The Integrative Action of the Nervous System

With serial stimuli of the same frequency of repetition the latent time of the scratch-reflex is shorter the more intense the individual stimuli. Stirling ^"^ conclusively traced length of latency to dependence on spinal summation of successive excita- tions. In accord with this in the "scratch-reflex," when the serial stimuli follow slowly, the reflex caeteris paribus is pro- longed. A single brief mechanical stimulation of the skin (rub, prick, or pull upon a hair) usually succeeds in exciting a scratch- reflex, though the reflex thus evoked is short ; but there is noth- ing to show that these stimuli, though brief, are really simple and not essentially multiple. A striking dissimilarity, therefore, between reflex-arc conduction and nerve-trunk conduction is that in reflex-arc conduction considerable resistance is offered to the passage of a single nerve-impulse, but the resistance is easily forced by a succession of impulses ; in other words, sub- liminal stimuli are summed.

It follows almost as a corollary from this that the threshold excitability of a reflex mechanism appears much more variable than that of a nerve-trunk, if the threshold excitability be meas- ured in terms of the intensity of the liminal stimulus. The value will be more variable in the case of the reflex mechanism, be- cause there the duration of the stimulus is a factor in its effi- ciency far more than in the case of the nerve-trunk. In the scratch-reflex a single stimulus which is far below threshold intensity is found, on its fortieth repetition and nearly four seconds after its first appplication, to become effective and pro- voke the reflex.

Irreversibility of direction of conduction. Another remarkable difference between reflex-arc conduction and nerve-trunk con- duction is the irreversibility of direction of the former and the reversibility of the latter. Double conduction, as it has been termed, is well-established for nerve-trunks both afferent and efferent. It was shown by du Bois Reymond for the spinal nerve roots, for peripheral nerves by Kuhne's gracilis experi- ment, for the great single electric fibre of Malapterurus by Babuchin,^^ for sympathetic nerve-cords by Langley and Ander- son,^^ and by myself ^^^ for certain fibres of the white tracts of the spinal cord. The nerve-fibres in all these cases, when ex- cited anywhere in their course, conduct nerve-impulses in all directions from the point stimulated ; that is, in their case both up and down, the only two directions open to them. Their substance may therefore be regarded as conductive in all direc- tions along their extension.

From the Bell-Magendie law of the spinal nerve-roots we know that reflex-arcs conduct only in one direction. The stimulation of the central end of a motor-nerve remains without obvious effect. Bell ^^ and Magendie ^^ and their followers estab- lished that excitation of the spinal end of the severed motor root evokes no sign of reflex action or sensation. Evidently the central nexus between afferent channel and efferent is of a kind that, though it allows conduction from afferent to efferent, does not allow it from efferent to afferent. The path is patent in one direction only. This is the special case which forms the first foundation of the law that conduction in the neural system pro- ceeds in one direction only, the " law of forward direction (W. James, 1880).^^ When the property of double conduction in nerve-fibres had been ascertained, the Bell-Magendie law of the

spinal roots became more instructive. Gad ^^ (1884) argued that the dendrites of the motor root-cell are capable of conduc- tion in one direction only, namely, toward and not away from the axone. It may, however, be that the irreciprocity of the conduction is referable to the synapse. The explanation of the valved condition of the reflex circuit may lie in a synaptic mem- brane more permeable in one direction than in the other. In other words, through intraneuronic conduction is reversible in direction, interneuronic may be irreversible.

Cell-chains of polarized conduction form the basis of the great majority of all the nervous reactions of the cerebrospinal system of higher animals. It appears, however, that not all pluricellular nervous circuits exhibit irreversible direction of conduction. The nerve-net of Medusa is a pluricellular con- ductor which exhibits reversibility of direction of conduction. In Medusa locomotion is effected by contraction of a sheet of muscle in the swimming-bell. When the swimming-bell, which resembles an inverted cup, contracts, its capacity is lessened, and some of the water embraced by it is expelled through the open end, the animal itself being propelled in the reverse direc- tion by recoil. The mechanism is like that of the heart, but the heart propels its contents, the swimming-bell propels itself against its contents. The contractions of both recur r>^thmi- cally, though Medusa, unlike the heart, has periods of prolonged diastolic inactivity. At such a period an appropriate stimulus restarts the swimming-bell. The contractive beat begins from the point stimulated and spreads thence over the whole muscu- lar sheet.''* It spreads rapidly enough for the contraction not to have culminated at the initial point before it has set in at the most remote part. The beat is thus not only everywhere in progress at the same time, but is practically in the same phase of progress everywhere, and similarly synchronously passes off."^^

