connections between orbital cortex and diencephalon in the macaque

CONNECTIONS BETWEEN ORBITAL CORTEX AND DIENCEPHALON IN THE MACAQUE

GERHARDT VON BONIN AND JOHN R. GREEN From the Department of Anatomy and the Department of Nmrologg and

Neurological Surgery, College o f Medicine, Universi ty of Illinois

FIVE FIGURES

The importance of the "orbital cortex" is nowadays generally recognized, after Spatz ('37) once more called attention to the changes in character following orbital (and basi-temporal) lesions.

The effect of stimulation of the orbital surface upon respiration and circulation was first discovered by Bailey and Sweet ('40), that on the extremities and on the kidney have recently been described by Livingston et al. ( '47).

This makes a knowledge of the connection of orbital cortex with diencephalic centers particularly desirable in order clearly to understand the clinical and experimental observations which have just been briefly mentioned. We are, of course, not quite without information. To mention only the most recent papers concerning the macaque, cortical lesions and subsequent searches for retrograde degenerations were made by Walker ('40) and Marchi preparations after cortical extirpations were studied by Mettler ( '47). All observations agree that the orbital cortex receives its thalamic radiations from the medial nucleus, in particular from the medial part of that nucleus.

But, as in every method, there are sources of error in the method of retrograde degeneration. Walker approached the orbital surface from the lateral side by elevating the frontal lobe and dissecting the cortex subpially. Inadvertent trauma, at least to the lateral edge of the frontal lobe, although un-

243

244 G. VON BONIN AND J. R. GREEN

likely, cannot be altogether excluded aiid may have been overlooked in the microscopical examination of the brain. Marchi preparations show, one assumes, only the cortico- thalamic fibers. While there is every reason to assume that thalamo-cortical relations are topographically reciprocal, there is no proof for this, so that a doubt may well linger on.

Physiological neuronography, employed by Ward and McCullocli ( ’47), has revealed connections from the “medial and anterior par t of the orbital surface (area 10, 47, 53)” to the paraventricular nucleus, and from the “posterior orbital cortex (area 47)” to the posterior area of the hypothalamus ( ’47, fig. 2).

Here again errors of interpretation may arise. For there are synapses which transmit impulses in a one-to-one fashion and strychnine spikes, so it will be argued, are no proof for direct neuronal connections. It is true that such monotonous conduction through synapses has only been observed in cockroaches (Pumphrey and Rawdon-Smith, ’ 37 ) , and the squid (Bullock, ’48) and that, even if they did exist in vertebrates, their functional effect might be precisely the same as that of a direct connection. Yet one prefers an anatomical proof, a demonstration ad oculos, as it were, and welcomes in any case a corroboration by a different method.

MATERIALS AND METHODS

To investigate therefore once more the connections of the orbital surface with the diencephalon, small lesions in vari-

ABBREVIATIONS FOR ALL FIGURES

The numbers refer throughout to the animals. Shading indicates cortical lesions. Stippling indicates gliosis. The number of the sections sketched a r e indicated.

A : Anterior nucleus of thalamus NC: Nucleus caudatus C1: Internal capsule Pt: Putamen CC: Corpus callosum CM: Center median T : Temporal lobe L: Lateral nucleus of thalamus V: Lateral ventricle hf: Medial nucleus of thalamus

S: Subthalamic body of Luys

oRB~TAI, CORTEX AND DIENCEPHALON 245

Fig. 1 Ventral views of brains of monkeys nos. 3, 6 and 7. These did not give rise to retrograde degeneration in the medial nucleus of the thalamus. For monkey no. 3, see figure 2.

246 G. VON BONIN A N D J. R. GREEN

ous parts of the orbital cortex were made in G macaques. A s suggested by Dr. Percival Bailey, the orbital surface was approached from the orbit. I n order to avoid any lesion to the rest of the frontal lobe, an eye (we always took tlie right one) was extirpated, the other contents of the orbit and the orbital roof partially removed. After incision of the dura mater, the cortex was subpially resected by means of suc- tion. The wound of the dura iriater was then closed, the orbit tightly packed with ,fibrin foam, and the conjunctiva and eyelids sewn together. In monkey no. 3 (see fig. I), retch- ing, coughing and forced expiration were observed while the orbital cortex was extirpated. All animals had an uncompli- cated recovery, ancl showed no obvious defects or alterations in behavior after tlie operation. They were kept alive for about 6 months. When sacrificed, the blood vessels were washed out with saline solution arid perfused with formalin. The brains were removed, photographed and Mocked. After embedding in celloidin, 20 p serial sections were made, every 10th section stained with thionine and mounted. Relevant sections were drawn by means of a projection apparatus and pathological changes marked under microscopic control. Dr. Percival Bailey suggested and demonstrated to us the opera- tive approach and placed the facilities of his laboratory at our disposal.

