|Mind, Brain and Adaptation in the Nineteenth Century: Cerebral Localization and Its Biological Context from Gall to Ferrier by Robert M Young|
FRITSCH AND HITZIG AND THE LOCALIZED ELECTRICAL EXCITABILITY OF THE CEREBRAL HEMISPHERES
All this has never yet been seen But Scientists who ought to know Assure us that it Must Be So: O, Let us never, never doubt What nobody is Sure About!
In 1870, Gustav Fritsch and Eduard Hitzig published a paper entitled 'On the Electrical Excitability of the Cerebrum', which demonstrated by experiment that
A part of the convexity of the hemisphere of the brain of the dog is motor . . . another part is not motor. The motor part, in general, is more in front, the non-motor part more behind. By electrical stimulation of the motor part, one obtains combined muscular contractions of the opposite side of the body.
This finding must be set apart from the foregoing analysis for two reasons. It stands apart, first, because of its significance. The work of Fritsch and Hitzig was a truly epoch-making classical experiment in the sense that all subsequent work in cerebral physiology was done with reference to this single publication. It dethroned a doctrine that had reigned for fifty years, and its appearance introduced order into the confused picture indicated above. The second reason is less obvious. It has to do with the context of the experiment and the psychological theory with which it is allied. Fritsch and Hitzig's psychological views neither arose from nor were they compatible with the sensory-motor associationist tradition which has been traced from Locke to Bain, Spencer, and Jackson. Their finding was one of the two direct stimuli for Ferrier's experiments, but their psychophysiology was part of the tradition which Jackson explicitly rejected. Consequently, the finding of Fritsch and Hitzig must be considered separately from its interpretation by them. This separation is relatively easy, since their comments
1 The original publication was Uber die elektrische Erregbarkeit des Grosshirns', and it appeared in Arch. f. Anat., Physiol. und wissenschaftl. Mediz., Leipzig, 37, 1870, 300-32. All quotations are taken from the translation in von Bonin, 1960, and page references refer to it.
2 Fritsch and Hitzig, 1870, p. 81.
on psychophysiology are incidental to their main thesis about the central places of muscular movement'.
Gustav Fritsch and Eduard Hitzig were two young German physicians. Their experiments were conducted on a dressing table in a small Berlin house, because the University had no space for such studies. Hitzig became a renowned psychiatrist with a reputation for 'incorrigible conceit and vanity complicated by Prussianism'. He continued to play a major role in the experimental work on localization in the ensuing decades and gave the 'Hughlings Jackson Lecture' in 1900. Fritsch was a man of independent means who spent much of his life travelling. His 1870 paper with Hitzig was his only important contribution to medicine.
Their report begins with a statement of the anomalous positions of the hemispheres with respect to the law of specific energies of the rest of the nervous system. 'Physiology ascribes to all nerves as a necessary condition the property of excitability, that is to say, the ability to answer by its specific energy all influences by which its properties are changed with a certain speed. While the artificial excitability of the brain stem and spinal cord had been hotly disputed, 'since the beginning of the century we were quite generally convinced that the hemispheres were completely inexcitable for all modes of excitation generally used in physiology'. They review the negative findings of Longet (1842), Magendie (1839), Matteucci (1843), and others, setting Flourens aside for fuller treatment. Their quotations from Weber and Schiff are instructive. Weber shows the confidence with which the dogma was held.
If one can conclude from the present standpoint of science that there are no motor fibers in a nervous part in which after excitation no contractions occur, one can say with the greatest certainty there is not one fiber in the hemisphere of the brain which goes to voluntary muscles. Not a single observer saw movements of such muscles after stimulation of the central parts.
Schiff is equally certain and extends the inexcitability from somatic muscular motion to the intestines, which also remain quiescent after excitation of the lobes of the brain. One can vicariously experience the
1 Haymaker, 1953, pp. 138-42.
2 von Bonin, 1960, p. xii.
3 Ibid. Cf. Grundfest, 1963.
4 Fritsch and Hitzig, 1870, p. 73. Helmholtz had measured the velocity of a nerve impulse in a motor nerve in 1850. See Boring, 1950, pp. 413, 47-9. Helmholtz's original report is translated and reprinted in Dennis, 1948, pp. 197-8. On specific energies of nerves, see Boring 1950, pp. 80-95. This topic deserves further study.
