Year: 2017
Type: article
Abstract: The homunculus made his first appearance in the field of neurology on 1 December 1937, when Wilder Penfield and Edwin Boldrey (Fig. 1) published in Brain a 55-page article entitled Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation (Penfield and Boldrey, 1937). The article is filled with painstakingly crafted summaries of data sourced from the cortical stimulation of 126 patients, who were operated under local anaesthesia by Penfield between 1928 and 1936. Compared to previous publications in animals, the authors had the advantage of operating on awake patients and relying on their verbal report of elicited movements and tactile sensation. All patient recordings were collated to obtain the first comprehensive map of motor and somatosensory localization in the human brain. This map was visualized as a distorted human-like figure—the homunculus—whose form indicates the amount of cortical area dedicated to motor or somatosensory functions of each body part. Wilder Penfield (left) and Edwin Boldrey (centre), creators of the homunculus (right). The paper had a long-lasting impact on both neurosurgical practice and scientific research. Clinically, it helped to establish direct cortical stimulation as an important method for functional mapping in neurosurgery; scientifically, it reinforced cortical localization as a valid paradigm to understand motor cognition, somatosensory perception and higher cognitive functions more generally. The homunculus was certainly their most striking proposition, but overshadowed other important conclusions made by the authors. First, while acknowledging the lack of histological analysis as a limitation of their study, they were confident they demonstrated the impossibility of confining ‘functional representation within strict cytoarchitectural boundaries’. Second, contrary to what others recorded in animals, the central sulcus of the human brain was not a clear boundary between motor and somatosensory areas. Many stimulations eliciting motor responses were indeed located in the somatosensory cortex of the postcentral gyrus and an even greater proportion of tactile responses in the motor cortex of the precentral gyrus. Surprisingly, the picture that emerged from their work was a clear degree of functional overlap between stimulation fields rather than an orderly sequence of segregated areas as their homunculus suggests. For the 80th anniversary of this seminal paper, the authors’ original findings are re-examined with the intent to clarify the substrate that generated the homunculus, arguably the most reproduced yet unreplicated figure in neuroscience. In the Middle Ages, a homunculus was an artificial humanoid created through alembics and mysterious alchemy. In modern times, Penfield and Boldrey brewed their own version of the homunculus using more controlled, though no less controversial, ingredients. Their approach was systematic and laborious. The neurological homunculus was generated from 170 summary maps of the number and location of stimulation points for each body part, each patiently sketched by Boldrey from Penfield’s operation notes, photographs and drawings. The maps that displayed the positive responses for the toes, legs, trunk, arm, digits, hand, face, eyes, mouth and tongue were used to extract three separate measures for the motor (Fig. 2) and the somatosensory (Supplementary Fig. 1) stimulations: (i) the area for each body part as a 2D surface displayed on the lateral aspect of the central fronto-parietal cortex (Fig. 2B); (ii) the count of the total number of stimulations located in front and posterior to the central sulcus (Fig. 2C); and (iii) the vertical extent of each body area along the central sulcus (Fig. 2D). Representation of the motor stimulations for different body parts. (A) Colour-coding of different body parts. (B) Areas of the surface maps enclosing all motor stimulation points for each body part. (C) Count of the number of stimulations and (D) measurements of the vertical length of the surface maps for each body part. Original data are derived from Penfield and Boldrey (1937). The asterisk indicates the impossibility of generating any measurement of the area and length from the few stimulations recorded for the trunk. Similar maps for the somatosensory stimulations are provided in Supplementary Fig. 1. In their attempt to visually summarize such a large amount of data, the authors faced challenges that are common to modern neuroimaging approaches (Friston et al., 2004). First, the problem of quality control and data transformation, a step that in their case included elimination of artefactual stimulations (e.g. due to epileptic activity, shift in the proximity of the tumour, inability to replicate an evoked response, etc.) and spatial normalization to a common template. These steps were performed solely by visual inspection and manual transcription, processes that are vulnerable to error as evident from the several incongruences between the text and the figures in their paper. In the original text, for example, Penfield and Boldrey report a total of 21 motor stimulations for the mouth and lips (p. 405), which is inconsistent with both Fig. 7 