Edwin Boldrey and Wilder Penfield's Homunculus: A Life Given by Mrs. Cantlie (In and Out of Realism)

Journal Pre-proof Edwin Boldrey and Wilder Penfield’s homunculus: a life given by Mrs. Cantlie (in and out of realism) Gurpreet S. Gandhoke, MD, Evgenii Belykh, MD, PhD, Xiaochun Zhao, MD, Richard Leblanc, MD, FRCSC, Mark C. Preul, MD PII:

S1878-8750(19)32272-7

DOI:

https://doi.org/10.1016/j.wneu.2019.08.116

Reference:

WNEU 13152

To appear in:

World Neurosurgery

Received Date: 21 June 2019 Revised Date:

15 August 2019

Accepted Date: 16 August 2019

Please cite this article as: Gandhoke GS, Belykh E, Zhao X, Leblanc R, Preul MC, Edwin Boldrey and Wilder Penfield’s homunculus: a life given by Mrs. Cantlie (in and out of realism), World Neurosurgery (2019), doi: https://doi.org/10.1016/j.wneu.2019.08.116. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Elsevier Inc. All rights reserved.

Edwin Boldrey and Wilder Penfield’s homunculus: a life given by Mrs. Cantlie (in and out of realism)

Gurpreet S. Gandhoke, MD1 Evgenii Belykh, MD, PhD2 Xiaochun Zhao, MD2 Richard Leblanc, MD, FRCSC3 Mark C. Preul, MD2

1

Department of Surgery

University of Missouri Kansas City Marion Bloch Neuroscience Institute Saint Luke’s Hospital of Kansas City Kansas, Missouri

2

The Loyal and Edith Davis Neurosurgical Research Laboratory Department of Neurosurgery Barrow Neurological Institute St. Joseph’s Hospital and Medical Center Phoenix, Arizona

3

Division of Neurosurgery

Department of Neurology and Neurosurgery McGill University Montreal Neurological Institute Montreal, Quebec

Correspondence: Mark C. Preul, MD c/o Neuroscience Publications; Barrow Neurological Institute St. Joseph’s Hospital and Medical Center 350 W. Thomas Rd.; Phoenix, AZ 85013 Tel: 602.406.3593; Fax: 602.406.4104 E-mail: [email protected]

DISCLOSURES: None FINANCIAL SUPPORT: The authors are grateful for funds from the Newsome Chair in Neurosurgery Research held by Dr. Preul and Barrow Neurological Foundation that supported this project. ACKNOWLEDGMENTS: The authors acknowledge the inspiration of the late Dr. William Feindel, who prompted and advised this study, among many others, and who mentored R.L. and M.C.P. The authors are grateful to the staff of the archives of the Osler Library of History of Medicine, McGill University, and the Neurophotography Department of the Montreal Neurological Institute and Montreal Neurological Institute archives for expert assistance with

this study (all rights are retained for all institutions). The authors thank the staff of Neuroscience Publications at Barrow Neurological Institute for assistance with manuscript preparation.

SUBMISSION CATEGORY: Historical Vignette

Gandhoke GS et al. 1

Edwin Boldrey and Wilder Penfield’s homunculus: a life given by Mrs. Cantlie (in and out of realism)

Gurpreet S. Gandhoke, MD1 Evgenii Belykh, MD, PhD2 Xiaochun Zhao, MD2 Richard Leblanc, MD, FRCSC3 Mark C. Preul, MD2

1

Department of Surgery

University of Missouri Kansas City Marion Bloch Neuroscience Institute Saint Luke’s Hospital of Kansas City Kansas, Missouri

2

The Loyal and Edith Davis Neurosurgical Research Laboratory Department of Neurosurgery Barrow Neurological Institute St. Joseph’s Hospital and Medical Center Phoenix, Arizona

Gandhoke GS et al. 2 3

Division of Neurosurgery

Department of Neurology and Neurosurgery McGill University Montreal Neurological Institute Montreal, Quebec

Correspondence: Mark C. Preul, MD c/o Neuroscience Publications; Barrow Neurological Institute St. Joseph’s Hospital and Medical Center 350 W. Thomas Rd.; Phoenix, AZ 85013 Tel: 602.406.3593; Fax: 602.406.4104 E-mail: [email protected]

DISCLOSURES: None FINANCIAL SUPPORT: The authors are grateful for funds from the Newsome Chair in Neurosurgery Research held by Dr. Preul and Barrow Neurological Foundation that supported this project. ACKNOWLEDGMENTS: The authors acknowledge the inspiration of the late Dr. William Feindel, who prompted and advised this study, among many others, and who mentored R.L. and M.C.P. The authors are grateful to the staff of the archives of the Osler Library of History of Medicine, McGill University, and the Neurophotography Department of the Montreal Neurological Institute and Montreal Neurological Institute archives for expert assistance with

Gandhoke GS et al. 3 this study (all rights are retained for all institutions). The authors thank the staff of Neuroscience Publications at Barrow Neurological Institute for assistance with manuscript preparation.

SUBMISSION CATEGORY: Historical Vignette

Gandhoke GS et al. 4 ABSTRACT For nearly 90 years, notions of the brain have been inextricably associated with a homunculus that has become embedded within medical education as the “precise” representation of rolandic cortical function. We sought to define the history, evolution, accuracy, and impact of this pictorial means of illustrating cortical representation. We mathematically defined the evolutionary accuracy of appropriate homunculi using image analysis techniques for all points defined by Penfield, Boldrey, Rasmussen, Jasper, and Erickson, calculating perpendicular distances and defining areas and distributions of rolandic and sylvian regions labeled for sensory and motor activity with comparison to all homunculi. Prerolandic sensory representation composed 13%-47% of total sensory area (mean 29%); postrolandic motor representation composed 15%-65% of total motor area (mean 31%). Discrepancy between cortical "perpendicular" length attributed to a particular function on 1937 diagrams was greater than that attributed on the 1950 homunculus (motor: mean 74%, range 63%-96%; sensory: mean 66%, 17%-92%) (P<.05). The homunculus, if truly drawn according to cortical mapping evidence, could never have been recognized as near humanoid, yet it has attained epic educational and practical longevity.