5 Fritsch and Hitzig, 1870. p. 73.
6 Ibid., p. 75.
inconoclastic excitement with which Fritsch and Hitzig conclude their review. 'Even in other fields than in physiology, there can hardly be a question about an opinion which seems so completely settled as that of the excitability of the cerebral hemisphere. It would be easy to give more citations in the same vein if there would be any point to it.'[l]
Flourens' findings were discussed in greater detail. There must be no question about the respect in which Fritsch and Hitzig held him. At the beginning of their review they say. 'This gifted and lucky observer by using as clean a method as possible came to results which deserve to be considered as a basis for all later experiments in this field. Flourens' ablations on birds and mammals had shown the 'signs of will and consciousness of sensations disappear, while nevertheless, by stimuli coming from the outside, quiet engine-like movements could be produced in all parts of the body'. He had quite naturally concluded that 'the cerebral hemispheres were not the seat of the immediate principle of muscular movements but only the seat of volition and sensation'.
Given Flourens' methods, Fritsch and Hitzig grant that these conclusions seemed satisfying. However, Flourens' further findings and the concepts associated with them were 'difficult to harmonize . . . with experience gained in other ways'. These further results had led Flourens to believe in cortical equipotentiality. If he ablated a hemisphere, the resulting blindness and occasional weakness on the opposite side were transient. Ablation of the grey matter of both cortices (apparently in a pigeon) was also followed by complete recovery. Progressive slicing away of the hemispheres led to 'a uniform gradual decrease of sensory perceptions and volition', which was regained within a few days, provided a sufficient amount of tissue was left intact. If the extirpations exceeded a certain limit all faculties disappeared and were not recovered. 'Flourens concluded that the cerebral lobes with their whole mass subserved their functions, and that there is no special seat either for the different faculties or for the different sensations.' Also, an intact remaining part of the hemispheres 'could relearn the complete use of all functions'.
The resulting view of 'the central places of muscular movement' was that there were muscular mechanisms in most parts of the brain stem and cord which could be excited reflexly from the periphery or centrally 'by way of volition or of the impulse of the soul'. The soul was believed
1 Fritsch and Hitzig, 1870, p. 75
2 Ibid., p. 76.
6 Ibid., pp. 76-7.
to have its seat in the grey matter of the hemispheres, 'without however, the parts of the psychic center being localizable on to parts of the organic center'. Unfortunately, the investigation of the probable seat or 'nearest tools' of the soul was closed, 'since the substrate will not answer with an overt reaction to any normal stimulus'.[l]
Fritsch and Hitzig thus raised three closely related issues: the excitability of the hemispheres, localization of functions, and the relation of the hemispheres to the immediate principle of muscular movements. Prior to their own experiments there had been equivocal results which bore on the traditional views on each of these points. In 1756, Haller and Zinn had seen convulsive movements after lesions of the white matter of the brain, but the limitation of the stimuli they used was not precise, and their findings were explained away as the likely result of pushing their instruments into the medulla oblongata. In 1867, Eckhard mentioned an unspecified source which noted movements of the anterior extremities on ablation of the anterior lobes. Neither of these results had any effect on the prevailing doctrines. Clinical findings had been discounted because of the notorious difficulties involved in interpreting post-mortem examinations. In any case, many congenital and acquired defects of parts of the brain involved no interference with cerebral functions. Nevertheless, it was such clinical findings which contributed to the gradual modification of the prevailing view. Bouillaud and Broca found aphasia 'caused by destruction of a small eccentric part of the brain', and cases had been reported in the literature of monoplegias of an arm or leg associated with postmortem findings of 'small defects of the cerebral hemispheres'. As early as 1834, Andral had expressed the frustration which these results engendered: in the present state of the science it is impossible to assign a distinct cerebral seat for limb movements, although the findings of monoplegias leave no doubt that such a seat exists.
