Against vivisection: Charcot and Pitres' discovery of the human motor cortex and the birth of modern neurosurgery and of the surgical treatment of epilepsy.

This article addresses the discrepancy between Edouard Hitzig's and David Ferrier's findings on the cortical localization of movements in animals and Jean-Martin Charcot's findings in humans. The results of Hitzig's and Ferrier's vivisections were criticized by experimentalists in England and France as discordant, irreproducible, and inconclusive, and they were rejected by clinicians as irrelevant. Charcot addressed the gap between animal and human motor function by correlating motor deficits and focal epileptic seizures in patients to their autopsy findings. By this method he discovered the functional organization of the human motor cortex and produced the first accurate human motor brain map. Ferrier, William Osler, and Hughlings Jackson acknowledged Charcot's findings, and his findings guided the first neurosurgeons in localizing and resecting intracranial mass lesions presenting with focal epileptic seizures. Although his contributions in these fields have been neglected by modern historians, Charcot made significant contributions to the neurobiology of the human motor system, to epileptology, and to the birth of modern neurosurgery.

Muscles or Movements? Representation in the Nascent Brain Sciences.

The idea that the brain is a representational organ has roots in the nineteenth century, when neurologists began drawing conclusions about what the brain represents from clinical and experimental studies. One of the earliest controversies surrounding representation in the brain was the "muscles versus movements" debate, which concerned whether the motor cortex represents complex movements or rather fractional components of movement. Prominent thinkers weighed in on each side: neurologists John Hughlings Jackson and F.M.R. Walshe in favor of complex movements, neurophysiologist Charles Sherrington and neurosurgeon Wilder Penfield in favor of movement components. This essay examines these and other brain scientists' evolving notions of representation during the first eighty years of the muscles versus movements debate (c. 1873-1954). Although participants agreed about many of the superficial features of representation, their inferences reveal deep-seated disagreements about its inferential role. Divergent epistemological commitments stoked conflicting conceptions of what representational attributions imply and what evidence supports them.

Nineteenth- and twentieth-century brain maps relating to locations and constructions of brain functions.

This article is an outline of the transition in "brain maps" used to illustrate locations of cortical "centers" associated with movements, sensations, and language beginning with images from Gall and Spurzheim in the nineteenth century through those of functional magnetic resonance imaging in the twenty-first century. During the intervening years, new approaches required new brain maps to illustrate them, and brain maps helped to objectify and naturalize mental processes. One approach, electrical stimulation of the cerebral cortex-exemplified by Fritsch and Hitzig in 1870, Ferrier in 1873, and Penfield by 1937-required brain maps showing functional centers with expanded and overlapping boundaries. In another approach, brain maps that linked cortical centers to account for the complex syndromes of aphasia, apraxia, alexia, and agraphia were initially constructed by Baginsky in 1871, Wernicke in 1874, and Lichtheim in 1885, then later by Lissauer in 1890, Dejerine in 1892, and Liepmann in 1920, and eventually by Geschwind in 1965 and others through the late twentieth century. Over that intervening time, brain maps changed from illustrations of points on the cerebral cortex where movements and sensations were elicited to illustrations of areas (centers) associated with recognizable functions to illustrations of connections between those areas that account for complex symptoms occurring in clinical patients. By the end of this period, advancements in physics, mathematics, and cognitive science resulted in inventions that allowed brain maps of cortical locations derived from cognitive manipulations rather than from the usual electrical or ablative manipulations. "Mental" dependent variables became "cognitive" independent variables.

Evolution of Human Brain Atlases in Terms of Content, Applications, Functionality, and Availability.

