Since the introduction of fluorescent calcium indicators and the subsequent development of capacities for real-time monitoring and imaging of calcium movements in the intact cells studied in isolation, in situ and in vivo, the complex and vital calcium signaling system has been illuminated, proving calcium signals to be excellent universal reporters of cellular activity. In "Calcium Measurement Methods," a team of renowned experts in the field contribute methods dedicated to calcium imaging in neural cells with a balance between the main principles of calcium imaging and specific applications of the technique to neural tissues. The book's contents show how the combination of different indicators and recently developed microscopic techniques lead to spectacular successes in the imaging of neural cells in the living brain in both physiological and pathophysiological models. As a volume in the successful Neuromethods series, the chapters provide authoritative reviews including up-to-date detailed protocols of the most commonly used approaches in the field.

Cutting-edge and concise, "Calcium Measurement Methods" serves as an ideal reference to aid the many scientists worldwide engaged in calcium imaging of the nervous system."

Many people believe that pleasure and desire are obstacles to reasonable and intelligent behavior. In The Pleasure Center, Morten Kringelbach reveals that what we desire, what pleases us--in fact, our most base, animalistic tendencies--are actually very important sources of information. They motivate us for a good reason. And understanding that reason, taking that reason into account, and harnessing and directing that reason, can make us much more rational and effective people. In exploring the many facets of pleasure, desire and emotion, Kringelbach takes us through the whole spectrum of human experience, such as how emotion fuels our interest in things, allowing us to pay attention and learn. He investigates the reward systems of the brain and sheds light on some of the most interesting new discoveries about pleasure and desire. Kringelbach concludes that if we understand and accept how pleasure and desire arise in the complex interaction between the brain's activity and our own experiences, we can discover what helps us enjoy life, enabling us to make better decisions and, ultimately, lead happier lives.

Electroreception has become one of the most revealing areas in the study of the neural basis of behavior, and neurobiologists recognize it as a model sensory system for experimental study. Through studies of electroreception, researchers have gained extensive knowledge about a complete sensory system, from molecular biology to computation, communication, and behavior. The book Electroreception will examine the behavior, structure, and function of the electrosensory systems of fish and other vertebrates. As a comprehensive volume on the subject, the book will serve as both an introduction to the study of electroreception and a reference and review volume for researchers in related fields.

The field of stem cell biology is geared towards translation into clinical practice through in vitro tissue production and regeneration therapy. Since the discovery of adult neurogenesis, much attention has been put on the study of differentiation of stem cells into neural cell types and the development of model systems for stroke and neurodegenerative diseases.

In addition to chapters on therapeutic applicability of embryonic, very small-embryonic like, mesenchymal stem and neural progenitor cells, this book covers signalling mechanisms guiding induction to differentiation and cell diversification. Furthermore, fundamental aspects of stem cell biology and neurogenesis, such as the importance of proliferation induction, programmed cell death and the function of glia in differentiation of stem cells and development of neuronal circuits, are also highlighted. In vitro cultures of embryonic, mesenchymal and neural stem cells as well as mobilization of endogenous stem and precursor cells for brain repair and replacement therapy in neurological disorders are important issues of this book.

Each chapter is written by researchers who are leaders in the field and provides an invaluable resource for information on the most current advances in the field and possible therapeutic applications, with discussions of controversial issues and areas of emerging importance. By providing an up-to-date and critical view of the state of Science, we hope that this book shall be a base for exciting scientific ideas regarding functions and therapeutic applications of stem cells in the adult brain. The book is directed to neuroscientists, physicians, students and all who are engaged and interested in the exciting and rapidly expanding field of modern neuroscience and stem cell biology.

This volume contains information on the diagnosis, therapy, and prognosis of spinal tumors. Various aspects of different major types of spinal tumors (astrocytomas, ependymomas, and oligodendroglioma) are discussed. Insights into the understanding of molecular pathways involved in tumor biology are explained. Classification of intradural spinal tumors, including the percentages of each of the three major types, is detailed. Symptoms, radiological features, and clinicopathological parameters of spinal cord tumors are explained. Diagnosis, outcome, and prognosis of primary spinal cord and oligodendroglioma are discussed. Diagnosis of some other spinal tumors (e.g., pilomyxoid and chordomas) is also explained. The useful role of neuroimaging in diagnosing spinal teratoid/rhabdoid and gangliogliomas is included. A wide variety of treatments of a number of spinal cord tumor types are presented in detail. Therapies discussed include chemotherapy, surgery, radiosurgery, stereotactic radiosurgery, Cyberknife stereotactic radiotherapy, standard radiation alone, and rhenium-186 intracavity radiation. Also are duiscussed embolozation and spondylectomy. The usefulness of transplantation of human embryonic stem cells-derived oligodendrocyte progenitors and motoneuron progenitors in the repair of injured spinal cord is emphasized. Symptoms of the advent of spinal tumors are pointed out. Introduction to new technologies and their applications to spinal cord tumor diagnosis, treatment, and therapy assessment are explained.

