Book - The brain of the tiger salamander 7
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Herrick CJ. The Brain of the Tiger Salamander (1948) The University Of Chicago Press, Chicago, Illinois.
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Part I. General Description and Interpretation 1. Salamander Brains | 2. Form and Brain Subdivisions | 3. Histological Structure | 4. Regional Analysis | 5. Functional Analysis, Central and Peripheral | 6. Physiological Interpretations | VII. The Origin and Significance of Cerebral Cortex | VIII. General Principles of Morphogenesis Part 2. Survey of Internal Structure 9. Spinal Cord and Bulbo-spinal Junction | 10. Cranial Nerves | 11. Medulla Oblongata | 12. Cerebellum | 13. Isthmus | 14. Interpeduncular Nucleus | 15. Midbrain | 16. Optic and Visual-motor Systems | 17. Diencephalon | 18. Habenula and Connections | 19. Cerebral Hemispheres | 20. Systems of Fibers | 21. Commissures | Bibliography | Illustrations | salamander
Chapter VII The Origin and Significance of Cerebral Cortex
THE human brain is the most complicated piece of mechanism that we know, and the products deHvered by this thinking machine are, for us, the most interesting. Detailed descriptions of it and some of its operations have been written, but where and how it fabricates its unique wares is still the basic problem of science and philosophy. Thinking is a part of our living, and apparently we think all over, just as we live in all parts of our bodies. Yet it is evident that some parts of us play crucial roles in our mental life, just as other parts do in our movements, our digestion, and so on. That the cerebral cortex as a whole is a specific organ of much of our mental life is as well established empirically as anything in biology, but how thinking is done and where the critical processes are carried on are still mysterious.
Study of origins and early stages of embryologic and phyletic development has resolved many biological and psychological problems, but essential features of the inception of cerebral cortex remain obscure. Interest in this theme instigated my program of research upon the amphibian nervous system. All reptiles possess well-organized cortex, that is, superficial laminae of gray substance in the pallial part of the cerebral hemisphere, simple in pattern but obviously comparable with, and ancestral to, the human cortical complex. They also exhibit enormous enlargement of some subcortical parts of the hemisphere, notably the strio-amygdaloid complex. In birds these subcortical areas are still further enlarged and complicated, with reduction in the amount and specialization of the cortical tissue. In mammals the subcortical parts of the hemisphere are relatively smaller, some of their functions apparently having been taken over by the progressively expanding cortex ('21, p. 452; '26, p. 122). Correlation of these structural peculiarities with the characteristic modes of life of these several classes of animals gives some clues to the significance of the cortex in the vital economy.
As already pointed out, structural differentiation of cortex is incipient in the hippocampal sector of the pallium in all Amphibia; more clearly defined primordia of cortex are seen in adult lungfishes and in embryonic stages of some other fishes (Rudebeck, '45) ; but well-differentiated cortex of typical structure first appears in reptiles. The problem set is : What morphogenic agencies were operative during the emergence of cortex from a noncorticated matrix?
Early in the attack upon this problem it became evident that the key factors were to be sought, not in the pallial field, but in its environs. What comes into this field and what goes out of it at successive stages of morphogenesis and how are these factors related one to another in both subpallial and pallial territory.^ This requires in the upshot a histological analysis of the entire nervous system directed toward the physiological interpretation of all visible structure. In my Brains of Rats and Men ('26) the available evidence regarding the origin of cerebral cortex was surveyed. Since that time additional evidence has been recorded, and in the present work the results of a renewed examination are summarized. The problems centering in corticogenesis have not been solved, but some progress has been made. The conclusions reached can, at best, be only tentative, pending physiological control; and for such experiments exact information about the anatomical arrangements of parts is indispensable.
MORPHOGENESIS OF THE CEREBRAL HEMISPHERES
There is reason to believe that in the early ancestors of vertebrates the central nervous system was a simple tubular structure comparable with that of living Amphioxus. Accompanying enlargement of the dominant sense organs — nose and eye — the anterior part of this tube was expanded in four places, which became cerebral hemispheres, hypothalamus, epithalamus, and tectum opticum. In most lower vertebrates the olfactory system is very large and has played a dominant role in the earlier stages of the morphogenesis of the hemispheres. In fishes this differentiation took a wide variety of forms, some of which were surveyed in two papers ('21, '22a). These diverse forms and patterns of internal structure were shaped in adaptation to various modes of life which employed different equipment of sensory and motor organs.
It has been mentioned that the more sluggish fishes, and especially mudfishes living in stagnant water, have enormously enlarged and highly vascular chorioid plexuses, the ventricles are dilated, and the walls of the brain are thin. This insures a supply of oxygen to the brain which is adequate for their quiescent existence. The more active fishes living in well-aerated water lack these features and cannot survive in stagnant water. Their brains have solid masses of tissue in great variety of forms and are sensitive to asphyxiation.
