Ferrier's mistake

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Perspectives Ferrier's mistake Mitchell Glickstein David Femer was a phystctan who hved and worked m London in the last part of the nineteenth century and the early part of the twentieth century In addmon to hzs clinical practtce he had an active scwnttfic career and pubhshed reports and books on the results of his research Ferrter worked during a crtncal period tn the development of neural science In the middle of the mneteenth century there were only vague and maccurate descriptions of the role of bram m sensation and movement By 1900 the emstence and location of cortical areas spectahzed for speech, movement, and vision had been estabhshed and related to their histological structure Ferrter participated tn these great discoveries, but he made one Important mistake On the basts of the effects of lesions m monkeys he identified the angular gyrus of the parietal lobe as the primary visual cortex A consideration of why Ferrter made this mistake ts useful for understandmg the origins of modern neural science and for interpreting some current problems on the functions of the cerebral cortex In 1850 p r u d e n t opinion held that there are not, and cannot be, functional subdivisions of the cerebral cortex By 1900 such a view was virtually untenable. Loeahzatxon of function was established as a basic principle of cortical organization The observations, experiments, and controversies that led to this conclusion influenced the later d e v e l o p m e n t of neurobiology and contributed to stronger links between the basic sciences and clinical neurology Physicians could now understand and interpret many of the formerly bewildering symptoms which follow injury to the brain In the first half of the n i n e t e e n t h century the major p r o p o n e n t of brain localization was Franz Joseph Gall Gall was a p r o m i n e n t anatomist who taught that the brain is composed of as many individual regions as there are psychological faculties H e argued that the shape of the skull reflects the form of the brain b e n e a t h it, hence personality and character traits can be evaluated directly by palpating the head Gall's dlsople, Spurzheim, took these ideas even further to develop the entire system of phrenology which in the early part of the n i n e t e e n t h century attracted some support from physicians 1 and an enthusiastic popular following But by 1850 the lack of evidence for the claims of phrenology gave the very idea of localization a bad n a m e to cautious scientists and physicians Such experimental ewdence as there was seemed against any cortical locahzation Pierre Flourens 2 reported that animals with lesions of the

forebraln seemed to have difficulties in sensation, perception and vohtlon But Flourens believed that these functions could not be separated, that they are all diffusely represented and controlled by the brain: 'Unity is the great principal, it IS everywhere, it dominates all The nervous system therefore forms one unitary system'. Sensible opinion favoured Flourens T h r e e discoveries changed all this In 1861 Broca 3 reported that a localized lesion of the left frontal lobe produced a p e r m a n e n t disorder of speech A few years later J o h n Hughlings-Jackson 4 described a type of epileptic seizure which begins with the rhythmic m o v e m e n t of a single body part, and then spreads to nelghbouring regions In a definite sequence or 'march' It seemed likely that the progression of convulsive movements might reflect an underlying somatotopic organization of m o t o r control within the brain_ But perhaps the single most important event initiating the m o d e r n view of cortical locahzation was the experiment of Frltsch and Hltzig 5 They stimulated electncally a region of the cortex of the frontal lobe of a dog, and found that the stimulation produced m o v e m e n t of a limb or other body part on the opposite side of the body. If stimulation of a given point on the cortex caused a limb to move, then ablating that region caused clumsiness in the same h m b One region of cortex appeared to be s p e o a h z e d for the control of movement, and the search was on for the locus of other functions David Ferrter began his experiments

on brain Iocahzatlon just after Frttsch and Hitztg's discovery He had graduated with a B A from the University of A b e r d e e n in 1863 with first class honours in classics and philosophy and an MB from Edinburgh in 1868 He wrote a thesis on the comparative anatomy of the superior and inferior colhcuh for which he was awarded the degree M D and a gold medal Ferrier was appointed Lecturer in Physiology at the Middlesex Hospital, L o n d o n in 1870 In 1871 he was appointed demonstrator in Physiology at the Medical School of King's College London where he remained for the rest of his academic life Later, he also became a staff p h y s l o a n at the National Hospital for the Paralyzed and Epileptic - now the National Hospital for Neurological Diseases at Q u e e n Square Ferrier began his first experiments in Yorkshire His friend, Dr James Crlchton Brown, was the director of The West Riding Lunatic Asylum, and offered Ferrler a laboratory there In his first paper in the Medical Reports of the West Riding Lunatic Asylum 6 Ferrrier said 'The objects I had in view in undertaking the present research were twofold first, to put to experamental proof the views entertained by Dr Hughhngs Jackson in the pathology of epilepsy, chorea, and hemiplegla by imitating artificially the "destroylng" and "discharging" lesions of disease, which his writings have defined and differentiated, and secondly, to follow up the path which the researches of F n t s c h and Hitzlg (who have shown the brain to be susceptible to galvanic stimulation) indicated to me as one likely to lead to results of great value in the elucidation of the functions of the cerebral hemispheres, and in the more exact locahzation and diagnosis of cerebral disease " In these first studies Ferrier studied the effects of faradic or alternating current stimulation of the brains of experimental animals_ He confirmed the existence of areas in the brain of birds and mammals which produced m o v e m e n t s when stimulated Later, at King's, Ferrier concentrated his attentions on the brain of monkeys_ He