Mechanisms of neural plasticity enable the encoding and memorization of information based on sensory inputs and can be harnessed to partially restore function after CNS assault such as stroke or head trauma. In the present book, experts from the field of visual system plasticity describe and evaluate the evidence for neural mechanisms proposed to underlie CNS plasticity in the major divisions of the brain dedicated to visual processing, the retina, sub-cortical structures and cortex. We present studies from a wide variety of disciplines that range from molecular biology to neurophysiology and computer modeling. Leading investigators discuss their own work, and integrate this research with colleagues from other specializations. The book points out future applications for this research including clinical uses and engineering within the biomedical sciences. This book is an exciting and thought provoking read for all levels of science enthusiast interested in the physical basis of learning and cognition.

High quality leads provide the foundation for the discovery of successful clinical development candidates, and therefore the identi?cation of leads is an essential part of drug discovery. The process for the identi?cation of leads generally starts with the screening of a compound collection, either an HTS of a relatively large compound collection (hundreds of thousands to one million plus compounds) or a more focused screen of a smaller set of compounds that have been preselected for the target of interest. Virtual screening methods such as structure-based or pharmacophore-based searches can complement or replace one of the above approaches. Once hits are identi?ed from one or more of these screening methods, they need to be thoroughly characterized in order to con?rm activity and identify areas in need of optimization. Finally, once fully characterized hits are identi?ed, preliminary optimization through synthetic modi?cation is carried out to generate leads. Parallel optimization of all properties, including biological, physicochemical, and ADME is the most ef?cient approach to the identi?cation of leads. Hit characterization is described in the previous chapter. The focus of this chapter is on hit optimization and the identi?- tion of leads. After a general overview of these processes, examples taken from the literature since 2001 will be used to illustrate speci?c points. There are also a number of excellent reviews covering the lead identi?cation process [1-6].

Singularity Hypotheses: A Scientific and Philosophical Assessment offers authoritative, jargon-free essays and critical commentaries on accelerating technological progress and the notion of technological singularity. It focuses on conjectures about the intelligence explosion, transhumanism, and whole brain emulation. Recent years have seen a plethora of forecasts about the profound, disruptive impact that is likely to result from further progress in these areas. Many commentators however doubt the scientific rigor of these forecasts, rejecting them as speculative and unfounded. We therefore invited prominent computer scientists, physicists, philosophers, biologists, economists and other thinkers to assess the singularity hypotheses. Their contributions go beyond speculation, providing deep insights into the main issues and a balanced picture of the debate.

This book discusses the main milestones of early brain development and the emergence of consciousness, within and outside the mother's environment, with a particular focus on the preterm infant. These insights offer new perspectives on issues concerning fetal pain, awareness in newborns, and the effects of current digital media on the developing infant brain. Among the topics covered: * Brain patterning, neural proliferation, and migration. * The stress of being born and first breaths. * The stream of consciousness. * Parenting and stimulating the brain of the child. * The moral status of the fetus and the infant. Infant Brain Development is an excellent resource for researchers, clinicians and related professionals, and graduate students across a variety of disciplines including developmental psychology, pediatrics, neurobiology, neuroscience, obstetrics, nursing and medical ethics. It is written with historic and philosophical remarks of interest for a broad readership. --- "This book is a joy to read for anyone interested in understanding where biology is heading in the 21st century, and it is essential for those who work in child development." Eric Kandel, University Professor, Columbia University, Co-Director, Mortimer B. Zuckerman Mind Brain Behavior Institute, Nobel Laureate in Medicine 2000 "With the precision of a scientist, the depth of a philosopher, and the heart and sensitivity of a pediatrician, Hugo Lagercrantz weaves a story as readable and engrossing as any mystery novel, linking brain, genes, the environment, and behavior to explain the development of the mind of a newborn. A tour de force!" Patricia K. Kuhl, The Bezos Family Foundation Endowed Chair in Early Childhood Learning, Co-Director, Institute for Learning & Brain Sciences, University of Washington "This book is a noble and valiant effort by Dr. Lagercrantz to explain the immensely complex issue of normal and pathological development of the human brain in simple terms that are accessible to the general public." Pasko Rakic, Duberg Professor of Neuroscience and Neurology, Yale University School of Medicine

