A Hole in the Head Page 7

46. Dupré, 2005.

  47. Gregg et al., 2001; Winer et al., 2002; Winer et al., 2003; Winer and Cottrell, 2004.

  4

  THE DISCOVERY OF MOTOR CORTEX

  The modern neurophysiology of the cerebral cortex began in 1870 with the discovery by Gustav Fritsch (1838–1927) and Edmund Hitzig (1838–1907) that electrical stimulation of the cerebral cortex produces movements. Their discovery was important for several reasons. First, it was the first clear experimental demonstration of a region of the cerebral cortex involved in motor function. Second, it was the first evidence that the cortex was electrically excitable. Third, it was the first experimental evidence of a topographically organized representation of the body in the brain. Finally, it was the first strong experimental evidence for localization of function in the cerebral cortex. Overall, as Fritsch and Hitzig somewhat immodestly put it,

  by the results of our own investigations, the premises for many conclusions about the basic properties of the brain are changed not a little. . . . some psychological functions, and perhaps all of them . . . need circumscribed centers of the cerebral cortex.1

  This chapter discusses their experiment and its background in the previous two centuries. Fritsch and Hitzig’s basic findings were soon replicated by David Ferrier (1843–1928).2 We consider the differences between the two studies in both method and interpretation and how these differences have continued to reverberate in research on motor cortex.

  FRITSCH AND HITZIG’S EXPERIMENT

  When Fritsch and Hitzig carried out their famous experiments they were young medical Privatdozents (roughly, assistant professors) at the Physiological Institute in Berlin. Previously Fritsch had worked on electric fish and carried out anthropological and geographical studies and served as a battlefield surgeon in the Franco-Prussian war.3 Hitzig was a psychiatrist who had tried the therapeutic use of electricity on his patients. After their collaboration Hitzig continued to work as a psychiatrist and to research on cortical localization in animals.4 Fritsch returned to his earlier interests in anthropology and was particularly concerned with using studies of the eye and hair to establish the superiority of the white race. In the course of the former he coined the terms “fovea” and “area centralis.”5 When the American anatomist C. L. Herrick (founder of the Journal of Comparative Neurology) met Fritsch and Hitzig after they were famous he described them as “splendid specimens of physical development and German culture at its best.”6 Hitzig, who came from a distinguished assimilated Jewish family, was characterized by one of his biographers as “a stern and forbidding character of incorrigible conceit and vanity complicated by Prussianism.”7 Portraits of Fritsch and Hitzig are shown in figure 4.1.

  In their now classic experiment, Fritsch and Hitzig strapped their dogs down on Frau Hitzig’s dressing table, as there were no animal facilities at the Physiological Institute.8 In their early experiments they used no anesthesia or analgesic, although ether surgical anesthesia had been introduced in 1846 and morphine analgesia in 1803.9 Later they did use “morphine narcosis.” They began by removing the cranium and cutting the dura, the dog showing “vivid pain.” They stimulated the cortex with platinum wires with “galvanic stimulation”: brief pulses of monophasic direct current from a battery at the minimum current that evoked a sensation on their tongue.

  Figure 4.1

  Gustav Fritsch (left) and Eduard Hitzig.

  The usual response to this stimulation was a muscle twitch or spasm (Zuckung). Their central findings were that (a) the stimulation evoked contralateral movements, (b) only stimulation of the anterior cortex elicited movements, (c) stimulation of specific parts of the cortex consistently produced the activation of specific muscles, and (d) the excitable sites formed a repeatable, if rather sparse, map of movements of the body laid out on the cortical surface (figure 4.2). They went on to show that lesion of a particular site impaired the movements produced by stimulation of that site. The loss of function was not complete, suggesting to them that there were other motor centers that had not been impaired by the lesion.10

  THE SITUATION BEFORE FRITSCH AND HITZIG

  The background of Fritsch and Hitzig’s discoveries lay in earlier developments stretching back many centuries.