RUNNING TITLE: Boldrey and homunculus KEYWORDS: Brain mapping; cerebral functional localization; cortical stimulation; Edwin Boldrey; homunculus; Montreal Neurological Institute; Wilder Penfield

ABBREVIATIONS: MNI, Montreal Neurological Institute

Gandhoke GS et al. 5 Sherrington – and with what better word could any study of cerebral function commence – has said (1902) that ‘Progress of knowledge in regard to the nervous system has been always indissolubly linked with determination of the localization of function in it.’ –

Edwin Boldrey, 1936

The Architectonic Subdivision of the Mammalian Cerebral Cortex

INTRODUCTION In 1936, Edwin Boldrey, then a first-year neurosurgical resident under Wilder Penfield, wrote his McGill University master’s degree thesis, The Architectonic Subdivision of the Mammalian Cerebral Cortex, including a report of electrical stimulation of one hundred and five human cerebral cortices, in which the origins of the homunculus can be traced (Fig. 1). This study traces the origins, life, realism, and impact of Penfield’s homunculus. The homunculus was officially shown for the first time in Penfield and Boldrey’s 1937 Brain publication, “Somatic Motor and Sensory Representation in the Cerebral Cortex of Man as Studied by Electrical Stimulation.”

A MASTERFUL THESIS Boldrey’s thesis documented the first large-scale study of human in vivo cortical stimulation under local anesthesia during surgery for epilepsy and brain tumors and the first such study to actively identify and separate motor and sensory functions, as well as other brain functions. In addition, it aimed at synthesizing a system of knowledge and a logic of cerebral function and localization. At the time, although only Otfrid Foerster had studied more cases,

Gandhoke GS et al. 6 Boldrey’s 303-page thesis attempted to bring together anatomic, physiologic, and experimental and clinical functional cerebral localization information. The last sections of the thesis, on electrical stimulation of the cortex, are the most noteworthy. One hundred and sixty patient cases and charts of Penfield and William Cone elucidating and depicting various cortical functions, as found by electrically stimulating the cortex, are condensed into 29 stimulation illustration maps. Stimulation was only done when there was “therapeutic justification for it.” Most of the patients had seizures or harbored tumors. There was no account for phenomena of brain shift and edema, and operative diagrams depicting stimulations omit pathology. No matter where the lesion, though, the rolandic fissure and the pre- and postrolandic gyri were always exposed. The summary interweaves the history of cerebral localization studies to date, correlated with pre-Penfield studies and the most recent Montreal Neurological Institute (MNI) evidence. The “Illustrations” section graphically crystallizes Boldrey’s analysis of the MNI data, while the bibliography is a complete survey of the most influential publications at the time. Details of the electrical exploration were recorded by a running dictation from surgeon to stenographer, who recorded the stimulation number, description of response, and time of each stimulation. Photographs to document the brain with locating surface tickets were taken with an ingenious operating theater camera system. The surgeon, with sterile paper and pencil, made a sketch at the close of stimulation, drawing the numbers on a uniform life-size half-brain preprinted diagram; 28 of these illustrative charts were reproduced in the thesis (Fig. 2). The methodology used by Boldrey and Penfield to represent the points on the brain, which on stimulation resulted in responses, was thorough yet not without occasional subtle

Gandhoke GS et al. 7 approximations. The points were placed in proper orientation according to the distance from the sylvian and the median longitudinal fissures. Boldrey remarked: Indeed, the Rolandic fissure can hardly be called a constant mark. In the earlier drawings estimations of [stimulation] position have been necessary in a few instances but the majority were found to be to scale…. The one hundred and sixty charts compiled as the first step in this study have been condensed into the twenty-eight charts which are illustrated in this chapter…. One side [right side maps] was used for the purpose of uniformity and not because either hemisphere is thought to be predominant.1 Boldrey included 28 charts that contained the greatest number of stimulation points to formulate an overall motor and sensory sequence chart. On the basis of results from many patients in whom motor and sensory sequence did not obey an “ideal” pattern, he concluded, “It would seem, therefore, that this cortex of ours is exceedingly capricious in its responses, even from the same regions at different times.”1 He attributed these conclusions to the large portions of the cortex buried in the sulci, silent areas in the human rolandic area, and to the phenomena of facilitation and inhibition, with variations that could cover several cortical centimeters. Boldrey concluded with comments on previous stimulation studies and whether the results were reliable and reproducible. He seems to have been concerned to ensure that the maps not assume a permanent credibility and significance other than for the current study conditions: The composite charts presented here do not uphold the present system of brain “maps” with sharply limited areas in regular sequence. Motor and sensory sequence charts made for the purpose do uphold the fact of a sequence as has been previously represented. The results of the one hundred and five positive human cerebral cortical stimulations constitute a record of one of the largest series of such stimulations existent today…. From 9 to 24 per cent of the cortical motor points are post central and from sixteen to fifty-four per cent of cortical sensory points are precentral in this series.

