The specific topic, "Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants - New Perspectives In Parkinson`S Disease Therapy," was chosen in light of accumulating neurobiological evidence indicating that, in addition to exogenous neurotoxins (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [MPTP]), endogenous compounds may play an important role in the most common neurodegenerative disorders (e.g., Parkinson`s disease). Two groups of amine related compounds, which appeared chemically like MPTP, were detected in human brain and cerebrospinal fluid (CSF): ss-carbolines (BCs) and tetrahydroisoquinolines (TIQs). These are heterocyclic compounds formed endogenously from phenylalanine/tyrosine (TIQs) and tryptophan, tryptamine, and 5-hydroxytryptamine (BCs), respectively and exert a wide spectrum of psychopharmacological and behavioral effects. The TIQs and BCs may bind to their own high affinity sites on neuronal membranes associated with or located close to the receptors of neurotransmitters. Research on TIQs and BCs is stimulated also by their possible role in pathological conditions, especially parkinsonism and alcoholism. Recently, clinical interest has been spurred by their role as neuroprotective, and even neurorestorative, anticonvulsant and antiaddictive, substances. In this book we are going to summarize, for the first time, the results from behavioral, neurochemical and molecular experiments, which demonstrate a wide spectrum of TIQs and BCs effects - from their rather mild neurotoxic actions to the important neuroprotective and antiaddictive properties. Additionally, the recent results of experimental studies in vivo have allowed a much better understanding and simultaneous comparison of the neurochemical and molecular mechanisms underlying the neuroprotective and neurotoxic actions of endogenous TIQs and BCs and have pointed to the possibility of their therapeutic applications in neurodegenerative diseases such as Parkinson's disease.

Valproic acid was first synthesized in 1882 by Burton, but there was no known clinical use until its anticonvulsant activity was fortuitously discovered by H. Meunier in 1963 in the laboratory of G. Carraz. The first clinical trials of the sodium salt of valproate were reported in 1964 by Carraz. It was marketed in France in 1967 and was released in the United States in 1978 for the treatment of epilepsy. Since then, valproate has established itself worldwide as a major antiepileptic drug against several types of seizures. Clinical experience with valproate has continued to grow in recent years, including use of valproate for diseases other than epilepsy, for example in bipolar disorders and migraine. In this book, emphasis is placed on the scientific background leading to the discovery of valproate and its clinical development into one of the most widely and successfully used antiepileptic drugs, a real milestone in drug therapy. The current state of knowledge of valproate is reviewed by experts in the field, including new hypotheses on its mechanisms of action, its metabolism into pharmacologically active metabolites, its unique distribution characteristics, its undesirable hepatotoxic and teratogenic adverse effects, and its various clinical uses. The monograph is aimed at a broad readership, particularly neurologists, psychiatrists and basic scientists working in the field of epilepsy research. Furthermore, the book also deals with structure-activity relationships of valproate as well as of its metabolites and analogs and should therefore attract researchers working in medicinal chemistry.

Fully updated with the latest AAP recommendations, this award-winning guide offers parents balanced, reassuring information to help them manage this condition. Topics include: evaluation and diagnosis, coexisting conditions, behavior therapy, ADHD and academics, the role of medication, and complementary and alternative treatments. Parents will also find inspirational and relatable stories from other caretakers.

The NPY-family of peptides encompasses several groups of neurotransmitters and hormones, which exert diverse biological and pathological actions that bear on all major vital systems. The recognition of the role of NPY in stimulation of food intake has already resulted in discovery of potent and selective NPY receptor Y-5 antagonists which are in clinical development for obesity while NPY Y1 receptors are targeted for cardiovascular indications. Research into the multiple functions of NPY and its receptors in neurological and affective disorders are also actively pursued.

This book is a unique compilation of the most recent breakthroughs in NPY/PYY neurobiology, cardiovascular and metabolic disorders, written by internationally renowned experts with the objective to synthesize leading concepts and data in support for translational medicine.

Cerebral amyloid angiopathy (CAA) is a distinctive abnormality of small cerebral blood vessels, one that has intrigued neuroscientists for decades. The time seems right for a book which examines the phenomenon of CAA using a multifaceted approach: What does it produce clinically? How might CAA be imaged? What are the crucial biochemical/cellular events within cerebral vessel walls that lead to CAA? How can in vitro or transgenic experimental systems be used to understand the etiology of, or even potential treatments for, CAA? The editors have assembled key figures in the field of CAA research to examine these (and other) questions in a series of focused chapters that address specific issues of importance in understanding CAA and its clinical manifestations. Comprehending the biology and pathogenesis of this fascinating vascular lesion may even provide clues to less common forms of cerebral microvascular disease that have been recognized for decades (hypertensive microangiopathy) or more recently (CADASIL).