Human brain atlases have been evolving tremendously, propelled recently by brain big projects, and driven by sophisticated imaging techniques, advanced brain mapping methods, vast data, analytical strategies, and powerful computing. We overview here this evolution in four categories: content, applications, functionality, and availability, in contrast to other works limited mostly to content. Four atlas generations are distinguished: early cortical maps, print stereotactic atlases, early digital atlases, and advanced brain atlas platforms, and 5 avenues in electronic atlases spanning the last two generations. Content-wise, new electronic atlases are categorized into eight groups considering their scope, parcellation, modality, plurality, scale, ethnicity, abnormality, and a mixture of them. Atlas content developments in these groups are heading in 23 various directions. Application-wise, we overview atlases in neuroeducation, research, and clinics, including stereotactic and functional neurosurgery, neuroradiology, neurology, and stroke. Functionality-wise, tools and functionalities are addressed for atlas creation, navigation, individualization, enabling operations, and application-specific. Availability is discussed in media and platforms, ranging from mobile solutions to leading-edge supercomputers, with three accessibility levels. The major application-wise shift has been from research to clinical practice, particularly in stereotactic and functional neurosurgery, although clinical applications are still lagging behind the atlas content progress. Atlas functionality also has been relatively neglected until recently, as the management of brain data explosion requires powerful tools. We suggest that the future human brain atlas-related research and development activities shall be founded on and benefit from a standard framework containing the core virtual brain model cum the brain atlas platform general architecture.

Cortical Brain Functions ­ The Brodmann Legacy in the 21st Century

In 1909, Korbinian Brodmann described 52 functional brain areas, 43 of them found in the human brain. More than a century later, his devoted functional map was incremented by Glasser et al in 2016, using functional nuclear magnetic resonance imaging techniques to propose the existence of 180 functional areas in each hemisphere, based on their cortical thickness, degree of myelination (cortical myelin content), neuronal interconnection, topographic organization, multitask answers, and assessment in their resting state. This opens a huge possibility, through functional neuroanatomy, to understand a little more about normal brain function and its functional impairment in the presence of a disease.

Brief history of electrical cortical stimulation: A journey in time from Volta to Penfield.

OBJECTIVE: To recount the evolution of Electrical Cortical Stimulation (ECS) in localizing brain functions with an emphasis on epilepsy, and a discussion of related instruments and personnel. DESIGN/METHODS: Literature review through historical archives implementing chain-referral sampling. RESULTS: There were important milestones leading to the incorporation of ECS into practice: 1. Aldini's (1802) first known stimulation of exposed brain to defend Galvani's views on excitability in the frog-leg experiment against Volta's, ironically by employing the Voltaic pile. 2. Animal experiments in the 19th-century to study the brain and to optimize the procedure: Rolando (1809) reported on motor induction, Fritsch and Hitzig (ca. 1870) introduced the concepts of bipolar and threshold stimulation, and Ferrier (1873) generated reproducible homunculi in animals. 3. Parallel to 2, advances were made based on clinical observations by Bravais, Todd, Jackson, and Broca among others. 4. First known stimulation in conscious humans by Bartholow (1874) led to catastrophic outcomes. Horsley (1886) performed first intraoperative stimulation on Jackson's epileptic patient. 5. Advances accelerated in the first-half of the 20th century with Cushing (1909) performing first awake-craniotomy eliciting sensory responses to Penfield's work culminating in standardization of clinical use and generation of detailed maps including the famous sensory-motor homunculi. Parallel advances in instrumentation were made from the Leyden jar (1745) to present customizable current-controlled stimulators. CONCLUSIONS: ECS is commonly used in neurosurgery for localization of brain functions and is the benchmark for research studies. Significant leaps have been made since ECS first used in the 19th century. It evolved to remain the gold standard for localization of human brain functions in the 21st century.

Impact of World War I on brain mapping.

Although much tragedy was experienced during World War I (WWI), the nature of the war and the advancements of weaponry led to a change in the quality and quantity of injuries which were conducive for study. This paper discusses how trauma during WWI led to advances in brain mapping from occipital injuries. Gordon Holmes was a British neurologist who was able to create a retinotopic map of the visual cortex from studying more than 400 cases of occipital injuries; his work has contributed immensely to our understanding of visual processing. There have been many extensions from Holmes' work in regard to how we analyze other sensory modalities and in researching how the brain processes complex stimuli such as faces. Aside from the scholastic benefit, brain mapping also has functional use and can be used for neurosurgical planning to preserve important structures. With the advent of more advanced modalities for analyzing the brain, there have been initiatives in total brain mapping which has added significantly to the body of work started by Holmes during WWI. This paper reviews the history during WWI that led to advances in brain mapping, the lasting scholastic and functional impact from these advancements, and future improvements.