The fossil record shows that amphibians were derived from generalized fishes similar to the living lungfishes. These are mudfishes with enlarged chorioid plexuses and thin-walled widely evaginated hemispheres. There is geological evidence that in early Devonian time, when the amphibians emerged from the water, there was general continental desiccation. The lakes and streams were drying up, and over extensive areas the freshwater fishes were faced with the alternative of adaptation to drought or extinction. The more highly specialized species perished, but some generalized and sluggish types of mudfishes made successful adjustment. Their extensive chorioid plexuses and widely expanded thin-walled hemispheres had survival value, for so they were tided over the critical period of oxygen deficiency during phyletic metamorphosis. These characteristics persist today in all urodeles, most of which have retained the ancestral mode of life.
In later evolutionary stages the expanded hemispheric vesicles had the further advantage that space is available for further differentiation, and especially for spreading out the correlation tissue in thin sheets, an arrangement which seems to be requisite for refinement of adjustment to the spatial relations of things and for high development of labile, individually modifiable behavior as contrasted with stable, heritable behavior of instinctive type. The interested reader will find further details about the origin and significance of the evaginated form of cerebral hemispheres in the two papers cited ('21, '22a) and in chapter xvi of my Neurological Foundations ('24c).
From the beginnings of differentiation of the evaginated hemispheres, their medial and lateral walls have shown striking and interesting differences. The telencephalic connections are variously arranged in the different groups of fishes; but in the Amphibia the cerebral hemispheres have acquired the definitive form with connections that are not fundamentally changed in the higher groups. There is no evidence that this arrangement is due to differences in the quality of the olfactory impulses transmitted from the olfactory
94 THE BRAIN OF THE TIGER Sx\LAMANDER
bulb, except for the possibility suggested (p. 54; '21a) that specific impulses pass from the vomeronasal organ to the accessory bulb and amygdala. The nervus terminalis is more evidently specific, but of its functions nothing is known. All other descending olfactory impulses seem to be physiologically homogeneous. From this it follows that local differentiations in the hemispheres are due mainly to differences in the distribution of the various systems of ascending nonolfactory fibers or to differences in the destination of descending fibers arising from various parts. Evidently both factors are involved.
The connections between the hemispheres and the lower levels are assembled in the basal forebrain bundles and the stria medullaris thalami. The former are roughly comparable with the subcortical components of the mammalian extrapyramidal systems plus large numbers of ascending fibers, and the details of their connections are given in chapter xx. The analysis of these systems of fibers provides the key to the interpretation of the hemispheres of Amblystoma; and similar analysis in reptiles, birds, and mammals is essential for an understanding of the history of cortical evolution.
The fibers of the stria medullaris system are efferent or commissural, passing from all parts of the hemisphere to the habenula or decussating in the habenular commissure and returning to the hemisphere. The arrangement of the components of the stria is shown in figure 20, and this is essentially similar to that of mammals. The stria medullaris, in fact, is remarkably similar in all vertebrates; and these fibers evidently belong to a different category from those of the basal bundles, which contain ascending and descending fibers in arrangements that vaiy widely from species to species as we pass from lower to higher vertebrates. These variations seem to be especially significant for interpretation of morphogenesis. In this section, accordingly, attention will be directed to the latter systems, and the reader is referred to chapters xiv and xviii for the interesting details of the habenular connections.
The basal bundles comprise three groups of fascicles, the descending components of which are shown diagrammatically in figure 6: (1) dorsally and laterally the lateral forebrain bundles (f.lat.t.) ; (2) ventrally and medially the medial bundles (f.med.t.) ; (3) the olfactopeduncular tract (tr.ol.ped.), lying between the two preceding and with connections which are intermediate between them at both ends. Fibers ascend in these bundles from two sources: (1) from the somatic sensory field of the dorsal thalamus, by way of the thalamo
THE ORIGIN AND SIGNIFICANCE OF CEREBRAL CORTEX 95
frontal tract (figs. 19, 111, tr.ih.f.) in the lateral forehrain bundle, and (2) from the visceral field of the hypothalamus, by way of the medial bundle (fig. 113). The first of these bundles connects with the lateral wall of the hemisphere, the second with the medial wall. In conformity with this, the descending path from the lateral wall goes by way of the lateral forebrain bundle to the somatic motor field in the peduncle, and the path from the medial wall goes by way of the medial bundle to the visceral field in the hypothalamus (figs. 6, 11, 111, 112, 113). These connections inaugurated the different types of differentiation seen in lateral and medial walls of the hemisphere, a difference in type which becomes more pronounced in higher animals. The amygdala is of intermediate type, with somatic and olfacto-visceral connections of both afferent and efferent fibers (fig. 19). . _
All parts of the hemisphere are under olfactory influence, with olfacto-visceral correlations effected medially and olfacto-somatic laterally. The motor responses are radically different, and this difference is probably the basic determining factor in shaping the structural plan, not only of the olfactory connections, but of the organization of the hemisphere as a whole.
