Margaret Kennard on Sparing and Recovery of Function: A Tribute on The 100th anniversary of Her Birth

Margaret Kennard was an American pioneer in the experimental study of sparing and recovery of function. Her most famous experiments were performed on monkeys and apes at Yale University during the late 1930s and early 1940s. By describing the behavioral effects of brain damage on infantile, juvenile, and older primates, she drew new attention to just how important developmental status can be at the time of neural insult. Kennard also conducted experiments which showed that even adult primates can exhibit significant sparing and recovery of function, especially if brain lesions are made in stages rather than all at once. In many respects, Kennard helped launch the modern era of research on sparing and recovery of function by demonstrating that several factors in addition to lesion locus can affect post-injury performance and by recognizing that, if neural reorganization does occur, it probably takes place in spared parts of the damaged system.     

Classic Studies on the Potential of Stem Cell Neuroregeneration

The 1990s and 2000s were the beginning of an exciting time period for developmental neuroscience and neural stem cell research. By better understanding brain plasticity and the birth of new neurons in the adult brain, contrary to established dogma, hope for therapy from devastating neurological diseases was generated. The potential for stem cells to provide functional recovery in humans remains to be further tested and to further move into the clinical trial realm. The future certainly has great promise on stem cells to assist in alleviation of difficult-to-treat neurologic disorders. This article reviews classic studies of the 1990s and 2000s that paved the way for the advances of today, which can in turn lead to tomorrow’s therapies.     

The Legacy of Camillo Golgi for Modern Concepts of Brain Organization

The experimental advance made by Camillo Golgi's ‘black reaction’ has been universally recognized as the start of the modern revolution in the study of the nervous system. By contrast, his concepts of nervous organization, particularly his support for the idea of a ‘nervous reticulum’, have been universally rejected. The premise of the present paper is that the ideas of a biologist of this stature deserve re-examination. Golgi's arguments for considering the holistic function of the brain seem to come from his experience as a physician, and presage the views of the gestaltists and, more recently, the conceptual underpinnings of artificial neural networks. His interest in the possible nutritional roles of neuronal dendrites can be seen to anticipate current investigations, at the cellular level, of the metabolic basis of brain imaging. These and other currents in Golgi's thought deserve further study.     

The Origin of the Term Plasticity in the Neurosciences: Ernesto Lugaro and Chemical Synaptic Transmission

The Italian psychiatrist Ernesto Lugaro can be regarded as responsible for introducing the term plasticity into the neurosciences as early as 1906. By this term he meant that throughout life the anatomo-functional relations between neurons can change in an adaptive fashion to enable psychic maturation, learning, and even functional recovery after brain damage. Lugaro’s concept of plasticity was strongly inspired by a neural hypothesis of learning and memory put forward in 1893 by his teacher Eugenio Tanzi. Tanzi postulated that practice and experience promote neuronal growth and shorten the minute spatial gaps between functionally associated neurons, thus facilitating their interactions. In addition to discovering the cerebellar cells known by his name and advancing profound speculations about the functions of the glia, Lugaro lucidly foresaw the chemical nature of Synaptic transmission in the central nervous system, and was the first to propose the usage of the terms “nervous conduction” and “nervous transmission” in their currently accepted meaning.     

The legacy of Camillo Golgi for modern concepts of brain organization

The experimental advance made by Camillo Golgi's 'black reaction' has been universally recognized as the start of the modern revolution in the study of the nervous system. By contrast, his concepts of nervous organization, particularly his support for the idea of a 'nervous reticulum', have been universally rejected. The premise of the present paper is that ideas of a biologist of this stature deserve re-examination. Golgi's arguments for considering the holistic function of the brain seem to come from his experience as a physician, and presage the views of the gestaltists and, more recently, the conceptual underpinnings of artificial neural networks. His interest in the possible nutritional roles of neuronal dendrites can be seen to anticipate current investigations, at the cellular level, of the metabolic basis of brain imaging. These and other currents in Golgi's thought deserve further study.     

