Brain (1975) 98, 297-308
THE CEREBRAL PATHWAYS OF OPTOKINETIC NYSTAGMUS: A NEURO-ANATOMICAL STUDY BY
W. BLACKWOOD, M. R. DDC AND PETER RUDGE {From the Institute of Neurology, National Hospital, Queen Square, London WC1, and the Medical Research Council, Hearing and Balance Unit)
THE underlying anatomical substrate of the optokinetic reflex has been the subject of continued controversy since Barany first introduced observation of optokinetic nystagmus into clinical use half a century ago. The advent of electronystagmography during the past two decades has contributed greatly towards the resolution of this long-standing problem. Recent studies of patients with lesions of the cortex and basal ganglia have provided support for the existence of two distinct mechanisms for the slow and fast components of optokinetic nystagmus with centres in the frontal and occipital cortex respectively and for a cortical association pathway between the two centres (Dix and Hood, 1971). The anatomical pathways of these mechanisms are illustrated in fig. 1. In the case of a
FIG. 1.—Schematic illustration of suggested nervous pathways subserving optokinetic nystagmus.
subject gazing passively at a succession of moving objects, afferent impulses from both the macula and peripheral retina are conveyed, by way of the visual pathways,
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to the occipital lobes from which, in turn, impulses to the oculomotor nuclei reflexly bring about the slow movement of the eyes. The fovea is not concerned with this movement. Concurrently, however, impulses are conveyed to the frontal eye field which, by way of its own separate and distinct projection pathways to the ocular muscle nuclei, initiates the fast component. Macular vision is important in this movement. In addition, by means of a further pathway, first proposed by Holmes (1938), an inhibitory controlling influence is exerted by the frontal centre upon inappropriate and undesirable activity of the occipital lobes. Although a recent elaboration of this scheme by Ling and Gay (1968) has been criticized by Feldman and Bender (1969), the present communication provides anatomical data obtained from a patient previously described by Dix and Hood (1971) which supports these concepts. This patient had bilateral cerebrovascular lesions thus enabling a precise correlation to be made between the abnormalities of optokinetic nystagmus and the areas of brain involved.
CASE REPORT
Case M. M., N.H. No. A49249 A right-handed electronics technician of 27 years was admitted to the National Hospital (Dr. R. E. Kelly) in 1963 complaining of right-sided weakness and speech disturbance which had been present for twenty-four hours. He had had three similar episodes in the preceding year, all of which resolved, although he had been more aggressive following the last. On admission he was severely dysphasic with right-sided pyramidal signs. There was no abnormality on general examination. A right carotid angiogram and ventriculogram were suggestive of a space-occupying lesion in the left parieto-temporal region and a provisional diagnosis of glioma was made. He slowly improved over the next few months but remained moderately dysphasic. In April 1965 he suddenly became confused, developed a left hemiparesis and had difficulty in swallowing and phonation. Carotid angiography showed occlusion of some of the branches of the middle cerebral arteries bilaterally. It was concluded that he had suffered multiple embolization of the cerebral circulation. No source of emboli was demonstrated in the carotid angiograms, at arch aortography and angiocardiography. No predisposing cause was found to account for these emboli in an extensive biematological and biochemical study. Anticoagulants were given and the left hemiparesis improved but he continued to have difficulty in swallowing and with speech. The anticoagulants were inadvertently stopped in August 1966 when he was admitted to another hospital for consideration of a pharyngoplasty and soon after this he had a further episode of loss of consciousness with twitching of the right leg and deviation of the eyes to the right. Over the next two days his conscious state improved and he was noted to be aggressive, euphoric and exhibited hypersexuality. He was anarthric and had great difficulty in swallowing. Extraocular movements were full. The facial reflexes were brisk, palatal movement poor and the tongue spastic. There was increased tone and some weakness in all limbs, greater on the left than the right. There was no definite sensory abnormality. Because of his personality disorder he was admitted to a psychiatric hospital for long-term care. He was given anticonvulsants and anticoagulants were administered again
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In 1968 he probably had a further ccrebrovascular accident but improved to his former state with physiotherapy. He was reassessed in 1971 at the National Hospital (Dr. R. Ross Russell) when the signs were essentially unchanged. Over the next year he had several episodes of aspiration pneumonia and died suddenly in January 1973.
Neuro-otological examinations at Queen Square on July 28, 1969, and December 13, 1971, gave essentially similar results. The patient was anarthric but able to co-operate well to spoken commands. He grimaced and dribbled constantly and could not protrude his tongue beyond his lips. The ears, nose, throat and larynx were normal. Cochlear function was normal. He was unable to close his eyes on command but could stand and walk unaided blindfolded. Caloric responses (Fitzgerald and Hallpike technique) were brisk with a slight abnormality in pattern, directional preponderance to left. Ocular movements, including command and following to points 30 degrees to his left or right and up and down, were full and normal. Convergence was normal. Doll's head movements were full to left and right and up and down. No spontaneous or positional nystagmus was observed. Optokinetic responses, elicited with a small Barany drum, appeared brisk and equal to left and right and present up and down. Electronystagmographic observations.—The electronystagmographic records, using the technique described by Hallpike, Hood and Trinder (1960) and obtained from this patient, are illustrated in fig. 2. Those obtained from a normal subject and a COMHAND
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'
L__l
I
FOLLOWING
OPTOKINETIC
MM. A42«9
FIG. 2.—Command, following and optokinetic responses in patient with bilateral cerebral lesions involving the inferior fronto-occipital fasciculi; present patient. Time scale seconds. Arrows indicate first two points of reversal of drum. Eye movement to right upwards; eye movement to left downwards, in this and subsequent figures.
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case of basal ganglia disease are shown in figs. 3 and 4 for comparison. As shown in fig. 2, eye movements to command were of normal velocity although somewhat stepped; following movements were entirely normal. Although records with the patient seated in a large rotating drum showed optokinetic nystagmus to be present, on close inspection there are certain striking differences from the normal. Thus whereas at the points of drum reversal, shown by the arrows, the eyes deviate initially
Fia. 3.—Command, following and optokinetic responses in a normal subject. Time scale seconds. Arrows indicate points of reversal of drum.
FOLLOWING
__i_.j
OPTOKINtTIC
••w-i.,/ 1
FIG. 4.—Command, following and optokinetic responses in a patient with basal ganglia lesion. Time scale seconds. Arrow indicates point of reversal of drum.
