The Lateralized Brain: The Neuroscience and Evolution of Hemispheric Asymmetries

By Sebastian Ocklenburg and Onur Güntürkün

The Lateralized Brain: The Neuroscience and Evolution of Hemispheric Asymmetries is an up-to-date teaching resource for neuroscience faculty members that teach courses concerning hemispheric asymmetries. The book provides students with all relevant information on the subject, while also giving aspiring researchers in the field an up-to-date overview of relevant, previous work. It is ideal for courses on hemispheric asymmetries, that is, the functional or structural differences between the left and the right hemispheres of the brain, and also highlights how the widespread use of modern neuroimaging techniques, such as fMRI and DTI has completely changed the way hemispheric asymmetries are currently investigated.

According to the preface, the main aim of The Lateralized Brain is to provide "an up-to-date teaching resource on hemispheric asymmetries … [and] to introduce undergraduate students of all levels to the fascinating topics of hemispheric asymmetries" (p. xv)… (Sebastian Ocklenburg and Onur Güntürkün) have succeeded admirably in their stated aim and are to be congratulated on undertaking the mammoth task they set themselves. They can be proud of what they have accomplished.~ Alan A. Beaton, Department of Psychology, Swansea University, Swansea, UK, in Laterality: Asymmetries of Body, Brain and Cognition, July, 2018.

• Includes references to key articles, books, protocols and online resources for additional, detailed study
• Presents classic studies that helped define the field
• Covers key concepts and methods that are explained in separate call out boxes for quick overview
• Provides introductory short stories (e.g. classic clinical cases) as a starting point for each chapter

• Language: English
• Publisher: Academic Press
• Release date: Nov 16, 2017
• ISBN: 9780128034538

Sebastian Ocklenburg

Sebastian Ocklenburg is a post-doc in the biopsychology lab at Ruhr-University Bochum in Germany. Born in Duisburg, Germany, he knew since primary school that he wanted to become a scientist. After obtaining his bachelor’s and master’s degree in psychology, Sebastian conducted his PhD thesis on the genetics and neurophysiology of hemispheric asymmetries. For this work, he was awarded the prestigious Heinz-Heckhausen award by the German Society for Psychology. Subsequently, he worked as a post-doc in the Bergen fMRI group in Norway, before returning to Germany. Since the very beginning of his career, Sebastian holds a deep fascination with understanding how hemispheric asymmetries develop. His work focuses on answering this question using an integrative multi-method approach including techniques from neuroimaging, electrophysiology and molecular genetics. Sebastian is member of the Global Young Faculty (GYF) and the International Society for Behavioral Neuroscience (ISBN). He authored more than 60 papers on hemispheric asymmetries and other topics in international peer-reviewed journals, including top journals like Neuron or eLife.

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Chapter 1

Brain Asymmetries—Two Millennia of Speculation, Research and Discoveries

Sebastian Ocklenburg and Onur Güntürkün

Abstract

Scientific inquiries on brain asymmetries in humans started in the early decades of the 19th century. They began with anatomical observations on lateralized cortical folding patterns and then became publicly known by the discovery of language asymmetry by Pierre Paul Broca in 1865. This then was not only a discovery—it was a scientific revolution. In a single step, it introduced two central concepts of neuroscience: first, functions can be cortically localized, and second, left and right hemispheres differ in certain functions. This great success in the discovery of language asymmetry could not be replicated for handedness. Still, the neural foundations of handedness are not fully understood. All attempts to relate it to gross neuroanatomical asymmetries or the crossing pattern of descending corticospinal fibers failed. So, we are still in dire need for a Broca of handedness. The last aspect on the history of brain asymmetries reviewed in this chapter is on facial asymmetries and their possible relation to brain functions. This story starts with the Venus of Milo—a Hellenistic statue that is on display in the Louvre. The story takes twists and turns with many scientists fighting battles against each other until it became firmly embedded in research on asymmetries of language and emotion.