  Before the Eighteenth Century

  From the earliest Western medical writings it was thought that the movement of the body was controlled by the brain. In the Edwin Smith Surgical Papyrus, whose origins lie in the Pyramid Age (about 30th century BCE) there are a number of descriptions of motor dysfunctions after head injury.11 For example, in case 5 the patient “walks shuffing with the sole on the side of him having that injury which is to his skull” (presumably a contracoup injury where a blow to one side of the head causes the brain to impact on the inside of the contralateral skull).

  The Hippocratic doctors (5th century BCE) wrote extensively on the treatment of head wounds and, unlike the author of the Surgical Papyrus, were well aware that head injuries produce contralateral symptoms. However, they were primarily interested in diagnosis and treatment and had little interest in studying the underlying anatomy or physiology.12

  Figure 4.2

  Drawing after Fritsch and Hitzig’s (1870) figure of stimulation sites on the dog’s cortex. Note that the topography is not impressive (Brazier, 1988).

  Galen (129– ca. 213) was the most important figure in classical medicine and biology and a brilliant experimental physiologist and anatomist. (See chapter 2.) His ideas dominated European medicine for more than 1,500 years. This was especially true for his views of brain function and the control of movement. His theories derived from many sources including his training in Alexandria (where human vivisection had been practiced13), his clinical experience (especially as physician to a gladiator school) and his experiments on the spinal cord and brain of animals. Galen distinguished between sensory and motor nerves; he thought nerves were hollow and carried “psychic pneuma.” The brain was supposed to act as a pump that moved the psychic pneuma from the sense organs into the ventricles, then into the motor nerves and finally into the muscles, causing their contraction by inflation.14

  René Descartes (1596–1650) elaborated these ideas by suggesting that the centrally located pineal body directed the pneumatic flow from sense organs into the muscles to expand them.15 Several lines of evidence soon refuted this pneumatic theory of movement. Francis Glisson (1597–1677) and, independently, Jan Swammerdamm (1637–1680) demonstrated that contraction of a muscle did not increase its volume, as it should if the pneuma were swelling it.16 Alexander Monroe (1697–1762) showed that ligating a nerve produced no distal swelling and nothing flowed from a cut nerve. Having disproved pneuma as a transmitter of nerve activity to muscle, Monroe suggested that, instead, electricity might be the mechanism.17

  Electricity and the Nervous System

  The eighteenth century was a period of great activity and interest in the new discoveries about electricity in both the salons and laboratories of the time. Among the intriguing gadgets were electrostatic machines, the Leydon jar (the original capacitor) and the gold leaf electroscope (which detects static electricity). At this time it was realized that man-made electricity and lightning were the same phenomenon as that found in the electric fish, an animal whose shocking properties had been known since classical times. There were a number of attempts to use electricity for therapeutic purposes, including by the French revolutionary Jean-Paul Marat (1743–1793) and the American savant and revolutionary Benjamin Franklin (1706–1790) as well as some ineffectual studies of electrical stimulation of various brains from frog to dead human.18

  The modern study of the electrical nature of nervous activity began with Luigi Galvani’s (1737–1798) demonstration that electrical stimulation of the sciatic nerve in a severed frog’s leg resulted in contraction of the attached muscle. These findings sparked a fierce debate between Galvani and Alessandro Volta (1745–1827) concerning the source of the electricity that caused the legs to become “reanimated.” Volta considered th
e cause to be the use of dissimilar metals, whereas Galvani was convinced that the electricity came from within (“animal electricity”).19 Eventually this led, on one hand, to the development of the electric battery and, on the other hand, through the work of Emil du Bois-Reymond (1818–1896), Julius Bernstein (1839–1917) and others to the discovery of the action potential. Galvani’s results soon prompted attempts to stimulate other nervous structures, but the vast majority of experiments on the electrical stimulation of the cerebral cortex were negative, reinforcing the prevailing view that the cortex had no significant functions.20

  Cortex as “Rind”

  In the eighteenth century, the cerebral cortex was usually dismissed as an insignificant “rind,” which indeed the Latin “cortex” means. The first to microscopically examine the cortex was Marcello Malpighi (1628–1694), professor in Bologna, the founder of microscopic anatomy and discoverer of capillaries. He saw it as made up of little glands with attached ducts. Similar “globules” were reported by many subsequent microscopists.21 Perhaps they were observing pyramidal cells. At least in Malpighi’s case, artifact is a more likely possibility, since modern studies have shown that his globules are more prominent in boiled tissue (which is what he used) than in fresh tissue.22 Malpighi’s view of the brain as a glandular organ was commonly held in the seventeenth and eighteenth centuries, perhaps because it fit with the much earlier, but still persisting, Aristotelian view that the brain was a cooling organ and the Hippocratic theory that it was the source of phlegm.23

