one or more of the subdivisions of the parvocellular portion should be qualified to a certain extent by 2 technical Brain Research, 15 (1969) 305-340

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considerations. The first of these relates to the size of the lesions themselves and to the identification of the part of the auditory area damaged. In many of the experiments the lesions are relatively large and may overlap boundaries of adjoining fields, particularly as the latter have been identified by reference to the maps of Rose 8° and Woolsey z8 rather than by an examination of Nissl-stained frozen sections. As there are no experiments in which there is selective damage of either the insular or the temporal regions we cannot differentiate between them, nor is there a lesion confined to the suprasylvian fringe as delimited by Rose 3°, although the lesion in the upper part of the anterior ectosylvian gyrus in experiment 271 would be in this field only, according to Woolsey as. The second qualification concerns the problem of whether the degenerating fragments in the thalamus represent orthograde or retrograde axonal degeneration. As undoubted degeneration was also found in the medial geniculate nucleus in two brains with survival periods of only 3 days, and, more important, numerous degenerating nerve endings have been observed in this nucleus with the electron microscope after similar lesions of the cortex 11, this question need not be discussed further, except to mention that, even after 3 days, differences in the size of the degenerating fragments - - as between the magno- and parvocellular elements, for example - - are readily distinguishable. Areas A I, A I I and EP all send fibers to the ventral nucleus; the insulo-temporal cortex sends fibers to the dorsal nucleus and probably to the lateroventral nucleus; and the suprasylvian fringe could be related to the superficial dorsal nucleus or the ventral nucleus. In addition, all fields are related to the deep dorsal nucleus and to the magnocellular division. Although similar in their target, the projections from A I, A I I and EP show an important difference since A I has the heaviest projection to the ventral nucleus, A II has a less heavy projection, and that from EP is least of all. These observations confirm the conclusion of Kusama et al. 12 that A II sends fewer fibers to the medial geniculate nucleus than A I. Concerning the similarity of all cortical fields in their projection to the deep dorsal nucleus certain qualifications must be added since it is uncertain whether the projection from A I and A I I is restricted to the deepest part. Small lesions confined to A I (e.g., experiment 200) unquestionably cause degeneration restricted to the deepestpart. In contrast, larger lesions cause more widespread degeneration, but it is difficult to exclude the possibility that some of the fragmentation could be degenerating fibers passing to other portions of the geniculate 17. Similar uncertainty exists about the projection of the insulo-temporal region to the deep dorsal nucleus as it is difficult to assess the extent to which the fiber degeneration in this nucleus, after selective damage of the insulo-temporal field, represents that of fibers of passage to the more posteriorly placed dorsal nucleus or that of a projection to the deep dorsal nucleus as well. We are less certain about the precise site of the termination of the fibers from the suprasylvian fringe than about the projection from the other cortical fields. It appears, however, that it projects to the deep dorsal and superficial dorsal nuclei; first, because the degeneration here was more extensive when the fringe was damaged in addition to A [ (see experiment 206) as compared with that after damage of A I alone (see experiment 200). Secondly, after the lesion in the upper part of the anterior ectosylvian Brain Research, 15 (1969) 305-340