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in the direction of the slow component, in normal optokinetic nystagmus the reverse is the case and deviation occurs in the direction of the fast component. In addition, reversal of nystagmus direction takes place with a change in direction of the fast component in the normal and with a slow component in the case of the patient. These changes are similar to those seen in patients with basal ganglia disease but in that case the following and command movements are abnormal (fig. 4). This is discussed later. Post-mortem findings (by Dr. W. S. Killpack, St. Bernard's Hospital).—Heart (250 g)—epicardium, myocardium and endocardium healthy. No evidence of endocarditis. Foramen ovale closed. No evidence of coronary atheroma. Recent pulmonary embolism. Lungs: widespread firm fibrosis at bases. In right middle lobe and lower part of left upper lobe evidence of organized pneumonia. Alimentary system: healthy. Kidneys showed large deep scars due to old healed infarcts. Spleen contained three old healed infarcts. Brain: large old ischasmic foci in both middle cerebral arterial territories. No atheroma seen. Brain sent intact to National Hospital, Queen Square. Pathological examination—Brain: the circle of Willis was complete; atheromatous or occluded arteries were not seen. Depressed regions were visible in each temporal lobe, towards the anterior end of the superior and middle temporal gyri. The cerebral hemispheres were cut coronally into eighteen slices about 8 mm thick, all of which were embedded in celloidin, sectioned and stained with hsmatoxylin and eosin, Gros-Bielschowsky and thionin, Loyez, and phosphotungstic acid haematoxylin. In particular, there were six slices between the anterior aspect of the pillars of the fornices and the posterior aspect of the splenium of the corpus callosum, some of which were cut and stained at several levels. It should be noted that the coronal sections were slightly tilted, so structures in the left hemispheres were at a slightly more posterior level than those on the right. The brain-stem was cut horizontally and the cerebellum vertically. Representative regions of the brain-stem and cerebellum were similarly embedded in celloidin and stained. Macroscopically in the left cerebral hemisphere, there was old infarction of the cortex and subjacent white matter of the central portion of F3, immediately anterior to the stem of the lateral fissure (fig. 5, Plate XXQ). Posterior to the stem, there was loss of grey and white matter from the frontal and temporal opercula and from the floor of the insula, the claustrum, external capsule and inferior to the external capsule (fig. 6). At the coronal level of the infundibulum, the extent of the lesion was similar but the frontal operculum was spared (fig. 7). At the coronal level of the red nucleus, the lesion sharply diminished in extent (fig. 8). On the right the first lesion appeared at the anterosuperior extremity of the corona radiata, where there was a cystic cavity in the white matter (fig. 6). At the coronal level of the infundibulum (fig. 7) the lesion had spread to involve the lateral aspect of 21
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the corona radiata, the frontal and temporal opercula, the superior part of the floor of the insula, and structures immediately subjacent to this. Posterior to this, the lesion rapidly diminished in size, at first involving the temporal operculum of the insula, T2 and the posterolateral striatum (cystic lesion) (fig. 8) and then only T2 and the subjacent white matter (figs. 9 and 10). It ceased at about the level of the posterior aspect of the corpus callosum (fig. 11). Microscopically: The lesions seen above were confirmed. Additional lesions were not found in the diencephalon, brain-stem or cerebellum apart from some descending degeneration in the pyramidal tracts (fig. 12). In the frontal lobes, the posterior parts of the middle frontal gyri, which had been marked in ink on the leptomeninges, were visible in levels 6 and 7 bilaterally and on the right in level 8. The cortex and underlying white matter were not abnormal. The corpus callosum appeared intact. Arterial narrowing was not seen. Examination of various regions relevant to the present paper revealed the following. No abnormality was found in other parts of the afferent visual systems from the optic tracts to the visual cortex. In the corticospinal pathways, on the left there was some damage to the inferior part of the corona radiata (figs. 5, 6, 7 and 8) and there was a slight generalized loss of myelinated fibres in the pons and the pyramid in the medulla (fig. 12). On the right there was more severe damage to the corona radiata, anterior but close to the genu of the internal capsule, superolateral to the corpus striatum (fig. 7). The anterior limb of the internal capsule, in the region where it is opposed to the globus pallidus, did not show any marked abnormality. The internal capsule, at and immediately posterior to the region of the genu, showed loss of myelinated fibres (fig. 8). There was a well-marked diffuse loss of myelinated fibres from the pons and pyramid of the medulla (compare figs. 12 and 13). The fronto-oculomotor pathways which are thought to pass through the genu of the internal capsule did not appear to be at risk on the left side, but did appear to be at risk on the right due to a lesion in the corona radiata (fig. 7). No abnormality was found in the occipito-oculomotor pathways thought to run from the para-occipital cortex, through the optic radiation, posterior limb of the internal capsule and thalamus (figs. 9, 10 and 11). Of the long tracts connecting the occipital and frontal lobes (fig. 14) the superior fronto-occipital, or subcallosal, fasciculus on the left appeared undamaged, and that on the right was possibly damaged (figs. 6 and 7). Both superior longitudinal and inferior fronto-occipital fasciculi were very severely damaged on both sides (figs. 6, 7 and 8).
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Superior fronto-occipital subcallosal fasciculus
Superior longitudinal fasciculus
Caudate
Claustrum
Inferior fronto-occipital fasciculus
Lentiform nucleus
Uncinate fasciculus
FIG. 14.—Diagram to illustrate the positions of connexions between occipital and frontal lobes.