indicating 64 motor points for the same body parts and Fig. 26 in which the stimulation points are more than 100. The second challenge was represented by steps that included statistical transformation and inference. This step must have been particularly arduous in a predigital era and was omitted by the authors. This explains why their maps do not take into account variations in stimulus intensity, the number of subjects stimulated, the number of stimulations per subject, and the degree of overlap and density of the stimulations—all variables that could greatly affect the final results in many ways if not appropriately weighted. For example, the outer borders of those maps, and therefore their overall surface and the vertical extent along the central sulcus are influenced by the dispersion of the data, which in turn is affected by the number of outliers and measurements obtained from each subject. This may have led to a non-uniform overestimation or underestimation of body areas and influenced the final silhouette of the homunculus. Despite these limitations, their work remains an admirable attempt to capture the complexity of the interindividual variability, a pioneering effort that generated one of the most popular and iconic figures in the history of brain mapping, the motor-sensory homunculus. In the original paper, the homunculus is nakedly portrayed as hanging upside-down with his head detached from the body and his pharynx and tongue extirpated from the mouth (Fig. 1). The corresponding figure legend explains that the homunculus ‘was prepared as a visualization of the order and comparative size of the parts of the body as they appear from above down upon the Rolandic cortex’. The terms ‘visualization’, ‘order’ and ‘comparative size’ deserve further scrutiny. Notwithstanding some of the methodological problems described previously, the visualization of the stimulation maps in an anthropomorphic form required omission of an important piece of information contained in the original maps: co-localization of stimulation sites for different body parts. This is clearly shown in Fig. 3, which represents a reanalysis of the original data for the somatosensory stimulations displayed as overlapping maps. Representation of the overlap between the somatosensory surface maps of different body parts. (A) Heat map of the degree of overlap ranging from blue (one body part) to yellow (four or more body parts). (B) Map indicating the overlapping body parts of the homunculus. CS = central sulcus. Original data are derived from Penfield and Boldrey (1937). These maps indicate a high degree of overlay between different body parts, especially in the proximity of the central sulcus. Interestingly, the range of functional overlaps varies from expected—such as tongue and mouth, or arm and hand—to intriguing—such as mouth, arm and hand. While the limitations of their stimulation method and group analysis may have contributed to generating some of the overlaps (Farrell et al., 2007), the frequent observation of co-stimulations in individual brains commonly reported by neurosurgeons during awake surgery (Foerster, 1936; Farrell et al., 2007; Desmurget and Sirigu, 2015) suggests that this result should not be dismissed as solely artefactual. Indeed, using much more sophisticated microstimulation techniques with trains of longer duration, complex coordinated actions can be elicited in the animal brain (Graziano et al., 2002). These have been interpreted as evidence of a functional aggregation of cortical output neurons dedicated to goal-directed synergic actions. It may prove difficult to find a correspondence between co-activations recorded at the micro- and macroscopic level (Desmurget and Sirigu, 2015), but it is interesting to note that Penfield and Boldrey (1937) also reported complex motor responses for single stimulation sites. Some of these responses were characterized by bilateral ‘grimacing’ or ‘vocalization’, both of which require the coordinated activity of several muscles. They also noticed that the most common response for the digits was the movement of all the fingers together or combinations of two fingers that usually cooperate to produce a specific action, such as flexion of the index and thumb. Despite being aware of the possible teleological implications of the anatomical overlapping and co-activation, Penfield and Boldrey chose to highlight functional segregation. Forced to think out a way of displaying their findings they conceived the controversial homunculus (Schott, 1993). Still used in contemporary teaching, the homunculus depicts two aspects of the organization of the pericentral cortex: the topographical order of body part representations and their altered proportions, reflecting the amount of cortex dedicated to a particular function. The motor cortical topography was already well established at the beginning of the 20th century in the brain of monkeys (Leyton and Sherrington, 1917) and humans (Foerster, 1936). Except for some marginal discrepancies, Penfield and Boldrey replicated previous findings in the sense that lower limbs are generally located above the areas of the upper arm, hand and fingers, and even more dorsal to the area of the