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gyrus (considered to be fringe a8) in experiment 271 (Fig. 13) the small amount of degeneration was so superficially situated as to suggest the superficial dorsal nucleus, although in this case it could have been in the most lateral part of the ventral nucleus. Only when the damage involved cortex lying ventral to A II was degeneration found in the lateroventral nucleus and in the dorsal nucleus, extending in the latter right to the caudal end of the medial geniculate. In summary, fields A I, A II and EP of the auditory cortex send the majority of their fibers to the main ventral nucleus, while the insulo-temporal region has its heaviest projection to the dorsal nucleus, but, in addition, all fields appear to project upon the deep dorsal nucleus. The differences in the form of the degenerating axonal plexuses in the several parts of the medial geniculate nucleus are striking and for several reasons are not considered to be artifactual in nature: they are seen on the same section, they are consistent through large parts of a series, and have been found in several different experiments. There is a range of size of degenerating fibers between the different subdivisions, and a degree of variation within some of these; the degenerating fibers are also arranged in distinctive patterns. In the ventral nucleus and in the deep dorsal nucleus after lesions in A I and A II degeneration of medium-sized fibers is present in both, but in the ventral nucleus the fibers are in curved, parallel rows between the cell columns, whereas in the deep dorsal there is an irregular arrangement of the fiber plexus. Following damage of EP the affected fibers are exceptionally fine, and probably o f even smaller diameter than those seen in the dorsal nucleus after lesions in the insulo-temporal region. To what extent these differences in diameter of the degenerating fibers are the result of axon branching or of differences in size of distinct groups of cortico-geniculate fibers must remain undecided, but both coarse and fine descending fibers to the geniculate nucleus are seen in Golgi preparations 17. If it is accepted, from the evidence which has been presented, that the architectonic and electrophysiological subdivisions of the auditory cortex send different patterns of fibers to distinct subnuclei of the medial geniculate nucleus, the important question which arises is whether these represent reciprocal connections. If there is sufficient evidence for accepting a principle of reciprocal connections, then the present findings can be considered as contributing to the elucidation of the difficult problem of the differential geniculate projection upon the various fields of the auditory cortex and also to answering the question of the topical organization within the projection to any one of these fields. In other words, finding an efferent projection from a cortical subdivision to a thalamic subdivision may be a more delicate measure of a thalamocortical projection than the retrograde cell degeneration method, but only if there is no question that one kind of projection implies the other. Since the retrograde degeneration method for determining thalamo-cortical projections is, of course, subject to difficulties in interpreting sustaining projections, and further, since the method of studying orthograde axonal degeneration after lesions of the thalamus is subject to technical difficulties in making restricted thalamic lesions without damage to several nuclear subdivisions, it is especially important to attempt to establish a principle of reciprocity. In the case of the visual and somatic sensory areas which also receive differential projections from the lateral geniculate and ventroposterior nuclei, there is Brain Research 15 (1969) 305-340

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accumulating evidence that the cortico-thalamic fibers from these areas indeed reciprocate, in quite a precise manner, the orderly arrangement of the thalamo-cortical projectionS,9,2s,2L We were persuaded that the same principle of reciprocity applies to the auditory system on grounds of the striking correlation between the extent of the fiber degeneration in the rostrocaudal dimension of the medial geniculate nucleus and the presence or absence of damage to the insulo-temporat region. The identical correlation has been reported in several studies of thalamic retrograde degeneration2,32, as. After removal of all of the auditory cortex dorsal to the insulo-temporal region there is severe cellular degeneration in the small-celled parts of the nucleus, but this is confined to the rostral two,thirds or so of its extent; cellular atrophy only occurs in the caudal third when the insulo-temporal region is involved, either selectively or in addition to more dorsal partsZ,Z2, 38. It would appear reasonable to conclude that a reciprocal projection exists and with this as a premise, we could then conclude that the dorsal nucleus, which constitutes most of the caudal third of the medial geniculate body, projects upon the insulo-temporal field, as fiber degeneration only occurs in this nucleus after damage of the insulo-temporal region. On the same basis, and once again relying on a principle of reciprocity, it could be postulated that the Ventral and deep dorsal nuclei are the major source of thalamo-cortical fibers to fields A I, A tI and EP, and that thalamic fibers passing to the suprasylvian fringe are derived from the superficial and deep dorsal nuclei or the ventral nucleus. The relationship of the more dorsal fields with the rostral two-thirds of the medial geniculate body may overlap with that of the insulo-temporal region to the caudal third of the geniculate as the insulo-temporal area may send fibers to the deep dorsal nucleus, suggesting that all fields may receive thalamo-cortical fibers from the deep dorsal nucleus. As degeneration is present in the magnocellular division after damage of each of the cortical fields it may be considered also to project upon all of them. In addition to differences in the distribution of axonal degeneration depending, upon which auditory field was damaged, we also found marked differences in the intensity of degeneration and also in the diameter of the fiber fragments. Similarly, in retrograde degeneration studies there are m a r k e d variations in the severity of cell change as well as the distribution of the cellular degeneration after damage to individual fields of the auditory cortex. Thus, Rose and Woolsey 32 found severe degeneration in the rostral two-thirds of the small=celled division following lesions confined to A I, little or no cellular change after selective lesions of A II or EP, but combined lesions of all 3 resulted in more profound and widespread atrophy than after damage of A I alone. F r o m these observations they conclude that A I alone receives essential projections, whereas A II and EP receive sustaining projections only. In regard to the magnocellular division, damage of no single field resulted in marked cellular degeneration; even if A I, A II and EP were all removed this nucleus was still mainly preserved, but if the insulo-temporal region was also involved, severe degeneration occurred. However, 'if a removal is made which is smaller only by the extent of A I than an ablation sufficient to cause a severe degeneration in the magnocellular division, the preservation of A I is sufficient to preserve this subdivision substantially unaltered'. In a similar study devoted primarily to the thalamic projection upon the insuloBrain Research, 15 (1969) 305-340