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342 reported 7 that stimulation on e~ther b a n k of the central sulcus produced m o v e m e n t of the trunk and hmbs of monkeys, stimulation of the angular gyrus of the parietal lobes caused the eyes to move F e r n e r suggested that ff stimulation of the angular gyrus produced a wsual sensation, the monkey might simply be moving .ts eyes in response to that sensation_ Perhaps the angular gyrus ts the sought-after visual area of the brain F e r n e r submitted this idea to e x p e n m e n t a l test by making lesions of the angular gyrus and observing the monkeys postoperatively W h e n he removed the angular gyrus, monkeys appeared to be unable to see in the eye opposite the lesion, ff both angular gyn were ablated the animals seemed to be completely b h n d (see Fig 1) F e r n e r gives some of the evidence for this conclusion m a report to the Royal Society and in his book, Function~ o f the Brain s

'In another experiment the angular gyrus was exposed on both sides, and accurately cauterized. For a long time I could devise no test of stght which should be free from the fallacy attending mere reflex reaction to visual impressions For the animal sat still and

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refused to stir from its place so that there was no means of determining whether it could walk steadily and avoid obstacles m Its path The pupils contracted to light and a light flashed m the eye caused the animal to wince. When a plecc ot apple was dropped near it so as just to come in contact with its hand it took it up, smelt ~t, and ate it with gusto W h e n called to, ~t would turn and look m the direction of the sound. Wsth the exception of the reluctance to move from its position arising evidently from a sense of insecurity, there was nothing to indicate decisively whether the animal was really blind I had found before the experiment was performed that this animal was exceedingly fond of tea and would run anywhere after it On placing a cup of tea close to its lips ~t began to drink eagerly The cup was then removed from immedmte contact, and the animal though intensely eager to d n n k further, as indicated by its gestures, was unable to find the cup, though its eyes were looking straight towards It This test was repeated several times with

exactly the same result A t last on the cup being placed to its lips, it plunged m its head and continued to drink though the cup was gradually lowered and drawn half way across the room ' Ferrler's conclusions were controversial_ The experiments were criticized by H e r m a n n Munk, Professor of Physiology at the B e r h n Veterinary School M u n k reported 9 that occipital, not parietal lesions produce blindness, and that each eye is connected to both hemispheres 'If one extirpates the whole cortex on the one side of the occipital lobe the monkey becomes hemioplc He is blind, corUcally blind for those halves of both retinae which are on the side of the lesion. If for instance, the left hemisphere has a lesion the monkey does not only not recognize but he does not see any objects whose picture is on the left side of his retina while he can see everything else m normal fashion and recognize when it falls on the right side of the retina As the s u t u n n g of first one eye and then the other eye shows without a doubt, the

FIGS. 90 a n d 91 - - B ~ a t e r a i L~smn, causing t e m p o r a r y comp'ete lv-~ of ~'~-t,J~

FIGS. 43 AND 44.--The Bhaded port ons m these figures indlc~te the leSiOnS of the cortex of the hemispheres tn the monkey, csusing bhndnees. (Roy, BOc,)

Fig. 1 Ferrler's figure from the first edition of his book T h e Functions of the Brain llhtstratmg location of Angular gyrus leswrt~ (Taken f r o m R e f 8, with permnssnon )

Fig. 2 Ferner's figure from the second edtnon of Functions ot the Brain Note the changes in the figure legendP (Taken from R e f 13, with permission )

