OCULOMOTOR ORGANISATION Arris and Gale Lecture delivered at the Royal College of Surgeons of England on 15th December 1955 by Roger Warwick, B.Sc., M.D. University Professor of Anatomy, Guy's Hospital Medical School; Late Lecturer in Anatomy, University of Manchester IT IS FIRST my duty and pleasure to acknowledge the honour done me by election to this Arris and Gale Lectureship. As I believe is customary, the subject which I bring before you is fundamentally of academic interest, and since I am by profession an anatomist, I must treat extensively of structure. However, a purely topographical account of the motor innervation of ocular muscles would doubtless be to you, and certainly to me, a topic of limited appeal. I am therefore sure you will be relieved to learn that we shall be concerned with the functional significance of the structures we are to consider at every stage. Elucidation of the linkages between form and function provides, of course, the keenest pleasure in any biological enquiry, medical or otherwise; and it is this pleasure which is often the mainspring of academic research, as in my own. Nevertheless, you will discover in the observations here presented some points of practical significance in the semantics of clinical neurology, regarding which many here will be more able judges than I. Oculomotor organisation has for long attracted minds of contrasting interests, and even a rapid glance at the century of endeavour behind us today will show how the efforts of pure anatomists, experimenters, clinical observers, and even the purely speculative, have combined in the evolution of present conceptions. Stilling (1846) might be called the prime topographer of the cranial nuclei. Certainly he first clearly revealed the sources of the third, fourth, and sixth , amongst others, and his descriptions remained unchanged until 1881, when von Gudden, an experimentalist, demon- strated the chronic atrophy produced in nerve cells by division of their in young animals. His chief contributions, achieved by this method, were that the trochlear decussation is complete, that some oculomotor fibres cross within the , and that each of the two third nerve nuclei is divided longitudinally into dorsal and ventral columns. Apart, however, from the obvious deduction that the trochlear and abducent nuclei are the motor pools of the superior oblique and lateral rectus, his technique yielded no results concerning the central arrangement of the motor cells of the remaining ocular musculature. A few years later Edinger (1885) and Westphal (1887) described the small-celled nuclei which still commemorate them, and in 1889 Perlia combined these and his own topographic findings to produce his well- known diagram of the oculomotor nuclei (Fig. 1). He added another paired and small-celled group, the anteromedian , situated 36 OCULOMOTOR ORGANISATION

Fig. 1. Topographical disposition of the oculomotor complex of nuclei according to Perlia (1889). Note inclusion of Darkschewitsch's nucleus as a radicular element, separateness of the Edinger-Westphal and anteromedian nuclei, and the inclusion of the nucleus centralis. cranially and in the midline, and caudal to this appeared his better known " central " nucleus. With both of these we shall be much concerned. He also favoured a more elaborate subdivision of the main, or lateral, than von Gudden (1881). He included in what might henceforward be called the oculomotor complex not only the above elements but also the recently discovered nucleus of Darkschewitsch (1889) and a further median group of somewhat scattered neurones caudal to the central nucleus, which does not appear in his diagram, but is usually referred to as the " diffuse midline nucleus of Perlia." Prior to Perlia's topographical foundation, Adamuk (1870) and Hensen and Volckers (1878) had already found by midbrain stimulation, 37 R. WARWICK

38 OCULOMOTOR ORGANISATION mechanical and electrical, in the vicinity of dogs' oculomotor nuclei, that motor cells of the individual muscles innervated by the third nerve were not intermingled, but segregated into a cranio-caudal string of motor pools or " centres " (Fig. 2). Clinicopathological observers, such as Kahler and Pick (1881) and Starr (1888), were also deducing similar schemes in man, but these may well have been influenced by the experi- mental findings. Knies (1891) went much further in assigning functional significances to the various elements of Perlia's diagram (Fig. 2). Little weight should ever have been attached to this arbitrary proceeding for it was founded on little substantial evidence. Unfortunately Knies' purely speculative labelling of Perlia's central nucleus as a centre for convergence, a superficially attractive innovation, aroused immediate and lasting interest, despite the fact that other clinicians, such as Siemerling (1891), who described the clinical and pathological findings in numerous cases of ophthalmoplegia, could not be equally dogmatic. The next great impetus to study of the problem of muscle representation within the oculomotor hierarchy was provided by Nissl (1892, 1894) when he evolved his method of tracing neuronal connexions by observation of the disappearance of chromatin granules in response to axonal injury. Several experimenters at once applied the Nissl technique by cutting the nerve supplies of extra-ocular muscles and studying the distribution of affected nerve cells in the oculomotor nuclei. Among these Bernheimer (1897) and Bach (1899) were prominent. Their results were markedly INTRINSIC MUSCLES