Under the Mind's Hood: What We Have Learned by Watching the Brain at Work.

Imagine you were asked to investigate the workings of an engine, but to do so without ever opening the hood. Now imagine the engine fueled the human mind. This is the challenge faced by cognitive neuroscientists worldwide aiming to understand the neural bases of our psychological functions. Luckily, human ingenuity comes to the rescue. Around the same time as the Society for Neuroscience was being established in the 1960s, the first tools for measuring the human brain at work were becoming available. Noninvasive human brain imaging and neurophysiology have continued developing at a relentless pace ever since. In this 50 year anniversary, we reflect on how these methods have been changing our understanding of how brain supports mind.

Multisensory Integration and the Society for Neuroscience: Then and Now.

The operation of our multiple and distinct sensory systems has long captured the interest of researchers from multiple disciplines. When the Society was founded 50 years ago to bring neuroscience research under a common banner, sensory research was largely divided along modality-specific lines. At the time, there were only a few physiological and anatomical observations of the multisensory interactions that powerfully influence our everyday perception. Since then, the neuroscientific study of multisensory integration has increased exponentially in both volume and diversity. From initial studies identifying the overlapping receptive fields of multisensory neurons, to subsequent studies of the spatial and temporal principles that govern the integration of multiple sensory cues, our understanding of this phenomenon at the single-neuron level has expanded to include a variety of dimensions. We now can appreciate how multisensory integration can alter patterns of neural activity in time, and even coordinate activity among populations of neurons across different brain areas. There is now a growing battery of sophisticated empirical and computational techniques that are being used to study this process in a number of models. These advancements have not only enhanced our understanding of this remarkable process in the normal adult brain, but also its underlying circuitry, requirements for development, susceptibility to malfunction, and how its principles may be used to mitigate malfunction.

[PET imaging for better understanding of normal and pathological neurotransmission]. / L'imagerie TEP pour une meilleure compréhension de la neurotransmission normale et pathologique.

Positron emission tomography imaging is still an expanding field of preclinical and clinical investigations exploring the brain and its normal and pathological functions. In addition to technological improvements in PET scanners, the availability of suitable radiotracers for unexplored pharmacological targets is a key factor in this expansion. Many radiotracers (or radiopharmaceuticals, when administered to humans) have been developed by multidisciplinary teams to visualize and quantify a growing numbers of brain receptors, transporters, enzymes and other targets. The development of new PET radiotracers still represents an exciting challenge, given the large number of neurochemical functions that remain to be explored. In this article, we review the development context of the first preclinical radiotracers and their passage to humans. The main current contributions of PET radiotracers are described in terms of imaging neuronal metabolism, quantification of receptors and transporters, neurodegenerative and neuroinflammatory imaging. The different approaches to functional imaging of neurotransmission are also discussed. Finally, the contributions of PET imaging to the research and development of new brain drugs are described.