DISCUSSION
There is much evidence, both in man and animals, that area 8 of the frontal regions is important in the control of eye movement. Thus stimulation of area 8 causes the eyes to deviate conjugately to the opposite side and many workers have mapped out two topographically organized frontal eye fields in each hemisphere (Mott and Schaefer, 1890; Foerster, 1936; Crosby et al, 1962; Brucher, 1964), although not all agree about precise localization (Pasik and Pasik, 1964). Single unit recording has indicated the importance of this area in eye movement control (Bizzi and Schiller, 1970). On the other hand, in man destruction of one frontal eye field results in only a temporary inability to gaze voluntarily towards the opposite side (Holmes, 1938). Reflex following movements are however unimpaired in such patients. Furthermore, there is evidence in primates with bilateral occipital lobectomy that the frontal eye fields can initiate eye movements independently of the occipital regions (Pasik and Pasik, 1964). The efferents from the frontal eye fields 1 and 2 intermingle and follow the same course to the extra-ocular nuclei (Brucher, 1964). The majority of fibres pass in the internal capsule adjacent to the globus pallidus, through the genu and into the thalamus, zona incerta and fields of Forel to the upper brain-stem. A minority, however, diverge from this in Dejerine's aberrant tract and traverse the pes pedunculi and substantia nigra. Others pass through the corpus callosum then follow a similar course but on the opposite side. There is equally strong evidence that eye movements can be influenced by the occipital lobes. Stimulation of this area, particularly area 19, results in conjugate deviation of the eyes to the opposite side both in man and animals (Foerster, 1936;
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Mott and Schaefer, 1890; Crosby, 1953). On the other hand, bilateral destructive lesions of the occipital lobes in man, not affecting visual acuity, probably cause inability to follow objects (Raff, 1967). Fibres from this area pass along the medial side of the optic radiation and through the posterior part of the internal capsule and posterior thalamus into the brain-stem in monkeys (Mettler, 1935). Some of these fibres decussate. Thus there are two distinctly separate areas of the cortex—frontal and occipital— from which eye movements can be initiated. In man the frontal subserves "voluntary" gaze while the occipital areas subserve reflex following. Gordon Holmes (1938) argued that it was necessary in such a system for the frontal centres to dominate the occipital. He stated, admitting the teleology of the proposition, that "the frontal centre became not merely an organ from which ocular movements could be evoked, it acquired also the power of inhibiting inappropriate and undesirable activities of the occipital lobes." There is some physiological evidence of such inhibition. Mott and Schaefer (1890) showed that if one frontal eye field and one contralateral occipital eye field were simultaneously stimulated at threshold levels the eyes always deviated away from the side of the frontal stimulation. On the other hand, when the frontal lobes are destroyed bilaterally, the speed of reflex following is increased and optokinetic nystagmus enhanced (Henderson and Crosby, 1952). If such inhibition exists by what pathways is it manifest? The simplest proposition would be that they involve intrahemispheric connexions between the frontal and occipital eye fields. It is known that the superior longitudinal fasciculus and the inferior fronto-occipital fasciculus connect these two regions. The positions of these tracts are shown diagrammatically in fig. 14. Lesions in these areas have been shown to produce "pseudo-hemianopia" in monkeys, the animals failing to look at objects. Thus Clark and Lashley (1947) produced this syndrome by damaging the superior longitudinal fasciculus and Crosby et al. (1962) state that it can be produced with lesions in the inferior fronto-occipital fasciculus. Anatomical studies by Brucher (1964) have shown that the majority of the association fibres from area 8 of the monkey pass in the inferior fronto-occipital fasciculus. Such pathways could be responsible for inhibition of the occipital region by the frontal eye fields. Presumably either frontal area could inhibit either occipital since each region is connected through the corpus callosum with its counterpart in the opposite hemisphere. Bilateral lesions in these areas would have no obvious clinical effect in man if the pathways from the frontal and occipital areas to the brain-stem remained unimpaired as following and command pathways would be intact. Such a lesion should only be apparent if the frontal areas could not inhibit the occipital at brain-stem level. Recent work on optokinetic nystagmus has increased our knowledge of the relationship between the frontal and occipital centres. It has been shown by Hood (1967) that if nystagmus is induced by rotation of a normal subject in the dark, the eyes tend to deviate in the direction of the slow component of the nystagmus.
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Furthermore, if the direction of the rotation is reversed, the nystagmus reverses with a change in direction of the slow component. In this situation the nystagmus is dependent upon the vestibular system and is clearly independent of the visual pathways. In contrast to this, if nystagmus is induced using a large striped drum, i.e. optokinetic nystagmus, in normal man the eyes deviate in the direction of the fast component and when the direction of rotation is reversed the nystagmus reverses with the fast phase as in fig. 3. This form of nystagmus has been shown by Hood (1967) to depend upon macular vision. Thus patients with bilateral central scotomata do not exhibit it. Instead they have the vestibular type of optokinetic nystagmus— deviation of the eyes in the direction of the slow component and reversal with the slow phase. It was suggested by Hood that the type of optokinetic nystagmus in the presence of macular vision is controlled through pathways involving the frontal eye fields. This suggestion was later fortified by the results of studies of patients with basal ganglia disease in whom voluntary gaze is impaired to a greater extent than following movements and the fast component of optokinetic nystagmus absent or severely deranged (Dix and Hood, 1971). In these patients the pathways from the frontal eye fields to the brain-stem are more involved by the pathological process than those from the occipital area. An example of the optokinetic nystagmus in this type of lesion is shown in fig. 4. From these studies it was postulated that the macula-visual input from the striped drum passes to the occipital lobes and is then relayed through cortical connexions to area 8. Impulses pass from here to the brain-stem to initiate the fast phase which takes the eyes away from the mid-line, and so the eyes deviate in the direction of the fast phase. If the frontal efferents to the brain-stem are damaged (fig. 4) this mechanism cannot operate and the patient exhibits the more primitive vestibular optokinetic nystagmus with deviation in the direction of the slow component. Now a similar situation should also exist if Hood's hypothesis is correct and connexions between the occipital and frontal centres are damaged bilaterally. In this situation the efferents to the brain-stem are left intact. As has been mentioned above, Holmes postulated that there must be such connexions, but in the reverse direction, so that the occipital lobes can be inhibited by the frontal areas and it was pointed out that there is physiological evidence for this. Such lesions would result in normal voluntary and reflex gaze but a primitive vestibular type of optokinetic nystagmus. The present case shows that this is probably so. It also indicates that the connexions are probably within the inferior fronto-occipital or the superior longitudinal fasciculi and not in the superior fronto-occipital or the subcallosal fasciculus. The occipital efferents to the brain-stem are clearly uninvolved bilaterally in the present case and following movements were normal in velocity and accuracy. The efferents to the brain-stem nuclei from area 8 seemed to be spared on the left if they follow the same course as in the monkey, Brucher (1964, fig. 5). On the right the
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infarct extended into the internal capsule and histologically the basal ganglia were involved to some extent putting the frontal-oculomotor fibres at risk. This may account for the broken-up voluntary movements with hypometric saccades (Hoyt and Daroff, 1971), but it is important to note that the velocity was normal to right and left. In contrast to this there was complete bilateral destruction of the frontooccipital connexions other than the subcallosal fasciculus bilaterally. In this situation we propose that the frontal eye fields would not be able to inhibit the occipital nor could impulses be transmitted from the occipital to the frontal areas. This lesion resulted in a vestibular type of optokinetic nystagmus and is good evidence in support of Hood's hypothesis and, indirectly, Holmes' proposition. Presumably the fact that it is necessary to interrupt these connexions bilaterally, whilst essentially sparing the fronto- and occipito-oculomotor efferents, accounts for previous failure to recognize these phenomena. It might be argued that the abnormal frontal efferents on one side in this patient contradict the above argument. This is not a valid objection as it is known that unilateral frontal destruction has no long-term effect upon optokinetic nystagmus. We think that the present case supports the concepts elaborated by Ling and Gay (1968) and is evidence against Feldman and Bender's criticism (1969).