LEVATOR RECTUS MEDIALIS PALPEBRAE (IN CONJUGATE SUPERIORIS DEVIATION) RECTUS SUPERIOR MEDIALIS OBLIQUUS ~~~~~RECTUSCONVERGENCE) INFERIOR ~~~~(IN

RECTUS INFERIO

ONBUQUUS US- - -TROCHLEAP. -'-.- NUCLEUS

Fig. 3. Oculomotor organisation according to Brouwer (1918). This is the diagram most frequently reproduced in text-books. Note dual motor pools for the medial rectus muscles. 39 4 R. WARWICK LEVATOR INTRINSIC MM.

Fig. 4. Bernheimer's schema of the oculomotor nuclei. Note varying degrees of crossed innervation of the rectus medialis (R. int.), rectus inferior (R. inf.), and and obliquus inferior (0. inf.) opposed (Fig. 2). Perhaps because he used monkeys, perhaps owing to Brouwer's approval at a later date, Bernheimer's schema was preferred, and still forms the main factual basis of the conception of oculomotor organisation followed in most current accounts (Fig. 4). Although, as we shall see, Bach's views were perhaps nearer the truth, Brouwer (1918) accepted Bernheimer's pattern of motor pools for the extra-ocular muscles, but he modified it by banishing innervation of intiinsic ocular musculature from the central nucleus of Perlia (Fig. 3). His own comparative observations, eked out by data from a single case of ophthalmoplegia, led him to support Knies' designation of the central nucleus as a convergence centre. His emphasis on this has doubtless helped to engrave it in orthodox teaching, and although during the subsequent thirty-seven years further clinical, comparative, and experimental studies have continued to appear, these have had little effect upon authoritative texts. 40 OCULOMOTOR ORGANISATION Hadidian and Dunn (1937) employed Nissl's retrograde degeneration technique in goldfish, as did Abd-el-Malek (1938) in cats. Cats were also used in experiments of Szentagothai (1942, 1943) and Danis (1948) but their method was to observe ocular movements caused by stereotaxically controlled stimulation of points in the midbrain, a somewhat indirect procedure also selected by Bender and Weinstein (1943), who were the first workers since Bernheimer (1897) to experiment on monkeys in studying this problem. The results of these later investigations not only differed from the classical Bernheimer-Brouwer picture of oculomotor organisations but also amongst themselves. The origin of parasympathetic fibres for the innervation of the sphincter pupillae and ciliaris oculi was thought to be in the Edinger-Westphal nuclei by Bernheimer (1897) and Brouwer (1918), but this was denied by Bach (1899), Latumeten (1924) and others. Further matters of uncer- tainty exist, such as the proportion of oculomotor fibres which decussate, the identity of muscles supplied by crossed fibres, the role of certain close neighbours of the accepted oculomotor components, like the nucleus of Darkschewitsch, and so on. Moreover, as often occurs in topography, confusion has not infrequently arisen through independent description and labelling of the same nuclear group by several observers. Thus Perlia's diffuse nucleus of the midline is evidently the same entity as the nucleus dorso-centralis of Panegrossi (1898) and the caudal central Rostral