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temporal region Diamond et al. 2 found cell degeneration in the caudal third of the medial geniculate nucleus after lesions restricted to this region; the severity and extent of the degeneration increased with larger lesions and was most severe when A II was also involved. These authors interpreted their findings as indicating that A I I received collaterals of axons that originate in the caudal part of the geniculate nucleus and which terminate in the insulo-temporal region, but that some of the cells in this part of the geniculate nucleus project entirely upon the insulo-temporal field. It is tempting to relate the observations of the variations in severity of retrograde degeneration to the present findings. For example, lesions in EP lead to little or no cellular change and similarly produce sparse and very fine axonal fragmentation while lesions in A I lead both to severe cellular change and to intense degeneration of medium fibers in the ventral subnucleus. Whether there is any correlation between the size of the cortico-geniculate axons and their branches terminating in the different nuclear subdivisions with the degree of branching of the geniculo-cortical axons must remain speculative. However, with this as an assumption and taken in conjunction with the principle of reciprocity outlined above, then the following pattern of differential geniculo-cortical projections may be suggested. (Here we assume that it is the collateral branches of a geniculo-cortical axon which sustain the thalamic neuron.) The cells of the magnocellular nucleus send their axons to A I, but strong, and probably equal numbers of collaterals to A II, EP and the insulo-temporal region. The cells of the ventral nucleus and either all or some of the cells of the deep dorsal nucleus send axons to A I and collaterals to A II and EP; the number of collaterals to EP from the ventral nucleus is probably far less than those to A I[. The neurons of the dorsal nucleus in the caudal part of the geniculate send axons which branch widely within the insulo-temporal region, and some of which may extend up towards the lower part of A II; in addition, the insulo-temporal field may receive collaterals of axons arising in the deep dorsal nucleus. The lesions in the present material are clearly too large to be of much value for determining the degree of topical organization within the geniculo-cortical projection, but when the present findings are taken in conjunction with those of a cellular degeneration study 32 and with the slight evidence on the representation of the basilar membrane in the medial geniculate nucleus, certain tentative conclusions may be drawn. Rose and Woolsey ~2 concluded that the dorsal border of field A I is almost certainly represented along the anterolateral margin of the principal division, and it was probable that the posterior boundary of the field was on the posterolateral margin of the nucleus. The distribution of the axonal degeneration in the medial geniculate nucleus after the three lesions in this field would be in accord with these conclusions, and in both the cellular degeneration experiments 32 and the present ones anterior lesions result in the degeneration being more medially situated than after posterior lesions (compare experiments 12b and 3b of Rose and Woolsey 32 with their 6b and 5b). This organization would be in agreement with the finding that stimulation of the base of the basilar membrane evokes responses in the medial part of the principal division of the nucleus and anterior part of A I whereas stimulation of the apex of the membrane activates the lateral part of the nucleus and posterior portions of A I. Brain Research, 15 (1969) 305-340