Other clinical results came from cases involving the corpus striatum and thalamus. As long as there was no question of a role for the cortex in movements, these had been taken into account by physiologists. However, once Fritsch and Hitzig began to take seriously the possibility of involvement of the cortex, they became wary of reasoning on the basis of such cases, since the corpus striatum and thalamus contained conduction pathways from the hemispheres and therefore could not
1 Fritsch and Hitzig, 1870, pp. 77-8.
2 Ibid., pp. 73-4.
3 Ibid., p. 75.
4 Ibid., p. 78.
give certain evidence regarding 'the first locus where the lost movement began'.
Clinical findings in favour of both localization and cortical representation of movements were supported by morphological investigations, notably those of Meynert. He considered the cerebral cortex to be a 'focus of perceptions' and argued that it could be 'subdivided into many, more or less circumscribed parts, the importance of which for the various perceptions is due to the nerve fibers of its so-called projection system'. Fritsch and Hitzig refer to Meynert as one of the few neurologists prior to their report who had 'talked in favour of a strict localization of psychological faculties, although differently from Gall'. This is the only mention of Gall in their paper. However, it may help to see the significance of his concepts for their work if it is recalled that what Flourens, Bouillaud, and Broca said about localization is directly related to Gall, and that these figures provided the issues which Fritsch and Hitzig are addressing. Their conclusion is that 'Such facts show that the origin of at least some function of the soul is bound up with circumscribed parts of the brain'. It is against this background that they began their own work. 'In the meantime, by the results of our own investigations, the premises for many conclusions about the basic properties of the brain are changed not a little.
In a previous experiment Hitzig had elicited eye movements by conducting galvanic currents through the 'posterior part' and temporal region of the head of a man. He claimed that these were 'the first movements of voluntary muscles elicited by direct stimulation of the central organ in man'. The question arose whether the temporal stimulations involved spread of current to subcortical centres 'or whether
1 Fritsch and Hitzig, 1870, p. 78.
2 Ibid., p. 79.
3 Ibid., p. 92.
4 Ibid., p. 78.
5 Jacksons name is conspicuously absent from Fritsch and Hitzigs's otherwise thorough review of work leading up to their discovery. It is true that in his Hughlings Jackson Lecture in 1900, Hitzig claimed that he was the first to confirm by experiment and to define more closely what Jackson had concluded from clinical facts. However, I have seen no evidence that Jackson's ideas played any role in leading Fritsch and Hitzig to conduct their experiments. The relationship seems to be that they arrived at their views on the basis of the work listed in their paper. Their findings, along with Jackson's theories, inspired Ferrier to conduct his experiments. The discoveries of Fritsch and Hitzig, and of Ferrier were, in turn, taken up by Jackson as confirming his earlier views and as a sure basis for extending them. A false impression could be gained from the way Sir Francis Walshe quotes Hitzig's remark about confirming Jackson. (Walshe, 1961, p. 119)
6 Fritsch and Hitzig, 1870, p. 79.
7 Fritsch and Hitzig, 1870, p. 79. Walker reports that Fritsch is said to have 'observed, while dressing a head wound some years earlier, that mechanical irritation of the brain caused twitching of the contralateral limbs'. He gives no reference, and no mention is made of this in the 1870 article. (Walker, 1957, p. 106.)
the cerebral hemispheres in contrast to the general assumption were after all electrically excitable'. A preliminary experiment on a rabbit by Hitzig gave a positive result, and he and Fritsch undertook a large number of further experiments on dogs which gave 'results . . . uniform even to the smallest details'.
Their findings overthrew three theories that had stood since Flourens: they established cortical excitability, a role for the cortex in the mechanism of movements, and cerebral localization. 'The possibility to stimulate narrowly delimited groups of muscles is restricted to very small foci which we shall call centers.' Five centres were specified in constant loci (see Fig. i): for the muscles of the neck, the extensorsand adductors of the anterior leg, flexion and rotation of the same leg, the posterior leg, and the facial nerve. Using minimal intensity of stimulation, the areas between these centres were not excitable, though a greater intensity or separation of the electrodes led to generalized movements on both sides of the body, and tetanic stimulation led to after-movements which, in two cases, developed into generalized epileptic attacks.