The hypothalamus is disproportionately large in lower vertebrates as compared with higher, and the olfacto-visceral functions of the hemisphere are correspondingly magnified. This doubtless accounts for the fact that differentiation in the pallial field is further advanced on the medial (hippocampal) side than elsewhere (fig. 99) and also for the fact that efferent projection fibers from this part of the pallium (fornix system, p. 254) appear in large numbers very early in phylogeny.
Fibers ascend from the dorsal thalamus to the hemisphere in fishes and in all higher animals. In Amblystoma these thalamo-frontal fibers arise in the generalized nucleus sensitivus, ascend in the lateral forebrain bundle, and end in the amygdala and middle part of the corpus striatum (figs. 19, 111, tr.th.f.). They are comparable with thalamo-striatal fibers of mammals and are precursors of mammalian sensory projection fibers, though in urodeles none have been seen to reach the pallial part of the hemisphere. This tract is small, and there is no evidence that different sensory systems are separately localized within it; its terminal nucleus, the corpus striatum, is correspondingly small and simply organized. The thalamo-frontal system is larger in reptiles and birds, where the striatal complex is magnified; but only in mammals are the several functional systems well segregated and separately localized, and here this localization is correlated with the differentiation of the sensory projection areas of the neopallium and the related nuclei of the dorsal thalamus. The course of the evolutionary differentiation of the cerebral hemisphere has been determined, in its main features, by the penetration of these nonolfactory fibers into its medial and lateral walls and the elaboration of related centers for the reception and correlation of these sensory impulses and appropriate motor discharge.
The entire ventrolateral wall of the hemisphere of Amblystoma is an olfacto-striatum. Its anterior end is under strong olfactory influence and is regarded as the primordium of the head of the caudate nucleus (figs. 98, 99). Posteriorly, the large amygdala (fig. 97) also receives many olfactory fibers. The middle sector receives fewer olfactory fibers and is a terminal station of the thalamo-frontal tract. From it fibers descend to the ventral thalamus and peduncle. It is, accordingly, regarded as paleostriatum, or somatic striatum, primordium of the mammalian lentiform nucleus.
The striatal gray of the middle sector is obscurely divided into dorsal and ventral nuclei, separated by a shallow sulcus striaticus (fig. 99, s.st.). Small cells of putamen type and larger cells of globus pallidus type are mingled in both nuclei, so that these structures are not separated as in mammals; yet their connections, as described in chapter xx, suggest that the ventral nucleus is the precursor of the globus pallidus. Both these nuclei receive fibers from the overlying piriform area, some of which descend into the lateral forebrain bundle (figs. 6, 111). The ventral nucleus is continuous with and intimately connected with the primordial caudate ('27, p. 298), and its efferent fibers go chiefly to the cerebral peduncle. The dorsal nucleus receives thalamo-frontal fibers and is in intimate relation with the amygdala and the piriform area. Its descending fibers have wide distribution to the tectum, thalamus, dorsal part of the peduncle, and dorsal, isthmic, and bulbar tegmentum as far back as the V nerve roots (fig. QJ.lat.t.d.). In Necturus (fig. HI; '336, p. 197; '33e) there is a complicated system of associational connections between the striatum and the piriform area; these are present also in Amblystoma, but the details have not been described.
Most of the white substance of the striatal field is occupied by a very dense and sharply circumscribed intermediate neuropil of peculiar texture (p. 53 and figs. 98, 99, 108, 109, 113; '27, p. 300; '42,
THE ORIGIN AND SIGNIFICANCE OF CEREBRAL CORTEX 97
p. 'iO'^Z; Necturiis, '336, p. 149). There is a web of interlaced branches of ependymal elements and among these a still more densely woven tangle of dendrites and slender, contorted, unmyelinated axons. The thicker descending axons of the dorsal and ventral fascicles of the lateral forebrain bundle are assembled within this neuropil (figs. Ill, 113). I have seen similar texture in Golgi impregnations of the head of the caudate in the opossum ('24c?, p. 342), a structure adapted for diffusion and summation of all nervous impulses entering it.
The urodele type of striatal structure could be transformed into that of mammals by reduction of the olfactory component; further differentiation of the caudate nucleus and amygdala; segregation of the large efferent neurons in the ventral nucleus, which becomes the globus pallidus; and segregation of the smaller elements in the putamen. In Ambly stoma these changes are only dimly foreshadowed. The ventral fascicles of the lateral forebrain bundle connect with the primary motor field of the ventral thalamus and peduncle and are comparable with those of the ansa lenticularis. The connections of the dorsal nucleus suggest relations with the reptilian neostriatum and the mammalian putamen. Here are probably to be found the earliest indications of those formative agencies which in later phyletic stages led to the differentiation of neopallium. In the still more primitive hemisphere of Necturus, these indications were recognized and discussed ('33e).