Gandhoke GS et al. 8 Boldrey’s thesis led directly into the 1937 Penfield and Boldrey Brain paper, “Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation” (Fig. 3A). Subtle differences included auditory, visual, and olfactory responses eliminated from the 1937 report. One hundred and seventy summarizing charts were made, which were condensed into 16 illustrative charts reproduced in the paper. All results were documented on right hemisphere map illustrations, as in Boldrey’s thesis. Great effort was made to obtain the data, sometimes with accepted risk, as all patients were operated on while under local anesthesia. Penfield and Boldrey wrote: It is essential that the patient should be in sympathy with the operator and anesthetist, and it is an interesting comment on the bravery and fortitude of mankind that almost without exception these subjects have gone through the ordeal of operation patiently and intelligently, even when young children. But however great may be their power of introspection, we make it a rule to re-stimulate all doubtful points without warning.2

With regard to the study of the movement and sensation of the trunk and legs, the authors commented: “Doubtless more responses would have been obtained had it been feasible to stimulate the edge of the hemisphere and the mesial surface in the median longitudinal fissure more frequently. The danger of bleeding from sinus and tributary veins makes it unwise to stimulate here unless it is clearly necessary.” This observation notwithstanding, there are records for 9 patients who underwent mesial cortical stimulation in the paper. Penfield and Boldrey suggest that the study was limited by virtue of the fact that patients were being operated on for epilepsy and brain tumors with often huge craniotomies and under local anesthesia, “even a greater subdivision of responses could have been obtained if time had been available.” One can only imagine the scene of the open brain during an epileptic attack, which would be rare to document in the current era: “Brain then bulged and for a few seconds

Gandhoke GS et al. 9 there was no pulsation in the cerebral arteries. Pulsation in the arteries began before the end of the attack and the brain began to recede. Pulse was present in wrist all the time.” The phenomenon of secondary facilitation was also shown in the thesis, that motor and sensory responses could be elicited from both pre-precentral and post-postcentral cortices when these points were stimulated in quick succession after stimulating the immediately corresponding points on the pre- and postcentral sulci. Penfield, however, argued that displacement or extension of function from its usual localization was most often due to the diffuse or local effect of a lesion giving rise to epileptiform seizures, or to the fact that “epileptic discharges habitually take place in the cortex even though no objective lesion can be found.”

EVOLUTION OF THE HOMUNCULUS 1937-1954 To represent the topography of his stimulation observations, Penfield devised a homunculus, drawn by Mrs. Hortense P. Cantlie and published for the first time in the 1937 article. The homunculus was shown as a 4-part humanoid image, yet not in association with the cortex, and was a relatively minor aspect of the publication: The sequence of relationships [motor and sensory functions] may be considered from another point of view illustrated by the homunculus … it is seen that toes begin at the top and the members follow in order as though representing a man hung upside down, but that the thumb is followed by the head as though the head and neck were erect and not inverted. The larynx represents vocalization, and pharynx swallowing and throat sensation. The homunculus gives a visual image of the size and sequence of cortical areas, for the size of the parts of this grotesque creature were determined not so much by the number of responses but by the apparent perpendicular extent of representation of each part when these responses were multiple for the same part…. The homunculus may be said to be both motor and sensory as the sequence pattern is roughly the same, although there are differences....Aside from these observations [stimulation data were

Gandhoke GS et al. 10 scant for a few regions, including neck, taste, and nose] the homunculus represents true sequence. (Fig. 3B)2

The homunculus was missing from Penfield and Boldrey’s 1939 paper, Cortical Spread of Epileptic Discharge and the Conditioning Effect of Habitual Seizures, which also contained many maps of motor and sensory stimulations.3 The 1937 homunculus reappeared in Penfield and Erickson’s 1941 Epilepsy and Cerebral Localization, nearly without explanation.4 An interesting feature in this book was a figure of the convexity of the brain with solid bars drawn in front of and behind the rolandic fissure, in which each solid band indicated the approximate extent of the functional cortical representation. This was the first and the last such representational homunculus to appear on the convexity of the brain. The 1947 paper by Penfield and Steelman discussed again the results of radical cortical excision for patients with epilepsy due to birth injury, head injury, and infection.5 This paper neither mentions nor depicts the homunculus. By 1950, the homunculi had multiplied. In Penfield and Rasmussen’s The Cerebral Cortex of Man, two new homunculi became directly apposed to the brain surface (Fig. 4).6 This diagrammatic coronal cross section of the cerebral hemispheres had solid bars drawn at the periphery, the length of the bars giving an indication of the relative cortical areas and perpendicular distances from which the corresponding responses were elicited. “The length of the underlying block lines indicates more accurately the comparative extent of each representation [function].”6 This homunculus showed motor and sensory representations separated, slightly modified, and corrected on the basis of further cortical stimulations and “reconsideration of our findings in regard to somatic motor representation in the precentral and postcentral gyrus.”6

Gandhoke GS et al. 11 Although they presented more homunculi and apparently placed greater emphasis on the idea, Penfield and Rasmussen became cautionary: “The motor homunculus may be used as an aid to memory in regard to movement sequence and the relative extent of cortex in which such movement finds representation. It is a cartoon of representation in which scientific accuracy is impossible.”6 The homunculus held a prominent place in the book, as within the first pages that they wrote: “[the homunculus of 1937] has served a useful purpose, but minor inaccuracies are now apparent in this figurine. Consequently, Mrs. Cantlie has brought forth a sensory homunculus and a motor homunculus … twin figures, seen in profile.”6 The 1951 monograph on epileptic seizure patterns by Penfield and Kristiansen described “initial sensori-motor phenomena” in epileptic patients and then intraoperatively compared these with localization of the initial epileptic discharge in each case. Surprisingly, there was neither mention nor illustration of the homunculus. In 1954, Penfield and Jasper illustrated three sets of homunculi: the 1937 original and other homunculi (with babies) were shown for other structural and functional associations in the insula, supplementary motor and sensory regions, and thalamus. The baby homunculi were drawn to “enable students to visualize the extrarolandic somatic areas” (supplementary motor, supplementary sensory, secondary sensory). Penfield and Jasper sought to highlight that the function of these supplementary areas was related to function involving bilateral body parts. Comments in Penfield’s 1954 work with Jasper reveal the influence that such a graphical, although symbolic, representation could produce and the attachment that Penfield felt for his offspring: “Rolandic Figurines. The size and position of the figurine parts correspond roughly with the extent of Rolandic cortex devoted to the sensation, or movement, of those parts”—and this associated to one of the most inaccurate of the homunculus sketches (Fig. 5). The 1950

