post-ganglionic nerves. The importance of this consideration from regenerated distal trunk. He was able in such cases by stimulating

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1 THE ARRANGEMENT OF NERVE FIBRES IN A RE- GENERATED NERVE TRUNK. BY W. A. OSBORNE AND BASIL KILVINGTON. (From the Physiotogicat Laboratory, University of Melbourne.) IN the course of our research on axon bifurcation as well as the researches of one of us (B. K.) on nerve regeneration the problem was constantly being suggested as to the arrangement 'of nerve fibres in a nerve trunk which has regenerated after section and suture. The fact that two branches of a single motor axon could grow down two such divergent routes as the external and internal popliteals or the radial and posterior interosseus led tus to believe that fortuitous apposition during suture was a leading factor in determining the route of regeneration. Each sprout in a regenerating stump would, according to this hypothesis, take the nearest path offered which possessed all the requirements for a regenerating fibre. If this were so a very considerable distortion or dissociation of the patterns above and below the neurome might result, and thus a dissociation of the receptor and medullary patterns in the case of afferent nerves or of the medullary and the' peripheral receptive substance patterns in the case of motor and preand post-ganglionic nerves. The importance of this consideration from a clinical as well as an academic standpoint is considerable. Lipschitzl has referred the frequent lack of co-ordination following regeneration of the cut facial in the human patient to arrangement of the fibres in the regenerated distal trunk. He was able in such cases by stimulating certain points on the skin near the scalp margin to produce contraction of discrete and widely divergent muscles or portions of muscles in the face. The important work of Langley in this connection will be discussed later. All of the experiments to be mentioned were carried out on animals used for the research on motor bifurcation, both primary and secondary I Abstracted in Neurolog. Centr. 1907, p. 380, and in Centr. f. Med. Wi8s. 1907, p. 141.

2 NERVE FIBRES IN REGENERATED NERVE. 277 operations being performed at the same respective times. For the sake of clearness all reference to these has been omitted in the paper on axon bifurcation, and, as they belong to a different research, are now collected and treated separately. REARRANGEMENT AFTER SECTION AND SUTURE. Exp. I. The sciatic was divided at the point of separation of the popliteals and at once sutured, the popliteals being maintained in correct apposition as far as was possible with a single suture. Stimulation was carried out 80 days after the primary operation. The popliteals were separated for some distance above the neurome and cut. Stimulation of EP and E (Fig. 1) gave strong contraction of both flexors and extensors of the toes, the flexors predominating. The external popliteal was now cut at P. Stimulation at E now gave only flexion of toes and greater than could be accounted for by the axon bifurcation which was proved to be present. Exp. II. This was in every particular, except period of regeneration (82 days), identical with Exp. I. The results were the same. Stimulation at E after cutting at E and P gave a very much stronger flexion of toes than could be obtained by axon reflex on stimulation at P Ėxp. III. The primary operation was the same. The period of regeneration was 70 days. On cutting the external popliteal at E and P and stimulating at E a slight flexion of toes was produced. Exp. IV. The sciatic was cut just above the separation of the popliteals, the correct apposition of these latter was, as far as possible, preserved on suturing. The period of regeneration was 137 days. The popliteals were separated for some distance above the neurome. The external popliteal was cut at E (Fig. 2). Stimulation of EP and P gave not only an axon reflex down the internal popliteal but also marked general reflex disturbance showing that sensory fibres properly connected with the central nervous system were being stimulated. The general reflex disturbance obtained by stimulating the internal popliteal at IP' was however much greater. Only a minority therefore of the sensory fibres in the proximal IP had crossed to the distal EP. Exp. V. The sciatic was cut just above the separation of the popliteals and the correct apposition preserved on suture. After 113 days the bulb was cleaned by dissection and stimulation carried out

3 278 W. A. OSBORNE AND B. KILVINGTON. eight days later. Stimulation of the external popliteal below the neurome gave strong reflex disturbances. The external popliteal was now cut at E (Fig. 2). Stimulation at P now gave sensory manifestations but considerably reduced in amount. E IP E IP EP p_.. Fig. 1. P1 p Fig. 2. Ip' Exp. VI. The musculo-spiral was divided and sutured after twisting the distal portion through an angle of When 189 days had elapsed the radial was separated out from the proximal musculo-spiral, i.e. above the neurome, and cut. After an interval of 11 days, or 200 days from the primary operation, the distal radial was stimulatedmarked reflex sensorv disturbances followed showing that sensory fibres of the posterior interosseus had grown down the radial. No axon reflex was obtained owing to an accidental injury to the distal posterior interosseus at the time of stimulation. The above experiments therefore demonstrate that when a nerve trunk is cut and sutured considerable distortion of the motor and sensory patterns occur during regeneration. It may be mentioned in this connection that the presence of wound fibres is in itself conclusive evidence of the disarrangement that occurs, at least with motor fibres, on section and suture.