Robotized Transcranial Magnetic Stimulation describes the methods needed to develop a robotic system that is clinically applicable for the application of transcranial magnetic stimulation (TMS). Chapter 1 introduces the basic principles of TMS and discusses current developments towards robotized TMS. Part I (Chapters 2 and 3) systematically analyzes and clinically evaluates robotized TMS. More specifically, it presents the impact of head motion on the induced electric field. In Part II (Chapters 3 to 8), a new method for a robust robot/camera calibration, a sophisticated force-torque control with hand-assisted positioning, a novel FTA-sensor for system safety, and techniques for direct head tracking, are described and evaluated. Part III discusses these developments in the context of safety and clinical applicability of robotized TMS and presents future prospects of robotized TMS. Robotized Transcranial Magnetic Stimulation is intended for researchers as a guide for developing effective robotized TMS solutions. Professionals and practitioners may also find the book valuable.

Efferent sensory systems have emerged as major components of processing by the central nervous system. Whereas the afferent sensory systems bring environmental information into the brain, efferent systems function to monitor, sharpen, and attend selectively to certain stimuli while ignoring others. This ability of the brain to implement these functions enables the organism to make fine discriminations and to respond appropriately to environmental conditions so that survival is enhanced. Our focus will be on auditory and vestibular efferents, topics linked together by the inner ear connection.

The biological utility of the efferent system is striking. How it functions is less well understood, and with each new discovery, more questions arise. The book that is proposed here reflects our vision to share what is known on the topic by authors who actually have made the observations.

Muller glial cells ensheath all retinal neurons in vertebrate retinae. There are a multitude of functional interactions between neurons and Muller cells, including delivery of the light stimuli to the photoreceptor cells in the inverted vertebrate retina, a 'metabolic symbiosis' with the neurons, and the processing of visual information. Muller cells are also responsible for the maintenance of the homeostasis of the retinal extracellular milieu (ions, water, neuro-transmitter molecules, and pH). In vascularized retinae, Muller cells may also be involved in the control of angiogenesis, and the regulation of retinal blood flow. Virtually every disease of the retina is associated with a reactive Muller cell gliosis which, on the one hand, supports the survival of retinal neurons but, on the other hand, may accelerate the progress of neuronal degeneration:

Muller cells protect neurons via a release of neurotrophic factors. However, gliotic Muller cells display a dysregulation of various neuron-supportive functions. This contributes to a disturbance of retinal glutamate metabolism and ion homeostasis, and causes the development of retinal edema and neuronal cell death. Moreover, there are diseases evoking a primary Muller cell insufficiency, such as hepatic retinopathy and certain forms of glaucoma. Any impairment of supportive functions of Muller cells, primary or secondary, must cause and/or aggravate a dysfunction and loss of neurons, by increasing the susceptibility of neurons to stressful stimuli in the diseased retina.

Muller cells may be used in the future for novel therapeutic strategies to protect neurons against apoptosis (i.e. somatic gene therapy), or to differentiate retinal neurons from Muller/stem cells. Meanwhile, a proper understanding of the gliotic responses of Muller cells in the diseased retina, and of their protective vs. detrimental effects, is essential for the development of efficient therapeutic strategies that use and stimulate the neuron-supportive/-protective - and prevent the destructive - mechanisms of gliosis.

The main topic of the book is a reconstruction of the evolution of nervous systems and brains as well as of mental-cognitive abilities, in short "intelligence" from simplest organisms to humans. It investigates to which extent the two are correlated. One central topic is the alleged uniqueness of the human brain and human intelligence and mind. It is discussed which neural features make certain animals and humans intelligent and creative: Is it absolute or relative brain size or the size of "intelligence centers" inside the brains, the number of nerve cells inside the brain in total or in such "intelligence centers" decisive for the degree of intelligence, of mind and eventually consciousness? And which are the driving forces behind these processes? Finally, it is asked what all this means for the classical problem of mind-brain relationship and for a naturalistic theory of mind.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in many physiological and pathological processes. The field of MMP research is very important due to the implications of the distinct paralogs in both human physiology and pathology. Over-activation of these enzymes results in tissue degradation, producing a wide array of disease processes such as rheumatoid arthritis, osteoarthritis, tumor growth and metastasis, multiple sclerosis, congestive heart failure, and others. Thus MMP inhibitors are candidates for therapeutic agents to combat a number of diseases. The present book discusses the design and development of different classes of inhibitors of important classes of MMPs, such as gelatinases and collagenases. The articles focus specifically on structure-activity relationships of all classes of compounds and on their modes of action and specificity of binding with the receptors based on experimental and theoretical studies. These studies constitute a valuable asset for all those involved in drug development.

