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.

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).

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.

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...

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.

"Hereditary Peripheral Neuropathies" deals with the Charcot-Marie-Tooth group of neuropathies and related primary hereditary neuropathies. The knowledge in this field has grown exponentially during the last ten years. The book is divided into two sections. The first section deals with the clinical presentation, electrophysiological features and differential diagnosis of these disorders as well as with the general biology of the peripheral nerve. The second section gives a detailed account of the known disease entities. The book will be interesting for both the clinician with a special interest in PNS diseases as well as for the researcher.

Neuronal phase response curves (PRCs) summarize the relationship between the timing of inputs within a neuron's spike cycle and the consequent shifts in output spike timing. The form of a neuron's PRC reflects its mechanism of spike initiation or excitability as well as other influences of membrane conductances on synaptic integration. PRCs are efficient encapsulations of the input-output processing of individual neurons to single perturbations and are powerful devices for the prediction and interpretation of patterned neuronal network activity including synchronization phenomena in connected networks or populations receiving shared input. Thus, application of phase response analysis to neural systems targets the interface of neural computation at the cellular and network levels, one of the most critical and expansive gaps in our understanding of the brain. This volume surveys the diversity of applications of phase response analysis by many of the prominent theoreticians and experimentalists in the Computational Neurosciences. Readers will find a thorough introduction to the foundational concepts underlying phase response analysis, advanced techniques for accurate estimation of neuronal PRCs, and impactful illustrations of both the cellular underpinnings of the phase response properties of neurons and the power of phase response analysis to explain network behavior. Throughout the book, the authors use phase response analysis to elucidate a number of neural systems that are current foci of exciting research in the Computational Neurosciences and are at the forefront of our advancing grasp of the complex mechanisms of brain function and dysfunction.

Many issues remain unresolved in sexuality. In some cases this is because the infor mation is not available to resolve them. In others it is, but the available conclusions the information supports block its acceptance, because they conflict with the posi tions of dominant groups in the politics of sexuality. Possibly the most obvious example is the determination of many theorists to ignore the evidence that while men rarely report being sexually assaulted, when questioned in community surveys, they make up a third of the victims, and a quarter of the perpetrators of sexual assault are women. These findings are incompatible with the feminist theory that sexual assault is not a sexual act, but normal male behavior motivated politically, to maintain men's dominance of women. Most research supporting the theory investigated women only as victims and men only as aggressors. Some feminists have dismissed the need for any research to support their beliefs on the ground that such research is "busy work" establishing what women already know. One belief considered not to require re search is that heterosexual pornography made for a male audience increases the prevalence of rape by encouraging rape-supportive attitudes of male aggression and female submission. No criticism has been directed at the soft-core pornography of "Mills and Boon" stories written for women that promote similar attitudes."

Written in honour of eminent historian Roy Porter by twenty of his colleagues and students, the collection renders cutting edge scholarship accessible. Historians from the three fields that Porter made his own - the histories of medicine, madness, and the Enlightenment - illustrate his influence while tackling major themes ranging from disability rights to the popularization of science. In their accounts, artisan gardeners jostle with anarchists, dentists, and hypnotists in a lively, and very Porterian, parade.

Parkinson's disease is a progressive neurodegenerative disorder charact- ized clinically by tremor, rigidity, slow movements, and postural instability. Pathologically, dopaminergic neurons of the substantia nigra bear the brunt of the degeneration, though other neuronal groups can be affected as well. Although Parkinson's disease is the only neurodegenerative disorder for which effective therapies are available, these treatment options are only symptomatic, do not influence the underlying degenerative process, and are associated with a high incidence of complications, particularly with their long-term use. The progressive nature of the disease and the limitations of its palliative therapies result in significant functional impairment. The chronic disability and the increased prevalence of the disease with the prolongation of life expectancy in developed countries make the social and economic impact of this disease quite high. For- nately, systematic basic and clinical research in this disease has yielded major new advances that render patients' hopes for a cure considerably closer to reality. The application of molecular biologic methodologies in the study of Parkinson's disease has begun to have a major impact only in recent years. Con- quently, the utility of these technologies is largely in the research arena, although their clinical applications are now being realized.

With recent advances of modern medicine more people reach the "elderly age" around the globe and the number of dementia cases are ever increasing. This book is about various aspects of dementia and provides its readers with a wide range of thought-provoking sub-topics in the field of dementia. The ultimate goal of this monograph is to stimulate other physicians' and neuroscientists' interest to carry out more research projects into pathogenesis of this devastating group of diseases.