The strio-amygdaloid complex as a whole is the highest center of dominance in the control of the skeletal musculature, a role which is enormously enlarged in reptiles and birds. In mammals, parallel with the elaboration of cortex, the part which the striatum plays in the patterning of behavior is progressively reduced, but it retains important functions of co-ordinating and stabilizing motor performance. Just as the cerebellum is added to the sensori-motor systems for facilitation of muscular co-ordination, so in mammals the striatal complex is interpolated in the efferent cortical systems as an accessory facilitating mechanism. ^
In the Amphibia we find a critical stage in the morphogenesis of the cerebral hemisphere. The definitive major subdivisions are here blocked out in recognizable form, and the pallial part is incompletely segregated from the stem part ; yet the most distinctive feature of the pallium — its superficial cortex — has not yet appeared. We want to know more about the agencies which are in operation here to initiate the separation of pallium from stem and what further changes led to the migration of the palHal gray from deep to superficial position and its subsequent compHcations. A beginning has been made, and I have at various times reported progress in this analysis and some discussion of its meaning ('24c, chaps, xv, xvi; 'Md, p. 354; '26; '27, p. 315; '33a; '336; '33e; '34a). Yet much remains to be done before we can fill in those finer details of structure which the physiologist needs to know in order to plan crucial experiments. Frogs are probably better adapted for such experiments than are salamanders, and to this end a more detailed analysis of the histological structure and connections of the forebrain of the frog is urgently needed. Sufl5cient knowledge of this structure is now available to enable the physiologist to explore the instrumentation of some components of the behavior pattern, as illustrated by a recent study by Aronson and Noble ('45).
More than thirty years ago I published some reflections under the title given to this chapter ('13a). Though parts of that paper require revision in the light of subsequent research, yet it sketches the background of the present discussion. Attention was called to Dewey's ('93) concept of the organic circuit as a substitute for the classical formulation of the reflex arc, as mentioned in the preceding chapter. Some illustrations of these organic circuits were given in my article. Here we need only to emphasize the fact that all behavior is the resultant of their interplay, for which provision is made in the cerebral mechanisms, such as are described in this and other works devoted to neuroanatomy. These are all circular reactions between receptor and effector organs or the related internal adjustors. In the course of phylogeny, cerebral cortex has been differentiated as the culminating member of a series of progressively more complicated integrating mechanisms adapted to make more efficient use of the preformed circuits of the brain stem in the interest of more flexible behavior in terms of individually acquired experience, as contrasted with the stereotyped patterns of the stem (for a convenient summary of the human connections see Papez, '44).
In this connection two sentences may be quoted from von Bonin ('45, p. 52) : "It is of the essence of cortical organizations that sensory and motor areas become divorced more and more from each other — are pulled farther apart as it were — as evolution proceeds As we ascend the evolutionary scale, the cortex assumes
THE ORIGIN AND SIGNIFICANCE OF CEREBRAL CORTEX 99
increasingly a structure which may be interpreted as leading to increased degrees of indeterminacy."
A fundamental feature of cortical functions is that they are delayed reactions (p. 78; '!24r, p. 271); there is, first, the arrest or inhibition of some lower and more primitive patterns of behavior of reflex or instinctive type. This allows time for cortical reorganization of the component factors of the situation, conditioning of reflexes, or other modifications of the stereotyped patterns of response. The cortex, accordingly, is lifted up away from the lines of through traflic in the brain stem, and the dorsal convexity of the evaginated cerebral hemisphere is conveniently located, with ample space for indefinite enlargement.
During the phylogenetic development of cortex, ascending and descending pallial projection fibers are added to the pre-existing systems of the underlying stem. They do not entirely supplant them, for even in mammals, where cortical projection systems are highly developed, the subpallial parts of the hemisphere retain their own diencephalic connections.
Primitively, as in cyclostomes, the entire cerebral hemisphere is little more than an olfactory bulb and a secondary olfactory nucleus. In Amblystoma the hemispheric evagination is more extensive, and there is a large increment of ascending nonolfactory fibers; yet here the pallial part of the hemisphere receives the largest olfactory tracts, and all of it is essentially an olfactory nucleus.