  Another common eighteenth-century view of the cortex was that it was largely made up of blood vessels. One of the earliest advocates of this idea was Frederik Ruysch (1638–1731), professor of anatomy in Amsterdam, who noted: “the cortical substance of the cerebrum is not glandular, as many anatomists have described it, nay have positively asserted, but wholly vascular.”24 In this view the convolutions were viewed as mechanisms for protecting the delicate blood vessels of the cortex.

  Willis Gives the Cortex Cognitive Function

  Prior to the nineteenth century there were only a very few figures who advocated significant functions for the cerebral cortex. The first and most important of these was Thomas Willis (1621–1675), who held the Chair of Natural Philosophy at Oxford and was one of the founders of the Royal Society. His Anatomy of the Brain was the first monograph on the brain and dealt with brain physiology, brain chemistry, and clinical neurology as well as brain anatomy.25 Many of its illustrations (such as figure 4.3) were by the architect Sir Christopher Wren, then professor of astronomy at Oxford.

  Willis implicated the “cortical and grey part of the cerebrum” in the functions of memory and will. In his scheme, sensory signals came along the sensory pathways into the corpus striatum where the common sense was located. They were then elaborated into perceptions and imagination in the overlying white matter (then called the corpus callosum, or hard body, since it was harder than the cortex) and then passed to the cerebral cortex where they were stored as memories. According to Willis, the cortex initiated voluntary movement whereas the cerebellum was involved only in involuntary movement.

  Figure 4.3

  Ventral view of the brain from Willis, Cerebri Anatome (1664), drawn by the architect Sir Christopher Wren. Note the detailed drawing and labeling of the cranial nerves and basal brain structures (including the circle of Willis) in contrast to the vague and partially obscured representation of the cerebral cortex, all of which has the single designation A.

  Willis’s ideas on brain function came not only from his dissections but also from his experiments on animals and his correlation of symptoms and pathology in humans. Willis noticed that whereas the cerebellum was similar in a variety of different mammals, the complexity of the cerebral convolutions varied greatly among different animals and this variation was correlated with intellectual ability.

  In spite of the relative importance of the cerebral cortex in Willis’s schema, there is no detailed drawing of the cortex in his works: he apparently never asked Wren or anybody else to produce one (see figure 4.3). In fact, for another 150 years the cortex continued to be drawn as Erasistratus of Alexandria (200 BCE) had first suggested: as coils of the small intestine (figure 4.4).26

  Although Willis was a major figure in his time, his ideas on the importance of the cerebral cortex soon disappeared and the views of the cortex as a glandular, vascular, or protective rind returned to their original dominance. There were two figures who did challenge this view. The first was François Pourfour du Petit (1664–1741), a French army surgeon. He carried out a series of systematic experiments on the effects of cortical lesions in dogs and related them to his clinicopathological observations on wounded soldiers.27 From these studies he realized that the cerebral cortex plays a critical role in normal movement and that this influence is a contralateral one. However, his observations were totally ignored until they were rediscovered much later. Perhaps this was because he did not hold an academic post and published his account in a very limited edition. Yet, his observation that the cortex was insensitive to touch was repeatedly cited to support the views of von Haller, who, as discussed below, was the dominant physiologist of the day. Thus, du Petit’s work demonstrating motor functions of cortex was probably ignored largely because of the anticortex ideology of the time, not because it was published in a minor journal.

  Figure 4.4

  The depiction of the cerebral convolutions by Giulio Casserio (1561–1617). The convolutions are not differentiated in any way and, following Erasistratus, look like intestines (Clarke and Dewhurst, 1972).