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The final point to be considered concerning the findings on the descending projections to the medial geniculate nucleus is their relation to the ascending afferents to this nucleus from the brain stem. The most obvious relation is the similarity in the size and arrangement of the axonal plexuses derived from the cortex and the brain stem: coarse fibers from both to the magnocellular division; a definite, curved parallel orientation of both groups of afferents to the ventral nucleus which run between the similarly arranged cell columns of this nucleus; fine and medium-sized terminal ramifications in the deep dorsal and fine fibers only, in the dorsal nucleus. The main difference is found in the ventral nucleus where the ascending axons are appreciably coarser than the descending cortico-geniculate axons. A second relation depends upon whether the suggestion made earlier, that the cortico-geniculate fibers do indeed reciprocate the geniculo-cortical fibers, is correct; if this is so, it would follow that not only do the fields of the auditory cortex receive subcortical afferents from different parts of the medial geniculate nucleus, but also that they would be influenced by impulses ascending through different structures and pathways from lower levels of the auditory system. It has been shown14,15, 25 that the inferior colliculus projects through its brachium only to the magnocellular division and the ventral nucleus of the parvocellular division, and unpublished material of our own confirms these accounts. The dorsal and deep dorsal nuclei, on the other hand, receive ascending afferents through a lateral tegmental system from less well-defined nuclei in the midbrain tegmentum and in the vicinity of the brachium is. These 2 systems are not completely independent as the inferior colliculus sends fibers to some of the sites of origin of the lateral tegmental system and also because both the lateral tegmental pathway and the brachium of the inferior colliculus contain axons which end in the magnocellular division of the geniculate nucleus. Although degeneration is present in the sites of origin in the midbrain of both ascending pathways in the present experiments it was not possible to determine whether there were differences in distribution depending upon which area of cortex was involved. The posterior group

The various subdivisions of the auditory cortex were found to project to the posterior group, which is not surprising in view of retrograde degeneration studies which showed that, after lesions of the auditory cortex, cellular changes occur in this group as well as in the medial geniculate aa. The finding that requires further discussion is that the projections from various subdivisions are not identical. Fields A I and A I I send fibers predominantly to the lateral division of the posterior group, while EP and the insulo-temporal region are related mainly to the more medial parts of the posterior group and particularly to the suprageniculate nucleus. It is difficult to be certain that there is no terminal degeneration in the lateral subdivision after lesions of EP, insulotemporal cortex or the anterior ectosylvian gyrus because most of the cortico-geniculate fibers, irrespective of their site of origin in the auditory cortex, pass in close relation to the lateral division. However, a definite trend can be discerned in the material with lesions in one or Brain Research, 15 (1969) 305-340

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other of the auditory fields in that more intense and extensive degeneration is present in the lateral division after lesions involving A I or A 1I, and little, if any, after damage of EP, the insulo-temporal region or the anterior ectosylvian gyrus. Conversely, although degeneration was found in some part of the posterior group other than ,its lateral division in most experiments, it was restricted to the suprageniculate nucleus in the experiments with lesions in EP, the insulo-temporal region or the upper part of the anterior ectosylvian gyrus. Following the small lesion well within the confines of A I in experiment 200 it was undoubtedly confined to the lateral division o f the posterior group. Since the posterior group is not part of the classical auditory pathway and since parts of the posterior group certainly receive fibers other than auditory, it is important to raise the question whether the pattern of projection from the cortex can be related to ascending auditory systems. A relationship has already been shown in the somatic sensory system : ascending fibers in the somatic sensory pathway terminate in a restricted rostral part of the medial division of the posterior group!3; and cortico-thalamic fibers arising from S I and S I1 end Jn the same restricted part of the posterior groupg,za,2L The present findings point to a similar correspondence between auditory cortical fibers descending to the posterior group and auditory brain stem fibers ascending to the posterior group. It would appear that A I and A I I send fibers predominantly to the lateral division of the posterior group which in turn receives fibers from the brachium of the inferior colliculus 14. Fibers from A I and the brachium of the .inferior colliculus also converge on the ventral nucleus thus establishing the pattern: 2 discrete targets each in a separate major nucleus receive the same set of ascending and descending fibers. The other fields of the auditory cortex, and especially EP and the insulotemporal areas, are mainly related to the more medial parts o f the posterior group, and it is significant that these parts of the posterior group receive fibers from the lateral tegmental system is. Once again the symmetry is established, since E P and the insulotemporal area on the one hand, and the lateral tegmental path on the other, project to the same parts of the medial geniculate, viz. the dorsal nucleus. Thus, the accumulating evidence would indicate that there is a definite interrelationship between the site of termination in the posterior group of ascending fibers of both the somatic and auditory pathways, the principal thalamic nuclei in which these same pathways end, and the area of cortex to which these nuclei project and which in turn send fibers back to them and to the posterior group. This statement should not be taken to imply that parts of the posterior group are distinct functional units, comparable to the principal nuclei, as there is electrophysiological evidence for considerable convergence of impulses from different sensory systems 2a. It may be noted that part of the posterior group illustrated as showing overlap of auditory and somatic responses 2a is in the region of termination of fibers from both the upper part of the anterior ectosylvian gyrus and the somati c sensory cortex. Axonal degeneration has been described in a region medial to the caudal part of the medial geniculate nucleus after lesions involving the insulo-temporal regionL This finding has been confirmed in the present experiments with damage in this field and in which a continuous band of degeneration, from the brachium of the inferior colliculus Brain Research, 15 (1969) 305-340