TITLE: L'imagerie TEP pour une meilleure compréhension de la neurotransmission normale et pathologique. ABSTRACT: La neuroimagerie des récepteurs cérébraux a commencé au début des années 1980. Aujourd'hui, quelque quarante ans plus tard, l'imagerie par tomographie d'émission de positons (TEP) est toujours un domaine en expansion dans les études précliniques et cliniques cherchant à explorer le cerveau et son fonctionnement normal et pathologique. Outre les améliorations apportées aux caméras TEP et à l'analyse d'images, la disponibilité de radiotraceurs est un facteur déterminant de cette expansion. De nombreux radiotraceurs (ou radiopharmaceutiques, lorsque injectés chez l'Homme) ont été mis au point par des équipes pluridisciplinaires pour visualiser et quantifier un nombre croissant de récepteurs, transporteurs, enzymes et autres cibles moléculaires du cerveau. Le développement de nouveaux radiotraceurs TEP représente un défi passionnant, du fait du grand nombre de cibles et de fonctions neurochimiques qui restent encore à explorer. Dans cet article, nous resituons le contexte de développement des premiers radiotraceurs précliniques et leur passage à l'Homme. Les principales contributions actuelles des radiotraceurs TEP sont décrites en termes d'imagerie du métabolisme neuronal, de quantification des récepteurs et des transporteurs, d'imagerie neurodégénérative et neuroinflammatoire. Les différentes approches d'imagerie fonctionnelle de la neurotransmission sont également abordées. Enfin, les apports de l'imagerie TEP à la recherche et au développement de nouveaux médicaments du cerveau sont décrits.

Jean Talairach: a cerebral cartographer.

Although French psychiatrist-turned-neurosurgeon Jean Talairach (1911-2007) is perhaps best known for the stereotaxic atlas he produced with Pierre Tournoux and Gábor Szikla, he has left his mark on most aspects of modern stereotactic and functional neurosurgery. In the field of psychosurgery, he expressed critique of the practice of prefrontal lobotomy and subsequently was the first to describe the more selective approach using stereotactic bilateral anterior capsulotomy. Turning his attention to stereotaxy, Talairach spearheaded the team at Hôpital Sainte-Anne in the construction of novel stereotaxic apparatus. Cadaveric investigation using these tools and methods resulted in the first human stereotaxic atlas where the use of the anterior and posterior commissures as intracranial reference points was established. This work revolutionized the approach to cerebral localization as well as leading to the development of numerous novel stereotactic interventions by the Sainte-Anne team, including tumor biopsy, interstitial irradiation, thermal ablation, and endonasal procedures. Together with epileptologist Jean Bancaud, Talairach invented the field of stereo-electroencephalography and developed a robust scientific methodology for the assessment and treatment of epilepsy. In this article the authors review Talairach's career trajectory in its historical context and in view of its impact on modern stereotactic and functional neurosurgery.

A brief history of cortical functional localization and its relevance to neurosurgery.

Modern cortical mapping is a cornerstone for safe supratentorial glioma resection in eloquent brain and allows maximal resection with improved functional outcomes. The unlocking of brain functionality through close observation and eventually via cortical stimulation has a fascinating history and was made possible by contributions from early physician-philosophers and neurosurgery's founding fathers. Without an understanding of brain function and functional localization, none of today's modern cortical mapping would be possible.

History of awake mapping and speech and language localization: from modules to networks.

Lesion-symptom correlations shaped the early understanding of cortical localization. The classic Broca-Wernicke model of cortical speech and language organization underwent a paradigm shift in large part due to advances in brain mapping techniques. This initially started by demonstrating that the cortex was excitable. Later, advancements in neuroanesthesia led to awake surgery for epilepsy focus and tumor resection, providing neurosurgeons with a means of studying cortical and subcortical pathways to understand neural architecture and obtain maximal resection while avoiding so-called critical structures. The aim of this historical review is to highlight the essential role of direct electrical stimulation and cortical-subcortical mapping and the advancements it has made to our understanding of speech and language cortical organization. Specifically, using cortical and subcortical mapping, neurosurgeons shifted from a localist view in which the brain is composed of rigid functional modules to one of dynamic and integrative large-scale networks consisting of interconnected cortical subregions.

Mapping language dominance through the lens of the Wada test.