The arrangement of the nervous system of Medusa, e. g., Rhizostoma, is, according to Bethe, of the following kind (Fig. II). The nerve-cell has on one hand thread-like arms that extend to the surface of the subumbrella, and on the other hand others which stretch down to the sheet of contractile cells Figure ii (A. Bethe 2W). — Nerve-net of Rhizostoma. A, radial section through a mus- cular field of the subumbrella ; Ep, epithelium ; i«, muscle-fibres in cross-section; M. K.^ their nuclei ; N.ply nerve-plexus with fibres running into the epithelium and to the muscles; B, nerve-plexus with scattered cells, from a horizontal section. Magnification 1200 in A, 200 in B.

on the under side of the bell. Each nerve-cell has also long side threads which join similar side threads from other nerve- cells. By virtue of these lateral connections the nerve-cells form a network of conductors spreading horizontally through the bell in a layer of tissue between a receptive sheet and a contractile sheet. From this nerve-net, throughout its extent, there pass nerve- threads to the adjacent muscle ; it also receives at many points of its extent nerve-threads from specially receptive areas of surface.

The circularly arranged sheet of muscle does not form a continuous field toward the centre of the disc ; there are wide radial gaps in it. Across these gaps the "conduction" passes: the microscope reveals no muscular tissue in these gaps, but the nerve-net can be seen to spread across them.^^ The presence of the nerve-net explains the conduction across them. It is therefore argued by Bethe that the spread of the contraction over the muscular sheet in Rhizostoma does not imply conduc- tion of the contraction from one muscle-cell to another, but is the result of the spread of nervous action over the nerve-net work. In its progress along the nerve-net, the nervous discharge, as it reaches each part of the nerve-net, spreads down the nerve- threads, descending thence to the underlying muscle-sheet. So long as the nerve-cell network is intact, wherever the point stimulated, the ensuing contraction is of the whole bell, that is, the nerve-impulses started at one point of the receptive surface, on entering the nerve network, spread over it in all directions. When the bell-shaped disc is spirally cut into a long band, to whichever end of the band the stimulus be applied, the conduc- tion spreads from that end to the other and over the whole strip (Romanes).'^^ The nerve-net therefore conducts nerve- impulses in both directions along its length. Therefore it is not a polarized conductor, conductive in one direction only. In the chains of nerve-cells of higher animals, such as Arthropods and Vertebrates, although the conduction is reversible in each nerve- cell, — at least along that piece of it which forms a nerve-fibre, — the pluricellular chain in toto constitutes a polarized conductor, conductive in one direction only.

In such cell-chains the indi- vidual nerve-cells are characterized morphologically by possess- ing two kinds of cell-branches, which differ one from another in microscopic form, the one kind dendrites, the other axones. The difference in appearance between dendrites and axones is marked enough for recognition by microscopical inspection. Since in many well-known instances the dentrites conduct im- pulses away from their free ends, while the axone conducts towards its free end, it is possible on mere microscopic inspection of nerve-cells of this type to infer by analogy the normal direction

of the conduction through the nerve-cell. But in the nerve-cells forming the nerve-network of Medusa there seems no such dis- tinct differentiation of their branches into two types. Their cell- processes are not distinguishable into dendrites and axones. Moreover, microscopic examination of the nerve-net of Medusa reveals another difference between it and the nerve-cell chains of higher animals. In these latter the neuro-fibrils of one nerve-cell are not found unbrokenly continuous with those of the next cell along the nerve-chain. Although the union may be close, there is not homogeneous continuity. The one nerve- cell joins another by synapsis. But in the nerve-net of Medusa the neuro-fibrils pass, according to Bethe, uninterruptedly across from one cell to another. Even if we admit the neuro-fibrils to be in a measure artifacts, the appearance of their continuity from one cell to another in one type, and of their discontinuity from one cell to another in the other type remains significant of a difference between the conduction-process from cell to cell in the two types. The nerve-net of Medusa appears an unbroken retiform continuum from end to end. Each nerve-cell in it joins its neighbours much as at a node in the myelinate nerve- fibre the axis-cylinder of each segment joins the next. Reversi- bility of conduction may be related to this apparent continuity of structure, and irreversibility to want of it. This points to the latter's being referable to the synapse ; if the synaptic membrane (Lect. I. p. 1 8) be permeable only in one direction to certain ions, that may explain the irreversibility of conduction. The polarised conduction of nerve-arcs would be related to the one-sided permeability of the intestinal wall, e. g, to NaCl (O. Cohnheim).