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to the suprageniculate nucleus and ventral to the magnocellular medial geniculate, is present. Whether this is a separate cortical projection or merely a pathway to more ventrally situated parts of the posterior group cannot be stated. The inferior colliculus

The finding of axonal degeneration in the inferior colliculus of both sides after damage of the auditory cortex is in agreement with earlier studies 1,12,a6. On the ipsilateral side degenerating fibers are found in all three parts of the colliculus, the dorsomedial cortex, the lateral nucleus and the central nucleus, but there are differences in the extent to which these are affected and in the nature of the degeneration. In the dorsomedial cortex marked fiber and terminal degeneration may occur throughout most of its extent, but in the lateral nucleus the appearance is mainly that of coarse fiber fragmentation and we would agree with Rasmussen 26 in being tentative about concluding that there is a termination here. In the central nucleus the degenerating fibers are of small diameter; and in coronal sections of the colliculus the degenerating fibers within the central nucleus are definitely orientated in parallel rows, running from dorsomedial to ventrolateral, and in the posterior part of the nucleus this arrangement is more obvious in the medial part of its extent. In coronal sections of the inferior colliculus of the cat stained with thionin, as in other species 2° the cells of the central nucleus can be seen to be arranged in distinct columns having the same dorsomedial to ventrolateral orientation, and in a brief report of Golgi-stained material 16 the dendritic field of one type of cell has been described as being arranged 'in obliquely vertical layers extending anteroposteriorly' and the 'coarse ascending fibers to these cells parallel the dendritic layers'. Although there is no physiological evidence for a columnar organization of best frequency responses in the central nucleus, the present findings and those of MoresO6 would strongly suggest that a suitably orientated electrode penetration would demonstrate this. Indeed, the observations of Rose et al.31 can be interpreted to support this suggestion. In their experiments microelectrodes were inserted through the lateral and central nuclei from the dorsal, caudal and lateral aspect. Two of their findings are of significance: first, 'when the best frequencies of successively encountered neurons or small clusters of neurons are determined they are found to be arranged in an orderly manner'; secondly, 'two sequences are apparent: a sequence of best frequencies from high to low, which is present upon penetration of the external nucleus, and a sequence from low to high, which may coincide with the limits of the central nucleus'. In our view these findings are best explained on the basis that the angle of penetration used by these workers was at right angles to the orientation of the columns. A further point made by Rose et al. al was that 'the sequence from low to high in the central nucleus was a consistent finding' indicating that low frequencies are represented more dorsally than high frequencies. In the present material, also, it was noted that degeneration after damage of the posterior part of A I (with representation of the apex of the basilar membrane and predominantly low frequencies) was more dorsolaterally placed than after the more anterior lesion in A I. Degeneration is found in all 3 parts of the inferior colliculus after damage of Brain Research, 15 (1969) 305-340

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each of the subdivisions of the auditory cortex, and no obvious difference was found in the distribution after damage of the various fields. In all experiments degeneration is also present in the colliculus of the contralateral side, but this was sparser and essentially restricted to the dorsomedial cortex and central nucleus. The fact that the contralateral lateral nucleus receives very few corticofugal fibers raises the possibility that this part of the inferior colliculus projects only to the thalamus of the ipsilateral side, whereas the dorsomedial cortex and central nucleus project bilaterally. Columnar organization in subcortical structures