The olfactory reflexes seem to be adequately provided for in the stem portion of the hemisphere. I have suggested ('33) that here, and especially in the corticated mammals, the olfactory sense, lacking any localizing function of its own, co-operates with other senses in various ways, including a qualitative analysis of odors (desirable and noxious) and also the activation or sensitizing of the nervous system as a whole and of certain appropriately attuned sensori-motor systems in particular, with resulting lowered threshold of excitation for all stimuli and differential reinforcement or inhibition of specific types of response. The olfactory cortex (and its predecessors in lower vertebrates) may, then, serve for nonspecific facilitation of other activities, in addition to its own specific olfactory functions. This facilitation may involve both general excitatory action and general inhibition. That the latter is present is indicated by the observation of Liggett ('28) that anosmic rats are more active than the normal controls. The organization of the olfactory system as a whole in all animals seems consonant with this interpretation; and in Aronson and Noble's study of the sexual behavior of frogs this facilitating action of the olfactory field is clearly demonstrated.
In primitive vertebrates the dominance of the entire anterior end of the brain by the olfactory apparatus implies more physiological homogeneity than in higher brains, where this tissue is invaded by larger numbers of nonolfactory fibers with more diverse specificities. The case is somewhat like the invasion of a hitherto isolated continent with homogeneous and primitive population by immigrants of numerous other races with very diverse cultural standards. When European peoples colonized North America, in some regions the newcomers intermarried with the natives and the two races amalgamated; in other places the indigenous population was driven farther and farther back or exterminated altogether. Something analogous to these processes has taken place during the invasion of the olfactory area by nonolfactory functional systems. In some regions there is blending of the old and the new, as in the amygdala, septum, and olfactory tubercle; in other places the indigenous olfactory system has more nearly retained its unmixed character, as along the margin of the olfactory bulb; and in other extensive regions of the hemisphere the indigenous elements have been almost entirely displaced by nonolfactory systems, as in part of the corpus striatum and the neopallial cortex. In the Amphibia this invasion of the olfactory field by nonolfactory systems is extensive, but the invading forces are not sufficiently diversified and localized to invoke the differentiation of cortical tissue in the pallial part of the hemisphere. This is probably correlated with the fact that amphibian behavior, by and large, is mass movement, with relatively little refined analysis into partial patterns.
The primitive differentiated cortex of reptiles has three welldefined sectors. These are spread, respectively, on the dorsomedial, dorsolateral, and dorsal convexities of the hemisphere. The first is archipallium, the precursor of the mammalian hippocampal formation. The second is paleopallium, or piriform cortex, represented in man by a relatively small area at the lower border of the temporal lobe and including the uncus and some adjoining areas. The third sector, the dorsal cortex, is of uncertain relationships. It occupies the position of the neopallium, which comprises the larger part of the
THE ORIGIN AND SIGNIFICANCE OF CEREBRAL CORTEX 101
human cortex, and probably is its precursor, though this apparently is not its only relationship.
In all amphibian brains these sectors of the pallial field can be identified, though no superficial cortical gray is present in any of them, as illustrated in figures 96-99. On the lateral aspect thepiriform area (figs. 85, 86, 111, p.pir.) shows no evidence of cortical differentiation; it is, in fact, the chief secondary olfactory nucleus (nuc.ol.d.L); nevertheless, its location and connections identify it unmistakably as the primordium of the piriform cortex of reptiles and lower mammals. Its neurons are small, simple, and similar to those most commonly seen in the brain stem (figs. 98, 99, 105). On the dorsal convexity there is an undifferentiated and poorly defined field (p.p.d.), which is the precursor of the reptilian dorsal cortex.
The medial sector — primordium hippocampi (p.hip.) — shows a first step toward cortical differentiation, for here the compact central gray layer is dispersed by outward migration of the cells throughout the thickened wall, and these are imbedded in dense neuropil. These neurons vary from small to quite large and, in general form, resemble those of other parts of the pallium, though they are evidently more specialized (figs. 97, 98, 99, 105). One to several thick and thorny dendrites arise from the cell body and spread widely, some reaching the external limiting membrane. The axon may arise from the cell body, but usually from the base of one of the dendrites, It may divide, sending one branch into the dorsal pallium and one to the septal nuclei or medial forebrain bundle (fornix). Some axons are short, branching freely within the area of spread of the dendrites (fig. 105; '396, fig. 44), but most of them send one or more long fibers from this arborization into tracts which leave this field. Close to the surface are a few tangential neurons which at one time I regarded as precursors of the reptilian cortical cells. Similar cells are found also throughout the brain stem, and in the. pallium (fig. 98) their axons take short courses as correlation fibers. They are more numerous in the frog (P. Ramon y Cajal, '22, figs. 6, 7). The differentiation of the hippocampal cells is further advanced in Amblystoma than in Necturus ('33a, p. 183) and less so than in anurans. The hippocampal neuropil increases in density and complexity as we pass from Necturus to Amblystoma and the frog.