Instrument Transfer as Knowledge Transfer in Neurophysiology: François Magendie's (1783–1855) Early Attempts to Measure Cerebrospinal Fluid Pressure

François Magendie's (1783–1855) experimental model for measuring blood pressure in animals, which he developed in 1838, had a major impact on French physiology in the nineteenth century, especially upon Etienne-Jules Marey (1830–1904) in Paris. In due course it was also adopted by other European investigators, such as the Leipzig physiologist Carl Ludwig (1816–1895), and by clinicians who developed it into a major measuring tool. Historians of science, however, have paid hardly any attention to Magendie's further laboratory investigations conducted with the assistance of Jean-Louis Marie Poiseuille's (1799–1869) sphygmomètre (blood pressure meter). After having used the apparatus to conduct his experiments on a variety of blood vessels, Magendie also applied the sphygmomètre in 1840 to the ventricular system of the brain in order to measure cerebrospinal fluid (CSF) pressure. But the scope of this new procedure had yet to be defined: the new measuring device invited many speculative interpretations about the meaning of CSF flow for the physiology of the ventricular system in healthy and diseased brain function. As such, Magendie's experiments produced phenomena in very heterogeneous knowledge areas, and CSF measurement was situated at the interface of quite disparate investigative spaces regarding the structure and function of the brain. In his textbook Leçons sur les Fonctions et les Maladies du Système Nerveux (Lectures on the Functions and Diseases of the Nervous System), Magendie described extending application of the measuring “apparatus of Poiseuille” from blood vessels to parts of the brain. The instrument thus became something of a liquidodynamomètre (liquor dynamometer), that paved the way for later applications, including (after 1896) diagnostic intracranial pressure (ICP) measurement by Theodor Kocher (1841–1917) and Harvey Cushing (1869–1939). The current paper focuses on the experimental contingencies that prompted the instrument transfer in Magendie's laboratory and opened up new epistemological perspectives for research in neurophysiology.     

The neurophysiological aspects of Pavlov's theory of higher nervous activity: in honor of the 150th anniversary of Pavlov's birth

Whereas Ivan P. Pavlov (1849-1936) is well-known for his work on classical conditioning, his contribution to neuroscience, particularly his interest in the function of neural centers in the central nervous system, is not as widely known. During the last three decades of his life, Pavlov explored cortical processes by salivary reflex conditioning, a method he used to develop his theory of higher nervous activity. This theory outlined the function of the brain in higher organisms in their interaction with the changing environmental contingencies. As early as 1908, Pavlov outlined a neurophysiological theory as the physiological basis of his theory of higher nervous activity. He maintained that the neural processes of excitation and inhibition irradiate and concentrate among the cortical neural centers. Most of all, he emphasized the plasticity of the cortex in higher organisms' in the Darwinian struggle for existence.     

A brief history of brain archiving

This paper narrates the history of the conservation of the human brain, tracking techniques of brain archiving from the first experiments in the preservation of soft tissue in spirits of alcohol to the latest refinements in cryogenic technology. It traces the changing social and legal conditions that permitted the collection of post mortem human tissue, as well as the increasingly sophisticated technologies that allowed for the preservation and storage of this material. This preliminary survey of brain archiving uses examples of specific collections in order to discuss changes in the techniques, goals and achievements of neural tissue collecting from the mid-eighteenth to the late twentieth centuries.     

A Brief History of Brain Archiving

This paper narrates the history of the conservation of the human brain, tracking techniques of brain archiving from the first experiments in the preservation of soft tissue in spirits of alcohol to the latest refinements in cryogenic technology. It traces the changing social and legal conditions that permitted the collection of post mortem human tissue, as well as the increasingly sophisticated technologies that allowed for the preservation and storage of this material. This preliminary survey of brain archiving uses examples of specific collections in order to discuss changes in the techniques, goals and achievements of neural tissue collecting from the mid-eighteenth to the late twentieth centuries.     

The legacy of the Wernicke-Lichtheim model

Wernicke established an integrated model of the relation between higher cognitive functions and neurophysiological structure of the human brain in 1874. The previous Bouillaud/Broca view envisaged a mosiac map of centres for specific functions, each of which had no clear inter-relation with other centres or with input/output pathways, and with no theoretical explanation of how each centre operated in relation to more basic neural elements. Wernicke's model overcame these objections, and, with Lichtheim's systematization in 1885, the "Wernicke-Lichtheim model" became the standard neuropsychological theory. In this model, each normal higher function is explained in terms of an underlying neural pathway that includes the input/output systems, related functions employ portions of the pathways used for other functions, pathological syndromes are explained by reference to where in the pathway damage occurred, and previously unobserved pathological syndromes can be predicted. Development of the model at the hands of Lissauer, Dejerine, Liepmann, Geschwind, Heilman, and Ellis and Young is traced.     