Integrating behavioral, psychoanalytic, and biological perspectives into a unique multi-modal approach, the authors present a new diagnostic and treatment methodology which is flexible enough to account for individual variations in sexually perverse disorders. Alongside this methodology, they highlight the key issues concerning these disorders to provide the general practicing clinician with a practical guide for treating the sexually deviant patient.

Processing of Vocalization Signals in Neurons of the Inferior Colliculus and Medial Geniculate Body; J. Syka, et al. Coding of FM and AM Sounds at the Auditory Midbrain; P.W.F. Poon, et al. Inhibition and Inhibitory Plasticity in the Mammalian Auditory Midbrain; M.B. Calford, Y. Saalmann. Neuronal Periodicity Coding and Pitch Effects; G. Langner. Specialization's of the Auditory System for the Analysis of Natural Sounds; I. Nelken, et al. The Processing of Species-Specific Complex Sounds by the Ascending and Descending Auditory Systems; N. Suga, et al. A Connected Mandarin Speech Recognition System Using Dynamic Programming Bayesian Neural Networks; C.-C. Huang, et al. A computational Model of Birdsong Learning by Auditory Experience and Auditory Feedback; K. Doya, T.J. Sejnowski. On Recent Results in Modeling of Sensory Neurons; P. Lansky. Interneurons Which Shape Response Properties in Dorsal Cochlear Nucleus; E.D. Young, I. Nelken. Behavioral and Physiological Studies of Sound Localization in the Cat; T.C.T. Yin, L.C. Populin. The Processing of Auditory Stimuli for Eye Movements in the Posterior Parietal Cortex of Monkeys; R.A. Andersen, et al. 9 Additional Chapters. Poster Abstracts of the Conference. Index.

At the end of September 1984 Dr. M. Velickovi and Prof. H. Prechtl with the help of the International Cerebral Palsy Society organized an international conference on "New develop ments in the assessment of early brain damage" in Bled, Yugo slavia. I was invited as a speaker at this conference and I went there, curious, but without too much knowledge about the central theme: cerebral palsy. During the conference and a satellite meeting I became impressed by the quality of various contributions and also by the great variety of problems related to the etiology, early diagnosis, management and psychosocial aspects of cerebral palsy. Today, in many areas of biology and medicine, progress seems to require concentration on a very narrow field. As a consequence many conferences are highly specialized and most (young) scientists rightly consider this as most useful for their own work. On the other hand the care of patients and counselling of parents and other close relatives require a multidisciplinary approach. Also, advances in the study of complicated un resolved medical biological pr'oblems are often made unex pectedly by using ideas, theories, approaches or methods from other disciplines."

Stroke is a global health problem affecting approximately 15 million people annually in the world and about 700,000 in the United States. It is the third leading cause of death and the most common cause of disability in most developed countries.

Acute Ischemic Injury and Repair in the Nervous System is intended to provide the most up-to-date knowledge of the mechanisms of neuronal death and repair after stroke. It is our belief that this volume of the Handbook of Neurochemistry and Molecular Neurobiology provides an excellent review of the tremendous advances of the past decades in the neurochemical and molecular biological aspects of cerebral ischemia. It is hoped that these advances will provide an impetus for basic scientists and clinicians to further their translational research and to promote the insights for development of therapeutic interventions for stroke.

Modern theories of brain function are increasingly concerned with dynamics. The task of organizing perception and behaviour in a meaningful interaction with the external world prompts the brain to recruit its various resources in a properly coordinated manner. Vis-a-vis the complexity and multitude of the dynamics involved, a careful orchestration of the various processing components, distributed over space and time, is essential. Hence, it should come as no surprise that a number of recent developments in both experimental and theoretical brain science have emphasized the aspect of spatio-temporal coordination.

This collection of papers intends to capture these various developments in the brain sciences. It brings together new insights and concepts from various branches of experimental and theoretical neuroscience, partly in the form of review chapters, partly in short, focussed contributions, or critical essays. Further it sets out to explore the problems of the processing of the temporal dimension of sensory input and of the generation of space-time patterns in the motor output, as well as the intervening storage and transformation of temporal patterns in nerve nets.

The publication is divided into four major sections: the first considers spatio-temporal aspects of brain function in the context of processing of sensory input and perception and the third, spatio-temporal aspects of brain function at the output end: planning and control of movement. The second section is dedicated to the intervening level of neuronal activity in the working brain and the various dynamics observed at different levels of resolution in space and time. The fourth part combines contributions that transcend this scheme.