Dtir g h~~~~~~~~~~~~Rgt

Dorsal Right~orsa

R. lateral aspect Dorsal Dorsal aspect

Rostral section Reproduced by permission of the Journal of Anatomy. Fig. 5. Diagrams showing the topographic structure of the monkey's oculomotor nuclei. The small celled, or accessory, components are shown in black. Contrast with the functional schemes displayed in Figs. 2 to 4. 41 4-2 R. WARWICK nucleus of Tsuchida (1906), a fact not always recognised in topographic and other accounts (Warwick, 1953c). Perlia's pioneer work on the arrangement of the oculomotor nuclei has, of course, been considerably amplified and modified by authorities such as Tsuchida (1906), Frank (1921), Le Gros Clark (1926), Pearson (1944), Crosby, Henderson and Woodburne (1943), and Olszewski and Baxter (1954). Indeed, although Perlia's diagram still figures in many modern textbooks, it has become clear that it does not offer an accurate blueprint of the conditions which obtain in primates. (Contrast Figs. 1 and 5.) The profound disagreements and doubts which have thus accumulated in connexion with the oculomotor complex are not reflected in current textbooks, and the impression gained from all but a few recent mono- graphs is that Perlia's topography and the Bernheimer-Brouwer plan of functional representation are not merely acceptable but reliably proved. It is noteworthy that the two schemes (cf. Figs. 1 and 3) are not closely comparable, as might reasonably be expected, and perusal of the original literature convinced me that in particular functional conceptions of ocu- lomotor organisation were still matters of uncertainty. I therefore began in 1947 what proved to be a lengthy investigation into these problems, the results of which I can here present only in epitome. My experiments were carried out almost entirely on rhesus monkeys, for obviously conclusions reached by observation on primate animals would be most likely to yield a reliable indication of conditions in man. Nissl's acute retrograde degeneration technique was selected in preference to stimulation methods, since many objections to the latter are apparent in the case of the present application. By punctate stimulation in such a region as the midbrain one cannot be certain even that nerve cells alone are responding; supra-nuclear and other fibre connexions, including possibly inhibitor axons, may also be activated. It is impossible so to stimulate all and only the neurons innervating a single ocular muscle, whereas division of its nerve supply can produce demonstrable changes, selectively and exclusively, in these same cells, whether they be segregated or intermingled with others. Stimulation, too, produces movements rather than individual muscle contractions, and the interpretation of these in terms of individual extra-ocular muscles can be extremely difficult and notoriously fallacious (Warwick, 1950 and 1955). Retrograde degeneration has been regarded as a capricious technique by some. Initial experiments were therefore intra-cranial divisions of the oculomotor trunk (six monkeys), the results of which served not only to test the method's reliability but also to determine afresh the precise radi- cular origins of the nerve. The chromatolytic changes produced were unequivocal in nature. The midbrains of these and all other animals involved were sections serially, and since each series comprised 3-400 sections, the preparation and examination of this material occupied a number of years. The results obtained can be hence only exemplified. 42 OCULOMOTOR ORGANISATION These initial experiments confirmed the main, large-celled oculomotor nucleus as the chief source of third nerve fibres, but also included their small-celled neighbours, the Edinger-Westphal and antero-median nuclei. The latter has been previously so included only by Levinsohn (1904). My results corroborated the suggestions of Panegrossi (1904) and Le Gros Clark (1926) that the caudal central nucleus is con- cerned with oculomotor function, but they went further in showing that it is a radicular component of the third nerve's nuclear complex (Warwick, 1953a). Excluded from this role were the nucleus of Darkschewitsch (1889), the interstitial nucleus of Cajal (1909), the subfascicular nucleus of Frank (1921), and the dorsal nucleus of the raphe, all of which have DORSAL

* . * **.**0 * 0 . 00 , 0 + * : *+*0 * . 0 @0.0 *_ 0 I -* ***** 0. 0 ** *I 0 . 0 .90 ** * * *** 0 0 .' 0 00 - 0 . WW* 0 * 0 * 0 +* *.*. * 0 * * *- * 0.0 0 0* 0 0 4p * 0*,;<* 0 ,*, ** . 00 * * * a * 0 . 00 0 *0 0.* 0 -* 0 0 0 0 0 0*