Gandhoke GS et al. 12 coronal motor and sensory diagram homunculi do not appear. The attempt at anatomical and illustrative precise correlation with earlier homunculi was abandoned: “The exact position of the parts of these figurines must not be considered topographically accurate. They are aids to memory, no more…. This diagram makes no pretense to detailed accuracy…. The figurines … have the defects, and the virtues, of cartoons in that they are inaccurate anatomically.” There was no homunculus in the 1958 book The Excitable Cortex in Conscious Man. The 1959 book Speech and Brain Mechanisms by Penfield and Lamar Roberts elaborated on centrencephalic integration and the subcortical connections and once again figures the pre- and postrolandic coronal sections of the brain with the solid bars at their periphery, although without the homunculus. Similarly, the somatotopic organization of the various body parts was labeled in the supplementary motor and sensory areas and the insula, but without the homunculitic babies.

ANALYSIS OF HOMUNCULUS-CORTEX MAPPING CORRELATION The homunculus was an ingenious graphical mnemonic tool, if a bit radical for the usually methodical Penfield and Cone. In this spirit, we mathematically analyzed the evolutionary accuracy of the homunculus-illustrated cortical function using image analysis techniques for all stimulation points within areas defined or described by Penfield, Boldrey, Rasmussen, Jasper, and Erickson and calculated perpendicular distances, defining areas, and distributions of rolandic and sylvian regions labeled for sensory and motor activity with comparison to all homunculi. Such an examination to determine realistic representation of the homunculus (i.e., if graphics represent results) has not been accomplished. In their 1937 Brain paper, Boldrey and Penfield did not describe their first homunculus accurately or in much detail, but rather vaguely, even after introducing it following a clear line

Gandhoke GS et al. 13 chart showing linear proportions of motor and sensory sequences. They did not clearly specify that the homunculus’ left side represents motor and right side represents sensation, but there are subtle differences observable between the sides. We assume that the left side is motor because that orientation corresponds to the half-brain maps and figures of Boldrey’s thesis and the 1937 Brain paper. The remark regarding perpendicular representation is likely why Penfield later shifted to a representation of the homunculus draped across coronal half-brain sections, where the perpendicular homunculus proportions are more obvious. We measured areas (MIPAR Image Analysis Software, Worthington, OH) of the stimulations results and then compared these data with the perpendicular linear dimensional aspects of the homunculi to analyze the evolution, conformity, constancy, and unity of the homunculi and thereby gauge representational realism. We used area calculations instead of merely analyzing the distribution of stimulation points, because area graphical depiction corresponds to illustrations of areas Boldrey documented as half-brain maps and rolandic stimulation functional areas in his thesis and areas Boldrey and Penfield later portrayed in other half-brain stimulation maps of the rolandic area (Tables 1-3) (area analyses used). Paired t-test was used for all the calculations, and a P value <.05 was considered to be significant. Prerolandic sensory representation composed 13%–47% of the total sensory area (mean 29%). Postrolandic motor representation composed 15%–65% of the total motor area (mean 31%). The discrepancy between the cortex “perpendicular” length attributed to a particular function on 1937 Brain diagrams was greater than that attributed on the 1950 homunculus (motor: mean 74%, range 63%–96%, P=.02; sensory: mean 66%, 17%–92%, P<.05) (Fig. 6). Homunculus anatomicalfunctional accuracy increased in 1950 (P<.01) but was less representational in 1954 (P<.01), compared with the 1937 Brain homunculus.

Gandhoke GS et al. 14 Within each anatomic structure studied, there were no significant differences between the prerolandic sensory (P= .84) and postrolandic motor (P=.16) representations on comparing the percentage of the pre- and postrolandic points of stimulation from the 1937 Brain paper with that from the percentage areas from the pre- and postrolandic cortices for sensory and motor function. Calculations of areas on stimulation maps showed a significant difference (all P<.05) between the percentage overshoot into the pre- and postrolandic cortex for motor functions and sensory for arm, hand, and mouth areas compared with other regions on the Boldrey brain stimulation maps (Fig. 6).

INSIGHTS FROM THE MAP ANALYSES AND STIMULATION STUDIES Our area analyses show that it is nearly impossible to fit a convexity stimulation map to the coronal map dimensions of function, let alone to then try to appropriate, derive, or correlate humanoid characteristics to the coronal display or apply such to later homunculi. The overshoot disparity of sensory and motor stimulation results for hand and mouth compared with other areas is not surprising, given the concentrated sensory and motor brain regions for these functions. The homunculus features display these translated results. The dimensions of the homunculus also varied over its life. The thesis might be considered a product of the work and influence of Sherrington and Foerster combined with Penfield’s original scientifically surgical orientation to neurology.7-10 Various subtle but important ideas began with Boldrey’s thesis. Boldrey and Penfield recognized the wide variability in outcome response that stimulation of a discrete cortical point could produce, especially in the diseased state. It is impossible to completely and accurately transform such outcome to a humanoid character, but nevertheless Penfield tried. Boldrey stated that all