The origin of the term plasticity in the neurosciences: Ernesto Lugaro and chemical synaptic transmission

The Italian psychiatrist Ernesto Lugaro can be regarded as responsible for introducing the term plasticity into the neurosciences as early as 1906. By this term he meant that throughout life the anatomo-functional relations between neurons can change in an adaptive fashion to enable psychic maturation, learning, and even functional recovery after brain damage. Lugaro's concept of plasticity was strongly inspired by a neural hypothesis of learning and memory put forward in 1893 by his teacher Eugenio Tanzi. Tanzi postulated that practice and experience promote neuronal growth and shorten the minute spatial gaps between functionally associated neurons, thus facilitating their interactions. In addition to discovering the cerebellar cells known by his name and advancing profound speculations about the functions of the glia, Lugaro lucidly foresaw the chemical nature of synaptic transmission in the central nervous system, and was the first to propose the usage of the terms "nervous conduction" and "nervous transmission" in their currently accepted meaning.     

The Neurophysiological Aspects of Pavlov’s Theory of Higher Nervous Activity: In Honor of the 150th Anniversary of Pavlov’s Birth

Whereas Ivan P. Pavlov (1849-1936) is well-known for his work on classical conditioning, his contribution to neuroscience, particularly his interest in the function of neural centers in the central nervous system, is not as widely known. During the last three decades of his life, Pavlov explored cortical processes by salivary reflex conditioning, a method he used to develop his theory of higher nervous activity. This theory outlined the function of the brain in higher organisms in their interaction with the changing environmental contingencies. As early as 1908, Pavlov outlined a neurophysiological theory as the physiological basis of his theory of higher nervous activity. He maintained that the neural processes of excitation and inhibition irradiate and concentrate among the cortical neural centers. Most of all, he emphasized the plasticity of the cortex in higher organisms’ in the Darwinian struggle for existence.     

Brown-Séquard's theory of recovery

Charles Edouard Brown-Séquard used observation of recovered patients and experimental animals to support his theory of cerebral localization. Recovery theories assume that the nervous system is composed of one organ or many, and that each organ has one function or many. From his own studies as well as others, Brown-Séquard concluded that the brain contained at least nine separate organs, each with a single distinct function, and that each organ is organized, not as a geographically isolated cluster of neurons, but as a widely disseminated network. According to his view, function is not uniformly distributed in an organ. Focal necrosis of part of an organ temporarily inhibits the action of distant, undamaged parts; resolution of this inhibition results in recovery. Using this theory of cerebral localization and recovery, Brown-Séquard practiced an early form of scientific neurology.     

Cerebral white matter--historical evolution of facts and notions concerning the organization of the fiber pathways of the brain

Gross and microscopic studies by early investigators led the cerebral white matter from being regarded as an amorphous mass to an intricately organized system of fasciculi that facilitate the highest expression of cerebral activity. Here we pay homage to the anatomists whose observations resulted in the evolution of ideas about the cerebral white matter. We also draw attention to limitations of the earlier methodologies and to some of the conflicts and controversies that have characterized this field and that persist in the current literature. We conclude with brief reference to the principles of organization of the fiber pathways derived from our studies in the monkey using the autoradiographic tract tracing technique, another step in the ongoing investigations of the cerebral white matter. This historical review has contemporary relevance because the fiber pathways of the brain are crucial components of the distributed neural circuits that subserve nervous system function; the clinical manifestations of white matter damage are recognized with greater frequency and clarity; and magnetic resonance imaging tractography has made it possible to view these fiber bundles within the living human brain.     

Instrument transfer as knowledge transfer in neurophysiology: François Magendie's (1783-1855) early attempts to measure cerebrospinal fluid pressure