4 NERVE FIBRES IN REGENERATED NERVE. 279 THE APPOSITION FACTOR Exp. VII. The sciatic was crushed by a silk ligature tied tightly just below the sciatic notch and then removed.. Stimulation was carried out 67 days after the primary operation. Stimulation of EP at P (Fig. 1.will serve for this exp.) gave strong sensory reflex disturbances. The external popliteal was now cut at E. Stimulation at P now produced no effect. Stimulation of the distal internal popliteal at IP produced sensory reflex disturbances. Exp. VIII. The crush by silk ligature was applied just above the separation of the popliteals. Stimulation was carried out 71 days later. Stimulation of both distal popliteals gave strong motor effects and sensory reflex disturbances. The popliteals were separated above the region of crush and the internal popliteal cut at IP' and IP. Stimulation of the distal internal popliteal at IP now gave no motor effects. Stimulation of the proximal internal popliteal at IP' gave no sensory manifestations. These experiments taken in conjunction with the absen'ce of bifur cation in crushed nerves show that though physiological and possibly physical continuity have been destroyed in the axons, yet disarrangement will not occur on regeneration if the apposition is perfect. Head and his collabortors have shown that in a crushed nerve " epicritic" sensation returns at the same date as the " protopathic," whereas if the trunk be cut the time required for epicritic regeneration is much longer than that for protopathic and may demand several years. Our experiments suggest that in this latter case the delayed or incomplete return of epicritic sensation is not a delayed or incomplete regeneration of nerve fibres but is due to the dissociation of the receptor and medullary patterns necessitating a new sensory co-ordination. The same dissociation can adequately explain the referred or multiple sensation following stimulation at a single. point in cases of regenerated cut nerves-a view which has been put forward by Langley'. Our experiments with sensory and motor fibres and those of Langley2 on post-ganglionic might lead one to suppose that fortuitous apposition is the single deciding factor in determining the route of regeneration. That this is not the case with pre-ganglionic fibres has been proved by the remarkable experiments of Langley in which certain PH. XXcXVIII. 1 Proc. Physiol. Soc. Jan. 25th, This Journal, xxi

5 280 W. A. OSBORNE AND B. KILVINGTON. upper thoracic white rami preserved their separate respective actions after section and regeneration of the cervical sympathetic. Some distortion, it is true, was noted, but, in the main, pupillo-ditlator preganglionic fibres regenerated along pupillo-dilator and not erector pili pre-ganglionic paths. Langley has suggested that here a specific chemiotactic agency is at work. This appears highly probable, but other factors may be exercising some influence. Thus differences idn distance from the nerve cell may mean differences in the time of sprouting of the proximal axon stump and of chemiotactic preparation of the distal paths. If the observations of Donaldson' are correct and the broader fibres in a nerve trunk bave a more proximal peripheral distribution the mere question of size may have to be considered in this connection. But certainly, so far as our experiments demonstrate, chance apposition seems to be a much more important factor with motor and afferent nerves thazt it is with pre-ganglionic fibres as evidenced in Langley's experiments. CONCLUSIONS. 1. If a nerve trunk containing sensory and motor fibres be cut and sutured, considerable distortion of the sensory and motor patterns takes place on regeneration. 2. If the nerve trunk be crushed and not cut no distortion is detectable on regeneration. 3. The dissociation of the nerve patterns above and below the neurome in a nerve which has regenerated after section must condition an inco-ordination of motor effects and a disturbance of sensory co-ordination or " sensual fusion." The expenses of this research were defrayed by a grant to one of us (B. K.) from the Government Grant Committee of the Royal Society. I Neurolog. Centr. 1908, p. 677.