The four layers of neuropil characteristic of the brain stem (p. 30) are very unequally developed in the amphibian hemisphere (Necturus, '336, p. 176). The periventricular neuropil is everywhere abundant. The deep neuropil of the alba contains an elaborate system of association fibers, which has been described in detail (figs. Ill, 113; '336, p. 194; '33e). The intermediate neuropil contains many of the recognizable long tracts, and in the striate area it is elaborately developed, as already described. Superficially of the striate neuropil is a strio-amygdaloid neuropil, which is continuous dorsally with the piriform and dorsal neuropil. This sheet as a whole is evidently the synaptic field of the pallial associations. It receives the dendrites of the underlying gray substance but contains no cell bodies. In higher animals this synaptic zone seems to exert a neurobiotactic influence, so that in embryonic stages all the neurons of the pallial field migrate outward and are incorporated within it, thus producing the laminate cortex.
In the amphibian primordium hippocampi, this movement has begun but is not consummated. The deep gray layer has been broken up, and its elements are dispersed. The periventricular neuropil of the grisea and the neuropil of the alba merge, so that the entire area is pervaded by a dense entanglement of dendrites and axons, within the meshes of which the cell bodies are imbedded. This neuropil is denser in two places — rostrally and ventrally, where subpallial connections predominate, and dorsally, where pallial associations predominate. In the reptiles, with differentiated cortex, the corresponding two parts of the hippocampal cortex are structurally different.
In Necturus the most rostral fascicles of the strio-pallial association go far forward and dorsally above the posterior end of the olfactory bulb to reach the dorsolateral sector of the anterior olfactory nucleus and territory adjacent to it (fig. 111). This is clearly a secondary olfactory nucleus of subpallial type, adjacent to the olfactory bulb and traversed by the great dorsolateral olfactory tract, from which it receives numberless terminals and collaterals. Its principal discharge is. backward into the primordium pirif orme, a pallial area (fig. Ill, tr.ol.pal.L). These connections would, perhaps, have no special significance in themselves, but comparison with reptiles shows that there the corresponding region exhibits remarkable peculiarities. In urodeles the area in question is one of the least differentiated parts of the hemisphere, except for the strong fascicles of the strio-pallial association, and perhaps this lack of specialization favors the role which it seems to play as germinative tissue for neopallial cortex.
Cortex of simple pattern is present in turtles in each of the three
THE ORIGIN AND SIGNIFICANCE OF CEREBRAL CORTEX 103
pallial fields seen in Amphibia; and the dorsal and lateral cortex (general cortex and piriform cortex) are related to a massive subcortical thickening of the lateral wall of the hemisphere, which was called the "dorsal ventricular ridge" by Johnston and "hypopallium" by Elliot Smith. The thalamic radiation, comparable with the amphibian tractus thalamo-frontalis, is large in turtles. It ends chiefly in the rostral part of the hypopallium, but some of these fibers pass through without synapse into the dorsal or general cortex. The latter fibers are true thalamic sensory projection fibers with connections of neopallial type. In front of this region there is a "pallial thickening," from which motor cortical projection fibers go out to the cerebral peduncle — again a neopallial type of connection — and this part of the cortex is electrically excitable (Johnston, '16).
In the alligator the topographic relations are very different. The dorsal, or general, cortex has no contact with the hypopallium except at its rostral end in the region of the pallial thickening of turtles, which Crosby ('17, pp. 358, 381, figs. 5, 6) calls "primordial general cortex." This primordium she regards as the germinal tissue or focal point in the differentiation of the general cortex, and she gives a clear statement of the factors which probably were operative in the differentiation of this general cortex.
The dorsolateral sector of the anterior olfactory nucleus of Necturus, together with some adjoining tissue, is just such an area of basal, i.e., subpallial, type as Crosby postulated; it is in the exact position with reference to other parts of the hemisphere as her primordial general cortex; and it receives especially strong fascicles of the strio-pallial association, which turn far forward to reach it. It is significant that in the alligator this primordium is the only region where both projection fibers of the lateral forebrain bundle and shorter fibers from the hypopallium and corpus striatum can connect with the general cortex (Crosby's figs. 5-9, 12-19, 37). Bagley and Langworthy ('26) have shown that in the alligator this area and parts of the cortex adjoining are electrically excitable, thus furnishing experimental proof that true motor projection fibers of neopallial type arise from it. The underlying hypopallium was tested and found to be unexcitable. Ariens Kappers ('29, p. 140) accepts Crosby's interpretation of the reptilian primordial neopallium and states that in the lizard, Varanus, a small number of thalamic projection fibers ascend directly to this area. This, he says, is the source of the neopallium of mammals, not the more differentiated general cortex of the dorsal convexity of the hemisphere.
The dorsolateral sector of the anterior olfactory nucleus and the rostral end of the primordial piriform area of Necturus may, accordingly, be regarded as critical points in further search for the earliest primordium of the neopallium. This region is related with the primordial general cortex of reptiles, which may be regarded as the precursor of the subiculum and other transitional fields rather than of neopallium, sen.su stricto. The preceding account of the probable history of cortical evolution is drawn largely from Crosby's graphic and discerning analysis published in 1917.