SUMMARY
Abnormalities of optokinetic nystagmus are described in a patient with pathologically proven bilateral infarcts in the middle cerebral artery territories. There were no other central nervous system lesions. These abnormalities of eye movement are interpreted as indicating an inhibitory effect of the frontal eye fields upon the occipital lobes. ACKNOWLEDGMENTS
We wish to thank Dr. R. W. Ross Russell, Mr. M. D. Sanders and Dr. R. G. Willison for their helpful advice in the preparation of this paper, Dr. W. S. Kilpack for the post-mortem findings, Mrs. J. Dawson for technical assistance and Mr. J. A. Mills for the photography.
REFERENCES Bizzi, E., and SCHILLER, P. H. (1970) Single unit activity in the frontal eye fields of unaruesthetised monkeys during eye and head movement. Expl Brain Res., 10, 151-158. BRUCHER, J. M. (1964) "L'Aire Oculogyre frontale du Singe." Bruxelles: Arscia. CLARK, G., and LASHLEY, K. S. (1947) Visual disturbances following frontal ablations in the monkey. Anat. Rec, 97, 326. CROSBY, E. C. (1953) Relation of brain centres to normal and abnormal eye movements in the horizontal plane. / . comp. Neurol., 99, 437-479. , HUMPHREY, T., and LAUER, E. W. (1962) "Correlative Anatomy of the Nervous System." New York: Macmillan.
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DDC, M. R., and HOOD, J. D. (1971) Further observations upon the neurological mechanism of optokinetic nystagmus. Acta otolar., 71, 217-226. FELDMAN, M., and BENDER, M. B. (1969) Neuro-ophthalmology: clinical tests of vestibular and oculomotor functions. Prog. Neurol. Psychiat., 24, 189-202. FOERSTER, O. (1936) "Handbuch der Neurologic," Band 6. Edited by O. Bumke and O. Foerster. Berlin: Springer. HALLPKE, C. S., HOOD, J. D., and TRINDER, E. (1960) Some observations on the technical and clinical problems of electro-nystagmography. Confinia neurol., 20, 232-240. HENDERSON, J. W., and CROSBY, E. C. (1952) An experimental study of optokinetic responses. AM.A. Archs Ophthal., 47, 43-54. HOLMES, G. (1938) The cerebral integration of the ocular movements. Br. med. J., 2, 107-112. HOOD, J. D. (1967) Observations upon the neurological mechanism of optokinetic nystagmus with special reference to the contribution of peripheral vision. Acta otolar., 63, 208-215. HOYT, WILLIAM F., and DAROFF, ROBERT B. (1971) Supranuclcar disorders of ocular control systems in man: clinical, anatomical and physiological correlations. In: "The Control of Eye Movements." Edited by P. Bach-y-Rita and C. C. Collins. New York and London: Academic Press, pp. 175-235. LING, B., and GAY, A. (1968) Optokinetic nystagmus. In: "Neuro-Ophthalmology Symposium of the University of Miami and the Bascom Palmer Eye Institute." Edited by J. L. Smith. St. Louis: Mosby. Vol. 4, pp. 117-123. METTLER, F. A. (1935) Corticofugal fiber connections of the cortex of Macaca mulatta. The occipital region. /. comp. Neurol., 61, 221-256. MOTT, F. W., and SCHAEFER, E. A, (1890) On associated eye movements produced by cortical faradization of the monkey's brain. Brain, 13, 165-173. PASIK, P., and PASIK, T. (1964) Oculomotor functions in monkeys with lesions of the cerebrum and the superior colliculi. In: "The Oculomotor System." Edited by M. B. Bender. New York: Harper and Row. RAFF, M. C. (1967) Discussion of case 26-1967, case records of the Massachusetts General Hospital. New Engl. J. Med., 276, 1432-1439. {Received January 8,1975)
LEGENDS FOR PLATES PLATE XXII Fio. 5.—Coronal section through anterior corpus striatum. Celloidin. Loyez myelin stain. Fia. 6.—Coronal section through anterior limb of internal capsule. Lines indicate area 8 {see text). Note: plane of section is slightly oblique in this and all subsequent sections, the structures on the right being cut more anteriorly than on the left. Celloidin. Loyez myelin stain.
PLATE XXIH Fio. 7.—Coronal section through genu of the left internal capsule. Lines indicate area 8 {see text). Celloidin. Loyez myelin stain. FIG. 8.—Coronal section through the posterior limbs of the internal capsules at the level of the red nucleus. Line indicates Area 8 on right side. This section through the left hemisphere was at a level slightly posterior to Area 8 {see text). Celloidin. Loyez myelin stain.
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W. BLACKWOOD, M. R. DIX AND PETER RUDGE PLATE XXIV
FIG. 9.—Coronal section through lateral geniculate bodies. Celloidin. Loyez myelin stain. FIG. 10.—Coronal section through the right posterior pulvinar. Celloidin. Loyez myelin stain.
PLATE XXV FIG. 11.—Coronal section through the splenium of the corpus callosum. Celloidin. Loyez myelin stain. FIG. 12.—Medulla. Horizontal section at level of inferior olivary nuclei. Celloidin. Loyez myelin stain. FIG. 13.—Normal medulla. Horizontal section at level of inferior olivary nuclei. Celloidin. Loyez myelin stain.
PLATE XXI [
FIG.
5.
FIG.
6.
To illustrate article by W. Blackwood, M. R. Dix and Peter Rudge.
PLATE XXIII
FIG. 7.
FIG. 8.
To illustrate article by IV. Blackwood, M. R. Dix and Peter Rudge.
PLATE XXIV
FIG.
9.
FIG.
10.
To illustrate article by W. Blackwood, M. R. Dix and Peter Rudge.
PLATE XXV
FIG.
FIG.
11.