Rhythm of response. One of the differences between nerve- trunk conduction and reflex-arc conduction is the less close correspondence in the latter between rhythm of stimulus and rhythm of end-effect. The number of separable excitatory states (impulses) engendered in a nerve-trunk by serially re- peated stimuli corresponds closely with. the stimuli in number and rhythm. Whether the stimuli follow each other once per second or five hundred times per second, the nervous responses

follow the rhythm of stimulation. Using contraction of skeletal muscle as index of the response the correspondence at rhythms above thirty per second becomes difficult to trace, because the mechanical effects tend at rates beyond that to fuse indistin- guishably. The electrical responses of the muscle can with ease be observed isolatedly up to faster rates : their rhythm is found to agree with that of stimulation ; thus, at eighty per second their responses are eighty per second. If the muscle note be accepted as an indication of the response of the muscle, its pitch follows /^r/ passu the rate of stimulation of the nerve through a still greater range.

The case is quite different with reflex-arcs. Schafer ^^ noted undulations of a frequency of ten to twelve per second on myo- grams of spinal reflexes evoked by excitation of the afferent nerve by faradic currents of frequency much above ten to twelve per second. In such a case we may assume the absence in the afferent nerve itself of any refractory period long enough to give a ten per second rhythm to the response. The refractory period in nerve-trunk conduction seems to last not longer than i c. The rhythm of discharge from the motor-cell, as far as the un- dulations noted indicate rhythmic response, are totally different in rhythm from that of the action induced in the afferent cell by the stimulation applied. In the reflex centre the rhythm has been transmuted from one rate to another. Schafer refers this change to the synapse.

Again, as noted above, undulations at rates varying be- tween 7.5 and 12 per second are seen in the flexion-reflex both in its after-discharge and during the excitation and quite inde- pendently of the rate of delivery of the induction shocks used as stimuli (Figs. 6 and 12), and even when the stimulus is a constant current. Again, reflexes of weak intensity, both in the case of the flexion-reflex and of the crossed extension-reflex, exhibit at their commencement a stepped form of myogram: the steps usually succeed each other at about eight per second, and their rate is independent of the rate of delivery of the electric stimuli (Fig. 12) exciting the reflex.

In such cases, therefore, the rhythm of the end-effect indi- Figure 12. — Flexion-reflex showing imperfect fusion under excitation of the skin with break shocks at the rate of 10 per second. Signal above shows the six interruptions of the primary circuit. Time below in seconds. cates that in transmission along the reflex-arc the impulses generated at the receptive end of the arc are not actually passed on from one cell element to another in the arc, but that new impulses with a different period are generated in the course of the reflex-conduction. This is confirmatory of a neurone- threshold as a feature in central conduction.

Refractory phase. A conductor which replies intermittently to a stimulus exhibits a refractory phase. It seems that even in nerve-trunk conduction a refractory phase must occur; other- wise, the conductor being capable of reversible direction of con- duction, a backward propagation of the excited state as well as a forward would ensue from every point of the conductor reached by the nervous impulse. The excited state would then, when once excited, maintain itself in a tetanic manner along the whole length of the conductor. The propagation would thus lose undulatory character such as we know it has; it would merely have an initial wave-front. But this refractory phase in nerve-fibres seems of very brief duration, not longer than i o-.

The reflex-discharge from nerve-cells seems to oe rhythmic even under continuous stimulation ; but the cases in which this has been examined are sparse. The existence of rhythm in nerve-cell discharge is presumptive evidence of a refractory phase in their reaction. Refractory phase was first called atten- tion to by Kronecker and Stirling ^^ in 1874, in the heart, and recognized by them as a fact of central importance for cardiac rhythm. In 1876 Marey ^' met the same phenomenon and gave it the name by which it is now known. A year later Romanes' fundamental work on Medusa demonstrated the existence of the same phenomenon there.^^ The inconspicuous duration of the phase in nerve-trunk conduction and the progress of the view that regards the heart beat as of myogenic origin have contributed to delay recognition of refractory phase as a character of reflex- arc reactions. But in 1899 Zwaardemaker and Lans^^® showed the supervention of a refractory phase in reflex eyelid-closure. By refractory period was originally meant by Marey the time during which the heart was inexcitable to a stimulus however intense. But to-day by refractory phase is understood a state during which, apart from fatigue, the mechanism shows less than its full excitability. The cardiac refractory phase is absolute for a short time after commencement of systole, but excitability then returns gradually. In the eyelid-reflex for nearly a full second after initiation of a reflex, the chance that a second stimulus then delivered will, though otherwise appropriate, ex- cite the reflex, is fifty per cent less than it is one second later. The refractory phase, therefore, is marked though not absolute : it operates longer for a visual stimulus than for a tactual or thermal.