Keywords

Gustave Dax; Pierre Paul Broca; language asymmetry; handedness; face asymmetry; Venus of Milo

Outline

Introductory Short Story 1

Early Reports on Brain Asymmetries 2

The Discovery of Language Asymmetry 4

Are Functions Localized at Cortical Level? 5

Pierre Paul Broca Enters the Scene 6

The Fight for Priority 9

The Many Mysteries of Handedness 10

Is Right-Handedness Caused by an Uneven Blood Supply to the Arms? 13

Are Genes Making the Right Arm Strong? 14

Handedness in the Brain 15

Face Asymmetries 16

Summary 21

Sample Questions 23

References 23

Introductory Short Story

"I have been betrayed. I have been humiliated. They stole my ideas; they neglected my insights and never allowed me to stand on the pedestal of fame that I deserve. I am from the south of France, deep from the province. They never said it publicly, but their eyes gave it away: With my short and pot-bellied stature, my thick southern accent and my lack of this special way of talking that they call ‘distinguished intellect’; I, Gustave Dax, will always be inferior to the academic elite of Paris. My father Marc Dax had discovered that language was governed by the left hemisphere. Yes, I know: Father’s methods of analysis were crude. But, still they were accurate enough to make the point. Father had presented his findings at a congress in Montpellier in 1836. Now the scientists in Paris say that no trace of such a presentation can be found. In 1863 I submitted the collection of findings from my deceased father and more than hundred further cases to the Academy in Paris. A huge data base; absolutely solid and with only a single possible way of interpretation: Language is controlled by the left hemisphere. Thus, the human brain is asymmetrically organized. What a discovery! But what did the Academy do? They sat on my manuscript for 20 months to then reject it in the most dismissive way!

Then came this young fellow; Pierre Paul Broca. Elegant, brilliant, good looking, and with a quality of his scientific work that was vastly superior to anything that I have ever seen. Broca gradually collected more and more cases and finally concluded in 1865 that language was controlled by the third convolution of the frontal lobe on the left side. Language had a cortical location and this location was in the left hemisphere. This is what Broca said. And he simply neglected my manuscript from 1863. He also neglected my paper from 1865 that I had published 2 months before Broca’s final publication. I was simply brushed aside. The Parisian elite can’t stand that a provincial fellow won the race. Broca turned into a scientific celebrity. Wherever he showed up, people kneeled before him as if he was royalty. None of these people ever heard my name. But mine is the priority and I will fight for it until my last day."

On June 12, 1966 a plaque was unveiled in front of the house in Sommières in which Gustave Dax was born. At the same time the little place in front of this house was renamed as Le Place des deux Docteurs Dax. The ceremony to which the President of the World Federation of Neurology had come was to commemorate the discovery by Dr. Marc Dax (1770–1837) and his son, Dr. Gustave Dax (1815–93) on the role of the left hemisphere for language. This discovery had happened about a century before and it was now high time to recognize the contribution of these two physicians. The plaque is small and hangs a bit too high for easy reading. But, on sunny days when people wait for an empty seat in one of the cafes, they may have time to read that it was father and son Dax, who discovered the location of language. And that it happened here, deep in the province.

Early Reports on Brain Asymmetries

The true scientific history of brain asymmetries starts in the second half of the 19th century. This was a time of extraordinary discoveries that completely changed the view on brain functions and set the scene for a modern account of neuroscience that persists today. The epicenter of most of these early breakthroughs on hemispheric asymmetries was France—the leading science nation of its time. But long before this golden era, several scholars foreshadowed what was to follow.

The oldest scientific account on brain asymmetries stems from late antiquity and was written as a medical treatise from an anonymous author who repeatedly refers in his writing to some even older Greek medical texts. His treatise survived about 1000 years possibly by diverse transcriptions, and was finally discovered in a codex that dates from the end of the 11th or the beginning of the 12th century. This codex bears the title De semine (On sperm) and was possibly in possession of the monastery of Saint Pantaleon in Cologne (Germany). In the part on brain asymmetries, the author states: There are accordingly two brains in the head. The one gives us our intellect, the other provides the faculty of perception. That is to say: the brain on the right side is the one that perceives, whereas the left brain is the one which understands (translation by Lokhorst¹, p. 302).

How did the author come to this conclusion? According to Lokhorst¹ the ancient view was that the soul was constituted by pneuma—a subtle entity that spreads from the heart to the whole body. Since ancient people often observed that in slaughtered animals and dead people the left cardiac ventricle and the aorta are relatively bloodless after death, it was assumed that the left part of the heart is filled with pneuma and so should be the seat of the soul. Then, it was further assumed that left and right brain hemispheres are connected to left and right heart ventricles, respectively. Since the intellect was seen as superior to the faculty of perception, the first scholarly text on brain asymmetries concluded that the superior faculty of intellect has its place on the left side of the brain, leaving the right hemisphere for the inferior faculty of perception.