12.
o illustrate article by W. Blackwood, M. R. Dix and Peter Rudge.
FIG.
13.
THE CEREBRAL PATHWAYS OF OPTOKINETIC NYSTAGMUS: A NEURO-ANATOMICAL STUDY BY
W. BLACKWOOD, M. R. DDC AND PETER RUDGE {From the Institute of Neurology, National Hospital, Queen Square, London WC1, and the Medical Research Council, Hearing and Balance Unit)
THE underlying anatomical substrate of the optokinetic reflex has been the subject of continued controversy since Barany first introduced observation of optokinetic nystagmus into clinical use half a century ago. The advent of electronystagmography during the past two decades has contributed greatly towards the resolution of this long-standing problem. Recent studies of patients with lesions of the cortex and basal ganglia have provided support for the existence of two distinct mechanisms for the slow and fast components of optokinetic nystagmus with centres in the frontal and occipital cortex respectively and for a cortical association pathway between the two centres (Dix and Hood, 1971). The anatomical pathways of these mechanisms are illustrated in fig. 1. In the case of a
FIG. 1.—Schematic illustration of suggested nervous pathways subserving optokinetic nystagmus.
subject gazing passively at a succession of moving objects, afferent impulses from both the macula and peripheral retina are conveyed, by way of the visual pathways,
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to the occipital lobes from which, in turn, impulses to the oculomotor nuclei reflexly bring about the slow movement of the eyes. The fovea is not concerned with this movement. Concurrently, however, impulses are conveyed to the frontal eye field which, by way of its own separate and distinct projection pathways to the ocular muscle nuclei, initiates the fast component. Macular vision is important in this movement. In addition, by means of a further pathway, first proposed by Holmes (1938), an inhibitory controlling influence is exerted by the frontal centre upon inappropriate and undesirable activity of the occipital lobes. Although a recent elaboration of this scheme by Ling and Gay (1968) has been criticized by Feldman and Bender (1969), the present communication provides anatomical data obtained from a patient previously described by Dix and Hood (1971) which supports these concepts. This patient had bilateral cerebrovascular lesions thus enabling a precise correlation to be made between the abnormalities of optokinetic nystagmus and the areas of brain involved.
CASE REPORT
Case M. M., N.H. No. A49249 A right-handed electronics technician of 27 years was admitted to the National Hospital (Dr. R. E. Kelly) in 1963 complaining of right-sided weakness and speech disturbance which had been present for twenty-four hours. He had had three similar episodes in the preceding year, all of which resolved, although he had been more aggressive following the last. On admission he was severely dysphasic with right-sided pyramidal signs. There was no abnormality on general examination. A right carotid angiogram and ventriculogram were suggestive of a space-occupying lesion in the left parieto-temporal region and a provisional diagnosis of glioma was made. He slowly improved over the next few months but remained moderately dysphasic. In April 1965 he suddenly became confused, developed a left hemiparesis and had difficulty in swallowing and phonation. Carotid angiography showed occlusion of some of the branches of the middle cerebral arteries bilaterally. It was concluded that he had suffered multiple embolization of the cerebral circulation. No source of emboli was demonstrated in the carotid angiograms, at arch aortography and angiocardiography. No predisposing cause was found to account for these emboli in an extensive biematological and biochemical study. Anticoagulants were given and the left hemiparesis improved but he continued to have difficulty in swallowing and with speech. The anticoagulants were inadvertently stopped in August 1966 when he was admitted to another hospital for consideration of a pharyngoplasty and soon after this he had a further episode of loss of consciousness with twitching of the right leg and deviation of the eyes to the right. Over the next two days his conscious state improved and he was noted to be aggressive, euphoric and exhibited hypersexuality. He was anarthric and had great difficulty in swallowing. Extraocular movements were full. The facial reflexes were brisk, palatal movement poor and the tongue spastic. There was increased tone and some weakness in all limbs, greater on the left than the right. There was no definite sensory abnormality. Because of his personality disorder he was admitted to a psychiatric hospital for long-term care. He was given anticonvulsants and anticoagulants were administered again
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In 1968 he probably had a further ccrebrovascular accident but improved to his former state with physiotherapy. He was reassessed in 1971 at the National Hospital (Dr. R. Ross Russell) when the signs were essentially unchanged. Over the next year he had several episodes of aspiration pneumonia and died suddenly in January 1973.
Neuro-otological examinations at Queen Square on July 28, 1969, and December 13, 1971, gave essentially similar results. The patient was anarthric but able to co-operate well to spoken commands. He grimaced and dribbled constantly and could not protrude his tongue beyond his lips. The ears, nose, throat and larynx were normal. Cochlear function was normal. He was unable to close his eyes on command but could stand and walk unaided blindfolded. Caloric responses (Fitzgerald and Hallpike technique) were brisk with a slight abnormality in pattern, directional preponderance to left. Ocular movements, including command and following to points 30 degrees to his left or right and up and down, were full and normal. Convergence was normal. Doll's head movements were full to left and right and up and down. No spontaneous or positional nystagmus was observed. Optokinetic responses, elicited with a small Barany drum, appeared brisk and equal to left and right and present up and down. Electronystagmographic observations.—The electronystagmographic records, using the technique described by Hallpike, Hood and Trinder (1960) and obtained from this patient, are illustrated in fig. 2. Those obtained from a normal subject and a COMHAND
J
'
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I
FOLLOWING
OPTOKINETIC
MM. A42«9
FIG. 2.—Command, following and optokinetic responses in patient with bilateral cerebral lesions involving the inferior fronto-occipital fasciculi; present patient. Time scale seconds. Arrows indicate first two points of reversal of drum. Eye movement to right upwards; eye movement to left downwards, in this and subsequent figures.
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case of basal ganglia disease are shown in figs. 3 and 4 for comparison. As shown in fig. 2, eye movements to command were of normal velocity although somewhat stepped; following movements were entirely normal. Although records with the patient seated in a large rotating drum showed optokinetic nystagmus to be present, on close inspection there are certain striking differences from the normal. Thus whereas at the points of drum reversal, shown by the arrows, the eyes deviate initially
Fia. 3.—Command, following and optokinetic responses in a normal subject. Time scale seconds. Arrows indicate points of reversal of drum.
FOLLOWING
__i_.j
OPTOKINtTIC
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FIG. 4.—Command, following and optokinetic responses in a patient with basal ganglia lesion. Time scale seconds. Arrow indicates point of reversal of drum.