It is hoped the book achieves its goal which is to raise an interest in theoretical models that actively seek confrontation with experimental data from the functioning brain, and by a didactic effort aimed at experimentalists to present their data in a format that makes them more amenable to theory.

THE RICHARD AND JUDY BOOK CLUB PICK

THE SUNDAY TIMES BESTSELLER

A BBC RADIO 4 BOOK OF THE WEEK

SELECTED AS A BOOK OF THE YEAR BY THE TIMES

SELECTED AS A SUMMER READ BY THE SUNDAY TIMES, FINANCIAL TIMES, DAILY TELEGRAPH, THE TIMES AND THE MAIL ON SUNDAY

'Revelatory' Guardian

'A miracle' Telegraph

'Remarkable' Daily Mail

'A landmark book' Financial Times

How do you build a life when all that you know is changing?

How do you conceive of love when you can no longer recognise those who mean the most to you?

A phenomenal memoir - the first of its kind - Somebody I Used to Know is both a heart-rending tribute to the woman Wendy Mitchell once was, and a brave affirmation of the woman dementia has seen her become.

Stover and Erdmann deal with the crises confronting today's world and argue that solutions will come not from new technology nor in retreating to an idealized agrarian past, but by overhauling the beliefs that structure society. They link the dilemmas facing civilization to a fundamental rift running through society--one between religion and the humanities, rooted in subjective experience, and science, which emphasizes objective knowledge. They suggest a promising way of closing this rift found in the work of Nobel Laureate and neuroscientist Roger W. Sperry.

They examine Sperry's lifework, including his famous split- brain research and show how it led him to propose a theory of consciousness that challenged science's dismissal of subjective experience as irrelevant. By seeing consciousness as an emergent, causal property of brain function, Sperry reinstated subjective experience into the scientific worldview, laid the foundation for the cognitive revolution that has since swept through psychology, and created a means by which science can help create ethical systems better able to deal with today's challenges. Stover and Erdmann conclude by looking at ways in which others have built upon Sperry's ideas, and they hold out the hope that, with the creation of belief systems more compatible with science, a way out of humanity's current troubles may indeed be found. The result is an excursion through a world of exciting ideas, and a book sure to absorb anyone interested in the fate of our species--and how that fate might be influenced for the better. Students, researchers, scholars, and concerned citizens particularly interested in cognitive psychology, science and society, and futures studies will find the book intriguing.

In spite of medical advances and the increasing number of severely brain-injured patients, the assessment and treatment of patients recovering from coma remain challenging. For over 10 years now, the Coma Science Group has been working on the scientific exploration of disorders of consciousness, with both scientific and clinical research agendas. This book is the result of all this work. The aim is to offer both clinicians and researchers an opportunity to acquire expertise in a field which is constantly developing. Besides diagnostic, prognostic and ethical issues, this book includes well-established findings on assessment techniques (i.e., behavioral scales, electrophysiological explorations and structural/functional neuroimaging) and treatment procedures, but also techniques under development (i.e., the use of classifiers, brain-computer interfaces, transcranial magnetic stimulation or deep brain stimulation) which will stimulate ideas for future research. The Coma Science Group presents here a comprehensive book for readers, regardless of whether they are already familiar with the difficult but exciting field of disorders of consciousness.

Few medical or scientific addresses have so unmistakeably made history as the presentation delivered by Alois Alzheimer on November 4, 1906 in T bingen.

The celebratory event, "Alzheimer 100 Years and Beyond" organized on the initiation of the Alzheimer community in Germany and worldwide, in collaboration with the Fondation Ipsen, was the highlight of the Year of Alzheimer. However, beyond these few months of tributes, the centennial offers a unique opportunity to assess both the progress achieved and the uncertainties remaining. This volume, a collection comprised mainly of articles by the invited speakers and also of a few other prominent researchers, is meant to be a record of those events.

Although the perioperative care of patients by anesthesiologists draws on diverse clinical skills, the principles of anesthesiology and pain management are rooted in the neurosciences. The Neuroscientific Foundations of Anesthesiology thoroughly examines the anesthetic modulation of the central, peripheral, and autonomic nervous systems and will help redefine anesthesiology as a fundamentally neuroscientific field. The book is organized by sections, with each focusing on a different part of the nervous system. State-of-the-art chapters written by thought-leaders in anesthesiology and neuroscience provide a novel and invaluable resource.