Gandhoke GS et al. 15 patients who were studied harbored either tumors, scars, or epilepsy, which are well known to produce cortical reorganization.1 His thesis depicted points on the cortex that, on stimulation, resulted in extremely variable responses due to induced seizures or included ipsilateral or bilateral sensation and movement that were missing in 1937. Boldrey’s 1936 thesis1 and Penfield and Boldrey’s 1937 Brain paper2 communicated landmark results for that era. If Boldrey can be criticized for neglecting to include any information, it is only that he did not refer to Fedor Krause’s extensive experience in mapping the brain.11 Penfield would have been aware of Horsley and Krause's electrical stimulation of the motor strip and of Harvey Cushing's stimulation of the postcentral gyrus.12, 13 But he learned firsthand how to perform electrocortical stimulation from Foerster during his stay in Breslau in 1928, before taking his position at McGill University. Homunculi did not figure in other concurrent articles in which they might have been expected, such as Penfield and Boldrey’s 1939 book, Cortical Spread of Epileptic Discharge and the Conditioning Effect of Habitual Seizures,3 which also contained many maps of motor and sensory stimulations. Although the homunculus did not appear in publications after the early 1950s, in illustrations where it had previously been combined, it is clear that Penfield was still using or showing the homunculus in talks or discussions at least into the late 1950s.

“THE ONLY SORT OF THING THAT PEOPLE IN GENERAL UNDERSTAND” Penfield’s homunculus, intended to graphically depict anatomical boundaries for function without exactitude, attained epic educational and practical longevity that Penfield did not expect and which he even tried to deemphasize. He received numerous letters (some amusing)

Gandhoke GS et al. 16 concerning the homunculus, including references to what Hughlings Jackson might have thought about such a creature.6 The homunculus topic came up several times between famed British neurologist F. (Francis) M.R. Walshe and Penfield as they corresponded over 3 decades about the development and philosophy of neurosurgery (Fig. 7A). In April 1943 Walshe asked Penfield “whether the ‘homunculus’ of your paper with Boldrey is not rather a deceptive monstrosity…. Can we believe that these proportions really represent anything obtaining in the cortical representation of movements?... I am convinced [that] our cortical mosaic artists [are] wrong.”14 In August 1946, Walshe wrote Penfield: I still fester about motor representation in the cortex and should have liked to talk with you. I feel that your “homunculus” does indicate graphically your observations, but that it does not represent any plan of organization in the motor cortex. It represents a partial aspect of the truth, an aspect so fragmentary that no inference can be drawn from it. I surmise that you will be heartily tired of its horrific appearance—copied uncritically from text to text—before you see the last of it. You may even have to slay it yourself—an infanticide that might find extenuation. Penfield replied kindly, but seemed surprised that Walshe, of all people, because of his affinity and familiarity with neurosurgery, might take the homunculus seriously: [The homunculus] was one of a number of illustrations which we used to try to illustrate the truth. Of course, there is nothing like the homunculus as far as cortical representation is concerned, but it seems to be the only sort of thing that people in general understand. I would gladly kill the damn thing if I could, but that is never possible. It does call attention to certain facts, such as the reversal of order of representation in the face and neck, as compared with the rest of the body. In October 1958, Walshe accused Penfield of repeating “half-hearted emendations” and “wide variations of factual and hypothetical statements” and of having a hypothesis about cortical integration and representation in “shreds and patches.”15 He wrote that Penfield’s ideas,

Gandhoke GS et al. 17 insinuating the homunculus, had “never had a sure morphological foundation, and in effect you have dropped an unbodied hypothesis, like a cuckoo’s egg into [Horace] Magoun’s reticular activating nest … and not at all wanting this preposterous foundling foisted upon them.” Penfield waited nearly 3 months to answer and took umbrage at the public teasing leveled at the homunculus: And your sneers and caustic wise-cracking, often spoken and sometimes printed, make me suspect personal animosity against me or my background. How often have you delighted in the laughs of your admirers when you made fun of the homunculus drawing? Be honest with yourself. Penfield elaborated on the objectivity and scientific integrity of his results and hypotheses: I did not get the impression that I had foisted a “preposterous foundling upon them” [attendees at the 1959 Laurentian Symposium], as you say…. I have spent a lifetime trying to collect and make available observations of value to Neurology…. my desire to draw correct conclusions is as sincere as yours. I would welcome your help. I resent your raillery…. And now that I’ve said these things at least, I feel better! I’d like to forget it all, like a fight in the days gone by. Not able to accept Penfield’s plea for professionalism, collegiality, and an end to argument, Walshe responded with a diatribe, his reply coming within 4 days! I just have no experience of emotionalism like this in a man of your age, this unrestrained intolerance of criticism, that virtually invites me to sound retreat, but refuses to admit that there may be some grounds for even a single one of my criticisms….but not to confess to particular sins, and you will admit to no single specific defect…. But your besetting pride, nourished on success, and that sugary lay press publicity that seems to be part of a prominent man’s life in Canada, seems to make you unable to take any criticism, or to laugh at yourself…. Of course, I have had many a laugh at your homunculi, anyone brought up on “Alice through the looking glass,” and knowing his Jabberwocky, could not refrain from finding them funny, and still funnier when you try to explain away their