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in the direction of the slow component, in normal optokinetic nystagmus the reverse is the case and deviation occurs in the direction of the fast component. In addition, reversal of nystagmus direction takes place with a change in direction of the fast component in the normal and with a slow component in the case of the patient. These changes are similar to those seen in patients with basal ganglia disease but in that case the following and command movements are abnormal (fig. 4). This is discussed later. Post-mortem findings (by Dr. W. S. Killpack, St. Bernard's Hospital).—Heart (250 g)—epicardium, myocardium and endocardium healthy. No evidence of endocarditis. Foramen ovale closed. No evidence of coronary atheroma. Recent pulmonary embolism. Lungs: widespread firm fibrosis at bases. In right middle lobe and lower part of left upper lobe evidence of organized pneumonia. Alimentary system: healthy. Kidneys showed large deep scars due to old healed infarcts. Spleen contained three old healed infarcts. Brain: large old ischasmic foci in both middle cerebral arterial territories. No atheroma seen. Brain sent intact to National Hospital, Queen Square. Pathological examination—Brain: the circle of Willis was complete; atheromatous or occluded arteries were not seen. Depressed regions were visible in each temporal lobe, towards the anterior end of the superior and middle temporal gyri. The cerebral hemispheres were cut coronally into eighteen slices about 8 mm thick, all of which were embedded in celloidin, sectioned and stained with hsmatoxylin and eosin, Gros-Bielschowsky and thionin, Loyez, and phosphotungstic acid haematoxylin. In particular, there were six slices between the anterior aspect of the pillars of the fornices and the posterior aspect of the splenium of the corpus callosum, some of which were cut and stained at several levels. It should be noted that the coronal sections were slightly tilted, so structures in the left hemispheres were at a slightly more posterior level than those on the right. The brain-stem was cut horizontally and the cerebellum vertically. Representative regions of the brain-stem and cerebellum were similarly embedded in celloidin and stained. Macroscopically in the left cerebral hemisphere, there was old infarction of the cortex and subjacent white matter of the central portion of F3, immediately anterior to the stem of the lateral fissure (fig. 5, Plate XXQ). Posterior to the stem, there was loss of grey and white matter from the frontal and temporal opercula and from the floor of the insula, the claustrum, external capsule and inferior to the external capsule (fig. 6). At the coronal level of the infundibulum, the extent of the lesion was similar but the frontal operculum was spared (fig. 7). At the coronal level of the red nucleus, the lesion sharply diminished in extent (fig. 8). On the right the first lesion appeared at the anterosuperior extremity of the corona radiata, where there was a cystic cavity in the white matter (fig. 6). At the coronal level of the infundibulum (fig. 7) the lesion had spread to involve the lateral aspect of 21
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the corona radiata, the frontal and temporal opercula, the superior part of the floor of the insula, and structures immediately subjacent to this. Posterior to this, the lesion rapidly diminished in size, at first involving the temporal operculum of the insula, T2 and the posterolateral striatum (cystic lesion) (fig. 8) and then only T2 and the subjacent white matter (figs. 9 and 10). It ceased at about the level of the posterior aspect of the corpus callosum (fig. 11). Microscopically: The lesions seen above were confirmed. Additional lesions were not found in the diencephalon, brain-stem or cerebellum apart from some descending degeneration in the pyramidal tracts (fig. 12). In the frontal lobes, the posterior parts of the middle frontal gyri, which had been marked in ink on the leptomeninges, were visible in levels 6 and 7 bilaterally and on the right in level 8. The cortex and underlying white matter were not abnormal. The corpus callosum appeared intact. Arterial narrowing was not seen. Examination of various regions relevant to the present paper revealed the following. No abnormality was found in other parts of the afferent visual systems from the optic tracts to the visual cortex. In the corticospinal pathways, on the left there was some damage to the inferior part of the corona radiata (figs. 5, 6, 7 and 8) and there was a slight generalized loss of myelinated fibres in the pons and the pyramid in the medulla (fig. 12). On the right there was more severe damage to the corona radiata, anterior but close to the genu of the internal capsule, superolateral to the corpus striatum (fig. 7). The anterior limb of the internal capsule, in the region where it is opposed to the globus pallidus, did not show any marked abnormality. The internal capsule, at and immediately posterior to the region of the genu, showed loss of myelinated fibres (fig. 8). There was a well-marked diffuse loss of myelinated fibres from the pons and pyramid of the medulla (compare figs. 12 and 13). The fronto-oculomotor pathways which are thought to pass through the genu of the internal capsule did not appear to be at risk on the left side, but did appear to be at risk on the right due to a lesion in the corona radiata (fig. 7). No abnormality was found in the occipito-oculomotor pathways thought to run from the para-occipital cortex, through the optic radiation, posterior limb of the internal capsule and thalamus (figs. 9, 10 and 11). Of the long tracts connecting the occipital and frontal lobes (fig. 14) the superior fronto-occipital, or subcallosal, fasciculus on the left appeared undamaged, and that on the right was possibly damaged (figs. 6 and 7). Both superior longitudinal and inferior fronto-occipital fasciculi were very severely damaged on both sides (figs. 6, 7 and 8).
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Superior fronto-occipital subcallosal fasciculus
Superior longitudinal fasciculus
Caudate
Claustrum
Inferior fronto-occipital fasciculus
Lentiform nucleus
Uncinate fasciculus
FIG. 14.—Diagram to illustrate the positions of connexions between occipital and frontal lobes.