1 Fritsch and Hitzig, 18070, P. 79.
2 Ibid., p. 81
Two points should be made about their presentation. First, their meticulous attention to operative techniques (especially the necessity to control bleeding) and stimulation parameters, is a new and important feature of their paper as compared with earlier work. The technology of neurophysiological research becomes more and more a matter of central concern in subsequent work. A second matter of increasing importance was a standard nomenclature of cerebral areas. This was provided for Fritsch and Hitzig by Richard Owen's On the Anatomy of the Vertebrates (1868).
Much of their discussion is concerned with issues that took a decade to settle. Were they really stimulating the cortex, or were current loops spreading to lower centres? They conducted experiments which convinced them that it was the convexity itself which was producing the contractions. Were the fibres alone, or the cells as well, excitable? This was a confusing question in 1870, which they felt unable to decide. One reason for their indecision is reflected in its statement as a dichotomy: fibres or fibres and cells. It should be remembered that the explicit statement of the neurone theory was almost twenty years away. Fritsch and Hitzig tentatively attempt to eliminate the dichotomous issue with an early statement of the theory. 'Since no other reason can be found why the fibers should come closer to the ganglion cells just here than to meet their fate to enter into them, one can assume that these ganglionic masses are predestined to produce organic stimuli just for these nerve fibers. They are quite properly not over-concerned with this last issue in their first publication, nor are they particularly worried about other questions they left open, such as the relation between the poles of their stimulating instrument or the character of the muscular twitches obtained. 'The new facts which were shown by these investigations are so manifold, and their consequences go into so many directions, that it would be of little advantage to try to follow all these trails at once.
They insist on only two firm conclusions. The first, 'that central
1 Standard cerebral anatomy has become the cornerstone of method in cerebral physiology. In 1908, Victor Horsley and A. H. Clarke designed a stercotaxic instrument which made it possible to use a standard atlas and standard three-dimensional co-ordinates for specifying any point on the surface and, more importantly, in the deeper portions of the brain. Subsequent developments of this technique have led to very impressive localized stimulation, ablation, electrical recording, and implantation of pharmacologic substances. 0.5 mm is the current acceptable standard of error for a good instrument and atlas. The original instrument was described in Horsley and Clarke, 1908. Several articles describing current stereotaxic technology appear in Sheer, 1961. The enormous bibliography to that work is a rich mine of sources.
2 Fritsch and Hitzig, 1870, p. 93.
3 Ibid., p. 84.
nervous structures answer our stimuli with overt reactions',[l] eliminates the anomaly with which they opened their paper. The hemispheres, like all other nervous structures, have the property of excitability that had formerly been denied to them alone. The second certain conclusion is that 'a large part of the nervous masses composing the hemispheres, about half of it, stands in immediate connection with muscular movements, while another part has evidently directly nothing to do with it.
Fritsch and Hitzig reveal the two most important principles of the new era in cerebral physiology which this paper begins as they attempt to answer the very pertinent question of 'how it came about that so many earlier investigators, among them the most illustrious names came to opposite results. To this we have only one answer, "Methods give the results"'. This statement is double-edged. It recalls Flourens' identical statement as he advocated the experimental method rather than Gall's anecdotal and correlative approach. Since it is being used by Fritsch and Hitzig as they overthrow Flourens' findings, the statement also shows that new methods give new results. From 1870 to the present day, this technology has provided increasingly more refined and fruitful techniques, which have largely determined the progress of experimental work: new surgical and aseptic techniques, stimulation sources, electrodes and methods of placing them accurately (and, later, of implanting them permanently). Beginning in the second quarter of the present century, the above methods were aided by the addition of very elaborate methods of recording the electrical activity of the brain as a whole, and very tiny regions of it down to a single neurone. Some appreciation of these advances can be gathered by comparing a modern stimulating and recording console with their measure of stimulus intensity-that which 'produced just a sensation on the tongue when it was touched by the heads'.
Their answer to previous failures was not only concerned with methods. In fact, they acknowledge that assumptions had, in large measure, determined the results.
It is impossible that our predecessors have laid bare the whole convexity, for otherwise they must have obtained contractions. The posterior lateral wall of the cranial vault of the dog, under which there are no motor parts, recommends itself by its configuration for the first trephine opening. Here one most likely began the operation and then did not go forward, assuming erroneously, that the various parts of the surface were equivalent. One based
1 Fritsch and Hitzig, 1870, p. 91.
2 Ibid., p. 92.
3 Ibid., p. 90.
4 Ibid., p. 81.
oneself on the supposition still widely disseminated and mentioned in the beginning, that all psychological functions are present in all parts of the cortex. Had one only thought of the localization of psychological functions, one would have considered the seemingly inexcitability of certain parts as something quite obvious and would have examined every part separately.