Gandhoke GS et al. 18 defects—and yet keep and breed them. Are your really unable to see that they have an element of the ridiculous?16 The homunculus even became fodder for criticism of the MNI: If I may say so, you were such a nice fellow in the early 20s, before success spoiled you, and before you entered on a long span of life in a place and an institution where no one dared criticize you…. You have never allowed anyone to get near the throne, and thus criticism from afar seems an outrage to you and can only possibly be determined by malice. Somebody has at last said to you “the emperor has no clothes on”. The answer is not to abuse anybody, but to put some clothes on. It is not too late. I am not without a considerable admiration for your gifts, but I pay you the compliment of having no illusions about you. In February 1959, Penfield wrote Walshe in a balanced, straightforward tone to promote and defend the integrity of his science and his accomplished MNI faculty (Fig. 7B): Of course, I have always laughed at the homunculus, and when I was President of the Neurological Association [a song was written] that made fun of the homunculus and me and which was enjoyed by all concerned…. You are wrong about my having no one near me who has the courage to disagree or to criticize. I have always preferred those as assistants who would criticize and who could keep me from falling into error. Cone and [Herbert] Jasper and [Theodore] Rasmussen and [Francis] McNaughton, [Preston] Robb, [K.A.C.] Elliott and [Gordon] Mathieson think independently and have become real powers in their separate fields…. I knew that [Karl] Lashley had said…that I really believed in the existence of a little man in the central organizing system. But he was wrong, and you are wrong when you go on interpreting my statements that way…. My own work is drawing to a close. You call me the Emperor who “has no clothes.” Well, he has no throne either, He never did sit on one, unless office administration and begging for money is that. Now he is preparing to work with his hands at a new job, as long as life’s tether lets him carry on. Peace over the homunculus and Penfield’s theories was made with Walshe’s introspective brief reply (within 2 days), as he cherished Penfield for his science, honesty, and friendship: Dear Penfield,

Gandhoke GS et al. 19 Perhaps you are right in your note received today. Let’s call it a day and end our disputations…. I am in my seventy-fourth year, and I ought to shut up. It can’t be long before I do, and then perhaps peace may descend upon the neurological scene. Until Then Forever, Francis Walshe17 The note was handwritten, and the fact that it was signed with Walshe’s full name indicates that it was a sincere gesture, since Walshe commonly signed only his initials. More had been made of the homunculus than was ever intended, and occasionally even absurdly so. The homunculus triggered significant personal and scientific rapprochement of Penfield; it was used as a convenient starting point to criticize and even ridicule his notions on central integration and cortical representation. Most of those who criticized him had never even seen an open living human brain, let alone experimented upon it, and there may have been an element of envy of Penfield that added to the criticism. Perhaps the controversial homunculus even caused Penfield to mature professionally in light of having to vigorously defend his theories. Never intending the homunculus to convey his ideas with exactitude, he was, however, loyal to it and defended its purpose. The lay press understandably seized on such an idea, and Penfield did not seem to seriously object. The homunculus put the actions or mechanism of the brain on a level that the public could not only grasp but also see. It gave the brain a life with a quirky, “grotesque” (by Penfield’s own description), rather adorable smiling humanness. The homunculus was, in fact, the sort of thing people in general can understand.

CONCLUSIONS Conceived within a thesis that described the culmination of the search for human cerebral localization, begun in earnest nearly a century earlier; correlating cytoarchitectural evidence for

Gandhoke GS et al. 20 disparate, specialized, and defined cerebral function; and evolving through a print lifespan of only 17 years, that fluctuated in and out of realism, Penfield’s homunculus, given caricature by Mrs. Cantlie, lives on in every neurosurgeon’s mind. The homunculus represented Penfield’s attempt to communicate a logic and philosophy of brain organization that he cleverly and creatively conceptualized into a life form—a means by which we still at least acknowledge rolandic area function. The homunculus became a powerful symbol of brain exploration, helped to make Penfield famous, and became associated with the reputation of McGill’s revolutionary neurological institute. Penfield and Cone were utterly determined to explore the living human brain upon their arrival in Montreal, the pursuit of which Boldrey clearly elucidated: Since 1928, Dr. Penfield and Dr. Cone at the Montreal Neurological Institute have stimulated portions of one hundred and forty human cerebral hemispheres. One hundred and five of these had positive responses ... sixty-three percent were males, thirty-seven percent were female, the oldest was fifty-nine years of age, and the youngest six; the average age was twenty-five years. The cortical stimulation was, in most instances, an adjunct to the precise removal of a cerebral tumor or scar. Under Penfield’s mentoring, Edwin Boldrey recorded a remarkable brain mapping achievement and set a beginning and perspective to it in his masterful 1936 thesis that forever altered conceptualization of brain organization. In fact, there is a homunculus in Boldrey’s thesis—it has a form only of words describing an idea, but it is there, his “abstract thing”1—a list of functions, both motor and sensory, in a sequential, typed, but spatial layout (Fig. 8). Might we call it the twinkle in Penfield’s eye?

Gandhoke GS et al. 21 REFERENCES 1. Boldrey EB. The architectonic subdivision of the mammalian cerebral cortex : including a report of electrical stimulation of one hundred and five human cerebral cortices. McGill University, Canada1936. 2. Penfield W, Boldrey EB. Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation. Brain. 1937;60:389-443. 3. Penfield W, Boldrey EB. Cortical spread of epileptic discharge and the conditionining effect of habitual seizures. Am J Psychiatry. 1939(96). 4. Penfield W, Erickson T. Epilepsy and Cerebral Localization: A Study of the Mechanism, Treatment and Prevention of Epileptic Seizures. Springfield, IL: Charles C Thomas; 1941. 5. Penfield W, Steelman H. The treatment of focal epilepsy by cortical excision. Ann Surg. Nov 1947;126(5):740-762. 6. Penfield W, Rasmussen T. The Cerebral Cortex of Man. New York: The Macmillan Company; 1950. 7. Feindel W. The physiologist and the neurosurgeon: the enduring influence of Charles Sherrington on the career of Wilder Penfield. Brain. Nov 2007;130(Pt 11):2758-2765. 8. Penfield W. Sir Charles Sherrington, poet and philosopher. Brain. Sep 1957;80(3):402-410. 9. Feindel W. Wilder Penfield (1891-1976): The man and his work. Neurosurgery. Sep-Oct 1977;1(2):93-100. 10. Penfield W. Sir Charles Sherrington, O.M., G.B.E., F.R.S. Nature. 1952(169):698. 11. Krause F. Chirurgie des Gehirns und Rückenmarks nach eigenen Erfahrungen. Vol Vol I and II. Berlin: Urban und Schwarzenburg; 1908-1911.