Research of 5-HT2c receptors stretches back twenty-five years, and while much of it has been productive, the past decade of research has been extraordinary in terms of both amount produced and insights gained. It is hardly surprising that 5-HT2c receptor research has grown so fruitful, given that it is a prominent central serotonin receptor subtype widely expressed within the central and the peripheral nervous system and is thought to play a major role in the regulation of numerous behaviors. It has further been shown by experimental and clinical observation that it may represent a possible therapeutic target for the development of drugs for a range of central nervous system disorders. The time, therefore, is more than appropriate to offer the first ever overview of the research of 5-HT2c receptors. Part of the popular and important series, "The Receptors," The 5-HT2c Receptor provides a thorough update of the functional status of the 5-HT2c receptor. It covers the molecular, cellular, anatomical, biochemical and behavioral aspects of this receptor so as to highlight its distinctive regulatory properties and the emerging functional significance of constitutive activity and RNA-editing in vivo. In addition, the book investigates the receptors' therapeutic potential in a range of different diseases, treated individually in separate chapters, including depression, drug abuse, schizophrenia, eating disorders, Parkinson's disease, Prader-Willi Syndrome, Alzheimer's disease and epilepsy. While not exhaustive, this text is a vital tool in understanding the past and inspiring the future of interdisciplinary research on the 5-HT2c receptor.

Plasma cell dyscrasias are common causes of peripheral neuropathy. Peri- pheral neuropathy may be the first manifestation of multiple myeloma, amyloidosis, or monoclonal gammopathy of undetermined significance (MGUS). Peripheral neuropathy occurs in more than one-half of patients with osteosclerotic myeloma. The hematologic disorders are such an important association with peripheral polyneuropathy that, for the last decade, we have obtained a metastatic bone survey and immunoelectrophoresis of serum and a 24-hour urine specimen on all patients older than 40 years with undiagnosed peripheral neuropathy. This textbook on polyneuropathies and plasma cell dyscrasia is welcome, because the subject is of considerable medical importance and because the authors are expert in these disorders. Kelly's studies have shown that a systematic search for monoclonal proteins in plasma and urine among patients with neuropathy of unknown cause increases diagnostic yield. Latov's studies have focused on the role of myelin associated glycoproteins (MAG) in the induction of neuropathy. Kyle, director of the Special Protein Laboratory at Mayo Clinic, brings a broad clinical and laboratory perspective and experi- ence. The timing of the textbook is just right, because there is much new information which needs to be summarized.

Gliomas are fatal diseases, but also represent good models for tumor research with the aim to eventually discover new and appropriate therapeutics against this disease. Glioma experimental research models are of help to investigate tumorigenesis (tumor stem cell theory versus "classical" opinions), tumor angiogenesis (since they are highly vascularized) and tumor invasion (since they grow without limits). In addition, they have a very special microenvironment (the brain) and limited tumor stroma cells (mainly microglia and endothelial cells). This book addresses the molecular mechanisms of the various tumor stages, describes the interaction with the tumor microenvironment and furthermore depicts experimental models for Glioma research and future therapeutic concepts. The book is composed and written for Scientists and Medical Doctors in Oncology, Neurosciences and Molecular Biology. "

Neuropsychologists are frequently asked to serve as experts for court cases where judgments must be made as to the cause of, and prognosis for, brain diseases and injuries, as well as the impact of brain dysfunction on legal competencies and responsibilities. This fully-updated second edition describes the application of neuropsychology to legal issues in both the civil and criminal courts. The book emphasizes the scientific basis of neuropsychology, as well as using a scientific approach in addressing forensic questions. All of the contributors are recognized experts in their fields, and the chapters cover common forensic issues such as appropriate scientific reasoning, the assessment of malingering, productive attorney-neuropsychologist interactions, admissibility of neuropsychological evidence, and ethics. Also covered are functional neuroimaging in forensic neuropsychology and the determination of damages in personal injury litigation, including pediatric brain injury (traumatic injury and perinatal birth injury), mild, moderate, and severe traumatic brain injury in adults, neurotoxic injury, chronic pain, post-traumatic stress disorder, and assessment of medically unexplained symptoms. Civil competencies in elderly persons with dementia are addressed in a separate chapter, and two chapters deal with the assessment of competency and responsibility in criminal forensic neuropsychology. The book closes with a perspective on trends in forensic practice and research. Like the previous edition, this new volume is an invaluable resource for neuropsychologists, attorneys, neurologists, clinical psychologists, psychiatrists, and their students and trainees.