Of the spinal reflexes of the dog's hind limb, one, namely, the scratch-reflex, shows marked refractory phase.^^^ When work- ing originally with this reflex, I noticed ^^^ that the rhythm of the scratching movement is in rate independent of the rhythm of the stimulus evoking it. In the dog, when the spinal cord has been transected in the neck, the scratch or scalptor reflex becomes in a few months prominent. A stimulus applied at any point within a large

Figure 13. — A. The "receptive field," as revealed after low cervical transection, a saddle- shaped area of dorsal skin, whence the scratch-reflex of the left hind limb can be evoked. /r marks the position of the last rib. B. Diagram of the spinal arcs involved. L, receptive or afferent nerve-path from the left foot ; r, receptive nerve-path from the opposite foot ; Ra, r^, receptive nerve- paths from hairs in the dorsal skin of the left side; FC, the final common path, in this case the motor neurone to a flexor muscle of the hip ; Pa, p/3, proprio-spinal neurones.

saddle-shaped field of skin (Fig. 13) excites a scratching move- ment of the hind leg. The movement is rhythmic alternate flexion and extension at hip, knee, and ankle. Each flexion recurs at a frequency of about four times per second. The stimuli provocative ^^ of it are mechanical, such as tickling the skin or pulling lightly on a hair. The receptive nerve-endings which generate the reflex lie in the surface layer of the skin, about the roots of the hairs. A convenient way of exciting the reflex is by feeble faradization, such as applied to one's own tongue is felt as a tickling sensation. For exciting the reflex electrically, I place a broad diffuse electrode on some indifferent part of the surface outside the receptive field of skin, and apply

Figure 14. — Tracing of the flexion of the hip in the " scratch-refiex " of a " spinal dog." In A the reflex is evoked by lightly rubbing the skin at a point behind the shoulder, in B and C by unipolar faradization with weak double-induction shocks applied to the same point of skin through a needle point lightly inserted among the hair roots. Time marked in seconds below. At the top in B and C an electric signal marks the double-induction shocks delivered, and at the bottom an electric signal marks the time of application of the stimulation.

a stigmatic electrode to some point in the saddle-shaped area of dorsal skin. This electrode may consist of a minute needle, or a gilt entomological pin ; it is inserted in the skin so lightly that its point just lies among the hair bulbs. If it be pushed further, other types of reflex may be produced and the scratch-reflex be inhibited. Prominent among the muscles active in this reflex are the dorso-flexors of the ankle, the flexors of the knee, and the flexors of the hip. If the rhythm of the last is recorded graphically, tracings,*^ as in Figure 14, are obtained. It is then demonstrable that the series of brief contractions succeed one another at a rate the frequency of which is independent of that of the stimulation. Thus, the rhythmic reflex is elicitable by the application of a heat-beam or a constant current. The make and break of the current are especially able to excite it (Fig. 15), but it is for a time maintained even by the continued passage of the current, though it lapses in intensity until the current is broken.

Figure 15, — Scratch-reflex evoked by a galvanic current with the kathode at a spot of skin behind the shoulder and a diffuse anode applied to the fore-paw. The make of the current excites a stronger reflex than the break; the break with the two weaker strengths of current Gi and G, did not suffice to excite the reflex at all; but in G^ it did. The signal line below indicates the time of application of the current. Current in G, was 1.5 milleamperes.

when it appears temporarily with renewed vigor. At make and break of the voltaic current the reflex-response is a short series of rhythmic flexions. The reflex is still more easily evoked by unipolar application of high frequency currents ; it can be evoked with great vigour and long duration by this mode of stimulation. Double-induc- tion shocks applied at frequencies from once per second to five hundred and twelve times per second and at various intermedi- ate rates all evoke it easily; so likewise do single break or make shocks applied at rates varying in my experiments between 1.33 times per second and forty times per second.