Gandhoke GS et al. 22 12. Leblanc R. Cushing, Penfield, and cortical stimulation. J Neurosurg. Jan 26 2018;130(1):7683. 13. Krause F. Surgery of the brain and spinal cord based on personal experience. New York: Rebman; 1912. 14. Walshe FM. Letter to Wilder Penfield (April 25, 1943). Osler Library of the History of Medicine: McGill University; 1943. 15. Walshe FM. Letter to Wilder Penfield (October 1, 1958). Osler Library of the History of Medicine: McGill University; 1958. 16. Walshe FM. Letter to Wilder Penfield (January 20, 1959). Osler Library of the History of Medicine: McGill University; 1959. 17. Walshe FM. Letter to Wilder Penfield (February 5, 1959). Osler Library of the History of Medicine: McGill University; 1959. 18. Feinsod M. Kershman's sad reflections on the homunculus: a historical vignette. Neurology. Feb 8 2005;64(3):524-525.

Gandhoke GS et al. 23 FIGURE LEGENDS Figure 1. (A) Attending physicians, house staff, and fellows of the Montreal Neurological Institute, 1936. Front row, left to right: W.M. Witherspoon, E.B. Boldrey, D.L. Reeves, R. Pudenz, I.M. Tarlov. Second row: R. Amyot, J. Saucier, C. Russel, W.G. Penfield, W.V. Cone, F.H. MacKay, J.N. Petersen. Third row: E. Walker, J.P. Evans, A.R. Elvidge, A.G. Morphy, A.W. Young, A.E. Childe, F.L. McNaughton. Back row: W.L. Reid, J. Kershman, T.C. Erickson, A.J. Cipriani, K. von Santha, J.S.M. Robertson (B) Title and contents pages from Boldrey’s 1936 McGill University master’s degree thesis.1 At the beginning of this study, it was found that only two hard copies of Boldrey’s thesis existed, one at McGill University and one in California with the Boldrey family. This study instigated the immediate image digitization of the copy at McGill University for preservation of this pivotal work in neuroscience. Figure 1A is courtesy of the Montreal Neurological Institute Archives. Figure 1B is courtesy of the Osler Library of the History of Medicine, McGill University. Figure 2. Examples of the stimulation maps that were recorded intraoperatively (A) and which Boldrey reproduced in his thesis (B). Courtesy of the Osler Library of the History of Medicine, McGill University. Figure 3. Penfield employed Hortense P. Cantlie (nee Douglas), a skilled medical illustrator who had taken her training under Max Brödel at Johns Hopkins University, to draw the homunculus. In his texts, Penfield always referred to her as “Mrs. Cantlie.” Mrs. Cantlie, completely deaf since her teens, had worked mainly at the Montreal General Hospital of McGill University since at least 1924, illustrating various surgical and medical topics, producing over her career a huge portfolio with illustrations featured in art galleries and various medical and surgical texts. Another expert McGill University medical illustrator, Eleanor A. Sweezey, drew the later

Gandhoke GS et al. 24 homunculi and other related illustrations for several of Penfield’s books and papers. (A) Penfield’s marked-up typed draft first page for the 1937 Brain publication. (B) The homunculus as first published in 1937 (right) along with what is likely the first, unpublished version of the homunculus (left), which Penfield did not find aesthetically pleasing and which Mrs. Cantlie revised. Courtesy of the Osler Library of the History of Medicine, McGill University. Figure 4. (A) Sensory and motor homunculi appear draped over coronal half-brain sections that attempted to improve the representation proportional extent of function. Note the sensory homunculus now displays representation for male genitalia. Penfield had the coronal 1950 homunculi drawn in an attempt to rectify problems with the 1937 representation: “This may be considered a new edition, or perhaps one member of the twinned offspring of the ‘sensory and motor homunculus’ which [Mrs. Cantlie] drew for us twelve years ago. Such drawings may easily become confusing if too much significance is attributed to the shape and comparative size.”6 Penfield was exploring means to communicate the relative dimensions of functional representation (B) and even including detailed information on response directionality upon stimulation. (C) A sketch of a motor homunculus by Sweezey, probably drawn in the early 1950s. (D) Penfield seems to have been so taken with the idea of the homunculus or its portrayal of a living brain concept that he even used an abstraction of the idea as a sketch for his 1975 book Mystery of the Mind (although the image was ultimately not included in the book). Courtesy of the Osler Library of the History of Medicine, McGill University. Figure 5. Multiple homunculi, including baby homunculi, in a sketch (left) and in final printed form (right), by Sweezey. Courtesy of the Osler Library of the History of Medicine, McGill University.