During the past decade a significant international research effort has been directed towards understanding the composition and regulation of the preocular tear film. This effort has been motivated by the recognition that the tear film plays an essential role in maintaining corneal and conjunctival integrity, protecting against microbial challenge and preserving visual acuity. In addition, research has been stimulated by the knowledge that alteration or deficiency of the tear film, which occurs in countless individuals throughout the world, may lead to desiccation of the ocular surface, ulceration and perforation of the cornea, an increased incidence of infectious disease, and potentially, pronounced visual disability and blindness. 7 To promote further progress in this field of vision research, the International Conference on the Lacrimal Gland, Tear Film and Dry Eye Syndromes: Basic Science and Clinical Relevance was held in the Southampton Princess Resort in Bermuda from November 14 to 17, 1992. This meeting was designed to assess critically the current knowledge and 'state of the art' research on the structure and function of lacrimal tissue and tears in both health and disease. The goal of this conference was to provide an international exchange of information that would be of value to basic scientists involved in eye research, to physicians in the ophthalmological community, and to pharmaceutical companies with an interest in the treatment of lacrimal gland, tear film or ocular surface disorders (e. g. Sjogren's syndrome).

This volume of Cerebral Cortex is dedicated to Sir John Eccles, who was an active member of the advisory board for the series until his death in May 1997. His input as to what topics should be covered in future volumes of this series will be sorely missed. The present volume is concerned with neurodegenerative disorders and age related changes in the structure and function of the cerebral cortex, a topic that has attracted increasing interest as longevity and the number of aged individuals in the population increase. Although much of the research on the neurodegenerative effects of aging has been centered on Alzheimer's disease, most of the aging popu lation will not be afflicted by this disease. They will, however, be affected by the consequences of normal aging, so the first few chapters of this volume are con cerned with that topic. Chapter 1, by Marilyn S. Albert and Mark B. Moss, gives an account of the cognitive changes that accompany normal human aging. Chapter 2, by Mark B."

Man has been pondering for centuries over the basis of his own ethical and aesthetic values. Until recent times, such issues were primarily fed by the thinking of philosophers, moralists and theologists, or by the findings of historians or sociologists relating to universality or variations in these values within various populations. Science has avoided this field of investigation within the confines of philosophy.

Beyond the temptation to stay away from the field of knowledge science may also have felt itself unconcerned by the study of human values for a simple heuristic reason, namely the lack of tools allowing objective study. For the same reason, researchers tended to avoid the study of feelings or consciousness until, over the past two decades, this became a focus of interest for many neuroscientists.

It is apparent that many questions linked to research in the field of neuroscience are now arising. The hope is that this book will help to formulate them more clearly rather than skirting them. The authors do not wish to launch a new moral philosophy, but simply to gather objective knowledge for reflection.

This book is the first to take into account the rapidly growing body of knowledge on the relation between sleep and PD. Gathering contributions from internationally recognized experts, it provides a unique source of in-depth information on sleep and circadian dysregulation in Parkinson's disease. The book is divided into two parts: the first comprises chapters on normal sleep-wake homeostasis, followed by changes that occur in PD and discussions of available tools for the assessment of sleep-wake cycles in PD. In the second part, sleep and circadian disorders associated with PD are described in individual chapters, including sections on epidemiology, etiology, pathogenesis, differential diagnosis, and treatment. Controversies in the field, such as the relations between cognition and sleep, fatigue and sleepiness, and the potential impact of surgical therapies on sleep-wake cycles are discussed separately. The book closes with a chapter on future directions and unmet needs in the field of sleep, circadian biology and PD. This comprehensive text offers a readily accessible resource for clinicians and researchers alike, addressing the needs of neurologists, sleep and movement disorders specialists, and all trainees and allied health professionals involved in the care of patients affected by Parkinson's disease.

The past decade has witnessed a revolution in the attempts of scientists to under stand the molecular basis of dementia. Although dementia, as defined by global cogni tive decline involving gradual loss of memory, reasoning, judgment, and orientation, presents most commonly in the form of Alzheimer's disease (AD), an assortment of other less common disorders, such as prion and Pick's disease, can also lead to symp toms that are similar to those observed in patients with AD. The primary goal of Molecular Mechanisms of Dementia is to address the various mechanisms and multi faceted approaches currently being employed to more clearly delineate the etiological and pathogenic events responsible for the onset of dementia. Perhaps the greatest boon to obtaining a clearer understanding of the causes of AD has come from genetic and molecular biological studies carried out over the past decade. At the genetic level, it has become increasingly clear that AD is a heteroge neous disorder that can be broadly classified into two categories. "Late onset" (>60 yr) cases, which account for the vast majority of AD, genetically involve "susceptibility" genes representing risk factors for the disease (e. g. , inheritance of the 84 allele of the Apolipoprotein E gene). In many cases, the susceptibility gene can act as a "modifier" that modulates the pathogenic cascade occurring subsequent to a separate etiological event "initiating" or "causing" the disorder.