L. R. DIVISION OF RIGHT CAUDAL THIRD Fig. 6. Chart recording the distribution of normal (dots) and chromatolytic (stars) nerve cells of the oculomotor complex in a particular transverse section of a midbrain series prepared from a monkey which was killed eleven days after division of the right oculomotor nerve. Most of the affected cells are in the right main or lateral third nerve nucleus, but some are also present on the left side, indicating decussation of some fibres. The median mass of cells situated dorsally is the caudal central nucleus, which evidently also contributes fibres to the oculomotor nerve. 43 R. WARWICK from time to time been mooted as sources of oculomotor axons (Warwick, 1953a). To facilitate quantitative evaluation of results a photographic method of recording permanently the distribution of normal and chromatolytic Dorsal Rostral C.C.N.

K. N

(a) Cudal third.

D.N. (e) Right lateral aspect.

(b) Middle third. Rostral V.N. |L R. (c) Rosiml third. 1 _ C . C . N~~~~~~~~~~~~~~~..N

D~.N.

(d) Rostral cid. (r) Dorsol aspect.

Rectus infcrior. Obliquus inferior.

- 1F Rectus medialis. Levator polpebroe superioris.

Rectus superior. Visceral nuclei. Reproduced by permzission of the Journal of Comparative Neurology. Fig. 7. These diagrams show in transverse sections (a-d), and in lateral and dorsal views (e and f), the disposition of the individual motor pools in the oculomotor complex of the monkey, according to the experimental results reported here. Contrast with the schemes of Bernheimer and Brouwer (Figs. 3 and 4). 44 OCULOMOTOR ORGANISATION cells in any given section was evolved (Warwick, 1950; Howarth and Warwick, 1952). These were distinguished by contrasting symbols marked upon cell images in a whole-plate enlargement of the particular field under microscopic inspection (Fig. 6). Such charts permitted accurate comparison of the scale and distribution of retrograde changes at varying levels of the same or of different oculomotor nuclei. By such means I was able to confirm that some oculomotor fibres decussate before emergence in the third nerve, and that these, amounting to 10 per cent., originate from cells in the caudal two-thirds only of the main nucleus and also, a finding not previously reported, from the caudal central nucleus. Although most strict criteria of retrograde reaction were adopted it was found that at least 42 per cent. of the oculomotor neurons reacted to unilateral third nerve division. Since only 50 per cent. could be expected to do so the residual 8 per cent. provides a meagre residue for connector or other integrating cells as favoured by Lorente de No (1947). Following these satisfactory preliminary operations unilateral orbital interruption of individual nerve-supplies to ocular muscles was effected in fifty-five monkeys. These manoeuvres were difficult and full technical description will be found elsewhere (Warwick, 1953b). The material was dealt with as above, the results being based upon examination of serial sections in every case, together with photographic charting in most series. Reference to Fig. 7 will demonstrate the final result of these protracted observations more clearly than verbal description. That the trochlear and abducent nuclei are respectively the motor pools of the superior oblique and lateral rectus muscles is well established and my experiments confirmed this and that these two innervations are wholly crossed in the former case, wholly direct in the latter. It was early apparent also that the neurones which innervate the remaining five extra-ocular muscles are indeed segregated within the large-celled or somatic nucleus of the ocu- lomotor complex. But contrary to the cranio-caudal sequence of globular centres, shown in the familiar Bernheimer-Brouwer scheme, my conclu- sion was that individual motor pools extend as elongated columns in the long axis of the oculomotor nucleus (Fig. 8). As will be seen, the motor column supplying the rectus medialis lies most ventrally, that for the rectus inferior most dorsally, with an intermediate column for the obliquus inferior. The motor pool for the rectus superior is less well demarcated, and lies on the medial aspect of the other three in the caudal two-thirds only of the somatic nuclear mass. An entirely new finding was innervation of the levator palpebrae superioris by the caudal central nucleus. Comparison of this fresh reconstruction of muscle representation in the third nerve's radicular complex with the widely accepted conception due to Bernheimer and Brouwer shows a complete contrast, the only point of resemblance lying in segregation of individual motor pools (Figs. 3 to 5). Apart from this there is obviously a fundamental difference in orientation, extent and disposition of the latter. My experimental results showed 45 R. WARWICK Rostrol