  Swedenborg’s Lost Speculations on Cortex

  The second major eighteenth-century figure advocating the importance of the cortex was Emanuel Swedenborg (1688–1772), the founder and mystical prophet of the “New Jerusalem” or Swedenborgian Church (which is still active in the United States and Great Britain). On the basis of reviewing the literature, Swedenborg arrived at an amazing set of prescient ideas on the importance of the cerebral cortex in sensation, cognition, and movement.28

  He argued that the cortex was the highest sensory and motor structure of the brain. In an anticipation of neuron theory, he called the cortical “glandules” described by Malpighi “little brains” (cerebella) and suggested that they were functionally independent and connected by thin fibers (see figure 1.11 in my previous Tales29). These fibers also ran through the white matter and medulla down to the spinal cord and then by way of nerves to parts of the body. The operations of these cerebella were the basis of sensation, mentation, and movement. He seems to have had the idea of somatotopic organization of motor function in the cerebral cortex: He (correctly) localized control of the foot in the dorsal cortex (he called it the “highest lobe”), the trunk in an intermediate site, and the face and hand in the ventral cortex, his “third lobe.”30

  Swedenborg’s philosophical and religious writing had a major impact on European and American philosophers, writers, and artists. Indeed, he continues to be a subject of religious, philosophical, and fringe science tracts. However, he never had any impact on the scientific study of the brain. There is no evidence that contemporary physiologists and anatomists even read his writings on the brain. He never held an academic post or had students, colleagues, or even scientific correspondents. He never seems to have carried out any systematic empirical work on the brain, and his speculations were in the form of baroque and grandiose pronouncements embedded in lengthy books on the human soul by one whose fame was soon to be that of a mystic or madman. Furthermore, some of his more advanced ideas, such as on the organization of motor cortex or the functions of the pituitary gland, did not appear in print until after they were no longer new.31

  Haller Declares the Cortex Insensitive

  In spite of Willis, du Petit, and Swedenborg, who all thought the cortex was a crucial brain structure, the opposite view was very much the dominant one in the eighteenth century. Much more representative and influential was Albrecht von Haller (1708–17
77), professor at Tuebingen and later Bern, who dominated physiology in the middle of the eighteenth century.32 In his monumental Elementa Physiologiae Corporis Humani and his Icones Anatomicae, he divided the organs of the body, as well as parts of the nervous system, into those “irritable” (such as muscle) and those “sensible” (such as the sense organs and nerves). Using animals, he tested the “sensibility” of various brain structures with mechanical stimuli such as picking with a scalpel, puncturing with a needle, and pinching with forceps as well as with electrical and chemical stimuli, such as silver nitrate, sulfuric acid, and alcohol. With these methods he found the cortex completely insensitive. By contrast, he reported the white matter and subcortical structures to be highly sensitive; their stimulation, he said, produced expressions of pain and movement. He concluded that all parts of the cortex had the same function because they were equally insensitive and all subcortical regions were also equivalent because their stimulation had equal effects. Because of his prestige and many students and followers, Haller’s views of the insensitivity and equipotentiality of cortex apparently suppressed contrary observations and ideas on the importance of cortex and persisted well into the next century.33

  Phrenology Calls Attention to the Cortex

  The systematic study of the localization of different psychological functions in different regions of the cerebral cortex begins with Franz Joseph Gall (1758–1828) and his collaborator J. C. Spurzheim (1776–1832), the founders of phrenology. Gall and Spurzheim viewed the brain as an elaborately wired machine for producing behavior, thought, and emotion and the cerebral cortex as a set of organs for carrying out these functions. Their phrenological system was an attempt to relate psychological functions to the organs of the cerebral cortex—to relate brain and behavior. Phrenology was based on four assumptions: (1) Intellectual abilities and personality traits are differentially developed in each individual. (2) These abilities and traits reflect faculties that are localized in specific organs of the cerebral cortex. (3) The development or prominence of these faculties is a function of the activity and therefore the size of the cortical organs. (4) The size of each cortical organ is reflected in the prominence of the overlying skull, i.e., in cranial bumps.34 Phrenological localizations of psychological functions are shown in figures 4.5 and 4.6. The drawing in figure 4.5 is arguably one of the first accurate drawings of the human cortex, reflecting the importance Gall and Spurzheim gave to the cerebral cortex.