The sodium amytal test, or Wada test, named after Juhn Wada, has remained a pillar of presurgical planning and is used to identify the laterality of the dominant language and memory areas in the brain. What is perhaps less well known is that the original intent of the test was to abort seizure activity from an affected hemisphere and also to protect that hemisphere from the effects of electroconvulsive treatment. Some 80 years after Paul Broca described the frontal operculum as an essential area of expressive language and well before the age of MRI, Wada used the test to determine language dominance. The test was later adopted to study hemispheric memory dominance but was met with less consistent success because of the vascular anatomy of the mesial temporal structures. With the advent of functional MRI, the use of the Wada test has narrowed to application in select patients. The concept of selectively inhibiting part of the brain to determine its function, however, remains crucial to understanding brain function. In this review, the authors discuss the rise and fall of the Wada test, an important historical example of the innovation of clinicians in neuroscience.

Roberts Bartholow: the progenitor of human cortical stimulation and his contentious experiment.

Roberts Bartholow, a physician, born and raised in Maryland, was a surgeon and Professor in Medicine who had previously served the Union during the Civil War. His interest in scientific research drove him to perform the first experiment that tested the excitability of the human brain cortex. His historical experiment on one of his patients, Mary Rafferty, with a cancerous ulcer on the skull, was one of his great accomplishments. His inference from this experiment and proposed scientific theory of cortical excitation and localization in humans was one of the most critically acclaimed topics in the medical community, which attracted the highest commendation for the unique discovery as well as criticism for possible ethical violations. Despite that criticism, his theory and methods of cortical localization are the cornerstone of modern brain mapping and have, in turn, led to countless medical innovations.

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

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 showing 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 with 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%; range, 17%-92%) (P < 0.05). 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.

Kanji (Morphogram) and Kana (Phonogram) Problem in Japanese Alexia and Agraphia.

The kanji and kana (or kanji vs. kana) problem in the Japanese language denotes the dissociation between kanji (morphograms) and kana (phonograms) in reading/comprehension and writing. Since paragraphia of kana in a patient with amyotrophic lateral sclerosis was first reported in 1893, kanji-kana dissociation has been the central topic in Japanese aphasiology. Recent advancements in lesion-to-symptom analyses and functional imaging studies have identified some areas whose damage causes dissociative disturbances of reading or writing between kanji and kana. That is, (1) angular alexia with agraphia causes kanji agraphia; alexia of kana with an angular gyrus lesion is the result of a damage to the middle occipital gyrus; (2) alexia with agraphia for kanji is caused by a posterior inferior temporal cortex (mid-fusiform/inferior temporal gyri; visual word form area) lesion, whereas pure agraphia for kanji is caused by a posterior middle temporal gyrus lesion; and (3) pure alexia, particularly for kanji, results from a mid-fusiform gyrus lesion (Brodmann's Area [BA] 37), whereas pure alexia for kana results from a posterior fusiform/inferior occipital gyri lesion (BA 18/19).

The physiological experiments of Constantin von Economo on the central pathways of mastication and deglutition.

The first study of Constantin von Economo on the mammalian brain was published in 1902. Experiments were carried out in rabbits at the Physiological Institute headed by Siegmund von Exner-Ewarten in Vienna to investigate the central pathways of chewing and swallowing. After placing cortical lesions, Economo applied cortical and subcortical electrical stimulation to obtain masticatory movements, and tracked degenerated fibers by means of the Marchi method. He traced fibers through the internal capsule, ventral nucleus of the thalamus, subthalamic nucleus, substantia nigra and its connections with the motor nucleus of the trigeminal nerve, and nucleus solitarius. He suggested that the substantia nigra is responsible for coordinating alimentation movements, with the involvement of cranial nerves V, VII, IX and X as well. We discuss these findings in a historical and a modern perspective, including the concept of a central pattern generator in the pontine reticular formation and its interaction with the nucleus solitarius. Today we understand that mastication is a voluntary action controlled by motor cortical areas, by motoneurons of the trigeminal, and by a neural pattern generator in the pons. On the other hand, deglutition comprises 'reflex swallowing' triggered by sensory fibers of cranial nerves V, IX and X, and 'voluntary swallowing' which may be controlled by both cortical fields and subcortical areas, such as the internal capsule, the hypothalamus and the mesencephalic reticular formation.