DoerslI

f . f

Ventral

Bernheimer-Brouwer. Present Interpretation. Rectus inferior Obliquus inferior Rectus mediolis U Levatorpalpebroe superioris ERectus superior U Visceral nuclei Reproduced by pernzission of the Journal of Comparative Neurology. Fig. 8. Comparison of the Bernheimer-Brouwer pattern of oculomotor organisa- tion with the results of this investigation. Both are lateral views. Note the entirely different orientation and interrelation of the motor pool for individual muscles. further that while it is true that some oculomotor axons do decussate in the midbrain, these are not concerned in supplying the recti inferior et medialis or obliquus inferior, as usually assumed. I found these supplies to be wholly direct in the monkey, as did Bach (1899) and Szentagothai (1942) in other mammals. On the other hand, and again in contradiction to the orthodox view and the recent findings of Bender and Weinstein (1943) and Danis (1948), my conclusions were that it is the rectus superior which receives a contralateral supply, while the levator's innervation is bilateral. Thus these results constitute a basically new plan of organisation within the oculomotor complex, contrasting not only at all points with standard teaching but also much at variance with the schemes evolved by recent stimulation studies, which are already beginning to receive occa- sional mention in neurological monographs. The scheme of organisation 46 OCULOMOTOR ORGANISATION presented here resembles in principle only the neglected conclusions of Bach (1889) and van Biervliet (1898). Unlike others, and particularly the Bernheimer-Brouwer scheme, the arrangement of motor pools deduced from my experimental results shows a very close conformity with the topographic subdivision of the main oculomotor nucleus. On the other hand, there exists a startling and indeed embarrassing disparity between current topographical accounts of the primate oculomotor complex and not only orthodox functional conceptions but also those arising from the most recent " physiological " investigations (Warwick, 1953b). My own topographic observations, which have concerned not only the midbrains of over 100 rhesus monkeys but in addition a number of human and chimpanzee series, have convinced me of the close parallel between structural and functional organization of the oculomotor com- plex. They have also led to the conclusion that Perlia's central nucleus, which has acquired much prominence as a " convergence centre " in the accounts of Knies (1891), Brouwer (1918) and most subsequent authors, is an entity at once anatomically inconstant and functionally uncon- scionable (Warwick, 1955). I found it absent in seventy-seven of 100 monkey midbrains and well-developed in only nine of them. In human and chimpanzee midbrains it is usually possible to identify a central nucleus such as Perlia (1889) described ; but Tsuchida (1906) recorded its absence in about 20 per cent. of thirty-two human midbrain series. Le Gros Clark (1926) directed attention to the excellent development of a central nucleus in the squirrel and tree-shrew, both animals with laterally placed eyes, and he contrasted with this its absence or ill-defined nature in the tarsier and monkeys, despite their habit of binocular vision. My own contribution to these grave criticisms, which I can confirm in so far as primates are concerned, lies in the observation that the simian central nucleus, when present, is composed of neurones supplying the rectus superior. They could scarcely, therefore, provide a second motor pool for the rectus medialis in convergence movements, as appears to have been the original supposition; nor can they be internuncial nerve cells for the integration of such activities. It is doubted whether they are sufficiently numerous to mediate even the joint actions of the medial recti, much less the accompanying adjustments of tone in all other extra- ocular muscles which almost certainly occur during convergence, as in any ocular movement. Current textbooks, some of which are dogmatic concerning the association of Perlia's nucleus with convergence, are nevertheless uniformly taciturn in respect of the precise manner in which it is supposed to work. The reiteration from one account to another of this, and indeed the rest of Brouwer's conception of oculomotor organi- sation, has gradually clothed it in a mantle of authority which obscures the unsatisfactory basis of premise and fact originally invoked in its support. When one considers the extremely labile type of integration necessary in the eye-moving muscles and their continual association with the conscious phenomena of vision, it is perhaps surprising that a small 47 R. WARWICK and anatomically inadequate group of midbrain cells should ever have been loaded with the complex task of mediating convergence. Whatever hypothetical criticisms might thus have rendered the concept initially stillborn, the accumulated facts of comparative and experimental anatomy can not admit its further perpetuation. Upon a more positive note, my own investigations have largely sub- stantiated the usual account of the ocular parasympathetic pathway as given in texts of neurology and ophthalmology. The commonly accepted route of these fibres is shown diagrammatically in Fig. 9, which also displays details of the experimental interruptions which I carried out in twenty-three monkeys. The outstanding uncertainty in regard to this pathway is the precise central origin of its pre-ganglionic fibres, reputed to arise from the relatively small motor cells of the Edinger-Westphal nuclei. Certain authorities have denied this; Latumeten (1924) did so with particular vigour. His much-quoted experiments were few in number and unconvincing on close scrutiny (Warwick, 1954a). Le Gros Clark (1926) and more recently Olszewski & Baxter (1954) have pointed out how little positive evidence has been recorded in support of this customary assumption. Iris and Iridectomy 3 Evisceration 2 Enucleation 2

