Common forms of preventable hearing loss are drug and noise-induced hearing loss which are believed to be produced by a similar mechanism. The generation of reactive oxygen species appears to be a common mechanism mediating hearing loss produced by these different sources. As such, a number of laboratories have focused their research towards identifying the sources of ROS production in the cochlea following administration of chemotherapeutic agents or noise exposure. This led to the identification of ROS generating enzymes, such as xanthine oxidases, nitric oxide synthase, and NADPH oxidases which are activated and/or induced during the development of hearing loss. A consequence of these findings was the implementation of antioxidants in preclinical studies for the treatment of hearing loss. These antioxidants have provided different levels of protection in animal and human studies, but none of these have been approved by the US Food and Drug Administration for the treatment of hearing loss. More recently, it was shown that noise-induced hearing loss was associated with recruitment of inflammatory cells and mediators in the cochlea. This finding would suggest that noise could produce injury to the cochlea which stimulates local and/or circulating inflammatory cells. A similar finding was observed in the cochlea following administration of the anticancer drug, cisplatin. In addition, our laboratory and others have provided a plausible mechanism by which noise or chemotherapeutic agents could stimulate the inflammatory response. Surprisingly, this mechanism involves ROS activation of transcription factors linked to inflammatory processes in the cochlea. These studies have led to the use of anti-inflammatory agents for the treatment of hearing loss. Preliminary studies targeting inflammatory cytokines appear especially promising in preclinical studies. A primary goal of this project is to describe our current understanding of the oxidant hypothesis of noise and drug-induced hearing loss and show how this relates to cochlear inflammation. Several different aspects of the cochlear inflammatory process will be discussed in detail, ranging from the sources of inflammatory cells, chemokines, inflammatory cytokines, and cochlea resident immune cells. Molecular pathways leading to activation of the local inflammatory process will be highlighted and treatment options will be discussed. The relevance of certain clinically used anti-inflammatory interventions, such as trans-typmanic steroids will also be discussed. Furthermore, we will examine recent patents focusing on the use of anti-inflammatory agents for the treatment of drug and noise-induced hearing loss.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors

The Auditory System at the Cocktail Party is a rather whimsical title that points to the very serious challenge faced by listeners in most everyday environments: how to hear out sounds of interest amid a cacophony of competing sounds. The volume presents the mechanisms for bottom-up object formation and top-down object selection that the auditory system employs to meet that challenge. Ear and Brain Mechanisms for Parsing the Auditory Scene by John C. Middlebrooks and Jonathan Z. Simon Auditory Object Formation and Selection by Barbara Shinn-Cunningham, Virginia Best, and Adrian K. C. Lee Energetic Masking and Masking Release by John F. Culling and Michael A. Stone Informational Masking in Speech Recognition by Gerald Kidd, Jr. and H. Steven Colburn Modeling the Cocktail Party Problem by Mounya Elhilali Spatial Stream Segregation by John C. Middlebrooks Human Auditory Neuroscience and the Cocktail Party Problem by Jonathan Z. Simon Infants and Children at the Cocktail Party by Lynne Werner Older Adults at the Cocktail Party by M. Kathleen Pichora-Fuller, Claude Alain, and Bruce A. Schneider Hearing with Cochlear Implants and Hearing Aids in Complex Auditory Scenes by Ruth Y. Litovsky, Matthew J. Goupell, Sara M. Misurelli, and Alan Kan About the Editors: John C. Middlebrooks is a Professor in the Department of Otolaryngology at the University of California, Irvine, with affiliate appointments in the Department of Neurobiology and Behavior, the Department of Cognitive Sciences, and the Department of Biomedical Engineering. Jonathan Z. Simon is a Professor at the University of Maryland, College Park, with joint appointments in the Department of Electrical and Computer Engineering, the Department of Biology, and the Institute for Systems Research. Arthur N. Popper is Professor Emeritus and Research Professor in the Department of Biology at the University of Maryland, College Park. Richard R. Fay is Distinguished Research Professor of Psychology at Loyola University, Chicago. About the Series: The Springer Handbook of Auditory Research presents a series of synthetic reviews of fundamental topics dealing with auditory systems. Each volume is independent and authoritative; taken as a set, this series is the definitive resource in the field.

This work is motivated by the ongoing open question of how information in the outside world is represented and processed by the brain. Consequently, several novel methods are developed. A new mathematical formulation is proposed for the encoding and decoding of analog signals using integrate-and-fire neuron models. Based on this formulation, a novel algorithm, significantly faster than the state-of-the-art method, is proposed for reconstructing the input of the neuron. Two new identification methods are proposed for neural circuits comprising a filter in series with a spiking neuron model. These methods reduce the number of assumptions made by the state-of-the-art identification framework, allowing for a wider range of models of sensory processing circuits to be inferred directly from input-output observations. A third contribution is an algorithm that computes the spike time sequence generated by an integrate-and-fire neuron model in response to the output of a linear filter, given the input of the filter encoded with the same neuron model.