Under all these various methods of excitation (heat-beam, constant current, double and single induced currents, high frequency currents, and mechanical stimuli) the rhythm of the flexor response remains — so long as the internal conditions of the reflex remain unaltered — almost the same.^®'^ It remains so also when, instead of a regular succession, a grouped succes- sion of stimuli is used for excitation, e. g,, stimuli grouped in twos and threes. It is obvious that this reflex exhibits a refractory phase. Take the instance where the stimulus applied consists of double-induction shocks, succeeding each other at a frequency of one hundred per second. The reflex-arc in response produces flexion at hip about four times per second. So few as three successive double-induction shocks will suffice to excite the reflex, but since in the instance taken about twenty such shocks correspond in time with each flexor beat, and each such beat is divisible into about equal periods of contraction and relaxation, let us make the assumption — a liberal one — that ten out of the twenty available shocks are serving as stimuli. The arc, while the following ten are being applied, fails in spite of them to excite the flexor muscles. To those ten it does not respond at all.

Nor can this refractory state be overcome by simply increas- ing the intensity of the stimuli. The reflex remains as perfectly rhythmic and clonic under the strongest stimuli as under weaker (Fig. 16). The frequency of the beats is under strong stimula- tion often somewhat higher than under quite weak, especially at outset of the reflex, but the difference is small, e. g,, 5.8 beats per second, instead of 4.5 beats per second. No mode or inten- sity of stimulation to which I have had recourse converts rhythmic clonic beat into a maintained steady contraction. In this respect, as in certain others, the scalptor reflex-arc closely resembles in its behaviour the mechanism of the Medusa bell and heart-wall. It resembles these more closely than it resembles the mamma- lian respiratory reflex-arc, which can under several circumstances be made to produce from the diaphragm an enduring tetanic contraction.

I refer to the contraction of the flexor muscles in the scalptor- reflex as a " beat," not implying that it is a single twitch, but rather because the term denotes a short-lasting phase of action in a rhythmic series, and because of its close analogy to the beat of Medusa and of the heart. What is the neuronic construction of the arc in the scalptor- reflex? The reflex is in a sense unilateral; stimulation of the left shoulder evokes scratching by the left leg, not the right. Search in the spinal cord ^^ for the paths of the reflex demon- strates that a lesion breaking through one lateral half of the cord anywhere between shoulder and leg abolishes the ability of the skin of that shoulder to excite the scratch-reflex, but leaves intact the reflex of the opposite shoulder. In the lateral half of the spinal cord which the reflex-path descends, severance of the dorsal column does not obviously interfere with the reflex; nor does the severance of the ventral and the dorsal columns together of that side ; no more does severance of the gray matter in addition. But severance of the lateral part of the lateral column itself permanently abolishes the conduction of the reflex ; and it does so even if all the other parts of the transverse extent of the cord remain intact. The paths of the

Figure 16 (opposite). — Scratch-reflex, provoked by 42 break shocks delivered at the rate of 40 per second. The interruptions of primary circuit producing these are recorded by electro- magnet giving the top line of the record. As the stimulus is without other change rendered more and more intense at 690, 11 00, 1900 and 3000 units of the Kronecker scale respec- tively, the reflexes A B C D show the differences seen. Instead of one beat during the stimulus and two afterwards, as in A, the reflex gives three beats during the stimulus and six beats afterwards, as in D. Time in seconds below.

reflex, therefore, descend the lateral part of the lateral column. These details help towards construction of the reflex-arc in- volved. For in the lateral part of the lateral column, as shown by the method of successive degeneration, lie long proprio-spinal fibres which directly connect the gray matter of the spinal seg- ments of the shoulder with the spinal segments containing the motor neurones for the flexor muscles of the hip, and knee, and ankle. The course of the descending proprio-spinal fibres can be traced and their number counted. The method of " successive degeneration " ^^^ enables one to unravel them from descending fibres of other sources, such as cerebral, mesencephalic, or bul- bar, and from proprio-spinal fibres descending from the foremost segments of the neck. This is done — as the term ** successive degeneration" implies — in a preHminary lesion by severing that part of the spinal cord it is desired to examine for the par- ticular proprio-spinal fibres sought, from all the central nervous system lying farther forward. To determine the proprio-spinal fibres descending from the third and fourth thoracic segments, the first step is to transect the cord between the second and third thoracic segments. There then ensues throughout the length of the cord behind that transection degeneration of all the fibres that enter it from the brain, mid-brain, bulb, and cer- vical and first two thoracic segments. This heavy degeneration, after developing, reaches a maximum and gradually passes away, all the debris of the degenerated nerve-fibres being in time removed. For this a period of a year suffices in a dog. The spinal cord is then ripe for determination of the proprio-spinal