This volume will cover a variety of topics, including child language development; hearing loss; listening in noise; statistical learning; poverty; auditory processing disorder; cochlear neuropathy; attention; and aging. It will appeal broadly to auditory scientists-and in fact, any scientist interested in the biology of human communication and learning. The range of the book highlights the interdisciplinary series of questions that are pursued using the auditory frequency-following response and will accordingly attract a wide and diverse readership, while remaining a lasting resource for the field.

This book discusses the ways in which mathematical, computational, and modelling methods can be used to help understand the dynamics of intracellular calcium. The concentration of free intracellular calcium is vital for controlling a wide range of cellular processes, and is thus of great physiological importance. However, because of the complex ways in which the calcium concentration varies, it is also of great mathematical interest.This book presents the general modelling theory as well as a large number of specific case examples, to show how mathematical modelling can interact with experimental approaches, in an interdisciplinary and multifaceted approach to the study of an important physiological control mechanism. Genevieve Dupont is FNRS Research Director at the Unit of Theoretical Chronobiology of the Universite Libre de Bruxelles; Martin Falcke is head of the Mathematical Cell Physiology group at the Max Delbruck Center for Molecular Medicine, Berlin; Vivien Kirk is an Associate Professor in the Department of Mathematics at the University of Auckland, New Zealand; James Sneyd is a Professor in the Department of Mathematics at The University of Auckland, New Zealand.

This volume represents a valuable and readily reproducible collection of established and emerging techniques for neuronal cell death research. Conveniently divided into four parts, sections cover a series of techniques for the molecular, structural, functional and genomic characterization of dying neurons, a number of protocols that are of primary interest in neuropathology and in experimental neuropathology, a series of gene engineering techniques to obtain and manipulate neuronal stem cells and progenitors, to prepare HSV-1 vectors for the gene therapy, and to CNS transplantation of bone marrow stem cells, and finally, some very interesting protocols for the study of cell death in non-mammalian models. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Neuronal Cell Death: Methods and Protocols seeks to serve a large audience of scientists that are currently active in the field or are willing to enter such an exciting and still expanding area of neurobiology.

Rapid advances in cognitive neuroscience and converging technologies have led to a vigorous debate over cognitive enhancement. This book outlines the ethical and social issues, but goes on to focus on the policy dimensions, which until now have received much less attention. As the economic, social and personal stakes involved with cognitive enhancement are so high, and the advances in knowledge so swift, we are likely to see increasing demands for government involvement in cognitive enhancement techniques. The book therefore places these techniques in a political context and brings the subsequent considerations and divisions to the forefront of the debate, situating their resolution within the milieu of interest group politics. The book will provide a starting point from which readers can develop a balanced policy framework for addressing such concerns.

This book illustrates remarkable roles of metal ions in the neuropathophysiology of stroke, which is a major cause of death and disability worldwide. Metal ions have unique chemical properties that allow them to play diverse roles in the brain. They regulate excitability and function as co-factors in cellular and genetic signaling pathways and therefore, have important roles ranging from essential to toxic. For the first time, the dyshomeostasis and pathophysiological actions of these metals in stroke are discussed systematically in thirty-six chapters in one volume. Highlighted metal ions include: Aluminum (Al) Arsenic (As) Cadmium (Cd) Calcium (Ca) Copper (Cu) Iron (Fe) Magnesium (Mg) Manganese (Mn) Mercury (Hg) Nickel (Ni) Potassium (K) Selenium (Se) Sodium (Na) Zinc (Zn)

This book introduces a new cyberphysical system that combines clinical and basic neuroscience research with advanced data analysis and medical management tools for developing novel applications for the management of epilepsy. The authors describe the algorithms and architectures needed to provide ambulatory, diagnostic and long-term monitoring services, through multi parametric data collection. Readers will see how to achieve in-hospital quality standards, addressing conventional "routine" clinic-based service purposes, at reduced cost, enhanced capability and increased geographical availability. The cyberphysical system described in this book is flexible, can be optimized for each patient and is demonstrated in several case studies.