A much more empirically driven early account on hemispheric asymmetries was the classic book by Arthur Wigan, The Duality of the Mind.² The discovery that sparked Wigan’s conviction was a chance finding that he had made as a young physician during an autopsy³: The brain of a dead man of about 50 years of age had only one hemisphere. But this person had conversed rationally and even wrote verses just days before his death. Thus, a single hemisphere was sufficient to process all aspects of the mind. Arthur Wigan concluded that if… one brain be a perfect instrument of thought—if it be capable of all the emotions, sentiments, and faculties, which we call in the aggregate, mind—then it necessarily follows that man must have two minds with two brains: And however intimate and perfect their unison in their natural state, they must occasionally be discrepant when influenced by disease, either direct, sympathetic, or reflex (Wigan², pp. 201–202). Indeed, it is possible that the loss of one entire hemisphere during very early ontogeny can be (nearly) fully compensated.⁴ However, from this fact it doesn’t follow that the two hemispheres harbor independent minds in the healthy brain. Wigan had published a very radical proposal that was not accepted, and was therefore neglected by the scientific community of his time. More than one century later, however, his thoughts on two parallel minds started to reverberate in a new and fresh way when a young PhD student in Pasadena tested a split-brain patient and discovered that this person indeed seemed to have two minds in one skull. But this is a different story and will be discussed in Chapter 3, The Connected Hemispheres—The Role of the Corpus Callosum for Hemispheric Asymmetries.

In the beginning of the 19th century the main scientific debate was on localization of function. Were the cortical fields doing the same everywhere in a holistic manner or was it possible to locate diverse functions in different areas? This debate also ignited the first discussions about possible asymmetries of cortical functions. Treviranus⁵ was the first to discover that: Der Mensch hat sehr zahlreiche, sehr tiefe und in beyden Hälften unsymmetrische Windungen. Am großen Gehirn der Affen findet das Gegentheil statt (Humans have a multitude and deep convolutions that are asymmetrically organized in the two hemispheres. This is different from the forebrain of monkeys).⁵ Similarly, Françoise Magendie, the founder of experimental physiology, surmised a few years later in 1824: They (the cortical gyri) are differently disposed in every individual; those of the right side are not disposed as those of the left. It would be an interesting approach to endeavor to discover if there exists any relation between the number of circumvolutions and the perfection, or imperfection, of the intellectual faculties—between the modifications of the mind and the individual disposition of the cerebral circumvolutions.⁶ Magendie’s ruminations run contrary to the basic assumptions of his time: Throughout the first half of the nineteenth century, Francois-Xavier Bichat’s⁷ theory of anatomical and functional symmetry of the cerebral hemispheres prevailed. Bichat’s theory implied that lesions of either side of the brain would have the same effects. But soon, Magendie’s ideas could be grounded on solid data. Together with his friend Louis Pierre Gratiolet, François Leurat, the first true comparative neuroanatomist, published a groundbreaking book in 1839 on the cortical organization of mammals, including humans.⁸ His goal was to understand the evolution of cognition based on the comparative analysis of cortical folding patterns. Leurat observed, similarly to Treviranus, that the arrangement of cortical gyri became more irregular and more asymmetric with phylogenetic proximity to humans. Was it conceivable that asymmetries of cortical functions exist, and that they represent an advanced organizational pattern of the human brain? The first functional evidences for this idea were, meanwhile, collected in a very unlikely place.

Marc Dax (1770–1837) was a local physician in Sommières, a picturesque little town in the far south of France. Dax worked at a home for the elderly and was a careful observer with a keen interest in the study of language. In 1836, one year before his death, he wrote a paper on the association between aphasic disorders and lesions of the left hemisphere for presentation at the Congrès Méridional, a celebration of achievements from the south of France, which was to be held in nearby Montpellier. The paper contained more than 40 clinical observations collected since the year 1800. Dax reported on the loss of word memory in a cavalry captain after a sabre blow to the left side of his head, the association of right-sided paralysis and the loss of speech after left a hemisphere stroke, and about many more similar cases.⁹ Not all cases represented his own observations as some only had been told to him. In no case did he have verification through autopsy and in several cases, he couldn’t even be sure that the brain had been damaged at all. Therefore, he knew that he was about to make a claim of exceptional importance. But he also knew that his data base was not fully convincing. As a result, he shied away from presenting his paper at the conference. Instead, his manuscript collected dust at his home. He also had, however, given several copies to colleagues. As will be outlined in the next section, these copies later played a significant role in a bitter fight on the priority of the discovery of language asymmetries.