Short ciliary nerves Division 5

Ciliary ganglion -Extirpation 3 Branch to inf. oblique Division 2

Oculomotor trunk Division 5

Antero-median nucleus Edinger-Westphal nucleus Total series 22

Reproduced by permission of t/e Journal of Anatomy. Fig. 9. Diagram of the reputed pathway of parasympathetic supply to the eyeball. It should be noted that while most standard works speak of the Edinger-Westphal nucleus as a central source of preganglionic fibres, practically none include the anteromedian nucleus. Also shown on the right are the points at which experimental interruptions were carried out in the present investigation. 48 OCULOMOTOR ORGANISATION In my experiments oculomotor division always produced clear degeneration in the ipsi-lateral Edinger-Westphal nucleus ; but in addition even more marked effects were observable in the anteromedian nucleus, which is composed of similar cells (Fig. 10) . The continuity of these small-celled nuclei, cranial and dorsal to the somatic oculomotor mass (Figs. 5, 6 and 8) has been widely recognized in recent years (Crosby, Henderson and Woodburne, 1943), although this is not yet a feature of standard teaching. The anteromedian nucleus has been almost entirely ignored in accounts of functional oculomotor organisation. My results showed that both nuclei give rise to oculomotor axons ; that these are in fact the preganglionic connexions of the nerve cells whose fibres reach the eye via the was proved by ciliary ganglionectomy. I found that this procedure, which is obviously the most crucial in testing the reputed ocular parasympathetic supply, did indeed produce retro- grade changes in Edinger-Westphal and anteromedian nuclei. Regarding the latter only Levinsohn (1904) reported like results, in cats. Kure et al. (1933) similarly produced a response in the Edinger-Westphal nucleus of dogs. Few others have studied the midbrain effects of ciliary ganglio- nectomy, and none of these have recorded positive results in the small- celled oculomotor mass. Division of the short ciliary nerves regularly produces retrograde degeneration in practically all the ganglion's cells. By removal of the ocular contents and iridectomy, in separate monkeys, I was able to estimate what proportion of these neurones innervate the ciliaris and sphincter muscles. The former procedure, which interrupts all axons entering both muscles, affected at least 96 per cent. of the cells, whereas only 3-3-5 per cent. showed changes after total iridectomy. It is thus evident that much the greater part of the ciliary ganglion axons mediate accommodation, not pupillo-constriction, as the comparative bulks of the two muscles would suggest. It is customary to speak of the ocular parasympathetic pathway as the motor limb of the light reflex arc, despite its accepted participation in accommodation. The illogicality of this is thrown into greater prominence by the present finding that only a very small minority of this pathway's neurones can be concerned in constriction of the . The nature of the ciliary ganglion cells has attracted much polemical interest in the past (Warwick, 1954a). Nevertheless, there is little information concerning them in current standard works, and it is therefore natural to assume that they do not differ from other autonomic ganglion cells. This is not the case (Fig. 1 1). In primates, including man, they are relatively large, resembling in size and some other characteristics somatic motor nerve cells rather than those of the autonomic (Warwick, 1954b). Comparison of Edinger-Westphal cells with other pre-ganglionic neurones, such as those in the lateral gray column, similarly shows marked dissimilarity between them. It is logical to presume that the peculiar character of the ocular parasympathetic nerve cells has some 49 R. WARWICK