The structure of the pallial field of Amblystoma and its connections were described in 1927 and subsequently in greater detail in several papers devoted to Necturus ('336, '336?, '34, '34a). In these papers and some earlier publications I commented on the fact that the first well-differentiated cortex appears in reptiles in three clearly defined areas; and the opinion was expressed that a prerequisite for this differentiation is the penetration into the pallial field of thalamic projection fibers in separately localized tracts with different physiological properties. This minimal localization of function in the projection systems goes hand in hand with local differentiation in the pallium and amplification of the cortical associational connections of these areas. This process of local cortical differentiation continues to advance in complexity of pattern in proportion as the systems of thalamic projection fibers are amplified and diversified.
This principle of cortical morphogenesis receives its first and clearest exemplification in the obvious difference in the subpallial connections of the medial and lateral parts of the pallial field, hypothalamic connections predominating medially and thalamic connections laterally. In Ichthyopsida the hypothalamic influence is much stronger than the thalamic, a relation which is strikingly reversed in higher vertebrates. These diencephalic influences are not sufficient to cause cortical differentiation in the amphibian pallium, though there are some local differences in the three recognizable pallial areas and Soderberg ('22) found clearer evidence of cortical incipience in some early larval stages. Holmgren ('22) found evidence of cortical differentiation in developmental stages of selachians and some other fishes, and in adult lungfishes a primitive cortex is clearly delaminated externally of the central gray (Rudebeck, '45).
THE ORIGIN AND SIGNIFICANCE OF CEREBRAL CORTEX 10.3
In none of the fishes and amphibians do we find so well-differentiated cortex as in reptiles. Why is this? The answer seems to be that in all Ichthyopsida the entire forebrain is dominated by the olfactory system to such an extent as to retain a measure of physiological homogeneity, which is not favorable for cortical differentiation. The basic feature of cortical function is the association of diverse components of the action system with separate localization of the functional systems involved. In fishes and amphibians this localization of function in the forebrain is incipient, but it is not sufficiently advanced to evoke cortex of definitive type. In reptiles, on the other hand, the great increase in the system of somatic sensory exteroceptive thalamic radiations is correlated with enlargement of the corpus striatum complex, including an extensive area quite free from olfactory and hypothalamic connections and the extension of some of the fibers of the thalamic radiation to the dorsal pallial field without interruption in the striatum. Thus the pallial field is subdivided into three well-circumscribed areas, each with a physiological specificity different from those of the others and one of which is emancipated from dominance of the olfactory system. Now for the first time in phylogenetic history the pallium possesses an intracortical system of association fibers adapted for the specific cortical type of function ('26, pp. 78, 123; '27, pp. 315 ff.; '33e; '34a).
In a survey of the history of cortical evolution the birds occupy an anomalous position. They are much more highly differentiated than reptiles, but in an aberrant direction, with no mammalian affinities. In most of them the olfactory system is reduced almost to the vanishing-point, and the optic system is greatly enlarged. There is extensive local differentiation of thalamic nuclei, but not in the mammalian pattern. The system of ascending thalamic pi-ojection fibers is larger than in reptiles, and most of these fibers end in the enormously enlarged and complicated corpus striatum. Correlated with the latter point is the striking fact that, despite the great increase in thalamic projection fibers, the cortex of many birds is scarcely more extensive than in reptiles and in some species is less well differentiated (Craigie, '40) . Birds are more highly specialized in both structure and behavior than are the lower mammals, and yet their cerebral cortex is rudimentary in comparison with even the most primitive mammals. The explanation for this is that the bird's more diversified behavior is largely stereotyped in instinctive patterns, adequately served by subcortical apparatus, while the patterns of mammalian behavior,
106 THE BRAIN OF THE TIGER SALAMi\NDER
even in the lowest members of the class, are in larger measure individually learned. And enhancement of learning ability goes hand in hand with cortical differentiation.
It is impossible to define a primordial boundary between pallial and subpallial territory ('27, p. 316; '33a). There is apparently no primitive (palingenetic) distinction between the pars pallialis and the pars subpallialis of the cerebral hemisphere; cortical types of structure and function may be differentiated out of such raw materials as are available, and the locations of these indefinite boundaries will vary from species to species. Even in the human brain the boundary is in some places obscure and controversial.
This, in outline, seems to be the history of the origin and evolution of the cerebral cortex. The details have not yet been filled in, and this can be done only by experimental methods, checked and controlled at every step by accurate histological analysis of the tissue operated upon. When the facts about the sequences of the evolution of cortical structure and function are colligated with experimental studies of behavioral capacities of the animals in question, we shall have a secure foundation upon which to build a sound comparative psychology, and this, in turn, will clarify much that is now obscure in human experience.