TINS- August 1985 disturbance is the same for both eyes and this hemiopla remains for weeks and months Only the monkey learns very soon to compensate his hemloplc hmltatlon of his visual field by movements of head and eyes ' 'If finally the same extirpation has been done on both occipital lobes the monkey is completely cortically blind, he sees nothing By nature so wide awake and mobile he sits now in his cage for hours quite apathetic and as though he dreamed without movement until a sound stirs him Taken out of the cage he will not move Making him move by beating him he bumps into all obstacles in his way, falls off the table, etc Very gradually his vision gets shghtly improved so far that he will not bump into things when he walks slowly Further restitution will only happen when as the post mortem shows, apart from the unapproachable cortex on the lower side of the occipital lobe, also large parts on the margin of the upper side of the lobe have remained ' In regard to Ferraer's work he said"In my first communication on the physiology of the cortex which I made in March of last year I did not say anything about Ferrler's work on the monkey because there was nothing good to be said about it But asked in the subsequent session I had to say that Mr Ferrler's declarations that the visual center in the monkey was satuated in the angular gyrus, right underneath in the gyrus temporo-sphenondahs superior, the acoustic center, in the lower part of the temporal lobe, the center for smell and taste, in the gyrus hlppocampx and hlppocampus major, the center for touch, finally In the occipital lobe, the center for hunger (v) that all these statements and what followed from them as far as the character and restitution of d~sturbances set by the operation are concerned, are worthless and gratuitous construct~ons since the operated animals were examined by Mr Ferrler in quite an insufficient manner and only at the time of general depression of brain func-

343 tion If I have gone too far in this statement which 1s based on a general survey of Mr Ferrler's experiments it was up to me to restore the InJury, the sooner the better However, as the experiments show now I have said at that time rather too little than too much, Mr Ferrler had not made one correct guess, all his statements have turned out to be wrong ' The controversy was bitter William James said in his text book ill 'the quarrel is very acrimonious; indeed the subject of localization of functions in the brain seems to have a pecuhar effect on the temper of those who cultivate it experimentally_ _ • Munk's absolute tone about his observations and his theoretical arrogance have led to his ruin as an authority'_ Munk was right, but questions remain Why did F e r n e r fail to see visual deficits after he made occipital lesion9 What Is it that Ferrler did see that led him to conclude that the parietal lobe is the visual area of the brain 9 The failure to find visual loss after occipital les:ons is not hard to explain In almost all cases Ferrier removed the monkey's occipital lobe well behind the lunate sulcus Even if all of the occipital cortex caudal to this sulcus is removed some anterior strlate cortex on the banks of the calcarine fissure would have been spared The sporing might constitute only a small percentage of the total area of strlate cortex, but because relatively large areas of the peripheral visual field are represented in relatively small areas of the visual cortex II just a few milhmeters of residual stratle cortex would lead to sparing of a sizeable portion of the peripheral visual field Ferrler's monkeys would have had a large central scotoma and poor acuity but they would not be blind Monkeys quickly learn to use the sighted portion of their visual field in solving visual tasks, because of the quickness with which they move their eyes and head, the visual impairment may be masked The occipital lobe lesions in Munk's monkey were probably more complete In this first series of experiments Ferrler's monkeys lived only a few days after he operated on them. hence he could not see if the symptoms improved with time The operations were performed without aseptic precautions, and If allowed to survive the animals inevitably died of infection

Hence F e r n e r killed almost all of his monkeys within 3 or 4 days after he operated on them. Ferrier's colleague in surgery at King's was Joseph Lister When Ferrler adopted Lister's antiseptic surgical procedures, his monkeys now lived longer and their vision got better In a paper written with Gerald Yeo ~2 Ferrler described the symptoms in a monkey with angular gyrus lesion, 'The cherry was laid on the floor in front of it but it was unable to find it though looking eagerly for It The animal enjoyed ItS food which It found by gropmg about with its hand m its cage' "On the fourth day there was some Indication of returning vision A piece of orange was held before it whereupon it came forward in a groping manner and tried to lay hold but missed repeatedly When the piece of orange was laid on the floor It stretched out its hand over it, short of it, and round about it before it succeeded m securing it 'On the fifth day the animal came out of its cage spontaneously and walked about It never now knocked its head It was evidently able to see its food, but constantly missed laying hold of it at first putting its hand beyond Jt or short of nt 'On the sixth day the animal walked about freely avoiding obstacles, but vision was evldently defective, as on several occasions it was seen as if about to chmb before it had come sufficiently near the ledge on which it wished to mount It was however, able to pick-up grains of rice scattered on the floor, but always with uncertainty as to the exact position 'Four weeks after the operation there was the same want of preclslons still seen as regards ItS power of putting its hands on objects it wishes to pick-up This was apparently equal in all directions ' Ferrler now knew that animals with angular gyrus lesions were not blind and changed the caption of his figure in the second edition of hi~ book. pubhshed in 1886 (see Fig 2) By 1900 the argument was all but over Schafer 14 and others had replicated Munk's experiments producing