The past decade has seen an exponential increase in our knowledge and understanding of adipose tissue biology. This has coincided with the continued rise in obesity across all generations. Clearly despite substantial advances in research into adipose tissue this still has had limited impact on the on-going obesity epidemic across a majority of countries in the world. This book brings together many leading experts in the field to provide an up to date and comprehensive review of the key aspects of adipose tissue. It therefore includes chapters on evolution, development and inflammation together with a detailed review of brown and beige adipose tissue biology and their potential significance in preventing or combating obesity. These chapters are complemented by those on genetics and gender influences, together with nutrition through the life cycle. Ultimately the book provides an overview of the complexities of adipose tissue biology and the continuing challenge to combat obesity in the 21st century.

This volume aims to connect current ideas and concepts about GI disorders with the search for novel therapeutics. Towards this goal, authors provide a timely state-of-the-art overview of the GI tract in health and disease, current treatment approaches and ongoing developments in drug discovery, and their potential for the better treatment of patients with GI disorders.

This book aims at gathering roboticists, control theorists, neuroscientists, and mathematicians, in order to promote a multidisciplinary research on movement analysis. It follows the workshop " Geometric and Numerical Foundations of Movements " held at LAAS-CNRS in Toulouse in November 2015[1]. Its objective is to lay the foundations for a mutual understanding that is essential for synergetic development in motion research. In particular, the book promotes applications to robotics --and control in general-- of new optimization techniques based on recent results from real algebraic geometry.

In this landmark work, V. S. Ramachandran investigates strange, unforgettable cases from patients who believe they are dead to sufferers of phantom limb syndrome. With a storyteller s eye for compelling case studies and a researcher s flair for new approaches to age-old questions, Ramachandran tackles the most exciting and controversial topics in brain science, including language, creativity, and consciousness."

This book is intended as a text for a one-semester course on Mathematical and Computational Neuroscience for upper-level undergraduate and beginning graduate students of mathematics, the natural sciences, engineering, or computer science. An undergraduate introduction to differential equations is more than enough mathematical background. Only a slim, high school-level background in physics is assumed, and none in biology. Topics include models of individual nerve cells and their dynamics, models of networks of neurons coupled by synapses and gap junctions, origins and functions of population rhythms in neuronal networks, and models of synaptic plasticity. An extensive online collection of Matlab programs generating the figures accompanies the book.

Should parents aim to make their children as normal as possible to increase their chances to "fit in"? Are neurological and mental health conditions a part of children's identity and if so, should parents aim to remove or treat these? Should they aim to instill self-control in their children? Should prospective parents take steps to insure that, of all the children they could have, they choose the ones with the best likely start in life? This volume explores all of these questions and more. Against the background of recent findings and expected advances in neuroscience and genetics, the extent and limits of parental responsibility are increasingly unclear. Awareness of the effects of parental choices on children's wellbeing, as well as evolving norms about the moral status of children, have further increased expectations from (prospective) parents to take up and act on their changing responsibilities. The contributors discuss conceptual issues such as the meaning and sources of moral responsibility, normality, treatment, and identity. They also explore more practical issues such as how responsibility for children is practiced in Yoruba culture in Nigeria or how parents and health professionals in Belgium perceive the dilemmas generated by prenatal diagnosis.

Animal models and tests have become increasingly important for biomedical research, enabling a better understanding of pathogenic pathways involved in various human disorders. Over the last decades, zebrafish (Danio rerio) have become a very popular model organism in biomedical research. Recently, this fish has entered the waters of neuroscience and biological psychiatry, quickly becoming an indispensable model species in this field. With a high genetic homology to humans (~75% based on coding regions), it is not surprising that humans and fish are very similar physiologically (and behaviorally). Therefore, it should not come as a surprise that zebrafish can be an excellent model of human neuropsychiatric disorders. While some classical psychiatrists may not too easily be persuaded by this generalization, the current book "The rights and wrongs of zebrafish: principles of behavioral phenotyping and CNS disease modeling" explains, in a domain-by-domain manner, how exactly zebrafish models can be used to target a wide range of human brain disorders and aberrant phenotypes. The contributors to this book are leading international scholars whose work spearheads innovative zebrafish neuroscience research around the world. Written by top experts in the field, this book makes for a useful, balanced and up-to-date reading that outlines the use of zebrafish to study the pathological mechanisms underlying neuropsychiatric disorders.