Gandhoke GS et al. 25 Figure 6. (A) Schematics for the arm (left) and tongue (right) based on Boldrey’s intraoperative areas for stimulation results from his thesis.1 (B-D) Graphs showing comparison of lengths of function between Boldrey’s rolandic intraoperative maps and the homunculus projection draped across the coronal section, including postshrink convexity versus coronal comparison for motor function (B) and sensory function (C) and comparison of percentage of area overshoot between motor and sensory functions for various organs (D). Asterisks indicate statistically significant differences. Figure 6A is courtesy of the Osler Library of the History of Medicine, McGill University. Figure 6B-D are used with permission from Barrow Neurological Institute, Phoenix, Arizona. Figure 7. (A) Penfield’s signed photograph of F.M.R. Walshe. (B) In a winter 1959 gift of his 1958 book The Excitable Cortex in Conscious Man, Penfield penned an appropriate inscription (in sly reference to Walshe’s condemnation) to Cone, who had helped enormously with cortical surgery cases in which stimulation and mapping were performed. On the back of Penfield’s letter to Walshe—which Rasmussen passed to Cone, McNaughton, and Jasper—are comments handpenned in energetic support: “This is only a truce, not a Peace treaty! FMN” (from McNaughton) and “It has been a good fight! H.J.” (from Jasper). Within a year, Penfield would retire as director of the MNI, and Cone would succumb to a tragic death in May 1959. Figure 7A is courtesy of the Osler Library of the History of Medicine, McGill University. Figure 7B book is in the private collection of Dr. Mark C. Preul and used with permission. Figure 8. In the winter of 1951, celebrations were held at the MNI to mark Penfield’s 60th birthday and publication of The Cerebral Cortex of Man. According to custom, junior staff members roasted their director with songs and skits, which included the infamy of the homunculus. The first homunculus was drawn without genitals (as well as showing no auditory,

Gandhoke GS et al. 26 olfactory, or other such abilities), which J. Kershman, a young member of Penfield’s staff and an electroencephalographer, lamented at the event.18 He penned lyrics (A) about the poor creature, to be sung to the tune of “Goodnight Irene.” (B) Outline lists in spatial format of sensory and motor functions found on pages 189 and 191 of Boldrey’s thesis.1 No doubt the ideas found on these pages crystallized into the humanoid image. Courtesy of the Osler Library of the History of Medicine, McGill University.

Preul MC et al. 1 Table 1. Individual number of stimulation points that resulted in response during Penfield and Boldrey’s surgeries Superior Total Function Precentral,a Postcentral,b no. (%) no. (%) Temporal Tongue (motor)

13 (81)

3 (19)

0

16

Tongue (sensory)

24 (19.2)

99 (79.2)

2

125

Mouth and lip (motor)

18 (86)

3 (14)

0

21

Mouth and lip (sensory)

21 (28)

53 (72)

0

74

Jaw (motor)

29 (71)

12 (29)

0

41

Jaw (sensory)

16 (29)

40 (71)

0

56

Eyelid (motor)

30 (94)

1 (3)

1

32

Eye (sensation)

4 (80)

0 (0)

1

5

Face (sensory)

20 (45)

24 (55)

0

44

Swallowing

23 (72)

9 (28)

0

32

Throat (sensory)

4 (31)

9 (69)

0

13

Finger (motor)

77 (75.5)

25 (24.5)

0

102

Finger (sensation)

28 (17.7)

130 (82.3)

0

158

Hand, arm, and shoulder (motor)

186 (83.8)

36 (16.2)

0

222

Hand, arm, and shoulder (sensory)

91 (32.6)

188 (67.4)

0

279

Trunk and legs (motor)

26c (76)

8 (24)

0

34

Trunk and legs (sensory)

4 (18)

18 (82)

0

22

Leg and foot (sensory)

16 d (33)

33e (67)

0

49

Sensation of movement and desire to move

15 (36)

27 (64)

0

42

a

Mean 20% of motor function attributed to the postcentral cortex. Mean 33% of sensory function attributed to the precentral cortex. c Two medial. d One medial. e Five medial. b

Preul MC et al. 1 Table 2. Precentral, postcentral, and overall area calculations on Boldrey’s maps for motor functions and sensory functions Function Motor Precentral Postcentrala Overall Sensory Precentralb Postcentral Overall a

Area, mm2 (% of overall area) Finger Hand

Tongue

Mouth

Face and Throat

188.45 45.53 (19.45) 233.98

516.11 117.92 (18.59) 634.03

446.99 75.61 (14.46) 522.6

498.6 257.7 (34.07) 756.3

69.62 (23.49) 226.73 296.37

175.87 (32.26) 369.24 545.11

41.48 (12.78) 282.86 324.34

215.84 (38.41) 561.86 777.7

Mean 30% motor function attributed to the postcentral cortex. Mean 31% sensory function attributed to the precentral cortex.

b

Arm

Trunk

433.9 82.74 (16.01) 516.63

314.8 580.77 (64.84) 895.58

… … …

212.17 (30.82) 476.11 688.28

391.02 (33.55) 774.25 1165.27

50.52 (13.57) 321.68 372.2

Leg and Foot

384.32 372.82 (49.24) 757.14 221 (46.78) 251.75 472.74

Preul MC et al. 1 Table 3. Perpendicular distances of the Rolandic cortex responsible for a particular function as calculated on the 1937 and 1950 maps Perpendicular distance, mm Function 1937 map 1950 map a Motor Tongue 20.79 3.56 Leg and foot 25.35 12.99 Arm 36.55 5.21 Hand 38.37 12.09 Fingers 40.89 8.57 Face and throat 44.88 11.93 Mouth 87.56 15.49 b Sensory Tongue 30.84 7.31 Leg and foot 20.1 13.57 Arm 49.45 1.47 Hand 42.83 4.41 Fingers 47.97 13.29 Face and throat 25.47 10.85 Mouth 41.91 17.36 Trunk 22.96 2.33 a P=.005 b P<.001

Preul MC et al. 1 ABBREVIATIONS: MNI, Montreal Neurological Institute