face, mouth and tongue. However, their homunculus suggested clear-cut and orderly pattern that has rarely been replicated in single patients (Farrell et al., 2007; Desmurget and Sirigu, 2015). In fact, quite often the movement or sensation of the same body part can be elicited by stimulations set widely apart, with other body parts occasionally interposed in between. These observations undermine the concept of a narrow functional localization of movement and somatosensory perception that the homunculus itself has greatly contributed to, and they are also at odds with the results of the precise topography documented in animals (Nelson et al., 1980). Despite the obvious methodological differences, the well-documented observation of a functional recovery after extirpation or damage of specific cortical body areas suggests some caution in interpreting those maps as indicative of a one-to-one correspondence with a specific localized function. In clinical settings, it is probably fair to say that the homunculus provides only a very rough approximation of the likelihood of where the neurosurgeon might find activation of specific body parts; there is no doubt that Penfield and Boldrey were well aware of this. When commenting, for example, on the maps of the face, which is strangely in an upright orientation compared to the rest of the body, the authors admitted that a lack of sufficient stimulation points, of the nose, and the well-established location of the eye movements outside the face representation—in a region anterior to the hands/arms—may have generated a misleading representation. Clearly, the homunculus cannot be taken at face value, but its most arresting feature of disproportionate body parts remains intriguing and largely valid to this day. With its long fingers, large mouth, and lumbering tongue, the homunculus has made a long-lasting impression. Its altered body proportions have been considered the expression of a basic physiological property of the pericentral cortex: the amount of pre- and postcentral cortex dedicated to a body part is not proportional to its size but to the degree of innervation that the cortex receives from or sends to that body part. Because body parts with highly skilled perceptual or motor functions receive a greater deal of neuronal innervation, the proportion of the homuncular body parts is generally thought to reflect specialization of function. This is quite obvious for the ability to discriminate two distant points, which is greater for those body parts that are enlarged in the corresponding cortical homunculus (Supplementary Fig. 2). This functional property of the cortex is certainly not exclusive to the sensory-motor neurons and one wonders why homunculus equivalents for the retinotopic representation of the eye (oculunculus?) or the tonotopic representation of the ear (aurinculus?) have not been put forward. Perhaps, Penfield and Boldrey were bold enough to propose something that they knew would have been considered a mere simplification by many others? After all, Leyton and Sherrington made a similar observation 20 years earlier in the brain of chimpanzees, orangutans and gorillas (Leyton and Sherrington, 1917). While Leyton and Sherrington used numbers to represent this property of the motor cortex (with each number corresponding to the stimulation of a specific group of muscles), Penfield and Boldrey made the controversial choice of using the vertical length along the pericentral cortex (Fig. 2D) to scale their homunculus. Somehow this information went missing when reproductions of the homunculus started to appear in popular textbooks, where its altered proportions were thought to reflect the extension of the area of each body part (Fig. 2B). To rectify this historical error, different versions of a modern motor-sensory homunculus have been generated using the data available in the original paper and presented in Fig. 4. The motor-sensory homunculus redrawn. (A) The proportions of this first homunculus correspond to those of the original reproduced in Fig. 1. All other homunculi in B–D are derived from an average of the motor and somatosensory maps produced in Fig. 2 and Supplementary Fig. 1. (B) Homunculus generated from the surface maps. (C) Homunculus derived from the vertical length measurements. (D) Homunculus derived from the number of stimulation points. All measurements are from Penfield and Boldrey (1937). A comparison of the different homunculi shows that the original version was not proportionally scaled according to the measures reported in the 1937 paper. For example, the size of the tongue was clearly exaggerated in the first homunculus, a misrepresentation that Penfield remedied in a following publication (Penfield and Rasmussen, 1950). Also, when using the surface area, the representation of the arm is much larger and closer to that of the hand and fingers. This is perhaps not surprising as humans engage in many activities that require coordination of reaching (arm) and grasping (hand) for object manipulation. While further homunculi can be generated from data presented in Fig. 2 and Supplementary Fig. 1, these diagrams are only of historical value for the impossibility of validation. Mapping