Following up on his groundbreaking 1990 work Sampling Normal and Schizophrenic Inner Experience, Dr. Hurlburt delineates the development of his descriptive sampling method across numerous case studies of depressed, anxious, bulimic, and borderline personalities. Though controversial, the method effectively demonstrates that an introspective' technique can provide compelling, vivid descriptions of patients, as well as make distinctions between diagnostic groups.

AsanadditiontotheEuropeanpostgraduatetrainingsystemforyoung neurosurgeons, we began to publish in 1974 this series of Advancesand Technical Standards in Neurosurgery which was later sponsored by the EuropeanAssociationofNeurosurgicalSocieties. This series was ?rst discussed in 1972 at a combined meeting of the Italian and German Neurosurgical Societies in Taormina, the founding fathersoftheseriesbeingJeanBrihaye,BernardPertuiset,FritzLoewand HugoKrayenbuhl. ThuswereestablishedtheprinciplesofEuropean- operationwhich havebeenbornfromthe Europeanspirit,?ourishedin theEuropeanAssociation,andhavebeenassociatedthroughoutwiththis series. ThefactthattheEnglishlanguageisnowtheinternationalmediumfor communicationatEuropeanscienti?cconferencesisagreatassetinterms ofmutualunderstanding. Thereforewehavedecidedtopublishallcont- butionsinEnglish,regardlessofthenativelanguageoftheauthors. All contributions are submitted to the entire editorial board before publicationofanyvolumeforscrutinyandsuggestionsforrevision. Ourseriesisnotintendedtocompetewiththepublicationsoforiginal scienti?cpapersinotherneurosurgicaljournals. Ourintentionis,rather,to present?eldsofneurosurgeryandrelatedareasinwhichimportantrecent advanceshavebeenmade. Thecontributionsarewrittenbyspecialistsin thegiven?eldsandconstitutethe?rstpartofeachvolume. Inthesecondpartofeachvolume,wepublishdetaileddescriptionsof standardoperativeproceduresandindepthreviewsofestablishedkno- edge in all aspects of neurosurgery, furnished by experienced clinicians. This part is intended primarily to assist young neurosurgeons in their postgraduatetraining. However,weareconvincedthatitwillalsobeu- fultoexperienced,fullytrainedneurosurgeons. We hope therefore that surgeons not only in Europe, but also throughouttheworld,willpro?tbythisseriesofAdvancesandTechnical StandardsinNeurosurgery. TheEditors Contents ListofContributors...XIII Advances .. Gene Technology Based Therapies in the Brain. T. Wirth1,4 and S. Yla- Herttuala1,2,3, 1A. I. Virtanen Institute,University of Kuopio, Kuopio,F- land, 2DepartmentofMedicine,UniversityofKuopioandGeneTherapyUnit, Kuopio, Finland, 3Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland,4ArkTherapeuticsOy,Kuopio,Finland Abstract...3 IntroductiontoGeneTherapy:ThePast,PresentandFuture...4 PotentialAreasforGeneTherapyintheBrain...6 GeneTherapyforParkinson'sDisease...7 GeneTherapyforAlzheimer'sDisease...8 GeneTherapyforVascularBrainDiseases...9 GeneTherapyforBrainTumours...11 ChallengesofGeneTherapyintheBrain...12 GeneTransferVectors...15 ViralGeneTransferVectors...17 Retroviruses...17 HerpesSimplexVirus-1(HSV-1)...17 Adenoviruses...18 Adeno-AssociatedVirus(AAV's)...18 Non-ViralVectors...19 Ethics...20 ConcludingRemarks...21 Acknowledgement...21 References...21 VIII Contents TechnicalStandards AnatomyoftheOrbitanditsSurgicalApproach. G. Hayek,Ph. Mercier,and H. D. Fournier, Laboratory of Anatomy, Faculty of Medicine, University of Angers,Angers,France Abstract...35 Introduction...36 AnatomyoftheOrbit...36 TheOrbitalCavity...36 TheOrbitalFasciaorPeriorbita...38 OrbitalContents...39 OrbitalMuscles...40 TheArteriesoftheOrbit...42 VeinsoftheOrbit...47 NervesoftheOrbit...48 LacrymalGland...55 ApproachRoutestotheOrbit...56 Incision...56 TheLateralApproachRoute...57 OsteoplasticTechniques...58 Non-OsteoplasticTechniques...58 TheSuperiorApproachRoute...60 TheHybridLateral/SuperiorRoute...63 Discussion...