The present findings of the parallel arrangement of the degenerating corticofugal fibers in the ventral nucleus of the medial geniculate nucleus and in the central nucleus of the inferior colliculus, when considered together with recent work on other thalamic nuclei, suggest certain principles of the columnar organization of such subcortical structures. The first of these is that when a thalamic or brain stem nucleus which has a columnar arrangement of its cells and of its ascending afferent fibers receives fibers from the cortex, the latter are also precisely organized and orientated between the cell columns. This arrangement has already been shown in the lateral geniculate nucleus 5,7, and the same is true of the ventral nucleus of the medial geniculate nucleus and the central nucleus of the inferior colliculus. Secondly, in each of these sites the corticofugal fibers enter the nucleus at the opposite end of the column from that of the ascending fibers from lower levels and the 2 groups of fibers run in opposite directions and overlap. This common feature of the columnar organization in subcortical structures would appear to distinguish them from the cerebral cortex where, within the columns, there are apparently no descending fibers derived from other regions of the cortex. A third point is that in the medial and lateral geniculate nuclei and in the inferior colliculus there is a distinct difference in the size of the ascending and descending fibers to the cell columns. Thus, the ascending fibers to the central nucleus of the inferior colliculus from the lateral lemniscus of the same side and to the ventral nucleus of the medial geniculate body15,17 (unpublished observations of our own) are larger than the cortico-geniculate fibers to the same sites, and while the majority of the optic tract afferents to the lateral geniculate nucleus are coarse, those from the cortex are appreciably finerS,6,11. Similarly, the ascending fibers to the ventroposterior nucleus are larger than cortico-thalamic fibers to this nucleus. Finally, there may be a correlation between these observations with a light microscope and certain features of the intrinsic organization of these thalamic nuclei as seen with the electron microscope. A c o m m o n feature of most thalamic nuclei zl and certainly of the three sensory relay nucleil0,~2, 35 is the presence of complex, glial-enveloped, glomeruli containing more than one type of nerve ending, including those of ascending afferent fibers, terminating both axo-axonically and axo-dendritically, and with the dendritic component often being short side branches of main stem dendrites upon which the corticofugal fibers terminate. Both the ascending and descending afferent fibers to the nucleus run between the cell columns, but in opposite directions, and they overlap by ending on the same dendrite though at different levels. It is therefore possible that the functional Brain Research, 15 (1969) 305-340

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segregation an d to allow the differential influence u p o n the cells an d their dendrites

significance o f the g l o m e r u l u s is to p r o v i d e some degree o f i n c o m i n g afferent fibers to exert a

along the length o f a c o l u m n . T h e presence o f g l o m er u l i in such nuclei as the v en t r o p o s t eri o r nucleus o f the t h a l a m u s in which, as yet, no c o l u m n a r a r r a n g e m e n t o f the cells has been f o u n d , is n o t at variance with this suggestion as it has been sh o w n that after a cortical lesion the cellular d e g e n e r a t i o n in a n o t h e r apparently h o m o g e n e o u s nucleus, the lateral geniculate nucleus o f the rabbit, is in the f o r m o f a c o l u m n ; in this nucleus, therefore, a c o l u m n o f cells projects u p o n a vertical c o l u m n o f the visual cortex, an d it is p r o b a b l e that the same is true for m o s t t h a l a m i c nuclei. On the other hand, the absence o f such g lo m e r u li in the sensory areas o f the n e o c o r t e x where there is no evidence for fibers descending between the cell c o l u m n s is in accord with this suggestion. Little need be said a b o u t the p r o j e c t i o n o f the a u d i t o r y cortex u p o n the other nuclei o f the t h a l a m u s a n d brain stem except to note that after lesions restricted to these sensory areas d e g e n e r a t i o n is f o u n d in those parts o f the p o n t i n e nuclei which p ro j ect u p o n the region o f the cerebellar cortex f r o m w h i ch responses m a y be e v o k e d by a u d i t o r y stimulation. F u r t h e r m o r e , a p a r t f r o m these and the c o r p u s striatum, it w o u l d a p p e a r that the m a j o r subcortical p r o j e c t i o n o f the a u d i t o r y cortex is to those t h a l a m i c nuclei receiving fibers f r o m the ascending a u d i t o r y p a t h w a y an d to the sites o f origin in t h e brain stem o f these ascending fibers.