The Springer Handbook of Auditory Research presents a series of comprehensive and synthetic reviews of the fundamental topics in modern auditory research. The v- umes are aimed at all individuals with interests in hearing research including advanced graduate students, post-doctoral researchers, and clinical investigators. The volumes are intended to introduce new investigators to important aspects of hearing science and to help established investigators to better understand the fundamental theories and data in fields of hearing that they may not normally follow closely. Each volume presents a particular topic comprehensively, and each serves as a synthetic overview and guide to the literature. As such, the chapters present neither exhaustive data reviews nor original research that has not yet appeared in pe- reviewed journals. The volumes focus on topics that have developed a solid data and conceptual foundation rather than on those for which a literature is only beg- ning to develop. New research areas will be covered on a timely basis in the series as they begin to mature.

Theoretical Mechanics of Biological Neural Networks develops an engineering science for the description of neuroclectric signalling of biological neural networks in terms of the underlying neurobiological mechanisms. The primary theoretical contribution of the book is to show how to describe the co-ordinated electrical activity of arbitrarily complex neural networks in terms of a single governing principle ' for each significant component in the same way that Newton's formulation of classical mechanics allows one to express force-motion relationships for arbitrarily complex mechanical systems in terms of one fundamental principle of motion for each constituent element.;Practically, the book shows how to generate mathematical and computational representations Of' the co-ordinated electrical activity of neural networks, ranging from individual neurons to composite systems of interconnected networks. Complete listings of several general purpose computer programs embodying the theory are included in the book.

Withtherecentlyperceivedincreaseinincidenceofautismandtherealizationthat "autism"mayactuallybe"autisms"withsubsetsofaffectedindividuals,researchers have been pursuing the possibility that there may be multiple etiologies for the disorder.Althoughmostautismstudieshavefocusedongeneticsandadvancedn- roimaging,thereisapaucityofresearchaimedatdeterminingtheneurochemical basisofautism.Identifyingcoreneuralsubstratesorkeybiomarkersisessentialto understandingthemechanisticbasisthatmayinpartunderlie"autisms."Alterations inmolecules,proteins,receptors,andsynapticelementsaresomeofthecontrib- ingsubstratesthatcouldresultinaltereddevelopmentalprocesses,changedsynaptic function,andaberrationsinconnectivity.Itisnowapparentthatmultiplebrainareas are affected in autism, and neuropathological defects have been described within corticalandsubcorticalnetworks.Althoughrecentprogresshasbeenmadeinid- tifyingsomeofthegenesthatmayunderliethedisorder,muchattentionhasalso beengiventoepigeneticand/orenvironmentalfactorsthatmaycontributetosubsets ofautisticindividuals. The contributors to this book were hand selected because of their expertise in their respective ?elds. Individually each chapter presents a unique perspective into the clinical, developmental, neurochemical, and/or physical chemical basis of autism. The contributing authors summarize current research ?ndings in their respective areas and also present novel ideas and propose hypotheses and p- sible mechanisms that may be operative during development and the potential consequencesofhavingdefectsinspeci?cmolecules,receptors,orgenes. Thesubtitle"FromMoleculestoMinicolumns"wasinsertedbecauseofmuch recent attention given to alterations in the basic organization of mini- or mic- columns of neurons in cerebral cortical areas in autism. These especially include prefrontalcorticalareasthatundergoanovergrowthduringearlypostnataldevel- mentinmanyindividualswithautism.Tothisend,theworldrenownedDr.Alan Peters,theneuroanatomistthatoriginallydescribedmini-ormicro-columnaror- nizationinthecerebralcortex,wasrecruitedtowriteachapterinthisbookgiving hisexpertperspectiveontheissueinautism. The book begins with highly respected clinician, Dr. Margaret L. Bauman, DirectoroftheLADDERSclinicintheBostonarea,withaclinicalandmedicalp- spectiveofautismdiscussingetiologies,clinicalpresentation,earlyidenti?cation, vii viii Preface advancementsinmedicalcare,andassociateddisorders. Inthechapter"TheMale Prevalence in Autism Spectrum Disorders: Hypotheses on its Neurobiological Basis",ItalianresearchersDrs.FlavioKellerandLilianaRutapresentneuroch- ical hypotheses as the basis for the predominance of male prevalence in autism discussing the possible roles of estrogen, testosterone, oxytocin, and vasopressin in the organization of brain circuits and hemispheric specialization. Psychiatrist Dr. Ricardo Vella relates neuropathologies in autism, in the limbic and cereb- lar regions, to speci?c behaviors and presents a developmental perspective and hypotheses regarding emotional and attachment behaviors in autistic individuals.