the human homunculus using non-invasive techniques, such as transcranial magnetic stimulation or high field functional MRI, is an alternative but these approaches have their own limitations. Ultimately, the key to understanding the meaning of homunculus does not lie in the details of its figure but in the complexity of its connectional anatomy (Lemon, 1988). It is difficult to guess what expectations Penfield and Boldrey had for their creation. In the original paper, the reader comes face-to-face with the homunculus after 42 pages and 27 figures, introduced with only a few lines of text and a single figure. Such modest presentation was followed by more than 10 years of silence from the authors, after which Penfield decided to replace the older homunculus with a new one, deemed to be of better proportions. But even for the second version of the homunculus Penfield did not have encouraging words: ‘[…] such drawings may easily become confusing if too much significance is attributed to the shape and comparative size’ (Penfield and Rasmussen, 1950). Still the homunculi multiplied in a rapid progression and were described in different regions of the human brain and in other species (Schott, 1993). The homunculus attracted also harsh criticism. Sir Francis Walshe, Consulting Physician to the National Hospital for Neurology and Neurosurgery, reading from his paper given at the Anglo-American Symposium in London stated: ‘[…] nor are the moderns with maps, for homunculi and have made their of to the fair face of but in something quite Penfield was in the and it must have been to his in those not aware of any that might have taken at the but it is evident from Penfield’s publications and after this that to his homunculus as the of a new of brain in his a central of the in all brain functions while to the pericentral as the motor and sensory areas an and a Its is to and with the of motor the of which in the and on out to the in for Penfield the homunculus was not the but the hand that the to its motor to the This was not a new concept as already that brain stimulation not only the but also an of neurons with those (Foerster, 1936). For this brain stimulation has been as a method for anatomy and rather than cortical localization (Lemon, 1988). The homuncular has been studied with (Lemon, et al., and and in animals more with in in The cortex of the homunculus is indeed highly and to of the and through (Lemon, 1988). and from and and to motor neurons or motor neurons receive from cortical neurons and single to several motor The final can be as stimulation or of But the from the motor cortex is not an as it with its to a control of movements in the same the motor cortex with other cortical areas of the and through (Fig. et al., It receives from those anterior areas a fronto-parietal dedicated to motor for reaching and grasping movements et al., It also receives direct from the postcentral somatosensory cortex through a of located the central sulcus. In the human brain these are particularly large in the hand region and in in the region of the mouth and tongue and region of the and et al., This anatomical pattern the homuncular maps derived from stimulation and a direct between the motor and somatosensory This the central sulcus between the motor and somatosensory homunculus is important for and motor movements as by and stimulation in the as well as in humans and patients with et al., In to grasping and the homunculus to less such as and In these the motor homunculus is by the that and sensory and from the anterior to motor regions that control movements et al., of large and of the homuncular (A) the precentral and postcentral In the hand these a large and a high degree of complexity in and yellow In the region of the face and tongue blue and and dorsal region of the and these are less (B) and long of the hand region from a lateral dorsal and posterior The indicates the of the central sulcus. The to the precentral regions of the hand area from the postcentral gyrus and the posterior regions of the and The are within the and the precentral gyrus to the the and the (C) The the cortex to the anterior The from the precentral and cortex are displayed in yellow and note that there is no correspondence between the used for these and the in the previous All from et In the above new on the for the connectional anatomy of the pericentral A modern of the homunculus it as the within an of and dedicated to into the homunculus the key to the precise that results in the coordinated activation of muscles. But the of the the of the homunculus an in the of this many other figures that may is a for the complex neurological that to in their It as a and for this it probably its in (Schott, 1993). For Penfield and Boldrey a hand. to and for some aspects of the homunculus in of their also to and from the for their on the final This work was by the from the This paper represents by the National for at London and and The are those of the and not those of the the or the of Supplementary is available at Brain
Source: Brain
DOI: 10.1093/brain/awx270
Author: Marco Catani
Institution: King's College London
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,570
OpenAlex ID: W2765761153