Fran?ois Magendie's (1783-1855) experimental model for measuring blood pressure in animals, which he developed in 1838, had a major impact on French physiology in the nineteenth century, especially upon Etienne-Jules Marey (1830-1904) in Paris. In due course it was also adopted by other European investigators, such as the Leipzig physiologist Carl Ludwig (1816-1895), and by clinicians who developed it into a major measuring tool. Historians of science, however, have paid hardly any attention to Magendie's further laboratory investigations conducted with the assistance of Jean-Louis Marie Poiseuille's (1799-1869) sphygmomètre (blood pressure meter). After having used the apparatus to conduct his experiments on a variety of blood vessels, Magendie also applied the sphygmomètre in 1840 to the ventricular system of the brain in order to measure cerebrospinal fluid (CSF) pressure. But the scope of this new procedure had yet to be defined: the new measuring device invited many speculative interpretations about the meaning of CSF flow for the physiology of the ventricular system in healthy and diseased brain function. As such, Magendie's experiments produced phenomena in very heterogeneous knowledge areas, and CSF measurement was situated at the interface of quite disparate investigative spaces regarding the structure and function of the brain. In his textbook Le?ons sur les Fonctions et les Maladies du Système Nerveux (Lectures on the Functions and Diseases of the Nervous System), Magendie described extending application of the measuring "apparatus of Poiseuille" from blood vessels to parts of the brain. The instrument thus became something of a liquidodynamomètre (liquor dynamometer), that paved the way for later applications, including (after 1896) diagnostic intracranial pressure (ICP) measurement by Theodor Kocher (1841-1917) and Harvey Cushing (1869-1939). The current paper focuses on the experimental contingencies that prompted the instrument transfer in Magendie's laboratory and opened up new epistemological perspectives for research in neurophysiology.     

Adolf Beck: A Forgotten Pioneer in Electroencephalography

Adolf Beck, born in 1863 at Cracow (Poland), joined the Department of Physiology of the Jagiellonian University in 1880 to work directly under the supervision of the prominent physiology professor, Napoleon Cybulski. Following his suggestion, Beck started experimental studies on the electrical brain activity of animals, especially in response to sensory stimulation. Beck placed electrodes directly on the surface of brain to localize brain potentials that were evoked by sensory stimuli. He observed spontaneous fluctuations in the electrical brain activity and noted that these oscillations ceased after sensory stimulation. He published these findings concerning the electrical brain activity, such as spontaneous fluctuations, evoked potentials, and desynchronization of brain waves, in 1890 in the German language Centralblatt für Physiologie. Moreover, an intense polemic arose between physiologists of that era on the question of who should claim being the founder of electroencephalography. Ultimately, Richard Caton from Liverpool showed that he had performed similar experiments in monkeys years earlier. Nevertheless, Beck added new elements to the nature of electrical brain activity. In retrospect, next to Richard Caton, Adolf Beck can be regarded, together with Hans Berger who later introduced the method to humans, as one of the founders of electroencephalography. Soon after his success, Beck got a chair at the Department of Physiology of the University at Lemberg, now Lviv National Medical University.     

Probing A Traffic Congestion Controversy: A Comment

Ohta (2001) claims to have resolved a die-hard controversy on traffic congestion modeling by defining an inverse aggregate demand function that has traffic density as its argument—in Ohta's terminology the 'primitive term.'Using this demand function, Ohta shows that 'hypercongestion' may very well be an optimal stationary state. This contribution argues that at least if what road users demand is completed trips, and if time spent on the road while traveling implies a cost, then Ohta's approach is fundamentally flawed. Also the conclusion that hypercongestion can be optimal is no longer valid.     

The Tulane Electrical Brain Stimulation Program a historical case study in medical ethics

In 1950 physicians at Tulane University School of Medicine began a program of research on the use of electrical brain stimulation that would span three decades and involve approximately 100 patients. Initially, electrical brain stimulation was used to treat of schizophrenia, but later it was applied to a variety of other conditions. Throughout its history the Tulane research was well publicized in both the professional and lay literature, and for almost twenty years, with rare exception, these accounts were laudatory. However, in the early 1970s this work began to draw sharp public criticism. Despite its public and controversial nature, the Tulane electrical brain stimulation program has received relatively little attention from historians. This review recounts the history of the Tulane program with particular emphasis on the ethical propriety of the work. Factors that shaped the historical context in which the Tulane experiments were conducted are discussed.     

Thomas Graham Brown (1882–1965): Behind the Scenes at the Cardiff Institute of Physiology

Thomas Graham Brown undertook seminal experiments on the neural control of locomotion between 1910 and 1915. Although elected to the Royal Society in 1927, his locomotion research was largely ignored until the 1960s when it was championed and extended by the distinguished neuroscientist, Anders Lundberg. Puzzlingly, Graham Brown's published research stopped in the 1920s and he became renowned as a mountaineer. In this article, we review his life and multifaceted career, including his active neurological service in WWI. We outline events behind the scenes during his tenure at Cardiff's Institute of Physiology in Wales, UK, including an interview with his technician, Terrence J. Surman, who worked in this institute for over half a century.