This book, the latest in the International Child Neurology Review series, is the first authoritative synthesis of the role of vitamin treatments in children with neurological disorders. It covers all the conditions seen in paediatric neurology that are treatable by vitamin supplementation and consists of up-to-date, concise reviews by an international group of experts in their specific fields. They cover: biotinidase deficiency; the role of vitamins in the developing nervous system, mitochondrial disorders and autism; homocysteinuria; conditions responsive to vitamin E or riboflavin; disorders of folic acid and vitamin B12 metabolism; folinic acid responsive seizures, and all aspects of pyridoxine-dependent and pyridoxine-responsive seizures. It is the first time that clinical and data research in this field has been drawn together in one source, making available previously unpublished material. This will be a unique data resource for anyone involved in the care of children with vitamin-responsive neurological disorders.

Important clinical issues as the outcome of long term treatment with antidepressants, the time of onset of the antidepressant response and the limitations of the antidepressants currently available are covered in this monograph. Leading researchers in the area of clinical and experimental psychopharmacology critically assess the progress in their specialist fields. The mechanisms of action of antidepressants are considered, followed by clinical research into the role of the hypothalamic-pituitary-adrenal axis and the immune system in the biology of depression and in response to treatment. The final chapter deals with the important chemical entities now undergoing development as antidepressants. The purpose of this monograph is not only to inform but also to stimulate research into the biology of depression and the mechanisms behind the action of effective antidepressants. This monograph is of interest to psychiatrists, psychologists, pharmacologists, neuroscientists and endocrinologists.

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In addition to surgery and radiotherapy, local treatment modalities for the management of brain tumours are increasingly being developed and clinically tested. This book describes for the first time basic tumour biology as well as all current procedures in progress at the most recent level of knowledge, presented by leading experts in the respective fields. Image guided resection procedures, fluorescence guided surgery, developments in interstitial radiosurgery are addressed, just as intracavitary chemotherapy and all current concepts and studies of interstitial targeted therapy. Owing to its topicality this book will remain for long the standard for this comprehensively treated subject.

We are at the midpoint in the "Decade of the Brain." Why do we know so much and yet understand so little about the brain? The field of neuroscience has exploded, and anyone who attends one of the large meetings has the impression of drinking from a fire hydran- as so aptly put by the late neuroanatomist Walle J. H. Nauta. Part of that feeling is a general-information problem, experienced in other fields of scienc as well. In brain research, however, the problem is accentuated by the rapid advances of molecular and cellular brain research. The dynamics created by these lines of research have multiplied published output, but have inevitably entailed a compartmentalization of scientific interests and research strategies. If the cost of gaining knowledge is a shrinking horizon of the individual scientist, neuroscience must develop strategies for organizing the acquisition of knowledge. Some of this guidance is given by the society -by medical and, perhaps, commercial needs. But who provides the backbone for establishing a generally accepted "schema" for basic brain research -a frame of reference onto which the millions of information fragments can be fitted, in a way acceptable to a multicultural and polymethodical neuroscience community? We believe that developmental and evolutionary biology has the potential to provide a commonly accepted frame of reference for that multilevel system approach needed to understand the workings of the brain.

As an addition to the European postgraduate training system for young neurosurgeons we began to publish in 1974 this series of Advances and Technical Standards in Neurosurgery which was later sponsored by the European Association of Neurosurgical Societies. This series was first discussed in 1972 at a combined meeting of the Italian and German Neurosurgical Societies in Taormina, the founding fathers of the series being Jean Brihaye, Bernard Pertuiset, Fritz Loew and Hugo Krayenbiihl. Thus were established the principles of European co operation which have been born from the European spirit, flourished in the European Association, and have throughout been associated with this series. The fact that the English language is well on the way to becoming the international medium at European scientific conferences is a great asset in terms of mutual understanding. Therefore we have decided to publish all contributions in English, regardless of the native language of the authors. All contributions are submitted to the entire editorial board before publi cation of any volume. Our series is not intended to compete with the publications of original scientific papers in other neurosurgical journals. Our intention is, rather, to present fields of neurosurgery and related areas in which important recent advances have been made. The contributions are written by specialists in the given fields and constitute the first part of each volume.