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344 visual defictts after lesions of the occipital lobe, and failed to confirm the existence of visual deficits after angular gyrus lesions Munk's discovery was quickly applied to the human brain In 1892 Henschen t5 identified the stnate cortex of the occipital lobe as the visual area m man, and in 1909 Inouye I6, studying brain-injured soldiers from the RussoJapanese war, produced a reasonably accurate map of the way m which the visual fields are represented on the human stnate cortex Ferrier's conclusions may be questioned but his findings should not be. His protocols show clearly that lesions of the angular gyrus of the parietal lobe profoundly Impair wsually guided movements. Why were the monkeys impaired? The areas which Ferrier ablated are part of a masswe system of cortical visual areas which extend from the occipital pole as far rostrally as the mtrapanetal sulcus and the temporal pole Nearly half of the monkey cortex seems to be devoted to processing of visual Information. A central and current question is what do all these visual areas do'~ The efferent connections of the cortical visual areas may provide a clue One of the pnnclpal circuits through the mammalian brain originates in the cerebral cortex and projects to the pontme nuclei Cells in the pontlne nuclei, in turn, send axons via the middle cerebellar peduncle to the cerebellar cortex, where they terminate as mossy fibers_ It seems hkely that this corftco-ponto-cerebellar circuit is one of the major pathways for the visual guidance of m o v e m e n t In monkeys the projection anses pnncipally from cells on both banks of the superior temporal fissure, the rostral bank of the parieto-occipital fissure and the adjacent parietal lobe 17. Most of these areas were included in F e r n e r ' s lesions of the angular gyrus Thus the lesions may have impaired visually graded movement by blocking visual information from reaching the cerebellum The angular gyrus also projects to the p r e m o t o r cortex, area 6, hence the effects may have been due m part to interruption of cortleo-cortlcal circuits from visual to motor areas t8 The deficit which Ferrler described improves with time I9 but impairment in visual guidance of the wrist and fingers may be p e r m a n e n t 2° The impairment is not restricted to visual guidance of the limb, since lesions of the angular gyrus and the adjacent parietal lobe

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cerebral cortex, pp 96--117. Thomas Springaffect eye movements as well zt.2-~. field IL The receptive field properties of 6 Ferner. D (1873) West Riding Lunatw ceils on both banks of the superior Asylum Med Rep 3, 30-96 temporal sulcus and the adjacent area 7 Ferner. D (1875)Proc R Soc (London) 7 of the parietal lobe are conststent Ser B 23. 409-432 with their role in visual guidance of the 8 F e m e r , D (1876) The Functton~ of the Brain, Smith, Elder and Co , London arm, the eyes, or the whole body Visual cells tn these areas can be 9 Munk, H (1881) Uber die Funktwnen der Grosshlrnrmde pp 28--53. A Hlrschwald modulated by eye p o s m o n , show an Berlin Enghsh Translation m Von Bonm. G enhanced visual response when the (1960) Some papers on the cerebral cortex, animal attends to a stimulus or uses it pp 97-117 Thomas Spnngfield IL as a target for a visually guided 10 James, W (1890) Principles of P~ychology, movement, and most respond preferHenry Holt, New York entially to the direction and speed of 11 Darnel. P and Whlttertdge, D (1961) J Physlol (London) 159,203--221 moving targets 23-~ Orientation, shape, or color of the target seem to 12 Ferner, D and Yeo, G (1884) Phd Frans R Soc (London)Ser B part II. pp 479--564 be irrelevant The sensitivity of units 13 Ferner, D (1886) FuncUor~ o f the Brmn (2nd in these areas to moving targets does edtnon) Smith Elder, London not necessarily mean that they are 14 Schafer. E (1888) Brain 11. l~fi concerned with 'seeing movement' 15 Henschen, S (1_892) KItmsche und Anatomtsche Bearage zur Pathologic des Gehtrns tl, Response to moving visual targets Alanqmst and Wiksell. Upsala would seem a useful way to organize visual reformation for the visual gutd- 16 Inouye, T (1909) Die Sehstorungen bel Schussvedetzungen der KorUkalen Sehsance of m o v e m e n t The fact that this phare, nach Beobachtungen an Verwundeten group of parietal lobe visual areas der letzten ]apantschen Krtege, W project to the pontlne nuclei and Engelmann, Leipzig p r e m o t o r cortex is consistent with such 17 Ghckstem. M , May, J and Mercier, B, (1985) J Comp Neurol (m press) a role The deficits which Ferrier discovered probably resulted from 18 Pandya. D and Kuypers, H (1969) Brain Res 13, 1-3-_36 interrupting connections between vis19 Faugler-Gnmaud, S , Frenols, C and Stem, ual and m o t o r areas of the brain D G (1978) Neuropsychologta I6. 151-168 Ferrler hved and worked m a time of 20 Buchbmder S . Dixon. B , Hwang, Y -W , major change in thinking, and his May. 1 -G and Ghckstem, M (1980) Soc Neurosct Abst 6, 675 work contributed to the modern view of brain function He was limited by 21 Lynch J C and McLaren. J W (1982)in Funcnonal basts of ocular monlity the evadable surgical and behavioural (Gle,eotrand, A , Zee, D and Keller, E . techniques but his reports were accureds), pp 501-510, Pergamon, New York ate and clear Ferrter's mistake was 22 Newsome, W T , Wurtz. R H , Darsteler. not such a bad one M and MlkamL A (1983) Soc Neuro~et