EXPERIMENTAL FTNDTNC8

Three monkeys (nos. 3, G and 7, see fig. 1) showed no clear-cut changes in the medial nucleus of the thalamus. The lesions in monkeys 6 and 7 a re small, hence may well have led to so circumscribed or so slight a gliosis that it could not be detected with certainty. The lesion in monkey’ no. 3 was but little smaller than that of monkey no. 5 (see below). While in monkey no. 3, too, the medial nucleus showed no changes, a gliosis could be followed clearly into the septa1 and hypothalamic regions (see fig. 2) . The lesion had caught the very elid of the orbital surface where it is covered by allocortex (see fig. 2, 900). This area, covering the anterior

ORBITAL CORTEX A N D D I E N C E P H A L O N 247

perforated substance, is comparable to area FI of Ecoiiomo and Roskinas ('25) in the human. From thc scar, a dense gliosis could be traced to the paraventricular nucleus of the

N0.3

Fig. 2 Three scctions through brain of monkey no. 3 (cf., fig. 1) . Section 900 is the frontal .

248 G. VON BONIN A N D J. R. GREEN

hypothalamus, but not beyond it (see fig. 2, 700 and 600). Many cells in the paraventricular nucleus looked well stained, had a clearly defined nucleus and nucleolus. Some cells, however, were shrunk and surrounded by numerous glia cells. Less than 10% seemed to have undergone retrograde degeneration.

This finding obviously corroborates Ward and AfcCul- loch's ( '47) observation of strychnine spikes propagated from area 47 to the paraventricular nucleus.

The existence of a cortico-hypothalamic tract can hardly be doubted, particularly in the light of further physiological evidence, recently summarized by Livingston et al. ('47). Its exact origin, however, cannot be determined from our observations. It may arise from area FF (see Boriin arid Bailey, '47), or it may arise from the frontal par t of the piriform cortex. I n the latter case, it might be par t or all of the medial forebrain bundle which Ingram ( '40) described in man, whicli can be assumed to be present in the macaque, too, but whose exact origin (see Ariens Kappers, Huber & Crosby, '36, p. 1433) is still a little in the dark.

Clear-cut changes in the medial nucleus were observed in morikeys 2, 4 and 5 (figs. 3-5) . As tlie figures show, the orbital lesions were all in about the same position and had led to gliosis of the medial and the ventral portion of the medial nucleus. Throughout, the occipital extremity of the nucleus and the parafascicular nucleus were normal. All cases had lesions on the posteroventral part of area F D of Bonin and Bailey ('41). To trace the gliosis from the traumatized cortex to the medial nucleus was impossible. Evidently the fibers fan out considerably in the medulla, to collect, however, in the internal lamina (see especially fig. 4, 650) and thus to reach the medial nucleus from the dorsal side.

These cases confirm to some extent Walker's ('40) hy- pothesis of a dorsoveiitral correspondence of frontal cortex and medial thalamic nucleus. But the thalamic degeneration is fairly elongated and gives more the impression of medio- lateral arrangement such as that suggested by Mettler ( '47).

ORBITAL CORTEX AND DIENCEPHALON 249

Fig. 3 Monkey no. 2 . Above: cortical lesion. Below: sections through the thalamus indicating by stippling locus of gliosis.

250 G. VON BONIN ANI) J. R. GREEN

Yet it woiiltl appear that the tlialamo-cortical projections of arezi FF were less than might have been expected, and one might also axsuinc that the projection from F D was more diffuse tlian tlic neat diagrams of Rlettler (’47) might lead one to assuinc.

650 i-’

N0.4

Q 575

s“ -J Fig. 4 Moilkey no. -1. Sce legend of figure 3 for further description.