This book presents the latest research in computational methods for modeling and simulating brain disorders. In particular, it shows how mathematical models can be used to study the relationship between a given disorder and the specific brain structure associated with that disorder. It also describes the emerging field of computational psychiatry, including the study of pathological behavior due to impaired functional connectivity, pathophysiological activity, and/or aberrant decision-making. Further, it discusses the data analysis techniques that will be required to analyze the increasing amount of data being generated about the brain. Lastly, the book offers some tips on the application of computational models in the field of quantitative systems pharmacology. Mainly written for computational scientists eager to discover new application fields for their model, this book also benefits neurologists and psychiatrists wanting to learn about new methods.

The novelty of this book's approach lies in addressing the impact of neurobiological factors as well as psychological influences on brain recovery. There is growing evidence that emotional, motivational, and cognitive factors along with personality traits play a crucial role in brain plasticity, resilience, and recovery. Topics include synaptic and neuronal plasticity, development of brain reserves, biological markers, environmental factors, psychological profile, emotional resilience, and personality traits. By combining the latest research on neural mechanisms and on psychological resilience the authors hope that this book can lead to the development of better treatment strategies for functional recovery from brain damage.

Inflammation has invaded the field of psychiatry. The finding that cytokines are elevated in various affective and psychotic disorders brings to the forefront the necessity of identifying the precise research domain criteria (RDoCs) that inflammation is responsible for. This task is certainly the most advanced in major depressive disorders. The reason is that a dearth of clinical and preclinical studies has demonstrated that inflammation can cause symptoms of depression and conversely, cytokine antagonists can attenuate symptoms of depression in medical and psychiatric patients with chronic low grade inflammation. Important knowledge has been gained on the symptom dimensions that inflammation is driving and the mechanisms of action of cytokines in the brain, providing new targets for drug research and development. The aim of the book "Inflammation-Associated Depression" is to present this field of research and its implications in a didactic and comprehensive manner to basic and clinical scientists, psychiatrists, physicians, and students at the graduate level.

The second edition of Neuroimmune Pharmacology bridges the disciplines of neuroscience, immunology and pharmacology from the molecular to clinical levels with particular thought made to engage new research directives and clinical modalities. Bringing together the foremost field authorities from around the world, Neuroimmune Pharmacology will serve as an invaluable resource for the basic and applied scientists of the current decade and beyond.

This book analyzes the psychological mechanisms critical to animal communication. The topics covered range from single neurons to broad-scale phylogenetic patterns, shedding new light on the sensory, perceptual, and cognitive processes that underlie the communicative behaviors of signalers and receivers alike. In so doing, the contributing authors collectively integrate research questions and methods from behavioral ecology, cognitive ethology, comparative psychology, evolutionary biology, sensory ecology, and neuroscience. No less broad is the volume's taxonomic coverage, which spans bees to blackbirds to baboons. The ultimate goal of the book is to stimulate additional research into the diversity and evolution of the psychological mechanisms that make animal communication possible.

This edited volume provides an overview the state-of-the-art in the field of cognitive neuroscience of memory consolidation. In a number of sections, the editors collect contributions of leading researchers . The topical focus lies on current issues of interest such as memory consolidation including working and long-term memory. In particular, the role of sleep in relation to memory consolidation will be addressed. The target audience primarily comprises research experts in the field of cognitive neuroscience but the book may also be beneficial for graduate students.

Our understanding of human color vision has advanced tremendously in recent years, helped along by many new discoveries, ideas, and achievements. It is therefore timely that these new developments are brought together in a book, assembled specifically to include new research and insight from the leaders in the field. Although intentionally not exhaustive, many aspects of color vision are discussed in this Springer Series in Vision Research book including: the genetics of the photopigments; the anatomy and physiology of photoreceptors, retinal and cortical pathways; color perception; the effects of disorders; theories on neuronal processes and the evolution of human color vision. Several of the chapters describe new, state-of-the-art methods within genetics, morphology, imaging techniques, electrophysiology, psychophysics, and computational neuroscience. The book gives a comprehensive overview of the different disciplines in human color vision in a way that makes it accessible to specialists and non-specialist scientists alike. About the Series: The Springer Series in Vision Research is a comprehensive update and overview of cutting edge vision research, exploring, in depth, current breakthroughs at a conceptual level. It details the whole visual system, from molecular processes to anatomy, physiology and behavior and covers both invertebrate and vertebrate organisms from terrestrial and aquatic habitats. Each book in the Series is aimed at all individuals with interests in vision including advanced graduate students, post-doctoral researchers, established vision scientists and clinical investigators. The series editors are N. Justin Marshall, Queensland Brain Institute, The University of Queensland, Australia and Shaun P. Collin, Neuroecology Group within the School of Animal Biology and the Oceans Institute at the University of Western Australia.