Fig. 10. Normal and chromatolytic nerve cells, on left and right respectively, from the anteromedian nucleus of a monkey subjected to ciliary ganglionectomy. Cresyl violet x 180.

Fig. 11. Nerve cells of the superior cervical sympathetic and ciliary ganglia, left and right respectively, removed from the same monkey, treated identically in histological preparation and photographed under identical conditions. The contrast in the two cell populations requires no emphasis. Cresyl violet x 80. 50 OCULOMOTOR ORGANISATION significance in function. Most of them are concerned with accommodation, which is an integral part of the conscious and commonly volitional processes of vision. It is, in fact, easily demonstrable by personal experiment that the tonus of the can be varied at will, an interesting anomaly in what Gaskell (1916) called "the involuntary nervous system." It seems not improbable that the peculiar nature of the ciliary ganglion cells at least, when compared with other autonomic neurones, may well be associated with the voluntary nature of accom- modation. This is, however, merely speculation, which will require further investigation. My own experiments have not demonstrated any nerve supply for the pupil's sphincter in addition to the above pathway, such as has been hypothecated in attempts to explain certain instances of Argyll Robertson pupil response. I can therefore pass no useful comment on this as yet ; nor is there time for me to encroach upon clinical topics in connexion with the new plan of oculomotor organisation which I have laid before you. It is in any event for others to apply these observations, and, if they can, the labour will have been not merely one of intense personal interest, but also, as I hope, of some usefulness. If, however, I may be permitted final comment, I would add that this lengthy enquiry has impressed on me the need to keep speculation in its due place in medical research. Around a small region in the midbrain a verbal flood has piled up over many decades, and it must regretfully be said that experiment and observation have been too often submerged in tidal waves of conjecture, surmisal, and hypothecation. Speculation, whether idle or germinative, is perhaps the most attractive element of thought and discussion. The responsibility of authorship is, however, a heavy one; and in our more formal contributions to science I submit that speculation should do no more than inspire our experiments, and should not unduly trespass beyond them without renewed appeal to the factual evidence. The experimental work on which this lecture was based was carried out in the Department of Anatomy, University of Manchester. My grateful thanks are due to its Director, Professor G. A. G. Mitchell, for the facilities afforded. The work was aided by grants from the Nuffield Foundation and Medical Research Council. I wish to thank Mr. R. A. Bailey and Dr. Alan Stanworth for skilled technical help at operations. It is a pleasure to acknowledge my indebtedness to Mr. Philip Howarth, of the Department of Anatomy, Manchester, for extensive photographic and histological assistance. All the diagrams were prepared by Miss Marjorie Beck. Mr. C. E. Engel and Mr. F. R. A. Plummer of the Department of Medical Illustration, Guy's Hospital Medical School, have also kindly helped with the illustrations.

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APPOINTMENT OF FELLOWS AND MEMBERS TO CONSULTANT POSTS W. K. JONES, M.R.C.S., F.F.A.R.C.S. Consultant Anaesthetist to Manchester Royal Infirmary and the South Man- chester Hospital Centre. A. H. MILLARD, F.R.C.S. Consultant Surgeon to the West Wales Hospital Management Committee. J. K. WRIGHT, F.R.C.S. Consultant Orthopaedic and Traumatic Surgeon to the Blackpool and Fylde Group of Hospitals.

G. G. BAIKIE, F.D.S.R.C.S. Senior Lecturer in Dental Prosthetics in the University of the Witwatersrand and Senior Dental Surgeon to the Uni- versity's Oral and Dental Hospital. 52