Tlie filial goal of iiioht espei*inieiital work is to elucidate the sti-uctnre of the I1unia11 brain and it is precisely for this reason that, primates a re clioseii rather tliaii cats or dogs. “The elaboration of the liuniaii frontal lobe is achieved not by the successive addition of meclianisms . . . but by the progressive elaboration of those fundamental arrangements present in lower prirnatcs,” to quote Rlettler (’47). The areal elaboration of the frontal cortex may not be as far reaching


as Brodmaiin’s maps suggest. It should be kept in mind, Iiow- ever, that the “orbital cortex” may comprise more areas in the larger brain of man than in the smaller. one of thc macaqne. I n fact, the shift of area FDT-if wliat Econonio

N0.5 p

252 G. VON BONlN A N D J. R. GREEN

and Koskiiias (’25) labelled by that symbol in man and what Bonin and Bailey (’47) so labelled in the macaque are homo- logus-would suggest just that. The fairly strong connection with the lateral edge of the orbital surface in the macaque may well have its homologon in a thalamo-cortical radiation to the orbital surface proper in man. Moreover, Brodmaiiii’s conceptioii that there was no counterpart in the moiikey to wliat he had labelled area 47 iii man has been denied by Boniri aiid Bailey who recognized an area FF in the macaque whicli in man’s brain corresponds to Rrod- mann’s 47. The observations liere reported suggest that area FF receives a t best a very scarce thalamic radiation.

The hypothalamus has probably become simpler rather than more elaborate, as Griinthal (’30, ’31) has tried to show, hence, the hypothalamic coiinectioiis may not have undergone great changes. They inay well not have been severed by the surgeon in the cases of frontal lobotomy which Freeman and Watts (’47) described. Indeed, their figures 3, 5, 8 and 10 suggest that. Cortico-hypothalamic fibers a re listed by Le Gros Clark (’48), on the basis not only of physiological neuronography but also of anatomical observations of 31. Meyer. We take this to be a correction of Neyer and Beck’s (’45) earlier statement that the fibers from frontal cortex to the magnocellular portion of the medial iiucleus coiitrihuted the only hypothalamic pre-f roiital connection “which, so far, has been definitely established. ”

There are puzzling discrepancies in the descriptions of the medial iiucleus of the macaque. In the macaque the lateral par t of the medial nucleus contains larger cells and has been described as pars magnocellularis by Krieg ( ’47). This con- tradicts Walker’s statement (’40, p. 88) that the magnocellular portion “lies along tlie mid-line of the anterior half of the nucleus.” Somewhat larger cells are present on both lateral and medial portions of the medial iiucleus, but to call the lateral group, with Rrieg, pars magnocellularis, may easily lead i o confusion. F o r in man only a medial magnocellular portion lias been described by Toncray and Krieg


('46) as well as by Sheps ('45) and others. The daculties just alluded to may, of course, point to functional differences still hidden from us. In any event, the statement now fairly generally accepted that in man the magnocellular part sends no radiation to the frontal cortex is well in agreement with our findings in the macaque. The possibility of a direct orbito-hypothalamic connection deserves careful scrutiny in human material.

To sum up: We have confirmed in a general way the thalamo-cortical relations between " orbital cortex " and medial thalamic nucleus of the macaque. We found these connections stronger on the lateral than on the medial part of the orbital surface, and found the medioventral part of the medial nucleus affected. We have also seen indications of an orbito-hypothalamic connection but we are unable to state whether this involves the neocortical area FF or the allocortical remnant of the piriform area which forms the occipital border of the orbital cortex. We have finally dis- cussed the bearing of these findings on human anatomy.

LITERATURE CITED

ARIENS KAPPERS, C. U., G. C. Husm AND E. C. CROSBY 1936 The comparative anatomy of the nervous system of vertebrates. New York, The Macmillan Co., 2 vols.

BAILEY, P., AND W. H. SWEET 1940 Effects on respiration, blood pressure and gastric motility of stimulation of orbital surface of frontal lobe. J. Neurophysiol., 3 : 276-281.

BONIPI', G. v., AND P. BAILEY 1947 The neocortex of Macaea mulatta. Ur- bana, Illinois. The University of Illinois Press. (Illinois Mono- graphs in the Medical Sciences, V. 4: X I + 163 pp.)

Properties of a single synapse in the stellate ganglion of the squid. J. Neurophysiol., 11: 343-364.

1948 The coiinexions of the frontal lobes of the brain. Lancet I, 353-357.

1925 Die Cytoarchitektonik der Hirnrjnde des erwachsenen Menschen. Wien und Berlin. J. Springer, xxxix + 860 pp.

Retrograde degeneration of the thalamus following prefrontal lobotomy. J. Comp. Neur., 8 6 : 65-93.

BULLOCK, T. H. 1948

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ECONOMO, C. v., AND G. N. KOSKINAS

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254 G. VON BONIN AND J. R. GREEN

GRUNTHAL, E. 1930 Vergleichend-anatomische und entwicklungsgeschichtliehe Untersuchungen iiber die Zentren des Hypothalamus der Sauger und des Menschen. Arch. Pspchiat. u. Nervenkrkht., 90 : 216-267.

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connections between orbital cortex and diencephalon in the macaque

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