Their paper closes ,with a reiteration of this rejection of cerebral equipotentiality and its replacement by cerebral localization.
This shows clearly, that in the former colossal destructions of the brain, either other parts have been chosen or that the final mechanisms of movements were not particularly noticed. It further appears, from the sum of all our experiments that the soul is not, as Flourens and others after him had thought, a function of the whole of the hemispheres, the expression of which one might destroy by mechanical means in the whole, but not in its various parts but that on the contrary, certainly some psychological functions and perhaps all of them, in order to enter matter or originate from it need certain circumscribed centers of the cortex.
The assumption of cerebral localization which was given its first firm experimental support in this publication by Fritsch and Hitzig was to dominate cerebral research (with dissent that took its meaning by contrast) until the 1930's, and is again the ruling assumption in clinical and experimental work.
Ontological Dualism and Interaction in Fritsch and Hitzig
The phrasing of the closing sentence in their paper raises the issue of the philosophic assumptions underlying Fritsch and Hitzig's experiments and their incompatibility with the assumptions of the associationist tradition to which Jackson and Ferrier belonged. Put simply, Fritsch and Hitzig were ontological dualists and believed in separate substances of mind and its mechanisms. The brain is the material instrument of the immaterial soul, and the grey matter of the cortices constituted the 'first tools of the soul. The soul can execute its orders by its property or faculty of will, and this provides an impulse which excites the motor mechanisms by interaction. Excitation by a mental act is an alternative means of exciting the motor mechanisms; reflex excitation from the periphery by purely physiological means being the other. They differed from Flourens, who held a similar interactionist view, in that they were prepared to localize at least some of the functions of the soul and to place some of its instruments for muscular
1 Fritsch and Hitzig, 1870, p. 90.
2 Ibid., p. 96.
3 See Zangwill, 1961; Krech, 1962.
4 Fritsch and Hitzig, 1870, p. 77.
motion in the hemispheres. Flourens had reserved the hemispheres for sensation and volition, holistic functions served by an equipotential and inexcitable cerebral mass.
Fritsch and Hitzig were not prepared to say that they had found the centres of volition or even that their centres were the first mechanical link in the execution of volitions. The methods they used could not tell them if their stimuli led to the same movements as normal mental and physiological mechanisms. The last sections of their paper are concerned with a tentatively-held view that their centres served an intermediate function between 'that part of the brain which harbors the origin of the volition of the movement' and lower muscular mechanisms which were less well-coordinated.[l] They conducted ablation experiments which, they believed, left room for 'purely psychological possibilities' 'more central' than their motor centres. These were presented very briefly and interpreted very tentatively. The result of ablating the centre for the right anterior extremity was not complete paralysis but only impairment of the ability to move the limb. They saw this finding as supportive of the existence of 'still other centers and pathways to originate and to run to the muscles of that leg'. The further interpretation of the partial nature of the impairment is reserved, but the whole discussion is in the service of an interactionist conception.
There is nothing to be gained for present purposes from a detailed examination of their interactionism and the complex problems it involves. (For example, like Flourens, they were involved in a double interaction: between will and its material substrate in the first instance, and then between the mental act of will and the muscular mechanisms it activates.) The point to be made is that the psychophysical parallelism of the Spencer-Jackson-Ferrier view eliminates all these complex issues by precluding interaction and even the discussion of psychological faculties in a physiological context. The support for his concepts which Jackson derived from Fritsch and Hitzig is confined to the involvement of the hemispheres in movement. The stimulus they gave to Ferrier is confined to their demonstration of the localized electrical excitability of the cerebral hemispheres. The philosophical assumptions of the Germans' view were anathema to the Englishmen, whose parallelism allowed them the luxury of ontological agnosticism while they got on with their work.
1 Fritsch and Hitzig, 1870, p. 92.
2 Ibid. p. 96.