Acknowledgement l am grateful to A Lieberman, M Morgan, P Wall and C Yeo for critical reading of an earher draft of this manuscript, and to Susan Gore, Medical Librarian at Universtty College London for continued help with historical sources

Selected references 1 Cooter, R (1981) in Madhouses, MadDoctors and Madmen (Scull, A , ed ), pp ":,8-I04, Athlone, London 2 Flourens, P (1824) Recherches ExperlmenIale~ sur les Propern6s et les funcnons du ~y~t~me nerveux dans les Antmaux Vertebras Chez Crevot, Paris 3 Broca, P (1861) Bull Soc Anat Parts 6, p "~30--357 Translated m Von Bonm, G (1960) Some papers on the cerebral cortex, pp 49-72, Thomas Springfield 1L 4 Hughhngs-Jackson, J (1870) Trans St Andrews Med Grad Assoc 3, OdeU and lves, London Reprmted m Selected Wramgs of John Hughhngs-Jackson (Taylor, J , ed ), (1931),, pp 8--36. Hodder and Stoughton, London 5 Frttsch, G and Hitzlg, E (1870) Arch f 4nat Phystol und wtssenschaftl M e d t z , pp 300-332, Leipzig Translated m Von Boron, Q I (1960) Some paperv on the

Abst 9 t54 23 Anderson. R and Mountcastle, V (1983) J Neuros~t 3,532-548 24 Bushnell, M . Goldberg M and Robinson. D L (1981)J Neurophystol_ 46, 755--772 25 Hyvarmen and Sherpm (1979) Brain R~s, 169. 561-564 26 Kawano, K , SasakL M and Yamashlta, M (1984) J Neurophystol 51,340-351 27 Kawano. K and Sasakl M (1984) J Neurophystol 51,352-360 28 Lemonen L (1980) Acre Phystol Scand 108,301-308 29 Lynch, J , Mountcastle, V . Talbot, W and Yen. T (1977) J Neurophyslol 40. 362-389 30 Mountcastle, V . Lynch, 1 Georgopoulos, A , Sakata, H and Acufia. C (1975) J Neurophystol 3g, 871-908 31 Robinson. D L . Goldberg, M andStanton, G (1978) J Neurophyslol 4t, 911-932 32 Sakata, H . ShtbutanL H and Kawano, K (1980) J Neurophystol 43, 1654-1672 33 Sakata, H . Shlbutani, H_ and Kawano, K (1983) J Neurophyszol 49, 1364-1379 34 Zek~, S ( 1 9 7 4 ) J Physlol (London)236, 549-573 35 ZekL, S (1980)J Physlol (London) 308. 116 M H Ohck~tem ts at the M R C Umt on Neural Mechamsms of Behavtour. 3 Malet Place, London W C I E 7JG, UK