One of the most important routes to chaos is the chaotic intermittency. However, there are many cases that do not agree with the classical theoretical predictions. In this book, an extended theory for intermittency in one-dimensional maps is presented. A new general methodology to evaluate the reinjection probability density function (RPD) is developed in Chapters 5 to 8. The key of this formulation is the introduction of a new function, called M(x), which is used to calculate the RPD function. The function M(x) depends on two integrals. This characteristic reduces the influence on the statistical fluctuations in the data series. Also, the function M(x) is easy to evaluate from the data series, even for a small number of numerical or experimental data. As a result, a more general form for the RPD is found; where the classical theory based on uniform reinjection is recovered as a particular case. The characteristic exponent traditionally used to characterize the intermittency type, is now a function depending on the whole map, not just on the local map. Also, a new analytical approach to obtain the RPD from the mathematical expression of the map is presented. In this way all cases of non standard intermittencies are included in the same frame work. This methodology is extended to evaluate the noisy reinjection probability density function (NRPD), the noisy probability of the laminar length and the noisy characteristic relation. This is an important difference with respect to the classical approach based on the Fokker-Plank equation or Renormalization Group theory, where the noise effect was usually considered just on the local Poincare map. Finally, in Chapter 9, a new scheme to evaluate the RPD function using the Perron-Frobenius operator is developed. Along the book examples of applications are described, which have shown very good agreement with numerical computations.

Although pain is widely recognized by clinicians and researchers as an experience, pain is always felt in a patient-specific way rather than experienced for what it objectively is, making perceived meaning important in the study of pain. The book contributors explain why meaning is important in the way that pain is felt and promote the integration of quantitative and qualitative methods to study meanings of pain. For the first time in a book, the study of the meanings of pain is given the attention it deserves. All pain research and medicine inevitably have to negotiate how pain is perceived, how meanings of pain can be described within the fabric of a person's life and neurophysiology, what factors mediate them, how they interact and change over time, and how the relationship between patient, researcher, and clinician might be understood in terms of meaning. Though meanings of pain are not intensively studied in contemporary pain research or thoroughly described as part of clinical assessment, no pain researcher or clinician can avoid asking questions about how pain is perceived or the types of data and scientific methods relevant in discovering the answers.

The evolution of vertebrate hearing is of considerable interest in the hearing community. However, there has never been a volume that has focused on the paleontological evidence for the evolution of hearing and the ear, especially from the perspective of some of the leading paleontologists and evolutionary biologists in the world. Thus, this volume is totally unique, and takes a perspective that has never been taken before. It brings to the fore some of the most recent discoveries among fossil taxa, which have demonstrated the sort of detailed information that can be derived from the fossil record, illuminating the evolutionary pathways this sensory system has taken and the diversity it had achieved.

This compelling volume provides a broad and accessible overview on the rapidly developing field of social neuroscience. A major goal of the volume is to integrate research findings on the neural basis of social behavior across different levels of analysis from rodent studies on molecular neurobiology to behavioral neuroscience to fMRI imaging data on human social behavior.

It has become evident over the last years that abnormalities in RNA processing play a fundamental part in the pathogenesis of neurodegenerative diseases. Cellular viability depends on proper regulation of RNA metabolism and subsequent protein synthesis, which requires the interplay of many processes including transcription, pre---mRNA splicing, mRNA editing as well as mRNA stability, transport and translation. Dysfunction in any of these processes, often caused by mutations in the coding and non--- coding RNAs, can be very destructive to the cellular environment and consequently impair neural viability. The result of this RNA toxicity can lead to a toxic gain of function or a loss of function, depending on the nature of the mutation. For example, in repeat expansion disorders, such as the newly discovered hexanucleotide repeat expansion in theC9orf72 gene found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a toxic gain of function leads to the formation of RNA foci and the sequestration of RNA binding proteins (RBPs). This in return leads to a loss of function of those RBPs, which is hypothesized to play a significant part in the disease progression of ALS and FTD. Other toxicities arising from repeat expansions are the formation of RNA foci, bi---directional transcription and production of repeat associated non---ATG (RAN) translation products. This book will touch upon most of these disease mechanisms triggered by aberrant RNA metabolism and will therefore provide a broad perspective of the role of RNA processing and its dysfunction in a variety of neurodegenerative disorders, including ALS, FTD, Alzheimer's disease, Huntington's disease, spinal muscular atrophy, myotonic dystrophy and ataxias. The proposed authors are leading scientists in the field and are expected to not only discuss their own work, but to be inclusive of historic as well as late breaking discoveries. The compiled chapters will therefore provide a unique collection of novel studies and hypotheses aimed to describe the consequences of altered RNA processing events and its newest molecular players and pathways.

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

This edited monograph provides a compelling analysis of the interplay between neuroscience and aesthetics. The book broaches a wide spectrum of topics including, but not limited to, mathematics and creator algorithms, neurosciences of artistic creativity, paintings and dynamical systems as well as computational research for architecture. The international authorship is genuinely interdisciplinary and the target audience primarily comprises readers interested in transdisciplinary research between neuroscience and the broad field of aesthetics.