DISCUSSION
There is much evidence, both in man and animals, that area 8 of the frontal regions is important in the control of eye movement. Thus stimulation of area 8 causes the eyes to deviate conjugately to the opposite side and many workers have mapped out two topographically organized frontal eye fields in each hemisphere (Mott and Schaefer, 1890; Foerster, 1936; Crosby et al, 1962; Brucher, 1964), although not all agree about precise localization (Pasik and Pasik, 1964). Single unit recording has indicated the importance of this area in eye movement control (Bizzi and Schiller, 1970). On the other hand, in man destruction of one frontal eye field results in only a temporary inability to gaze voluntarily towards the opposite side (Holmes, 1938). Reflex following movements are however unimpaired in such patients. Furthermore, there is evidence in primates with bilateral occipital lobectomy that the frontal eye fields can initiate eye movements independently of the occipital regions (Pasik and Pasik, 1964). The efferents from the frontal eye fields 1 and 2 intermingle and follow the same course to the extra-ocular nuclei (Brucher, 1964). The majority of fibres pass in the internal capsule adjacent to the globus pallidus, through the genu and into the thalamus, zona incerta and fields of Forel to the upper brain-stem. A minority, however, diverge from this in Dejerine's aberrant tract and traverse the pes pedunculi and substantia nigra. Others pass through the corpus callosum then follow a similar course but on the opposite side. There is equally strong evidence that eye movements can be influenced by the occipital lobes. Stimulation of this area, particularly area 19, results in conjugate deviation of the eyes to the opposite side both in man and animals (Foerster, 1936;
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Mott and Schaefer, 1890; Crosby, 1953). On the other hand, bilateral destructive lesions of the occipital lobes in man, not affecting visual acuity, probably cause inability to follow objects (Raff, 1967). Fibres from this area pass along the medial side of the optic radiation and through the posterior part of the internal capsule and posterior thalamus into the brain-stem in monkeys (Mettler, 1935). Some of these fibres decussate. Thus there are two distinctly separate areas of the cortex—frontal and occipital— from which eye movements can be initiated. In man the frontal subserves "voluntary" gaze while the occipital areas subserve reflex following. Gordon Holmes (1938) argued that it was necessary in such a system for the frontal centres to dominate the occipital. He stated, admitting the teleology of the proposition, that "the frontal centre became not merely an organ from which ocular movements could be evoked, it acquired also the power of inhibiting inappropriate and undesirable activities of the occipital lobes." There is some physiological evidence of such inhibition. Mott and Schaefer (1890) showed that if one frontal eye field and one contralateral occipital eye field were simultaneously stimulated at threshold levels the eyes always deviated away from the side of the frontal stimulation. On the other hand, when the frontal lobes are destroyed bilaterally, the speed of reflex following is increased and optokinetic nystagmus enhanced (Henderson and Crosby, 1952). If such inhibition exists by what pathways is it manifest? The simplest proposition would be that they involve intrahemispheric connexions between the frontal and occipital eye fields. It is known that the superior longitudinal fasciculus and the inferior fronto-occipital fasciculus connect these two regions. The positions of these tracts are shown diagrammatically in fig. 14. Lesions in these areas have been shown to produce "pseudo-hemianopia" in monkeys, the animals failing to look at objects. Thus Clark and Lashley (1947) produced this syndrome by damaging the superior longitudinal fasciculus and Crosby et al. (1962) state that it can be produced with lesions in the inferior fronto-occipital fasciculus. Anatomical studies by Brucher (1964) have shown that the majority of the association fibres from area 8 of the monkey pass in the inferior fronto-occipital fasciculus. Such pathways could be responsible for inhibition of the occipital region by the frontal eye fields. Presumably either frontal area could inhibit either occipital since each region is connected through the corpus callosum with its counterpart in the opposite hemisphere. Bilateral lesions in these areas would have no obvious clinical effect in man if the pathways from the frontal and occipital areas to the brain-stem remained unimpaired as following and command pathways would be intact. Such a lesion should only be apparent if the frontal areas could not inhibit the occipital at brain-stem level. Recent work on optokinetic nystagmus has increased our knowledge of the relationship between the frontal and occipital centres. It has been shown by Hood (1967) that if nystagmus is induced by rotation of a normal subject in the dark, the eyes tend to deviate in the direction of the slow component of the nystagmus.
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Furthermore, if the direction of the rotation is reversed, the nystagmus reverses with a change in direction of the slow component. In this situation the nystagmus is dependent upon the vestibular system and is clearly independent of the visual pathways. In contrast to this, if nystagmus is induced using a large striped drum, i.e. optokinetic nystagmus, in normal man the eyes deviate in the direction of the fast component and when the direction of rotation is reversed the nystagmus reverses with the fast phase as in fig. 3. This form of nystagmus has been shown by Hood (1967) to depend upon macular vision. Thus patients with bilateral central scotomata do not exhibit it. Instead they have the vestibular type of optokinetic nystagmus— deviation of the eyes in the direction of the slow component and reversal with the slow phase. It was suggested by Hood that the type of optokinetic nystagmus in the presence of macular vision is controlled through pathways involving the frontal eye fields. This suggestion was later fortified by the results of studies of patients with basal ganglia disease in whom voluntary gaze is impaired to a greater extent than following movements and the fast component of optokinetic nystagmus absent or severely deranged (Dix and Hood, 1971). In these patients the pathways from the frontal eye fields to the brain-stem are more involved by the pathological process than those from the occipital area. An example of the optokinetic nystagmus in this type of lesion is shown in fig. 4. From these studies it was postulated that the macula-visual input from the striped drum passes to the occipital lobes and is then relayed through cortical connexions to area 8. Impulses pass from here to the brain-stem to initiate the fast phase which takes the eyes away from the mid-line, and so the eyes deviate in the direction of the fast phase. If the frontal efferents to the brain-stem are damaged (fig. 4) this mechanism cannot operate and the patient exhibits the more primitive vestibular optokinetic nystagmus with deviation in the direction of the slow component. Now a similar situation should also exist if Hood's hypothesis is correct and connexions between the occipital and frontal centres are damaged bilaterally. In this situation the efferents to the brain-stem are left intact. As has been mentioned above, Holmes postulated that there must be such connexions, but in the reverse direction, so that the occipital lobes can be inhibited by the frontal areas and it was pointed out that there is physiological evidence for this. Such lesions would result in normal voluntary and reflex gaze but a primitive vestibular type of optokinetic nystagmus. The present case shows that this is probably so. It also indicates that the connexions are probably within the inferior fronto-occipital or the superior longitudinal fasciculi and not in the superior fronto-occipital or the subcallosal fasciculus. The occipital efferents to the brain-stem are clearly uninvolved bilaterally in the present case and following movements were normal in velocity and accuracy. The efferents to the brain-stem nuclei from area 8 seemed to be spared on the left if they follow the same course as in the monkey, Brucher (1964, fig. 5). On the right the
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infarct extended into the internal capsule and histologically the basal ganglia were involved to some extent putting the frontal-oculomotor fibres at risk. This may account for the broken-up voluntary movements with hypometric saccades (Hoyt and Daroff, 1971), but it is important to note that the velocity was normal to right and left. In contrast to this there was complete bilateral destruction of the frontooccipital connexions other than the subcallosal fasciculus bilaterally. In this situation we propose that the frontal eye fields would not be able to inhibit the occipital nor could impulses be transmitted from the occipital to the frontal areas. This lesion resulted in a vestibular type of optokinetic nystagmus and is good evidence in support of Hood's hypothesis and, indirectly, Holmes' proposition. Presumably the fact that it is necessary to interrupt these connexions bilaterally, whilst essentially sparing the fronto- and occipito-oculomotor efferents, accounts for previous failure to recognize these phenomena. It might be argued that the abnormal frontal efferents on one side in this patient contradict the above argument. This is not a valid objection as it is known that unilateral frontal destruction has no long-term effect upon optokinetic nystagmus. We think that the present case supports the concepts elaborated by Ling and Gay (1968) and is evidence against Feldman and Bender's criticism (1969).