PHYSIOLOGY AND PSYCHOLOGY
Returning, now, to a general survey of the factors involved in the differentiation and normal operation of the central nervous system, we find that these fall into two categories. Some of them conform perfectly with well-known laws of traditional mechanics of the inorganic realm, as formulated in the Newtonian system and its modern derivatives. Others have not been successfully fitted into this frame of reference. From the beginning of inquiry into this problem, there has been a tendency to set these refractory components apart from the natural order in some mystic realm of vitalism. To the naturalist this solution is not acceptable, for the two classes of phenomena are empirically indissociable.
That the operations of nature are not bound by the man-made rules of Newtonian mechanics is now evident. It has been shown that the formulas of Newtonian mechanics, Euclidean geometry, and Aristotelian logic are not universals. They are valid in a restricted field but not in the realm opened up by current conceptions of relativity and quantum mechanics. In view of this situation, the field of neurological inquiry is immeasurably enlarged and complicated.
THE ORIGIN AND SIGNIFICANCE OF CEREBRAL CORTEX 107
In our search for the laws of growth and normal action of the nervous S3^stem, we naturally and properly look, first, for those features which can be fitted into the conventional formulations of inorganic mechanics. Up to the present time the science of neurology has been concerned almost exclusively with this aspect of the problem, with eminently successful results. Mechanical stress and tension, pressure and movements of fluids, local chemical action, surface tensions and permeabilities, electrical phenomena of many kinds — these and other physical factors now under investigation are bringing to light many basic principles of nervous action. In a wider field D'Arcy Thompson's great work. On Growth and Form ('44), does not trespass beyond these boundaries, for he says (p. 15) : "When we use physics to interpret and elucidate our biology, it is the old-fashioned empirical physics which we endeavour, and are aloije able, to apply." A useful general summary of Medical Physics, edited by Otto Glasser ('44), has recently been published. But this line of attack sooner or later reaches limits beyond which it has not yet been possible to go.
In human neurology the major problem of all times has been the relation of these physicochemical processes to the conscious experience which emerges from them. The normal subjective life is not disorderly, but the laws of this order as revealed by introspective psychology seem to be incommensurable and disparate with those of the underlying physicochemical system as known objectively. This gap has not been bridged by any acceptable formulation in terms of Newtonian mechanics, and more and more of the experts in this field are coming to believe that this cannot be done. This does not imply any appeal to mysticism. Quantum mechanics takes its place in the order of nature along with Newtonian mechanics, and it may well be that the solipsistic qualities of that "private" conscious experience which is not objectified are related to the events of the objectively known "public" physicochemical world in accordance with principles as different from those of Newtonian mechanics as the latter are from quantum mechanics. If so, these principles of the mind-body relationships have not yet been formulated, and we live in hope that some day this will be done. Just as quantum mechanics has added a time dimension to the three Cartesian co-ordinates of space and additional dimensions beyond our range of experience in theoretic mathematical physics, so it may well be that introspective experience and objective or extraspective experience are related in terms of dimensions not yet recognized and given scientific expression, defining a dimension as "any manifold which can be ordered," as Reiser ('46, p. 89) does in an interesting discussion of this problem.
The theories of mind-body relationships are mentioned here because I regard mentation as a vital process as truly as are muscular contraction and glandular secretion. The laws of operation of these three processes are different, their products are different, and the apparatus employed is different. All these operations have locus in place and time. The organs which perform them have been slowly differentiated and matured during embryonic and phyletic history. We have reason to believe that mind is not an exclusive prerogative of mankind. Mental capacity has developed parallel with the growth of its organs. The genetic and phylogenetic approach to the mindbody problem has already yielded significant data; and, as this study is carried backward toward earlier stages (embryonic and phyletic), the unresolved problems of human psychophysics do not disappear. Something akin to the mental as we experience it may be a common property of all living things and even of the cosmos as a whole, as some suppose. Or it may be that, just as life emerged on our planet from the nonliving in some as yet undiscovered way, so mind appeared as an emergent at some unknown stage of organic evolution. If so, the naturalist must assume that the emergence in both cases occurred in lawfully ordered ways within the frame of the natural. In the present state of knowledge an open-minded skepticism on this question is the only safe attitude.
More intensive study of the properties of the nervous tissues seems to be the most promising approach to these unsolved problems. In the past, escape from mystery has too often been sought through verbalisms and mysticism. Rigid adherence to scientific method — accepting as evidence not wishful thinking but verifiable experience — will avoid this pitfall. Obviously, conventional methods of inquiry must be pushed to the limit of their availability, and in the meantime new formulations of problems must be sought with all the resourcefulness that scientific imagination can command, not neglecting the possibility that some of these formulations may lie outside the frame of current Newtonian and quantum mechanics.