The Discovery of Language Asymmetry

According to the official version, brain asymmetries of language were discovered by Pierre Paul Broca (1824–80) between 1861 and 1865. Broca’s findings must be understood within the context of two important scientific disputes of his time.¹⁰ The first dispute was ignited by the second volume of the book by Leuret and Gratiolet¹¹ (1859). This book came with an extended analysis of the comparative description of the cortex and also contained a review on cortical ontogeny. The authors made the case that the left hemisphere was developing faster than the right one. As a result, it became possible that behavioral asymmetries like handedness were a mere result of the differential developmental speed of the cortex.¹² Thus, suddenly two highly respected scientists alluded to the possibility that a well-known behavioral asymmetry (handedness) may have grounding in neuroanatomy. The second dispute that was laid out before Broca’s discoveries can be called the most important clash of neuroscience of the first two thirds of the 19th century. The central question was: Do different functions have different cortical localizations? The person who brought this discussion to the table was seen by some as a genius, but by others as a charlatan.

Are Functions Localized at Cortical Level?

Back in 1800 Franz Joseph Gall (1758–1828), a German neuroanatomist and physiologist, published his conception that came to be known as phrenology.¹³ Based on casual observations on people in his immediate surrounding, Gall developed the idea that 27 psychological faculties—like courage, vanity, memory for words, or the sense of speech—had separate cortical localizations. Individuals with a preponderance of some of these psychological qualities had a higher cortical volume at the respective localization and thus developed a cortical bump at this spot. Gall was convinced that the elevations on the human skull were caused by pressure exerted from the cortex underneath. Consequently, a personality inventory could be achieved by reconstructing the uneven landscape of the human skull—a method that Gall named Cranioscopy and that would later be known as phrenology (Fig. 1.1).¹⁴ Gall’s idea became a huge success story and gave him a formidable income. However, soon the scientific audience saw him as nothing more than a mere swindler. This negative reaction to his theory overshadowed the possibility that Gall could have been partly right albeit for the wrong reasons and that brain functions might indeed have cortical localizations. In mid-19th century, the word phrenology was associated so much with a grotesquely unscientific approach to brain function, that even today, more than 200 years after the appearance of Gall’s book, critiques of modern brain imaging studies use this catchword to express their rejection for a kind of science that too easily associates superficially assumed psychological entities with certain brain regions.

Figure 1.1 Franz Joseph Gall and his concept of phrenology. According to Gall, small elevations on the skull hint to pronounced mental faculties that are located in the underlying area of the cortex. On the right side, some of these faculties are shown alongside with their location on the skull. Some examples are: 1: religious thoughts; 2: benevolence; 4: memory for items; 9: memory for places; 18: pride; 19: vanity; 24: love; 25: bravery. Language (location 12) is in the lateral upper part of the eye sockets, beneath the location of the memory of physiognomies (location 13) and that of words (location 14). Reproduced from the Wellcome Library, London, licensed under CC-BY 4.0.

It was the famous neurologist Hugo Liepmann (1863–1925) who, about a century after Gall’s publication, succinctly formulated what is wrong with phrenology: It is known that Gall discounted his merits by departing from too naïve propositions. On the one side, he saw the morphological parcellations of the brain in lobes and gyri, and on the other side he knew about folk psychological entities like sense of ownership, sense of language, sense of religion, etc. Then he assumed that his task is to find a brain location for all of these mental functions. The critical point for functional localizations, however, starts with the insight that not every mental entity that is demarcated in language, in folk psychology, or psychological science has to have a corresponding localization in the brain. Thus, not every conceivable entity that is drawn from our mental life has to have a place in a lobe or in a cortical region (translated from Liepmann¹⁵, pp. 1–2).

After Gall’s advent, the concept of functional localization was so strongly dismissed among scientists that only a person with great courage and an immaculate scientific record could openly defend the idea that the cortex had functional localizations. Jean-Baptiste Bouillaud (1796–1881) was such a person. Bouillaud was president of the French Académie de Médicine, dean of the Faculty of Medicine in Paris and commander of the legion d’honneur. Bouillaud was convinced that brain diseases were scientific windows into the mechanisms of mind but have to be analyzed with upmost care and verified by subsequent autopsies. He also was convinced that, not so much in single cases, but large numbers of carefully conducted studies would reveal the truth. Towards the end of his career, Bouillaud had accumulated about 500 perfectly analyzed cases with diverse brain injuries and could derive detailed insights from this wealth of data. Bouillaud strongly defended Gall’s claim that language was governed by the frontal lobes and even announced that he would give 500 Francs to anyone who would be able to present an example of a deep lesion of the anterior lobes that did not affect language.¹⁶