ABBREVIATIONS USED IN FIGURES BI BS C Cd CM D DD

=

DO GL GM

= = =

GMp

--

L

LL LP MD ML NI

-= = -=

P

PB

=

brachium of inferior colliculus brachium of superior colliculus central nucleus of inferior colliculus caudate nucleus centermedian nucleus dorsal nucleus of small-cell division of medial geniculate nucleus deep dorsal nucleus of small-cell division of medial geniculate nucleus dorsal cortex of inferior colliculus lateral geniculate nucleus large-cell division of medial geniculate nucleus small-cell division of medial geniculate nucleus lateral nucleus of inferior colliculus lateral lemniscus lateroposterior nucleus mediodorsal nucleus medial lemniscus interstitial nucleus of brachium of inferior colliculus pulvinar parabrachial region

PF, Pf -- parafascicular nucleus intermediate division of posterior POi group of thalamus lateral division of posterior group PO1 of thalamus POm -- medial division of posterior group of thalamus Pt = pretectum Put -- putamen R -- reticular nucleus of thalamus SC -- superior colliculus superficial dorsal nucleus of smallSD cell division of medial geniculate nucleus SG -- suprageniculate nucleus SP -- suprapeduncular nucleus habenulo-peduncular tract TH TO -- optic tract V -- ventral nucleus of small-cell division of medial geniculate nucleus VL = ventrolateral nucleus of small-cell division of medial geniculate nucleus VP -- ventroposterior nucleus of thalamus IV -- nucleus of fourth cranial nerve

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I.T. DIAMOND et,al.

SUMMARY

The site of termination in the diencephalon and brain stem of fibers arising in the auditory cortex of the cat has been studied with the method of Nauta and Gygax. Such corticofugal fibers end in the corpus striatum, the reticular nucleus of the ventral thalamus, the medial geniculate and the posterior group of the dorsal thalamus, in the interstitial nucleus of the brachium of the inferior colliculus, the parabrachial region and adjoining midbrain tegmentum, the inferior colliculus (of both sides) and the pontine nuclei. All fields of the auditory cortex contribute to this projection, but there are different patterns of connections to the subdivisions of the medial geniculate body and to the posterior group of the thalamus. A I, A II and EP send fibers to the ventral and deep dorsal nuclei of the medial geniculate body, but in varying proportions to each of these nuclei, A I sending the greatest number and EP the fewest number of fibers to the ventral nucleus. The insulo-temporal region is related to the dorsal and deep dorsal nuclei. This cortico-geniculate projection is well organized and probably reciprocates the geniculo-cortical projection. There appears to be a correlation between the field of origin in the auditory cortex and the site of termination of corticothalamic fibers in the medial geniculate body and in the posterior group respectively: those fields (A I and A II) which send a considerable number of fibers to the ventral nucleus of the medial geniculate body are related predominantly to the lateral division of the posterior group, whereas the insulo-temporal region and EP, which send most of their fibers to the dorsal division of the medial geniculate nucleus, project to more medial parts of the posterior group. The 3 parts of the inferior colliculus - - the dorsomedial cortex, the lateral nucleus and the central nucleus - - all receive fibers from the auditory cortex. In the ventral nucleus of the medial geniculate body and in the central nucleus of the inferior colliculus the degenerating corticofugal fibers have a parallel arrangement between the cell columns present in these nuclei, are of smaller diameter than the afferent fibers to these nuclei from lower levels of the auditory pathway, and enter the nuclei at the end of the column opposite to that of the ascending afferent fiber; these observations have suggested certain principles of the columnar organization in subcortical sensory relay nuclei. ACKNOWLEDGEMENTS

This work was supported by a grant from the Medical Research Council, and was done during the tenure of a Special Research Fellowship of the U. S. Public Health Service by I.T.D. on leave from Duke University, Durham, N.C., U.S.A., and of a Nuffield Dominions Demonstratorship by E.G.J. on leave from the University of Otago, Dunedin, New Zealand. REFERENCES 1 DESMEDT,J. E., AND MECHELSE,K., Corticofugal projections from temporal lobe in cat and their possible role in acoustic discrimination, J. Physiol. (Lond.), 147 (1959) 17-18. 2 DIAMOND,I. T., CHOW, K. L., AND NEFF, W. D., Degeneration of caudal medial geniculate body

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