SUMMARY
Abnormalities of optokinetic nystagmus are described in a patient with pathologically proven bilateral infarcts in the middle cerebral artery territories. There were no other central nervous system lesions. These abnormalities of eye movement are interpreted as indicating an inhibitory effect of the frontal eye fields upon the occipital lobes. ACKNOWLEDGMENTS
We wish to thank Dr. R. W. Ross Russell, Mr. M. D. Sanders and Dr. R. G. Willison for their helpful advice in the preparation of this paper, Dr. W. S. Kilpack for the post-mortem findings, Mrs. J. Dawson for technical assistance and Mr. J. A. Mills for the photography.
REFERENCES Bizzi, E., and SCHILLER, P. H. (1970) Single unit activity in the frontal eye fields of unaruesthetised monkeys during eye and head movement. Expl Brain Res., 10, 151-158. BRUCHER, J. M. (1964) "L'Aire Oculogyre frontale du Singe." Bruxelles: Arscia. CLARK, G., and LASHLEY, K. S. (1947) Visual disturbances following frontal ablations in the monkey. Anat. Rec, 97, 326. CROSBY, E. C. (1953) Relation of brain centres to normal and abnormal eye movements in the horizontal plane. / . comp. Neurol., 99, 437-479. , HUMPHREY, T., and LAUER, E. W. (1962) "Correlative Anatomy of the Nervous System." New York: Macmillan.
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DDC, M. R., and HOOD, J. D. (1971) Further observations upon the neurological mechanism of optokinetic nystagmus. Acta otolar., 71, 217-226. FELDMAN, M., and BENDER, M. B. (1969) Neuro-ophthalmology: clinical tests of vestibular and oculomotor functions. Prog. Neurol. Psychiat., 24, 189-202. FOERSTER, O. (1936) "Handbuch der Neurologic," Band 6. Edited by O. Bumke and O. Foerster. Berlin: Springer. HALLPKE, C. S., HOOD, J. D., and TRINDER, E. (1960) Some observations on the technical and clinical problems of electro-nystagmography. Confinia neurol., 20, 232-240. HENDERSON, J. W., and CROSBY, E. C. (1952) An experimental study of optokinetic responses. AM.A. Archs Ophthal., 47, 43-54. HOLMES, G. (1938) The cerebral integration of the ocular movements. Br. med. J., 2, 107-112. HOOD, J. D. (1967) Observations upon the neurological mechanism of optokinetic nystagmus with special reference to the contribution of peripheral vision. Acta otolar., 63, 208-215. HOYT, WILLIAM F., and DAROFF, ROBERT B. (1971) Supranuclcar disorders of ocular control systems in man: clinical, anatomical and physiological correlations. In: "The Control of Eye Movements." Edited by P. Bach-y-Rita and C. C. Collins. New York and London: Academic Press, pp. 175-235. LING, B., and GAY, A. (1968) Optokinetic nystagmus. In: "Neuro-Ophthalmology Symposium of the University of Miami and the Bascom Palmer Eye Institute." Edited by J. L. Smith. St. Louis: Mosby. Vol. 4, pp. 117-123. METTLER, F. A. (1935) Corticofugal fiber connections of the cortex of Macaca mulatta. The occipital region. /. comp. Neurol., 61, 221-256. MOTT, F. W., and SCHAEFER, E. A, (1890) On associated eye movements produced by cortical faradization of the monkey's brain. Brain, 13, 165-173. PASIK, P., and PASIK, T. (1964) Oculomotor functions in monkeys with lesions of the cerebrum and the superior colliculi. In: "The Oculomotor System." Edited by M. B. Bender. New York: Harper and Row. RAFF, M. C. (1967) Discussion of case 26-1967, case records of the Massachusetts General Hospital. New Engl. J. Med., 276, 1432-1439. {Received January 8,1975)
LEGENDS FOR PLATES PLATE XXII Fio. 5.—Coronal section through anterior corpus striatum. Celloidin. Loyez myelin stain. Fia. 6.—Coronal section through anterior limb of internal capsule. Lines indicate area 8 {see text). Note: plane of section is slightly oblique in this and all subsequent sections, the structures on the right being cut more anteriorly than on the left. Celloidin. Loyez myelin stain.
PLATE XXIH Fio. 7.—Coronal section through genu of the left internal capsule. Lines indicate area 8 {see text). Celloidin. Loyez myelin stain. FIG. 8.—Coronal section through the posterior limbs of the internal capsules at the level of the red nucleus. Line indicates Area 8 on right side. This section through the left hemisphere was at a level slightly posterior to Area 8 {see text). Celloidin. Loyez myelin stain.
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W. BLACKWOOD, M. R. DIX AND PETER RUDGE PLATE XXIV
FIG. 9.—Coronal section through lateral geniculate bodies. Celloidin. Loyez myelin stain. FIG. 10.—Coronal section through the right posterior pulvinar. Celloidin. Loyez myelin stain.
PLATE XXV FIG. 11.—Coronal section through the splenium of the corpus callosum. Celloidin. Loyez myelin stain. FIG. 12.—Medulla. Horizontal section at level of inferior olivary nuclei. Celloidin. Loyez myelin stain. FIG. 13.—Normal medulla. Horizontal section at level of inferior olivary nuclei. Celloidin. Loyez myelin stain.
PLATE XXI [
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6.
To illustrate article by W. Blackwood, M. R. Dix and Peter Rudge.
PLATE XXIII
FIG. 7.
FIG. 8.
To illustrate article by IV. Blackwood, M. R. Dix and Peter Rudge.
PLATE XXIV
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10.
To illustrate article by W. Blackwood, M. R. Dix and Peter Rudge.
PLATE XXV
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o illustrate article by W. Blackwood, M. R. Dix and Peter Rudge.
FIG.
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