Pierre Paul Broca Enters the Scene

Bouillaud’s son-in-law was Simon Alexandre Ernest Aubertin, who was chef de clinique at the Charité. Aubertin presented on April 4, 1861 at the Société d’Anthropologie in the Rue René Panhard Nr. 1 a case of a patient who had shot himself in the head, and so exposing his brain. This man was still alive but dying. Aubertin decided to run a simple experiment with this patient by gently pressing a spatula on the anterior cortex while the man was talking. Immediately the man stopped, but continued talking when as soon as the spatula was taken away.¹⁷ This presentation was followed by a heated debate between Aubertin and Gratiolet. Aubertin strongly believed in functional localizations. Gratiolet accepted developmental asymmetries of the cortex, but denied functional localizations. In the audience was Pierre Paul Broca, the young secretary of the Société. Broca leaned towards the localizationist view of Bouillaud and Aubertin since his own microscopic studies had shown how heterogeneous the microarchitecture of the cortex is. In addition, his clinical cases seemed only to make sense when assuming differences of function across the cortex. What was missing was a perfect clinical case in which a close relationship between structure and function could be shown. It came 8 days after the heated debate that followed Aubertin’s presentation.

On April 12, 1861, an epileptic patient named Leborgne was transferred to Broca’s surgical ward at the hospital Bicètre. The man had lost his speech long before and could only utter the word Tan-Tan, which had become his nickname. Due to gangrene in his paralyzed right leg, Leborgne was bound to die soon. Broca invited Aubertin to jointly analyze the patient. Aubertin accepted this invitation and was impressed by the clarity of the case. He predicted that Leborgne had a lesion in the frontal cortex. A few days later, Leborgne died. An autopsy was done and Broca could reveal that the starting point of the brain disease was the third convolution of the frontal lobe on the left side. In two successive presentations in front of the Société d’Anthropologie, Broca could demonstrate, after meticulous analysis, a close relationship between the functional language deficit and the anatomical reconstruction of the lesion.¹⁸,¹⁹ Shortly thereafter, another patient was brought to Broca. His name was Lelong and he could only utter the words oui, non, tois, toujours, and Lelo. His language comprehension was intact and he had no paralysis of the mouth or the tongue. Lelong died a few months later and an autopsy revealed a lesion at exactly the same location (Fig. 1.2)²⁰ as that found in Leborgne. This time it was Broca’s turn to come under heavy fire from Louis Pierre Gratiolet. The line of the battlefield was like before: Broca defended localization and dismissed asymmetry; Gratiolet was willing to accept asymmetry but regarded the localizationist’s claims as nonsense and mere phrenology.

Figure 1.2 The brains of Leborgne (A, B) and Lelong (C, D) as a whole and with a higher magnification of the location of the lesion in the 3rd convolution of the frontal lobe. Figure from Dronkers NF, Plaisant O, Ilba-Zizen MT, Cabanis EA. Paul Broca’s historic cases: high resolution MR imaging of the brains of Leborgne and Lelong. Brain 2007;130:1432–1441, used with permission from the publisher.

Broca started to collect more cases. And he developed his trademark approach that made him to one of the towering scientists of his time: Broca was very careful in his observations and his thinking. He always thought of all possible counterarguments and tested them. He was cautious not to call a deficit an aphemie (what later became today’s aphasia) without checking all options that could produce a similar deficit without really reflecting a deficit in the production of language. In addition, he meticulously conducted autopsies to verify all possible lesions in the brain. In 1863, Broca presented eight cases with lesions in the third convolution of the frontal lobe with severe aphasia.²¹ He commented with amazement that they were all in the left hemisphere, but that he would refrain to draw too strong conclusions from this before having collected more cases (Fig. 1.3).

Figure 1.3 Drawing of the lateral view of the brain from Pierre Paul Broca. The lesions of his patients with aphemie were always located in the 3rd convolution (labeled 3) of the frontal lobe on the left side. Portrait by P. Petit reproduced from the Wellcome Library, London, licensed under CC-BY 4.0.

Finally, on June 15, 1865 Pierre Paul Broca presented a large number of cases before the members of the Société Anthropologie. All the collected cases had left hemisphere lesions in a region that was later called the Broca area of the brain. In all the analyzed cases, the patients had suffered from a deficit to produce language without having major difficulties to understand language. Broca concluded his insights with the sentence: Nous parlons avec l’hémisphère gauche (We are talking with the left hemisphere) (Broca²², p. 384). This sentence uttered in the Rue René Panhard Nr. 1 of Paris is the official starting point of brain asymmetry research (Fig.